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Acid resisting, alkali resisting, heatresisting, mechanically strong,Pfaudler glassed-steel equipment isthe perfect answer to the corrosionmenace in chemical plant.The Pfaudler range, which includesstorage, processing and reactionvessels for high and low pressures,condensers, receivers, evaporatingpans, transport tanks, pipes andvalves, has the following importantadvantages :Highly resistant to most acids andalkalis.Can be used at temperatures lip to450°F for some applications.Product does not adhere to linitrg-undesirable build-up of pofj.mPrizcdproducts eliminated.No catalytic effects.Ease of cleaning ensures consintitpurity of product and low maiiitcticiricecosts.Flexibility of applicatioii-procrs.wsand chemicals can be charigtd atshort notice.ENAMELLEDMETAL PRODUCTSBALFOUR GROUP CORPORATION (1933) LTDLeven, Fife.Telephone : Leven 1371.Artillery House, Artillery RowLondon, S.W.l. Telephone: ABBey 7411A member of Pfaudler Permutit IncJOHNSONpH TEST BOOKS andINDICATOR PAPERSforSCIENCE AND INDUSTRYDetails and prices from:F. DARTON & COO LTD.Established I834WATFORD, ENGLANDDistant Record i ng Th er mog ra p hMERCURIAL BAROMETERSMAN OM ETERS HYGROMETERSBAROGRAPHS HYGROGRAPHSTHERMOGRAPHSAvailable through your Laboratory SupplierMAKERS OCatalysis and Inhibition of ChemicalReactionsBy P. G. Ashmore, M.A., Ph.D., 375 pages 75s.Chemical Aspects of NuclearReactorsBy I . K. Dawson, Ph.D., F.R.I.C. and R. G. Sowden, M.Sc., Ph.D.,F.R.1 .C.In three volumes * Vol. I 55s.: Vol. 2 75s.: Vol. 3 50s.ChemisorptionThe Chemistry of NaturalProducts-2By D. 0. Hayward, M.A., Ph.D. andB. M. w . Trapnell, M.A., Ph.D.Second Edition 323 pages 60s.lnternational Union of Pure and AppliedChemistryChemistry of the SteroidsInorganic Polymer ChemistryProgress in Medicinal Chemistry-3224 pages 60s.By Charles w. Shoppee, D.Phil.. D.Sc., F.A.A., F.R.S.Second Edition 463 pages 85s.By F. G. R. Gimblett, M.Sc.452 pages 90s.Edited by G. P. Ellis, B.Sc., Ph.D., F.R.I.C. and G. B. West, B.Pharm.,DSc., Ph.D.407 pages 80s.Progress in Organic Chemistry-6Spectrophotometric Datalnternational Union of Pure and AppliedChemistryEdited by Sir James Cook, D.Sc., F.R.S. and W. Carruthers, Ph.D.264 pages 57s.6d.626 pages 130s.BUTTERWORTHS 4 & 5 Bell Yard, London, W.C.MELLOR’SCOMPREII[ENSIVE TREATISE ONINORGANIC AND THEORETICAL CHEMISTRYVOL. VIII Supplement I; NITROGEN PART IThis, the first of two supplementary volumes on Nitrogen, presentsup-to-date and authoritative information on the inorganicchemistry of the element. It covers the chemistry of nitrogenitself, of metal nitrides, and of ammonia and the more impor-tant ammonium salts. There is also an extensive section on thebiological activity of nitrogen and its compounds.280s netAnnual Reports on theProgress of ChemistryBack Numbers (less certain volumes now out of print)are available-Volumes (1904) to LIX (1962)AlsoCollective Index of Volumes I to XLVIInquiries are invited by:THECHEMICAL SOCIETYBurlington House .London, W.ORGANICULTRA PUREELEMENTS & COMPOUNDSBIOCHEMICALSENZYMESSTEROIDS PEPTIDESSUBSTRATES ALKALOIDSAMINO ACIDS RARE SUGARSPHOSPHOLIPIDS WOELM ALUMINASPHOTOSENSITISING DYES DRElDlNG STEREOMODELSWrite for our new literature:“Pentex Blood Proteins”“Enzymes, Coenzymes and Substrates I964/5”“New Compounds”“Custom Synthesis”“Metabolic Pathways Chart”-3rd edition“Automatic Melting Point Apparatus”LABORATORIES Ltd.phone COLNBROOK 2262BuckinghamshirBOOKSSCIENTIFIC & TECHNICALLARGE STOCK OF BOOKS on the Biological, Physical,Chemical and Medical Sciences supplied from stock, or obtained to order.FOREIGN DEPARTMENT. Books not in stock obtained toorder with the least possible delay.LENDING LIBRARYSCIENTIFIC AND TECHNICALAnnual Subscription from f 2 5s.Prospectus post free on application.Bi-monthly list of New Books and New Editions added to the Librarysent post free to any address regularly.THE LIBRARY CATALOGUE, revised to December, 1956, con-taining a classified Index of Authors and Subjects, to Subscribers,12s.6d.net; to Non-Subscribers, Z(;I IS. net; postagezs. 6d. Supplementto December 1959. To Subscribers, 2s. 6d. net, to Non-Subscribers,5s. net., postage gd. A new edition revised to December 1963will be available in late 1964.____p -~ _ _____-H. K. LEWIS & CO. LTD. 136, Gower Street, WCI. EUSton 4282JSK THE CHEMICAL SUPPLY CO LTDfor details of the chemicals they are manufacturingEster Solvents AZkyl & Aryl Ester PlasticisersFormaldehyde & HexamineSpecial Plastic GradesCadmium Colours Arowatic ChemicalsMolybdic Products Copper FungicidesFull technical details and sampleswill be sent on requestTHE CHEMICAL SUPPLY CO LTD7 IDOL LANE, EASTCHEAP, LONDON EC3Tel: Mansion House 6854Grams: Kemsupply, Phone Londo

ISSN:0365-6217    

DOI:10.1039/AR96360FP001

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRYGENERAL AND PHYSICAL CHEMISTRY1. INTRODUCTIONBy R. E. RichardsWE have again selected a limited number of topics to be reported. Ahuge volume of work is published each year on the properties of ionicsolutions. Two reports are therefore included. The first is concernedespecially with equilibrium properties of electrolyte solutions and with theinformation obtained about interactions between ions and between ions andsolvent molecules. The second is concerned with kinetic processes in solu-tion, especially with reactions involving the transfer of electrons or protons.The report on photo-chemical reactions cannot hope to cover the whole field since it was lastreviewed in 1950, so we have selected work concerned with the primaryphotochemical process.The other report deals with homogeneous poly-merisation in the liquid phase, as this important topic has not been coveredsince 1958.Recent developments in infrared and in Raman spectroscopy are re-viewed in the fifth report. There is still a great deal of exciting progress inthis important branch of spectroscopy.Mass spectrometry has become a technique of great importance, andnew developments in this field are also reviewed.Finally, we present a review of progress in the microwave spectroscopyof gases.There are also two reports on chemical reactions2. ELECTROLYTE SOLUTIONSBy A. K. Covington and J. E. h eTHE general aim of work in this field is the understanding and quantitativedescription of interactions between ions and between ions and neutralmolecules, including those of the solvent.One notable feature of recentpapers is the attention paid to ion-solvent interaction. Not only has in-formation come from spectroscopic techniques and the study of ’very fastreactions by relaxation methods, but the extensive results of conductancemeasurements on solutions in non-aqueous and mixed solvents increasinglyemphasise the need to take some account of the molecular nature of solventmolecules in direct contact with ions. The classical theories of electrolytesare of course based on a model which treats the (spherical) ions as immersedin a solvent which is a continuous dielectric.It is convenient to discuss separately the results obtained by use of thevarious techniques.A vast number of papers is published each year whichreport the determination of equilibrium constants for reactions involvingions. To refer to all of these would be an impossible task, and we restrictdetailed discussion to those determinations of protolytic and complex-ionequilibria which are of rather general interest in the present context, or ofoutstanding precision.Books on ionic equilibria have recently been written by representativesof both the “ electrolyte solution ” 132 and the “ complex-ion ” 3-5 sectors.Taube6 has written an interesting and penetrating review of the extent andlimitation of knowledge of the hydration of ions in solution. A new volumeof Landolt-Bornstein 7 provides an invaluable source of data on conduc-tivities, electrophoretic mobilities and electrokinetic potentials, reversibleand irreversible electrode potentials, and on protolytic equilibria.The745 pages devoted to the conductivities of fused salts, pure liquids, andaqueous and non-aqueous solutions is outstandingly comprehensive. Acritical compilation of the dissociation constants of organic acids in aqueoussolution (organic bases are presumably to be separately dealt with) has beenpublished 8 under the auspices of I.U.P.A.C. The papers presented a t asymposium held in Trieste in 1959 have belatedly a~peared.~C. W. Davies, “ Ion Association,” Butterworths, London, 1962.2 C. B. Monk, “ Electrolytic Dissociation,” Academic Press, New York, 1961.F. J. C. Rossotti and H.Rossotti, “ The Determination of Stability Constants,”* K. L. SchlBfer, “ Komplex-bildung in Losung,” Springer-Verlag, Berlin, 1961.J . P. Hunt, “ Metal Ions in Aqueous Solution,” W. A. Benjamin, Inc., NewYork and Amsterdam, 1963.6 H. Taube, “ Progress in Stereochemistry,” Vol. 3, ed. P. B. D. de la, Mare andW. Klyne, Butterworths, London, 1962, ch. 3: “ Steric Problems in the Hydrationof Ions in Solution.”7 Landolt-Bornstein, “ Zahlenwerte and Funktionen,” 6th edn., Vol. 11, Part 7,Springer-Verlag, Berlin, 1960.8 G. Kortiim, W. Vogel, and K. Andrussow, ‘L Dissociation Constants of OrganicAcids in Aqueous Solution,” Butterworths, London, 1961.“ Electrolytes-An International Symposium,” Trieste, June 1959, ed. B. Pesce,Pergmon, Oxford, 1962.McGraw-Hill, New York, 1961COVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 9A matter of general concern to those who wish to make precise calcula-tions of results for aqueous solutions is the dielectric constant of water.New measurements of this over a temperature range by a bridge method loand by a resonance method 11 have been reported. In the latter work thepressure-dependence was also investigated.Perhaps surprisingly, the valuesof the dielectric constant near O", and even more so the temperature andpressure coefficients, are not yet established as closely as is desirable. Forexample, the two recent papers give for the dielectric constant at 0" a valueof 87-90, compared with 87-74 reported l2 by workers at the National Bureauof Standards.Ultraviolet and Visible Spectrophotometry.-Halide ions in solution haveabsorption bands in the ultraviolet region, which are designated as charge-transfer-to-solvent bands, the upper state being one in which the excitedelectron is located in an orbital with which solvent molecules are intimatelyconcerned.The position and intensity of the band is therefore a usefulindicator of the state of solvation of the halide ion, and several papers reportstudies of the effect of change of solvent and of other ions on the spectrumof the iodide ion in solution. An absorption band, with a maximum at390 mp, for very dilute (< 10-4M) solutions of tetra-n-butylammoniumiodide in carbon tetrachloride 13914 has been ascribed to a transition withinan ion-pair NBu4+I- with the two ions in direct contact, the upper statebeing one in which the excited electron is intimately associated with thecation.The band diminishes in intensity as methanol is added, and it issuggested that this is caused by solvation of the iodide ion with conversionof the " contact " or inner-sphere ion-pairs to ones in which the two ions areseparated by a layer of solvent molecules, NBu,+(CH,OH),I- (the termouter-sphere complex is frequently used for such a species). It is alsosuggested that the enhancement of solution polarisation, compared withthe additive value, consequent upon mixing tetra-n-butylammonium iodide-carbon tetrachloride with methanol-carbon tetrachloride, has a similarorigin. Quantitative estimates 13J* of the efficiency of methanol in destroy-ing the " contact '' ion-pairs are very different.Rummens 15 has studiedthe effect of lithium, potassium, and tetra-n-butylammonium cations on theI- band in dioxan-water mixtures. The maximum at 226 mp is specifiallyaffected by the cation when the mole fraction of dioxan exceeds 0.4. In puredioxan, maxima at 216, 317.5, and 234 mp are ascribed to Li+(dioxan),I-,K+(dioxan),I -, and NBu, +(dioxan),I -, respectively ; it is suggested thatin the last species the cation is only very weakly solvated. On additionof water, the position of the maximum for tetra-n-butylammonium iodidedecreases smoothly down to the steady value reached a t a mole fraction oflo G. A. Vidulich and R. L. Kay, J. Phys., Chem., 1962, 68, 383.l1 B.B. Owen, R. C. Miller, C. E. Milner, and H. L. Cogan, J . Phys. Chew., 1961,65, 2065.l2 C. G. Malmberg and A. A. Maryott, J . Res. Nat. Bur. Stand., Sect. A , 1956,56, 1.l3 T. R. Griffiths and M. C. R. Symons, MoZ. Phys., 1960, 3, 90; M. J. Bland-amer, T. E. Gough, T. R. Griffiths, and M. C. R. Symons, J. Chem. Phys., 1963, 38,1034.l4 F. S. Larkin, Trans. Faraday Soc., 1963, 59, 403.l5 F. H. A. Rummens, Rec. Trav. chim., 1962, 81, 75810 GENERAL AND PHYSICAL CHEMISTRYdioxan of 0.4, probably owing to gradual replacement of dioxan in theiodide solvation-sheath by water. In the cases of lithium and potassiumiodides, as little as 3% of water causes a dramatic increase of the maximumto 225 mp, which is ascribed to the complete replacement of dioxan by waterin the solvation-sheaths of lithium and potassium ions in the ion-pairs.Theposition of the halide charge-transfer band in various solvents has beenstudied. The effect of small quantities of water on the spectra in methylcyanide suggests l6 that the halide ion is strongly preferentially solvated bywater molecules. Very small additions of polar solvents cause the dis-appearance of the charge-transfer band of the ion-pair of the iodide ion (orbromide and other oxidisable ions such as thiocyanate) with a quinoliniumcation in low dielectric solvents.17The 1- band is shifted to shorter wavelengths by a few mp, in concen-trated solutions of electrolytes. The effects are specific ; weakly hydratedcations and strongly hydrated anions seem to be most effective.ls Thelong-wavelength edge of the ultraviolet absorption band of the cupric ion(probably an electron- transfer- from - solvent transition) is shifted to longerwavelengths by alkali-metal and alkaline-earth perchlorates.l9 High con-centrations of perchloric acid have no effect, and the specific effects of thealkali-metal cations increase in the sequence lithium to caesium. The suc-cessive replacement of two water molecules in CU(H,O),~+ by added ethanolor acetone can be followed spectrophotornetrically, and equilibrium con-stants have been reported.20 A study of the spectra of CoCl, and COC~,~-in non-aqueous solvents provides strong evidence for equilibria involvingspecies with solvent molecules, such as nitromethane and dimethylform-amide, in the first co-ordination sphere.Information on the relative amounts of inner- and outer-sphere com-plexes of Np4+ and Np02Z+ with SO,Z-, C1-, and NO3- can be obtained 22by the combined study of the ultraviolet and visible spectra of the cations;only the ultraviolet spectra are sensitive to outer-sphere complex-formation.A careful study has been made by spectrophotometric and e.m.f.methodsof the formation of FeC12+ in aqueous lw-perchloric acid, with a thoroughdiscussion of the assumptions implicit in the analysis of the res~lts.~3Calorimetric measurements were also made. An independent spectro-photometric study of the formation of FeC12+ has also been reported.24The hydrolysis of the hydrated thallic ion to form T10H2+ in perchloratemedia has been studied 25 spectrophotometrically at 25" and 45" in bothwater and deuterium oxide; the absorption spectra (but not the pK values)differ in the two solvents.A scheme proposed to explain the results ofl6 I. Burak and A. Treinen, Trans. Paraday SOC., 1963, 59, 1490.1' G. Briegleb, W. J u g , and W. Herre, Z. phys. Chern. (Frankfurt), 1963, 38, 253.l8 D. Meyerstein and A. Treinen, J. Phys. Chem., 1962, 66, 446.l9 P. A. Zagorets and G. P. Bulgakova, Zhur. $2. Khirn., 1962, 36, 2132.2o N. J. Friedman and R. A. Plane, Inorg. Cherra., 1963, 2, 11.z1 S. Buffagni and T. M. Dunn, J., 1961, 5105.z2 K. W. Sykes and B. L. Taylor, Proc. Internat. Conf. Co-ordination Chem.,23 M. J. M. TVoods, P. K. Gallagher, and E.L. King, Inorg. Chem., 1962, 1, 55.2 4 R. N. Heistand and A. Clearfield, J. Amer. Chern. SOC., 1963, 85, 2566.2 5 T. E. Rogers and G. M. Waind, Trans. Faraday SOC., 1961, 57, 1360.Stockholm, 1962, p. 31COVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 11ultra-centrsuge and e.m.f. studies of the hydrolysis of uranium(m) in achloride medium has been supported by spectrophotometric measure-ments. 26Other complex-ions, the stability of which has been measured by spectro-photometric methods, are (in aqueous solution unless otherwise stated) :UO,Cl+ (50% ethanol), U02S0, (20% methanol) ;27 Br3- (methanol andmethanol-water mixtures) ;2s 1,CNS -, 12N3-, &Br-, and 12Cl-;29 AgCl(pyridine) ;30 CUB^,^- and CuBr3- (aqueous and organic solvents) ;31 mixedhalide complexes between HgBr,2- and HgI,2- ;32 plutonium(1v) acetatecomplexes ; 33 CoCNS + and NiCNS + ; 34 and outer-sphere complexes ofPt(en),4+ with anions.35 The equilibrium CuSO, + Cu2+ + hasbeen used 36 as an indicator equilibrium in studying the formation of Also,+,GaS04+, and InSO,+.The stability of complexes of alkali metals and somedivalent cations with OAc- in acetic acid has been measured 37 by studyingthe effect of added acetates on the absorption of cobaltous acetate, assumingCo(OAc), + 20Ac- + CO(OAC),~- as an indicator equilibrium. Studieswith organic ligands include ferric salicylate, 38 copper 5-sulphosalicylate,39complexes of Solochrome Violet R (an o,o’-dihydroxyazo-dye) with severalcations, 40 and complexes of aliphatic dicarboxylate anions with alkaline-earth cations studied 41 by using an acid-base indicator to follow the shiftin the pH of a buffer on adding a cation which forms a complex with thedicarboxylate anion.Studies of the effects of increased pressure on the transition-metal ions 4 2and on the iodide ions 43 in solution have been reported. A point of generalinterest is the ob~ervation,~~ in pulse radiolysis and flash photolysis ex-periments, of a band with a maximum at $00 mp, ascribed to hydratedelectrons.Spectrophotometric measurements remain both popular and useful forthe study of protolytic equilibria.A precision indicator comparison ofHP042-/P043- buffers with HC0,-/C032- buffers gave 45 pK = 12-37, forHP0,2-. Workers at the National Bureau of Standards have made precise26 R.M. Rush and J. S. Johnson, J . Phys. Chem., 1963, 67, 821.27 D. E. B. Morgans and C. B. Monk, Trans. Paraday SOC., 1961, 57, 463.28 J. E. Dubois and H. Herzog, Bull. SOC. chim. France, 1963, 57.29 D. Meyerstein and A. Treinen, Trans. Paraday SOC., 1963, 59, 1114.30 S. Bruckenstein and J. Osugi, J . Phys. Chem., 1961, 65, 1868.31 J. C. Barnes and D. N. Hume, Inorg. Chem., 1963, 2, 444.32 T. G. Spiro and D. N. Hume, Inorg. Chem., 1963, 2, 340.33 E. Nebel and I(. Schwabe, 2. phys. Chem. (Leipzig), 1963, 224, 29.34 T. Williams, J . Inorg. Nuclear Chern., 1962, 24, 1215.a6D. C. Giedt and C. J. Nyman, J . Phys. Chem., 1963, 67, 2491.36 R. K. Nanda and S. Aditya, 2. phys. Chem. (Frankfurt), 1962, 35, 139.3 7 P.J. Pro11 and L. H. Sutcliffe, Trans. Faraday SOC., 1961, 57, 1078.38 Z. L. Ernst and J. Menashi, Trans. Faraday SOC., 1963, 59, 1794.39 V. S. K. Nair, Trans. Faraday SOC., 1961, 57, 1988.4O E. Coates and B. Rigg. Trans. Faraday Soc., 1962, 58, 2058.41 R. H. Jones and D. I. Stock, J., 1962, 306.42W. S. Fyfe, J. Chem. Phys., 1962, 37, 1894.43 M. J. Blandamer, T. E. Gough, and M. C. R. Symons, Trans. Paraday SOC.,4 4 M. S. Matheson, W. A. Mullac, and J. Rabani, J . Phys. Chem., 1963, 67, 2613;45 C. E. Vanderzee and A. S. Quist, J . Phys. Chem., 1961, 65, 118.1963, 59, 1748.E. J. Hart and J. W. Boag, J. Amer. Chem. SOC., 1962, 84, 409012 GENERAL AND PEYSICAL CHEMISTRYdeterminations of the acidity constants of a number of nitrophenols, oftenover a temperature range (o-nitrophen01,46~ m-nitr~phenol,~~~ p-nitro-phenol,4cC 4-nitro-m-cres01,4~~ dinitrophenol~,46~ picric acid,46e methylpicricacid,46f and dimethylpicric acid 468).Except for the picric acids, wheremeasurements were made in hydrochloric acid solutions, the indicator ratiowas either determined in a buffer of an acid-base system of known pH orspectrophotometric results and e.m.f. measurements of [H +]yH+ycl- werecombined. 3,4-Dinitrophenol was used as an indicator for measurementson hydr~xylamine.~~ Measurements on dinitrophenols have also beenmade 48 in dioxan-water mixtures and in water and deuterium oxide (thedinitrophenols were then used as indicators for the study of nine carboxylicacids). Parallel studies in water and deuterium oxide are interesting inconnexion with the relationship, if any, between pK values in the twosolvents.I n this context a word of caution is appropriate in connexionwith a paper by McDougall and Long 49 which tabulates pK values in waterand deuterium oxide which were obtained by themselves and others byvarious methods. The discrepancy between many of the values recorded forwater and the values obtained by the Bureau of Standards workers, orreported by Kortum, Vogel, and Andrussow 8 or Robinson and Stokes,50casts serious doubt on the reliability of the tabulated values. Measurementson phenol, the three cresols, the six xylenols, and o-chlorophenol have beenmade over a temperature range.51 The AHo values derived therefrom indi-cate that earlier microcalorimetric determinations of this quantity byLaidler et al.are seriously wrong. The pK values of 21 substituted anilinesand 13 substituted phenols have been used 52 for a test of a Hammett-typerelation. The frequently found linearity of plots of pK against mole fractionof organic components in mixed solvent systems suggests 48 the importanceof short-range interaction between solvent and solute species. A spectro-photometric study 53 of the ionisation equilibrium of sulphurous acid over aconcentration range suggests an astonishingly large variation of ionicactivity coefficient with the concentration of undissociated species. Otherdeterminations of pK in water relate to aminonitr~phenols,~~ aromaticdiammonium salts, 55 substituted salicylic acidsY56 and 5-sulphosalicylica ~ i d .5 ~ 9 ~ ~ The measurement of Hammett acidity functions, particularlyfor correlation with rate measurements, remains a popular activity. One46 ( a ) R. A. Robinson and A. Peiperl, J . Phys. Chem., 1963, 67, 1723; ( b ) p. 2860;(c) G. F. Allen, R. A. Robinson, and V. E. Bower, ibid., 1962,66,171; ( d ) R. A. Robinson,M. M. Davis, M. Paabo, and V. E. Bower, J . Res. Nut. Bur. Stand., Sect. A , 1960,64, 347; ( e ) M. M. Davis and M. Paabo, ibid., 1963, 67, 241; (f) 1960, 64, 533; (9) M. M.Davis, M. Paabo, and R. A. Robinson, ibid., p. 531.47 R. A. Robinson and V. E. Bower, J . Phys. Chem., 1961, 65, 1279.48 R. P. Bell and R. R. Robinson, Trans. Faraday Soc., 1961, 57, 965.4g A. C. McDougall and F.A. Long, J . Phys. Chern., 1962, 66, 429.61 D. T. Y . Chen and K. J. Laidler, Trans. Faraday SOC., 1962, 58, 480.6 2 A. I. Biggs and R. A. Robinson, J., 1961, 388.63 D. A. Ratkowsky and J. L. McCarthy, J . Phys. Chem., 1962, 66, 516.54 H. G. Hansson, Acta Chem. Scand., 1962, 16, 1956.A. V. Willi, 2. phys. Chena. (Frankfurt), 1961, 27, 233.‘6 Z . L. Ernst and J. Menashi, Trans. Faraday SOC., 1963, 59, 230, 1803.57 R. Nasanen and K. Paakkola, Suornen Kern., 1961, 34U, 19.R. A. Robinson and R. H. Stokes, “ Electrolyte Solutions,” 2nd edn., Butter-worths, London, 1959, pp. 517-537COVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 13observation of general interest 58 is that the concentration-dependence ofsuch a function for concentrated alkali-metal hydroxide solutions providesevidence for trihydrated OH- (cf.H,O,+). A large specific salt effect oftetra-alkylammonium ions on the acetate buffer-Bromcresol Green equili-brium is possibly due to a specific interaction between the cations and eitherdoubly charged indicator ions or acetic acid molecules.59In non-aqueous solvents, the pK of phenol in ethanol and methanol hasbeen determined 6o and indicator studies of acid strengths in dimethylsulphoxide 61a and methylcyanide 61b have been made. Some interestingstudies are reported 6 2 9 6 3 of the equilibria between amines and nitrophenols.Excitingadvances in the study of electrolyte solutions may confidently be expectedin the next few years as the result of the commercial availability of highlystable and sensitive photoelectric-recording Raman spectrometers.Suchstudies, if properly carried out, will afford more direct evidence of specificinteractions in electrolyte solutions than can be obtained by use of thermo-dynamic and conductometric methods. Unfortunately, the method isrestricted to fairly concentrated solutions (> 0.5~).The effect of theaddition of electrolytes on the Raman water-bands has been investigated,and careful study of the variation with concentration, of intensity, half-width, and frequency of bands due to ionic species, has revealed deviationsfrom strict proportionality between the area under a Raman band and theconcentration of the scattering species, due to various environmental effects.Combination of these two lines of attack on suitable systems, particularly onmixed electrolyte solutions, will be profitable in association with otherspectroscopic techniques.The Raman spectrum of water consists broadly of two regions, an OHstretching band between 3000 and 3500 cm.-l and an OH bending vibrationband between 1500 and 2300 cm.-l. Busing and Hornig 64 have investigatedthe effect of the addition of KBr, KOH, and HC1 on the OH stretching region.This was considered to be made up principally of one band at 3450 cm. -1,which increased, and one at 3250 cm.-l, which decreased with addition ofKBr or HCl. This preliminary study was followed by the more systematicstudy of Schultz and Hornig 65 who investigated the effect of addition oflithium, potassium, and caesium fluorides, chlorides, and iodides on boththe stretching and bending regions.It was concluded that the intensitiesof the bands were affected markedly by the nature of the anion in thesequence F < C1 < I, with fluorides producing a decrease and the others anincrease. No cation-effect was distinguishable. Walrafen 66 extended theRaman and Infrared Spectroscopy.-( a) Raman spectroscopy.Progress has been made on two important aspects.5 8 S. Yagil and M. Anbar, J . Anzer. Chem. SOC., 1963, 85, 2376.5 9 A. Indelli and G. Saglietto, Trans. Paraday SOC., 1962, 58, 1033.6 o B. D. England and D. A. House, J., 1962, 4421.61 (a) I. M. Kolthoff and T. B. Reddy, Inorg. Chem., 1962, 1, 189; ( b ) I. M. Kolthoff,S. Bruckenstein, and M.K. Chantooni, J . Amer. Chena. SOC., 1961, 83, 3927.6 2 M. M. Davis, J . Amer. Chern. SOC., 1962, 84, 3623.63 J. W. Bayles and A. F. Taylor, J., 1961, 417.6 4 W. R. Busing and D. F. Hornig, J . Phys. Chena., 1961, 65, 284.65 J. W. Schultz and D. F. Hornig, J . Phys. Chem., 1961, 65, 2131.66 G. E. Walrafen, J. Chern. Phys., 1962, 36, 103514 QENERAL AND PHYSICAL CHEMISTRYstudy to cover the lower-frequency region. The effect of Br- was foundto be greater than that of C1-, as expected. Certain intensities (e.g., at1645 cm.-l) which increase on addition of potassium chloride or bromidealso increase on lowering the temperature, whereas those (e.g., at 3225 cm. -1)which decrease on salt addition decrease on lowering the temperature.These spectral effects were related to variations in water structure inducedby ions and temperature change.Weston 67 further extended the study topotassium halide solutions in water-deuterium oxide mixtures and con-firmed the sequence of anion-effects. While the effects of added electrolyteson intensities are the more marked, shifts in the OH and OD stretching fre-quencies also occur which are similar to those produced by an increase intemperature. The sequence of frequency shifts and decrease in band-widthfollowed the sequence of solvent structure-breaking tendency for the anions,suggested by other properties. Weston considered that the large anion-effects might mask smaller cation-effects, and this has been confirmed byLauwers and van der Kelen 68 who, from observation of the OH stretchingregion only and study of mixed halide solutions at constant halide ion con-centration, determined the sequence of cation effects: K < Na < Li.These workers dispute previous interpretations of bands in the OH stretchingregion, in particular the explanation of that at 3225 cm.-l as a Fermiresonance, and consider that any interpretation of the observed results interms of the structure of water should wait until the nature and number ofthe component bands is established.While the resolution of the ban& inthe OH stretching region is uncertain at present, the method undoubtedlyshows promise. Similar studies have been made G9 of the influence of per-chlorates on the CO and CH, stretching vibrations in methanol and acetone.Vollmer, 70 using Young’s Chicago instrument, has studied changes infrequency, band-width (at half-height), and band-area of the 1048 cm.-lnitrate ion stretching vibrations in concentrated (0.5-10~) solutions of anumber of nitrates.He finds half-width changes to be proportional to aset of hydrated-cation radii derived by applying Stokes’s Law to ionicmobilities; an ion which shows a large frequency increase shows a smallhalf-width change and vice versa. He explains this by suggesting thatstrongly hydrated cations break down the solvent structure and create amore variable environment for the nitrate ions, which therefore vibrate overa wider frequency range; water attached to such cations is, however, stillavailable to form hydrogen bonds with nitrate ions, whose mean frequencyremains unchanged.Frequency changes occur when weakly hydratedcations shed their water to form contact ion-pairs with nitrate ions. Thecation-hydration sequence required by this interpretation agrees with theevidence from proton nuclear magnetic resonance, conductance, and activitycoefficient results. Small or highly-charged ions such as Li+ or A13+ headthe list. The slight effect of the ammonium ion is explained by its com-patibility with the water structure. Changes in specific intensity (area67 R. E. Weston, Spectrochim. Acta., 1962, 18, 1257.6 8 H. A. Lauwers and G. P. van der Kelen, Bull. SOC. chim. belges, 1963, 72, 477.69 S. Mine and S . Kurowski, Spectrochim. Acta, 1963, 19, 339; S.Mine, 2. Kecki,‘O P. M. Vollmer, J . Chem. Phys., 1963, 39, 2236.and T . Gulik-Krzywicki, {bid., p. 353COVINGTON A N D PRUE : ELECTROLYTE SOLUTIONS 15under curve divided by molarity of exciting species) with concentration areparalleled by shifts to shorter wavelengths of the 3015 A ultraviolet absorp-tion band, and are interpreted as resonance Raman effects.71 The differencesin specific intensity (of a few per cent) between different salts raises thequestion of the correct salt to use as standard for determining the degree ofdissociation of an acid by the Raman method.Exploratory studies have been made of the spectra of many perchlor-ates 72 and ~ u l p h a t e s . ~ ~ Seven perchlorates showed lines other than thoseto be expected from the perchlorate ion, and will repay detailed study.Ofthe sulphates, only indium showed any evidence 73 of complex-formation,the species being either InSO4+ or In(S04)2-. Previous Raman evidence 74for the existence of these species was based on the erroneous assignmentof the 1040 cm.-l HS0,- line to a complex. Ion-pairs in other sulphates,since they do not give rise to Raman lines, are probably solvent-separatedor outer-sphere complexes..Broadening of the 1433 cm.-l line (which is probably the CO stretchingfrequency) in trifluoroacetic acid solutions, compared with sodium tri-fluoroacetate, has been interpreted by Kreevoy and Mead 75 as due to protonexchange between trifluoroacetate ion and the acid. They have derived apseudo-fist-order rate constant for the process, directly from the line-broadening, but no further interpretation of this constant in terms of therate of the proton-transfer reaction has been made.Young and Walrafen7s have postulated the presence of an additionspecies H,SO,+ (Le., H,Of,H2SO4), in the range 90-100% H2S04, to explaina shift in frequency of the 1040 cm.-l HSO,- band.The maximum fre-quency of the new species is thought to be 1055 cm.-1, but two peaks havenot been resolved. An independent examination 77 by Russian workershas not confirmed a shift. These workers 77 have quantitatively re-exam-ined the spectra of sulphuric acid solutions. A shift in the 910 cm.-lfrequency due to H2S04 molecules occurring at concentrations as low as15%, is attributed to the formation of the ion-pair HS04-,H,0+, but theseauthors appear to have overlooked the HO-S stretching frequency of thehydrogen sulphate ion 78 at 895 cm.-l.The presence of such an ion-pairhas been suggested by Gillespie and Robinson,78 who have also questioned V9the interpretation of Young and Walrafen's work on oleum. The twogroups used photographic and photoelectric-recording methods, respec-tively. Itseems that the complementary use of both techniques is desirable.Weak lines are not observed by use of the latter technique.'1 L. A. Woodward, Ann. Reports, 1959, 56, 67.72 M. M. Jones, E. A. Jones, D. F. Harmon, and R. T. Semmes, J. Amer. Chem.Soc., 1961, 83, 2038; G. B. Bonino, P. Chiorboli, and P. Mirone, Atti. Accad. naz. Lincei,Rend.Classe Sci. 3s. mat. nut., 1962, 32, 814.7s R. E. Hester, R. A. Plane, and G. E. Walrafen, J . Chem. Phys., 1963, 38, 3-49.74B. McCarroll and M. H. Lietzke, J. Chem. Phys., 1960, 32, 1277.75 M. M. Kreevoy and C. A. Mead, J . Amer. Chem. Soc., 1962, 84, 4596.7G T. F. Young and G. E. Walrafen, Trans. Farccday Xoc., 1961, 57, 34.7 7 N. G. Zarakhani and M. I. Vinnik, Zhur. $2. Khim., 1963, 37, 503.R. J. Gillespie and E. A. Robinson, Canad. J. Chem., 1962, 40, 644.7 9 R. J. Gillespie and E. A. Robinson, Canad. J. Chem., 1962, 40, 658.T. F. Young and G. E. Walrafen, Trans. Faraday Xoc., 1960, 56, 141916 GENERAL AND PHYSICAL CHEMISTRYWalrafen has reported results of a quantitative study of selenic acid 8 1(also selenious acid 82). The overall picture is very similar to that for sul-phuric acid;83 the maximum concentrations of HSe0,- and H,SeO, areroughly comparable with those of HSO,- and H,SO, but that of SeO,2-is only about half the maximum concentration, indicating that thedegree of dissociation of HS0,- is greater than that of HSe0,- althoughthe pK values are roughly the same.Plane and his colleagues have investigated complex-formation in zinc,Their assignment of two ofthe observed frequencies found in zinc bromide 86 solutions has been chal-lenged by workers who used the valuable technique of solvent-extraction toconcentrate a species.The existence 87 has been shown similarly, in etherealsolutions, of CuC1,- and CuBr2-, which are not present in aqueous solution.The covalently bonded ion CH3Hg-OH2+ has been founds8 in aqueoussolutions of methylmercuric nitrate and perchlorate ; the uncomplexed ionCH3Hg+ was not observed.( b ) Infrared spectroscopy. A careful quantitative comparison of theinfrared spectra of water (2-9 p) and concentrated aqueous solutions ofacids, alkali hydroxides, and halides has been carried out by A~kermann.~~The salts cause only small changes in frequency, whereas the effects of acidsand hydroxides are large and strikingly similar.The changes in acids andhydroxides are ascribed to the influence on the water spectrum of stronghydrogen-bonded complexes of H30 + and OH-. Earlier reports of bandsdue to H30+ in aqueous solutions are very questionable.The water absorption bands in the 1.1-1.3 p region have been resolved 91into three bands which are attributed to water molecules forming no, one,or two hydrogen bonds.The effect on these bands of the addition of anumber of electrolytes 92 was studied, and the influence of the ions as“ structure breakers ” or “ structure makers ” was found to lie in the samesequences as those found by other methods.With the aid of a recently available water-insoluble transmitting material,the spectra of aqueous alkali-metal, zinc, and cadmium sulphates, and somenitrates and nitrites, have been obtained.93 Broadening of bands is observedcompared with spectra obtained with potassium bromide discs, but the areasof bands obeyed Beer’s Law up to 50 mmole 1 . - l of the anion and were in-dependent of the cation used.Other investigations of aqueous (sometimesand gallium bromide 85 solutions.G. E. Walrafen, J . Chem. Phys., 1963, 39, 1479.Solutions,” ed. W. J. Hamer, Wiley, New York, 1959, p. 35.8 2 G. E. Walrafen, J . Chem. Phys., 1962, 36, 90.83 T. F. Young, L. F. Maranville, and H. M. Smith, “ Structure of Electrolytic84 W. Yellin and R. A. Plane, J . Amer. Chem. SOC., 1961, 83, 2448.85 J. Nixon and R. A. Plane, J . Amer. Chem. SOC., 1962, 84, 4445.86 D. F. C. Morris, E. L. Short, and D. N. Waters, J . Inorg. Nuclear Chern., 1963,J. A. Creighton and E. R. Lippincott, J . , 1963, 5134.88 P. L. Goggin and L. A. Woodward, Trans. Faraduy Soc., 1962, 58, 1495.T. Ackermann, 2. phys. Chern. (Frankfurt), 1961, 27, 253.M. Falk and P. A.Gigukre, Canad. J . Chem., 1957, 35, 1195.91 K. Buijs and G. R. Choppin, J . Chm. Phys., 1963, 39, 2035.9 2 G. R. Choppin and K. Buijs, J . Chem. Phys., 1963, 39, 2042.93 A. L. Underwood, M. W. Miller, and L. H. Howe, Anulyt. Chim. Acta, 1963,25, 975.29, 79COVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 17deuterium oxide) solutions are reported for hexa-amminecobalt(1n) solu-t i o n ~ , ~ * EDTA complexes,95 some perchlorates,96 and cyanide complexes 97of Group IIB. The fact that free water, but not co-ordinated water, doesnot absorb a t 3740 cm.-l in nitromethane has been used to determine 98 theconcentration of aquocopper( 11) ion and hence its formation constant in nitro-methane. The result is in agreement with that from a polarographic method.It has been suggested from an infrared study that the hydrogen maleateion is internally hydrogen bonded in water, but that maleic acid itself isnot .99 Calculations suggest that the assumption of internal hydrogen bond-ing is not necessary to account for the observed pK values.A suggestion,loOto explain pKvalues obtained from hydrogen-calomel cells, that the hydrogenmalonate ion is similarly internally hydrogen bonded is not borne out Iolby infrared evidence. Addition of tetra-alkylammonium salts to systemssuch as methanol or prop-2-ynyl bromide in carbon tetrachloride pro-duces 1023103 shifts in the OH or CH stretching frequencies and the appearanceof new broad bands, which are attributed t o hydrogen bonding to the anionof the salt. Earlier interpretation 1°4 of similar effects in t-butyl alcohol-carbon tetrachloride mixtures as being due to salt stabilisation of polymericforms of the alcohol is discredited, but the possibility of hydrogen bonding toanions was recognised by these workers.Nuclear Magnetic Resonance Spectroscopy.-Nuclear magnetic resonance(n.m.r.) in electrolyte solutions was fully discussed last year,lo5 so only themost recent papers will be mentioned.has written a compre-hensive review of n.m.r. measurements on electrolyte solutions. Thestudy 107 of the effect of ions on the proton chemical shift in water leads to ageneral picture of relative ionic hydration consistent with that suggestedby other methods. At -75" a solution of magnesium perchlorate in meth-anol-water shows lo8 separate n.m.r.lines for hydroxyl protons of water andmethanol in the solvation sheath of magnesium ions, and also for free solventprotons. From the line-areas, the relative amounts of water and methanolin the sheath of six solvent molecules around a magnesium ion can be deter-mined. Hydration numbers for aluminium and beryllium ions of six andfour, respectively, have been obtained 109 from the intensity of separateoxygen-17 lines which appear when aluminium and beryllium chloride aredissolved in oxygen-17-enriched water containing the paramagnetic C02-t ion.Hertzg4 R. Larsson, Acta Chem. Scand., 1962, 16, 2460.95 D. T. Sawyer and J. E. Tackett, J. Amer. Chem. SOC., 1963, 85, 314.96 S. A. Shchukarev, S. N. Andreev, T.G . Balicheve, and L. N. Nechaeva, Vestnik:Leningrad Univ., 1961, 16, 120 (Chem. Abs., 1962, 56, 1066).9 7 R. A. Penneman and L. H. Jones, J. Inorg. Nuclear Chem., 1961, 20, 19.9s R. C. Larson and R. T. Iwamoto, Inorg. Ghewz., 1962, 1, 316.99 R. E. Dodd, R. E. 3!T.iller, and W. F. K. Wynne-Jones, J., 1961, 2790.loo S. N. Das and D. J. G. Ives, Proc. Chem. Soc., 1961, 373.lol D. R. Lloyd and R. H. Prince, Proc. Chem. SOC., 196 1, 464.lo2 J. Bufalini and K. H. Stern, J. Amer. Chem. Soc., 1961, 83, 4362.103A. Allerhand and P. von R. Schleyer, J. Amer. Chem. SOC., 1963, 85, 1233.104 J. B. Hyne and R. M. Levy, Canad. J . Chem., 1962, 40, 692.l o 5 R. A. Craig, Ann. Reports, 1962, 59, 63.Io8 H. G. Hertz, 2. Elektrochem. 1963, 67, 311.lo' J. C. Hindman, J.Chem. Phys., 1962, 36, 1000.lo* J. H. Swinehart and H. Taube, J. Chem. Phys., 1962, 37, 1579.lo9 R. E. Connick and D. N. Fiat, J. Chem. Phys., 1963, 39, 134918 GENERAL AND PHYSICAL CHEMISTRYIn 50% dioxan-water mixtures, the water proton resonance line is shifted onaddition of electrolytes, but that of dioxan is unaffected.ll0 Craig andRichardslll have studied the lithium-7 chemical shift and rate of nuclearspin relaxation in concentrated solutions of lithium chloride in water,methanol, formic acid, dimethylformamide, and dimethylformamide-watermixtures. The shift was insensitive to solvent, and only in the case ofdimethylformamide was there evidence of specific ion-solvent interactionfrom the longitudinal relaxation time which Wered from that in the othersolvents by more than could be accounted for by the viscosity change.Lithium chloride (mole fraction 0.11) greatly reduced the change of protonshift on addition of dimethylformamide to water.The times of re-orienta-tion of water molecules in the hydration sphere of alkali-metal and halideions have been investigated 112 by studies of longitudinal relaxation times ofproton resonances.Conductivity.-Results of outstandingly high precision ( &0-005%) havebeen obtained 113 for dilute aqueous hydrochloric acid solutions at 25 and 50".Measurements of such quality require careful attention to various insidiouscauses of error; three recent contributions 114 deal with the technique ofconductance measurements. Precision data for hydrochloric acid solutionsin water and in ethanol-water mixtures over the range 10-3-10-4~ havealso been reported by other workers,l15 whose A, value in water is 0*05y0lower than that which Stokes 113 obtained.Stokes finds that his resultsare better fitted by the Pitts conductance equation 116 than by that of Fuossand Onsager.117 It is worth noting that the three sets of workers 116-118who have tackled the problem of extending the Debye-Onsager limiting-conductance equation agree that, to the first approximation, the effect ofincorporating an ion-size term is to reduce the electrophoretic term by afactor (1 + xa)-l and the relaxation term by [(l + xa)(l + 42xa)l-l. Itis about the higher terms that there is as yet no agreement. Fuoss andOnsager now promise a treatment with " built-in " provision for ion associa-tion,llg i.e., the conductance equation will take full account of higher termsin the Poisson-Boltzmann equation, and the additional concept of ionassociation due to coulombic interaction will be unnecessary.Using thefirst approximation mentioned above to describe the behaviour of free ions,results for bi-bivalent sulphates can be analysed 120 to obtain an ion-pairdissociation constant. The addition of the higher terms of the Pitts equation1loA. Fratiello and D. C. Douglas, J. Chem. Phys., 1963, 39, 2017.112H. G. Hertz and M. D. Zeidler, 2. Elektrochem., 1963, 67, 774.118 R. H. Stokes, J. Phys. Chem., 1961, 65, 1242; B. M. Cook and R. H. Stokes,114 R. H. Stokes, J .Phys. Chem., 1961, 65, 1277; J. E. Prue, ibid., 1963, 67, 1152;115 B. L. Murr and V. J. Shiner, J . Amer. Chent. SOC., 1962, 84, 4672.116 E. Pitts, Proc. Roy. SOC., 1953, A , 217, 43.117 R. M. Fuoss and L. Onsager, J. Phys. Chem., 1957, 81, 668; R. M. FUOSS,J . Amer. Chem. SOC., 1959, 81, 2659; D. S. Berns and R. M. FUOSS, ibid., 1960, 82,6585.R. A. Craig and R. E. Richards, Trans. Faraday SOC., 1963, 59, 1972.ibid., 1963, 67, 511.K. J. Mysels, ibid., 1961, 85, 1081.M. Leist, 2. phys. Chem. (Leipzig), 1955, 205, 16.119 R. M. Fuoss and L. Onsager, J. Phys. Chem., 1963, 67, 621, 628.lZo J. E. Prue, " Ionic Equilibria," Pergamon Press, Oxford, to be publishedCOVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 19leads to little change in the value, but the dissociation constant is markedlyless if the Fuoss-Onsager equation 117 is used.The Fuoss-Onsager equationalready contains some built-in provision for ion association ; thus, becauseresults for some aromatic m- and p-disulphonates of bivalent cations can befitted 121 by this equation without introducing the idea of ion association, itdoes not necessarily follow that these disulphonates are completely dissoci-ated. The association of bivalent ions with separated charges is greatlyenhanced when the charge separation in the cation is similar to that in theanion.Lindsay 123 has carefully measured and analysed the conductanceof aqueous thallous hydroxide solutions. The association constant(3.0 1. mole-I), obtained by using the Fuoss-Onsager conductance equationand setting the ion-size parameter equal to 3 A, agrees with that obtained bya reaction-kinetic method.lZ4 The nature of the binding in the associatedspecies is discussed; an interesting suggestion 125 about this is that on theapproach of a hydroxyl ion, the 6sz electrons of T1+ are re-accommodatedin it 68693 orbital on the side of T1+ remote from OH-, thereby decreasingthe effective ionic radius of the thallous ion and leaving a vacant 68623 orbitaldirected towards the hydroxyl ion.The association of the ferricyanidesand cobalticyanides of trivalent lanthanide cations in water and in water-dioxan mixtures has been measured.126 The association of KPP, in wateris small but unambiguous. 27 The association of long-chain alkyltrimethyl-ammonium cations with arenesulphonate anions has been studied 128 byconductance methods, but measurements 129 on sodium decylsulphate showthat below the critical micelle concentration it is a normal uni-univalentstrong electrolyte, contrary to earlier reports that association of anionsoccurs.The conductance of aqueous solutions of sodium octanoate hasalso been studied 130 up to high concentrations. The limiting molar con-ductance of ,Li+ is 131 @%yo higher than that for 7Li+. Other measure-ments in water are for cadmium perchloratel32 and for sodium sulphateand cupric ~hl0ride.l~~ For the estimation of the degree of dissociationfrom conductance measurements, Wirth134 points out that it is much simplerand probably preferable to use an equation which is linear in cc rather thanequations which are cubic (Fuoss~~~) or quadratic (Shedl0vsky13~) in a*.lZ1 G.Atkinson and S. Petrucci, J. Phys. Chem., 1963, 67, 337, 1880.lZ2 J. E. Lind and R. M. FUOSS, J. Phys. Chem., 1962, 66, 1749.123 W. T. Lindsay, J. Phys. Chem., 1962, 66, 1341.lZ4 R. P. Bell and J. E. Prue, J., 1949, 362.125 M. H. Panckhurst, Austral. J. Chem., 1962, 15, 194.128 H. S. Dunsmore, T. R. Kelly, and G. H. Nancollas, Trans. Paraday SOC., 1963,12' R. A. Robinson, J. M. Stokes, and R. H. Stokes, J. Phys. Chem., 1961, 65, 542.12* A. Packter and 31. Donbrow, Proc. Chem. SOC., 1962, 220.lZ9 G. D. Parfitt and A. L. Smith, J. Phys. Chem., 1962, 66, 942.130A. N. Campbell, E. M. Kartzmark, and G. N. Lakshminarayanan, Canad.J.131 R. W. Kunze and R. M. FUOSS, J. Phys. Chem., 1962, 66, 930.132 R. A. Matheson, J. Phys. Chem., 1962, 66, 439.133 M. Kahlweit, 2. phys. Chem. (Frankfurt), 1961, 27, 297.134 H. E. Wirth, J. Phys. Chem., 1961, 65, 1441.135 R. M. FUOSS, J. Amer. Chem. SOC., 1935, 57, 488.13* T. Shedlovsky, J . Franklin Inst., 1938, 225, 739.59, 2606.Chem., 1962, 40, 83920 GENERAL AND PHYSICAL CHEMISTRYMany measurements have been made in solvents other than water, bothpure and mixed. Uncertainties about the conductance equation at presenthinder analysis. The ion-size parameter which fits results 137 for potassiumchloride in hydrogen cyanide-water mixtures (0') shows a marked andcomplex dependence on composition ; specific solvation effects are presum-ably responsible.Justice and Fuoss have continued a study of the (incom-pletely dissociated) alkali halides in dioxan-water mixtures. 13* The con-ductance equation ion-size parameter which fits the results, varies with thecomposition of the solvent and according to the method of computation. Avalue of A, = 152.8, int. ohm-l cm.2 mole-1 for caesium chloride in watera t 25" is in startling disagreement with a value of 153.7, reported 139 fromanother programme of work on the conductance of electrolytes in mixedsolvents. Caesium iodide in dioxan-water mixtures has been studied aspart of a Russian programme 140 of investigation of ion association. Resultsfor potassium chloride in mixed solvents have been reviewed.141Prue and Sherrington 142 report results for a number of salts in dimethyl-formamide.The comparison of crystallographic, Fuoss-Onsager, andStokes's law ion-sizes suggests that in dimethylamides and dimethyl sulphox-ide, perchlorate and halide anions are unsolvated whilst alkali-metal cationsmove with a solvation sheath, which although not penetrated on encounterwith perchlorate ions may be penetrated by halide ions. In methanol, bothcations and anions are solvated, but penetration of the solvent sheath occursmore readily. The dielectric constants of dimethylformamide (36.7) andmethyl cyanide (37.5) are very similar but the perchlorates of the alkalimetals are associated in methyl cyanide 143 (the association steadily increasesfrom lithium to caesium) and the A, values also suggest that the cationsare less effectively solvated than in dimethylformamide. Specific solvationeffects have also recently been invoked by D'Aprano and Fuoss 144 in thelatest of a series of papers on electrolyte-solvent interactions. Tetra-n-butylammonium bromide has an association constant of 1200 1. mole-l ina methyl cyanide-dioxan solvent of dielectric constant 13.2, but is unassoci-ated in a p-nitroaniline-dioxan mixture of the same dielectric constant. 144aThis is ascribed to specific solvation of the bromide ion by p-nitroaniline.A little p-nitroaniline has a dramatic effect on the dissociation of the samesalt in pure methyl ~yanide.144~ A similar explanation is advanced toexplain differences in the behaviour of tetra-n-butylammonium picrate inmethyl cyanicle-dioxan and in p-nitroaniline-dioxan mixtures.144c Hynehas discussed the results given in earlier papers of the same series. Evidencefor the specific solvation of Br- by methanol also comes 145 from its effecton the O-H stretching frequency in carbon tetrachloride-methanol mix-137 G. Kortiim and H. Reber, 2. Elektrochem., 1962, 66, 345.13* J. C. Justice and R. M. FUOSS, J . Phys. Chem., 1963, 67, 1707.139 L. G. Pedersen and E. S. Amis, 2. phys. Chem. (Frankfurt), 1963, 36, 199.140 E. M. Ryzhkof and A. M. Sukhotin, Zhur. fiz. Khim., 1962, 36, 2205.141 S. Petrucci, Acta Chem. Scand., 1962, 16, 760.142 J. E. Prue and P. J. Sherrington, Trans. Faraday SOC., 1961, 57, 1795.143 S. Minc and L. Werblan, Electrochim.Acta, 1962, 7 , 257.146 J. B. Hyne, J . Amer. Chem. SOC., 1963, 85, 304.(a) A. D'Aprano and R. M. FUOSS, J . Phys. Chem., 1963, 67, 1704; ( b ) p. 1722;( c ) p. 1871COVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 21tures. It is suggested 145 that a tetrabutylammonium bromide ion-pair canbe stabilised by sympathetic interaction with the highly dipolar nitrobenzenemolecule. It may be for a similar reason that the addition of 0.1% of nitro-ethane or nitromethane increases the pK for the association of silver nitratein methanol by 1.0 and 2.5 units, respectively.146 Other additives such aspyridine, acetonitrile, benzonitrile, water, and benzene have much smallereffects. Precise results have been reported for quaternary ammoniumbromides and chlorides in nitromethane.14' The association is greater thanthe simple electrostatic model predicts.Accurate values of transport num-bers were also 0btained,l4'~ and it is shown how the variation of these withconcentration can be used to calculate separately the contribution of theelectrophoretic effect to the conductance. The dipole moments of tetra-alkylammonium salts in bromo- and chloro- benzene mixtures with benzenecorrespond to charge separations which are 2.3 A less than those calculatedby means of the simple electrostatic model for the association constant. lg8Kraus and his co-workers 149 have continued a study and discussion of theconductances of quaternary ammonium salts in benzene and p-xylene up tohigh concentrations, and at temperatures which permit comparison with thefused salts.Conductance measurements have also been reported for the following :silver, potassium, and lithium nitrates in ethanol, water, and in mixturesof the two ;150 silver nitrate and potassium iodide in ethanol ; l 5 l various saltsin acetic anhydride ;152 tetra-alkylammonium salts of PF6- in methylcyanide ;153 lithium, ammonium, and tetrabutylammonium iodides inn-butanol ; 154 quaternary ammonium toluene-p-sulphonates in triarylphos-phates ;155 hydrogen, lithium, and sodium chlorides and hydrogen and sodiumperchlorates in aqueous acetone;156 lithium and zinc chlorides and mag-nesium bromide in tetrahydrofuran and tetrahydrofuran-water mixtures ;15'triarylcarbonium salts in sulphur dioxide ;158 various electrolytes in N -methylacetamide ; 159 acetates and nitrates in formamide ; l60 alkali halidesin methanol-water mixtures ;l6I barium halides in dioxan-water mixtures ;Is2146 R.E. Busby and V. S. Griffiths, J., 1963, 902.14' ( a ) A. K. R. Unni, L. Elias, and H. I. Schiff, J. Phys. Chem., 1963, 67, 1216;148 W. R. Gilkerson and K. K. Srivastava, J. Phys. Chem. 1961, 65, 272.149 L. C. Kenausis, E. C. Evers, and C. A. Kraus, Proc. Nat. Acad. Sci. U.S.A.,150 G. D. Parfitt and A. L. Smith, Trans. Faraday SOC., 1963, 59, 257.151 H. Brusset and M. Kikindai, Bull. SOC. chim. France, 1962, 1150.152 G. Jander and H. Surawski, 2. Elektrochem. 1961, 65, 384.153 J. Eliassaf, R. M. FUOSS, and J. E. Lind, J. Phys. Chem., 1963, 67, 1941.154 H. V. Venkatasetty and G.H. Brown, J . Phys. Chem., 1962, 88, 2075; 1963,155 C. M. French and R. C. B. Tomlinson, J., 1961, 311.lS6V. M. Atkins and C. B. Monk, J., 1961, 1817.15' W. Strohmeier, A. E. S. Mahgoub, and F. Gernert, 2. Elektrochem., 1961, 65, 85.158N. N. Lichtin, P. E. Rowe, and M. S. Puar, J. Amer. Chem. Soc., 1962, 84,4259.159 L. R. Dawson, J. W. Vaughn, hl. E. Pruitt, and H. C. Eckstrom, J. Phys.Chem., 1962, 66, 2684; L. R. Dawson, J. W. Vaughn, G. R. Lester, M. E. Pruitt, andP. G. Sears, ibid., 1963, 67, 278.160 P. H. Tewari and G. P. Johari, J. Phys. Chem., 1963, 67, 512.161 B. P. Panda, P. B. Das, and B. Nyak, J. Indian Chem. SOC., 1962, 39, 537.162 P. B. Das and D. Patnaik, J. Indian Chem. SOC., 1961, 38, 411.(b) R. L. Kay, S. C.Blum, and H. I. Schiff, ibid., p. 1223.1963, 49, 141.67, 95422 GENERAL AND PHYSICAL CHEMISTRYorganic chlorides in antimony trichloride ;163 cyanocarbon salts in waterand non-aqueous solvents ;Is4 and various electrolytes in hydrogenchloride.An outstanding study of a protolytic equilibrium is the precise measure-ment 166 of the conductance of electrophoretically purified water over atemperature range. An estimated value for the conductivity of perfectlypure water leads to a value of K, consistent with that obtained frome.m.f. measurements, thereby removing a small discrepancy between thelatter results and the earlier results of Kohlrausch and Heydweiler.167 Therate constants for the reactions H20 + H30 + --j. H30 + + H20 andH,O + OH- --+ HO- + H,O have been determined 168 from n.m.r.measure-ments, and are consistent with the enhanced conductance of the ions H30+and OH- compared with the values for other ions. The pK values ofHC0,H and DC02H have been determined:169 ApK = 0.035 & 0.002, thefirst acid being the stronger. The pK value for HC0,H of 3-737 agrees withan earlier conductance value but differs from the value of 3.753 obtainedby Harned and Embree.170 Radiotracer analysis has been combined withconductance measurements to give 171 the value pK = 7.06 for the firstacidity constant of H2S a t 25". Other protolytic equilibria which havebeen studied conductometrically are : nitrogen bases in methyl cyanide ;172sulphuric acid and tetraethylammonium hydrogen sulphate in methylcyanide ;173 and acetic acid in N-methylacetamide.159New high-field conductance measurements on 2 : 2- and 3 : 3-electrolyteshave been made.174 Pearson and Munson 175 discuss, with a rough experi-mental test, a way of determining ionic mobilities directly from resistancemeasurements without the need for transport-number data.Transport Numbers.-Spiro and his co-workers 176 continue the deter-mination of transport numbers of weak acids by the moving-boundarymethod.The anion-constituent transport number of D-tartariC acid, usingacetic acid as indicator electrolyte, was found to vary with current. Thiswas attributed to Joule heating which is much more pronounced with weakthan with strong electrolytes. Values extrapolated to zero current werefound to be almost independent of concentration between 0.01 and 0 .1 ~ .The limiting equivalent conductance obtained was in good agreement with arecalculated value derived from conductance data 17' for ammonium hydro-gen tartrate, making proper correction for hydrolysis. Kerker and his163A. G. Davies and E. C. Baughan, J., 1961, 1711.l e 4 R . H. Boyd, J . Phys. Chem., 1961, 65, 1834.l e 5 M . E. Peach and T. C. Waddington, J., 1963, 69.166 H. C. Duecker and W. Haller, J. Phys. Chem., 1962, 66, 225.167 F. Kohlrausch and A. Heydweiler, 2. phys. Chem., 1894, 14, 317.16* S. Meiboom, J. Chem. Phys., 1961, 34, 375.1139 R. P. Bell and W. B. T. Miller, Trans. Paraday Soc., 1963, 59, 1147.l 7 O H. S. Hmed and N. D. Embree, J. Amer. Chem. SOC., 1934, 56, 1042.I i 2 W.S. Muney and J. F. Coetzee, J. Phys. Chem., 1962, 68, 89.li3 I. M. Kolthoff and M. L. Chantooni, J. Phys. Chem., 1962, 66, 1675.174 G. Atkinson and M. Yokoi, J. Phys. Chem., 1962, 66, 1520.175 R . G. Pearson and R. A. Munson, J. Phys. Chem., 1961, 65, 897.176 K. N. Marsh, M. Spiro, and M. Selvaratnam, J. Phys. Chem., 1963, 67, 699.H. L. Loy and D. M. Himmelblau, J. Phys. Chem., 1961, 65, 264.N. E. Topp and C. W. Davies, J., 1940, 87COVINGTON AND P R U E : ELECTROLYTE SOLUTIONS 23colleagues 178 report transport numbers for sulphuric acid solutions a tmolarities up to 0.05, and for three tungsto-polyacids. The existence of amaximum 179 in the cation transport number of perchloric acid at about0 . 0 6 ~ and 25" has been confirmed,l80 but the observed maxima differ.Themaximum is found also a t 30, 40, and 50". The new measurements weremade with potassium perchlorate as indicator electrolyte, and methylorange, added to make the boundary visible, enabled measurements to bemade fo low concentrations where the transport number was found to varylinearly with the square root of the molarity, permitting extrapolation toobtain the limiting transport number. The same technique has been usedto measure lS1 transport numbers in nitric acid. Here the discrepancy withprevious work by the autogenic method is serious, a linear variation withthe square root of the molarity being found up to 0 . 0 9 ~ . The basic equationfor the determination of transport numbers from moving-boundary experi-ments has been derived 182 by the methods of irreversible thermodynamics.The use of the calculated volume change for the reaction at the closedelectrode, to correct values obtained to Hittorf numbers, is only valid ifvolume changes on mixing of the solutions at the liquid boundary arenegligible.The Hittorf method continues to be employed to determine solvationnumbers by the addition of supposedly inert reference non-electrolytes.This method, originally employed by Washburn, has long been known to beinvalid, as pointed out by Spir0.18~ The quantities which can be obtainedfrom such experiments are the transference numbers (Scatchard lS4) orWashburn numbers l S 5 of the non-electrolyte. Feakins 186 has indicatedhow Washburn numbers for water can be derived from silver-silver chlorideand hydrogen concentration cells with liquid junctions formed between HC1solutions of the same activity in water and methanol-water mixtures.When certain assumptions are made, the difference between the standardelectrode potentials of the silver-silver chloride electrode in the two solventscan be obtained from these cells and compared with the directly determinedvalues from cells without transport.The agreement is not very satisfactory( &2 mv). Transport numbers derived from silver-silver chloride concen-tration cells with transport are reported 187 for hydrochloric acid solutionsup to 1 4 . 7 ~ a t 15, 25, and 35".Rutgers and Hendrikx lS8 have made an interesting attempt to derivesolvation numbers by studying the transport of solvent by ions betweencompartments of H20 and D20 separated by a cellophane membrane.By17BM. Kerker, J. Keller, J. Siau, and E. Matijevic, Trans. Faraday SOC., 1961,57. 780.17*A. K. Covington and J. E. Prue, J., 1957, 1567.lB0 K. Banerjee and R. D. Srivastava, 2. phys. Chem. (Frankfurt), 1963, 38, 234.lB1 K. Banerji, R. D. Srivastava, and R. Gopal, J . Indian Chem. SOC., 1963, 40, 651.lS2 R. J. Bearman, J . Chem. Phys., 1962, 36, 2432.lB3 M. Spiro, J . Inorg. Nuclear Chem., 1963, 25, 902.lB4 G. Scatchard, J . Amer. Chem. Soc., 1953, 75,. 288:.la5 J. N. Agar, " Structure of Electrolytic Solutions,New York, 1959, p. 200.lB6 D. Feakins, J., 1961, 5308.ed. W. J. Hamer, Wiley,S. Lengyel, J.Giber, and J. Tamas, Acta Chim. Acacl. Sci. Hung., 1962, 32, 429.A. J. Rutgers and Y. Hendrikx, Trans. Faraday SOC., 1962, 58, 218424 GENERAL AND PHYSICAL CHEMISTRYcombining the results of measurements made with membranes permeable toboth ions and to anions only, values were obtained for. individual ionichydration numbers which are somewhat higher than those derived fromother methods and usually based on assumptions that the solvation num-ber of the chloride ion, here found to be 5 , is small or zero. Schneider andStrehlow lS9 have continued the investigation of the transport of solvent byions in mixed solvents.Kinetics.-The development of relaxation methods has made possiblethe study of the rates of reactions with half-times over the whole range fromthe flow-method limit of about The rates ofmany reactions involving simple ions are in this range and were traditionallydescribed as immeasurably fast.A thorough account of the techniques forrelaxation measurements has appeared.lS0 Eigen has reviewed 191 in twoplaces the results of recent studies of the rates of complex-ion and protolyticreactions, and a general review 192 of the rates of fast reactions has alsoappeared recently. By relaxation methods, the process of formation of acomplex-ion in solution can be dissected into several stages. The rate offormation of outer-sphere complexes is non-specific and diffusion-controlled.Large differences are found in the values of formation of inner-sphere com-plexes by different cations.With very weakly hydrated cations, such asthose of the alkali metals, the rate is comparable with that of outer-spherecomplex-formation ; with polydentate ligands, the arrangement of theligand around the cation is rate-determining. With more firmly hydratedcations, the rate of entry of the ligand to the inner-sphere is normally inde-pendent of its nature and the rate-controlling step is the detachment of awater molecule. For non-transition-metal ions this varies in a simple waywith the radius and charge of the cation, whilst with transition-metal ionsligand-field effects are important. In a few cases of very strongly hydratedions (e.g., Al(H,0),3 +), removal of a proton by the ligand to form a hydrolysedspecies precedes substitution. From relaxation methods, the relative popula-tions of inner- and outer-sphere states are now known for a number ofcomplexes.The bi-bivalent sulphate complexes lg3 are predominantly outer-sphere as is also that of aluminium s ~ 1 p h a t e . l ~ ~ ~ Of ferric complexes,194bthat with chloride ion is roughly equally distributed between inner- andouter-sphere states, whilst those with thiocyanate and sulphate ion arepredominantly inner-sphere. With vanadyl sulphate 194c there are twice asmany inner-sphere as outer-sphere complexes.Interesting specific salt effects continue to be reported for reactionsstudied by classical kinetic techniques. Studies lg5 of thereaction T1+ + T13 +189 H. Schneider and H. Strehlow, 2. Elektrochem., 1962, 66, 309.l90 M. Eigen and L.de Maeyer, “ Techniques of Organic Chemistry,” VIII, Part 2,ed. S. L. Friess, E. S. Lewis, and A. Weissberger, Wiley, New York, 1963, p. 895.ln1 M. Eigen, Pwe Appl. Chem., 1963, 6, 97; Ber. Bunsen Gesellschaft Phys. Chem.,1963, 67, 753.lea L. de Maeyer and K. Kustin, Ann. Rev. Phys. Chem., 1963, 14, 5.Ig3 M. Eigen and K. T a m , 2. Elektrochem., 1962, 66, 93, 107.In4 ( a ) B. Behr and H. Wendt, 2. Elektrochem., 1962, 66, 223; ( b ) H. Wendt andH. Strehlow, ibid., p. 228; ( c ) H. Strehlow and H. Wendt, Irz.org. Chem., 1963, 2, 6.ln5 S. Gilks, T. E. Rogers, and G. M. Waind, Trans. Faraday Soc., 1961, 57, 1371;E. Roig and R. W. Dodson, J . Phys. Chem., 1961, 65, 2175; H. J. Born, H. Vogg,and G. Vogt, 2. Elektrochem., 1962, 66, 372.sec. down to 10-10 secCOVINGTON AND PRUE : ELECTROLYTE SOLUTIONS 25provide a good illustration of the subtleties of ionic catalytic and salt effects,and the way in which apparent differences of interpretation can arise froman inadequate knowledge of the equilibria in solutions.It seems that atlow concentration C1- and, probably to a lesser extent, OH- are inhibiting,but C1- accelerates at higher concentrations. Over this latter range thereis no kinetic deuterium isotope effect. S042 - accelerates ; absorption spectraindicate that this can, in contrast with C1-, only form outer-sphere com-plexes with T13+. For the reaction Fez+ + Fe3+, it is noteworthy that lS6for nine complexing agents the rate constant, k, is given by the equationlog,, II: = 1.1 + 5 I A log K 1 , where A log K is the difference in the stabilityconstants of the complexes of the ligand with ferrous and ferric ions.Indellil97 has continued the study of specific salt effects with particularreference to tetra-alkylammonium ions.These cations exert a large retard-ing effect on the reaction between ferricyanide and iodide the normalsalt effect being reversed, There is no specific effect on the alkaline hydroly-sis of potassium ethyl adipate and sebacate. lSTb A semi-empirical correla-tion of salt effects and rates has been published.l98 Metal-ion catalyticeffects on the thermal decomposition of Co( Ox),3- have been discussed.1s9A mechanism has been proposed which correlates the rates of both thermaldecomposition and racemisation with the rate of electron-exchange withPhysical organic chemists are becoming increasingly interested in specificsalt effects on a variety of reactions, e.g., the specific effect of cations on thehydrolysis of t-butyl chloride 2oo and the specific effect of alkali-metal ionson the reaction of the methoxide ion with 2,4-dinitrochlorobenzene inmethanol and benzene.201 The necessity for a distinction between inner-sphere, '' contact " or " intimate " ion-pairs and outer-sphere or " solvent-separated " pairs in analysing the mechanism for organic reactions continuesto be disputed.202Specific solvation effects strongly influence the nucleophilic reactivityof halide ions.Their reactivity is greatly reduced by hydroxylic solvents.An interesting review by Parker 203 discusses the effects of solvation ofanions on reactivity, solubility, conductance, spectra, and acidity constants.Guggen-heim 204 has extended his numerical integration of the Poisson-Boltzmannequation to electrolytes of 2 : 1 charge type.He concludes, in contrast tohis finding for 2 : 2 electrolytes, that the Debye-Huckel approximation givesan adequate representation of the behaviour of 2 : 1 electrolytes up to ionicCo( o x ),2 -.Thermodynamic Properties.-(a) General and theoretical studies.lo6 K. Bachmann and K. H. Lieser, Ber. Bunsen Gesellschaft Phys. Chem., 1963,lQ7 ( a ) A. Indelli, J . Phys. Chem., 1961, 65, 972; ( b ) Trans. Faraday Soc., 1963,Ig8 J. W. Gryder, J . Chem. Phys., 1962, 37, 718.ls9 W. Schneider, Helv.Chim. Acta, 1963, 46, 1863.2oo G. A. Clarke and R. W. Taft, J. Amer. Chem. SOC., 1962, 84, 2295.201 J. D. Reinheher, J. T. Gerig, and J. C. Cochran, J . Amer. Chern. SOC., 1961,202 C. G. Swain and G.-I. Tsuchihashi, J. Amer. Chem. SOC., 1962, 84, 2021.2os A. J. Parker, Quart. Rev., 1962, 16, 163.204 E. A. Guggenheim, Trans. Faraday Soc., 1962, 58, 86.67, 802.59, 1827.83, 283726 UENERAL AND PHYSICAL CHEMISTRYstrengths of 0.1 mole 1.-1. Fuoss and Onsager 205 have integrated thePoisson-Boltzmann equation with alternative boundary conditions, andsuggest that a theoretical account of the specific behaviour of differentelectrolytes due to short-range effects cannot be derived from further exten-sions of the Poisson-Boltzmann equation but should be sought by a projec-tion of a theory of fused salts.Scatchard 206 has extended his earlier theoretical treatment of mixedelectrolytes and has applied the result to the interpretation of freezing-point,isopiestic vapour pressure, and e.m.f. results.The relation to Bronsted’sPrinciple of Specific Interaction of Ions, Harned’s rule, and Friedman’sdevelopment of the cluster theory is discussed. Friedman 207 has publishedan account of his treatment in book form. Scatchard prefers a standardvalue of 1.5 mole-% I., for the parameter multiplying the term in the squareroot of ionic strength in the denominator of the Debye-Huckel expression,even for 1 : 1 electrolytes. Daviesl now prefers 0.3 mole-1 1. instead of0.2 in the linear term of his standard equation.Guggenheim’s theory 208of mixed electrolytes has often been criticised as an oversimplification, butits use in interpreting e.m.f. results of only moderate precision for variationsof composition of two 2 : 1 electrolytes at constant ionic strength has beendemonstrated. Zo9Moriyama 210 has noted that the minimum values of the osmotic co-efficients (and activity coefficients 211) of electrolytes of the same charge typewhen plotted against the square root of the molality at which these occur,fall on a common curve, and has accounted for this and another regularityby consideration of Glueckauf’s theory 212 of concentrated electrolytes.The distribution of ions around a central ion has been discussed byand radial distribution functions have been evaluated.Thedefinition of ion-pairs is discussed, but an examination of the precise signifi-cance of experimental association constants is avoided. Several papersreport attempts to sophisticate the theoretical model for the interactionbetween adjacent ions or adjacent ion and solvent molecules. Magnusson 214discusses in detail the interaction of the fluoride ion with cations having arare-gas electronic configuration, and the interactions of alkali-metal ionswith water molecules has been discussed by V a s l ~ w . ~ ~ ~ Rosseinsky 216has carefully considered the effects of dielectric saturation on ion associa-tion with bi-bivalent sulphates, and related questions concerning the distri-bution of ions between outer- and inner-sphere complexes.Fre-quencies which are normally infrared-inactive have been observed for sul-phates 111 and perchlorates 112 in the solid state.In the case of barium,cadmium, and lead sulphates, it has been shown 113 that the infrared absorp-tion spectra can be interpreted on the basis of C,, symmetry arising fromperturbation of the sulphate Td symmetry by an adjacent bivalent cation.A reduction in symmetry of the nitrate ion from DSh-nitrate to C,,-nitrato,as a result of strong hydrogen bonding, has been observed in infrared studiesof hydrated thorium nitrate.l14 In very thick films at low temperatures,the Raman-active frequency of CO, has been observed in the infraredspectrum. 115Activated nitrogen has been shown 116 to cause infrared emission fromCO, and N,O.Activated nitrogen contains a large number of vibrationallyexcited nitrogen molecules, and this energy is presumably transferred bycollision to the other molecules. This mechanism might be able to providepopulation-inversion. Infrared emission has also been observed fromsystems involving atomic hydrogen,l17 e.g., H + NOC1. The reaction isconsidered to be H + NOCl = HC1* + NO, where HC1* implies vibration-ally excited HC1 in the ground electronic state. HCl* was present in levelsup to v = 9 or 10, and the distribution amongst the levels was non-Boltzmann.The effect of pressure-modulation on infrared spectra has been investi-gated.ll8 Pressure-modulation at a frequency of 8 c.sec. -l, with compres-sion ratios varying from 2 : 1 to 6 : 1, produces high temperatures in the gasand, as a result, rotational lines of GO with initial J values as high as 40were observed for samples in which J = 32 is the normal limit.The tech-nique can be used for the study of hot bands not readily observable byconventional techniques, and for the production of pressure-modulatedemission spectra.The use of electric fields to induce infrared absorption has been dis-cussed. 119Selection rules and symmetry may be modified in the solid state.l08 G. B. Savitsky and D. F. Hornig, J. Chem Phys., 1962, 36, 2634.loo M. St. C. Flett, Proceedings of the 4th Molecular Spectroscopy Conference110 R. A. Schroeder, C. E. Weir, and E. R. Lippincott, J . Chem. Phys., 1962, 36,ll1 S.D. ROSS, Spectrochim. Acta, 1962, 18, 1575.112 S. D. ROSS, Spectrochim. Acta, 1962, 18, 225.113 J. C. Decius, E. H. Coker, and G. L. Brenna, Spectrochim. Acta, 1963, 19, 1281.114 J. S. Cho and M. E. Wadsworth, U.S. At. Energy Comm., 1962, TID-16465, 1.115 M. E. Jacox and D. E. Milligan, Spectrochim. Acta, 1961, 17, 1196.116 F. Legay and P. Barchewitz, Compt. rend., 1963, 256, 5305.117 J. K. Cashion and J. C. Polanyi, J . Chem. Php., 1961, 35, 600; P. E. Charters,l18 R. R. Patty and D. Williams, U.S. Dept. Comm. Ofice Tech. Serv., P.B. Rept.,118 R. W. Terhune, C J S . Dept. Comm., Ofice Tech. Serv., P.B. Rept., 1959, 147,275,l.(Bologna, 1959), Pergamon, London, 1962, Vol. 2, p. 703.2803; J . Res. Nut. Bur. Stand., Sect. A, 1962, 66, 407.B. N.Khare, and J. C. Polanyi, Nature, 1962, 193, 367.1962, 153,657, 1; J . Opt. SOC. Amer., 1961, 51, 1351.This has increased importance, both for derivingmolecular information and for chemical analysis. Improved precision indetermining relative intensities was reported 23 for measurements made in aStark-modulated cavity. More recently, it is preferred to retain theadvantages of a waveguide cell, 24 mismatch difficulties being minimised bygood design and, especially, by placing ferrite isolators a t each end of thecell. Dymanusand his co-workers 25 also made careful studies of intensities and line widthsin cavity cells. Other techniques for line-width measurement have beendescribed. 26Double resonance and beam maser spectrometers. Changes in level-populations on irradiation at a frequency different from that used fordetection offer promising new means of studying molecules.27 When thepumping absorption frequency lies above that of the detected transition,the latter may be observed in emission, and this three-level maser actionhas been discussed by Shimoda and others.28 With formic acid, forexample,29 it is possible to pump at 46.581 Gc./sec. (110-+211 line) andobtain emission at 4.916 Gc./sec. (211+212 line). An attractive feature 28 isthat transitions a t high frequencies, where detectors work poorly, can bestudied through their effects on transitions which can be efficiently detected.A strong transition may also be used to detect a weak one. Such methodsoffer valuable possibilities in checking assignments in complex spectra,and in other ways.30Beam maser spectrometers, with their immense resolving power, havebeen applied to a variety of simple molecules.In HCN 31 emission isobtained a t 88.6 Gc./sec., but most of the work is a t lower frequencies.Studies of rotational lines in stimulated emission at only a few megacycles,for example the 431+432 line of formaldehyde at 4.5769 M~./sec,~~ show21 R. L. Poynter and G. R. Steffensen, Rev. Sci. Instr., 1963, 34, 77.22 M. P. Klein and G. W. Barton, jun., Research Report UCRL-6727, University23 P. H. Verdier and E. B. Wilson,. jun., J . Chem. Phys., 1958, 29, 340.24 A. S. Esbitt and E. B. Wilson, jun., Rev. Sci. Instr., 1963, 34, 901.25 A. Dymanus, H. A. Dijkeman, and G.R. D. Zijderveld, J. Chem. Phys., 1960,26 E. A. Rinehart, R. H. Kleen, and C. C. L h , J.'Mol. Spectroscopy, 1960, 5, 458;2' A. Battaglia, A. Gozzini, and E. Polacco, Arch. Sci., 1960, 13, Fasc. spbcial,28 K. Shimoda, J . Phys. SOC. Japan, 1955,14,954,966; T. Yajima and K. Shimoda,2BT. Yajima, J . Phys. Soc. Japan, 1961, 18, 1594, 1709.30A. P. Cox and E. B. Wilson, jun., Symposium on Molecular Structure and31 D. Marcuse, J. Appl. Phys., 1961, 32, 743.32 K. Shimoda, H. Takuma, and T. Shimizu, J . Phys. SOC. Japan, 1960, 15, 2036.Intensity measurement.Intensity ratios could be measured to within a few per cent.of California, October 5th, 1962.32, 717.E. A. Rinehart and C. C. Lin, Rev. 8 c i . Instr., 1961, 32, 562.171.ibid., 1960, 15, 1668.Spectroscopy, Ohio State Univ., 1963SHERIDAN : MICROWAVE SPECTROSCOPY OF GASES 163what a remarkable extension of the range of rotational spectroscopy can bemade.Improvements in sensitivity attainable by maser techniques arediscussed byAnalysis of Spectra.-The period has seen many advances in the theoryof spectra and the application of electronic computation to their analysis.Although all such work is essentially concerned with expressing energylevels, it is possible to make a rough classification according to the specialemphasis.Electronic computation of these hasbeen greatly extended. The tabulation of reduced rotational energies hasbeen published 34 to nine figures for J-values up to 9 and intervals of only0.001 in Ray’s asymmetry parameter.A second, very similar, tabulation 3jhas also been made available. Several other computer programmes are inuse for evaluation of energy levels, prediction of spectra from molecularmodels, and calculation of other quantities necessary for spectral analysis. 36Other papers deal with aspects of the computations, some 37 specifically fornearly symmetric rotors, others 38 more generally. Computation of thecentrifugal-distortion corrections to the energy levels has also receivedattention. 39General treatments of hyperfine struc-ture have appeared,40 and the case of an asymmetric rotor with resultantelectronic and nuclear spin has been disc~ssed.~l Papers have appeared onstrong-field Stark effects 42 and corrections to the Stark effect in linearmolecules.43 An extended table of “ line strengths,” useful in the analysisof fine-structures and field-effects as well as in dealing with line intensities,has appeared.44There are now many papers on theeffects of restricted internal rotation of methyl or silyl groups on micro-wave spectra.Lin and Swalen 45 give an extensive review up to 1959.Asymmetric-rotor energy Zevebs.Fine-structures and Jiebd-eSfects.Vibration-rotation interactions.33 C . H. Tomes, Phys. Rev. Letters, 1960, 5, 428.34 M. Sidran, F. Nolan, and J. W. Blaker, J . Mol. Spectroscopy, 1963, 11, 79.35 H. Dreizler and R. Peter, Tabellen zur Analyse von Rotationsspektren mitZentrifugalaufweitung und Torsionsfeinstruktur, Physikalisches Institut, Universityof Freiburg, W.Germany, August, 1963.R. Beaudet, Dissertation, Harvard University, 1961 ; F. Kneubuhl, T. Gaumann,and H. H. Gunthard, J . Mol. Spectroscopy, 1959,3,349; C. T. Fike, J . Chem. Phys., 1959,31, 568; N. Jannuzzi and S. P. S. Porto, J . MoZ. Spectroscopy, 1960, 4, 459; R. H.Schwendeman, ibid., 1961, 6, 301.37 S. C. Wait, jun. and M. P. Barnett, J . Mol. Spectroscopy, 1960,4, 93; H. L. Davisand J. E. Beam, ibid., 1961, 6, 312; J . Chem. Phys., 1960, 33, 1255.38 V. A. Genusa and P. M. Parker, J . Chem. Phys., 1962, 37, 2615; J. M. Bennett,I. G. Ross, and E. J. Wells, J . Mol. Spectrcscopy, 1960, 4, 342.39 G. Erlandsson, Arkiv. Fysik., 1959, 16, 181; G. A. Khachkuruzov, Optics andSpectroscopy, 1960, 9, 380; P. M. Parker, J . Chem.Phys., 1962, 37, 1596.40 D. W. Posener, Austral. J . Phys., 1958, 11, 1; K. K. Svidzinskii, Optics andSpectroscopy, 1961, 11, 385.41 R. F. Curl, jun. and J. L. Kinsey, J . Chem. Phys., 1961, 35, 1758.4a J. A. Howe and W. H. Flygare, J . Chem. Phys., 1962, 36, 650; B. G. West andM. Mizushima, ibid., 1963, 38, 25.4 3 M. Mizushima, Proceedings of the 4th Molecular Spectroscopy Conference,(Bologna, 1959), Pergamon, London, 1961, p. ‘!167.4 4 R. H. Schwendeman and V. W. Laurie, Table of Line Strengths,” Pergamon,London, 1958.45 C. C. Lin and J. D. Swalen, Rev. Mod. Phys., 1959, 31, 841164 GENERAL AND PHYSICAL CHEMISTRYTabulations of eigenvalues, coefficients, corrections, etc., which facilitateanalysis of the spectra, have been published.46 These partly extend to mole-cules with two similarly located rotor groups, on which work is very active,and for which the theory has been given in detail.*', 48, 49 Kirtman 50 hasdeveloped extensively the theory of effects of interactions between hinderedrotation and other vibrations on the rotational energy.The interactionbetween rotation and certain vibrations, particularly degenerate bendingmodes, has been treated in much closer detail, especially by Amat and hiscollaborator^,^^ and the analysis of certain spectra of vibrationally excitedmolecules has been considerably improved.Computation of Molecular Geometry from Rotational Constants.-Thederivation of reliable structure-parameters from average reciprocalmoments of inertia in known vibrational states has been recognised as acomplicated procedure, on account of zero-point energies, their changeson isotopic substitution, and anharmonicity in vibrations.It is nowgenerally accepted that substitution (rs-) parameters, obtained from thechanges of rotational constants for isotopic substitution a t each atom inturn, are closer to the equilibrium parameters than those of the r,-structure,which merely yield a best fit with ground-state rotational constants. Pre-ference has therefore been given in this Report to r,-structures when pos-sible, and it is probable that, in favourable cases, r,-distances are within afew thousandths of an Angstrom unit of the equilibrium distances.52Better ways of treating the data, however, with assistance from vibrationalinformation, are being sought, and it has been shown 53 that the averagemolecular configuration over the ground vibrational state can be computedfor simple molecules by using the harmonic force constants to correct therotational data.Although the derivation of equilibrium parameters requirescorrections depending on the little-known anharmonicity factors, theaverage parameters in the ground state have a well-defined physical meaning,and are calculated for some simple cases by Herschbach and L a ~ r i e . 5 ~ Theaverage distances exceed the ro- and r,-values, the differences usually beingless than 0.01 8.Such average distances should be close to similar average distancesdetermined by means of electron diffra~tion,~~ and this seems to be borneout where the data justify comparison.Differences between the r,-distanceand the electron-diffraction average have been demonstrated for CH and46 D. R. Herschbach, J. Chem. Phys., 1959, 31, 91 ; M. Hayashi and L. Pierce, ibid.,1961, 35, 1148; Tables for the Internal Rotation Problem, Parts I to VI, University ofNotre Dame, Indiana, 1963.4 7 R. J. Myers and E. B. Wilson, jun., J. Chem. Phys., 1960, 33, 186; H. Dreizler,2. Naturforsch., 1961, Ma, 477, 1354; H. Dreizler, H.-G. Schirdewahn, and B. Starck,ibid., 1963, 18a, 670.48 J. D. Swalen and C. C. Costain, J. Chem. Phys., 1959, 31, 1562.4 9 L. Pierce, J. Chem. Phys., 1961, 34, 498.5 0 B. Kirtman, J. Chem. Phys., 1962, 37, 2516.51 M.-L. Grenier-Besson, J. Phys. Radium, 1960, 21, 555; M.-L. Grenier-Besson,G.Amat, and H. H. Nielsen, J. Chem. Phys., 1962, 36, 3454; J. T. Hougen, ibid., 1962,37, 1433; S. Maes, J . Mol. Spectroscopy, 1962, 9, 204.52 C. C. Costain, J. Chem. Phys., 1958, 29, 864.5 3 D. R. Herschbach and V. W. Laurie, J. Chem. Phys., 1962, 37, 1668, 1687; Y.Morino, K. Kuchitsu, and T. Oka, ibid., 1962, 36, 1108SHERIDAN : MICROWAVE SPECTROSCOPY OF GASES 165CD bonds in methane,54 and, when each distance is appropriately correctedfor vibration, the equilibrium distances are in agreement.While certain factors must be neglected in deriving molecular geometryfrom rotation constants, there can be no doubt that many postulated featuresof the structures of molecules receive very strong support from the analyseswhich can be made at present, and these aspects have been emphasisedhere.Mo1ecula;r Structures.-Valuable literature summaries of microwave-structure determinations have recently appeared.That from the Univer-sity of Freiburg 55 lists all papers since 1945, classified according to thenature and symmetry of the molecules. A complete list of papers, includingmany on technique and theory, is issued by the University of Padova 56 for1954 onwards, in continuation of the bibliography of Townes and S c h a w l o ~ . ~ ~Work appeared on about a hundred molecules during the period. Aselection is classified here in accordance with chemical complexity andsimilarities, with some regard for spectroscopic features which are commonto groups of molecules.A small proportion of the microwave work in thisperiod was mentioned, in another context, in the Report by Millen andWhite in 1962.58Refined measurements continue on metallic halides.Rusk and Gordy 59 obtained new data in the millimetre ra,nge for all thealkali bromides and iodides, very sharp lines being obtained by passing thesubstances as beams across the cell. Microwave studies by the molecularbeam resonance method have added very accurate data on LiF60 andBa0.61 Equilibrium nuclear separations are quoted with uncertaintiesusually less than 0.0001 A. Detailed work on the monohalides of gallium,indium, and thallium 62 has been extended by German work 6 3 and by astudy of AlF.64 Ionic character, as indicated by quadrupole couplings inthese molecules, is clearly less than in the alkali halides.In A1F thecoupling of 27Al is almost the same as in the 2P3,2 state of aluminium,indicating a covalent bond. In TlBr the bromine coupling is remarkablylittle affected by vibration, while that of 1151n in InCl falls roughly linearlywith increasing mean bond length on vibrational excitation.The sameauthors report detection of SO, analysis being presumably complicated bymagnetic h e structure. Stark effects for deuterium halides in the 1 mm.54 L. S. Bartell, K. Kuchitsu, and J. R. deNeui, J. Chem. Phys., 1961, 35, 1211.5 5 B. Starck, Ber. Bunsen Gesellschaft Phys. Chem., 1963, 67,. 553,56 P. G. Favero, Microwave Gas Spectroscopy Bibliography, University of Padova,5 7 C. H. Townes and A.L. Schawlow, “ Microwave Spectroscopy,” McGraw-Hill,5 8 D. J. Millen and R. F. M. White, Ann. Reports, 1962, 59, 189.5 9 J. R. Rusk and W. Gordy, Phys. Rev., 1962, 127, 817.6o L. Wharton, W. Klemperer, L. P. Gold, R. Strauch, J. J. Gallagher, acd V. E.61 L. Wharton and W. Klemperer, J. Chem. Phys., 1963, 38, 2705.62 A. H. Barrett and M. Mandel, Phys. Rev., 1958, 109, 1572.63 H. G. Fitzky, 2. Physilc., 1958, 151, 351; J. Hoeft, ibid., 1961, 163, 262.64D. R. Lide, jun., J. Chem. Phys., 1963, 38, 2027.6 5 R. Kewley, K. V. L. N. Sastry, M. Winnewisser, and W. Gordy, J. Chem. Phys.,Diatomic molecules.Refined data on the short-lived molecule CS are given.651963.New York, 1955.Derr, J. Chem. Phys., 1963, 38, 1203.1963, 39, 2856I66 GENERAL AND PHYSICAL CHEMISTRYregion are reported,66 and also Zeeman effects and molecular g-factors.67A thorough study of six isotopic forms of carbon monoxide68 includesmeasurement of isotopic effects on rotational magnetic moment, and allows,for the first time, fairly confident conclusions about the sign-orientation of amolecular dipole, here CO.Data for TI 68 and DI 67 similarly allow thedirection DI to be deduced; here, though not in CO, the conclusion followsexpectations based on electronegativities. The spectrum of IBr, with itscomplex nuclear coupling, has been assigned;69 the nuclear effects show theexpected evidence of a contribution from BrI.Nitric oxide has now been studied in both the 2111,2 and 2r13,2 states.70The Stark effect in the former state 71 fits predictions 72 and yields a dipolemoment of 0.158 & 0.006 D.Theoretical work on fine-structures in spectraof NO has continued.73 The Stark effect of the A-doublet line of OH 7 4meets difficulties in resolution and interpretation, but a dipole moment of1.65 & 0.25 D is deduced.New examples studied in the period are fluorinecyanide and fluoroacetylene, while new data on isotopic forms of otherhalogen cyanides and chloroacetylene '5 have allowed extensive determina-tion of r,-distances in these molecules. The CF bonds are the shortest yetfound, that in FCN being only 1.262 A in length. The CN distance is1.159 13, in all the halogen cyanides, although there is a considerable variationin nitrogen quadrupole coupling along the series.The unstable substanceHCP has been studied;7s it contains what is probably the first carbon-phosphorus triple bond to be measured, of length 1.542 & while the dipolemoment, 0.390 & 0.005 D, is only one-tenth of that of HCN. Other workon linear molecules is largely concerned with the force fields. Thus veryhigh transitions of BrCN6 allow estimation of the higher-order stretchingconstant, H , in the term following the usual DJ correction; H is only aboutone-millionth of DJ. The Z-type doublet spectra of HCN have been studied 7 7for four new isotopic forms.Xymmetric-top molecules. A full account has been published of thespectra of ReO,F, ReO,Cl, and Mn0,Cl.78 The quadrupole coupling of the-4-+-- +Linear molecules.66 C.A. Burrus, J . Chem. Phys., 1958, 28, 427; 1959, 31, 1270.6 7 C. A. Burrus, J. Chem. Phys., 1959, 30, 976.* 8 B. Rosenblum, A. H. Nethercot, jun., and C. H. Tomes, Php. Rev., 1958, 109,e 9 T. S. Jaseja, J . Mol. Spectroscopy, 1960, 5, 445.'O P. G. Favero, A. M. Mirri, and W. Gordy, Phys. Rev., 1959, 114, 1534.71 C. A. Burrus and J. D. Graybeal, Phys. Rev., 1958, 109, 1553.7 2 M. Mizushima, Phys. Rev., 1958, 109, 1557; 1958, 111, 1746.73 C. C. Lin, Phys. Rev., 1960,119, 1027; C. C. Lin, K. Hijikata, and M. Sakamoto,J . Chem. Phys., 1960, 33, 878; M. Yamazaki, M. Sakamoto, K. Hijikata, and C. C. Lin,ibid., 1961, 34, 1926.74R. T. Meyer and R. J. Myers, J . Chem. Phys., 1961, 34, 1074.7 s J. K. Tyler and J. Sheridan, Trans. Faraday SOC., 1963, 59, 2661.76 J.K. Tyler and J. W. C. Johns, Symposium on Molecular Structure and Spectro-7 7 T. Torring, 2. Physik., 1961, 161, 179.7 8 J. F. Lotspeich, A. Javan, and A. Engelbrecht, J . Chem. Phys., 1959, 31, 633;400.scopy, Ohio State Univ., 1963.J. F. Lotspeich, ibid., p. 643SHERIDAN: MICROWAVE SPECTROSCOPY O F GASES 167metal atoms shows effects of atom-core polarisation ; in Re0,F the p-electronunbalance in the symmetry axis is almost zero, accounting for the strongdependence of the coupling on vibrational state. The substance NSF, isa C,, molecule, of structure N=SF3;79 rs(SN) is 1.416 A, acceptable for atriple bond, while the angle FSF, at 94", shows a tendency towards octa-hedral geometry. The nitrogen coupling constant, + 1.19 Mc./sec., is quitedifferent from that of a cyanide nitrogen.Silyl cyanide 8o is the normalcyanide, with the expected nitrogen coupling; r,(CSi) is 1.850 8, only0.017 A shorter than that in methylsilane. In silylacetylene,81 r,(CSi) isnoticeably shorter at 1.826 8. These CSi lengths do not parallel the CClengths in methyl cyanide and methylacetylene, which are equal and muchless than that in ethane; the differences in the CSi lengths are possibly dueto H,Si=C=X being more stable when X = CH than when X = N.There is-little evidence of hyperconjugation by SiH, in SiH,CN. Silylisothiocyanate is a symmetric top,s2 the rs length of the linear SiNCS chainbeing 4.486 8; the SiN distance, 1-71 8, reflects the double-bond characterof the form H,Si=N-C=S, the contribution of which decides the molecularsymmetry.Silyl azide 83 is reported to be an asymmetric top, and henceto have a non-linear SiN, group; the charge distribution in H,Si=N=N=Nperhaps prevents it being important. The C,, molecules SF,Cl 84 andSF,Br 85 have been studied; r,(SCl), at 2-030& is a little longer than mostSC1 linkages, and a similar situation probably holds for SBr. Steric effects,involving also displacement of the equatorial fluorines towards the axialfluorine, may be responsible. The substances C,H,Tl, C,H5Mn( CO),,C,H,Cr(CO),, and C,H,NiNO 86 are cases where the presence of symmetryaxes (Sfold and higher) can be readily proved by the regularity of thespectra. The bonding round thenickel is very strong, while the CT1 distances are large, probably on accountof ionic character.A number of symmetric tops studied contain internally rotating groups.A full structure of methylgermane 87 was obtained from 28 isotopic forms;although the CGe bond has an r,-length as great as 1.9458, the internalbarrier remains fairly high, 1239 2 25 cal./mole.Quadrupole coupling of73Ge is very small, .showing very little asymmetry in the electrons at that7 9 W. H. Kirchhoff and E. B. Wilson, jun., J . Amer. Chern. SOC., 1962, 84, 334.J. Sheridan and A. C. Turner, Proc. Chem. SOC., 1960, 21: N. Muller and R. C.Bracken, J . Chent. Phys., 1960, 32, 1577; J. Sheridan, A. P. Cox, J. K. Tyler, L. F.Thomas, and A. C. Turner, Arch. Sci., 1960, 13, Pasc. special, 135.81 J.S. Muenter and V. W. Laurie, J . Chem. Phys., 1963, 39, 1181.82 D. R. Jenkins, R. Kewley, and T. M. Sugden, Trans. Faraday Soc., 1962,58,1284.83 E. A. V. Ebsworth, D. R. Jenkins, M. J. Mays, and T. M. Sugden, Proc. Chem.84 R. Kewley, K. S. R. Murty, and T. M. Sugden, Trans. Faraday Xoc., 1960, 56,s s E . W. Neuvar and A. Jache, J . Chem. Phys., 1963, 39, 596.86 J. K. Tyler, A. P. Cox, and J. Sheridan, Nature, 1959, 183, 1182; A. P. Cox,L. F. Thomas, and J. Sheridan, ibid., 1958, 181, 1157.87 V. W. Laurie, J . Chem. Phys., 1959, 38, 1210; A. I. Barchukov and A. M.Prokhorov, Optilca i Spektroskopiya, 1958, 4, 799; A. I. Barchukov and Y. N. Petrov,ibid., 1961, 11, 129.+ -+ -- + + -The NiNO group must also be linear.SOC., 1963, 21.1732168 GENERAL AND PHYSICAL CHEMISTRYnucleus. In methylstannane 88 the barrier is considerably lower, 650 & 30cal./mole.Many molecules with three symmetrically disposed methylgroups have been studied. In trimethylamine, 89 trimethylphosphine,90 andtrimethylarsine 91 the internal barrier falls progressively from about 4400cal./mole in Me,N to about half that value in Me,As; similarly, the barrierin isobutane exceeds that in trimethyl~ilane.~~ The structures of thelast two compounds, and also of t-butyl fluoride, chloride, cyanide, andt - butylacetylene 93 have been extensively studied by isotopic substitution,and the quadrupole couplings in t-butyl chloride 93 and bromide 94 deter-mined. The CX bond in Me,CX is in general longer than that in MeX, andthe former also is more ionic when X is a halogen.The dipole moment ofMe,CD is 6-7% higher than that of Me,CH, an unusually large change foran isotopic substitution.95A number of papers deal with vibrational effects in symmetric-topspectra. Assignment of spectra of molecules in degenerate bending modeshas improved with the use of more refined theory,51, 96 to the point whereinformation on the force field so obtained is much more reliable. A verythorough study of rotation spectra of vibrationally excited fluoroformmolecules 97 shows anomalies which will doubtless stimulate further studiesof vibrational perturbations of rotational levels.Non-linear triatornic molecules. Work continues on the hyperfinestructures in the spectra of HDO and D20, with absorption cells 7 3 98 andwith beam masers.99 Lines only a few kc./sec.wide are obtained withlarge cavity cells. Analysis yields the value of the electric-field-gradienttensor a t the hydrogen nucleus. Extension of the work on H2Se loo allowsaverage ground-state distances to be stated to less than 0.001 8, withr,(SeH) = 1.460 & 0.003 8; the average and equilibrium HSeH angles areboth within a few minutes of 90" 50'.Centrifugal-distortion treatment, with vibrational data, yields, in addition to forceconstants, a ground-state average OF distance of 1.412 8 and an averageangle of 103" 10'; the dipole moment is 0-297 0.005 D. Magnetic hyper-fine splittings have been analysed for high-J transitions of F20.102 InOxygen difluoride, F20,101 has been studied in detail.S a p . Cahill and S.Butcher, J. Chem. Phys., 1961, 35, 2255.8g D. R. Lide, jun. and D. E. Mann, J. Chem. Phys., 1958, 28, 572.D. R. Lide, jun. and D. E. Mann, J. Chem. Phys., 1958, 29, 914.91 D. R. Lide, jun., Xpectrochim. Acta, 1959, 15, 473.9 2 L. Pierce and D. H. Petersen, J. Chem. Phys., 1960, 33, 907.93 D. R. Lide, jun. and M. Jen, J. Chem. Phys., 1963,38,1504; W. Zeil, W. Huttner,94 W. Zeil, M. Winnewisser, and W. Huttner, 2. Naturforsch., 1961, lea, 1248.Q 5 D . R. Lide, jun., J. Chem. Phys., 1960, 33, 1519.Q6 M.-L. Grenier-Besson and G. Amat, J. Mcl. Spectroscopy, 1962, 8, 22; G. G.Weber, ibid., 1963, 10, 321; P. Venkateswarlu, J. G. Baker, and W. Gordy, ibid., 1961,6, 215; C. Matsumura, E.Hirota, T. Oka, and Y. Morino, ibid., 1962, 9, 366.and W. Plein, 2. Naturforsch., 1962, Ira, 823.9 7 C. C. Costain, J. Mol. Spectroscopy, 1962, 9, 317.D. W. Posener, Austral. J. Phys., 1960, 13, 168.99 P. Thaddeus and J. Loubser, Nuovo cim., 1959, 13, 1060.loo T. Oka and Y. Morino, J. Mol. Spectroscopy, 1962, 8, 300.lol L. Pierce, R. H. Jackson, and N. DiCianni, J. Chem. Phys., 1961, 35, 2240;1°2L. Pierce and N. DiCianni, J. Chem. Phys., 1963, 38, 2029.L. Pierce, N. DiCianni, and R. H. Jackson, ibid., 1963, 38, 730SHERIDAN : MICROWAVE SPECTROSCOPY O F GASES 169C1,O 103 the quadrupole coupling constant of 35Cl in the bond direction hasthe unusually high value of - 143Mc./sec., ascribed to contributions ofMuch work on chlorine dioxide has appeared,l**, 4 l and reasonably firmconclusions have been reached regarding rotational constants of threeisotopic forms and assignment of fine structures.The splittings can bereasonably accounted for with a model having the odd electron in a b, anti-bonding orbital. Stark effects yield a dipole moment of 1.784 * 0.01 D, andthe Zeeman effect fits expectation for interaction of a free electron with themagnetic field. Other theoretical work on hyperfine constants in bothC10, and NO, has appeared.lo5Nitrosyl chloride enriched with oxygen- 18 has been investigated. lo6The geometry and the quadrupole coupling of chlorine about the NC1 bondsuggest that this linkage has both considerable ionicity and appreciabledouble-bond character. The substance NSF has the bent structureNeS-F, lo7 contrary to earlier indications. Both bonds are considerablylonger than those joining the same atoms in NSF3.79 The electron-diffrac-tion worklo* which favoured the SNF arrangement obviously needsrepeating.Bond lengths and dipole moment were obtained log for the unstablespecies S,O, present in the products of a discharge in S + SO,, illustratingthe power of microwave spectroscopy not only to identify unstable sub-stances, but also to establish details of their structure.Other planar molecules.There has been much work on formalde-hyde.ll0, 32 Structure parameters have been refined, while Zeeman effectsand the fine-structures resolved in maser work have given additional informa-tion about the electronic structure. The substituted formaldehydes,HCOF,ll1 COF,,l12 and COFCl 113 have been studied; in HCOF the CFlength is 1.34 A and the CO distance 1.18 A, while in COP, the CF bond isshorter, 1.312 8.The CF and CO distances quoted for COFCl seem shorterthan expected, but work on more species is needed in this case.Nitryl chloride, NO2Cl,ll4 has a considerably shorter NC1 distance, anda considerably longer NO distance, than were found in nitrosyl chloride.106Quadrupole effects show that the C1N bond in N0,Cl has less ionic character,and less double-bond character, than that in MQC1. The structure of nitricacid, based on data for three isotopic forms, has been given.115 Of themany studies of formic acid, mention may be made of those 116 from whichimproved structure parameters are derived, and which show that the dipolemoment is directed a t 42.4 & 2" to the C=O, along a line roughly joiningthe two oxygen atoms.Accurate internuclear distances in keten 117 and diazomethane 118 havebeen obtained by means of the substitution method.The HCH angle indiazomethane (126.1") is very probably larger t h m that in keten (122.6").Measurement of relative intensities of keten lines in the ground and vibra-tionally excited states 119 has greatly clarified the assignment of the lowestfundamental modes, the results being confirmed by new infrared work.l2ODiazomethane, though very unstable, was studied in great detail. Thebond lengths and nuclear quadrupole couplings in general confirm theaccepted structure, but the non-terminal nitrogen nucleus has a moreasymmetric electronic environment than would be predicted, or than isfound from the nuclear coupling of the analogous nitrogen in hydrazoicacid.Millimetre-wave measurements on HNCO and HNCS lZ2 have con-siderably refined the data for these substances.Formaldoxime, though not very stable, has been studied very effec-tively.123 The molecule is planar, the OH bond, contrary to predictions frominfrared studies, being directed away from the CH, group. A full r,-structurewas obtained, and it is notable that the CH, group is not symmetric aboutthe NC direction, being tilted 3" away from the side of the NO bond.The study of propynal 124 was especially thorough; the complete rs-structure demonstrates the likelihood of a small bend (about 1.5") mainly a tthe central carbon of the formally linear CCCH chain.A large group of papers deals with substituted ethylenes. Vinylfluoride,125 chloride,126 and bromide 127 have all been extensively investi-114 D.J. Millen and K. M. Sinnott, J., 1958, 350; L. Clayton, Q. Williams, and T. L.Weatherly, J. Chern. Phys., 1959, 30, 1328; 1959, 31, 554.115 D. J. Millen and J. R. Morton, J., 1960, 1523.116 H. Kim, R. Keller, and W. D. Gwinn, J . Chem. Phys., 1962, 37, 2748; G. H.Kwei and R. F. Curl, jun., ibid., 1960,33, 1592; A. M. Mirri, Nuovo cim., 1960, 18, 849.1 1 7 A. P. Cox, L. F. Thomas, and J. Sheridan, Spectrochim. Acta, 1959, 15, 542.118 A. P. Cox, L. F. Thomas, and J. Sheridan, Nature, 1958, 181, 1000; J.Sheridan,Proceedings of the Molecular Spectroscopy Conference (Bologna, 1959), Pergamon,London, 1961, p. 139.l19A. P. Cox and A. S. Esbitt, J. Chern. Phys., 1963, 38, 1636.lZo C. B. Moore and G . C. Pimentel, J . Chem. Phys., 1963, 38, 2816.1 2 1 R. A. Forman and D. R. Lide, jun., J. Chem. Phys., 1963, 39, 1133.122 R. Kewley, K. V. L. N. Sastry, and M. Winnewisser, J. MoZ. Spectroscopy, 1963,123 I. N. Levine, J. Mol. Spectroscopy, 1962, 8, 276; J . Chem. Phys., 1963, 38, 2326.124 C. C. Costain and J. R. Morton, J. Chern. Phys., 1959, 31, 389.125 D. R. Lide,. jun. and D. Christensen, Spectroclzim. Acta, 1961, 17, 665; A. M.126 D. Kivelson, E. B. Wilson, jun., and D. R. Lide, jun., J. Chern. Phys., 1960, 32,127 R. E. Goedertier, Ann.SOC. sci. Bruxelles, 1961,75,174; S . de Hepct5e, ibid., p. 194.10, 418.Mirri, A. Guarnieri, and P. G. Favero, Nuovo cim., 1961, 19, 1189.205SHERIDAN : MICROWAVE SPECTROSCOPY OF GASES 171gated; earlier views on their structures appear to be mainly confirmed.Work on difluorethylenes 128 extends to many species, and indicates a pro-gressive shortening of both the CC and CF bonds as ethylene is increasinglyfluorinated. Data on C ~ ~ - C H F C H C ~ , ~ ~ ~ C~S-CKC~CHC~,~~~ and CF2CHC1 131show chlorine couplings which generally conform to expectation. Accuratedistances were determined for vinyl cyanide.132 In f l ~ o r o p r e n e , ~ ~ ~ a planartrans-butadiene skeleton is established, although the effects of easy torsionaloscillation are apparent.A substance with some formal similarity to theforegoing is difluorodiazine, N2F2; spectra of the cis-PN=NF form 134indicate an NN distance of 1.214 -+ 0.005 A.Bak and his collaborators have obtained complete r,-structures offuran 135 and thiophen l 3 6 and all the parameters of pyridine 13' fromextensive isotopic enrichment work. A complete r,-study was also made ofbenzonitrile.138 Although in the range where molecular complexity couldbegin to limit the accuracy as compared with simpler structures, the placingof all atoms in such cases is a notable achievement, indicating as probablesuch features as the close similarity of both CC bond lengths in pyridine,and the slight distortion of the benzene ring by the CN group. Otheraromatic ring structures being similarly studied are thiazole and thia-diaz01es.l~~ Nitrobenzene l 4 1 and phenol 142 are planar; in the latter, thetwo-fold barrier to OH rotation is assessed as 3150 & 300 cal./mole.Rota-tional analysis of the spectrum of 2-fluoronaphthalene has been made;143this represents approximately the upper limit of molecular size for effectivestudy, and the authors give a critical survey of the factors affecting moredetailed investigation.Discussion will first be restrictedt o cases where there are no major effects due to torsion or inversion of groups.One of the simplest cases is difluoroamine, NHF2,144 which proved to beNon-planar mymmetric-top molecules.128 V. W. Laurie, J . Chern. Phys., 1961, 34, 291; V. W. Laurie and D.T. Pence,129 J. A. Howe, J . Chem. Phys., 1961, 34, 1247.130 W. H. Flygare and J. A. Howe, J . Ghem. Phys., 1962, 38, 440.131 D. R. Jenkins and T . M. Sugden, Trans. Faraday SOC., 1959, 55, 1473.132 C. C. Costain and B. P. Stoicheff, J . Chem. Phys., 1959, 30, 777.133 D. R. Lide, jun., J . Chem. Phys., 1962, 3'9, 2074.134 R. L. Kuczkowski and E. B. Wilson, jun., J . Chem. Phys., 1963, 39, 1030.135 B. Bak, D. Christensen, W. B. Dixon, L. Hansen-Nygaard, J. Rastrup-Andersen,and M. Schottliinder, J . Mol. Spectroscopy, 1962, 9, 124.136 B. Bak, D. Christensen, L. Hansen-Nygaard, and J. Rastrup-Andersen, J . MoZ.Spectroscopy, 1961, 7, 58.B. Bak, L. Hansen-Nygaard, and J. Rastrup-Andersen, J . Mol. Spectroscopy,1958, 2, 361r138 B.Bak, D. Christensen, W. B. Dixon, L. Hansen-Nygaard, and J. Rastrup-Andersen, J. Chem. Phys., 1962, 37, 2027.139 B. Bak, D. Christensen, L. Hansen-Nygaard, and J. Rastrup-Andersen, J . Mol.Spectroscopy, 1962, 9, 222.14'JB. Bak, D. Christensen, L. Hansen-Nygaard, L. Lipschitz, and J. Rastrup-Andersen, J . Mol. Spectroscopy, 1962, 9,225; V. Dobyns and L. Pierce, J . Amer. Chem.Soc., 1963, 85, 3553.ibid., 1963, 38, 2693.141 K. E. Reinert, 2. Naturforsch., 1960, 15a, 85.142 T. Kojima, J . Phys. SOC. Japan, 1960, 15, 284.B. Bak, D. Christensen, L. Hansen-Nygaard, and J. Rastrup-Andersen, Spectro-chim. Acta, 1962, 18, 229.144 D. R. Lide, jun., J . Chem. Phys., 1963, 38, 456172 GENERAL AND PHYSICAL CHEMISTRYsuitable for particularly full investigation.The NF bonds, as expectedfrom data on similar systems, are slightly longer than those in NF3. Thedipole moment of 1.93 rfr 0.02 D makes an angle of 19" with the NH bond.Nuclear quadrupole effects were interpreted to give a complete field-gradienttensor. In N2F4145 a form with a dihedral angle of 60-70" between theNF, groups was found. The related F202 molecule (FO-OF) 146 has adihedral angle of 87.5 & 0.5"; the OF distance is longer than that in F,O 101by 0.16 8, while the 00 distance, 1-217 0.003 8, is very short, and possibleexplanations are discussed. Sulphur monofluoride, S,F,, gave spectra dueto FS-SF7l4' but also lines due to the isomer S=SF2,1*8 in further demon-stration of the diagnostic powers of the method. Study of sulphurtetrafluoride 149 defines the structure much more closely than previously,the greater length of the polar SF bonds, as compared with the equatorialones, being clear.Very accuratemeasurement of quadrupole effects in CH,CI, l50 fail to reveal appreciablebending of CC1 bonds.Other substances investigated are CHF2C1,l51CH,FCN, prop- 2 - yn yl fluoride , 154 chloride, 155 bromide , 156and malononitrile. 15' In general, the results follow expectation, but closercomparisons will be possible when further isotopic forms have been studied.Spectra of malononitrile in excited vibrational states were unusually fullyanalysed. 158Two three-ring molecules of low stability, cyclopropene 159 and dia-zirine,l60 both proved to be suitable for detailed structure determinations.Cyclopropyl derivatives were investigated, 161 1 , l -dichlorocyclopropane inparticular; 162 quadrupole effects in its spectrum showed no indication ofbent CC1 bonds.A rather full examination of cyclobutanone 163 led to theview that the C,-ring is planar. Bromocyclobutane 164 and cyclopentene 165were studied; in the latter, the plane of the three saturated carbon atoms isThere are many studies of simple methane derivatives.CH,CICN,145 D. R. Lide, jun. and D. E. Mann, J . Chem. Phys., 1959, 31, 1129.148 R. H. Jackson, J., 1962, 4585.1 4 7 R. L. Kuczkowski, J . Amer. Chem. Soc., 1963, 85, 3047.1 4 8 R. L. Kuczkowski and E. B. Wilson, jun., J . Amer. Chem. SOC., 1963, 85, 2028.1 4 9 W. M. Tolles and W. D. Gwinn, J .Chem. Phys., 1962, 36, 1119.150 W, H. Flygare and W. D. Gwinn, J . Chem. Phys., 1962, 36, 787.151 E. L. Beeson, T. L. Weatherly, and Q. Williams, J . Chem. Phys., 1962, 37, 2926;152 B. E. Job and J. Sheridan, Nature, 1961,192,160; J. D. Graybeal and D. W. Roe,153 I<. Wada, Y. Kikuchi, C. Matsumura, E. Hirota, and Y . Morino, Bull. Chem. SOC.154 B. E. Job and J. Sheridan, Nature, 1962, 193, 677.155 E. Hirota and Y . Morino, Bull. Chem. SOC. Japan, 1961, 34, 341.156 Y. Kikuchi, E. Hirota, and Y . Morino, Bull. Chem. Soc. Japan, 1961, 34, 348.157 E. Hirota and Y . Morino, Bull. Chem. SOC. Japan, 1960, 33, 158, 705.158 E. Hirota, J . Mol. Spectroscopy, 1961, 7, 242.159 P. H. Kasai, R. J. Myers, D. F. Eggers, jun., and K. B. Wiberg, J . Chem. Phgs.,180 L.Pierce and V. Dobyns, J . Amer. Chem. Soc., 1962, $4, 2651.le2 W. H. Flygare, A. Narath, and W. D. Gwinn, J . Chem. Phys., 1962, 36, 200.163 A. Bauder, F. Tank, and H. H. Gunthard, Helv. Chim. Acta, 1963, 46, 1453.164 W. G. Rothschild and B. P. Dailey, J . Chem. Phys., 1962, 36, 2931.1 G 5 G. W. Rathjens, jun., J . Chern. Phys., 1962, 36, 2401.D. B. McLay and C. R. Mann, Canud. J . Phys., 1962, 40, 61.J . Chem. Phys., 1962, 37, 2503.Japan, 1961, 34, 337.1959, 30, 512.J. P. Friend and B. P. Dailey, J . Chem. Phys., 1958, 29, 577SHERIDAN : MICROWAVE SPECTROSCOPY OF GASES 173inclined at about 22" to the plane of the remainder of the ring. Possibilitiesof investigating ring-flexing vibrations in similar systems are emphasisedby the success of the work of Gwinn and his co-workers on tri-methyleneoxide,166 which revealed considerable detail about the double-minimumpotential of the ring-puckering motion.Thelast-mentioned molecules might well have been placed in this group, thusillustrating the arbitrary nature of such classifications.Effects of easyinversion of NH, groups on microwave spectra have recently been wellrecognised in amides, which might be termed quasi-planar molecules in thesense that the -NH, pyramid is rather readily inverted about the plane ofthe rest of the molecule. These effects were first detected in f ~ r m a r n i d e , ~ ~ ~and carefully studied by means of isotopic substitutions. They are alsovery apparent in the spectrum of cyanamide. The double-minimumform of the potential function for inversion leads to an abnormally lowfirst vibrational level. In cyanamide, perturbations of rotational levels bylow vibrational levels are noted.In nitramide 1 G 9 inversion splitting producesan exceptionally low excited level, possibly less than 10 cm.-l above theground level in NH,NO,; in ND,NO, the upper level is only about 1 cm.-labove the ground level, and a microwave inversion spectrum is observednear 1 cm. wavelengths. Rotational constants were assigned for each low-lying state of three isotopic forms of nitramide. Such studies emphasisethe power of microwave spectroscopy to reveal subtle detail of molecularforce fields.Inversion and torsion are both possible in hydrazine, and the complexspectra have now been analysed 170 to give values of the energy-barriersconcerned with each.Further work on methanethiol 1 7 1 indicates that thetorsion potential is sinusoidal to better than 1%.a barrier of 1960 & 20 cal./mole is found.Ethyl fluoride,173 chloride,174 and bromide 175 have been extensivelystudied by means of isotopic substitution. I n the chloride and bromide,the CC bonds are both close to 1.52 A in length, and corrected values forthe torsion barriers are equal a t 3685 cal./mole. It may be noted that theV6 term in the potential restricting rotation has been estimated from infra-red data for ethyl fluoride 176 as -15 cal./mole; it is believed 177 that V6for methyl groups generally does not exceed 3% of Y3, and may be of either166 S.I. Chan, J. Zinn, J. Fernandez, and W. D. Gwinn, J . Chem. Phys., 1960, 33,1643; S . I. Chan, J. Zinn, and W. D. Gwinn, ibid., 1961, 34, 1319.167 C. C. Costain and J. M. Dowling, J . Chem. Phys., 1960, 32, 158.IB8 J. K. Tyler, L. F. Thomas, and J. Sheridan, Proc. Chem. Soc., 1959, 155; J . Opt.SOC. Amer., 1962, 52, 581; D. R. Lide, jun., J . Mol. Spectroscopy, 1962, 8, 142; D. J.Millen, G. Topping, and D. R. Lide, jun., ibid., p. 153.lB9 J. K. Tyler, J . Mol. Spectroscopy, 1963, 11, 39.170 T. Kasuya and T. Kojima, J . Phys. SOC. Japan, 1963, 18, 364.171 T. Kojima, J . Phys. SOC. Japan, 1960, 15, 1284.172 T. Kojima, E. L. Breig, and C. C. Lin, J . Chem. Phys., 1961, 35, 2139.173 B. Bak, S. Detoni, L. Hansen-Nygaard, J. T. Nielsen, and J. Rastrup-Andersen,174R. H. Schwendeman and G. D. Jacobs, J. Chem. Phys., 1962, 36, 1845.175 C. Flanagan and L. Pierce, J . Chem. Phys., 1963, 38, 2963.176 G. Sage and W. Klemperer, J . Chem. Phys., 1963, 39, 371.17' W. G. Fateley and F. A. Miller, Spectrochim. Acta, 1963, 19, 611.Asymmetric-top molecules showing eflects of inversion or torsion.In methylphosphineSpectrochim. Acta, 1960, 16, 376174 GENERAL AND PHYSICAL CHEMISTRYsign. Barrier heights have also been estimated for ethyl iodide 178 andethyl cyanide.179 Careful work on the quadrupole effects in ethyl chlorideand bromide 1749 175 indicates a virtually cylindrical field about the carbon-halogen bond, with very little evidence of bond bending.The elegant studies of the barrier problem in epoxypropane have beenfully published, 203 and a new investigation of thioepoxypropane 204 confirmsthat its barrier (3240 & 160 cal./mole) is some 700 cal./mole higher thanthat in epoxypropane, as indicated by infrared weasurements.The rs-structures of dimethyl ether 205 and dimethyl sulphide 206, 207 have beendetermined. I n each, the methyl groups are staggered with respect to theopposite CO or CS bond, and are tilted away from each other by smallangles. Torsion effects in dimethyl sulphide have been studied in greatdetail, particularly by Dreizler and R~dolph,~O~ and Rudolph 208 has alsoaccurately predicted centrifugal corrections to the spectra. Orientation ofthe methyl groups is similar in propane;194 this, and similar work on hydro-carbons, is remarkable in view of the small dipole moments of some of thesubstances, that of propane being determined as 0.083 &- 0.001 D. Veryfull data are available for dimethyl~ilane,~~ and work has recently appearedon dimethylphosphine. 209 Acetone 48 and isobutene 210 are carefully studiedcases where two methyl groups are attached to a trigonal carbon atom. I nisobutene a CH bond of each methyl group lies in the C,-plane, pointingaway from the double-bond axis; the barrier is reported to be considerablyhigher than in acetone. The barrier in ~is-2,3-epoxybutane,~~~ where twomethyl groups are attached to different atoms of a ring, has been deter-mined as 1607 & 150 cal./mole.Microwave spectroscopy is proving to be a powerful tool in the studyof rotational isomerism. Thus n-propyl fluoride 312 exists as trans- andThe situation in nitric acid 115 is comparable.Work on double-top molecules has been extremely active.2oo J. M. O’Reilly and L. Pierce, J . Chem. Phys., 1961, 34, 1176.201 R. F. Curl, jun., J . Chem. Phys., 1959, 30, 1529.2n2 W. B. Dixon and E. B. Wilson, jun., J . Chem. Phys., 1961, 35, 191.203 D. R. Herschbach and J. D. Swalen, J . Chew%. Phys., 1958, 29, 761.204 S . S . Butcher, J . Chem. Phys., 1963, 38, 2310.2n5 U. Hlukis, P. H. Kasai, and R. J. Myers, J . Chenz. Phys., 1963, 38, 2753.206 L. Pierce and M. Hayashi, J . Chem. Phys., 1961, 35, 479.207 H. Dreizler and H. D. Rudolph, 2. Naturforsch., 1962, Ira, 712.208 H. D. Rudolph, 2. Naturforsch., 1962, Ira, 288.209 R. Nelson, J . Chem. Phys., 1963, 39, 2382.210 V. W. Laurie, J . Chem. Phys., 1961, 34, 1516; L. H. Scharpen and V. W. Laurie,211 M. L. Sage, J . Chem. Phys., 1961, 35, 142.212 E. Hirota, J . Chem. Phys., 1962, 37, 283.ibid., 1963, 39, 1732176 GENERAL AND PHYSICAL CHEMISTRYgauche-forms in the gas phase, the latter being more stable by about 0.5lrcal./mole. Barriers to methyl rotation, and the components of the dipolemoment, were determined for each isomer. The gauche-form is unusual inthat dipole components in all three inertial axes were measured. Similar,but less precise, results are reported for n-propyl chloride,213 and spectra oftrans- and gauche-forms of butyronitrile 214 have also been assigned. Wemay expect much further activity here, as in other parts of the field, onaccount of the unrivalled ability of microwave spectroscopy to give clear-cut precise information about details of molecules.213 T. N. Sarachman, J . Chem. Phys., 1963, 39, 469.214 E. Hirota, J . Chem. Phys., 1962. 37, 2918

ISSN:0365-6217    

DOI:10.1039/AR9636000007

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

INORGANIC CHEMISTRY*1. INTRODUCTIONBy A. K. Holliday and D. NichollsTHE number of papers published has increased markedly this year and someaspects of the subject have necessarily received only the briefest treatment.It has been thought desirable to maintain overall coverage of the subjectrather than to review some specific topics in more detail despite the obviousconsequences. The year’s most spectacular advances have been concernedwith the noble-gas compounds. It is now clear that, for xenon at least,an extensive chemistry exists and that the noble gases properly belong to agroup beyond Group VII in the Periodic Table. The designation “ GroupVIII ” is, however, still used, as in the original Mendeleef Table, to meanthe “transitional triads ” (e.g., Fe, Co, Ni), and we have preferred to retainthe unambiguous “ Group 0 ” for the noble gases.“Inert ” or “rare ”are now inappropriate for the description of these gases; the name “ aero-gens ” has been suggested.1 Other rapidly developing areas of study amongthe typical elements include the new boron-carbon family (the carboranes),the stereochemistry of tin( IV), and compounds containing sulphur-fluorinebonds. Improved methods of synthesis and of structure determinationhave shown the great ease with which ring structures containing two, three,or more typical-element atoms can be formed; these commonly range fromdimeric t o hexameric forms.Much attention has been paid to the preparation and development ofnew ligands, and the boundary between inorganic and organic chemistrybecomes increasingly difficult to define.Spectacular structural discoverieshave been made this year using X-ray diffraction techniques and it seemslikely that this field will provide most important results in the next fewyears.The first volume of a new collection, “ Technique of Inorganic Chem-istry,” has appeared,2 as has Vol. VII of “ Inorganic Syntheses.” 3 Generalreviews published during the year are concerned with the Mossbauer effect,4uses of electrical discharges in preparative inorganic chemistry, reactionswitsh arc-heated gases, perfluoroalkyl derivatives of the elements, inorganicIR. M. Noyes, J. Amer. Chem. SOC., 1963, 85, 2202.“ Technique of Inorganic Chemistry,” ed. H. B. Jonassen and A. Weissberger,Inorg. Synth., 1963, ‘7.E.Fluck, W. Kerler, and W. Neuwirth, Angew. Chem., 1963, 75, 461; P. R.Brady, P. R. F. Wigley, and J. F. Duncan, Rev. Pure Appl. Chem., 1962, 12, 165.A. G. Massey, J . Chew&. Educ., 1963, 40, 311.H. Harnisch, G. Yemer, and E. Schallus, Angew. Chem., Internat. Edn., 1963, 2,H. C. Clark, Adv. Fluorine Chem., 1963, 3, 19.Vol. I, Interscience, New York, 1963.238.* Throughout this section, numbers in parentheses at the end of references toRussian periodicals indicate the corresponding page in the English or U.S. translation178 I N O R G A N I C C E E M I S T R Yheterocycles, effective charges and ele~tronegativity,~ and stereochemistryof five-co-ordination, l o8 H. Garcia-Fernandez, Bull. SOC. chim. France, 1963, 416.Ya.K. Syrkin, Upsekhi Khim., 1962, 31, 397 (197).lo R. J. Gillespie, J., 1963, 4672, 46792. THE TYPICAL ELEMENTSBy A. I(. HollidayGroup 0.-Since the report last year of the first stable noble gas com-pounds, there has been intense activity in this field. Besides the com-pounds of xenon (discussed below), a difluoride and tetrafluoride ofkrypton, and a fluoride of radon have been prepared, and the existence ofhelium difluoride has been predi~ted.~ Contrary to earlier observations,xenon difluoride appears to be stable and can be prepared by direct unionof the elements under a variety of conditions or by reaction of xenon withtetrafluoromethane in a high voltage discharge.6 The structure is linear(cf. the IC1,- ion) with Xe-F = 2.0 8,' and, like the tetrafluoride, the heatof sublimation is abnormally high (12.3 kcal./mole) suggesting electro-static attraction between polar molecules.8 What was thought to be ahigh-density polymorph of the tetrafluoride is now shown to be the mole-cular addition compound XeF,,XeF,.g Several new methods 10 for pre-paring the tetrafluoride have been published; passage of xenon and fluorinethrough a nickel tube at dull red heat appears to be the simplest.1l Themolecule is square-planar (cf.Ic14-)7, l2 with a Xe-F bond length similarto that in the difluoride. The bonding in the difluoride is considered toinvolve only the 5p0 and 2130 atomic orbitals of the xenon and fluorine atoms,with one bonding pair of electrons for the two bonds; this requires consider-able charge migration from xenon to fluorine ( >50% ionicity), which ex-plains the high heat of sublimation already noted.*, l3 In the tetrafluoride,one other xenon p-orbital is used in bonding, and a still further increase inthe co-ordination number of the xenon should therefore be possible; this1 D.R. Mackenzie, Science, 1963, 141, 1171.A. V. Grosse, A. D. Kirschenbaum, A. G. Streng, and L. V. Streng, Science,8 P. R. Fields, L. Stein, and M. H. Zirin, J . Amer. Chem. SOC., 1962, 84, 4164.G. C. Pimentel and R. D. Spratley, J . Amer. Chem. SOC., 1963, 85, 827.R. Hoppe, H. Mattauch, K. M. Rodder, and W. Dahne, 2. anorg. Chem., 1963,324, 214; J. L. Weeks, C. L. Chernick, and M. S. Matheson, J . Amer. Chem. SOC., 1962,84, 4612.S.Siege1 and E. Gebert, J . Amer. Chew. SOC., 1963, 85, 240; L. L. Lohr, jun. andW. K. Lipscomb, ibid., p. 240; H. A. Levy and P. A. Agron, ibid., p. 241; D. F. Smith,J . Chem. Phys., 1963, 38, 270.J. Jortner, E. G. Wilson, and S. A. Rice, J . Amer. Chem. SOC., 1963, 85, 814;J. H. Waters and H. B. Gray, ibid., p. 825; J. Jortner, S. A. Rice, and E. G. Wilson,J . Chem. Phys., 1963, 38, 2302.J. H. Burns, R. D. Ellison, and H. A. Levy, J . Phys. Chem., 1963, 67,1569.lo J. Slivnik, B. BrGid, B. VoIavSek, A. smak, B. Frlec, R. ZemljiE, A. Anfur, andZ. Veksli, Croat. Chem. Acta, 1962, 34, 187; A. D. Kirschenbaum, L. V. Streng, A. G.Streng, and A. V. Grosse, J . Amer. Chem. SOC., 1963,85,360; D. R. Mackenzie and R. H.Wiswall, jun., Inorg.Chem., 1963, 2, 1064.l1 J. H. Holloway and R. D. Peacock, Proc. Chem. SOC., 1962, 389.l2 L. C. Allen and W. de W. Horrock, jun., J . Amer. Chem. SOC., 1962, 84, 4344;H. H. Claassen, C. L. Chernick, and J. G. Malm, ibid., 1963,85, 1927; D. H. Templeton,A. Zalkin, J. D. Forrester, and S. M. Williamson, ibid., p. 242.l3 R. E. Rundle, J . Amer. Chem. SOC., 1963, 85, 112; R. M. Noyes, ibid., p. 2202.1963, 139, 1047.6 D. E. Milligan and D. R. Sears, J . Amer. Chem. SOC., 1963, 85, 823180 INORGANIC CHEMISTRYhas been achieved in the preparation of xenon hexafluoride by prolongedheating of xenon with excess of fluorine,14 or by reaction at high pressure.15There is also evidence for a still higher fluoride, possibly XeF8.16 Incom-plete hydrolysis of the hexafluoride gives the oxyfluoride XeOF,, with asquare-pyramidal structure and appreciable double bond character in theXe-0 b0nd.l' Complete acid hydrolysis of the hexafluoride gives Xe( OH),,14and this is also obtained in the acid hydrolysis of the tetrafluoride.18 It hasstrong oxidising properties, and can be titrated as an acid [cf.Te(OH),] withbarium hydroxide to give the slightly soluble barium xenate, Ba,XeO,; thelatter decomposes at 250 O :I9Ba,XeO, + 3Ba0 + Xe + 1.50,.Hydrolysis of XeF, in presence of air,l* or slow hydrolysis of XeF,,'O yieldsthe non-volatile explosive solid XeO, which has a trigonal-pyramidalstructure with dimensions similar to the isoelectronic 10, - ion. 21 Alkalinehydrolysis of xenon hexafluoride gives a solution containing xenon ( VIII)and from this the salt sodium perxenate hexahydrate, Na4Xe06,6H20, hasbeen isolated; the XeOG4- ion has a regular octahectral structure, withXe-0 = 1-84 Xenon tetrafluoride dissolves in liquid antimony penta-fluoride to give the yellow, diamagnetic solid XeF2,2SbF5, and a similarcompound with tantalum pentrafluoride has been prepared ; the structureF5Sb-.F-Xe-F-SbF, is suggested.23 Xenon hexafluoroplatinate has alsobeen obtained, by exploding a platinum wire in an atmosphere of xenon andfluorine. 24Group 1.-Most of the alkali-metal nitrates, and the nitrites of sodiumand potassium, can be distilled from the melts, at 350-500' under reducedpressure, without significant decomp~sition.~~ The 1 : 1 complexes of thealkali metals with uramildiacetic acid have stabilities increasing in theorder K+ < Ne+ < Li+.26 The nature of the " alkali carbonyls," e.g.," KCO," has been re-investigated; reaction of any one ofthe alkali metals, M,with carbon monoxide in liquid ammonia gives, as one product, 'the acetylenediolate MOCECOM ; however, direct reaction of potassium with carbonmonoxide appears to give initially a substance K,02C,02, which on methyla-tion yields Me,C,04 ; the salt of hexahydroxybenzene, K6C6067 is finallyl4 F. B.Dudley, G. Gard, and G. H. Cady, Inorg. Chem., 1963, 2, 228.l5 J. G. Malm, I. Sheft, and C. L. Chernick, J . Amer. Chem. Soc., 1963, 85,J . Slivnik, B. VolaGsek, J. Marsel, V. VrgEaj, A. Smalc, B. Frlec, and Z. ZemlkiE,l7 D. F.Smith, Science, 1963, 140, 900; M. H. Studier and E. N. Sloth, J. Phys.18 S. M. Williamson and C. W. Koch, Science, 1963, 139, 1046.lo A. D. Kirschenbaum and A. V. Grosse, Science, 1963, 142, 580.20 D. F. Smith, J. Amer. Chem. SOC., 1963, 85, 816.21 D. H. Templeton, A. Zalkin, J. D. Forrester, and S. M. Williamson, J. Anzer.2 2 A. Zalkin, J. D. Forrester, D. H. Templeton, S. M. Williamson, and C. W. Koch,z3 A. J. Edwards, J. H. Holloway, and R. D. Peacock, Proc. Chem. SOC., 1963, 275.2 4 F. Mahieux, Compt. rend., 1963, 257, 1083.2 5 C. J. Hardy and B. 0. Field, J., 1963, 5130.z6 H. Irving and J. J. R. F. da Silva, J., 1963, 448.110.Croat. Chem. Acta, 1963, 35, 81.Chem., 1963, 67, 925.,Chem. SOC., 1963, 85, 817.Science, 1963, 142, 50iHOLLIDAY: THE TYPICAL ELEMENTS 181formed.,7 Unlike t-butyl-lithium, n-butyl-lithium is almost entirely hexa-meric in hydrocarbon solvents;2* in ether, a solvated dimer is formed.29Perfluorovinyl-lithium has been prepared by transmetallation of phenyl-lithium with phenyltrisperfluorovinyltin in ether a t -40" ; it decomposesat 0 0.30 Pure potassium peroxodicarbonate has been obtained by reactionof potassium peroxide with carbon dioxide in presence of water a t 0°.31The compound originally formulated as " CsHC1, " is now considered to bea mixed oxonium salt, 4Cs+C1-,3H30 +C1-. 32Group II.-The alkaline earth organometallic compounds have beenreviewed.33 A detailed examination of the M-MX, solid systems (M = Ca,Sr, Ba ; X = halogen) gives no evidence for M + ions.34 Pure alkaline-earthamides have been prepared by reaction of the metals with liquid ammonia;calcium amide yields the imide CaNH on heating, the latter forming a solidsolution in the amide.35 The anhydrous nitrates of beryllium and mag-nesium have been prepared ; the beryllium compound is strongly covalentand yields nitrate and nitrite ions in water, the reaction probably involvinginitial formation of BeO(N03) and NO, radicals.36 The reaction of dimethyl-beryllium with hydrogen cyanide in ether gives methane and berylliumcyanide etherate, Be(CN),, 0.6Et,0.37 The nature of the beryllate ion pre-sent in solution of sodium beryllate changes from a simple ion to a range ofpolymeric ions as the Na20 : Be0 ratio decreases.38 Pyrolysis of diethyl-magnesium etherate yields the ethoxide EtMgOEt rather than the com-pound MgC,H,.39 The related ethoxy-hydride HMgOEt has been preparedby reaction of diethylmagnesium with monosilane in ether ; with diboranethe compound Mg(OEt)BH, is f~rmed.~O Calcium hydride has been usedto prepare hydrides of boron and silicon from the corresponding fluorides.41The molar extinction coefficients of calcium-liquid ammonia solutions havevalues approximately twice those of the alkali metals a t most wavelengths,suggesting 2 moles of solvated electrons for each gram atom of calcium.42Group III.-Boron.Boron of purity >99% and with a tetragonal27 E. Weiss and W. Buchner, Helv. Chim. Acta, 1963, 46, 1121; W. Buchner, ibid.,p. 2111; W. F. Sager, A.Fatiadi, P. C. Parks, D. G. White, and T. P. Perros, J. Inorg.Nuclear Chem., 1963, 25, 187.28 D. Margerison and J. P. Newport, Trans. Faraday SOC., 1963, 59, 2058; cf. Ann.Reports, 1962, 59, 130.29 Z. K. Cheema, G. W. Gibson, and J. F. Eastham, J. Amer. Chem. SOC., 1963, 85,3518.30 D. Seyferth, D. E. Welch, and G. Raab, J. Amer. Chem. SOC., 1962, 84, 4266.31 A. Kh. Mel'nikov, T. P. Firsova, and A. N. Molodkina, Zhur. neorg. Khim., 1962,32 A. G. Maki and R. W. West, Inorg. Chem., 1963, 2, 657.33 G. A. Balueva and S. T. Ioffe, Uspekhi Khim., 1962, 31, 940 (439).3 4 H-H. Emons, 2. anorg. Chem., 1963, 323, 114.35R. Juza and H. Schumacher, 2. anorg. Chem., 1963, 324, 278.36 C. C. Addison and A. Walker, J., 1963, 1220.37 R. Masthoff, 2.Chem., 1963, 3, 269; G. E. Coates and R. N. Mukherjee, J., 1963,38 D. A. Everest, R. A. Mercer, R. P. Miller, and G. L. Millward, J . Inorg. Nuclear39 W. H. Birnkraut, Inorg. Chem., 1963, 2, 1074.40 R. Bauer, 2. Naturforsch., 1962, 17b, 626.41 R. de Pape, Ann. Chim. (France), 1963, 8, 185.4 2 C. Hallada and W. L. Jolly, Inorg. Chem., 1963, 2, 1076.7, 1228, 1237 (633, 637).229.Chem., 1962, 24, 525182 INORGANIC CHEMISTRYstructure has been prepared by heating the beryllium boride, BeB,,, withboron t r i ~ h l o r i d e . ~ ~ The first alkali-metal boride, NaB,, has been syn-thesised from the elements a t 1000"; it is thermally and hydrolyticallystable . 44Reaction of decaboranewith triethylamine-borine gives a high yield of the anion B1,H122- (as theEt3NH+ salt); in air, the ion [B12H,1*OH]2- is formed.46 Several newboron hydrides are reported ; hexaborane- 12, B6H12, prepared by decomposi-tion of tetramethylammonium triborohydride-8 with polyphosphoric acid,decomposes slowly a t room temperat~re.~' The hydride B2OH16, obtainedby slow passage of decaborane and hydrogen through an a.c.discharge, isthermally stable and gives a strongly acid solution ; icosaborane-26, (BloH13)2,and decaborane- 16, B10H16, are formed by radiation-induced reactions inpenta- or de~a-borane.~s The first example of a B,,.-hydride has beenobtained as the anion B,,H,,- by reaction of an alkali borohydride withdecaborane a t 90" in ether; in presence of a strong base a proton is lost t ogive B11H1,2-.49 The nonaborane B9H15, previously known only as an inter-mediate, has been obtained from pentaborane-11 as a solid, m.p. 2.6°,50and salts of the new ion B,H1,- have been prepared by base hydrolysis ofdecabomne.51 Addition of the latter to aqueous potassium borohydridegives the ion BloHl,2- (1).52 The hydride B18H22, first reported last year,The chemistry of diborane has been reviewed.45(Term.inal H atomsomitted )H3C- Chzexists in two isomeric forms; both of these possess a structure of twodecaborane-14 cages joined by common boron atoms a t the 5,6-positions,but the cages " open up " in opposite directions in the two f0rms.~3 Tetra-alkyldiboranes have been prepared by reduction of dialkylboron chlorides43 H. J.Becher, 2. anorg. Chem., 1963, 321, 217.44 P.Hagenmuller and R. Naslain, Compt. rend., 1963, 257, 1294.4 5 B. M. Mikhailov, Useplchi Khim., 1962, 31, 417 (207).413 N. N. Greenwood and J. H. Morris, Proc. Chem. SOC., 1963, 338.4 7 D. F. Gaines and R. Schaeffer, Proc. CJAem. SOC., 1963, 267.48 L. H. Hall and W. S . Koski, J . Amer. Chem. SOC., 1962,84,4205; L. B. Friedman,4 g V. D. Aftandilian, H. C. Miller, G. W. Parshall, and E. L. Muetterties, Inorg.60 A. B. Burg and R. Kratzer, Inorg. Chem., 1962, 1, 725.51 L. E. Benjamin, S. F. Stafiej, and E. A. Takacs, J . Amer. Chem. SOC., 1963,85,52 E. L. Muetterties, Inorg. Chem., 1963, 2, 647; cf. Ann. Reports, 1962, 59, 132.63 P. G. Simpson, K. Folting, and W. N. Lipscomb, J . Amer. Chem. SOC., 1963, 85,1879; P. G. Simpson and W.N. Lipscomb, J . Chem. Phys., 1963,39,26; P. G. Simpson,K. Folting, R. D. Dobrott, and W. N. Lipscomb, ibid., p. 2339; cf. Ann. Reports, 1962,59, 131.R. D. Dobrott, and W. X. Lipscomb, J . Amer. Chem. SOC., 1963, 85, 3505.Chem., 1962, 1, 734.2674HOLLIDAY: THE TYPICAL ELEMENTS I83with sodium borohydride in absence of solvent.54 Alkylation of penta-borane-9 in presence of a Lewis acid gives the l-alkyl (apex substituted)derivative, but direct alkylation with an ole& at 150" givesa base substituted2-alkyl compound ; rearrangement of apex- to base-substitution accurs a t200" and is thought to involve the intermediate ion EtB,H7-.55 Bridgingof two boron atoms by the NR, group, hitherto only known in B,H,*NR,-type compounds, is shown to exist (2) in the compound EtNH,,B,H1,*NHEt.56The blue nitrosohydroborate anion, [B,,H,8*N0]3-, is formed when bis-triethylammonium decahydroborate is treated with nitrogen dioxide ; it isreadily reduced to give [B,,H,,*NH,]3-.57 The reactions of penta- anddeca- borane with alkyl- and aryl-phosphines give yellow solids which losehydrogen when heated.58 Diphosphinodecaboranes were reported lastyear ; reaction of either B1,H13MgI or B,,H,,Na with chlorodiphenyl-phosphine gives the monophosphino-compound B,,H1,*PPh, which with acidsyields B,H,,-PPh, and the ion B,,H,,*PPl~,-.59 Trialkyl phosphites andthiophosphites react with decaborane to give compounds B,,H,,[ P( XR),12(X = S,0).60 Glycol and diborane react in etherto give the dioxaborolan (3)which is monomeric.6l Monochlorodiborane has now been isolated in aHpure state, stable at O O .6 2 Magnesium borohydride has been prepared ingood yield by reaction of magnesium hydride with diborane in a glycolether ; reaction of the product with boron trichloride releases diborane.6,Hydroboration of alkali-metal addition compounds with naphthalene ortriphenylboron is a convenient route to the triborohydride ion, which isisolated as the tetramethylammonium salt. 64The second member of the carborane series B,C,H,+2, carborane-4(n = 4), has been obtained in two isomeric forms; the more stable sym-form54 L. H. Long and M. G. H. Wallbridge, J., 1963, 2181.6 5 W. V. Hough, L. J. Edwards, and A. F. Stang, J. Amer. Chem. SOC., 1963, 85,830; T.P. Onak and F. J. Gerhart, Inorg. Chem., 1962, 1, 742; G. E. Ryschkewitsch,S. W. Harris, E. J. Mezey, H. H. Sisler, E. A. Weilmuenster, and A. B. Garrett, ibid.,2,890; G. E. Ryschkewitsch, E. J. Mezey, E. R. Alwicker, H. H. Sisler, and A. B. Garrett,ibid., p. 893.66 R. Lewin, P. G. Simpson, and W. N. Lipscomb, J. Amer. Chem. Soc., 1963, 85,478; cf. Ann. Reports, 1962, 59, 132.6 7 R. A. Wiesboeck, J . Amer. Chem. SOC., 1963, 85, 2725.58 W. Jeffers, J., 1963, 1919.E. L. Muetterties and V. D. Aftandilian, Inorg. Chem., 1962,1,731; H. Schroeder,Inorg. Chem., 1963,2, 390; H. Schroeder, J. R. Reiner, and T. A. Knowles, ibid., p. 393;cf. Ann. Reports, 1962, 59, 135.6 o V. I. Stanko, A. I. Klimova, and L. I. Zakharkin, Izvest. Alcad. Nauk X.S.S.R.,Otdel. khim.Nauk, 1962, 919 (856).61 S. H. Rose and S. G. Shore, Inorg. Chem., 1962, 1, 244.6 2 H. W. Myers and R. F. Putnam, Inorg. Chem., 1963, 2, 655.63 H. D. Batha, F. D. Whitney, T. L. Heying, J. P. Faust, and S. Papetti, J. Appl.6 4 D. F. Gaines, R. Shaeffer, and F. Tebbe, Inorg. C'hem., 1963, 2, 526.Chenz., 1962, 12, 478184 INORGANIC CHEMISTRYhas the tetragonal bipyramid structure (4) with 5-co-ordinate carbon atoms,and the other isomer is obtained by exchanging one of the carbon atomswith any boron atom.65 Compounds of type B,H,,C,R, are now recognizedto be derivatives of dihydrocarboranes (e.g., B,C,H,), and these yieldcarboranes on pyrolysis, the particular carborane obtained depending onconditions.66 The structure of B4H6,C,R, ( 5 ) is considered to involvedonation from the carbon-carbon n-bond to the available sp2 orbital of theapical boron atom.67 The reaction of carboxylic acids with trialkylborons,BR,, yield dialkylboron carboxylates, e.g., Me,B*O*COMe which is mono-meric in the vapour state ; further reaction gives MeB( O*COMe), whichdecomposes to give acetic anhydride and BB’-diacetyldimethylborate. 68There now appears to be no evidence for the existence of tetraphenylboricacid, HBPh,. 69 Tris(pentafluoropheny1)boron has been prepared from penta-fluorophenyl-lithium and boron trichloride ; it has acceptor properties and inpresence of excess of pentafluorophenyl-lithium forms the compoundLi[B(C6F,),].70 Various diboric acids (HO),B*[CH,];B( OH), and their estershave been prepared, e.g., by hydroboration of butadiene, 71 triallyborine,’, andtrialkylborons ; 73hydrolysis of the ester (BuO),B-CHMe*B( OBu), gives theethane- 1 , l -diboric acid, MeCH[ B( OH),],. 74 Several dialkylaminoborines,(R,N),BR’ (R’ = H,Me) , have been prepared by hydrogenation or alkylationof the corresponding chlorides; with R = Me and R’ = Me or H, addition ofhydrogen chloride gives the compound [ ( Me2NH),BR’C1]C1,75 whereas withR’ = H and R = Et, Pr, or Bu, normal addition to give R,NH,BR’Cl,occurs. 76 In the two isomers of (methylphenylamino)methylphenylborine,the boron- and nitrogen-attached phenyl rings have different orientations. 77Evidence that the adduct of diborane and ethylenediamine has the open-chain structure H3B,NH2[CH2]2NH2,BH, has been reported.78 Ethanol-amine-borine, HO*CH,*CH,*NH,,BH,, and tris(ethano1amineborino) borate,B( O*CH,.CH,*NH,,BH,),, have been prepared from diborane and ethanol-amine in tetrahydrofuran. 796 5 I. Shapiro, B. Keilin, R. E. Williams, and C. D. Good, J . Amer. Chem. Soc., 1963,85, 3167.6 6 T. P. Onak, F. J. Gerhart, and R. E. Williams, J. Amer. Chem. SOC., 1963, 85,3378.67 W. E. Streib, F. P. Boer, and W. N. Lipscomb, J. Amer. Chem. SOC., 1963, 85,2331.68 G. S. Kolesnikov, S. L. Davydova, M. A. Yampol’skaya, and N. V. Klimentova,Izvest. Akad. Nauk S.S.S. R., Otdel. khim. Nauk, 1962, 841 ; J. Goubeau and H. Lehmann,2. anorg. Chem., 1963, 322, 224.6 9 J. N. Cooper and R. E. Powell, J. Amer. Chem. SOC., 1963, 85, 1590.7 0 A.G. Massey, A. J. Park, and F. G. A. Stone, Proc. Chem. Soc., 1963, 212.71 L. I. Zakharkin and A. I. Kovredov, Izvest. Alcad. Nauk S.S.S.R., Otdel. khim.Nauk, 1962, 357, 362 (331, 337); Zhur. obshchei. Khim., 1962, 32, 1421 (1408).72 L. I. Zakharkin and A. I. Kovredov, Izvest. Akad. Nauk S.S.S.R., Otdel. khim.Nauk, 1962, 1564 (1480).7 3 B. M. Mikhailov and V. F. Pozdnev, Izvest. Akad. Nauk S.S.S.R., Otdel. khim.Nauk, 1962, 1861 (1769).74 D. S. Matheson and J. G. Shdo, J. Amer. Chern. Soc., 1963. 85, 2684.7 5 H. Noth, W. A. Dorochov, P. Fritz, and F. Pfab, 2. anorg. Chem., 1962,318, 293.V 6 H. Noth and P. Fritz, 2. anorg. Chem., 1963, 322, 297.7 7 H. Baechle, H. J. Becher, H. Beyer, W. S. Brey, jun., J. W. Dawson, M. E.7 8 H.C. Kelly and J. 0. Edwards, Inorg. Chem., 1963, 2, 226.7 9 H. C. Kelly and J. 0. Edwards, Inorg. Chem., 1963, 2, 39.Fuller 11, and K. Niedenzu, Inorg. Chem., 1963, 2, 1065HOLLIDAY: THE TYPICAL ELEMENTS 185Two new boron-nitrogen ring systems have been reported; removal ofhydrogen chloride from di- (t - buty1amino)boron chloride, and subsequentheating, gives 173-diaza-2,4-boretane (6) as a mixture of two geometricalisomers.80 Reaction of dimethylallylamine with trimethylamine-borineI 7 BuBu-8, N-HH-N B-BU (7)1H Bugives the liquid Me2N +[CH,],B -H2 and trimethylamine.sl The existence of(BH,*NH,), as cyclotriborazane (hexahydroborazole), first reported in 1961 ,has been confirmed,82 and two isomers of 1,3,5 trimethylcycloborazane, bothof chain form but differing in the orientation of the methyl groups, have beenseparated.83 Interest in borazoles continues ; the interaction of methyl-substituted borazoles with various acceptor molecules has been investi-gated,s4 and iso- and isothio-cyanato,85 mixed B-amino- and B-chloro-,s6BBB-trifluoro- 87 and BBB-trifluoro-NNN-trialkyl-,88 and BBB-tri(sily1-ethyl) -NNN-triphenylborazines have been ~repared.8~ Diboron compoundscontaining B-N bonds have also received attention ; B,(NMe,), yields(Me,N),BH and B(NMe2), on pyrolysis, and the latter compound is alsoformed on oxidation.90 The 1 , 2 dialkyl- 1, 2-bis(dimethylamino) diboronshave also been prepared by reaction of the alkyl( dimethy1amino)boronchloride with sodium or potassium ; they exhibit considerable thermalstability, but the B-B bond is broken in reactions with donor or acceptormolecule^.^^ The reaction,Me,N,BCl, + B,(SMeJ4 -+ (Me,N),B,Cl, + (Me,N),BCI + Me,PIT,yields the stable monomeric dichlorobis( dimethylamino)diboron, and thisadds on hydrogen chloride to give Me2NH,BC1,*BCl2,NHMe,.92 The chem-istry of borates has been reviewed;93 the boroxine B,O,H:, is obtained byM.F. Lappert and M. K. Majumdar, Proc. Chem. SOC., 1963, 88.R. M. Adams and F. D. Poholsky, Inorg. Chem., 1963, 2, 640.-82 S. G. Shore and C. W. Hickam, Inorg. Chem., 1963, 2, 638; cf. Ann. Reports,8 3 D. F. Gaines and Riley Schaeffer, J. Anaer. Chem. SOC., 196.3, 85, 395.8 4 E. K. Mellon, jun. and J. J. Lagowski, Nature, 1963, 199, 997.8 5 M.F. Lappert and H. Pyszora, J., 1963, 1744.86 R. H. Toeniskoetter and F. R. Hall, Inorg. Chem., 1963, 2, 29; H. C. K’ewsom,8 7 A. W. Laubengayer, K. Watterson, D. R. Bidinosti, and R. F. Porter, Inorg.8 8 K. Niedenzu, H. Beyer, and H. Jenne, Chena. Ber., 1963, 96, 2649.8sD. Seyferth and M. Takamizawa, Inorg. Chem., 1963, 2, 731.1961, 58, 84.W. G. Woods, and A. L. McCloskey, ibid., p. 36.Chew., 1963, 2, 519.A. G. Massey and N. R. Thompson, J. Inorg. Nuclear Chem., 1963, 25, 175; L. L.s1 R. J. Brotherton, H. M. Manasevit, and A. L. McCloskey, Inorg. Chew?,., 1962, 1,s 2 M. P. Brown and H. B. Silver, Chem. and I n d . , 1963, 85; cf. Ann. Reports, 1962,s3 H-A. Lehmann, 2. Chem., 1963, 3, 284.Petterson and R. J. Brotherton, Inorg. Chena., 1963, 2, 423.749; H.Noth and P. Fritz, 2. anorg. Chem., 1963, 324, 129.59, 133186 INORGANIC CHEMISTRYcondensing the product of the reaction of water with boron-boric oxide mix-tures at high temperatures, and is also formed in the oxidation of penta-borane-9; it loses diborane when warmed and is considered t o have a6-membered ring structure.94 Polymers of borazole units linked throughB-O-B bonds were reported last year; some further examples have beenobtained by pyrolysis of BBB-t- butoxyborazoles.95 The reaction ofdi-n-butylboric acid with hydroxylamine gives a compound ( Bun,EONH,),which on the basis of its infrared spectrum is considered to be a 6-memberedheterocycle (7), " bon-bon." 96 Gas-phase displacement reactions give theacceptor power of boron trihalides towards trimethylamine in the orderBBr, > BCl, > BF,( > &B,H6).97 Dimethylaminoboron difluoride has beenprepared in good yield by the reaction of aluminium with the adduct di-methylamine-boron trifl~oride,~~ and reaction of vinylboron difluoride withhydrated potassium fluoride gives the vinyltrifluoroborate K[CH, :CHBF,],resistant to hydrolysi~.~~ Rapid halogen exchange between the ions BF,-and BCl,- occurs in solution, and mixed anions may therefore be formedin adducts Ph,CX,BY, (Le., as [Ph,C][BY,X] (X or Y = F or C1).lo0 Theboron chloroperchlorates BCl,( ClO,), and BC1( C10,) ,, and the triperchlorateB(ClO,),, have been prepared by reaction of boron trichloride with perchloricacid or silver perchlorate; they are stable a t low temperatures, but are easilyhydrolysed or decomposed. lol I n the alkyldimethylaminoboron halidesBR(X)NMe,, dimerisation is facile if the alkyl R and the halogen X aresmall; X is easily replaced in the monomer.1o2 The " boroniurn " ion[Cl,B(NHMe,),]+ reported last year as the chloride, has been prepared byother methods and with other anions, and the corresponding [Cl,B(OEt),]+obtained.lo3 Alkyl- and aryl-boron dihalides have been prepared by reactionof the trihalide with alkylaluminium and arylmercury halides, respe~tive1y.l~~Sulphonyldichloroborinates, RSO,*O*BCl,, are produced by reaction of borontrichloride with esters of sulphonic acids.105 Reaction of the thiol EtSHwith an alkylboron dichloride, RBCl,, gives a mixture of RB(SEt), andRB( SEt)Cl.lOs Reaction of heptasulphur imide with boron tribromidegives dibromo(heptasu1phur imido)-boron, S,N*BBr,.lo' Diboron tetra-94 W. P. Sholette and R. F. Porter, J. Phys. Clzem., 1963, 67, 177; s. K. Gupta andR. F. Porter, ibid., p. 1286; G. H. Lee, jun., W. H. Bauer, and S. E. Wiberley, ibid.,p. 1742.95 B. E. Larcombe and H. S. Turner, Chem. and In&., 1963, 410.96 L. P. Kuhn and M. Inatome, J. Amer. Chem. SOC., 1963, 85, 1206.9 7 J. M. Miller and M. Onyszchuk, Canad. J. Chum., 1963, 41, 2898.98 L. L. Shchukovskaya, M. G. Voronkov, and 0. V. Pavlova, Izvest. ALad. Nauk99 S . L. Stafford, Canad. J. Chem., 1963, 41, 807.S.S.S.R., Otdel khim. Nauk, 1962, 366 (341).100 R. D. W. Kemmitt, R. S. Milner, and D.W. A. Sharp, J., 1963, 111.101 R. A. Mosher, E. K. Ives, and E. F. Morello, J. Amer. Chem. SOC., 1963, 85,lo2 H. Noth and P. Fritz, 2. anorg. Chem., 1963, 324, 270.lo3 B. M. Mikhailov, V. D. Sheludyakov, and T. S. Shchegoleva, Izvest. Akad. Nauklo4 W. Gerrard, M. Howarth, E. F. Mooney, and D. E. Pratt, J., 1963, 1582.lo5 J. Charalambous, M. J. Frazer, and W. Gerrard, J., 1963, 826.lo6 B. M. Mikhailov and T. K. Kozminskaya, Izvest. Akad. Nauk S.S.S.R., Otdel.lo7 H. G. Heal, J., 19G2, 4442.3037.S.S.S.R., Otdel. khim. Nauk, 1962, 1698 (1618); cf. Ann. Reports, 1962, 59, 133.khim. Nauk, 1962, 256 (234)HOLLIDAY: THE TYPICAL ELEMENTS 187fluoride has been synthesised by reaction of tetra-alkoxydiborons withsulphur tetrafluoride : lo8B,(OR)4 + 4SF4 + B,F4 + 4SOF, + 4RF.Reactions of diboron tetrachloride with various nitrogen and phosphoruscompounds have been investigated ; phosphorus trichloride gives the adductB,Cl4,2PC1,, and it mixed adduct B,Cl,,P,Me,NMe, has been obtained.logSome further properties of tetraboron tetrachloride are reported ; methyla-tion gives mainly B4C1,Me, and with dimethylamine B,(NMe,), is obtained.l1°Flash photolysis of boron chlorides supports the view that BC1, and not BCl,,radicals are involved in the formation of diboron tetrachloride, Reactionof bis(dimethy1amino)sulphane (Me,N),S, with diborane in ether, givesfirst the sulphane-borine, (Me,N),S,BH,, and this on standing givesMe,N-SBH,,HNMe, as one product.112 Some further thioborates, e.g.,NaBS,, Na,BS,, have been prepared,lf3 and the substance BPS, has beenobtained by direct union of the elements.ll*There now seems little doubt that the adduct A1H3,2NMe,is monomeric, having a trigonal-bipyramidal structure with the two ligandsaxial;l15 it is suggested that the tendency to give complexes AlH,, 2D isin the order (D =) tetrahydrofuran > trimethylamine > diethyl ether.ll6Trimethylamine complexes with alkyl aluminium hydrides have beenobtained by several methods (e.g., reduction of alkylaluminium halide-trimethylamine adducts) and appear to be associated in cyclohexane to anextent which depends on the number and size of the alkyl groups.117 Aseries of compounds H3-,Al(BH,),,NMe, (x = 1,2, or 3) have been preparedby reaction of lithium borohydride with the appropriate chloro-aluminiumhydride-trimethylamine ; reaction of the product with mercuric chloridegives (e.9.) C1,AlBH,,NMe,.l18 Reaction of the complex hydride NaAlR,H(R = Bui, Et) with acetylene gives the compound Na,[R,A1CiCAlR,].119Complex hydrides of the type MIA1(XH,), (M = Li,Na; X = N, P, or As)have been prepared from XH, and M1AlH4,120 and complexes MI(A1 H,-,R,)(x = 2,3,4; R = Me, Et, Pr) from MIAlH, and alkali-metal alkyls, and bydirect union of the elements My Al, and H, in presence of the appropriateAluminium.Crystallographic data show that bis(triphenylphosphine)nickel(rI) chloridecontains tetrahedrally co-ordinated nickel atoms 159 with the P-Ni-P angles117 O and the Cl-Ni-C1 angles 123".Diphenylphosphine reacts with nickel(I1)l50 J.Chatt, A. E. Field, and B. L. Shaw, J . , 1963, 3371.151 L. Malatesta and R. Ugo, J., 1963, 2080.152 E. D. Whitney and R. F. Giese, Nature, 1963, 197, 1293.lSs D. M. L. Goodgame and M. Goodgame, J., 1963, 207.lS4 D. H. Brown, R. H. Nuttall, and D. W. A. Sharp, J . Inorg. Nuclear Chena.,ls5 A. B. P. Lever, J. Lewis, and R. S. Nyholm, J . , 1963, 5042.lS6 D. M. L. Goodgame and L. M. Venanzi, J., 1963, 616.15' R. 0. Gould and R. F. Jameson, J . , 1963, 5211.158 J. T. Donoghue and R. S. Drago, Inorg. Chem., 1963, 2, 572.159 G. Garton, D. E. Hem, H. M. Powell, and L. M. Venanzi, J., 1963, 3625.1963, 25, 1067218 INORGANIC CHEMISTRYhalides in non-ionising solvents to yield trans-[ (NiX,(HPPh,J,] and the five-m-ordinate complexes, [NiX,(HPPh,),].16* In contrast to the phenyl-phosphine derivatives, the newly synthesised trimet hylphosphine complexesof the nickel(1r) halides, [NiX,(Me,P),], are oxidised to nickeI(m) by atmo-spheric oxygen. The oxidation is smoothly effected by reaction of thecomplexes [MX,(R,P),] (M = Ni or Co) with the appropriate nitrosylhalide, giving [MX,(R$’),], which are nonomeric in solution. A zero dipolemoment was found for CoC13(Et,P),, so that this has the trigonal-bipyramidalconfiguration. 161 Crystal-structure determinations of the diarsine com-plexes Pt(c€iars),Cl, and Ni(diars)& show that these have distorted octa-hedral arrangements around the metal atoms; shortening of the nickel-assenic bond length is attributed to interaction between filled metal dorbitals and vacant d orbitals on the ligand.lC2 Dichloro(te6rakisthiourea)-nickel(n) also has the distorted octahedral structure.l@The magnetic properties of 8chiff-base complexes of nickef(I1) have con-tinued to arouse great interest. In the bis-(N-alkylsa1icylideneamine)-nickel(n) compounds, the open-chain paramagnetic complexes (R = iso-propyl, s-butyl, and t-b-atyl) have an essentially tetrahedral ertructure,whereas closed-chain diamagnetic complexes (R = cyclopentyl, cyclohexyl,and cyclo-octy€) have a planar structure. Cryoscopic measurements showthat solute association is responsible for only a part of the paramagnetismexhibited by all these complexes when dissolved in inert solvents. Indeedthere is now overwhelming evidence to support the existence of a con-formational equilibrium between diamagnetic planar, and paramagneticfetrahedral isomers in solution, both in toluene and in melts.*6* A similarequilibrium has been proposed for solntions of bisnickel(I1) chelates ofatminotroponeimines.1~5 The effect of temperature on this type of equi-librium has been investigated for the case of the (N-arylsalicy1idemamine)-nickel(n) complexes. Three forms of such complexes can exist in solution,tihe paramagnetic polymeric (A), the diamagnetic planar (B), and the para-magnetic tetrahedral (C).An increase in temperature increases the per-centage of (C) decreasing the percentage of (A) ; the same shift of equilibriumocears on diluting the solutions at constant temperature.*66 The structureof the paramagnetic bis- (N-isopropylsalicylideneamine)nickeI(n) has beenconfirmed to be distorted-tetrahedra1 by X-ray crystallographic measure-ments.167 Blue-violet, paramagnetic complexes of the type bis(ethy1ene-diamine)nickel( u) hemioxalate perchlorate, are probably dimeric, thela0 R.G. Hayter, Inorg. Chem., 1963, 2, 932.161 K. A. Jensen, P. H. Nielsen, and C. T. Pedersen, Acta Chem. Scand., 1963, 17,162 N. C. Stephenson and G. A. Jeffrey, Proc. Chem. SOC., 1963, 173.163 A. Lopez-Castro and M. R. Truter, J., 1963, 1309.16* L. Sacconi, P. Paoletti, and M. Ciampolini, J . Amer. Chem. SOC., 1963, 85, 411;R. H. Holm and K. Swamhathan, Inorg. Ckem., 1963, 2, 181; L. Sacconi, J., 1963,4608.1e6 D.R. Eatm, W. D. Phillips, and D. J. Caldwell, J . Amer. Chem. Soc., 1963,85, 397.lB6 L. Sacconi and M. Ciampolini, J. Amer. Chem. SOC., 1963, 85, 1750.16’ M. R. Fox, E. C. Lingafelter, I?. L. Orioli, and L. Sacconi, Natwre, 1963, 197,1104.1125; K. A. Jensen, B. Nygmrd, and C. T. Pedersen, ibid., 1126NICHOLLS : THE TRANSITION ELEMENTS 219oxalate ion acting as a bridging group and linking two nickel tetra-aminecations.168Diethylphosphine and ethylphenylphosphine react with palladium( n)halides and with [PdCl,(PR,)], to give complexes [PdX,LL'J (L = L'= Et,PH, 3EtPhPH; or L = Et,PH, EtPhPH, L' = PR,). In the pre-mnce of a base these complexes lose hydrogen halide, giving the phosphorus-bridged complexes trans-[ PdX( PR,)L],, which react with chelate ligands togive [ Pd,( PR,),(chelate),]X,.169 The crystal-structure determination on[Pd(PPr3n)2(CNS)2] has confirmed that the palladium is bound to thenitrogen atom of the thiocyanate group.170 The so-called " anomalous "ammine-nitrile complexes of platinum(II), [Pt(NH,) B(RCN),]X,, do not infact contain co-ordinated nitriles. The nitriles react with ammonia mole-cules so that co-ordination is from amidine molecules (4), the platinumbeing square-planar with the two ammonia molecules in tram-positions. 171The crystal structures of di-iodo- (o-phenylenebiedimethylarsine) -platinum( II)and -palladium( a) have been investigated ; both compounds have distortedoctahedral stereochemistry . A shortening of the Pt-As distiance suggeststhat d,-d, bonding is occurring; the Pt-I and Pd-I distances are muchlonger than normal single-bond di~tances.1~2 Azide ions react with pal-ladium( 11) in hydrochloric acid-acetone solutions, giving [ Pd(N,),ClJ2 - and[ Pd(N&]2- complex ions.173 Platinum(v) complexes, KPtF,, ClF,*PtF,and IF',,PtP,, have been prepared by reaction of the respective fluorideswith 0, +PtF, -.With bromine trifluoride and selenium tetrafluoride, de-rivatives of platinurn(rv) are obtained, wiz., (BrF,),PtF, and (SeFp)zPtP4.174Copper, Silver, and Gdd.-Trimethyl- and triphenyl-phosphe displaceethylenediamine from its bis(trirnethyl)gold(I) complex, (Me,Au),en.Thermal decomposition of Bh,PAuMe, gives gold, ethane, and triphenyl-phmphine. The infrared spectra of the complexes have been studied;175the Au-P stretching €requencies lie in the range 347-391 cm.-l.Doublesalts of silver bromide and iodide with the corresponding thallium halides,e.g., AgBr,ZTIBr, have been prepared and chara~tePised.l~~ The a b r p -tion spectra of solutions of the interesting ds system of silver(r1) in per-chloric and nitric acids have been determined. These spectra, coupledwith kinetic studies on these systems, clearly indicate the formation ofsilver(I1) complexes with nitrate and perchlorate anions. A mechanism isproposed for the reduction of silver@) to silver(1).177 The oxidation of[ Ag(phen),]NO, to [Ag(phen),}(NO,), (phen = o-phenanthroline) with ozoenoccurs in glacial acetic acid, nitromethane, and nitr0ethane.1~8 ColourlessltsN.F. Curtis, J., 1963, 4109, 4115.16g R. G . Hayter and F. S. Humiec, Inorg. Chern., 1963, 2, 306.171 N. C. Stephenson, J . Inorg. Nuclear Ckem., 1962, 24, $01; Yu. Ya. Kharitonov,17*N. C. Stephenson, J . Inorg. Nuclear Chem., 1962, & 791, 797.173 F. G. Sherif and K. F. Michail, J . Inorg. Nuclear Chern., 1963, 25, 999.174N. Bartlett and D. H. Lshmann, J., 1962, 5253.175 G. E. C o a b and C. Parkin, J., 1963, 421.176 H. Hirsch, J., 1963, 1318.E. Fmsson, C. Panatoni, and A. TUMO, Nature, 1963, 199, 803.Si. Chia-Chen, and A. V. Babaeva, Zhur. neorg. Kkim., 1962, 7, 997 (513).J. B. Kirwin, F. D. Peat, P. J. Proll, and L. H. Sutcliffe, J . Phy. Chem., 1963,67, 1617.178 J. Selbin a d €3. Shamburger, J . Inoqq. Nuclear Chem., 1962, 24, 1153220 INORGANIC CHEMISTRYcrystalline diamagnetic copper( I) acetylacetonate has been obtained as anammoniate by the addition of acetylacetone to a solution of copper(1) iodidein liquid ammonia.It disproportionates in a high vacuum.179 The mag-netic properties of some aryl-carboxylates of copper(r1) have been investi-gated; the structure and presence of metal-metal bonding in these compoundscan be related to the polarisability of the ligand.lS0 The copper atoms haveessentially square-planar co-ordination in bis-( 1 -aminocyclopentanecarboxyl-ato)copper(rr), two nitrogen atoms being at 1-98A and two oxygen atomsat 1.91 A distant.lsl Mono- and poly-nuclear copper(I1) complexes areformed in aqueous solution with cysteine and 2,7-diaminosuberic acid.182Discrete planar [CU,C~,]~- dimers are found in crystalline KCuCl, andNH,CuC13.Monoclinic LiCuC13,2H,0 contains [CU,C~,]~- ions joined bylonger Cu-C1 links to form chains; half of the water molecules are co-ordinated to copper.ls3 Bromide complexes of copper(I1) have been studiedin acetonitrile and in a variety of aqueous and organic solvents.185 Thehighest complex formed is the purple CuBr,,- ion; the absorption spectrumof this ion has been discussed.lss Considerable doubt has been-cast uponthe existence of previously reported three-co-ordinate copper@) complexes.A binuclear structure is proposed for the so-called three-co-ordinated com-plexes possessing a normal magnetic moment.187 A number of five-co-ordinated copper complexes have been reported.Diaquo(acety1acetonato)-copper(=) picrate contains copper atoms surrounded by five oxygen atomsin a square pyramid; discrete anions are found in potassium pentanitro-cuprate@), the copper atoms being co-ordinated through nitrogen to fiveNO, groups.ls8 The 2’2’-dihydroxyazobenzene (dye) complex with copper(I1)ions reacts with ethylenediamine to form [Cu(dye)en] containing five-co-ordinate copper; the solid complex [Cu(dye)L] (L = ethanolamine) is adirner.ls9 Other five-co-ordinate complexes include those of copper@) ionswith the ligands 2,9-dimethyl-1 ,lo-phenanthroline 190 and 6-aminomethyl-2-methy1-pyridine,lQ1 and the alcohol addition compounds of some Schiff’sbase copper complexes.lQ2 The thermal properties of ethylenediamine com-plexes of copper@) sulphate have been investigated. The thermogravi-metric curve for [Cu(en),]SO, shows the expected deamination of one of theethylenediamine molecules.193 Monoethanolamine (mea) normally gives theR. Nast, R. Mohr, and C. Schultze, Chem. Ber., 1963, 96, 2127.lE0 J. Lewis and R. C. Thompson, Nature, 1963, 200, 468.lS1 G. A. Barclay and F. S. Stephens, J., 1963, 2027.18% C. J. Hawkins and D. D. Perrin, Inorg. Chem., 1963, 2, 839.l a 3 R. D. Willett, C. Dwiggins, R. F. Kruh, and R. E. Rundle, J. Chem. Phys.,1963, 38, 2429; P. H. Vossos, D. R. Fitzwater, and R. E. Rundle, Acta Cryst., 1963,16, 1037.W. Schneider and A. V. Zelewsky, Helv. Chim. Acta, 1963, 46, 1848.J. C. Barnes and D. N. Hume, Inorg. Chem., 1963, 2, 444.P.S. Braterman, Inorg. Chem., 1963, 2, 448.18’ M. Kubo, Y. Kuroda, M. Kishita, and Y. Muto, Amtral. J. Chem., 1963, 16, 7.188 R. D. Gillard and G. Wilkinson, J., 1963, 5399.lE9 E. J. Gonzales and H. B. Jonassen, J. Inorg. Nuclear Chem., 1962, 24, 1595.l 9 0 J. R. Hall, N. K. Marchant, and R. A. Plowman, Austral. J . Chem., 1963,lgl G. J. Sutton, Austral. J. Chem., 1963, 16, 373.192 C. M. Harris and E. D. McKenzie, Nature, 1962, 196, 670.lS3 W. W. Wendlandt, J. Inorg. Nuclear Chem., 1963, 25, 833.16, 34NICHOLLS : THE TRANSITION ELEMENTS 22 1complex ion [C~(rnea)~]Z+ but a t high pH values an uncharged speciesCu(NH,*C2H,*O), is formed.194 The 2 : 1 complexes of a-hydroxyamidineswith copper(I1) salts have been isolated and characterised,lg5 as have thetriethylenetetramine complexes of copper and nickel containing the tetra-chlorozincate anion, e.g ., [ Cu( trien)]ZnC14.196 Acidodiethylenetriaminegold(m) salts [Au(dien)X]X, (X = C1, Br) are acids in aqueous solutionthrough ionisation of a proton from one of the amine nitrogen atoms.lg7Zinc, Cadmium, and Mercury.-A new molecular species (ZnX), has beenfound in the zinc-zinc( 11) halide system at 285-350 '. It disproportionatesupon cooling to room temperature.lg8 Complex halides, and particularlymixed halide complexes, are conveniently prepared by the reactions ofbis( pyridine)zinc( 11) halides and bis( quinoline)cadmium( 11) halides withanhydrous hydrogen halides. Typical products are (pyH),ZnBr,I,,(quinH),CdCl,, and (q~inH),CdCl~I,.~~~ Dibromo- and di-iodo-bis(tripheny1-phosphine)cadmium(n) complexes are converted by ethyl bromide intobis( triphenylethylphosphonium)tetrabromocadmate( n), 200 viz.:(Ph,P),CdI, + 2EtBr -+ [Ph,PEt],CdBr, + 2EtI.The hydrolysis of the cadmium ion Cd2+ has been studied in some detail.201I n the concentration range above 0 . 1 ~ ~ the principal product of hydrolysisis the species Cd,0H3+. Raman spectra of mercury(n1 halides in themolten state are in accord with the view that linear X-Hg-X molecularspecies are retained in the melts.202 When potassium or ammoniumchlorides are added as solutes, the predominant species then are HgX,,HgX,-, and HgX42-. Mercury(I1) complexes of p-diketones are betterformulated as enolates Hg( 0-CR': CH-COR), rather than as cyclic chelates.203Anionic complexes of mercury(I1) with nitrate ions, i.e., [Hg(N0,)4]2 -, canbe extracted from nitric acid solutions of mercury(I1) with methyldioctyl-amine in chloroform.294 A crystal-structure analysis on the compoundoften formulated as K,Hg(NO,) ,,H20 shows that this compound containsfour nitrite groups tetrahedrally arranged around mercury, and is indeedK3[Hg(N02)41N03.205Ig4 C. W. Davies and V. C. Patel, J., 1963, 4716.IS5 R. 0. Gould and R. F. Jameson, J., 1963, 15.lS6 D. A. House and N. F. Curtis, J., 1963, 3149.W. H. Baddley, F. Basolo, H. B. Gray, C. Nolting, and A. J. Poe, Iizorg. Chem.,lS8 D. H. Kerridge, J., 1963, 1178.lSs H. Buss, H. W. Kohlschutter, and H. Deckert, 2. Naturforsch., 1963, 18b, 416;H. Buss, H.W. Kohlschutter, and D. Maulbecker, ibid., 86, 87.* O 0 G. B. Deacon, J. Inorg. Nuclear Chem., 1962, 24, 1221.,01 G. Biedermann and L. Ciavatta, Acta Chem. Scand., 1962, 16, 2221 ; D. Dyrssen202 G. J. Janz and D. W. James, J. Plays. Chem., 1963, 38, 902, 905.203 D. C. Nonhebel, J., 1963, 738.204 S. S. Choi and D. G. Tuck, Inorg. Chem., 1963, 2, 781.205 D. Hall and R. V. Holland, Proc. Chem. SOC., 1963, 20.4.1963, 2, 921.and P. Lumme, ibid., 17854. COMPLEXESBy D. NichoIlsGeneral.-General reviews that have appeared throughout the yearhave been concerned with the polarographic behaviour of co-ordinationand oxygen-bridge bonding.2 Parts two and three of the serieson the coupling of vibrational and electronic motions in degenerate elec-tronic states of inorganic complexes have also appeared ; part two concernsstates of triple degeneracy and systems of lower symmetry, and part threedeals with non-degenerate electronic states.3The necessity for X-ray structural data on transition-metal complexeshas assumed even greater importance than previously.Two papers haveappeared during the year in which the crystallographically determinedstructures of complexes are found to differ from those predicted on the basisof magnetic and spectroscopic data. I n the green paramagnetic form ofbis( benzyldiphenylphosphine)nickel(II) bromide (p = 2.7 B.M.) a newstereochemical complication has been dis~overed.~ The triclinic unit-cellcontains three single molecules; one molecule has its nickel atom in a centreof symmetry and has the trans-square-planar configuration.The wholeis a crystalline molecular compound of different magnetic forms, zlix.,Ni( PPh*CH,*Ph,),Br,( square), 2Ni( PPh*CH,*Ph,),Br,( tetrahedral). Althoughmagnetic and spectral data suggest tetrahedral co-ordination of cobalt inbis( trimethylphosphine oxide)cobalt(n) nitrate, it is found that cobalt issix-co-ordinate with a very irregular arrangement of ligand atoms, themolecule possessing no strict symmetry elements whate~er.~ The co-ordin-ated nitrate ion is bidentate in this compound-yet none of the indirectevidence clearly suggested this. Clearly these studies raise the question ast o whether structural inferences in other cases may similarly be in error.A crystal-structure determination of Se,Fe,(CO), has led to the discoveryof a new type of seven-co-ordinated metal atomq6 The molecule consistsof a square pyramid with an iron atom a t the apex and alternate iron andselenium atoms located a t the corners of the basal plane.Each iron atomhas three CO groups bonded to it, so that the apical iron atom exists in thenew seven-co-ordinated position. The principal factors influencing theconfigurations in eight-co-ordinated complexes have been discussed.Crystal and molecular structure determinations of zirconium complexesshow that zirconium(1v) acetylacetonate belongs to the square-antiprismaticco-ordination group while [Zr(C,04)4]4- is of the dodecahedra1 [Mo(CN)J4-1 A. A. VlEek, Progr. Inorg.Chem., 1963, 5, 211.2 B. Jezowska-Trzebiatowska and W. Wojciechowski, J . Inorg. Nuclear Clxnz.,A. D. Liehr, Progr. Inorg. Chem., 1962, 4, 455; 1963, 5, 385.B. T. Kilbourn, H. M. Powell, and J. A. C. Darbyshire, Proc. Chem. SOC., 1963,F. A. Cotton and R. H. Soderberg, J . Amer. Chem. SOC., 1963, 85, 2402.L. F. Dahl and P. W. Sutton, Inorg. Chem., 1963, 2, 1067.559; J. L. Hoard and J. V. Silverton, Inorg. Chem., 1963, 2, 235.1963, 25, 1477.207.' R. J. H. Clark, D. L. Kepert, R. S. Nyholm, and J. Lewis, Nature, 1963, 199NICHOLLS : COMPLEXES 223type. * Crystallisation of bis( dibenzoylmethanato)zinc( II) from 4-methyl-pyridine gives a tetra-(4-methylpyridine) adduct which may contain eight-co-ordinate zinc.gA rule has been formulated concerning n-bonding in transition-metalcomplexes ;lo “ for distorted octahedral complexes with tetragonal symmdry(lblL,X), nearly all the n-ban- is axially directed and involves the metaldm and d, orbitals.” As a good approximation, the planar n-bonding maybe neglected and the metal d,, orbital considered as non-bonding.A mole-cular orbital treatment for square-planar complexes has been presented,and the spectra of halide and cyanide complexes of Ni2+, Pd2+, Pt2+, andAu3+ discussed in terms of the derived scheme.11 The one-electron LCAOmethod, in which all valence orbitals are included, has provided a semi-quantitative basis for John-Teller distortions in VCl,, CuC142 -y NiC1,2 -,and CuFG4-, and for the spectra of these ions.12 Further studies havebeen made on the electronic spectra of ,!Miketone complexes particularly onthose of copper(@; a new theory has been proposed to account for theelectron-transfer spectra of this type of complex.13 Pseudo-lattice energies,i.e., energies required to separate a crystalline compound containing complexions into gaseous species so that the complex ions remain intact, have beencalculated. These lattice energies can then be used to calculate ligationenergies, i.e., the energy released when a gaseous complex ion is formedfrom a gaseous metal ion and gaseous ligands.14 A theory has been proposedwhich accounts for the increase in size of a spherically symmetrical complexwith temperature; it has been applied to tetrahedral and octahedral acetatecomplexes of cobalt(II).15 Orbital electronegativities of the neutral transi-tion metals of the first transition series have been calculated by the Mullikenformula for a wide variety of hybrid states.16Among the new techniques used throughout the year is the determina-tion of magnetic susceptibilities at high temperatures.17 Gas-phase chroma-tography has been successfully applied to the separation of mixtures ofmetal chelates of acetylacetone and of geometrical isomers of metal trifluoro-acefylacetonates.l8 A non-empirical method for determining the chiralityof metal complexes containing conjugated ligands has now been proposed.It is based upon the sign of the rotatory power of the ligand transitions inthe complex without reference to a standard molecule having known absoluteconfiguration.l9 Rotatory dispersion curves have been described for large8 J. L. Hoard and J . V. Silverton, Inorg. Chem., 1963, 2, 235; G. L. Glen, J. V.Silverton, and J. L. Hoard, ibid., p. 250.D. P. Graddon and D. G. Weeden, Proc. Chem. SOC., 1963, 247.lo C. J. Ballhausen and H. B. Gray, Inorg. Chem., 1963, 2, 426.l1 H. B. Gray and C. J. Ballhausen, J. Awaer. Chena. ~ o c . , 1963, 85, 260.12 L. L. Lohr and W. N. Lipscomb, Iraorg. Chem., 1963, 2, 911.l3 J. P. Fackler, F. A. Cotton, and D. W. Barnum, Inorg. Chem., 1963, 2, 97;J. P. Fackler and F. A. Cotton, ibid., 102; C. K. Jsrgensen, Acta Chem. Scad., 1962,16, 2406.14 A. B. Blake and F. A. Cotton, Inorg. Chem., 1963, 2, 906.l5 F. D. Peat, P. J. Proll, and L.H. Sutc€iffe, J . Inorg. Nuclear Chem., 1963,2!5,1491.I6 J. Hinze and H. H. Jaff6, Canad. J . Chem., 1963, 41, 1315.l 7 W. W. Wendlandt and J. P. Smith, J . Inorg. Nuclear Chem., 1963, 25, 1266.R. E. Sievers, B. W. Ponder, M. L. Morris, and R. W. Moshier, Incrrg. Chem.,1963, 2, 693.1 9 A. J. McCaffery and 5. F. Mason, Proc. Chem. SOC., 1963, 211224 INORGANIC CHEMISTRYnumbers of cobalt(rr1) and chromium(II1) complexes, and the absolute con-figurations of some of the complexes have been assigned from their relationt o the rotatory dispersion curve of the D-( +)-[Co en3I3+ Theobservation that solutions of chromium( 11) shift the nuclear magnetic reson-ance absorption for 170 in ClO, - suggests that substantial net replacementof water in [Cr(H20),J2+ by ClO,- takes place.21 The use of the method ofcontinuous variations with mixed-ligand complexes has been examined.The molar ratio a t which the concentration of a mixed complex reaches amaximum is generally different from the molar ratio of the reactants inthe complex.22The first example of linkage isomersion with the thiocyanate ion hasbeen reported.2 3 The reaction of the tetrathiocyanatopalladate(rr) ion withtriphenylarsine or 1,2'-bipyridyl, at low temperature, yields sulphur-bondedisomers which rearrange a t 150" to the nitrogen bonded isomers, e.g.,Ph,As NCS :\ /'Pd'SCN ' 'AsPh3A variety of metal-ion-his(#?-diketone) polymers containing Be, CU(II),Ni(n), Zn(n), and CO(II) have been prepared. Polymers derived frombis( benzoylacetones) and bis( dibenzoylmethanes) are thermally more stablethan those derived from the corresponding bis( acetylacetones).24 Com-plexes of tervalent metal ions M3+ (M = Cr, Co, Rn, Al, Ga, In, Mn, Fe)with 1 , 1 ,l-trifluoropentane-2,4-dione have been characterised ; cis- and trans-isomers have been distinguished for some of the complexes using nuclearmagnetic resonance and X-ray diffraction techniques.25 The substitution-addition reactions of an excess of beryllium(rr) and chromium(II1) acetyl-acetonates with diphenylphosphinic acid, carried out in melts, yield thedimera [Be(C5H70,)(OPPh20)], and [Cr(C5H7O,),(OPPh2O)1, in which thediphenylphosphinate anion acts as a catenating gr0up.~6 The reactivity ofco-ordinated acetylacetone in its complexes with CU(II), Ni(rr), Pt(II), a.ndA~(III) has been investigated.Dinitrogen tetroxide gives y-nitro-substitutedcomplexes, while nitrosyl chloride yields nitroso- or chloro-complexes,depending upon conditions; nitrite ions in the presence of ammonia a t pH 7yield diamagnetic, square iminoacetylacetone derivatives of nickel and2O T. E. MacDermott and A. M. Sargeson, Austral. J. Chem., 1963, 18, 334; T.Biirer, Helv. Chim. Acta, 1963, 46, 242, 2388.2l J. A. Jackson, J. F. Lemons, and H. Taube, J. Chem. Phys., 1963, 38, 836.22 K. 0. Watkins and M. M. Jones, J. Inorg. Nuclear Chern., 1962, 24, 809.23 F. Basolo, J. L. Burmeister, and A. J. Poe, J . Amer. Chem. SOC., 1963, 85, 1700.24 J. S. Oh and J. C. Bailar, J. Inorg. Nuclear Chem., 1962, 24, 1225.25 R.C. Fay and T. S. Piper, J. Amer. Chem. SOC., 1963, 85, 500.26 B. P. Block, E. S. Roth, C. W. Schaumann, and L. R. Ocone, Inorg. Chew,.,1962, 1, 860NICHOLLS : COMPLEXES 225palladium.27 The destructive autoxidation of metal acetylacetonates doesnot follow a conventional chain mechanism ; the autoxidation of iron(II1)acetylacetonate a t 100" under pure oxygen, in diphenyl ether as solvent, isinhibited by benzoyl peroxide and azobisisobutyronitrile, both of whichusually serve as good autoxidation initiators. 28 Thermogravimetric analysisstudies on metal oxalates show that oxalates of Cr(nI), Mi(@, Fe(n), Fe(In),and Zn(rr) give oxides on thermal decomposition in air or nitrogen; oxalatesof CO(II), Ni(rr), and CU(II) give the metal when decomposed in nitrogen.29Compounds containing a range of valence states of vanadium, chromium,and manganese have been studied in sulphuric acid and oleum systems.Amonomeric chromium( v) complex arises when potassium chromate is addedto 65% oleum; in the same solvent, potassium permanganate givesmanganese( 1v) sulphato-complexes. 30 Detailed absorption spectra of crystalscontaining octahedral cobalt( 111) and chromium(n1) have been measuredand assignments discussed in relation to a four-parameter crystal-fieldtheory.31 The fist compound with a stable boron-metal a-bond has beenprepared by reaction of chlorobis( dimethylamino) borane with sodium penta-carbonylmanganate(1) ; the orange, crystalline product, (Me,N),BMn(CO) 5,decomposes at 60".32The preparation and magnetic properties of complex fluorides havingthe perovskite structure have been examined.The iron, cobalt and nickelcompounds, KMI1F3, are antiferromagnetic ; KCuF, has a structure distortedfrom the cubic perovskite to one with tetragonal symmetry. The sodiumsalts NaMIIF, (MI1 = Mn, Fe, Co, Ni, Zn) are not isomorphous with thecorresponding potassium compounds ; the nickel compound at least isferr~magnetic.~~ The fluorides AIBVF, fall into five structural types, thestructure adopted depending upon the sizes of the ions A and B.34 Metal-halogen stretching frequencies in tetrahedral complex metal halides havebeen examined; M-C1 stretches occur at 380 and 290 cm.-l for the MII1and MI1 chlorides, respectively.In the carbonyl halides the metal-halogenfrequencies lie in the region 200-300 cm. -1.35 Complexes containing onlynitrate anions as ligands have been isolated by stabilising the large nitrato-ions in the crystal lattice with large cations, e.g., [Co(DMS0)J2+ and[Ph,AsMe] + (DMSO = dimethyl sulphoxide), vix. :MeCN MCl, + BPh,AsMeI + 4AgN0, + [Ph,AsMe],[M(NO,),] + 2Ag;Cl + 2AgIwhere M = CO(II), Mn(II), Ni(II), CU(II). The tetranitratometallates ofCU(II) and Ni@) appear to be six-co-ordinate, from spectral and magnetic27 C. Djordjevic, J. Lewis, and R. S. Nyholm, J., 1962, 4778.28 E. M. Arnett and M. A. Mendelsohn, J. Amer. Chem. SOC., 1962, 84, 3520, 3824.29 D. Dollimore, D. L. Griffiths, and D. Nicholson, J., 1963, 2617.30 H. C. Mishra and M.C. R. Symons, J., 1963, 4490.31 J. Ferguson, D. L. Wood, and K. Knox, J. Clbem. Phys., 1963, 39, 881; D. L.Wood, J. Ferguson, K. Knox, and J. F. Dillon, ibid., 890.32 H. Noth and G. Schmid, Angew. Chem., 1963, '75, 861.33 D. J. Machin, R. L. Martin, and R. S. Nyholm, J., 1963, 1490; D. J. Machinand R. S. Nyholm, ibid., 1500.3 4 R. D. W. Kemmitt, D. R. Russell, and D. W. A. Sharp, J., 1963, 4408.35 R. J. H. Clark and T. M. Dunn, J., 1963, 1198; M. A. Bennett and R. J. H.Clark, Chem. and Ind., 1963, 861.226 INORGANIC CHEMISTRYdata, and so must contain bridging (or chelate) and termina.1 nitrate groups,36cf. ref. 5. Octahedral co-ordination is also found in the perchlorate di-hydrates of bivalent manganese, cobalt, and nickel, the anions being presentas bidentate groups.Unidentate perchlorate groups me found in copper(=)perchlorate dih~drate.~’ The observed magnetic and spectroscopic pro-perties of the d* (n = 0,1,2,8,9,10) transition-metal cyamide complexeshave now been rationalised on ligand-field the0ry.~8 Infrared data showthat in these cyanides the extent of metal to cyanide n-bonding increasesas the number of de electrons increases and as the effective nuclear kernelcharge decreases.39 The Lewis basicity of complex cyanides has beendemonstrated by their reaction with boron trifluoride to give a new class ofcompounds containing cyanide bridges between the transition metal andboron (e.g., E”--BF,). Representative compounds are K2Ni(CN),,4BF3,K,Fe(CN),,6BF3, and K,MO(CN),,~BP,.~~ Peroxy-complexes of transition-metal ions have received considerable attention.The peroxy-speciesFe3+(H,0),(H,02) and Fe3+(H,0),0,H- are responsible for the catalyticactivity of ferric ions in the decomposition of hydrogen peroxide. Over awide range of H,02-H,O compositions tungstate and molybdate ions formsingle peroxy-complexes existing in two conjugate forms, MOg2- andHMOS- (M = W, Mo). The decomposition of hydrogen peroxide-watermixtures by chromate and vanadate ions has also been studied. Thestructures of the tetraperoxy-dimolybdate and -ditungstate anions has beeninvestigated and the basic formula for these compounds established 41 asAmides invariably co-ordinate to transition-metal ions through oxygen,giving, for example, the octahedral [NiL,](ClO,), and [CrL,](ClO,),(L = iV-methylformamide, NN-dimethylformamide, acetamide, NN-di-methylacetamide).The complexes with amides which have hydrogenatoms on the nitrogen give rise to a higher Dq value than those with alkylgroups on the nitrogen; steric repulsion between alkyl groups attached tonitrogen appears to be more important than inductive effects in these com-po~ds.*2 The infrared spectra of EDTA and its salts in aqueous solutionhave been recorded as a function of solution acidity, and the positions of theacidic protons on the ligand established. Two of the protons are on nitrogenatoms, and the other two are on two of the four carboxylate groups.43Several new complexones have been prepared, e.g. , N-( 2-furfury1imino)-diacetic acid (5) and N - (tetrahydropyran-2-ylmethy1)iminodiacetic acid (6)in which donor oxygen atoms are incorporated in either an aromatic (5),(M2Oll) -*36 D.K. Straub, R. S. Drago, and J. T. Donoghue, Inorg. Chem., 1962, 1, 848.37 B. J. Hathaway, D. G. Holah, and M. Hudson, J., 1963, 4586.3* J. R. Perumareddi, A. D. Liehr, and A. W. Adamson, J . Amer. Chem. SOC.,39 L. H. Jones, Inorg. Chem, 1963, 2, 777.40D. F. Shriver, J. Amer. Clzem. Soc., 1963, 85, 1405.4 1 T. J. Lewis, D. H. Richards, and D. A. Salter, J., 1963, 2434; P. Flood, T. J.Lewis, and D. H. Richards, ibid., 2446, 5024; A. J. Dedman, T. J. Lewis, and D. H.Richards, ibid., 2456, 5020; W . P. Griffith, ibid., 5345.42 R. S. Drago, D. W. Meek, M. D. Joesten, and L. Laroche, Inorg.Chem., 1963,2, 124; W. E. Bull, S. K. Madan, and J. E. Willis, ibid., 303.43 D. T. Sawyer and J. E. Tackett, J. Arner. Chem. Soc., 1963, 85, 314.1963, 85, 249NICHOLLS : COMPLEXES 227or aliphatic environment. Complexes of N-( 2-pyridylmethy1)iminodiaceticacid have stability constants only slightly less than those for the correspond-ing complexes of the much more basic aliphatic analogue, ethylenediamine-NN-diacetic acid; the enhanced stability of the former complexes isattributed to n-bonding (pyridine being the n-acceptor). Stability constantsCHZ*CO~H),0'(5) (61of metal complexes with several other iminodiacetic acid derivatives andwith piperazine-l,4-diacetic acid have been measured and compared withdata for similar complexones.4* Complexes of 2-hydroxyethyliminodiaceticacid are apparently of two distinct types.In the octahedral K,[Ni(HO-A),]and Na[Co(HO-A),] the ligand co-ordinates through the nitrogen and twocarbonyl oxygen atoms. Co-ordination to the alcoholic OH groups as wellas to one carboxylate appears to occur in [Ni(HO-AH),] and [CO(HO-AH),].~~Experimental evidence is consistent with the formulation of the pinknickel(=) salt of 1,9-diamino-5-(6-amino-~-azabutyl)-5-ethyl-3,7-diaz~no~-ane, (NiC,,H3,N6)I,, as containing a sexidentate chelating ligand.46 In theethylene-urea complexes CdC1,,2EU, ZnCl,,ZEU, CuCl,,ZEU, CoC1,,3EU,and FeCl,,ZEU, infrared evidence suggests that the metals are bound tooxygen.*' Similarly, metal complexes of ZY6-dimethyl-4-pyrone andZY6-dimethyl-4-thiopyrone contain metal-oxygen and metal-sulphur co-ordinate bonds, re~pectively.~~ Croconate and squarate (diketocyclo-butenediol di-anion) ions give polymeric complexes with bivalent metalions; the former have the composition MC,05,3H,0 (M = Cu, Fe, Zn, Ni,Mn, Co, Ca).49 Some new co-ordination compounds of amine N-oxides havebeen characterised.Picolinic acid N-oxide forms octahedral non-electrolytes(7) where M = bivalent Mn, Fe, Coy and Ni. These complexes are spin-freeexcept for the diamagnetic cobalt (11) cornp0und.5~ Complexes formed by2,2'-bipyridyl NN'-dioxide are electrolytes and contain the complex cations[M(bipyO,),ln+ (M = Cr3+, Mn2+, Fe3+, Go,+, N2+, Cu2+, Zn2'+, and4 4 H. Irving and J. J. R. F. da Silva, J., 1963, 1144, 945, 3308; H.Irving and4 5 R. A. Krause, Phorg. Chem., 1963, 2, 297.R. W. Green, K. W. Catchpole, A. T. Phillip, and F. Lions, Inorg. Chem., 1963,4 7 R. J. Berni, R. R. Benerito, W. M. Apes, and H. B. Jonassen, J. Inorg. Nuclear4 8 H. B. Gray, E. Billig, R. Hall, and L. C. King, J. Inorg. Nuclear Chenz., 1962,4 9 R. West and H. Y. Niu, J. Amer. Chem. Soc., 1963, 85, 2586.soA. B. P. Lever, J. Lewis, and R. S. Nyholm, J., 1962, 5262.L. D. Pettit, ibid., 3051.2, 597.@hem., 1963, 25, 897.24, 1089228 INORGANIC CHEMISTRYCdZ +).51 Intensely coloured compounds have been obtained by reaction ofphenanthraquinone and chrysinequinone with metal halides in acetic acid.Typical products are phenqu,MnBr, (tetrahedral), ZphenqqNiBr, (tetra-hedral or octahedral), and 3phenqu,FeBr, (~ctahedral).~, Spectrochemicalstudies on primary amine complexes show that the amines occupy a higherposition in the spectrochemical series than water.One very importantfactor, influencing the greater stability of ammonia than amine complexes inwater, is the higher heat of hydration of methylamine than ammonia.53Extensive studies have been made on the stabilities of complexes of 1 , l O -phenanthroline and its derivative^.^^ The 1 : 1 metal complexes with1 ,lo-phenanthroline have stabilities which follow the Irving-Williams order ;for the 3 : 1 complexes, however, the order of increasing stabilities isMn < Cd < Zn < Co < Cu < Fe < Ni. The anomalous stability of theferrous tris-complex arises because K , (the stepwise stability constant) isgreater than both K , and K,, owing to the formation of a spin-paired complex.Complexes of 2-methyl-l , 10-phenanthroline are appreciably less stable thanthose of 1,lO-phenanthroline ; complexes with 2,9-dimethylphenanthrolineare still less stable owing to the increased steric hindrance. With Ei-methyl-1 ,lo-phenanthroline, however, there is no possibility of steric hindrance, andits metal complexes are more stable than those of the unsubstituted ligand.Thermodynamic data for complexes of 2,2'-bipyridyl with the M~(II), Ni(II),CU(II), and Zn(I1) ions have been tabulated.55 Intensely coloured neutralcomplexes, L,M, are readily formed with the terdentate chelating agents (8).Their stability is such that (8) can readily remove iron, cobalt, and nickelfrom their EDTA comple~es.~~ Hexamethylphosphoramide forms 1 : 4adducts with perchlorates of bivalent zinc, cobalt, and these com-plexes contain the tetrahedral cations M[PO(NMe,)3],2 +.The preparationand detailed characterisation of some compounds containing the anion[ (EtO),P( O)CHCOCH,] -( L) is reported ; the cobalt complex (CoL,), is apale pink solid containing octahedrally co-ordinated cobalt, and evidentlyinvolves association of CoL, molecules. 58 The copper(1) iodide complexesof bis(diethy1amino)phenylphosphine are of two types; the 1 : 1 complex is atetramer whilst the 1 : 2 complex [ PhP(NEt,),],CuI is monomeric, apparentlycontaining three-co-ordinate copper. 59 From a comparison of stabilityconstants of some bivalent-metal complexes with ligands containing oxygenand sulphur donor atoms, it is concluded that copper and nickel have alarger affinity towards sulphur than oxygen, whilst the reverse is true forzinc, cadmium, and palladium.60 The position of sulphur ligands in the51 P.G. Simpson, A. Vinciguerra, and J. V. Quagliano, Inorg. Chem., 1963, 2, 282.62 P. J. Crowley and H. M. Handler, Inorg. Chem., 1962, 1, 904.53 R. S. Drago, D. W. Meek, R. Longhi, and M. D. Joesten, Inorg. Chem., 1963,54 H. Irving and D. H. Mellor, J., 1962, 5222, 5237; W. A. E. McBryde, D. A.s5 G. Atkinson and J. E. Baumann, Inorg. Chem., 1962, 1, 900.56 J. F. Geldard and F. Lions, Inorg. Chem., 1963, 2, 270.57 J. T. Donoghue and R.S. Drago, Inorg. Chem., 1962, 1, 866.F. A. Cotton and R. A. Schunn, J. Amer. Chem. SOC., 1963, 85, 2394.59A. P. Lane and D. S. Payne, J., 1963, 4004.60 K. Suzuki and K. Yamasaki, J . Inorg. Nuclear Chem., 1962, 24, 1093.2, 1056.Brisbin, and H. Irving, ibid., 5245NICHOLLS: COMPLEXES 229spectrochemical series is related to the number of lone-pair electrons availableon the sulphur atom ; thus, diethyl dithiophosphate < diethyldithiocarbam-ate < di(2-aminoethyl) sulphide < sulphite ion.61 Two distinct types ofcompound are formed by 2-mercaptoethylamine (L) and transition-metalions. One type consists of monomers, ML, (M = Ni, Pd) and CoL,; thenickel compound gives adducts with aqueous solutions of several metalsalts, i.e., [M(NiL2)J2+ ( M = CU(I), CU(II), Pd(II), Pt(II), and Cd(I1)).Nickel(n) and palladium(I1) also form [M(ML,),]Cl, type compounds ; thenickel trimer (9) is diamagnetic, indicating that all three nickel atoms areNi‘5contained in planar co-ordination polygons.62been reported for the configurational equilibrium,Thermodynamic data haveCoL,X, (tetrahedral) + 2L f CoL,X, (octahedral),in chloroform solution, where L = pyridine or 2-methylpyridine, andX = C1, Br, I, OCN, SCN, or SeCN.The nature of L and X has a strikingeffect on the degree of co-ordinative unsaturation of the metal ion in thetetrahedral state. Data are interpreted in terms of steric and electroniceffects, and correlations made with the preferred configuration of CoL2X,in the solid state.s3 Errors inherent in competitive methods of determiningstability constants of mononuclear complexes have been analysed andmethods suggested for minimising these errors.64Mechanisms of Reactions of Inorganic Complexes.-Space restrictionforbids any but the briefest review of the literature in this field.Twoimportant reviews have concerned the kinetics and mechanism of replace-ment reactions of co-ordination c0mpounds,6~ and the trans-effect in metalcomplexes. 66Fast-reaction techniques continue to give important results in this field.The pressure-jump method has been developed to give a useful, sensitive,and widely applicable tool for the investigation of fast chemical reactions insolution. The application of the method is described and the rate constantsof the reaction V02+ + SO,z- + VOSO, determined.67 The stopped-flowtechnique has been more widely used, e.g., in an investigation of the stepwisenature of the dissociation of nickel@)-polyamine complexes.Using appro-priate polyamine ligands, the effect of the number of rings, ring size, ligand61 C. K. Jsrgensen, J . Inorg. Nuclear Chem., 1962, 24, 1571.6 2 D. C. Jicha and D. H. Busch, Inorg. Chem., 1962, 1, 872, 878, 884.~ 3 3 H. C. A. King, E. Koros, and 8. M. Nelson, J., 1963, 5449.6 4 S. Cabani, J., 1962, 5271.6 6 R. G. Wilkins, Quart. Rev., 1962, 16, 316.66 F. Bas010 and R. G. Pearson, Progr. Inorg. Chem., 1962, 4, 381.H. Strehlow and H. Wendt, Inorg. Chem., 1963, 2, 6230 INORGANIC CHEMISTRYbranching, and strain factors on complex reactivity can be assessed.G* Thetechnique has also been used in the study of chloride elimination reactions ofchlorw(ethylenediaminetetraacetateo)cobaltate(m) catalysed by variousmetal ions; the dominant reaction occurring when ferrous ion is used aspotential catalyst is the reduction of cobalt(1n) to cobalt(11).6~ A mixtureof the sexidentate and aquoquinquedentate cobalt(II1)-EDTA complexes isproduced when the aquoquinquedentate cobalt@)-EDTA complex isoxidised by hexachloroiridate(1v) ions in aqueous solution.70 The tempera-ture-jump technique has been used to establish that the rate-determiningstep in the formation of nickel(I1) and cobalt(I1) complexes with variousglycines, following the initial formation of an ion-pair, is the dissociation ofa water molecule from the inner hydration sphere of the metal ion.71Extreme pressures (1040,000 atmospheres) increase the rate of racemisa-tion of potassium trioxalatocobaltate(rI1) in the solid state ; the negativevoIume of activation is consistent with an intramolecular mechanism.72The trisacetylacetonates of Cr(III), CO(III), and Rh(m) can be chromato-graphically resolved on a 16 ft.column of d-lactose hydrate. Upon electro-philic substitution, the optically active chelates retained their activity,which suggests that the chelate rings are not ruptured during the substitu-t i ~ n . ~ ~ Partial resolution of some p-ketoimines of CU(II) and Ni(I1) intooptically active forms has also been achieved using this type of c0lumn.7~A start has been made towards the study of exchange rates of complexes inliquid ammonia using 15N tracer and 14N nuclear magnetic resonance tech-niques ; as compared to water, however, considerable difficulties arise, e.g.,specific ion effects with nitrate and perchlorate ions are present even inconcentrations which are low by aqueous standards.75 Proton resonancespectra of cobalt(m) complexes show differences between cis- and trans-ammine groups. Separate rates of replacement of protons on nitrogens cisand trans to the other ligand can consequently be measured by following therelative decreases in intensity of the separate lines. 76Evidence has been obtained for both geometric and optical isomers of[tetren CoCl12 + (tetren = tetraethylenepentamine) by utilising an electron-transfer reaction.Reduction of this cation with bivalent chromium orvanadium in aqueous perchloric acid yields a rate plot which shows twocomponents to be present. The effect of chelation by non-bridging ligandson the rate of reduction of cobalt(rr1) sulphato- and acetato-complexes hasalso been examined." Reactions of halogenopenta-amminecobalt (111)cations with " one-electron " and " two-electron " oxidants have been68 G. A. Melson and R. G. Wilkins, J., 1963, 2662.6s R. Dyke and W. C. E. Higginson, J., 1963, 2788; A. Pidcock and W. C. E.TOR. Dyke and W. C. E. Higginson, J., 1963, 2802.7 1 G. C. Hammes and J. I. Steinfield, J. Amer. Chem. SOC., 1962, 84, 4639.7% J. Brady, F. Dachille, and C. D. Schmulbach, Inorg.Chem., 1963, 2, 803.73 J. P. Collman, R. P. Blair, R. L. Narshall, and L. Slade, Inorg. Chem., 1963,7 4 T-M. Hseu, D. F. Martin, and T. Moeller, Inorg. Chem., 1963, 2, 587.75 J. P. Hunt, H. W. Dodgen, and F. Klanberg, Inorg. Chem., 1963, 2, 478; T. W.76 P. Clifton and L. Pratt, Proc. Chem. SOC., 1963, 339.7 7 R. T. M. Frazer, Proc. Chem. SOC., 1963, 262; Inorg. Chem., 1963, 2, 954.Higginson, ibid., 2798.2, 587.Swaddle, L. F. Coleman, and J. P. Hunt, ibid., 950NICHOLLS : COMPLEXES 231studied kinetically. The most novel aspect of this work is the extraordinaryefficiency found for the transfer of halide ions to the co-ordinationsphere of cobalt(nI), in particular for the reactions of [Co(NH,),II2+ and[Co(NH,),Br]2 + with chlorine, where quantitative yields of [Co(NH3) ,Cl12+are obtained.78 The reactions of reducing agents with the dicobalt peroxo-complex [(NH,),Co*O,*Co(NH,) ,I5+ fall into two groups.With the ionsI-, S2032-, and with Fe(II), Sn(n), and V(IV), an electron-transfer processgives rise to [(NH,) ,Co*O,*Co(NH,) ,I4 + which breaks down rapidly to givecobalt(=) and oxygen. When SO,2- or NO2- ions are used as the reducingagent the mechanism appears to be one of group rearrangement rather thanelecfron-transfer, and equivalent amounts of cobalt(=) and Con* (NH,) ,Xn+(X = SO,, n = 1, or X = NO,, n = 2) are formed.79 A series of papershave been concerned with the kinetics of formation and dissociation ofcomplexes of copper(=) and nickel(I1) with multidentate ligands.A chainreaction mechanism is proposed for the exchange of triethylenetetramineand ethylenediaminetetra-acetate between their nickel(1) and copper(=)complexes, i.e.,The chain reaction is initiated by a trace of either of the multidentateligands; metal ions terminate the chain, so that the reaction can be usedfor trace-metal determination.80Mechanistic studies on the aquation and base hydrolysis of numerousoctahedrally co-ordinated cobalt(II1) cations have been carried out, but ithas not usually been possible to determine the steric course of substitutionwith certainty. In the cations [Co(NH,),X]+ an SNlm hydrolysis mech-anism is proposed when X = C1-, Br-, and NO,- and an &ZCB mechanismwhen X = F-;81 other cations studied include the azide {CON,(NH,),]+,~~[ Co en,CNCl] +,83 trans-[Co en,NO,Br] +,84 cis- and trans-[Co en2(H,0)C1]2+,s5[Co en,NO,( SCN)] +, 86 [ Co en2( SCN)N,] +* (en = ethylenediamine) and [ Cotrien Cl,] + (trien = triethylenetetrammine). 88 Some striking differenceshave been found between the hydrolysis of (chloroammine)rhodium( III)complexes and the analogous cobalt(n1) systems.The rate of reaction ofa rhodium complex is insensitive to the charge on the complex, and alkalihas little or no effect on the rate of hydrolysis. Further, reactions ofrhodium( 111) complexes occur with almost complete retention of configura-t i ~ n . ~ ~ The r61e of cyanide ion as a substituting agent towards trans-[Co en,Cl,] + has been investigated ; it is conclusively shown that cyanide isNiT2+ + CuY2--+ CuT2+ + NiY2-.'*A.Haim and H. Taube, J. Arner. Chern. SOC., 1963, 85, 495, 3108.' ~ 3 A. G. Sykes, Trans. Farad. SOC., 1963, 59, 1325, 1334, 1343.D. W. Margerum, D. B. Rorabacher, and J. F. G. Clarke, Inorg. Chem., 1963,2, 667; T. J. Bydalek and D. W. Margerum, ibid., 678, 683; D. C. Olson and D. W.Margerum, J . Amer. Chem. SOC., 1963, 85, 297.81 M. Green and H. Taube, Inorg. Chem., 1963, 2, 948.82 G. C. Lalor and E. A. Rloelwyn-Hughes, J., 1963, 1560.83 S. C. Chan and M. L. Tobe, J., 1963, 514.84 C. H. Langford and M. L. Tobe, J., 1963, 506.8 5 S. C. Chan, J., 1963, 5137.86 A. Rogers and P. J. Staples, J., 1963, 4749.37 P. J. Staples, J., 1963, 3226.8 8 A. M. Sargeson and G. H. Searle, Nature, 1963, 200, 356.8n S.A. Johnson, F. Basolo, and R. G. Pearson, J. Amer. Chern. SOC., 1963,85, 1741232 INORGANIC CHEMISTRYeffective as a reagent only when cobalt(I1) species are present to act ascatalysts, the mechanism being a redox process.g0 Kinetic studies on thereactions [Ru phen,py,12+ + X- -+ cis-[Ru phen,pyX]+ + py (phen =o-phenanthroline, py = pyridine) show that only those anions, X, whichhave potentially vacant p-orbitals for n-bonding (N, -, NO, -, CN -) engagein bimolecular substitution, the anions Cl-, Br-, I-, NCS-, and OH- conse-quently substituting by a unimolecular process.91Carbonyk-The chemistry of the metal carbonyls has been revie~ed.~2The rare-gas rule for the electronic structure of metal carbonyls and othercomplexes has been discussed in relation to changes in the electrostaticpotential field of the metal caused by the ligands.Support is found for theview that when the a-bonds are formed by ligand lone-pair donation, therare-gas rule will apply only if there is substantial electron-transfer fromthe metal n - ~ r b i t a l s . ~ ~ The bonding in metal hexacarbonyls and hexa-cyanides has been described in terms of molecular orbitals, and a molecularorbital energy level scheme presented which is able to account for theobserved d-d and charge transfer absorption bands in the d6 metal com-p l e ~ e s . ~ ~ A simple model has been proposed for analysing and assigninginfrared-active carbonyl stretching frequencies of simple and substitutedmetal carbonyls of the type ML,(C0)6-z, i.e., those with essentially octa-hedral distribution of ligands around the metal atom.The method hasbeen applied to molecules in which M = Cry Mo, W, and L = a variety ofamines, and the results discussed in terms of the n-bonding abilities of thel i g a n d ~ . ~ ~The first example of a hexanuclear metal carbonyl is Rh6(CO)16 [previ-ously reported as Rh,(CO),J. In each molecular unit the rhodium atomsare located at the corners of an octahedron; twelve of the CO groups areterminal groups and four are located on three-fold axes above four of theoctahedral faces.96 A polynuclear tetracarbonyl of technetium [Tc(CO),],is formed during treatment of the pentacarbonyl Tc,(CO),, with sodiumamalgam and subsequent acidifi~ation.~' Reaction of the pentacarbonylwith halogens gives Tc( CO),X and [Tc(CO),X], ; high-resolution infrareddata suggest that the latter has a halogen bridged (DZh) structure.So faronly traces of the pentacarbonyl hydride HTc(CO), have been prepared.98Besides giving organometallic complexes, the reaction of Fe,( CO),, withmethylphenylacetylene and, in particular, with pent-1 -yne gives smallquantities of a new type of polynuclear complex iron carbonyl carbideFe5( C0)15C. In this compound there is an approximately equilateral tetra-gonal pyramid of iron atoms with three terminal carbonyl groups attached90 S. C. Chan and M. L. Tobe, J., 1963, 966.O 1 B. Bosnich, Nature, 1962, 196, 1196.92 E. W. Abel, Quart. Rev., 1963, 17, 133.03 D. P. Craig and G. Doggett, J., 1963, 4189.94 H.B. Gray and N. A. Beach, J. Amer. Chem. SOC., 1963, 85, 2922.95 F. A. Cotton and C. S. Kraihanzel, J. Amer. Chem. SOC., 1962, 84, 4432; idem,96 E. R. Corey, L. F. Dahl, and W. Beck, J. Amer. Chem. Xoc., 1963, 85, 1202.97 H. D. Kaesz and D. I<. Huggins, Cunud. J. Chem., 1963, 41, 1250.9s J. C. Hileman, D. K. Huggins, and H. D. Kaesz, Inorg. Chem., 1962, 1, 933;Inorg. Chem., 1963, 2, 533.M. A. El-Sayed and H. D. Kaesz, ibid., 1963, 2, 158NICHOLLS : COMPLEXES 233to each iron atom; a five-co-ordinate carbon atom is located slightly belowthe centre of the basal plane of iron atoms and at approximately equaldistances from-each of the five iron at0ms.9~ Mossbauer studies have beencarried out on some iron carbonyls; the observed isomer shifts are in agree-ment with a trigonal-bipyramidal structure for Fe(CO), and Fe2(C0)9, butthe data for Fe,(CO),, strongly suggest the linear structure and cannot beaccounted for by the trigonal-bipyramidal arrangement of the three ironatoms which has been proposed on the basis of X-ray data.100 The highresolution nuclear magnetic resonance spectra of hydrido-, methyl, andethyl derivatives of metal carbonyl and n-cyclopentadienyl carbonylcomplexes have been recorded, and the data compared with those fornon- transition- metal compounds. 101 Bis( pentacar bony1manganese)germane ,H,Ge[Mn(CO),],, has been isolated as a yellow solid from the reaction ofmanganese pentacarbonyl hydride with germane in tetrahydrofuran.lo2The reduction of nickel carbonyl with lithium amalgam in tetrahydrofurangives Li,[Ni,(CO)8] ; sodium, potassium, and magnesium amalgams give lo3derivatives of the anion [Ni4(C0)9]2-.The new complex ions [M(CO),X]-(M = Cr, Mo, W; X = C1, Br) have been isolated as tetra-alkylammoniumsalts in diethylene glycol dimethyl ether, vix. :lo4R,N+X- + M(CO), + R,N+[M(CO),X]- + CO.Hexacarbonyls of molybdenum and tungsten give carbonyl cyanides,K,[M(CO),( CN),], when treated with potassium cyanide in liquid ammonia ;Na,[W,(CO),,] can also be prepared in liquid ammonia, at 60°, by the actionof sodium borohydride on tungsten he~acarbonyl.10~ The reactions ofalkali-metal derivatives of metal carbonyls with organic halogen compoundshave been extensively studied. log The orange crystalline iron complexes(n-C,H,)Fe(CO),CO[CH2]nCOFe(CO)2(n-C5H5), where n = 3 and 4, areobtained when NaFe(CO),(n-C,H,) reacts with the appropriate acid chloride.Reaction of the same alkali-metal derivative with om-dibromides,Br*[CH,];Br (n = 3, 4, 5 , 6), gives stable, orange crystalline solids[ CH21n[(7c-C ,H ,)Fe( CO),],, and with 1,4-dichlorobut -2-yne the acetylenederivative (n-C,H,)Fe(CO),CH,*C:C~CH,Fe(CO),(n-C,H,) is produced as wellas [(n-C,H,)Fe(CO),],.Exchange studies with W O on manganese penta-carbonyl halides reveal that the axial CO group in these compounds is moreinert than the other four CO groups, and this fact has been used in a mole-cular-orbital treatment of the bonding in Mn(C0) ,X.107 The isomerscis- and trans-Mn(CO),L,Br, [L = P(OPh),, P(Ph)Cl,, P( O-n-C,H,),, andP(C,H,),] have been prepared; the cis-isomer obtained from the reactiong9 E.H. Braye, L. F. Dahl, W. Hubel, and D. L. Wampler, J. Amer. Chem. SOC.,loo R. H. Herber, W. R. Kingston, and G. K. Wertheim, Inorg. Chem., 1963, 2, 153.lol A. Davison, J. A. McCleverty, and G. Wilkinson, J., 1963, 1133.lo2 A. G. Massey, A. J. Park, and F. G. A. Stone, J. Amer. Chem. Soc., 1963,85,2021.lo3 W. Hieber and J. Ellerman, 2. Naturforsch., 1963, 18b, 595.lo4 E. W. Abel, I. S. Butler, and J. G. Reid, J., 1963, 2068.Io5 H. Behrens and J. Vogl, Chem. Ber., 1963, 96, 2220.R. B. King, J. Amer. Chem. SOC., 1963, 85, 1918, 1922; Inorg. Chem., 1963,10' H. B. Gray, E. Billig, A. Wojicki, andM. Farona, Canad. J.Chem., 1963,41,128~.1962, 84, 4633.2, 531234 INORGANIC CHEMISTRYof Mn(CO),Br with L, isomerises to the trans-form in solution, the extentof isomerisation increasing with increase in the size of L.l0* The structureof [C,H,SFe(CO),], is interesting in that it has a remarkably acute symmetri-oal bridging Fe-S-Fe angle of 68.3"; it is believed that a bent metal-metalbond arising from the use of octahedral type iron orbitals, which overlapat an angle of approximately 113", is largely responsible for this.lO9A large number of publications have been concerned with the reactionsof metal carbonyls with donor molecules. In liquid ammonia at 20°,Fe(C0) and Fe,(CO), form ammonium carbonylferrates,llO vix. :Monosubstitution products, Ni(CO),B, are the intermediates formed whenpyridine and other nitrogen bases (B) react with nickel carbonyl; valencedisproportionation subsequently occurs giving, e.g., [Ni(py),][Ni,(CO), 1.111The carbonyl group cis to the bipyridyl group in Mo(CO),(bipy) is readilyreplaced by ligands to give the diamagnetic non-electrolytes Mo(CO),(bipy)L(L = Ph,P, Ph,S, C5H,N).l12 In the mono- and di-substituted acrylonitrilecomplexes of the Group VI carbonyls, e.g., (CH,CHCN)W(CO),, the acrylo-nitrile is bonded not via the C-C double bond but through the lone pair onnitrogen.113 Substitution complexes with aliphatic and aromatic nitriles,e .g . , W(CO),(CH,CN), and Ni(CO),(PhCN), also contain only a-bondednitrile gr0ups.11~ The rates of reaction of Mn(CO),LX with a variety ofreagents L' to form Mn(CO),LL'X, are independent of the nature and concen-tration of L' but increase with increasing atomic number of X and decreasewith changes of L in the order PPh, > AsPh, > P(C4H9), > P(OPh),.Itseems, therefore, that a dissociation mechanism operates, in which the bulki-ness of L determines the rate of CO dissociation.l15 A similar conclusionwas reached in a kinetic study of the dissociation of acylcobalt tetracarbonylsand of n-allylcobalt tricarbonyl with triphenylphosphine as substitutingagent.116 A monosubstituted product of dicobalt octacarbonyl has beenobtained by using Nujol as the reaction medium to reduce reaction rates;multisubstitution products of triphenylphosphine precipitate while thesolution contains CO,( CO)7PPh3.117 A volatile, chelated, nickel dicarbonyl(C0)2Ni(CF3),P*CH,*C€€2*P(CF3)2 has been prepared by reaction of anequimolar mixture of nickel carbonyl and the bisphosphine.1l8 Phosphorus-bridged carbonyls are obtained when 1,Z-bisdiphenylphosphinoethane reactswith iron pentacarbonyl to give [Fe(CO),],(diphos), and similar manganesecompounds have been prepared in which o-phenylenebisdimethylarsineFe(CO), + 4NH3 --+ (NH,),[Fe(CO)J + CO(NH,),-lo8 R.J. Angelici, F. Basolo, and A. J. Poe, J . Amer. Chem. SOC., 1963, 85, 2215.log L. F. Dahl and C-H. Wei, Inorg. Chem., 1963, 2, 328.1l0 H. Behrens and H. Wakamatsu, 2. anorg. Chem., 1963, 320, 30.112 M. H. B. Stiddard, J., 1963, 756.113 A. G. Massey, J . Inorg. Nuclear Chem., 1962, 24, 1172; B.L. ROSS, J. G. Grasselli,114 I. W. Stolz, G. R. Dobson, and R. K. Sheline, Inorg. Chem., 1963, 2, 323; M.115 R. J. Angelici and F. Basolo, Inorg. Chem., 1963, 2, 728.116 R. F. Heck, J . Amer. Chem. SOC., 1963, 85, 651, 655, 657.11' G. Bor and L. Mark6, Chem. and Ind., 1963, 912.118 A. B. Burg and G. B. Street, J . Amer. Chem. Xoc., 1963, 85, 3522.W. Hilber, J. Ellerman, and E. Zahn, 2. Naturforsch., 1963, 18b, 589.W. M. Ritchey, and H. D. Kaesz, Inorg. Chem., 1963, 2, 1023.Bigorgne, Bull. SOC. chirn. France, 1963, 295NICHOLLS : COMPLEXES 235behaves as the bridging gro~p.119 Phosphorus bridging occurs also in(CO) 5MnPMe,MnfCO)4*PMe2, which is obtained as yellow crystals by reactionof chlorodimethylphosphine with sodium pentacarbonylmanganate( - 1) .120Other new derivatives with Group V ligands include Ph,MFe(CO), (M =P, As, S b) , z- C ,H ,Mn( CO) ,PPh,, Ni( CO) ,( BiEt,) , Mo( C 0) 5( S bE t ,) ,Mo(CO),(S~E~,),,~~~ and (Tdp),Ni(CO), l24 (Tdp = tris(dimethy1amino)-phosphine). The complex W(CO),(diars) (diars = o-phenylenebisdimethyl-arsine) is oxidised at room temperature with two equivalents of iodineand bromine, producing the seven-co-ordinate tungsten@) derivatives[W(CO),(diars)I]I, and [W(CO),(diars)Br,], respectively.The use of anexcess of bromine has led to the isolation of the first seven-co-ordinatetungsten( 111) complex, namely [ W(CO),(diar~)Br,]Br.~~~Dimethyl sulphide reacts with [(n-C,H,)Cr(CO),], and [(~C,H,)MO(CO),]~in refluxing methylcyclohexane, giving complexes (n-C,H5),Cr,(MeS)3 and[(~c-C~H~)MO(M~S)~],.Red, volatile, crystalline and diamagnetic com-plexes, C,H6S2Fe2(CO) 6, C,F,S,Fe,(CO) 6, and C,H,S,Fe,(CO) 6, have beenobtained by reaction of iron pentacarbonyl with toluene-3,4-dithiol, bis-(trifluoromethyl)dithiet, and 1,2-ethanedithi01.12~ Tri-iron dodecacarbonylreacts with cyclohexene sulphide in refluxing benzene, giving cyclohexeneco 0Y’l / 0 \Yand purple red, diamagnetic, and volatile Fe,(C0)9S,( The newdimeric series of compounds, MII(CO)~SR, and [(n-C,H,)*M(CO),SR],(M = Mo, W), result from reactions of alkyl disulphides with the carbonylhydrides M i ( CO ) 5H and (n-C ,H B)M( CO)3H. 28Nitro&.-Substitution reactions of nitrosyltricarbonyl cobalt lead tostepwise replacement of carbon monoxide, forming Co(N0) (CO),L andCo(NO)(CO)L, (L = triaryls of P, As, or Sb) ; reaction of the monosubstitutedderivatives with thiols gives the complexes [Co(NO)(L)( SR),].In alco-holic and basic solution the following reaction occurs :I293Co(CO),NO +90H- +[Co(CO),]- +2Co(OH), +2HCO,- + 3COS2- +N, +NH,.119 J. Lewis, R. S. Nyholm, A. G. Osborne, S. S. Sandplu, and M. H. B. Stiddard,121 A. F. Clifford and A. K. Mukherjee, Inorg. Chem., 1963, 2, 151.122 W. Strohmeier and C. Barbeau, 2. Naturforsch., 1962, 17b, 848.lZ3 D. Benlian and M. Bigorgne, Bull. SOC. chim. France, 1963, 1583.lZ4 R. B. King, Inorg. Chem., 1963, 2, 936.lZ5 J. Lewis, R. S. Nyholm, C. S. Pande, and M. B. H. Stiddard, J., 1963, 3600.126 R. B. King, J. Amer.Chem. SOC., 1963, 85, 1587, 1584.12’ R. B. King, Inorg. Chem., 1963, 2, 326.128 P. M. Treichel, J. H. Morris, and F. G. A. Stone, J., 1963, 720.129 W. Hieber and J. Ellerman, Chem. Ber., 1963, 96, 1643, 1650, 1667.Chem. and Ind., 1963, 1398.R. G. Hayter, 2. Naturforsch., 1963, 18b, 581236 INORGANIC CHEMISTRYThe infrared spectra of mono- and di-substituted derivatives of Co(NO)(CO),have been recorded ; the n-electron accepting abilities of co-ordinated carbonmonoxide and nitric oxide are compared and a “ spectrochemical series ”for n- bonding ligands is proposed. 130 The nitrosyltricarbonylferrate( - 1)anion is formed by the action of nitrite ion on iron pentacarbonyl or tetra-carbonylferrate( - 1 ), and also in the reaction of dinitrosyldicarbonylironwith alkali in rnethan01.l~~ Stable, golden brown, diamagnetic crystals ofthe iridium nitrosyl K [IrBr,NO] which contains co-ordinated NO + havebeen prepared from potassium hexabromoiridate(rrr) by use of potassiumnitrite and hydrobromic acid.132 Diamagnetic K,Mo(CN) 5N0 is alsoformulated as containing NO + with molybdenum in a formally zero oxidationstate.133 The analogous chromium compound, K,[Cro(CN) ,NO], isolatedas blue crystals from the electrolytic reduction of aqueous K3[Cr1(CN) 5N0],is very sensitive to aerial oxidation. By treatment of a suspension ofchromium( 11) chloride in liquid ammonia with nitric oxide, paramagneticpentamminenitrosylchromium(1) chloride, [Cr( NO)(NH,),]Cl,, is obtained. l 3 4(Phosphine oxide)chromium( 11) halides form diamagnetic complexes,Cr(NO),( OPPh3),X2, with nitric oxide.135 The nitroprusside ion has C,,symmetry, the Fe-N-0 portion of the ion is strictly linear as are theFe-CzN groups.136 The structures of nitrosylcyano-complexes have beenreviewed.137 Dimeric dinitrosyliron halides, [Fe(NO),X],, and monomerictrinitrosyliron halides, Fe(NO),X, react with a variety of ligands, formingthe complexes Fe( NO),LX ; in molten triphenylphosphine, dinitrosylironbromide uudergoes valence disproportionation, giving Fe( NO) (PPh,),Br,and Fe(NO),(PPh,),.13* The bridging nitrosyls [ (~-C,H,)CT(NO)~], and[n-C,H,MnCO(NO)], are formed in the reduction of (n-C,H,)Cr(NO),Cl and[ (n-C,H,)Mn(CO),NO] +, respectively, with sodium borohydride ; infraredevidence suggests that the bridged chromium nitrosyl has the structureO l e 5 and n-AUylic Complexes.-The chemistry of metal n-complexeswith di- and oligo-olefinic ligands has been reviewed.14* Allylamine com-plexes of platinium PtCl,(L)HCl (L = CH,:CH*CH,*NR,) have been shown(1 1 ) .139130 W.D. Horrocks and R. C. Taylor, Inorg. Chem., 1963, 2, 723.131 W. Hieber and H. Beutner, 2. anorg. Chem., 1963, 319, 285; ibid., 1963, 320,132 L. Malatesta and M. Angoletta, Angew. Chem., 1963, 75, 209.133 R. F. Riley and L. Ho, J . Inorg. Nuclear Chem., 1962, 24, 1121.134 W. P. Griffith, J., 1963, 3286.135 W. Beck and K. Lottes, Chem. Ber., 1963, 96, 1046.P. T. Manoharan and W. C. Hamilton, Inorg. Chem., 1963, 2, 1043.137 B. Jezowska-Trzebiatowska and J.Ziolkowski, 2. Chem., 1963, 3, 333.138 W. Hieber and R. Kramolowsky, 2. anorg. Chem., 1963, 321, 94.R. B. King and M. B. Bisnette, J . Amer. Chem. SOC., 1963, 85, 2528.140 E. 0. Fischer and H. Werner, Angew. Chem. (Internat. Edn.), 1963, 2, 80.103; Chem. Ber., 1963, 98, 1659NICHOLLS : COMPLEXES 237to be olefin complexes (12) of the cationic species LHf, analogous to Zeise'ssalt.141 Cyclo-octa-l,3,5-trieneiron(O)-cyclo-octa-l,5-diene, C8Hl,FeC8Hl,,has been prepared as red crystals, m.p. 86-88" and sublimable in a highvacuum; it contains only olefinic functional groups bonded to iron.142Olefinic ligands react with di-iron enneacarbonyl, giving n-olefin-iron tetrs-carbonyls and liberating iron pentacarbonyl :Fe,(CO), + L --+ (n-L)Fe(CO), + Fe(CO),where L = ethylene, hexatriene, maleic, fumaric, acrylic, and cinnamicacids.Electron-withdrawing substituents on the olefin stabilise the n-bondformed by the latter with zero-oxidation state transition metals.143The bicyclo[ 2,2,2]octatriene derivative (13) gives the olefin complexesC14H14F,Fe(CO),, (~-C,H,)COC,~H~,F,, and C14H14F,Mo(C0)47 when treatedwith the carbonyls Fe(CO),, (n-C,H,)Co(CO),, and Mo(CO),, respectively.Proton and 19F magnetic resonance on the iron and cobalt derivativessuggests the existence of isomers which involve bonding of different pairsof the three double bonds of the ligand to the metal at0m.14~ Tricarbonyl-cyclo-octatetraeneiron (14) is protonated in strong acids, forming the ion[C8H,Fe(CO),]+ (15) ; hydride attack (using sodium borohydride) on thiscation produces the olefin complex(14) (1 5)CBHl,Fe(CO), (16).The formation of a Diels-Alder adduct (17) with tetra-cyanoethylene provides further evidence that tricarbonylcyclo-octatetraene-iron contains a non-bonded 1,3-diene systern.l4, The newly prepared1461 -cyanoalkyl complexes (n-C,H,)Fe(CO),R (R = CH,CN*CH,*CH,*CN andCHMeCN), are readily and reversibly protonated by strong acids, form-ing cationic ketenimine complexes [ (n-C,H,)Fe(CO),RH] +. Reduction ofthe benzenemanganese tricarbonyl cation with lithium aluminium hydrideFe K O ) 3 (cN)zE3 (CNL ( 1 7)or sodium borohydride gives small quantities of a neutral product as wellas n-cyclohexadienylmanganese tricarbonyl. Reactions and infrared studieson the new compound 147 suggest its formulation as cyclohexadienemanganesetricarbonyl hydride ( 18).14lR.G. Denning and L. M. Venanzi, J., 1963, 3241.149 E. 0. Fischer and J. Muller, 2. Naturforsch., 1963, 18b, 413.143 H. D. Murdoch and E. Weiss, Helv. Chim. Acta, 1963, 46, 1588; E. Weiss, K.144 R. B. King, J . Amer. Chern. SOC., 1962, 84, 4705.1 4 5 A. Davison, W. McFarlane, L. Pratt, and G. Wilkinson, J., 1962, 4821.146 J. K. P. Ariyaratne and M. L. H. Green, J . , 1963, 2976.1 4 7 G. Winkhaus, 2. anorg. Chem., 1963, 319, 404.Stark, J. E. Lancaster, and H. D. Murdoch, ibid., 288238 INORGANIC CHEMISTRYn-Ally1 complexes of iron have now been described. Methallyl iodidereacts with iron pentacarbonyl at 40 O to give 2-methyl-n-allyliron tricarbonyliodide.l48 The a-ally1 complexes (n-C,H,Fe(CO),(CH,CH=CHR) lose amolecule of carbon monoxide under ultraviolet irradiation, forming themallyl derivatives (n-C,H,)Fe(CO)(n-C,H,R) ; reaction of the o-allyls withhydrogen chloride results in protonation of the ally1 group, giving14Qn-ethylenic compounds (n-C,H,)Fe(CO),(n-C,H,R) +, and analogous re-actions with molybdenum compounds proceed ~irni1arly.l~~ The firstn-allylic complex of rhodium(rn), n-cyclododeca- 1,5,9-trienylrhodium(n1),has been isolated; it is believed to be polymeric with halogen bridge bonds.151When hydrocobalt tetracarbonyl reacts with buta- 1,3-diene and other dienes,n-allylcobalt tricarbonyls are produced ; isomers have been found for com-plexes of buta-173-diene, penta-1,3-diene, and penta-1,4-diene.l52Acetylene Complexes.-Air-sensitive tricarbonyltrialkynylchromium(0)complexes are prepared in liquid ammonia according to the equation:Cr(CO),NH, + 3KC:CR + K,[Cr(CO),(C:CR),] + NH,where R = H, Me, or Ph.A pale yellow, tungsten-acetylene complex,(CH,*CH,*CiC*CH,*CH,),WCO, which may contain tungsten tetrahedrallysurrounded by one CO group and three acetylene groups, has been synthesisedby refluxing (CH,CN),W( CO), in he~-3-yne.l~~ Cadmium acetylide,Cd(CiCH),,xNH,, formed in liquid ammonia from cadmium amide andgaseous acetylene, decomposes at 0 O forming the carbide CdC,.0,5NH3 ;Cd(CiCPh), is a soluble non-electrolyte in t~mm0nia.l~~ Acetylene com-plexes of platinum, M[PtCl,,L] and trans-[PfCl,(L)(amine)] (L = a tertiarya-hydroxyalkyl or a-methoxyalkylacetylene, M = Na, K) have been des-cribed in which both the CFC bond and the hydroxyl groups are involvedin the bonding.156 Two new types of compound have been discovered withthe ligand hexafluorobut -2-yne.Irradiation of tricarbonyl-n-cyclopenta-dienylmanganese(1) in the presence of this ligahd gives the complex (19),and reaction of hexafluorobut-2-yne with the compounds (Ph,M),Pt(PhCiCH)(M = P, As) leads to displacement of phenylacetylene giving, e.g., (20).157Diphenylbutadiyne gives a variety of derivatives with iron and cobalt148 R. A. Plowman and F. G. A. Stone, 8. Naturforsch., 1962, 17b, 575.149 M. L. H. Green and P. L. I. Nagy, J., 1963, 189.l s o M . Cousins and M. L.H. Green, J., 1963, 889.161 G. Pajaro and R. Palmbo, Angew. Chem., 1963, 75, 861.lS2 J. A. Bertrand, H. B. Jonassen, and D. W. Moore, Inorg. Chem., 1963, 2, 601.15s P. Sast and H. Kohl, 2. anorg. Chem., 1963, 320, 135.154 D. P. Taye and J. M. Augl, J. Arner. Chem. SOC., 1963, 85, 2174.lS5 P. Nast and C. Richers, 8. anorg. Chem., 1963, 319, 320.166 J. Chatt, R. G. Guy, L. A. Duncanson, and D. T. Thompson, J., 1963, 5170.J. L. Boston, S. 0. Grim, and G. Wilkinson, J., 1963, 3468NICHOLLS: COMPLEXES 239carbonyls ; typical products are ~e,(CO),(PhC,C,Ph), Fe(CO),(PhC,CzPh)2,and [CO,(CO),],(P~C,C,P~).~~~Complexes with Aromatic Systems.-The last ten years of progress inmetallocene chemistry has been revie~ed.1~~ A general synthesis of tetra-phenylcyclobutadiene-metal complexes uses ligand transfer from tetra-phenylcyclobutadienepalladium( 11) halides to a metal carbonyl.UsingFe(CO), and Mo(CO),, the complexes obtained are (21) and (22), respec-tively (X = halogen).160Fecooc’ I ‘ c ooc -Mo-oc ’I ‘xcoX co 0(23) 0Magnetic anisotropy measurements on ferrocene provide further evidencein favour of a single d,-pn bond between each ring and the iron atom.lslThe structure of C,H~NiC,H,C,(CO,Me), consists of discrete molecules inwhich a nickel(I1) atom is covalently bonded to a n-cyclopentadienyl anionand a norbornadienyl anion which co-ordinates to the metal via a o-bondfrom the bridged carbon atom and a p-bond from the olefinic group to whichthe methyl carboxylate substituents are attached.In this compound thereis structural evidence for a small localised interaction between the nickel(I1)atom and the cyclopentadienyl anion; this interaction is ascribed to theperturbation of the n-electron density on the cyclopentadienyl anion by therings’ molecular-orbital interaction with the dsp2 hybrid orbitals of thenickel(@ atom. 162 The stereochemistry and conformation of n-cyclopenta-dienyl- 1 -phenylcyclopentadienylcobalt has been reported. The short bondlength of 1.38 for the 3,4-bond (23) in the cyclopentadiene ring and thedeviation of C(I) from the plane of the ring indicate that the cyclopentadienering is bonded to the cobalt by one n- and two a-bonds, an unusual mode ofbonding already postulated for tricarbonyl(tetrakistrifluoromethylcyc1o-pentadien0ne)iron.163 The sandwich structure for n-cyclopentadienyl-n-cycloheptatrienylvanadium has been confirmed.164 New cyclopentadienylsprepared include the air stable, white prisms of (n-C5H5)PtIVte,,165 and the158 W. Hubel and R. MerBnyi, Chem. Ber., 1963, 96, 930.159 M. D. Rausch, Canad. J . Chem., 1963, 41, 1289.160 P. &I. Maitlis and M. L. Games, J . Amer. Chem. SOC., 1963, 85, 1887; Chem. and161 L. N. Mulay and M. E. Fox, J . Chem. Phys., 1963, 38, 760.162L. F. Dahl and C. H. Wei, Inorg. Chem., 1963, 2, 713.1133 M. R. Churchill and R. Mason, Proc. Chem. SOC., 1963, 112; cf. Ann. Reports,164 G. Engebretson and R. E. Rundle, J. Amer. Chem. SOC., 1963, 85, 481.113~ S. D. Robinson and B. L. Shaw, 2. Naturforsch., 1963, 18b, 507.Ind., 1963, 1624.1962, 181240 INORGANIC CHEMISTRYdic y clopent adien yl- lant hanide chlorides, (n- C ,H , ) ,MCl .66 The reactionbetween [ (C,H,),RhCl], and sodium cyclopentadienide in tetrahydrofuranyields the novel ethylene complex (n-C,H,)Rh(C,H4), as a yellow crystallinesolid.l67 The complexes (n-C,H,)CrX,,D (X = C1, Br, I; D = tetrahydro-furan, pyridine, or Ph,P) have been characterised; the deep blue solutionsformed upon the reaction of Cr(C,H,), with hydrochloric or hydrobromicacid contain the anions [C,H,CrX,]- which can be isolated as ammoniumsalts.168 Thiophenol and ethane- and methane-thiol react with (z-C~H,),Ni in benzene at room temperature to give black diamagnetic compounds,(n-C,H,)NiSR,.169 The diamagnetic, purple-black complex prepared from(n-C,H,),Ni and azobenzene contains the azo-group bonded to nickel in amanner similar to that in unsaturated carbon systems.l70 In contrast tothese reactions, the Lewis-basicity of tungsten in (n-C,H,),WH, has beendemonstrated by the formation of a 1 : 1 adduct with boron trifluoride.171New cyclopentadienyl carbonyls described during the year are thered, diamagnetic dimer [(n-C,H,)PtCO], 172 and the orange crystalline(n-C,H,)Nb(C0)4.173 The red-brown monomeric nitrosyl (n-C,H,)PdNO isobtained by reaction of Pd(N0)Cl with sodium cyclopentadienide inpentane. l 7 4 Vanadium hexacarbonyl behaves as an oxidising agent innon-polar solvents; it reacts with (n-C,H,),V in the presence of carbonmonoxide at atmospheric pressure to give the hexacarbonylvanadate( - 1)of the new cation dicyclopentadienyldicarbonylvanadium(1n) : 17,v11(C5H5)2 + v0(co)6 + 2co [v1”(~~H~)2(~~)~l[v-1(~~)~Iron pentacarbonyl reacts with (n-C,H,),Ni to give the brown diamag-netic complex (24), and with acetylene complexes of (n-C,H,),Ni, giving@ c,/J coI - a .’ ‘Fe(CO)C5H5 .. C,H,Ni -i ’ (24) M .: ‘ c o /(25) M (26)(n-C ,H ,Ni) ,RC:CR’Fe( CO ) 3, ( JC-C ,H ,Ni) ,RC :CR’Fe,( CO ) 6, and(n-C,H,NiRC:CR’),Fe(CO),. l 7 6 Cyclopentadienylcarbonyl cyanide com-plexes of iron, molybdenum, and tungsten, e.g., [Fe(CN),(n-C,H,)(CO)] -have been described. Alkylation of [Mo(CN),(n-C,H,)(CO),] - with methyliodide yields [Mo(n-C,H,)(CO),(CNMe),]I ; similar tungsten complexes are166 R.E. Maginn, S. Manastyrskyj, and M. Dubeck, J. Amer. Chem. SOC., 1963,ltz7 R. B. King, Inorg. Chem., 1963, 2, 528.168 E. 0. Fischer, K. Ulm, and P. Kuzel, 2. anorg. Chem., 1963, 319, 253.16% W. K. Schropp, J. Inorg. Nuclear Chem., 1962, 24, 1688.170 J. P. Kleiman and M. Dubeck, J. Amer. Chem. SOC., 1963, 85, 1544.171 D. F. Shriver, J. Anaer. Chem. SOC., 1963, 85, 3509.172 E. 0. Fischer, H. Schuster-Woldan, and K. Bittler, 2. Naturforsch., 1963, 18b,173 R. B. King, 2. Nuturforsch., 1963, 18b, 157.17* E. 0. Fischer and A. Vogler, 2. Naturforsch., 1963, 18b, 771.175 F. Calderazzo and S. Bacciarelli, Inorg. Chem., 1963, 2, 721.176 J. F. Tilney-Bassett, J., 1963, 4784.85, 672.429NICHOLLS : COMPLEXES 241described. 1 7 7 Protonation of (n-C ,H ,)Fe( CO),( a-C ,H e) with hydrogenchloride in petrol affords l 7 8 the ethylenic complex cation[(n-C,H,)Fe(CO),(n-C,H,)] +.The reaction between an isomeric mixtureof cycloctatrienes and dicarbonyl-n-cyclopentadienylcobalt leads to twoproducts. Under mild conditions, the product obtained has the structure(25), whilst under more severe conditions a compound of structure (26)[M = Co(n-C,H,)] is obtained.179 The compound [(n-C,H,)V(MeS),],obtained by reaction of (n-C,H,)V(CO), with dimethyl sulphide or methan-ethiol is unique in having four bridging MeS groups, and appears t o containformally vanadium(O), each sulphur atom being a three-electron donor tothe pair of metal atoms.180, 1 2 6 A novel ethyl-transfer reaction has beendiscovered ; when (n-C,H,)Mo(CO),C,H, is heated in a sealed evacuatedtube for two hours at 100" the ethyl group transfers to the ring to give thebinuclear [ (n-C,H,Et)Mo( CO),],.The X-ray data on bisbenzenechromium have been re-investigated inview of the discrepancy between the theoretically unnecessary distortionand the experimentally reported alternating bond lengths around the rings.It is now found that the symmetry of Cr(C6H,), does not diverge greatlyfrom six-fold, the C-C bond lengths in the rings being all about 1.40 A .l S 2A new synthetic method for bisarene-n-complexes uses a mixture of tri-ethylaluminium, a transition-metal halide, and an arene in n-heptane at130-140". The reaction mixture is digested with a small amount ofmethanol below 0" and the slurry produced hydrolysed in water; the filtratecontains the n-complex ion (hydroxide) which can be isolated as, e.g., theiodide or tetra~heny1borate.l~~ The use of this method with chromium(II1)chloride and trans-stilbene has enabled isolation of the first bridged bisarene-n-complex (27).18, A novel ring-expansion occurs when cyclopentadienyl-benzene-metal-n-complexes are acylated viz. :CH2ICHPhICH PhICH29 I . M~ COCI/A IC.I - 2 . H y d r o l .Q".MThe yellow-green, paramagnetic cycloheptatrienylchromium(1) cation,[(n-C,H,)CrC,H,]+, has been prepared by treatment of C5H5CrC6H6 withcyclohepta- 1,3,5-triene under nitrogen in the presence of aluminium chloride ;177 C. E. Coffey, J. Inorg. Nuclear Chem., 1963, 25, 179.178 M.L. H. Green and P. L. I. Nagy,'Z. Nuturforsch., 1963, 18b, 162.179 W. McFarlane, L. Pratt, and G. Wilkinson, J., 1963, 2162.180 R. H. Holm, R. B. King, and F. G. A. Stone, Inorg. Chem., 1963, 2, 219.lS1 J. A. McCleverty a,nd G. Wilkinson, J., 1963, 4096.lE2 F. A. Cotton, W. A. Dollase, and J. S. Wood, J. Amer. Chem. SOC., 1963, 85,183M. Tsutsui and G. Chang, Cunud. J . Chem., 1963, 41, 1255.18* M. Tsutsui and M. N. Levy, Proc. Chem. SOC., 1963, 117.1543; cf. Ann. Reports, 1960, 149242 INORGANIC CHEMISTRYafter hydrolysis the cation can be precipitated as the hexafluorophosphateor reduced with dithionite to give cyclopentadienylcycloheptatrienyl-chromium(0).ls5Organometallic Compounds of the Transition Elements.-The stable com-plexes [RhBr(l-naphthyl),L,] (L = PPP, or PEt,Ph), prepared by theaction of 1 -naphthylmagnesium bromide on the halide complexes [ RhBr,L,],are diamagnetic and monomeric and are so far the only known five-co-ordinatecomplexes of tervalent rhodium. While alkylnickel complexes have onlytransient existence, the perfluoroalkyl complexes [ Ph2P*CH,*CH,*PPh,]NiRFI(RF = C2F5 or n-C,F,) are crystalline and air-stable; their red-brown colourand diamagnetism indicate that they have the square-planar structure.187Treatment of Fe( CF,),(CO), with the diphosphine Ph,P*CH,*CH,*PPh,yields the complex Fe(CF,),(CO),Ph,P*CH,~CH,*P*Ph,; in view of thestability of this complex it is believed that steric factors are more importantthan electronic ones in determining the stability of the Fe-C o-bond insubstituted carbonyls.lss The molybdenum alkyl, (n-C,H,)Mo(CO),Et, isobtained by reduction of the p-ethylenic cation [n-C5H,Mo( CO),CH,:CH,] +with sodium b o r ~ h y d r i d e . ~ ~ ~ The molecular stereochemistry of this newalkyl approximates to that of the ion; there is an unexpectedlylarge difference between the Mo-C(ethy1) bond length (2.38A) and theMo-CO bond length (1-97 A) and consequently the o-bond is weaker for theMo-Et bond than for the carbonyl interaction. lS9 Trimethyltitanium iodideexists as yellow needles stable only at low temperatures and in the absenceof air and moisture;lgO it is prepared by treating TiMe, with CF,I at -78".Dimethylzinc yields crystalline chelates with 1,4-dioxan and 1,4-0xathian ;its 1 : 2 complexes with aliphatic ethers are so stable that they can be dis-tilled without decompo~ition.~~~ Organomercury(n) salts react with dithi-zone, giving intensely coloured 1 : 1 complexes of general formula RHgDz(R = a variety of alkyl and aryl groups).lg2 Oscillometric titrations inbenzene solution show the formation of complexes Hg(RF),L and Hg( RF),L,(RF = fluoralkyl or fluoroaryl, L = a variety of nitrogen, phosphorus, andarsenic donors). lg3Molecular Hydrides of the Transition Elements.-The detailed chemistryof the platinum hydrido-complexes trans-[PtHX( PR3)2] (X = univalentradical, R = aryl or alkyl) has now been presented. Many of the com-pounds show surprising resistance to thermal decomposition, oxidation, andhydrolysis. Ethylene reacts reversibly with truns-[PtHCl(PEt,),] to givethe alkyl trans-[PtClC,H,( PEt,),].lg4 Hydrido-complexes of rhodium(m)containing non-n-bonding nitrogen ligands such as ethylenediamine havebeen obtained by nucleophilic displacement of chloride ions, using sodiumE. 0. Fischer and S. Breitschaft, Angew. Chem., 1963, '75, 167, 94.D. W. McBride, S. L. Stafford, and F. G. A. Stone, J., 1963, 723.186 J. Chatt and A. E. Underhill, J., 1963, 2088.lE8 T. A. Manuel, Inorg. Chem., 1963, 2, 854.189 M. J. Bennett and R. Mason, Proe. Chem. SOC., 1963, 273.190H. J. Berthold and G. Groh, Angew. Chem., 1963, 75, 576.1 9 1 K-H. Thiele, 2. anorg. Chem., 1963, 319, '183; ibid., 320, 71.1 9 2 H. Irving and J. J. Cox, J . , 1963, 466.193H. B. Powell, M. T. Maung, and J. J. Lagowski, J., 1963, 2484.l g 4 J. Chatt and B. L. Shaw, J . , 1962, 5075NICHOLLS : COMPLEXES 243borohydride as the source of hydride ion; in water, e.g., [Rhen,Cl,]+ gives[Rhen,H,]+. No evidence could be obtained for the formation of anycobalt hydrides using this method.lg5 The five-co-ordinate compounds ofrhodium( I) and iridium(1) , [MH( CO) (Ph,P),], have been synthesised byreaction of an alcoholic solution of [MCl(CO)(Ph,P),] (M = Rh,Ir) with anexcess of hydrazine. An X-ray study on the rhodium compound showsit to have the trigonal-bipyramidal configuration; the Rh-H bond lengthis 1-72 0.15 A, i e . , '' normal " and not short as has been suggested.lg6Hydrido-complexes have been obtained in the reactions of cyclopentadienyl-metal carbonyls and their sodium salts with dialkylphosphorus chlorides.Thus reaction of Na[ (n-C,H,)Mo(CO),], with Me,PCl gives orange-red[ (n-C,H,),Mo,H( PMe,)(CO) J, and Na[ (n-C,H ,)Fe(CO),] gives with R,PCl[(n-C,H,)Fe(PR,)(CO)], and [(n-C,H,),Fe,H(PR,)(CO),] both of which con-tain bridging PR, groups.lg7 X-Ray data on solid K,ReH, and K,TcH,show that the metal atoms are widely spaced so that they must exist indiscrete MHS2- ions with no metal-metal bonding.198Ig5 R. D. Gillard and G. Wilkinson, J., 1963, 3594.lS6 S. S. Bath and L. Vaska, J . Arner. Chem. SOC., 1963, 85, 3500; S. J. Laplaca and10' R. G. Hayter, Inorg. Chem., 1963, 2, 1031; J. Anaer. Chem. SOC., 1963, 85, 3120.198 K. Knox and A. P. Ginsberg, Inorg. Chern., 1962, 1, 945.J. A. Ibers, ibid., 3501

ISSN:0365-6217    

DOI:10.1039/AR9636000177

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

ORGANIC CHEMISTRY1. INTRODUCTIONBy L. Crombie and V. GoldTHIS year’s Report follows the same general pattern as last year’s but withthe inclusion of a short section on the study of equilibria and a report onpeptides. Steroids were only briefly covered in the Report for 1962 and arather longer section is devoted to this subject in the present volume.Increasing use of physical methods in the study of all types of organicstructures is very evident this year. We would particularly draw attentionto wide interest in temperature effects on nuclear magnetic resonance(n.m.r.) spectra, leading to detailed information on conformational equilibriaand rates of interconversion. The technique has also been applied to theproblem of the existence of non-classical carbonium ions, which remains asubject of controversy and imaginative experimental work.Measurementof the temperature dependence of circular dichroism likewise promises tobe an interesting technique.Kinetic isotope effects involving the isotopes of hydrogen continue to beexploited in detailed studies of reaction mechanism but an important trendis the increasing use of isotopes of heavier elements (particularly carbon,nitrogen, and oxygen) in a like manner, as in the demonstration of a one-stepDiels-Alder retrogression. Mechanisms of cis-addition and eliminationreactions have been discussed.Definitive assessment of the enamine synthesis is available and a usefulprocedure for “ crossed-aldolisation ” is reported. The enormous literatureon metal hydrides as general reagents is continuing to expand.Thenewer synthetic routes will encourage extended study of the chemistry ofthe group in which there are still some surprising gaps.As in 1962, aconsiderable number of new polyacetylenic compounds have been isolatedfrom higher plants and fungi. Considering how few members were known adecade ago, this increase indicates the possible scope of intensive searches inother groups of less-well-known natural products. Applications of photo-chemistry in various fields continue to provide novel reactions, interestingstructures, and topics for mechanistic speculation.The scope of syntheses in the terpenoid field is extended to a large varietyof types. On the structural side, papers on four transformation productsof santonic acid make interesting reading and assignments to the tenulingroup of guianolide relatives rest on a firmer basis as a result of X-rayanalysis. The past two years have seen the publication of much syntheticwork on steroids and this is reflected in the Report.As usual, this area ofchemistry provides a rich harvest of reactions which are applicable in widercontexts.Several cyclic systems of unusual theoretical interest have been syn-thesised. They include a non-planar non-aromatic hydrocarbon havingAllene chemistry, a rather neglected area, is coming to the fore246 ORGANIC CHEMISTRYthe bond arrangement of the Dewar formula for benzene and a “hexa-homobenzene ” which is likewise non-aromatic. cis-cis-cis- 1,4,7-Cyclonona-triene has been prepared by two independent routes: the question of itsaromaticity as a cyclic six n-electron system is still open.A spectaculardevelopment has been the synthesis of “ bullvalene,” a system combiningunusual possibilities for tautomerism and mesomerism.The impact of X-ray crystallography, mass-spectrometry, and n.m.r.spectrometry is reflected in faster general progress on the structural side ofalkaloid’ chemistry. Among the year’s synthetic achievements are a com-plete stereospecific synthesis of ( &)-atkine and a biologically patternedsynthesis of emetine, with particular stress on considerations of high yieldand efficiency. Last year the Report on carbohydrate chemistry gaveprominence to monosaccharides. This year emphasis is placed on structuralwork on polysaccharides, especially those from plants and microbes.Although the space devoted to peptide chemistry is limited, the Reportconveys an impression of tremendous activity and progress.Syntheticwork on natural peptides has made great strides, developments in the fieldof pituitary hormones being in the fore-front2. REACTION MECHANISMSBy B. Capon and C. W. ReesSEVERAL books 1 dealing wholly or largely with organic reaction mechanismswere published in 1963. Each of the following sections has been writtenas a continuation of the corresponding section in last year’s Report.Nucleophilic Substitution at Saturated Carbon. Carbonium Ions. Ali-phatic Rearrangements.-Chsical and non-classical carbonium ions.Anexcellent review on carbonium ion rearrangements in bridged bicyclicsystems has appeared.2Brown’s criticism of the non-classical carbonium ion concept (see ref. 3)is stimulating considerable efforf to determine the structure of carboniumions more rigorously. Both Brown and Winstein 5 and their co-workershave used the borohydride trapping technique of Brown and Bell (see ref. 3)in attempts to determine the structure of the intermediates in the solvolysesof anti-norbornen-7-yl and nbrbornadien-7-yl derivatives. Brown nowaccepts that these reactions proceed with participation by the double bond,ie., involve transition states as (1)’ but prefers to formulate the cationic(a) “ Advances in Physical Organic Chemistry,” Vol. 1, ed. V. Gold, AcademicPress, New York, 1963; ( b ) “Progress in Physical Organic Chemistry,” Vol.!l ed.S. G. Cohen, A. Streitwieser, and R. W. Taft, Interscience, New York, 1963; (c) Ad-vances in Photochemistry,” Vol. 1, ed. W. A. Noyes, G. s. Hammond, and J. N. Pitts,Interscience, New York, 1963; ( d ) J. E. Leffler and E. Grunwald, “ Rates and Equilibriaof Organic Reactions,” Wiley, New York, 1963; ( e ) “ Reactions of Co-ordinated Ligandsand Homogeneous Catalysis,” Advances in Chemistry Series No. 37, A.C.S., 1963;(f) D. V. Banthorpe, “ Elimination Reactions,” Elsevier, London, 1963; (9) C. A.Bunton, “ Nucleophilic Substitution at Saturated Carbon,” Elsevier, London, 1963;( h ) “ Investigation of Rates and Mechanisms of Reactions,” Part 2, ed. S. L. Friess,E.S. Lewis, and A. Weissberger, Interscience, New York, 1963; (i) “ Molecular Re-arrangements,” Part 1, ed. P. Mayo, Interscience, New York, 1963; (j) P. F. G. Praill,“ Acylation Reactions,” Pergamon, London, 1963; (Ic) P. G. Ashmore, “ Catalysis andInhibition of Chemical Reactions,” Butterworths, London, 1963 ; ( I ) “ Friedel-Craftsand Related Reactions,” Vol. 1, ed. G. A. Olah, Wiley, Xew York, 1963; (m) L. N.Ferguson, “ The Modern Structural Theory of Organic Chemistry,” Prentice-Hall,New York, 1963.J. A. Berson in ref. l(i), p. 111.Ann. Reports, 1962, 59, 207.H. C. Brown and H. M. Bell, J. Amer. Chem. SOC., 1963, 85, 2324.5 S. Winstein, A. H. Lewin, and K. C. Pande, J . Amer. Chem. SOG., 1963,85,2324248 ORGANIC CHEMISTRYintermediate as (2) rather than as (3).However, the exclusive formationof anti-norbornen-7-01 from the hydrolysis of anti-norbornen-7-yl toluene-p-sulphonate seems to exclude the classical structures (2) unless the alcohol (4)expected to be formed from them were unstable under the reaction condi-tions. This possibility does not seem likely but cannot be excluded sincethe alcohol is as yet unknown. In the presence of 1-8M-sodium borohydridein 65% aqueous di-(2-methoxyethyl) ether (diglyme), the reaction productsare almost exclusively hydrocarbons. It was shown5 that, for norbornen-7-ylchloride, the addition of sodium borohydride did not appreciably changethe rate of hydrolysis. Hence, for this and the other compounds, theborohydride is presumably trapping the intermediate carbonium ion.Theanti-norbornen-7-yl derivatives yield mainly norbornene ( 5 ) and a smallamount of tricyclo[4,1 ,0,039 7]heptane (6), while norbornadien-7-yl chlorideyields 83% tricyclo[4,1,0,03, 7]hept-4-ene (7) and 12% norbornadiene (8).It is difficult to explain the formation of the norbornene and norbornadienefrom classical ions as (2), but the formation of all products of solvolysis andof reaction with borohydride can be readily explained by the non-classicalions as (3), for which the relative rates of attack a t positions (l), (2), and (7)vary with the nucleophile.5 The nuclear magnetic resonance (n.m.r.)spectrum of what is thought to be norbornadien-7-yl fluoroborate has beenexamined.6 The 2,3- and 5,6-olefinic protons are not equivalent, but bothpairs are coupled to the bridge proton a t position 7.Story and his co-workers interpreted these results as indicating an unsymmetrical structure,as (9a), for the norbornadienyl cation; this lack of symmetry presumablyresults from the fluoroborate being an unsymmetrical ion pair, as shownin (9b).Brown and Chloupek have shown that the rates of ethanolysis of thetertiary chlorides, camphene hydrochloride ( 10) and exo-2- chloro-2 -methyl-norbornane (1 l), though considerably greater than that of t-butyl chloride,are not appreciably greater than those of the analogously substitutedl-methylcyclopentyl chlorides (12) and (13). The high reactivity is there-fore due to steric acceleration and does not require the postulation of non-classical intermediates.P.R. Story, L. C. Snyder, D. C. Douglass, E. W. Anderson, and R. L. Kornegay,H. C. Brown and F. J. Chloupek, J . Amer. Chem. SOC., 1963, 85, 2322.J. Amer. Chem. SOC., 1963, 85, 3630CAPON AND R E E S : REACTION MECHANISMS 249The acetolyses of endo- and exo-bicyclo[2,2,2]oct-5-en-2-yl toluene-p-sulphonates have been investigated.*, 9, lo The reaction of the optically(10) ACIi ( 1 ‘) & (12) bCI (13)& 4 4 OAcactive endo-isomer (14) yields 98.60/, of racemic ezo( axial)-bicyclo[3,2, lloct-3-en-2-yl acetate (16) and hence proceeds via the symmetrical ion (15)formed by methylene migration. The preferential formation of the axialisomer is explained as resulting from the formation of quasi-axial bondsbeing stereo-electronically preferred to the formation of quasi-equatorialbonds. The acetolysis of the exo-isomer (17) is anchimerically assisted,0 Ts(‘4) (15) (16)proceeding with participation of the double bond to yield mainly the tricyclicacetate (18).Ar SOr..>& ,* Aco& & ... + *‘..._..*‘ -. - -. 0 Ts- OTs --_...-------(17) (18) ( ‘ 9 ) XA methoxyl substituent in the 4’ position of anti-benzonorbornen-7-ylp-bromobenzenesulphonate causes a 50-fold increase in the rate of acetolysisand a chloro-substituent causes a 20-fold decrease.lla These results supportthe view lib that the reaction proceeds through the transition state (19).The solvolyses of the following bicyclic systems have also been investi-gated : 2-(endo-5-norbornen-2-yl)ethyl p-bromobenzenesulphonate,12 exo-and endo-bicyclo[ 2,1,l]hex-5-y1 toluene-p-sulphonate,13 5,5-dimethylbicyclo-[ 2,1,l]hex-2#l-yl toluene-p-sulphonate, l4 bicyclo[ 5,l ,O]oct -2-, -3-, and -4-ylderivatives, l5 cis- and trans-bicyclo[ 6,l ,O]nonane, l6 and bicycloheptylderivatives.8 H .L. Goering and D. L. Towns, J . Amer. Chem. SOC., 1963, 85, 2295.R. R. Fraser and S. O’Farrell, Tetrahedron Letters, 1962, 1143.(a) Hiroshi Tanida, J . Amer. Chem. SOC., 1963, 85, 1703; (b) P. D. Bartlett and10 N. A. LeBel and J. E. Huber, J. Anzer. Chem. SOC., 1963, 85, 3193.W. P. Giddings, J. Amer. Chem. SOC., 1960, 82, 1240.l2 E. L. Allred and T. J. Maricich, Tetrahedron Letters, 1963, 949.l 3 K. B. Wiberg and R. Fenoglio, Tetrahedron Letters, 1963, 1273.l4 J.Meinwald and P. G. Gassman, J. Agner. Chem. SOC., 1963, 85, 57.l5 A. C. Cope, Sung Moon, and Chung Ho Park, J. Amer. Chem. SOC., 1962,84,4850.l6 A. C. Cope and J. K. Hecht, J. Amer. Chem. SOC., 1963,85, 1780; A. C. Cope andl7 W. Huckel and D. Volkmann, Annalen, 1963, 664, 31.Gar Lok Woo, ibid., p. 3601250 ORGANIC CHEMISTRYThe rates of solvolysis of alkyl mercuric perchlorates (Scheme 1) areparticularly sensitive to structural features in the alkyl group which stabilisethe carbonium ion, such as cc-methyl substituents and the presence of neigh-bouring groups.l*, l9 This has been ascribed to rehybridisation of theR-HgClO, + R+ + Hg + C10,- 4 R'OKROR' + H+SCHEME 1mercury to a spherical configuration in the transition state, making it lessable to stabilise the developing carbonium ion than, say, bromide or arenesul-phonate, thus increasing the need for self-stabilisation by the carboniumion. The reactions of a series of but-2-enyl mercurials, RHgX, have alsobeen investigated.20 In @02~-perchloric acid in acetic acid, when X ishalide, a rapid electrophilic substitution to yield but-l-ene by an SEl pathoccurs, but when X is acetate a rapid nucleophilic substitution to yield therearranged secondary acetate takes place.Details have now been published of two important investigations onaryl participation, which have previously been briefly mentioned.Thefirst is that of Huisgen and his co-workers 21 on the solvolyses of 1,2-benzo-cyclen-4-yl toluene-p-sulphonates (20) and 1,2-benzo-Al-cyclen-3-yl-methyltoluene-p-sulphonates (21).The compounds (20), m = 4 and 5, and (21),SCHEME 2m = 3 and 4, undergo formolysis with exclusive aryl participation to yieldthe same product (22), as shown in Scheme 2. Aryl participation is muchless effective when m = 6 and n = 5, presumably because the phenoniumion (23) is then highly strained. The second is that of Baird and Winstein 22on the solvolysis of the anion of p-hydroxyphenethyl bromide already16 S. Winstein, E. Vogelfanger, K. C. Pande, and H. F. Ebel, J . Arner. Chern. SOC.,1962, 84, 4993.l9 F. R. Jensen and R. J. Ouellette, J . Amer. Chern. SOC., 1963, 85, 363, 367; F. R.Jensen, R. J. Ouellette, G. Knutson, and D. A. Babbe, Tetrahedron Letters, 1963, 339.2o P.D. Sleezer, S. Winstein, and W. G. Young, J . Amer. Chern. SOC., 1963, 85,1890.21 R. Huisgen and G. Seidl, Chem. Ber., 1963, 98, 2730, 2740; cf. A. Strejtwieser,Chem. Rev., 1956, 56, 719; R. Huisgen, Angew. Chem., 1957, 69, 356.22 R. Baird and S. Winstein, J. Arner. Chem. SOC., 1963, 85, 567CAPON AND REES: REACTION MECHANISMS 251described in these reports.23 It has also been shown that radical anions canact as neighbouring groups.24An interesting example of Ar2-6 participation occurs in the acetolysisof [9]paracyclophane 4-toluene-p-sulphonate (24) which reacts rapidly to+ +SCHEME 3yield the products shown in Scheme 3.25 The analogous 5-toluene-p-sulphon-ate (26) also yields these products but in different proportions, and probablyreacts with simultaneous participation of hydrogen and the benzene ring.Participation by the [ 2,2]paracyclophane group in the solvolysis of com-pound (26) has been shown to occur.26 This participation is more effectivethan that observed with compound (27), suggesting that positive charge inOTs(25)one ring of the paracyclophane nucleus is transferred into the other byn,+ charge delocalisation.Several examples of homoallylic rearrangements have been reported.27LCAO calculations have been reported for several non- classical car-bonium ions.2*The aluminium chloride- catalysed reactions of alkyl chlorides have beenreinvestigated 29 and it is concluded that they do not involve primarycarbonium ions as suggested previously.The ultraviolet (u.v.) and n.m.r.spectra of some cyclopentenyl, cyclo-hexenyl, and alkenyl cations have been reported 30 and the rearrangements23 P. B. D. de la Mare, Ann. Reports, 1957, 54, 161.24 D. J. Cram and C. K. Dalton, J . Amer. Chem. SOC., 1963, 85, 1268.25 D. J. Cram and M. Goldstein, J . Amer. Chem. SOC., 1963, 85, 1063.26 D. J. Cram and L. A. Singer, J . Amer. CJzem. SOC., 1963, 85, 1075.27 A. C. Cope, Chung Ho Park, and P. Scheiner, J . Amer. Chem. SOC., 1962, 84,4862; H. Hart, J. L. Corbin, C. R. Wagner, and Chin-Yong Wu, ibid., 1963, $5, 3269;M. Hanack and H. Eggensperger, Annalen, 1963,663, 31; C. A. Grob and J. Hostynek,Helv. China. Acta, 1963, 46, 2209.28 M. E. H. Howden and J. D. Roberts, Tetrahedron, 1963,19, Suppl. 2, 403; R. J.Piccolini and S .Winstein, ibid., p. 493.2D G. J. Karabatsos and F. M. Vane, J . Amer. Chem. Soc., 1963, 85, 729; G. J.Karabatsos, F. M. Vane, and S. Meyerson, ibid., p. 733.*O N. C. Deno, H. G. Richey, N. Friedman, J. D. Hodge, J. J. Houser, and C. U.Pittman, J . Amer. Chem. SOC., 1963, 85, 2991; N. C. Deno, N. Friedmaa, J. D. Hodge,and J. J. Homer, ibid., p. 2995; N. C. Deno, J. Bollinger, N. Friedman, K. Hafer,J. D. Hodge, and J. J. Houser, ibid., p. 2998252 ORGANIC CHEMISTRY(28) -+ (29) and (30) -+ (31) have been studied by following the changesin these spectra. Ion (28) undergoes rearrangement a t the same rate in70% H2S04 as in 96% H,S04, and is the same whether measured in 0 . 1 ~ -solution by n.m.r. or in 10-5M-SOlUtiOn by U.V. spectroscopy.The re-arrangement of ion (30) is, however, faster in 70% H2S04 than in 96% H,SO,,a result which is interpreted as base catalysis ascribed to the intervention ofa proton removal step. Several other investigations on stable carboniumions have been reported.31There have beenseveral investigations in which the products from carbonium ions generatedby solvolytic and non-solvolytic reactions have been compared. Corey andhis co-workers 32 have shown that the deamination in acetic acid of opticallyactive endo- and exo-norbornylamine and the oxidative decarboxylation ofoptically active exo- and endo-norbornylcarboxylic acids 33a with lead tetra-acetate all yield predominantly exo-norbornyl acetate with some retentionof optical activity. These reactions, therefore, cannot involve only asymmetrical non-classical carbonium ion as postulated for the acetolyses ofexo-norbornyl arenesulphonates 33b which yield racemic exo-acetates.Itwould seem that there is an energy barrier between the classical and non-classical norbornyl cations and hence, if the solvolyses of the arenesul-phonates involved initial ionisation to a classical ion, there is the possibilitythat this might be trapped. Corey and his co-workers 32 attempted to doCarbonium ions from deamination and related reactions.31 P. von R. Schleyer, D. C. Kleinfelter, and H. G. Richey, J . Amer. Chem. SOC.,1963, 85, 479; G. A. Olah, W. S. Tolgyesi, S. J. Kuhn, M. E. Moffat, I. J. Bastien,and E. B. Baker, ibid., p. 1328; H. Hart, T. Sulzberg, and R.R. Rafos, ibid., p. 1800;M. Sundaralingam and L. H. Jensen, ibid., p. 3302; D. G. Farnum and B. Webster,ibid., p. 3502; H. Hart and J. S. Fleming, Tetrahedron Letters, 1962,983; C. B. Anderson,E. C. Friedrich, and S. Winstein, ibid., 1963, 2037; J. W. Blunt, M. P. Hartshorn, andD. N. Kirk, Chem. and Ind., 1963, 1955.32 E. J. Corey, J. Casanova, P. A. Vatakencherry, and R. Winter, J . Amer. Chem.SOC., 1963, 85, 169; see also J. A. Berson and D. A. Ben-Efraim, ibid., 1959, 81, 4094.33 ( a ) E. J. Corey and J. Casanova, J . Amer. Chem. SOC., 1963, 85, 165; ( b ) S. Win-stein, and D. Trifan, ibid., 1952, 74, 1147, 1154CAPON AND REES: REACTION MECHANISMS 253this by utilising the m-carboxybenzenesulphonate (32), which yields them-sulphonoxybenzoate (33) with only a small amount of molecular move-ment after ionisation. They used the optically active compound, andtrapping of a classical ion, as (34), would have yielded optically activebenzoate.However, they obtained racemic benzoate and hence, if theinitial ion is classical, it must have a very short lifetime, but more likelydirect ionisation to a non-classical ion occurs.Deuterium labelling experiments showed that the deamination of cis-bicyclo[ 3,l ,O]hexylamine involves very little 1,3-valence rearrangement. 34This reaction, therefore, does not involve a trishomocyclopropenyl cation assuggested for the solvolysis of the corresponding toluene-p-sulphonate. 35Indeed, some doubt has been thrown on the intervention of this ion in thesolvolysis by the observation of Corey and Hisashi Uda 3~ that the 1,5-diphenyl-substituted compound (35) does not react at an increased rate.Phenyl substitution stabilises the cyclopropenyl cation 36b and, therefore,would be expected to stabilise a trishomocyclopropenyl cation.Hence, ifthis ion were the initially formed intermediate, phenyl substitution shouldcause an increased rate. Corey, therefore, prefers a mechanism involving arapidly equilibrating set of isomeric ions (36), in which there is a weakinteraction between the vacant orbital at position 3 and the polarisableelectrons of the three-membered ring. Some evidence for the existence of astable trishomocyclopropenyl catidn has, however, been reported. 36cPh(35) (36)Cartier and Bunce 37 have studied the nitrous acid deamination of2-cyclopropyl[ l-14C]ethylamine. This yields a mixture of 1- and 2-cyclo-propylethanol, and cyclopentanol in the ratio 0.76 : 1.00 : 0-18 (Scheme 4).Surprisingly, the 14C distribution in the 1 -cyclopropylethanol was 77.4,22.0, and 0.6% on carbons 1 and 2 and the cyclopropyl ring, respectively.It is postulated 37 that loss of nitrogen from the diazonium ion to form an~ C H L * C H I - N H ~ I)-CH2.CH2-OH -+ I>.CHMe +OH1.00 0.76 0-1 8SCHEME 4open planar carboniumion are raDid comDaredion (37) and the subsequent rearrangement of thisI I with rotation about the C-2-C (cyclopropyl) bond.The initially formed carbonium ion in conformation (37) would then yield3 4 E.J. Corey and R.L. Dawson, J . Amer. Chem. SOC., 1963, 85, 1782.35 S. Winstein and J. Sonnenberg, J . Amer. Chem. SOC., 1961, 83, 3235, 3244.36 (a) E. J. Corey and Hisashi Uda, J . Amer. Chem. SOC., 1963, 85, 1788; ( b ) R.Breslow, J. Lockhart, and H. W. Chang, ibid., 1961, 83, 2375; (c) R. R. Sauers, Tetra-hedron Letters, 1962, 1015.37 G. E. Cartier and S. C. Bunce, J . Arner. Chin. SOC., 1963, 85, 932254 ORGANIC CHEMISTRYan ion with conformation (38), on migration of the cyclopropyl group, whichis stabilised by the cyclopropyl group being over the positive charge. Thecarbonium ion (39) formed by subsequent hydrogen migration would alsobe in a suitable conformation for stabilisation by the cyclopropyl group.Formation of 1 -cyclopropylethanol by this route would therefore be favouredand hence the 14C distribution in the product is accounted for.IICCsH _jl ,.C,-$-H --3 C--c _f "C - Me.CHH ' H OH1 +f.-H H ..H' 'H 'H H'+( 3 7) ('3'8) (39)Investigations on the deamination of the following amines have alsobeen reported : cis- and trans-4-t-butylcycl0hexylamine~~~ endo- and exo-fen~hylamine,~~ 3-methylbutyl-2-amine and isopentylamine,40 1,1,2-tri-phenyl- et hylamine , optically active 2 - phenylbut yl-2 -amine , cis- andtrans- 1 - aminometbyl-4- t - butylcyclohexanol,43 and alicyclica-aminoketones .g4Ion-pair return and related phenomena. Goering and his co-workershave continued their elegant work on ion-pair return using [carbonyl- oretlier-180]-labelled p-nitrobenzoate~.~~, 46 The rate constant for the equili-bration of the l80 label in optically active p-chlorobenzhydryl p-nitro-[mrb~nyl-~~O]benzoate in aqueous acetone is 2-3 times greater than thatfor racemidation, indicating that ion-pair return does not result in completeracemisation of the substrate.Hence, racemisation does not measure totalion-pair return. It is of course still not possible to say if the l80 equilibra-tion is measuring total ion-pair return since, a t present, there is no methodof detecting ionisation which does not result in randomisation of the carboxyloxygen atoms. Kinetic studies on closely related solvolyses have also beenreported.47, 48The rate constants for racemisation of the ester (krac), solvolysis (lit),the equilibration of the carboxyl oxygen atoms (liees), and scrambling of thecarboxyl oxygen atoms in each enantiomer ( 7 ~ ~ ) have been measured foroptically active trans-1 -methylbut -2-enyl p-nitrobenzoate in 60% aqueousacetone aiid compared with the results previously obtained for 90% acetone.46The rates of all the reactions are considerably increased, consistent with thehypothesis that all the reactions involve ion-pairs.The results show thatthe ion-pair should be regarded as (40) rather than (41). This contrasts38 W. Huckel and K. Heyder, Chem. Ber., 1963, 96, 220.39 W. Hiickel and J. Scheel, Annalen, 1963, 664, 19.40 M. S. Silver, J . Org. Chem., 1963, 28, 1686.4 1 C. J. Collins and B. M. Benjamin, J. Amer. Chem. SOC., 1963, 85, 2519.42 E. H. White and J.E. Stuber, J . Amer. Chem. SOC., 1963, 85, 2168.43 H. Fame and D. Gravel, Canad. J . Chem., 1963, 41, 1452.44 0. E. Edwards and M. Lesage, Canad. J . Chem., 1963, 41, 1592.4 5 H. L. Goering, R. G. Briody, and J. F. Levy, J . Amer. Chem. SOC., 1963, 85,413 H. L. Goering, M. M. Pombo, and K. D. MeMichael, J . Amer. Chem. SOC., 1963,4 7 J. R. Fox and G. Kohnstam, J., 1963, 1593.4sM. S. Silver and G. C. Whitney, J . Org. Chem., 1963, 28, 2479.3059.85, 965CAPON AND REES: REACTION MECHANISMS 255with the solvolysis of cis-5-methyl-2-cyclohexenyl p-nitrobenzoate 46 forwhich kB/krac = kes,/krac = 1, indicating that in the intermediate bothoxygen atoms are equivalent. It is suggested that conformation (42) forH Hthe ion-pair intermediate (40) is favoured, and that this is prevented steric-ally for the cyclohexyl compound.It is interesting to note that a similarconformation for the transition state in a Cope rearrangement has alsorecently been demonstrated (see ref. 49). It is clear that investigations ofthis type could throw considerable light on the classical-non-cla,ssicalcarbonium ion controversy.The solvolyses of 1 -methylheptyl arenesulphonates have been intensivelyinvestigated by Sneen 50 and Streitwieser and their co-w0rkers.5~ Theamount of racemisation observed in the hydrolysis of the p-bromobenzene-sulphonate in aqueous dioxan increases with the dioxan content of thesolvent. This observation supports the view that the racemisation is dueto the intervention of the oxonium ion (43), formed by nucleophilic att'ackby dioxan, rather than to the intervention of a carbonium ion (see ref.52).Acetone also acts as a nucleophile in the solvolysis of this compound in 80%methanolic acetone. 53a (Nucleophilic participation by the solvent has alsobeen observed with NN-dimethylformamide-water mixtures.)53b In 25%aqueous dioxan, the addition of sodium azide does not affect the rate ofsolvolysis but diverts much of the product to l-methylheptyl azide ofinverted configuration. This is strong evidence for an ion-pair mechanismand it is suggested that a similar mechanism may also occur in 75% aqueousdioxan, for which the addition of sodium azide diverts the product tol-methylheptyl azide and causes an increase in the reaction rate. Thislatter observation could be accommodated if the reaction involved a rate-qetermining attack by azide ion on a reversibly formed ion pair.WeinerSneen 50 have in fact made the quite reasonable suggestion that other7 , which have been allocated an XN2 mechanism from their kineticAn ion-pair mechanism may also proceed by this mechanism.eports, 1962, 59, 237.*ler and R. A. Sneen, Tetrahedron Letters, 1963, 1309.twieser and T. D. Walsh, Tetrahedron Letters, 1963, 27..eports, 1962, 59, 214.Weiner and R. A. Sneen, J . Amer. Chem. SOC., 1963, 85, 2181 ; ( b ) J. R.H. Jensen, Canad. J . Chem., 1963, 41, 1679256 ORGANIC CHEMISTRYhas also been demonstrated for the acetolysis of 1 -methylheptyltoluene-p-~ulphonate.~~Fava and his co-workers 54 have investigated the rates of exchangeof a series of substituted benzhydryl thiocyanates with labelled sodiumthiocyanate in acetonitrile under conditions designed to minimise salteffects and dissociation of the ionised reactants. It was fourid that4-nitrobenzhydryl thiocyanate obeyed a second-order rate law, rate =Ic[RSCN][NaSCN], and that the 4,4'-dimethylbenzhydryl compound obeyeda first-order rate law, rate = k[RSCN], and these results were interpreted asindicating X$ and SN1 mechanisms, respectively.Benzhydryl and 4-chloro-benzhydryl thiocyanate obey mixed first- and second-order rate laws and itwas suggested that these compounds react by simultaneous SN1 and SN2mechanisms. " Borderline " nucleophilic substitution has also been dis-cussed by Casapieri and S ~ a r t .~ 5The partial molar heats of solution of t-butyl chloridein water-ethanol mixtures have been measured.56 The results show thatmost of the variation with solvent composition in AH2 for the solvolysis oft-butyl chloride can be accounted for by changes in ground state solvation.Measurement 57 of the variation of the activity coefficients and the activitycoefficients of the transition states for the solvolyses of some substitutedbenzhydryl chlorides in aqueous acetone shows that most of the variationin rate with solvent composition, of these reactions also, is due to an initialstate effect. Similar measurements 5' show that the activity coefficient forthe bimolecular transition state for the solvolysis of 4-nitrobenzyl chloridevaries much more with solvent composition than that for the above-mentioned unimolecular reactions, but this variation is still less than thatobserved for the activity coefficient of the starting material.Further work substantiating the use of the value of ACJ/AX$ as a criterionof mechanism for SN reactions in aqueous acetone has appeared.58 Productanalyses from some of the XN2 reactions showed that these were accompaniedby less than 0.3% concurrent E2 reactions.Murr and Shiner 59 have developed a conductometric method capableof determining first-order rate constants for the solvolyses of alkyl chlorideswith a precision of 0.03y0, and have used it 6o to show that the successivesubstitutions of 1, 2, and 3 hydrogen atoms of one methyl group in t-butylchloride by deuterium are not quite cumulative.This supports the view 61that the @-deuterium isotope effect is hyperconjugative in origin and isdependent on the spatial orientation of the isotopic bond, solvolysis via thetrans-transition state (44) being slower than via the gauche (45).The volume of activation for the acid-catalysed racemisation of ( - IGeneraE reactions.5 4 A. Fava, A. Iliceto, and A. Ceccon, Tetrahedron Letters, 1963, 6855 5 P. Casapieri and E. R. Swart, J., 1963, 1254.56 E. M. Amett, P. M. Duggleby, and J. J. Burke, J. Amer. Chem. S57 W. Featherstone, E. Jackson, and G. Kohnstam, Proc. Chem. f '5 8 G. R. Cowie, H. J. M. Fitches, and G. Kohnstam, J., 1963, -'59 B. L. Murr and V. J. Shiner, J .Amer. Chem. SOC., 1962, 84,6 0 V. J. Shiner, B. L. Murr, and G. Heinemann, J . Amer. Chem. SOC.,61 V. J. Shiner, J . Amer. Chem. SOC., 1960, 82, 2655; V. J. Shiner a t1350.phrey, ibid., 1963, 85, 2416C A P O N A N D REES: R E A C T I O N M E C H A N I S M S 267butan-2-01 in aqueous HC10, supports the view that the mechanism of thisreaction is unimolecular. 62 The oxygen exchange and rearrangement ofsome bicyclic alcohols63 and the oxygen exchange and racemisation of4-methoxydiphenylmethanol 64 have also been investigated.D MeaMe H , H (44)61 -t! "'aMe (45)H . Dcl-The hydroperoxide anion is a stronger nucleophile than the hydroxideion in bimolecular displacement reactions but a much weaker base.65Addition of hydrogen peroxide to a reacting mixture of a substrate andhydroxide ion should therefore result in a rate increase if the reaction is anucleophilic substitution but a decrease if it involves a pre-equilibrium protonabstraction, and hence distinction between these mechanisms is possible.The use of the H- function for similar purposes has also been explored.668-Quinolineboronic acid is a polyfunctional catalyst for the hydrolysisof 2- and 3-chloro-alcohols.67 The reaction proceeds with inversion ofconfiguration 68 and presumably involves binding of the chloro-alcohol bythe boronic acid group, the mechanism possibly being as shown in Scheme 5.2-(2-Boronophenyl)- and 2 4 2-boronobenzyl)-benzimidazole can actsimilarly.69 .It has been shown 7O that the rate of acetolysis of the toluene-p-sulphonate(46) is considerably enhanced by charge-transfer complexing with aromatichydrocarbons.+* + P r o d u c t sHO/ 'OH 0' ' H '9 d B ' O I I6?H RCH - CHR R-CH -CHRRCH - CHR I G ICISCHEME 56 2 R.J. WitheyandE. Whalley, Canad. J . Chem., 1963, 41, 546; cf. C. A. Bunton,A. Konasiewiez, and D. R. Llewellyn, J., 1955, 604; J. F. Bennett, J. Amer. Chem,.SOC., 1961, 83, 4979.63 C. A. Bunton, K. Khaleeluddin, and D. Whittaker, Tetrahedron Letters, 1963,1825.64 C. A. Bunton and R. B. Henderson, Tetrahedron Letters, 1963, 1829.65 R. G. Pearson and D. N. Edgington, J . Amer. Chem. SOC., 1962, 84, 4607.66 R. A. More O'Ferrall and J. H. Ridd, J., 1963, 5030, 5035.6 7 R. L. Letsinger, S. Dandegaonker, W. J. Vullo, and J.D. Morrison, J. Amer.6 8 R. L. Letsinger and J. D. Morrison, J . Amer. Chem. SOC., 1963, 85, 2227.6 0 R. L. Letsinger and D. B. Ma.clean, J. Amer. Chem. SOC., 1963,85,2230; see also7 o A. K. Colter and S. S. Wang, J . Amer. Chem. SOC., 1963, 85, 114.Chem. SOC., 1963, 85, 2223.R. L. Letsinger and A. J. Wysocki, J . Org. Chew., 1963, 28, 3199.258 ORGANIC CHEMISTRYcis - 1 -Met h y 1 - 2 - p hen ylc y clo pr opanol is isomerised to 4 - p hen yl bu t an- 2 -onein basic solution, but gives a mixture of this compound and 3-phenylbutan-2-one in acid solution.71 When the reactions were performed in D,O with0 2 N mNO2 \(46)O HAr-SOzthe optically active cyclopropanol, the 4-phenylbutan-%one obtained wasactive because of asymmetric carbon-4.The optical rotation of that obtainedfrom the acid-catalysed reaction, however, was of opposite sign to thatobtained from the base-catalysed reaction. It was suggested that t,he latterproceeded with inversion and the former with retention of configuration, asshown in Schemes 6 and 7, respectively.SCHEME 6CH2 H,*r CH, ,OH H, / \ ,OH dI p/ 3 c\. . Ph’ I + M e Ph’ I ..c’ * c ,D+we D D meSCHEME 7The effect of the addition of small amounts of protic solvents on therate of reaction of methyl iodide with chloride ion in dimethylacetamide hasbeen investigat,ed.An investigation 35 of reactions between propiolactone and organo-metallic compounds has shown that lithium derivatives usually give 1 ,l-di-substituted propane- 1 ,3-diols7 organocadmium derivatives, benzylmagnesiumchloride, benzyl-lithium, and allylmagnesium bromide give 3-substitutedpropionic acids, and organomagnesium compounds usually lead to alkyl oraryl vinyl ketones, probably through the corresponding ,8-hydroxyethylketones.Diphenylketen and p - chlorophenyldiazocyanide give the correspondingadduct (15), which on heating rearranges to the tricyclic system (16).36 Thestructure of tetrafluoro-3,4-dihydro-l,2-diazete (17), obtained from cyanogenand silver (11) fluoride, has been firmly established from its n.m.r.~pectrum.~'cis- and trans-2,4-Diphenylthietan 1 , 1 -dioxides, obtained from thethietans and performic acid, give different 1,2-diphenylcyclopropanesulphinicacids with ethylmagnesium bromide, and at 250" sulphur dioxide is split outfrom both dioxides with the formation of a mixture of 1,2-diphenylcyclo-pr0panes.~8 Thietan-3-one at 20 O with secondary amines gives a mixtureof the amide (18) and l-mercaptopropan-2-one, and it is considered thatl-thionopropan-2-one may be an intermediate.39 Thietan-3-one 1 ,l-dioxide(19) has been obtained 40 from the diethyl acetal 41 with hydrochloric acid,and from 3-morpholinothiet 1,l-dioxide by treatment with an acidic ion-aa W.J. Linn, 0. W. Webster, and R. E. Benson, J . Amer. Chem. SOC., 1963, 85,aaG. B. Payne, J . Org. Chem., 1962, 27, 3819.S5C. G. Stuckwisch and V. J. Bailey, J . Org. Chem., 1963, 28, 2362.aeC. W. Bird, Chem. and Ind., 1963, 1556.87 E. A. V. Ebsworth and G. L. Hurst, J., 1962, 4840.88 R.M. Dodson and G. Klose, Chem. and Ind., 1963, 450, 1203.40 W. E. Truce and J. R. Norell, Tetrahedron Letters, 1963, 1297.2032.K. F. Funk and R. Mayer, J. prakt. Ghem., 1963, 21, 65.Ann. Reports, 1962, 59, 322ACHESON : HETEROCYCLIC COMPOUNDS 381exchange resin.42 It forms a 2,4-dinitrophenylhydrazone and is reduced bydiborane to the known 3-hydroxythietan l,l-dio~ide.~O Although the ketonewas surprisingly acidic (pK, = 4 ~ 1 ) ~ ~ ~ and dissolved in aqueous sodiumhydrogen carbonate with the liberation of carbon dioxide, no trace of theen01 tautomer was detected by infrared or n.m.r. (singlet at 4-98 z only)spectroscopy. 40, 42Theoretical studies 43 suggest that lY2-dithiet (ZO), derivatives of whichwere reported last year,44 possesses considerable delocalisation energy andthat its stability is comparable to that of 1,2-dithiolan.The products fromnitrosobenzene and diethyl methylenemalonate are not oxazetidines asoriginally claimed,45 but have structures (21) and ( ~ 4 . ~ 6 The 1 ,e-thiazetidin-%one (23) with alkyl iodides gives N-derivatives in the presence of alkali,and O-derivatives if silver oxide is used; the four-membered ring of theO-isopropyl derivative opened on attempted chromatography (alumina)yielding the ester (24)) and ammonia gave a mixture of the correspondingiminoester and amidine.47Five-membered Rings and Condensed Derivatives.-Pywoh. Furan-amines (25) are efficiently converted to pyrroles (26) by hydrogen overplatinum at 300°.48 l-Hydroxypiperidin-2-one, with hot polyphosphoricacid, loses carbon monoxide to yield l-~yrroline.~~ A redetermination of thepK, of pyrrole gave 50 a value (-3.8) much below that (0.4) currentlyaccepted.51 Further n.m.r.studies 50, 52 have shown that, while a number ofalkylpyrroles form stable a-protonated salts in aqueous sulphuric acid,competitive protonation at the /I-position can occur, particularly in strongeracid. From the n.m.r. and electronic spectra it has proved possible todeduce the pK,’s of the protonation sites. The n.m.r. spectrum of pyrrolyl-magnesium chloride in ether suggests 53 that the compound is (27) or is ionic.N a 0 3 S i i S 0 3 N aNH(28)I F m Y (27) NHCH2-CH2*CHR*NH2 P r “MgC I(26)(25)42 R. H. Hasek, P. G. Gott, R.H. Meen, and J. C. Martin, J . Org. Chem., 1963, 28,4 3 G. Bergson, Arkiv Kemi, 1962, 19, 181, 265.4 4 Ann. Reports, 1962, 59, 323.45 C. K. Ingold and S. D. Weaver, J., 1924, 1456.46 N. F. Hepfinger, C. E. Griffin, and B. L. Shapiro, Tetrahedron Letters, 1963, 1365.4 7 B. J. R. Nicolaus, E. Bellasio, and E. Testa, HeEv. Chim. Acta, 1963, 46, 450.48 I. F. Bel’skii, Zhur. ohhhei Khim., 1962, 32, 2905, 2908.4 9 G. Di Maio and P. A. Tardella, Proc. Chem. SOC., 1963, 224.50 Y. Chiang and E. B. Whipple, J . Amer. Chem. SOC., 1963, 85, 2763.51 R. M. Acheson, “ Introduction to Heterocyclic Chemistry,” Interscience and5 2 E. B. Whipple, Y. Chiang, and R. L. Hinman, J . Amer. Chem. SOC., 1963, 85, 26.63 M. G. Reinecke, H. W. Johnson, and J. F. Sebastian, J .Amer. Chem. SOC., 1963,2496.Wiley, New York and London, 1962, p. 54.85, 2859382 ORGANIC CHEMISTRYThe reactions of the corresponding bromide with a number of alkyl halides,giving alkylpyrroles, have been carefully examined and compIete inversion ofconfiguration took place in the formation of 2- and 3-s-butylpyrroles from( - ) -2-bromobutane. 54Pyrrole is stated 55 to react with 2 mols. of sodium hydrogen sulphitea t 100" forming the salt (28) which, with reagents such as hydroxylamine,gave succindialdehyde derivatives. Further examples of acetylenedi-carboxylic acids undergoing Diels-Alder reactions with pyrroles have beenfomd.56 Pentamethylpyrrole and hydrogen peroxide give 57 the pyrrolone(29), and the structure of the product 58 from Knorr's pyrrole and thionylSpectral studies 59 have shown that the pyrrolone (31) doesappreciably to the corresponding 3- hydroxypyrrole.chloride is (30).not tautomeriseMe(29 1(30) (32)Pyrrole-2-carboxylic acid, readily obtainable from the aldehyde and silveroxide,60 has been found for the first time as an ester component in analkaloid.61 Partial alkaline aerial oxidation of the colourless (32) yields 62a paramagnetic blue solid.The 1,l-dimethyl-2-phenylpyrrolidinium cationundergoes ring enlargement with sodamide yielding the benzazocine (33) .63truns-4-Methyl-~-proline and the CiS-D-iSOmer have been synthesised, andare identical with material from natural sources. 64HThe Fischer indole synthesis has been revie~ed.6~ Cyclisation ofcyclohexan- 1,4-dione bisphenylhydrazone by sulphuric acid gives the linearcarbazole (34) and other products.66 The anilide (35; R = H) with potas-64 P.S. Skell and G. P. Bean, J. Amer. Chem. Soc., 1962, 84, 4660; and precedingpapers.5 5 A. Treibs and R. Zimmer-Galler, Annalen, 1963, 664, 140.66 R. M. Acheson and J. M. Vernon, J., 1963, 1008; L. Mandell, J. U. Piper, andC. E. Pesterfield, J . Org. Chem., 1963, 28, 574.5 7 D. Seebach, Chem. Ber., 1963, 96, 2723.6 8 J. H. Mathewson, J . Org. Chem., 1963, 28, 2153.6 9 R. S. Atkinson and E. Bullock, Cunud. J. Chem., 1963, 41, 625.6 o P. Hodge and R. W. Rickards, J., 1963, 2543.61 A. Goosen, J., 1963, 3067.6 2 A . R. Forrester and R. H. Thompson, Proc. Chem. SOC., 1962, 360.G 3 G.C. Jones and C. R. Hauser, J. Org. Chern., 1962, 27, 3572.64 J. S. Oelby, G. W. Kenner, and R. C. Sheppard, J., 1962, 4387.65 B. Robinson, Chem. Rev., 1963, 63, 373.*6 B. Robinson, J., 1963, 3097; J. Harley-Mason and E. D. Pavri, ibid., p. 2504ACHESON : HETEROCYCLIC COMPOUNDS 383samide in liquid ammonia yields 2-methylbenzoxazole, but if an N-methylgroup is present the oxindole (36) is f0rrned.6~ As the chemical shift of theH-2 atom in indole, in contrast to the H-3 atom, differs markedlyin polarand non-polar solvents, the position of substitution may be ascertainable.68In cis- and trans-2,3-dimethylindolines the coupling constant between the2- and 3-hydrogen atoma depends strongly on the nature of the N-sub-stituent .G9The n.m.r. spectrum of indolylmagnesium bromide in tetrahydrofuransuggests that the compound is largely ionised.70 Nitration of 1-acetyl-2,3-dimethylindole gave a mixture of the 6-nitro-derivativeY 2-acetamidoaceto-phenone and the trans-diol(37).71 Nitrosation, reduction, and diazotisationof 2-phenylindole gave 2-phenyl-3-diazoindole, which coupled with 2-naphthol in chloroform. '2 Bromination of the triester (38) in anhydrousacetic acid gave the 6-bromo-derivative, but if water was present rearrange-ment to the oxindole (39) took place.73Hantzsch's structure for methylisatoid (40), the product of aerial oxida-tion of O-methylisatin, has been confimed.74 N-Methylisatin p-thionosemi-carbazone appears to be an extremely valuable prophylactic agent againstsmallpox, and is the first synthetic compound found possessing this type ofanti-viral activity.75Triphenylamine and methyldiphenylamine, on illumination in hexaneexposed to air, gave N-phenyl- and AT-methyl-carbazole (65%) through theintermediate species (41).761,3-Triphenylisoindole has been obtained in 78% yield from 1,3-di-phenylisobenzofuran with aniline sulphoxide (PhN:S :0) and boron tri-fluoride etherate.V7 l-Phenylisoindole, from N-( 2-benzoylbenzy1)phthali-mide and ethanolic hydrazine, gives a blue Ehrlich reaction and resinifies6 7 J.F. Bunnett, T. Kato, R. R. Flynn, and J. A. Skorcz, J . Org. Chem., 1963,28,1.6 s R . V. Jardine and R. K. Brown, Canad. J. Chern., 1963, 41, 2067.6 9 F. A. I;. Anet and J. M. Muchowski, Chem. and Ind., 1963, 81.70 M.G. Reinecke, H. W. Johnson, and J. F. Sebastian, Tetrahedron Letters, 1963,7 1 C . M. Atkinson, J. W. Kershaw, and A. Taylor, J., 1962, 4426.72H. P. Patel and J. M. Tedder, J., 1963, 4593.7 3 R. M. Acheson and R. W. Snaith, Proc. Chem. SOC., 1963, 344.7 4 C. W. Bird, Tetrahedron, 1963, 19, 901.75 D. J. Bauer, L. St. Vincent, C. H. Kempe, and A. W. Downie, Lancet, 1963, ii, 494.76 K. H. Grellmann, G. M. Sherman, and H. Linschitz, J. Amer. Chern. SOC., 1963,7 7 M. P. Cava and R. H. Schlessinger, J . Org. Chem., 1963, 28, 2464.1183.85, 1881384 ORGANIC CHEMISTRYwith acids and on standing in air. Spectral studies show that tautomers (42)and (43) are in equilibrium and that about 9% of (43) is present indeuterochloroform, but could not detect the lH-ta~tomer.~8(40) (4 1) (4 2) (4 3)2,3-Dimethylindolizine gave a mixture of the 1H- and 3H-salts 79 withacids, although indolizines usually protonate at position 3.Heating in-dolizine with acetoacetic ester in xylene gave the 1 -acetoacetyl derivative.80A largely stereospecific cyclisation of 1 -chloro-2-n-butyl-piperidine to anoctahydro-3-methylindolizine was effected by ultraviolet irradiation insulphuric acid.81N.m.r.S2 and ultraviolet spectrum 83 studies have shown thatpyrrol0[2,1,5-cd]indolizine (44) protonates on position 1, and the electronspin resonance low-temperature spectrum of the anion has been e~amined.~4(4 4)met-^^HoQ-AHHo ' N CO,'HOZC bco::"' H1 -(p-Chlorobenzoyl)-5-methoxy-2-methylindol-3-ylacetic acid is a power-ful anti-inflammatory and antipyretic agent .85 Pimprinine, a metabolite ofXtreptomyces pimprina, has been identified as 5-indol-2-yl-2-methyloxazoleand synthesised.86 L-Tryptophan is incorporated g7 by Aspergillus amstelo-dami into echinulin (45),ss showing that the side-chains are introduced bydirect alkylation of the indole system.Of the remaining possible structuresD. F. Veber and W. Lwowski, J . Amer. Chem. SOC., 1963, 85, 646.79 M. Fraser and D. H. Reid, J., 1963, 1421.F. N. Steronov and N. I. Grineva, Zhur. obshchei Khim., 1962, 32, 1529, 1532.81 3%. F. Grundon and B. E. Reynolds, J., 1963, 3898.82 V. Boekelheide, F. Gerson, E. Heilbronner, and D. Meuche, Helv. Chim. Acta,S3 F. Gerson, E. Heilbronner, N. Joop, and H.Zinunermann, Helv. Chim. Acta,8 4 F. Gerson and J. D. W. van Voorst, Helv. Chim. Acta, 1963, 46, 2257.8 5 T. Y . Shen, T. B. Windholz, A. Rosegay, B. E. Witzel, A. N. Wilson, J. D.Willett, W. J. Holtz, R. L. Ellis, A. R. Matzuk, S. Lucas, C. H. Stammer, F. W. Holly,L. H. Sarett, E. A. Risley, G. W. NUSS, and C. A. Winter, J. Amer. Chew,. SOC., 1963,1963, 46, 1951.1963, 46, 1940.85, 488.19, 1437.86 B. S. Joshi, W. I. Taylor, D. S. Bhate, and S. S . Karmarkar, Tetrahedron, 1963,8 7 A. J. Birch and K. R. Farrar, J., 1963, 4277. . .88 Ann. Reports, 1962, 59, 327ACHESON : HETEROCYCLIC COMPOUNDS 385for betanidin,ss that shown (46) must be correct. The di-O-acetyl derivativehas been prepared 89 and the stereochemistry follows from the conversion g9of ~-p-(3,4-dihydroxyphenyl)alanine into a derivative of the optically active2,3-dihydro-5,6-dihydroxyindole-2-carboxylic acid which has been obtainedfrom betanidin by oxidation.A biogenetic scheme which accounts for theformation of betanidin from 2 mol. of #I-( 3,4-dihydroxyphenyl)alanine hasalso been put forward.89 Sepiomelanin has been degraded to 5,6-dihy-droxyindole and t o pyrrole-2,3,4- tri- and -2,3,4,5- tetra-carboxylic acidsN.m.r. spectrum studies 91 have shownthat there is less extensive conjugation in furans than in thiophens, and thatsubstituents a t position 3 are less affected by the heteroatom than those atposition 2. The dehydrogenation of 3,4-diphenyltetrahydrofuran by sulphurto 3,4-diphenylfuran is stated 92 to be the first example of the dehydrogena-tion of a tetrahydrofuran.Furan combines with diazomethane in theFurans and condensed furans.presence of cuprous bromide yielding the oxole (47; R = H) and 5% of theoxalan (48),93 while photolysis with methyl diazoacetate 94 yields the ester(47; R = C0,Me). Methanolic hydrogen chloride converts the ester to thealdehyde (49). Benzophenone, often used as a photosensitiser, gives anadduct (50) with furan in the presence of light.95 2,5-Di- and tetra-methyl-furan with peracetic acid yield g6 the corresponding peroxides (51).It has been shown 97 from n.m.r. studies that, in methyl cyanide, furanand maleic anhydride yield the exo-adduct twice as fast as the endo-isomer,which has now been isolated, while maleic acid gives the endo-adduct fourtimes as fast as the exo-form; the exo-adducts are the thermodynamicallymore stable.3,4-Dimethylenetetrahydrofuran (52), which forms the expected adductswith maleic anhydride and quinone, was obtained in a similar way to thethiophen analogue 98 by the pyrolysis of 3,4-di( acetoxymethy1)tetra-hydrof~ran.~~While 3-furylmercuric chloride rearranges with some reagents, it isconverted by iodine into 3-iodofuran which has proved a useful entry to the3-substituted series.lO0 Although benzyltriphenoxyphosphonium bromideas H.Wyler, T. J. Mabry, and A. S. Dreiding, Helv. Chim. Acta, 1963, 46, 1745.M. Piattelli, E. Fattorusso, and S. Magno, Rend. Accad. Sci. j i s . mat. (NapoZi),91 S. Gronowitz, G. Sorlin, B. Gestblom, and R.A. Hoffmann, Arkiv Ken& 1963,e2D. G. Farnum and M. Burr, J . Org. Chem., 1963, 28, 1387.93 E. Muller, H. Kessler, H. Fricke, and H. Suhr, Tetrahedron Letters, 1963, 1047.s4 G. 0. Schenck and R. Steinmetz, Annalen, 1963, 668, 19.s6 G. 0. Schenck, W. Hartmann, and R. Steinmetz, Chern. Ber., 1963, 96, 498.s6 D. Seebach, Chem. Ber., 1963, 96, 2712.9 7 F. A. L. Anet, Tetrahedron Letters, 1962, 1219.9 g W. J. Bailey and S. S. Miller, J . Org. Chern., 1963, 28, 802.1962, 29, 57, 168.19, 483.Ann. Reports, 1962, 59, 329.l o o S. Gronowitz and G. Sorlin, Arkiv Kemi, 1963, 19, 515.386 ORGANIC CHEMISTRYhas been used in tetrahydrofuran, this solvent reacts exothermically withtriphenoxyphosphine dibromide giving triphenylphosphate and lY4-dibromo-butane.101Coumarone has been prepared from phenol, acetylene, and carbondioxide a t about 650" over alumina.lO2 The racemic form of the majortoxic component of Eupatorium urticaefolium, tremetone (53) , which causes" milk sickness " in man and " trembles " in cattle, has been synthesised.lO3(5 1) (52) (5 3) (54)Thiophens and condensed derivatives. Nitration of thiophen usingbenzoyl nitrate in methyl cyanide gave the 2- and 3-nitrothiophens in6.2 : 1 ratio, and with [2-3H]thiophen a weak secondary a-isotope effect wasobserved.lo4 The nitration of 2-nitrothiophen with fuming nitric acid gave56% of 2,4- and 44% of 2,5-&nitr0thiophen.~~~ 2-Fluorothiophen has beenprepared from 2 - thienyl-lit hium and perchloryl fluoride. 106 Thiophen-2 - 01and its alkyl derivatives have been obtained from the thien-2-ylboronicacids with hydrogen peroxide; the conjugated keto-form is the sole or pre-dominant tautomer present.lo' Thienotropylium perchlorate (54) has beensynthesised and, in contrast to the oxygen analogue, can be recrystallisedfrom water without decomposition. lo* Homolytic phenylation of diben-zothiophen occurs at positions 1, 2, 3, and 4 in approximately 3 : 1 : 2 : 3ratio.loS Naphtho[2,3-b]thiophen forms a meso-adduct with maleic anhy-dride but with much more difficulty than anthracene; bromination of thethiophen gives first a mono- and then the 4,9-dibromo-derivative.lfo1 -Phenylpyrazoles acylate under Friedel-Craffs 111 conditions,brominate and nitrate with acetyl nitrate at position 4, but in concentratedsulphuric acid protonation of the heterocyclic ring is thought to occur andaccount for bromination and nitration in this solvent 112 taking place a t the4' position. The isomer ratio obtained in the homolytic phenylation ofl-phenylpyrazole is 30 : 55 : 6 : 9 at positions 3, 2', 3', and 4', re~pectively.1~3Pyrazoles undergo acid- and base-catalysed N-cyanoethylation, 114 andAzoles.l o l A .Zamojski, Chem. and Id., 1963, 117.l 0 2 T. Lesiak, Rocxniki Chem., 1962, 36, 1533.Io3 J. I. DeGraw, D. M. Bowen, and W. A. Bonner, Tetrahedron, 1963, 19, 19.lo4 B. ostman, Arkiv Kemi, 1963, 19, 499.lo5 B. Ostman, Arkiv Kemi, 1963, 19, 527.l 0 6 R. D. Schuetz, D. D. Taft, J. P. O'Brien, J. L. Shea, and H.M. Mork, J . Org.lo7 A. B. Hornfeldt and S. Gronowitz, Arkiv Kemi, 1963, 21, 239.108 D. Sullivan and R. Pettit, Tetrahedron Letters, 1963, 401.l o Q E. B. McCall, A. J. Neale, and T. J. Rawlings, J., 1962, 5288.1lOW. Carruthers, J., 1963, 4477.111 I. I. Grandberg, L. G. Vasina, A. S. Volkova, and A. N. Kost, Zhur. obshchei112 M. A. Khan, B. M. Lynch, and Yuk-Yung Hung, Canad. J . Chwt., 1963,41,1540.113 B. M. Lynch and M. A. Khan, Canad. J . Chem., 1963, 41, 2086.114 I. I. Grandberg and A. N. Kost, Zhur. obshchei Khim., 1961, 31, 3700.Chem., 1963, 28, 1420.Khim., 1961, 31, 1887ACHESON : HETEROCYCLIC COMPOUNDS 3874-diazo-3,5-dimethylpyrazole, which is obtained from the pyrazole withnitrous acid, couples with p-naphthol to give the expected red azo-dye.l15Powerful hydrogenation of pyrazolines opens the ring and forms 1,3-di-aminopropanes.l162- Amino-NN-dimethylaniline and its benzoyl derivatives are cyclised byperformic acid to 1 -methylbenzimidazole, possibly via the N-oxide.117Benzimidazole is oxidised by lead dioxide to the derivative (55) which doesnot react with maleic anhydride.11* 2-Phenylbenzimidazole N-oxide isformed from nitrosobenzene and phenyl cyanate. 119 Rearrangement ofbenzimidazole N-oxide with cold and with hot acetic anhydride gives,respectively, N-acetyl- and NN'-diacetyl- benzimidazolone.120 A newaromatic system (56) is formed from 2,2'-bipyridyl and methylene iodide.1215-Aryloxazoles are obtained from aryl aminomethyl ketone hydrochloridesand ethyl orthoformate.122 The ketone (57), with aqueous alkali, undergoesan interesting reaction yielding 2,1-benzisoxazole-3-carboxylic acid (58), andsimilar condensations giving otherdescribed.123r 0(57) [ o3 'OH4,5-Dichlorothiazole is obtainedacetamidomethanesulphonate.1z4 Inheterocyclic products have been(58)from thionyl chloride and sodiumthiazole and its alkyl derivatives,butyl-lithium displaw-s a hydrogen atom at position 2 more readily than onea t position 5; the most active methyl group is at position 2.1251 ,l-Dicyano-2,2-disodiomercaptoethylene is easily cyclised to isothia-zoles, e.g., chlorine in carbon tetrachloride gives 3,5-dichloro-4-cyano-isothiazole.126 Isothiazole-4- and -&aldehyde reduce ammoniacal silvernitrate, undergo the Cannizzaro reaction, and condense with the usual carbonyl~agents.1~7115H. P.Patel and J. M. Tedder, J., 1963, 4589.116 A. N. Kost, G. A. Golubeva, and R. G. Stepanov, Zhur. obshchei Khim., 1962,117 0. Meth-Cohn and H. Suschitzky, J., 1963, 4666.118 J. H. M. Hill, J . Org. Chem., 1963, 28, 1931.119 F. Minisci, R. Galli, and A. Quilico, Tetrahedron Letters, 1963, 785.120 N. F. Cheetham, W. F. Forbes, D. J. Kew, and P. F. Nelson, Austral J. Chem.,121 I. C. Calder, T. M. Spotswood, and W. H. F. Sasse, Tetrahedron Letters, 1963, 96.l Z 2 N . P. Demchenko and A. P. Grekov, Zhur. obshchei Khim., 1962, 32, 1219.123 J. D. Loudon and G. Tennant, J., 1963, 4268.124 P. Reynaud, M. Robba, and R. C. Moreau, Bull. SOC. chim. France, 1962, 1735.125 J.Beraud and J. Metzger, Bull. SOC. chim. France, 1962, 2072.126 W. R. Hatchard, J . Org. Chem., 1963, 28, 2163.127 D. Buttimore, D. H. Jones, R. Slack, and K. R. H. Wooldridge, J., 1963, 2032.32, 2240.1963, 16, 729388 ORGANIC CHEMISTRYTwo new rearrangements involving opening and closing of the thia-zolidine ring have been reported in the penicillin series. The acid chloride(59) with triethylamine gives (60),12* and the sulphoxide (61) is convertedby toluene-p-sulphonic acid to the thiazine (62) which has also been syn-thesised from a cephalosporin derivative.12905-Amino-1,2,4-selenadiazoles (63) have been obtained from N-bromo-acetamidine and - benzamidine with potassium selenocyanate. They aredecomposed by alkali. l30 A number of dimeric condensation products ofmonohydrazones of 1 ,Z-diketones, thought originally to be lY2,5,6-tetra-azacyclo-octatetraenes, have been identified as triazolotriazoles (e.g., 64),and the compound shown was oxidised by potassium permanganate to4-methyl- 1,2,3 - triazole-5- carboxylic acid.31 Sporidesmin, present in thesaprophytic mould Pithomyces chartarum and the cause of facial eczema inNew Zealand sheep, has structure (65).132 &:x MeMe r yc> Me HOSe(63) (64) Me0 NMe (65)HOzC- COZH CI ”’.. .. N. ... ..Rk-p N. ~ N H ~0 MeMiscellaneous. 1,2-Dithiolium salts (66) are obtainable from 1,3-dike-tones and hydrogen disulphide in the presence of strong acids 133 and havealso been prepared 134 from 1,3-dithiacyclohexenes (67) by oxidation withbromine, when ring contraction occurs with the elimination of an aldehyde.Ph128 S.Wolfe, J. C. Godfrey, C. T. Holdrege, and Y. G. Perron, J . Amer. Chem. SOC.,1S9R. B. Morin, B. G. Jackson, R. A. Mueller, E. R. Lavagnino, W. B. Scanlon,13* J. Goerdeler, D. Cross, and H. Klinke, Chem. Ber., 1963, 96, 1289.131 M. Brufani, W. Fedeli, G. Giacomello, and A. Vaciago, Chern. Ber., 1963, 96, 1840.132 J. Fridrichson and A. M. Mathieson, Tetrahedron Letters, 1962, 1265.133 D. Leaver, W. A. H. Robertson, and D. M. McKinnon, J., 1962, 5104.134 A. Luttringhaus, M. Mohr, and N. Engelhard, AnnaZen, 1963, 661, 84.1963, 85, 643.and S. L. Andrews, J. Amer. Chern. SOC., 1963, 85, 1896ACHESON : HETEROCYCLIC COMPOUNDS 389The 3-chloro-l,2-dithiolium cation (68) is extremely reactive to nucleophilicreagents,l35 and such salts with hydrazine yield pyraz01es.l~~a-Oxoalkyl dithiocarboxylates (69) cyclise to 173-dithiolium salts (70)with hydrogen sulphide in perchloric acid-acetic acid, or under milder con-ditions. l33 3-Methyl-Ei-phenyl-1,2-dithiolium and 2-methyl-4-phenyl- 1,3-dithiolium salts possess activated methyl groups and give styryl derivativeswith 4-dimethylaminobenzaldehyde, but the 4-methyl-2-phenyl-l,3-di-thiolium cation does not react under the same condition.l33 The anti-biotic holomycin (7 1) has been synthesised.37"""0"G~ H. (71)Triphenylphosphine , with dimethyl acetylenedicarboxylate 138 anddicyanoacetylene, l39 gives the corresponding phosphacyclopentadienes(72 ; R = C0,Me and CN, respectively) ; a zwitterionic formulation sug-gested 140 for the former adduct is incompatible with n.m.r.data. Thephosphole (73) , from triphenylphosphine and tetracyanoethylene, is splitby hot concentrated hydrochloric acid to triphenylphosphine oxide andbutanetetracarboxylic a~id.13~ Diphenylacetylene and selenium tetra-chloride cyclise to the heterocycle (74), which yields 1,2-diphenylethane withRaney nickel under hydrogen.141 2-Biphenyldialkylboranes at 180-200 Olose alkane to give the B-alkyldibenzborole (75). 142t 72) (73) (74) (75)Six-Membered Rings and Condensed Derivatives.--Pyridines. Theresonance energy of pyridine, calculated from new experimental data,143 is31.9 & 2.0 kcal. mole-l. Diethyl 4-ethoxybuta-l,3-diene-l,l-dicarboxy-late (76) from 1,l73,3-tetraethoxypropane, acetic anhydride, and ethylmalonate, is cyclised by polyphosphoric acid to ethyl 2-pyrone-3-car-boxylate, while treatment with primary amines (including ammonia) andthen sodium ethoxide gives a new route to pyridones (77).14* Ketendimerand glycine in basic solution form the pyridone (78),l45 and the product136 J.Faust and R. Mayer, Angew. Chem., 1963, 75, 573.136 E. Klingsberg, J. Org. Chern., 1963, 28, 529.19' G. Buchi and G. Lukas, J. Amer. Chem. SOC., 1963, 85, 647; U. Schmidt and F.138 J. B. Hendrickson, R. E. Spencer, and J. J. Sims, Tetrahedron, 1963, 19, 707.13D G. S. Reddy and C. D. Weiss, J. Org. Chem., 1963, 28, 1822.140A. W. Johnson and J. C. Tebby, J., 1961, 2126.141 R.F. Riley, J. Flate, and P. McIntyre, J. Org. Chem., 1963, 28, 1138.142 R. Koster and G. Benedikt, Angew. Chem., 1963, '95, 419.143 A. F. Bedford, A. E. Beezer, and C. T. Mortimer, J., 1963, 2039.144 T. B. Windholz, L. H. Peterson, and G. J. Kent, J. Org. Chem., 1963, 28, 1443.S. Garratt and D. Shemin, J. Org. Chem., 1963, 28, 1372.Geiger, Annalen, 1963, 684, 168390 ORGANIC CHEMISTRYfrom dicyanomethane, chloroform, the sodium ethoxide has been identified 146as the pyridine (79).OEt' COzEt fi COMe+ / 0- Me + / 0- 0 N N 0 C02Et Co2Et. CH2.CO2H(78) (79)(76) (77)The electronic, infrared, and Raman spectra of some monosubstitutedpyridines have been recorded and discussed. 147 The bromination of pyridinein fuming sulphuric acid at 130" yields 3-bromopyridine with some 2,5-dibromopyridine, and the rate of substitution is much reduced in 90% acid,the by-product being 3,5-dibrom0pyridine.l~~ The partial rate factor forthe homolytic 2-nitrophenylation of pyridine is greatest for the 3-po~ition.l~~The first assessment of the electrophilic reactivity of the neutral pyridinemolecule has been made l50 from the rates of pyrolysis of the 2-, 3-, and4-pyridylethyl acetates (80) which follow the order 3 > 2 > 4.This isalso the order of the stability of the carbonium ions attached to thesepositions and which are formed when bond " a " breaks.6 MeHPh HZCNMe Et R Me Me(80) (8') (82) (83) (84)The free radical (81) has been obtained after distillation as an extremelyoxygen-sensitive emerald-green oil which is moderately stable at 25".Itgives no n.m.r. signal and its magnetic susceptibility corresponds to 60-100%of free radical.151 The rates of reaction of the chloropyridines and theirN-oxides with sodium methoxide decrease in the order 4 > 2 > 3, but forthe chloro-l-methylpyridinium chlorides it is 2 > 4 > 3.152 The fluorineatom of 3-fluoropyridine N-oxide is very readily replaced by nu~leophiles.~~~cc-Bromo- and a-chloro-pyridines give the corresponding fluoropyridines withpotassium fluoride in dimethyl sulphoxide. 154 Dichlorocarbene reducespyridine N-oxide to ~ y r i d i n e . l ~ ~14.5 A. P. Krapcho and P. S. Huyffer, J . Org. Chem., 1963, 28, 2461.147 E. Spinner, J., 1963, 3855.148 H.J. den Hertog, L. van der Does, and C. A. Landheer, Rec. Trav. china., 1962,140 R. A. Abrramovitch and J. G. Saha, Tetrahedron Letters, 1963, 301.I5O R. Taylor, J., 1962, 4881.151 E. M. Kosower and E. J. Poziomek, J. Amer. Chem. Xoc., 1963, 85, 2035.152 M. Liveris and J. Miller, J., 1963, 3486.lS3 M. Bellas and H. Suschitzky, J., 1963, 4007.154 G. C. Finger, L. I). Starr, D. R. Dickerson, H. S. Gutowsky, and J. Hamer,1 6 6 E . E. Schweimr and G. J. O'Neill, J . Org. Chem., 1963, 28, 2460.81, 864.J . Org. Chem., 1963, 28, 1666ACHESON : HETEROCYCLIC COMPOUNDS 391Polarographic reduction of pyridine-4-carboxylic acid and its N-ethylderivative at about pH 3 gives up to 70% of the corresponding a1deh~des.l~~This appears to be the first instance of the direct reduction of a pyridine acidto the corresponding aldehyde.M. tuberculosis uses aspartic acid, includingthe nitrogen atom, in its synthesis of nicotinic acid.157 A complete analysisof the ultraviolet and visible absorption spectra of the 3-hydroxypyridine-4-aldehyde Schiff's base with valine has been carried 2-Phenacyl-pyridine exists in the solid state as the enol, stabilised by a strong intra-molecular hydrogen bond.159Spectral data show that 2- and 4-pyridones protonate on the oxygenatoms.160 The cyclopentadienyl derivative (82 ; R = Me) protonates onboth possible positions of the smaller ring,lsl and the dipole moment of theN-benzyl derivative (8.9 D) suggests that charged structures contributeabout 27% to the resonance hybrid.lB23,3-Dimethylpentane- 1 ,&%one and methylamine yield 1,4-dihy&o- 1,4,4-trimethylpyridine which protonates 163 a t position 3 and appears to have aplanar ring.This is in agreement with the conclusion from n.m.r. studiesthat the two C-4 protons of 1 -benzyldihydronicotiamide and reducedcoenzyme I are in equivalent environments, so the rings must be planar orundergo rapid interconversions. 16*The dihydropyridine cation (83) partially isomerises to (84) on heatingin ethanol.165Condensed pyridines. The cyclisation of p,/?-dimethylcinnamaldehydeoxime by acetic anhydride to 3,4-dimethylquinoline lB6 and of the acetylene(85) to the quinoline (86) by a copper catalyst 16' constitute new syntheses ofthe ring system. 3-Amino-1 -bromo- or -iodo-isoquinolines are obtainedfrom 2-cyanobenzylcyanides with anhydrous hydrogen bromide or iodide ;hydrogen chloride does not cause reaction.168 2-Methoxy-6-vinylben-aldehydes and aromatic amines in alkaline ethanol yield the correspondingN-aryl- 1,2,3,4,-tetrahydroisoquinolines.The methoxy-group is essential forcyclisation.169 The conjugate acids of quinoline 170 and isoquinoline 1 7 1are the species nitrated in concentrated sulphuric acid, and in the formercase the proton is present in the transition state.l70 Quinoline N-oxide156 H. Lund, Acta Chem. Scand., 1963, 17, 972, 1077.lS7 D. Gross, H. R. Schutte, G. Hubner, and K. Mothes, Tetrahedron Letters, 1963,158 D. Heinert and A. E. Martell, J . Amer. Chem. Soc., 1963, 85, 183.159 R.F. Branch, A. H. Beckett, and D. B. Cowell, Tetrahedron, 1963, 19, 401.160 A. R. Katritzky and R. E. Reavill, J., 1963, 753; C. L. Bell, J. Shoffner, andlel G. V. Boyd and L. M. Jackman, J., 1963, 548.le2 W. D. Kumler, J . Org. Chern., 1963, 28, 1731.le3 E. N. Kosower and T. S. Sorensen, J . Org. Chern., 1962, 27, 3764.16* W. L. Meyer, H. R. Mahler, and R. H. Baker, Biochem. Biophys. Acta, 1962,l e 6 E . M. Fry, J . Org. Chern., 1963, 28, 1869.lee C. Troszkiewicz and J. Glinka, Roczniki Chem., 1962, 36, 1387.168 F. Johnson and W. A. Nasutavicus, J . Org. Chem., 1962, 27, 3953.169 D. Beke, K. Harsgnyi, and P. Kolonites, Acta Chirn. Acad. Xci. Hung., 1963,17OM. W. Austin and J. H. Ridd, J., 1963, 4204.R. B. Moodie, I(. Schofield, and M.J. Williamson, Chem. and Ind., 1963, 1283.541.L. Bauer, Chem. and Ind., 1963, 1435.64, 363.N. R. Easton and D. R. Cassady, J . Org. Chem., 1962, 27, 4713.35, 205392 ORGANIC CEEMISTRYmethosulphate with potassium nitrate or calcium nitrate in dimethyl sul-phoxide a t 140 O gives 3-nitroquinoline N-oxide. 1721-Hydroxyquinolizinium salts, prepared from 1,2,3,4-tetrahydro-l-oxoquinolizinium bromide by dibromination (position 2), aromatisation to the1-acetoxy-2-bromoquinolizinium salt with acetic anhydride, debromination,and hydrolysis, have phenolic properties.173 Methyl sulphate methylatesl-oxoquinolizine on the oxygen atom.17* Nitric acid converts unsub-stituted benzoquinolizinium salts (87) to the pyridine (88), but when methoxylgroups are present (87; R = ONe) the quinolizinium derivative (89) isobtained.175 The product of acid hydrolysis of tetramethyl 4H-quinolizine-1,2,3,4-tetracarboxylate has been identified as the chloride (90) which, onpassing through a basic ion-exchange resin, isomerises to the conjugated3,4-dihydro-isomer.176 The quinolizine (91) appears to combine initiallywith hot dimethyl acetylenedicarboxylate across the 6,9-positions, since theproducts from this reaction are dimethyl phthalate and tetramethyl 2-methyl-pyridine-3,4,5,6-tetracarboxylate. 177represented by the structure (92).178striking anticancer activity, has been identified 179 as (93).( :)- 1 -0xoquinolizidine isStreptonigrin, a metabolite of Streptomyces Jlacculus whichabsolutelyexhibits a172E.Ochiai and A. Ohta, Chem. and Pharm. Bull. (Japan), 1962, 10, 349.173A. Fozard and G. Jones, J., 1963, 2203.174 G. A. Reynolds and J. A. van Allan, J . Org. Chem., 1963, 28, 527.1 7 5 M. W. Barker, Diss. Abs., 1963, 24, 68.176 R. M. Acheson, J. M. F. Gagan, and G. A. Taylor, J., 1963, 1903.1 7 8 S. F. Mason, K. Schofield, and R. J. Wells, Proc. Chem. SOC., 1963, 337.179 K. V. Rao, K. Biemaan, and R. B. Woodward, J . Amer. Chem. SOC., 1963, 85,R. M. Acheson, A. R. Hands, and M. J. Woolven, J., 1963, 2082.2532ACHESON : HETEROCYCLIC COMPOUNDS 393Pyridazine and maleic anhydride give theadduct (94) .I80 The borazaphenanthrene (95) with sodium nitrate in aceticacid gives the diazonium salt (96) which, after addition of sodium acetate,cyclises to benzo[c]cinnoline (97) ; the diazonium salt with boiling water, incontrast, loses nitrogen yielding 9,10-dihydro-9-oxa- lo-boraphenanthren-1O-ol.lSl Nitration of benzo[c]cinnoline (97) occurs at positions 1 and 4.182Axines and condensed axines.N=N5HN =_B -OH B (OH), a - - - - *m3 - -9 10 I 2(95) (96) (97)Irradiation of the pyrimidine (98) at 2537 A in anhydrous or aqueousmedia opens the ring to give compound (99) quantitatively, possibly asindi~ated.l8~ Willardine (loo), which occurs in plants with albizziine(a-amino-/,?-ureidopropionic acid), is formed from the latter with aqueousformylacetic ester and base at room temperature.184The resonance energy of pyrazine, 24.3 2.7 kcal.mole-l, calculated 143from a new value for the heat of formation of piperazine, differs markedlyfrom that (8.1 kcal.mole-1) reported last year.lB5 A new synthesis 186 andnew rearrangements l S 7 of quinoxaline N-oxides have been described. Theproduct from 2,3-dimethylquinoxaline and maleic anhydride has structureUndecachlorophenothiazine, from the chlorination of phenothiazine, at180" loses three atoms of chlorine to form the very stable free radical (102)(101).1S80 Ul8oR. C. Cookson and N. S. Isaacs, Tetrahedron, 1963, 19, 1237.l s l M . J. S. Dewar and W. H. Poesche, J . , 1963, 2201.J. Corbett, P. F. Holt, and M. L. Vickery, J., 1962, 4860.l e 3 K. L. Wierzchowski and D. Shugar, Photochem. and Photobiol., 1963, 2, 377;K. L. Wierzchowski, D. Shugar, and A. R. Katritzky, J .Amer. Chem. SOC., 1963,85, 827.ls4Yu. P. Shvachkin and M. T. Azarova, Zhur. obshchei Khirn., 1962, 32, 3448.lB5 Ann. Reports, 1962, 59, 338.186G. Tennant, J., 1963, 2428.187 A. S. Elina, Zhur. obshchei Khim., 1962, 32, 2967.188 E. C. Taylor and E. S. Hand, J . Amer. Chem. SOC., 1963, 85, 770394 ORGANIC CHEMISTRYwhich can be sublimed and is stable in sulphuric acid for many ~eeks.18~A fungal pigment has been identified as 2-amino- 1 -formyl-3-oxophenoxazine-9-carboxylic acid, and with chromic acid yields 2-oxobenzoxazole-4-car-boxylic acid. lgo NN'-Dimethylurea combines with di( chlorosulphony1)amineforming a strongly acidic derivative (103) of a new heterocyclic sy~tern.1~1New pterins isolated from 3000 bee pupae and identified by comparisonwith synthetic material are neopterin [2-amino-3,4-dihydro-4-0~0-6(~-erythro- 1,2,3-trihydroxypropyl)pteridineI and violapterin (lY2,3,4-tetrahydro-'i-hydroxy-2,4-dioxopteridine) .I92Differing views exist concerning the status of theoretical work on purine.193Its n.m.r.spectrum has been examined lg4 and it is clear that the 6-proton isthe least shielded. An efficient new synthesis of uric acid is available,l95 andthe 3-riboside has been obtained in 90% yield from tetrakistriethylsilyluricacid.lg6 The 8-chlorine atom of 2,8-dichloropurine is the more easily dis-placed by nucle~philes.~~~ Adenine has been obtained by electron irradia-tion of methane, ammonia, and water. I98 The radiation decomposition ofaqueous adenine gives 4 , 6- diamino - 5 - for mamidopyrimidine, hypoxant kine,and 8-hydro~yadenine.~~~Oxygen and sulphur heterocycZes.Benzenediazonium chloride and4-nitroso-NN-dimethylaniline react with the methyl group of 2-methyl-4,6-diphenylpyrylium chloride.2oo 2,4,6-Triphenylpyrylium oxide (104) withvisible light is reversibly converted to the unstable intermediate (105) whichisomerises to the photostable pyridone (106). 201 2,4,6-Triphenylpyryliumfluoroborate is converted by sodium sulphide and fluoroboric acid to thecorresponding thiopyrylium derivative. 2a2 Other pyrylium perchlorateswith an excess of triphenylphosphine methide yield azulenes. 203 Struc-tural transformations of flavylium salts in acid and in alkaline solution havebeen examined 204 as has the hydrogen peroxide oxidation of these sa1tsYmband of chalcones,206 to benzofuran-3-carboxylic acids and other compounds.189 C.Dogea and I. Silberg, Nature, 1963, 198, 883.l90 J. Gripenberg, Acta Chern. Scand., 1963, 17, 703.l91 M. Becke-Goehring and H. A. Schlotter, Naturwiss., 1963, 50, 353.1 9 2 H. Rembold and L. Buschmann, Annalen, 1963, 662, 72.193 P. G. Lykos and R. L. Miller, Tetrahedron Letters, 1963, 1743, and papers therein194 S. Matsuure and T. Goto, Tetrahedron Letters, 1963, 1499.196 C. W. Bills, S. E. Gebura, J. S. Meek, and 0. J. Sweeting, J . Org. Chem., 1962,196 L. Birkofer, A. Ritter, and H. P. Kiihlthau, Angew. Chem., 1963, 75, 209.197 A. F. Lewis, A. G. Beaman, and R. K. Robins, Canad. J . Chrn., 1963, 41,198 C. Ponnamperuma, R.M. Lemmon, R. Manner, and M. Calvin, Proc. Nut. Acad.199 C. Ponnamperuma, R. M. Lemmon, and M. Calvin, Radiation Res., 1963,18, 540.200 N. V. Khromov-Borisov and L. A. Gabrilova, Z h w . obshchei Khim., 1962, 32,2 o l E . F. Ullman, J . Amer. Chem. Soc., 1963, 85, 3529.209 K. Kanai, M. Umehara, €3. Kitano, and H. Fukui, J . Chem. SOC. Japan, 1963,903K. Dimroth, K. H. Wolf, and H. Wache, Angew. Chern., 1963, 75, 860.204 L. Jurd and T. A. Geissman, J . Org. Chem., 1963, 28, 2394.2 0 6 L . Jurd, Chern. and Ind., 1963, 1165; Tetrahedron Letters, 1963, 1151.206 B. Cummins, D. M. X. Donnelly, J. F. Eades, H. Fletcher, F. 0. Cinnhide, E. M.cited.27, 4633.1807.Sci., U.S.A., 1963, 49, 737.3211.84, 432.Philbin, J. Swirski, T. S. Wheeler, and R.K. Wilson, Tetrahedron, 1963, 19, 499ACHESON : HETEROCYCLIC COMPOUNDS 395The 2-pyrone constitutes at least 98% of the equilibrium mixture formedfrom 4- met hoxy- 6 -met hyl-2 - pyrone and 2 -methoxy - 6 -me thyl-4-pyrone and a~atalyst.~07 4-Pyrone and its 2,6-dimethyl derivative protonate on theoxygen atom,208 and the second compound with hydroxylamine gives4 - hydroxyamino-2,6 -&met hylp yridine N - oxide. 209 Ultraviolet irradiationof Z76-dimethyl-4-pyrone at high dilution 210 yields 4,5-&methylfurfural,whereas irradiation of the solid 211 yields the dimer (107). 4-Chlorocou-marin is converted by alkali to benzofuran-2-carboxylic acid. 212The first cyclopenta[c]pyran identified (108) is the red by-productobtained in the thermal decomposition of phenacyltrimethylammoniumhydroxide to tribenzoylcyclopropane.213The parent heterocycle, 1-oxaphenalene (log), was synthesised 214 afterbiflorin, the antibiotic from Cupraria biflora, L., had been identified as thequinone (l10).215 A new structure (111) is proposed 2i6 for cyanomaclurin.Hydrolysis of amorphin, a glycoside of the insecticidal seeds of Amrphafruticosa, gives glucose, arabinose, and the new aglucone arnorphigeninOMeHOt’ 1 ’ )207 P. Beak, Tetrahedron Letters, 1963, 863.208D. Cook, Canad. J . Chem., 1963, 41, 505.209 P. Yates, M. J. Jorgenson, and S . K. Roy, Canad. J . Chem., 1962, 40, 2146.210 P. Yates and I. W. J. Still, J . Amer. Chem. SOC., 1963, 85, 1208.211 P. Yates and M. J. Jorgenson, J . Amer. Chena.SOC., 1963, 85, 2956.21a V. A. Zagorevskii and N. V. Dudykina, Zhur. obshchei Khim., 1962, 32, 2383.213 J. Harley-Mason and C. R. Harrison, J . , 1963, 4872.214 S. O’Brien and D. C. C. Smith, J., 1963, 2907.215 J. Cornin, 0. G. de Lima, H. N. Grant, L. M. Jmkman, W. Keller-’Schierlein,$16 P. M. Nair and K. Venkataraman, Tetrahedron Letters, 1963, 317.and V. Prelog, Helv. Chim. Acta, 1963, 46, 409396 ORGANIC CHEMISTRY(1 l2).217are attached to the primary alcohol group.Amorphin is the first rotenoid glycoside recognised and the sugarsThe aphid colouring matters erythroaphin-jb and -sZ (113) and (114)respectively.218 Munetone has been identified as the isoflavone (1 15).21QMaclurxanthone (116) is the first example of a plant phenol possessing a1,l -dimethylprop-2-enyl group.220 The structure of the ergot pigmentergoflavin (117) has been established by chemical 221 and X-ray work,222and some other ergot pigments have been identified.223 Racemic brazilinhas been synthesised. 224 The absolute configuration of D-a-tocopherolhas been determined 225 and the chemistry of the tocopherols has beenreviewed. 226Sulphur and other heterocydes. Isothialene (118), a red solid, has beenobtained from the dehydrogenation of the perhydroderivative 227 and alsofrom cyclopentadienylsodium and 3-methylthiazolinium bromide. 228 Thia-217 L. Crombie and L. Peace, Proc. Chem. SOC., 1963, 246.Lord Todd, Pure Appl. Chem., 1963, 6, No. 4, 709.219 S. F. Dyke, W. D. Ollis, and M. F. Sainsbury, Proc. Chem.SOC., 1963, 179;C . S. Barnes, J. L. Occolowitz, N. L. Dutta, P. M. Nair, P. S. Phadke, and K. Venkatara-man, Tetrahedron Letters, 1963, 281.120 M. L. Wolfrom, F. Komitsky, G. Fraenkel, J. H. Looker, E. E. Dickey, P.McWain, A. Thompson, P. M. Mundell, and 0. M. Windrath, Tetrahedron Letters,1963, 749.221 J. W. ApSimon, J. A. Corran, N. G. Creasey, K. Y. Sim, and W. B. Whalley,Proc. Chem. SOC., 1963, 209.223 J. D. M. Asher, A. T. McPhail, J. Monteath Robertson, J. V. Silverton, andG. A. Sim, Proc. Chem. SOC., 1963, 210.J. W. ApSimon, 3. A. Corran, N. G. Creasey, W. Marlow, W. B. Whalley, andK. Y . Sim, Proc. Chem. SOC., 1963, 313.2240. Dann and H. Hopmann, Annulen, 1963, 667, 116.2 z 5 H. Mayer, P. Schudel, R. Ruegg, and 0. Isler, Helv.Chim. Actu, 1963, 46, 963.22* E. 0. Isler, P. Schudel, H. Mayer, J. Wursch, and R. Ruegg, Vitamins und227 A. G. Anderson, W. F. Harrison, and R. G. Anderson, J. Amer. Chem. Xoc.,z a 8 R. Wagner and R. Mayer, 2. Chem., 1963, 3, 25.Hormones, 1962, 20, 389.1963, 85, 3448ACHESON : HETEROCYCLIC COMPOUNDS 397pyrylium salts with phenyl-lithium give the l-phenylthio( 1V)benzenes almostexclusively, but with phenylmagnesium bromide the 2-phenyl-2H-thiapyransare 0btained.2~~ The n.m.r. spectrum of the thiabenzene (1 19) supports itsformulation, as absorption only took place at about 32.229 The radical-cation derived from thianthrene has been studied. 230 Disodium dimer-captomaleonitrile with thionyl chloride gives the thiole (120) and underdifferent conditions the dithiin (121) which is thought to be formed via3,4-dicyano-l,2-dithiet. Reactions of the dithiin (121) examined includethermal decomposition which gives tetra~yanothiophen.~~l Tetra-fluoroethylene and hot sulphur gives a mixture of (122) with (123) or thetrithiepan (124) according to the conditions.2321 , l -Diphenylphosphabenzene (127) has been obtained as a yellow powderfrom the alcohol (125) by dehydration to the olefin, addition of bromine,dehydrobromination to the cation (126), and treatment with sodium hydrox-ide.233 It is extremely easily oxidised in solution.The iodide (128) ispresent in solution as a tautomeric mixture.234OH229 C. C. Price, M. Hori, T. Parasaran, and M. Polk, J . Amer. Chem. SOC., 1963, 85,2278.230 E.A. C. Lucken, J., 1962, 4963; H. J. Shine and L. Piette, J . Anaer. Chem. SOC.,1962, 84, 4798.2 3 1 H. E. Simmons, R. D. Vest, D. C. Blomstrom, J. R. Roland, and T. L. Cairns,J . Amer. Chem. SOC., 1962, 84, 4746, 4756, 4772.232 C. G. Krespan and W. R. Brasen, J . Org. Chem., 1962, 27, 3995.Z33 G. Mhkl, Angew. Chem., 1963, 75, 669.234 F. G. Mann, J., 1963, 4266398 ORGANIC CHEMISTRYSeven-Membered Rings.-Transannular reaction occurs when thia- 1 -cycloheptan-4-one l-oxide is treated with perchloric acid, the salt (129) beingformed. 235 sym-Divinylethylene carbonate, on pyrolysis over lithiumchloride, gives a mixture of 2,3-divinyloxiran and 4,5-dihydrooxepin (130)which, with aqueous acids, contracts to l-formylcyclopent-l-ene.236 Thebenzoxepin (132), obtained together with 2-methyl-2H-chromen from thealdehyde ('131) and sodium ethoxide, rearranges to this chromen on refluxingwith the ethoxide ; this is the first example of an oxepin rearrangement wherethe oxygen remains in the cyclic system.237Br' A 0( 1 30) (131) (132) ('33)The sodium derivatives of 2,6-dialkylphenols with chloramine give1,3-dihydro-2H-azepin-2-ones (133) .23* Azidoformic ester undergoes aphotochemical reaction with benzene giving an excellent yield of N-ethoxy-car bonylazepine . 39 2,3,4 , 5-Tetrahydro - 7 , 8 -dimethyl-2,5-dioxobenzo[fl-aze -pine has marked activity against Crocker sarcoma.240 Dibenzo[ bflazepinewith concentrated hydrochloric acid rearranges to 9-methylacridine. 2412 3 5 N . J.Leonard and W. L. Rippie, J . Org.. Chem., 1963, 28, 1957.236 R. A. Braun, J. Org. Chem., 1963, 28, 1383.237 E. E. Schweizer and R. Schepers, Tetrahedron Letters, 1963, 979.2s* L. A. Paquette, J. Arner. Chem. SOC., 1962, 84, 4987; 1963, 85, 3288.e8s K. Hafner and C. Konig, Angew. Chem., 1963, 75, 89.MOD. M. James and A. H. Rees, J. Medicin. Chem., 1962, 5, 1231.24lP. Rumpf and R. Reynaud, Bull. SOC. chim. Prance, 1962, 224110. ALEALOIDSBy K. W. BentleyBiogenesis-Feeding experiments with Datura stramonium have shownthat [ 1,4-14C] putrescine is incorporated into hyoscyamine, the radioactivitybeing confined in the resulting alkaloid equally to C-1 and C-5.l Phenyl-alanine is a precursor of the c,-c, unit of lycorine but not of the cgcz unit,while the reverse is the case with tyrosine and tyramine.2 Two units oftyrosine are incorporated into hydrastine and berberine in Hydrastis cana-densis, but the incorporation is not uniform in the two parts of the molecules,and with dihydroxyphenylethylamine as precursor only one unit is in-corporated in the alkaloids ; these results favour the classical biogeneticalpathway to the bases rather than the alternative route through prephenicacid.3 The so-called “ berberine-bridge ” carbon atom of the berberinealkaloids, forming a link between the nitrogen and one of the aromaticnuclei, has been shown to be the residue of an oxidised N-methyl group bythe biosynthesis of berberine from isoquinoline alkaloids labelled a t thisposition in Hydrastis canademis 4 and Berberis japonica.6 The incorpora-tion of sodium [l-W] acetate into ajmaline and serpentine in RauwoZ$aserpentinu affords bases labelled exclusively at four centres and these resultsfavour the elaboration of the unit (2) as an intermediate in the biosynthesisof alkaloids of the indole group, as suggested by Wenkert.’HeCHO*coo-&CHI0 0CH2ooc’ ‘coo-t*COO CHO[3- 14C]Reticuline has been incorporated into morphine but tetrahydro-papaverine is not, indicating that phenolic groups are required for thecoupling to give the morphine system as is required by Barton’s biogeneticalhypotheses.8 It was originally suggested by Bentley that the 4,5-oxygenbridge in the morphine alkaloids is closed by an allylic expulsion of theC-7 oxygen substituent ; this has now received experimental support.TheE. Leete and M. C. L. Louden, Chem. and Ind., 1963, 1725.R. A. Suhadolnik, A. G. Fisher, and J. Zulalian, J . Amer. Chem. Soc., 1962,J. R. Gear and I. D. Spenser, Canad. J. Chem., 1963, 41, 783.D. H. R. Barton, R. H. Hesse, and G. W. Kirby, Proc. Chem. SOC., 1963, 267.A. R. Battersby, R. J. Frmcis, M. Hirst, and J. Staunton, Proc. Chm. SOC.,E. Leete and S. Ghosal, Tetrahedron Letters, 1963, 1179.7 E. Wenkert, J . Amer. Chem. SOC., 1962, 84, 98.*A. R. Battersby, R. Binks, D. M. Foulkes, R. J. Francis, D. J. McCaldin, andE[. Ramuz, Proc. Chem. SOC., 1963, 203. * K. W. Bentley, Ezperientia, 1956,12,251; K. W. Bentley and H. M. E. Cardwell,J., 1955, 3252.84, 4348.1963, 268400 ORGANIC CHEMISTRYintermediate dienone (4) resulting from the oxidative coupling of the di-phenol (3) has been synthesised from thebaine and found to show no tendencyt o cyclise, but on reduction with sodium borohydride both resulting diastereo-isomeric allylic alcohols (5) afford thebaine at pH 4 at room temperature.A very low yield of the dienone (4) has been obtained by the manganesedioxide oxidation of the diphenol (3).10 The theories of the biogenesis ofalkaloids and the experimental support for these have been lucidly reviewedby Battersby l1 and by Barton.12MeoQ HOMe0HOMe0m o l e and Pyricline Groups.-The structures of the Senecio alkaloidsretusamine, otosenine, renardine, and onetine, all derived from the N-methyl-containing otonecine, have been elucidated by X-ray studies.Retusaminehydrochloride has structure (6) and presumably otonecine is a resonancehybrid of the canonical forms (7) and ($).I3 In this group also the epoxideMe CH2.0MeOA Me(7)Me0(8)2 O - \Me a CHMe-C.CH2-OH/(9)(9) has been shown to be a naturally occurring base,14 angularine has beenproved to be the seneciphyllic acid ester of rosmarinecine,15 and a newstructure (10) has been assigned to scleracinecic acid.le The alkaloid teco-manine from Tecoma stam Juss. has been shown by n.m.r. studies to havethe structure of an oxodehydroskytanthine (11).17 A total synthesis of( &)-matrine has been reported; ,!Lalanine and diethyl 3-oxo-pimelate wereconverted by stages into the lactam (l2), the keto-lactam (13), and thebiscyanoethyl derivative (14), which yielded (&)-matrine (15) on catalyticlo D. H.R. Barton, G. W. Kirby, W. Steglich, and G. M. Thomas, Proc. Chem.l1 A. R. Battersby, Proc. Chem. SOC., 1963, 189.l2 D. H. R. Barton, Proc. Chem. SOC., 1963, 293.l3 J. A. Wunderlich, Chem. and Ind., 1962, 2089.l4 C. C. J. Culvenor, J. D. Morrison, A. J. C. Nicholson, and L. W. Smith, Austral.l5 L. A. Porter and T. A. Geismann, J. Org. Chem., 1962, 27, 4132.l6 H. L. deWaal, A. Wiechers, and L. F. Warren, J., 1963, 953.l7 G. Jones, H. M. Fales, and W. C. Wildman, Tetrahedron Letters, 1963, 397.SOC., 1963, 203.J . Chem., 1963, 18, 131BENTLEY: ALKALOIDS 401reduction.lS The biogenesis of matrine has also been studied by feedingexperiments with lysine, cadaverine, and Al-piperideine ; the results suggestthat lysine is incorporated into the alkaloid via cadaverine and that Al-piperideine is incorporated directly into the C,-N part and through tetra-hydroanabasine (16) (by fission of the tetrahydropyridine nucleus andrecyclisation) into the Clo-N portion of the molecule.1sThe alkaloids of Ormosia species have been examined and a number oflupin alkaloids obtained in this way; dasycarpine has been examined but nostructure has been assigned to it,20 but the Cz0 bases ormojanine and ormo-samine from 0.jumuicensis have been formulated.21 Ormosamine is (17)and ormojanine must have the constitution (18) since a consideration ofmodels reveals that an alternative N-C-N link is sterically impossible.These bases fit into the general pattern of lupin alkaloids, i.e., (C,N), + C5composed of straight -chain C units with only Cl-C, links and with nitrogenatoms joined only at the ends of the carbon chains.Quinoline and Isoquinoline Groups.-Ifflaiamine from Hlindersia ifiaianaF.Muell has been shown by n.m.r. studies to have constitution (19).22The fragmentation pattern of the bases of the quinine group in the massspectrometer has been reported. 23 In the isoquinoline series the previously18L. Mandell, K. P. Singh, J. T. Gresham, and W. Freeman, J. Amer. Chem.SOC., 1963, 85, 2682.lg S. Shibata and U. Sankawa, Chem. and Id., 1963, 1161.So R. T. Clarke and M. F. Grundon, J., 1963, 535.2l Z. Valenta, P. Deslongchamps, M.H. Rashid, R. H. Wightman, and J. M.22 J. A. Bosson, M. Rasmussen, E. Ritchie, A. V. Robertson, and W. C. Taylor,23 G. Spiteller and M. Friedmann-Spiteller, Tetrahedron Letters, 1963, 147.Wilson, Tetrahedron Letters, 1963, 1559.Austral. J . Chem., 1963, 16, 480402 ORGANIC CHEMISTRYunknown oxolaudanosine has been prepared 24 and found to suffer molecularfission on Hofmann degradation like the corresponding alcohol and the diolsobtained from narcotine and hydrastine by lithium aluminium hydridereduction; all four compounds suffer similar fission on pyrolysis of amineoxides, which reaction however follows a course similar to normal Hofmanndegradation in other alkaloids examined in this series.25 A further usefulreaction for degradation in this series is the sodium-ammonia reduction ofquaternary salts.26 Oxolaudanosine methiodide readily suffers autoxida-tion and reduction by the iodide ion to the carbinolamine salt (20), tauto-meric with the corresponding benzi1.24 A similar oxidation of alkaloids ofthe berberine group to cryptopine and related bases, simulating the probablemode of biogenesis of the latter, has been achieved by the potassium chromateinduced rearrangement of the corresponding N-oxides followed by N-methyl-a t i ~ n . ~ ' I n this way norcoralydine was converted into the base (21 ; R = H,R' = OMe) incorrectly formulated in the original paper as cryptopalmatine(21; R = OMe, R' = H), previously prepared by Haworth, Koepfli, andPerkin;28 it is of interest to note that the alkaloid muramine, from Papavernudic.de amurense, has recently been assigned the constitution (21 ; R = OMe,R' = H)29 but that its m.p.(177") differs from those of cryptopalmatine(150") and the new base (21; R = H, R' = OMe) (210-212.5"). Thisdiscrepancy is being investigated.The alkaloid argemonine, from Argemone mexicana,. has been identifiedas N-methylpavineY30 and this is the first reported occurrence of this ringsystem outside the laboratory.I n the bisbenzylisoquinoline series minor modifications have been madet o the accepted structure of tiliacorine following n.m.r. spectral studies,31the full stereochemical constitutions of trilobine and isotrilobine have beenelucidated by a two-step sodium-ammonia fission of these bases,32 -34 and24 K.W. Bentley and A. W. Murray, J., 1963, 2487.25 K. W. Bentley and A. W. Murray, J., 1963, 2491.26K. W. Bentley and A. W. Murray, J., 1963, 2501.27 K. W. Bentley and A. W. Murray, J., 1963, 2497.2sR. D. Haworth, J. B. Koepfli, and W. H. Perkin, J., 1927, 2261.29 von M. MEaturovB, B. K. Moza, J. Sita?, and F. santavf, Zeit. Arzneipjlanzen-30 M. J. Martell, T. 0. Soine, and L. B. Kier, J . Amer. Chem. SOC., 1963, 85, 1022;31 B. Anjeneyulu, K. W. Gopinath, T. R. Govindachari, and B. R. Pai, J. Sci.32 Y. Inubushi and K. Nomura, Tetrahedron Letters, 1963, 1133.33 Y. Inubushi, K. Nomura, and M. Miyawaki, J. Phawn. SOC. Japan, 1963,83,282.34Y. Inubushi and K. Nomura, J . Pharm. SOC. Japan, 1963, 83, 288.forsch., 1962, 10, 345.F.R. Stermitz, S . - Y . Lwo, and G. Kallos, J. Amer. Chem. SOC., 1963, 85, 1551.Ind. Res., 1962, 2lB, 602BENTLEY: ALKALOIDS 403isopilocereine has been shown to have the dimeric structure previouslyassigned to pilocereine, now known to be trimeri~.3~ Both pilocereine andisopilocereine have been obtained by the ferricyanide oxidation of thephenolic base lophocereine (22), and the quaternary salts have been inde-pendently prepared in the same way.3sA novel bisbenz ylisoquinoline alkaloid, thalicarpine, comprising onebenzylisoquinoline and one aporphine unit, has been discovered. It hasthe composition C,,H,,N,O,, contains seven methoxyl groups, and onsodium-ammonia fission yields ( - )-6'-hydroxylaudanosine and ( + )-3,6-dimethoxyaporphine.The alkaloid is evidently 3 ,5,6- trimethoxyaporphineand laudanosine linked by an ether bridge in the 4-6' manner, and this hasbeen confirmed by its synthesis by the Ullmann condensation of (-)-6'-bromolaudanosine and isocor ydine ,Theracemic ketone (23) when heated with (-)-camphor-10-sulphonic acid yieldswholly the (-)-isomer which by the Wittig reaction followed by reductionaffords 70% of the (-)-2,3-trans-ester (24), convertible by known methodsvia (+)-O-methylpsychotrine to (-)-emetine and isoemetine; of these theunwanted component can be transformed back into ( + )-O-methylpsycho-trine by N-chlorination and alkali treatment, thus minimising losses ofmaterial. A biogenetically patterned synthesis of the same alkaloid hasbeen achieved 39 from homoveratrylamine, formaldehyde, and the oxo-triester(25), via the intermediates (26), (26a), and (24), and a third synthesis viaAn efficient total synthesis of (-)-emetine has been rec0rded.~8pro t oem e t ine , the aldehyde correspondingreported.40to thef--ester (24), has also beenM.Tomita, T. Kikuchi, K. Bessho, and Y. Inubushi, Tetrahedron Letters, 1963,36 J . M. Bobbit, R. Ebermann, and M. Schubert, Tetrahedron Letters, 1963, 575;37 S. M. Kupchan and N. Yokoyama, J . Amer. Chem. SOC., 1963, 85, 1361.ssH. T. Openshaw and N. Whittaker, J., 1963, 1461.39 E. E. van Tamelen, G. P. Schiemenz, and H. L. Arons, Tetrahedron Letters,4 0 C. Sz&ntay and L. T6ke, Tetrahedron Letters, 1963, 1323.127.B. Franck and G. Blaschke, ibid., p.569.1963, 1005404 ORGANIC CHEMISTRYThe mass-spectral fragmentation patterns of the benzylisoquinoline,tetrahydroberberine, aporphine, and cularine alkaloids have been studied. 4 1Papaverine shows only three significant peaks, M-1, M-15, and M-31, butthe bases derived from tetrahydropapaverine have characteristic spectraresulting from fragmentation to units such as (27) and the loss of methylgroups from these; in some cases the molecular-ion peak is absent altogether(e.g., hydrastine) as a result of the doubly benzylic bond being made weakerstill by an oxygen function, and in such cases the absence of the peak issignificant. In the tetrahydroberberine group cleavage of the ring system,as shown in the case of xylopinine (28), is of prime importance, and the modeof cleavage is not dependent on the substituents, so from m/e ratios of theproducts (29) and (30) it is possible to determine the substitution patternto a large degree. The spectra produced by the aporphines are morecomplex.A molecular-ion peak is very strong, but is accompanied byMe0Me0(27)OMe 6M€2peaks corresponding to M-31 (32), and M-15 (33), presumably arising byinitial fragmentation to the ion (31) ; some bases, e.g., bulbocapnine, of coursecannot form ions such as (32). All bases containing NH show an M-29 peakwhereas in the N-Methyl compounds this is replaced by M-43, and thesepresumably arise by loss of a methyleneimine as shown in (34); the product(35) being an odd-electron ion can lose part or all of the extra-nuclearmethoxyl group to give even-electron ions.Me0 MeoQQH \Me0 Meop; Me0 ’Meo$ (35) Meo$; Me0041 M.Ohashi, J. M. Wilson, H. Budzikiewicz, M. Shamma, W. A. Slusarchyk,and C. Djerassi, J . Amer. Cheriz. SOC., 1963, 85, 2807BENTLEY: ALEALOIDS 405Constant peaks a t m e = 152 and 165 are present in all aporphine spectraand, although their origins are obscure, they serve a useful diagnostic pur-pose. Cularine shows, in addition to the molecular ion, only one significantpeak a t M-15 due to the stabilised ion (36).In the aporphine group, nuclear reduction has been achieved by sodiumand ammonia, corytuberine dimethyl ether yielding by this process1,2,3,3a,11 b,Ilc-hexahydro 10-methoxy-2-oxoaporphine as well as 10-hydro~y-2-methoxyaporphine.~~ Ushinsunine and roemerine on oxidationwith chromic acid in pyridine yield liri~denine,~~ and analogues of the latterhave been prepared in the same way from glaucine, corytuberine dimethylether, and n~ciferine.~* Norglaucine methiodide has been isolated from theproducts of ferricyanide oxidation of quaternary salts of norlaudanosine.45The total synthesis of cularine (38) has been achieved by the Pomeranz-Fritsch conversion of the ketone (37) into the isoquinoline, followed byN-methylation and reduction ; resolution of the racemate afforded ( + )-cular-ine.46 This work constitutes the first unambiguous proof of the positions ofthe methoxyl groups in this alkaloid, since the chemical evidence never ruledout the structure in which the 6 rather than the 7 position of the isoquinolineunit bore the methoxyl.OH0OMe0 1Me0OMeMeo$+;0Two new alkaloids, crotonosine and linearisine, from Croton linearisJacq.were originally assigned to the morphine group. Crotonosine containsa cross-conjugated enedione system isolated from the aromatic nucleus andwhen heated with concentrated acid yields an aporphine. N.m.r. spectralstudies led initially to the suggestion of structure (39)47 for the alkaloid,but more careful study revealed that the correct structure is (40) and theRO Rfog: 042 M. Tomita and K. Fukagawa, J . Pharrn. SOC. Japan, 1963, 83, 293.43 T. H. Yang, J . Pharm. SOC. Japan, 1962, 82, 194.44 M. Tomita, T. H. Yang, H. Furukawa, and H. M. Yang, J . Pharm.SOC. Japan,45 B. Franck and G. Schlingloff, Annalen, 1962, 659, 123.T. Kametani and K. Fukumoto, Chem. and Ind., 1963, 291; J., 1963, 4289.4 7 L. J- Haynes and K. L. Stuart, J., 1963, 1784, 1789.1962, 82, 1574406 ORGANIC CHEMISTRYrelates aporphine is (41), the precise orientation of hydroxyl and methoxylbeing undefined.**Pronuciferine is the ON-dimethyl etherof crotonosine, andits strucfure wascorrectly deduced independently of the above work sodium borohydridereduction of the base gives the dienol which yields the aporphine alkaloidnuciferine (41a) with acid.49 It is of interest to note that it was postulated,in advance of the discovery of these bases, that such structures were inter-mediates in the formation of such aporphine alkaloids as anonaine, roemerine,and nuciferine .50In the morphine series the so-called isosinomenine has been shown to bethe 7-ethoxy-analogue of sinomenine. 51 The reduction of 14-bromocodein-one with sodium borohydride has been alleged to give an isomer of codeinewith the nitrogen atom attached to (3-14 instead of C-9,52 but the evidenceon which this structural assignment is made is not wholly convincing.Thenew base on reduction, oxidation, and further reduction yields an isomer ofdihydrothebainone and /I-dihydrothebainone and this cannot be a metathe-bainone derivative since the Hofmann degradation of the original baseyields #3-codeimethine. On the grounds that a separation of medicinallydesirable and undesirable effects of morphine could better be achieved bymaking molecules unacceptable by virtue of their greater complexity anddifference in peripheral shape at some of the receptor surfaces triggering offthe various physiological effects than by the synthesis of flexible fragmentsof the alkaloid molecule, a series of new highly potent analgesics of generalstructure (42) has been prepared.Of these several are more than 1000 timesas potent as morphine and two, (42; R = H, R1 = Me, R2 = isopentyl) and(42; R = Ac, R1 = Me, RZ = Pr”), are approximately 10,000 times asactive as the alkaloid and are the most powerful analgesics so far reported;the toxicities of the compounds are very low relative to their analgesicactivities.53, 54 The alcohols readily suffer acid-catalysed rearrangementto 14-alkenylcodeinones and m0rphinones.5~The Diels-Alder adducts of thebaine with acetylenic dienophils haveL.J. Haynes, K. L. Stuart, D. H. R. Barton, and G. W. Kirby, Proc. Chem.Festschrift A. Stoll,” Birkhauser, Basle, 1957,Soc., 1963, 280.117.48 K. Bernauer, Helv. Chim. A~%a:~l963, 46, 1783.5 0 D. H. R. Barton and T. Cohen,51 Y . Sasaki and K. Okabe, J . Pharm. Soc. Japan, 1963, 83, 418.5 2 S. Okuda, K. Tsuda, and S. Yamaguchi, J . Org. CAem., 1963, 27, 4121.5 3 K. W. Bentley and D. G. Hardy, Proc. Chem. SOC., 1963, 219.5 4 B.P. 902,659, 925,723, and 937,214BENTLEY: ALKALOIDS 407been shown to suffer ready thermal rearrangement to phenylfuranobenzazo-cines, e.g., the adduct with methyl acetylenedicarboxylate (43) at about 140"is rapidly converted into the base (44); the stereochemistry and chemicaldegradation of this and other similar rearrangement products have beenstudied.55By using (N)-trideuteriomethylmorphine, the rate of N-demethylation ofmorphine by rat-liver microsomal enzymes has been studied and the resultshave provided no support for Beckett's theory of the mechanism of analgesicaction or of Axelrod's hypothesis for the development of tolerance.56 Alsoin the analgesic field deoxycodeine-E has been converted into an analogueof phenazocine, still containing the 4,5-oxygen bridge, by N-demethylationand phenethylation followed by the opening of ring c by hydroxylation,lead tetra-acetate oxidation, and reduction of the resulting dialdeh~de.~'Indole Group.-A considerable amount of work in this group has beenreported during the year, much of it devoted to the allocation of structureswithin the sub-groups on the basis of n.Iy1.r.and mass-spectral data. Thedegradation of strychnine to 3-hydroxy-l6~-strychindol and the synthesisof (-J-)-l&-strychindol, have been reported, from which the absolute con-figuration of strychnine has been deduced.58 Nor-c-curarine-111, from whichc-curarine-I11 is available, has been prepared from strychnine via theWieland-Gumlich aldehyde, which on reduction successively with sodiumborohydride and hydrogen and palladium yields the base (45), and this onOppenauer oxidation yields dihydronor-c-curarine-I11 , from which therequired base is obtained by autoxidati~n.~~ 0;qq CH2*OH "";i 0-(-$ N H o \CH2.OH(4 7)"il(45) (46)MeOzC CHyOHThe molecular formula of mitragynine has been corrected and the baseshown to have the structure of 9-methoxycorynantheidine.60 A new basefrom Vimxz ro.seu Linn., sitsirikine, also belongs to the corynantheine group,and has been shown to have the structure (as), largely by spectral studies,and a direct correlation of dihydrositsirikine with the sodium borohydridereduction product of demethyldihydrocorynantheine has been made.61 Thealkaloid burnamicine, from Hunteriu eburneu Pichon, has been shown byspectral studies to be the first representative of a group of cryptopine-like55 H.Rapoport and P. Scheldrick, J . Amer. Chem. SOC., 1963, 85, 1636.66 C. Elison, H. W. Elliott, M.Look, and H. Rapport, J . Med. Chem., 1963,6,237.57 L. J. Sargent and J. H. Ager, J . Med. Chem., 1963, 6, 569.68 K. Nagarajan, C. Weissmann, H. Sehmid, and P. Karrer, Helu. Chim. Acta,6 @ H. Fritz, E. Besch, and T. Wielmd, AnnaZen, 1963, 663, 150.6 o B. S. Joshi, R. Hamet, and W. I. Taylor, Chem. and Ind., 1963, 573.61 J. P. Kutney and R. T. Brown, Tetrahedron Letters, 1963, 1815.1963, 46, 1212408 ORGANIC CHEMISTRYbases in the indole series; it is related to corynantheol and has the structureIt has been suggested that the so-called (&-)-mitraphylline, which re-presents one of the two apparent exceptions to the uniformity of configura-tion of the indole alkaloids at C-15, is in fact (-)-mitraphylline contaminatedwith isomitraphylline, which is dextrorotatory and is easily formed from( -)-mitraphylline.63 New bases reported in this sub-group of oxindolealkaloids are stipulatine, 64 identical with rot~ndifoline,~5 and speciofoline,66which are cis-tram-isomers of structure (48) and are representatives of therare group of 4-oxygenated indoles and carapanaubine.The structure ofthe last of these was largely elucidated by mass spectrometry, during thecourse of which the principal patterns of fragmentation of alkaloids of theoxindole group have been elucidccted, by the use of deuterium-labelling andthe variation of substituents in the aromatic and alicyclic portions of themolecule. The fragmentation patterns in this group are sufficiently char-acteristic to enable easy assignment of bases to the group to be made.67In this way carapanaubine was shown to have structure (49).The previ-ously recorded method of conversion of alkaloids of the yohimbine-ajmalicine(47). 62IG3Me..(49)group into oxindole bases 68 is only of practical value in the D/E trans-series,and it has more recently been found that the oxidation of yohimbine andsimilar bases with lead tetra-acetate affords acyloxyindolenines, from whichoxindoles are accessible, even in the D/E cis-series, by refluxing with meth-anolic acetic acid. In this way carapanaubine has been prepared fromreserpiline. 69Alkaloids of the vincamine group have been examined mass spectro-metrically and previously assigned structures confirmed ; 709 '1 in additionthis technique has been shown to be of value in the identification of thecomponents of crude mixtures of bases.72 The structures previously62 M.F. Bartlett and W. I. Taylor, J . Amer. Chem. SOC., 1963, 85, 1203.63 N. Finch and W. I. Taylor, Tetrahedron Letters, 1963, 167.6 4 J. B. Hendrickson and J. J. Sims, Tetrahedron Letters, 1963, 929.6sA. H. Beckett and A. N. Tackie, Chem. and Ind., 1963, 1122.66 A. H. Beckett, C. M. Lee, and A. N. Tackie, Tetrahedron Letters, 1963, 1709.67 B. Gilbert, J. A. Brissolee, N. Finch, W. I. Taylor, H. Budzikiewivz, J. M.68 N. Finch and W. I. Taylor, J . Amer. Chem. SOC., 1962, 84, 1318; J. Shave1 ande S N. Finch, C. W. Gemenden, I. Hsiu-Chu Hsu, and W. I. Taylor, J. Amer. Chem.70 J. Holubek, 0. Strouf, J. TrojBnbk, A. K.Bose, and E. R. Malinowski, Tetra-71 0. Clauder, K. Geszetes, and K. Szasz, Tetrahedron Letters, 1963, 1147.72 H. K. Schnoes, A. L. Burlingame, and K. Biemann, Tetrahedron Letters, 1963,Wilson, and C. Djerassi, J . Amer. Chem. SOC., 1963, 85, 1523.H. Zinnes, ibid., p. 1320.SOC., 1963, 85, 1520.hedron Letters, 1963, 897.993BENTLEY: ALKALOIDS 409assigned tentatively to the bases catharanthine and cleavamine have beenconfirmed by n.m.r. studies.73 Structure (50) has been suggested forquebrachidine on the basis of mass-spectral studies and chemical trans-formations ; on N-formylation and lithium aluminium hydride reduction ityields an N-methylated diol which on oxidation with lead tetra-acetateaffords the hydroxy-aldehyde (51) whereas on lead tetra-acetate oxidationfollowed by borohydride reduction it gives polyneuridine. 74 The mass-spectral fragmentation pattern of ajmalidine has also been reported.75 Thestructure (52) has been independently suggested for ly-akuammigine veryMelargely on the basis of mass and n.m.r.spectra;7*, 77 apo-y-akuaminiginemust be formed by a skeletal rearrangement? and Smith and his co-workersfavour structure (53) for this base on the grounds that the U.V. spectrum inconcentrated acid corresponds to that of a 3-H-indolium cation and basifica-tion leads to complete recovery of the apo-ba~e.'~ On the other hand, twoconflicting structures have been suggested for the closely related picraline,(54)" and (55);78, 79 of these (54) has been supported by spectral studies,but stronger spectral evidence and in particular the mass-spectral fragmenta-tion pattern has been cited in favour of (55).The presence of a methoxy-carbonyl group in picraline has been demonstrated and its orientation isindicated by a study of the properties of flavopicraline, for which thestructure (56) is suggested, the acid-rearrangement product of picraline,analogous to apo-y-akuammigine. 79 A further base, corymine, from Hun-teria corymbosa, has been included in this series, the assigned structure, onthe basis of spectra and chemical transformations, being (57).SOIn the aspidospermine sub-group a further series of bases has been un-covered containing a tetrahydrofuran ring. The general skeleton is that of(58), the bases so far reported being aspidoalbine (R1 = R2 = R3 = OMe,7 3 M.Gormann and N. Neuss, Ann. Chirn. (Italy), 1963, 53, 43.7 4 M. Gormann, A. L. Burlingame, and K. Biemann, Tetrahedron Letters, 1963,39.75 K. Biemann, P. Bommer, A. L. Burlingame, and W. J. McMurray, TetrahedronLetters, 1963, 1969.76 A. Z. Britten, P. N. Edwards, J. A. Joule, G. F. Smith, and G. Spiteller, Chena.and Ind., 1963, 1120.7 7 L. Olivier, J. Levy, J. Le Men, M.-M. Janot, C. Djerassi, H. Budzikiewicz,J. M. Wilson, and L. J. Durham, Bull. SOC. chirn. France, 1963, 6, 646.7 8 A . Z. Britten and G. F. Smith, J., 1963, 3850.8o A. K. Kiang and G. F. Smith, Proc. Chem. Soc., 1962, 298.A. Z. Britten, G . F. Smith, and G. Spiteller, Chem. and Ind., 1963, 1492410 ORGANIC CHEMISTRYco-0R4 = COEt),81 aspidolimidine (R1 = H, R2 = OMe, R3 = OH, R4 = COMe),82haplocine (R1 = R2 = H, R3 = OH, R4 = COEt), haplocidine (R1 = R2 = H,R3 = OH, R4 = COMe),83 and dichotamine (R1 = R2 = H, R3 = OMe,R4 = CHO, with a lactonic function in the oxygen ring).s4 The structuresare assigned to these bases largely on the basis of mass and n.m.r.spectra.The structures of the bases kopsine, fruticosine, and fruticosamine 85 andthe mass-spectral fragmentation patterns of the pleiocarpa bases of the samegroup 86 have been reported. Vincadine, from Vinca minor with 5~-hydro-chloric acid yields de( methoxycarbonyl) vincadine, which has been identifiedas (+)-quebrachamine from which the structure of the alkaloid as 3-methoxy-carbonyl-( + )-quebrachamine follows ; vincaminoreine is id-N-methyl-vin~adine.~~ The mass-spectral fragmentation pattern of quebrachaminehas been reported in detail.88 A total synthesis of aspidospermine has beenannoun~ed.~~ Butyraldehyde was condensed by the enamine method firstwith methyl acrylate and then with methyl vinyl ketone to give the ketone(59) which with ammonia yielded the keto-amide (60) in cis- and trans-forms. This amide in the Fischer indole synthesis gave only the linearcompound (61), the nature of which was deduced from the mass spectrum,but conversion of the amide (60) into the ketone (62) and then via the N-chloroacetyl compound and the amide (63) into the base (64) yielded aketone that in the Fischer synthesis gave the non-linear aspidospermineskeleton.With O-methoxyphenylhydrazine an indolenine was formed thatC. Djerassi, L. D. Antonaccio, H. Budzikiewicz, J. M. Wilson, and B. Gilbert,s 2 B. Gilbert, J. A. Brissolee, J. M. Wilson, H. Budzikiewicz, and C. Djerassi,83M. P. Cava, S. K. Talapatra, K. Nomura, J. A. Wiessbach, B. Douglas, and8* K. S. Brown, H. Budzikiewicz, and C. Djerassi, Tetrahedron Letters, 1963, 1731.8 6 A. R. Battersby and H. Gregory, J., 1963, 22.86 C. Djerassi, H. Budzikiewicz, R. J. Owellan, J. M. Wilson, W. G. Kump, D. J.Le Count, A. R. Battersby, and H. Schmid, Helv. Chim. Acta, 1963, 46, 742.8' J. Mokrf, I. Kompii, L. DGbravkova, and P. SefEoviG, Tetrahedron Letters, 1962,1185.88 K. Biemann and G. Spiteller, J. Amer. Chem. SOC., 1962, 84, 4578.8 9 G.Stork and J. E. Dolfini, J. Amer. Chem. SOC., 1963, 85, 2872.Tetrahedron Letters, 1962, 1001.Chem. and Ind., 1962, 1949.E. C. Shoop, Chem. and Ind., 1963, 1242BENTLEY: ALKALOIDS 41 1yielded aspidospermine on reduction and acetylation, whereas the indoleninefrom the phenylhydrazone on reductive cleavage with sodium borohydridegave quebrachamine. 89Syntheses have also been recorded of the calycanthus alkaloids, chimon-anthine and folicanthine. The action of iodine on the sodium salt of theamide (65) gives two diastereoisomeric dimers (66), one of which yields( &)-chimonanthine with lithium aluminium hydride whereas the other givesthe base (67), which is isomerised by aqueous acid to one of the other possiblebmes of this group, the last may be identical with hodgkinsine; some indica-tion has also been obtained of the formation of calycanthine from chimon-anthine in acid.g0 The synthesis of folicanthine, which is NN-dimethyl-chimonanthine, follows the 8ame lines.g1EtOzCC02Et(65)'NH(66) ICO?EtHMe (67)Sporidesmin, the toxic agent responsible for producing facial eczema insheep, has been shown to have the structure (68) by X-ray studies 92 andtuberostemonine has been assigned the precise structure (69) on the basisof n.m.r.spectral data.gsJ. B. Hendrickson, R. Rees, and R. Goschke, Proc. Chem. SOC., 1962, 383.O1 T. Hino and S. Yamada, Tetrahedron Letters, 1963, 1757.9a J. Fridrichsons and A. McL. Mathieson, Tetrahedron Letters, 1962, 1265.93 0. E. Edwards, and G.Feniak, Canad. J. Chem., 1962, 40, 2416412 ORGANIC CHEMISTRYSteroid Group.-A novel steroidal alkaloid, cyclobuxine from Buxussempervirens L., containing a cyclopropane ring, has been isolated. Thestructure was deduced from n.m.r. data, by selenium dehydrogenation ofthe base, studies of the cyclopropane ring-opened base, and by ozonolysisstudies ; correlation with cycloeucalenol, and optical rotatory dispersionstudies of the base and its degradation products, allows the assignment ofthe complete structure (70).g4 The substitution pattern at C-4 and C-14 isintermediate between the steroid and lanosterol groups. The structure (71)has been assigned to the lactonic base pa~arallidine.~~~ 96HMe 4.- NHMe nIn the conessine group the microbiological oxidation of conessine to theepimeric 7-hydroxy-compounds 97a and to the A*-3-oxo-base 97b has beenreported, syntheses of ( -J )-conessine and (&)-latifoline achieved by methodsanalogous to Johnson's synthesis of the f0rmer,~8 and the mass-spectralfragmentation of the alkaloids has been st~died.9~ The synthegis of demissi-dine from 3b-acetoxypregn-5-en-20-one has been accomplished by familiarmethods, except that the final stage involved photolysis in alkaline solutiong4 K.S . Brown and S . M. Kupchan, J . Arner. Chem. Soc., 1962, 84, 4590, 4592.J. Le Men, C. Kan, and R. Beugelmans, Bull. SOC. chim. France, 1963, 6, 597.g6 R. Beugelmans, C. Kan, and J. Le Men, Bull. SOC. ch;m. France, 1963, 6, 1306.9 7 (a) S. M. Kupchen, C. J. Sih, S .Kubota, and A. M. Rahim, Tetrahedron Letters,1963, 1767; ( 6 ) J. de Flines, A. F. Marx, W. van der Waard, and D. van der Sijde, it&.,1962, 2357.g* W. Nagata, J. Teresawa., and T. Aoko, Tetrahedron Letters, 1963, 869.9 9 W. Vetter, P. Longeville, F. Khuong-Huu-Laine, Q. Khuong-Huu, and R.Goutarel, Bull. SOC. chirn. France, 1963, 6, 1324BEENTLEY: ALKALOIDS 413of an N-chloro-base of the tomatidine group;lm in this sub-group also nitro-solasodine has been converted into 3/?-acetoxypregna-5,16-dien-20-one.101The stereochemistry of veratramine has been elucidated,lo2 and a pro-cedure has been developed for the elimination of the nitrogen-containingportion of this alkaloid by N-chlorination and alkaline degradation of theN-chloro-compound (72) to the base (73), which is split by acids t o thenitrogen-free ketone (74).l03 The availability of this ketone should be usefulfor relay purposes in the total synthesis of alkaloids of this group, and someprogress in synthesis has' been made by the stepwise conversion of thesteroid-like intermediate (75) into the ring-contracted substance (76).104Lycopodium and Terpenoid Bases.-Lycoclavine, from L.clavutum, onoxidation gives lycoclavinone, an a-acetoxy-ketone which on hydrolysissuffers aerial oxidation to an a-diketone accessible also by the selenium di-oxide oxidation of lycofoline. From these reactions, n.m.r. spectra, andoptical rotatory dispersion data the structure of the new alkaloid has beenshown to be (77).105 Atisine has been correlated with the resin acids bydegradation to the hydrocarbon (78) and the synthesis of this from abieta-6,S-diene.106 The bridged carbon skeletons present in atisine and garyfolinehave been synthesisedY1*7 a partial synthesis of atisine has been accom-plished l08 from the base (79), via the ketone (80) which on a-methylattion,a-bromination, and dehydrobromination yields the unsaturated ketone (81),reduction of which yields an alcohol previously converted lo9 into atisine.Finally, a complete stereospecific synthesis of (A)-atisine has been reportedstarting from the ketone (82), which by a 21-stage process is converted alsoMe( 7 9 ) Il o o G.Adam and K. Schreiber, Tetrahedron Letters, 1963, 923.lol K. Schreiber and H. Ronsch, Tetrahedron Letters, 1963, 937.lo2 D.M. Bailey, D. P. G. Hamon, and W. S. Johnson, Tetrahedron Letters, 1963, 555.lo3 R. W. Franck and W. S. Johnson, Tetrahedron Letters, 1963, 545.lo4 P. W. Schiess, D. M. Bailey, and W. S. Johnson, Tetrahedron Letters, 1963, 549.lo5 W. A. Ayer and D. A. Law, Canad. J . Chem., 1962, 40, 2088.lo6 W. A. Ayer, C. E. McDonald, and G. G. Iverach, Tetrahedron Letters, 1963, 1095.lo' R. A. Bell and R. E. Ireland, Tetrahedron Letters, 1963, 269.lo* S. W. Pelletier and P. C. Parthasarathy, Tetrahedrolz Letters, 1963, 205.109 S. W. Pelletier and W. A. Jacobs, J . Amer. Chsm. SOC., 1956, 78, 4144414 ORGANIC CHEMISTRYinto the ketone (81) and thence by previously reported pathways intoatisine.l1° Mevalonic acid has been found not to be incorporated intodelpheline, and it is suggested that this efficient terpene-precursor is con-verted into non-alkaloidal terpenes before it reaches the site of alkaloidsynthesis.1flMiscellaneous Bases.-The colchicine skeleton has been synthesised byan oxidative coupling of the phenolic tropolone ( 83).l12 p-Lumicolchicinehas been shown to have the structure (84) by n.m.r.studies, and the a-isomerhas been found to be a head-to-head dimer of the /3-form.l13 Irradiation ofisocolchicine, however, gives the isomeric base (85) and a methanol-contain-ing base related to y-lumicolchicine.114Lunarine, C25H31N304, on alkali fusion yields spermidine(H~CH,*CK,*CH,*NH*CH,*CH,*CH,*CH,*NH,), 2,4'-dihydroxydiphenyl-3',5-dicarboxylic acid, the lactone (86), and 3-methyl-, 3-ethyl-, and 3-n-propyl-4-methoxybenzoic acid.These results together with n.m.r. dataand functional group studies show that the alkaloid must have the structure(87) or the alternative diamide structure in which the spermidine portion isreversed. l1 500 0 ( 8 6 )HAJ011* W. Nagata, T. Sugasawa, M. Narisada, T. Wakabayashi, and Y. Hayase, J .111 E. J. Herbert and G. W. Kirby, Tetrahedron Letters, 1963, 1505.11* A. I. Scott, F. McCapra, J. Nabney, D. W. Young, A. J. Baker, T. A. Dwidson,llS 0. L. Chapman, H. C. Smith, and R. W. King, J . Amer. Chem Soc., 1963, 85,11* W. G. Dauben and D. A. Cox, J . Amer. Chem. SOC., 1963, 85, 2130.115 P. Potier, J. Le Men, M.-M. Janot, P. Bladen, A. G. Brown, and C. S. Wilson,Amer.Chem. SOC., 1963, 85, 2345.snd A. C. Day, J . Amer. Chem. SOC., 1963, 85, 3040.803, 806.Tetrahedron Letters, 1963, 29311. STEROIDSBy J. S. WhitehurstA JOURNAL devoted to steroids has been started, and a book 2 on steroidreactions has appeared. Veratrum alkaloid chemistry has been revie~ed.~Physical Measurements.-The application of mass spectrometry to steroidscontinues apace.4 To investigate the hydrogen-transfer processes involved,Djerassi and his colleagues have synthesised a large number of deuterio-steroids.4C One interesting result is that 5a-androstan-1 l-one exchangesits 9cc and 12a(axial) protons for deuterium much more readily than the12,8 (equatorial) proton. The relative merits of circular dichroism (c.d.)and optical rotatory dispersion (0.r.d.) have been discussed.5 C.d.measure-ments a t the boiling point of liquid nitrogen 6 promise to be of special valuein conformational studies. One interesting result concerns 5a-androstan-ll-one where the positive curve at 25" changes to a negative one at -192".The curve for 2cc-isopropylcholestan-3-one (1) becomes more positive a t thelower temperature and indicates a preponderance of the rotamer (la).0.r.d. studies 7 have been made on a large numberG. ..A Hof saturated ketonesincluding those, such a.s 5a-cholestan- 1 -one, possessing substituents in'' front " octants. Further work has been done * on 3-ketones having bulky(halogen, methyl) substituents a t the 2- and 4-positions. N.m.r. measure-ments can be used to determine the configurations of 6-substituents inSteroids, Holden-Day Press, San Francisco, U.S.A.C.R. Narayanan, Fortschr. Chem. erg. Naturstoffe, 1962,20,298.2 " Steroid Reactions," ed. C. Djerassi, Holden-Day, Inc., San Francisco,4 (a) R. H. Shapiro, J. M. Wilson, and C. Djerassi, Steroids, 1963, 1, 1; (b) C.Djerassi, J. M. Wilson, H. Budzikiewicz, and J. W. Chamberlin, J. Amer. Chem. Soc.,1962, 84, 4544; (c) D. H. Williams, J. M. Wilson, H. Budzikiewicz, and C. Djerassi,ibid., 1963, 85, 2091; ( d ) Z . Pelah, M. A. Kielczewski, J. M. Wilson, M. Ohashi, H.Budzikiewicz, and C. Djerassi, ibid., 1963, 85, 2470; (e) L. Dolejs, V. Hanns, V. Czerny,and F. Sorm, Coll. Czech. Chem. Comm., 1963, 28, 1584; (f) W. Vetter, P. Longevialle,F. Khuong-Huu-Laine, Q.Khuong-Huu, and R. Goutarel, Bull. SOC. chim. Frunce, 1963,1324; (9) H. Audier, M. FBtizon, and W. Vetter, ibid., 1963, 19715 C. Djerassi, H. Wolf, and E. Bunnenberg, J . Amer. Chem. SOC., 1962, 84, 4552;K. Mislow, E. Bunnenberg, R. Records, K. Wellman, and C. Djerassi, ibid., 1963, 85,1342; C. Djerassi, H. Wolf, and E. Bunnenberg, ibid., 1963, 85, 324.6 K. M. Wellman, E. Bunnenberg, and C . Djerassi, J. Amer. Chem. SOC., 1963,85, 1870.7C. Djerassi and W. Klyne, J., 1962, 4929; 1963, 2390.8 N. L. Allinger and M. A. DaRooge, J. Amer. Cham. SOC., 1962, 84, 4561; R. J.Abraham and J. 8. E. Holker, J . , 1963, 806; P. Witz, H. Herrmann, J-M. Lehn, andG. Ourisson, Bull. SOC. chim. France, 1963, 1101.1963416 ORGANIC CHEMISTRYA4-3-oxo-steroids,g and of epoxide bridges l o p l1 at 4,5- and 5,6-positions.The position of the U.V.low-intensity carbonyl absorption is also decisive in4,6-disubstituted A4-3-ketones.12 Zurcher l3 has published n.m.r. data forthe 18- and 19-methyl groups of 265 steroids. The symmetry of the freehydroxyl i.r. absorption band of a hydroxy-steroid is of value in deter-mining l4 the conformation of the hydroxyl group. G.1.c. of steroids isbecoming firmly established.B-Nor-Steroids.-A re-examination l6 has been made of the catalyticreduction of B-norcholesteryl acetate (2), and the chief product is nowknown to possess the A/B cis-configuration. bondin t,his series, however, gives as sole products the ~t-epoxides.~~, l7 TheEpoxidation of the A5,8-epoxides [e.g., (3)] can be prepared l7 from the brornohydrins. Whereasthe action of acetic acid on compound (3) gives the rearranged product (4),use of boron trifluoride-ether 18 yields (5).Sorm and his colleagues 19have presented evidence to show that, in the 5fl-~-nor-steroids, ring A is more(7)flexible than in the 5p-steroids and that in compound (6), ring A adopts a(twist) boat conformation. Compound (7) shows considerable internalhydrogen-bonding (8). In B-nor-steroids possessing a 6-keto-group, theD. J. Collins, J. J. Hobbs, and S . Sternhell, Tetrahedron Letters, 1963, 197;T. A. Wittstruck, S. K. Malhotra, and H. J. Ringold, J. Amer. Chem. SOC., 1963,85, 1699.lo D. J. Collins, J. J. Hobbs, and S . Sternhell, Tetrahedron Lettera, 1963, 623.A.D. Cross, J . Amer. Chem. SOC., 1962, 84, 3206.l2 M. T. Davies and V. Petrow, Tetrahedron, 1963, 19, 1771.1sR. F. Ziircher, Hslw. Chim. Acta, 1963, 46, 2054; 1961, 44, 1380.14 H. S. Aaron and C. P. Rader, J . Anzer. Chem. SOC., 1963, 85, 3046.15 B. A. Knights and G. H. Thomas, J., 1963, 3477.l6 W. G. Dauben, G. A. Boswell, W. Templeton, J. W. McFarland, and G. H.Berezin, J . Amer. Chem. SOC., 1963,85, 1672; see also G. H. R. Summers, J., 1959, 2908;T. Goto and L. F. Fieser, J . Amer. Chem. SOC., 1959,81, 2276; J. Joska, J. Fajkas, andF. sorm, Coll. Czech. Chem. Comm., 1960, 25, 2341.1' J. Joska, J. Fajkos, and F. sorm, Coll. Czech. Chem. Comm., 1963, 28, 82, 621.l8 J. Joska and J. Fajkos, Coll. Czech. Chem. Comm., 1963, 28, 2605.F. Fajkos, J.Joska, and F. sorm, Coll. Czech. Chem. Comm., 1963, 28, 605WHITEHURST : STEROIDS 417most stable configuration for the B/C junction is trans 2O when carbon 3 istrigonal (e.g., CO) and cis when tetrahedral (e.g., CH,, CH*aOH), this being anexample of the Barton effect. Ozonolysis of cholesteryl acetate in methyl-ene chloride-methanol is a convenient way of preparing 21 compound (9).Rearrangement of androst-l,4-diene-3,17-&one (10) to the phenol (11) proceeds 22 by the accepted path, viz., methylGeneral Reactions.--Ring A.migration from C-10 to C-1. An alternative path, migration t o C-5 followedby further rearrangements has been disproved by l4C labelling. In a recentcase 23 (not a steroid), derivatives of three possible reaction paths have beenobtained.The action of zinc on 3-keto-1 ,4-dienes in pyridine, dirnethylformamide,or even toluene (containing some water) gives 24 aromatic products, oftenin high yield.Typical transformations are (12) + (13), (14) -+ (15),0 81 HO 81 \(15) o /(16) (17)HO(16) -+ (17), and (18) + (19).methane.being formed (except for the B-ring examples).If the methyl group is expelled it appears asZinc-acetic acid reduction contrasts markedly, dimeric products2o W. G. Dauben, G. A. Boswell, W. Templeton, and J. W. McFarland, J . Amer.21 K. Tanabe and Y. Morisawa, Chem. and Pharm. Bull. (Japan), 1963, 11, 536;22 E. Caspi and P. K. Grover, Tetrahedron Letters, 1963, 591.2 3 P. J. Kropp, Tetrahedron Letters, 1963, 1671.2 4 K. Tsuda, E.Ohki, and S. Nozoe, J . Org. Chem., 1963, 28, 783, 786, 789, 795;K. Tsuda, J. Suzuki, and S. Iwasaki, Chem. and Pharm. Bull. (Japan), 1963, 11, 405.Chem. Soc., 1963, 85, 2302.H. Lettr6 and A. Jahn, Annalen, 1957, 608, 43.418 ORGANIC CHEMISTRYIn the acid-catalysed isomerisation 25 of 3-methylenecholestene to3-methylcholest-2-eneY the 2a-hydrogen atom is lost preferentially. Earlierclaims, that 2a-chlorocholestan-3-one on bromination and 2a-bromochole-stan-3-one on chlorination give the same 2,2-product, are incorrect : in bothcases the new halogen atom 26 takes up the 2a-position. Bromination studiesof cholestan-2-one have been reported. 27 Treatment of 17#?-acetoxy-2a-bromo-5a-androstan-3-one (20) with propane-l-thiol, and then with mineralacid, yields 28 a readily separable mixture of 17/3-acetoxy-5a-androstan-2-and -3-ones. The compound obtained by lithium aluminium hydride reduc-tion of the A5 (lo) -isomer (21) of 19-nortestosterone has the 3a-hydroxy-c~nfiguration.~~ Solvolysis of the mesylate of this compound yields theinteresting 3#?- 5-cyclosteroid (22).In #?punsaturated 3-ketones of 19-nor-steroids, the A5(6)-compounds undergo isomerisation to the A4-ketones muchfaster than do the A5(10)-isomers.30 19-Nor-3-keto-steroids with halogen,or halogen and hydroxyl, substituents a t the 5,6-positions very readilyundergo aromatisation of ring A.31While the simple quinomethine system (23) in steroids is as yet unknown,more highly conjugated analogues have been made.32 The action ofN-chlorosuccinimide on A5(10)-3-ketonesY followed by base has yielded 33the compounds (24). The diene system in (24) is readily moved to the5( lo), 9( ll)-positions.34 A4-3-Ethylene ketals have been made 35 fromA4-3-keto-steroids by cautious experimentation, the double bond migratingto the 5,6-position under more vigorous conditions.Ketalisation of4-methyltestosterone acetate gives 36 exclusively the A4-ketal.The reduction of a number of steroid enamines and imines has been2 5 R. C. Cookson, D. P. G. Hamon, and R. E. Parker, J., 1962, 5014.26 E. W. Warnhof, J. Org. Chem., 1963, 28, 887.27 T. Nakano, M. Hasegawa, and C. Djerassi, Chem. and Pharm. Bull. (Japan),Z 8 R. L. Clarke, J. Org. Chem., 1963, 28, 2626.2 0 S. G. Levine, N.H. Eudy, and E. C. Farthing, Tetrahedron Letters, 1963, 1517.30 W. R. Nes, E. Loeser, R. Kirdani, and J. Marsh, Tetrahedron, 1963, 19, 199.31 R. Gardi and C. Pedrali, Steroids, 1963, 2, 387.32 E. Schwenk, C. G. Castle, and E. Joachim, J. Org. Chem., 1963, 28, 136.33 F. Mukawa, R, I. Dorfman, rtnd H. J. Ringold, Steroids, 1963, 1, 9.34 J. J. Brown and S. Bernstein, Steroids, 1963, 1, 113.35 J. J. Brown, R. H. Lenhard, and S. Bernstein, Ezperient&z, 1962, 18, 310;J. W. Dean and R. G. Christiansen, J. Org. Chem., 1963, 28, 2110.36 D. Burn, G. Cooley, B. Ellis, A. R. Heal, and V. Petrow, Tetrahedron, 1963, 19,1757.1963, 11, 465; C. W. Shoppee and T. E. Bellas, J., 1963, 3366WHITEHUBST: STEROIDS 419investigated. The compounds (26; R, = Me, (conessine series), [CH,],(cholestane series) on treatment with sodium borohydride in &ethyleneglycol diethyl ether underwent little reduction 37 until acetic acid was added,and it seems likely that the reaction involves the immonium cation (26).When the 3-pyrrolidine enamine of progesterone was treated 3* with diboranethe product had the structure ( 2 7 ) which was readily reduced catalyticallyto the A/B trans-dihydro-derivative. The imine (28) was reduced at theCK= bond yielding the 3/3-benzylamino-derivative corresponding to (27).Reduction of saturated steroid 3-ketones (5a or 58) is readily achieved withformic acid and pyrrolidine to yield 3-pyrrolidino-compounds with thenitrogen substituent equatorially oriented. The action of formic acid aloneon compounds such as (26,R2 = [CH2I4) yielded compounds of type (27).The a- and B-oxides of cholest-4-en-3-one and the a-epoxide of cholest-l-en-3-one do not undergo ring contraction with methanolic sodium hydrox-ide.Instead, 4-methoxycholest-4-en-3-one and Z-methoxycholest-l-en-%one are formed,39 respectively. The action of Grignard reagents on3-acyloxy-4,5a-epoxy-steroids has been investigated 4O as a general route to4-substituted steroids. The photosensitised oxidation 41 of cholest-4-en-3p-01 yields cholest-4-en-3-one and its a-epoxide, the relative proportions ofwhich vary enormously with the sensitiser employed.The methylation 42 of cholestane- 1,3-dione afforded the 2,2-dimethylcompound, the 1 - and 3-methyl-en01 ethers, and, unexpectedly, Z-methyl-cholest-l-en-3-one, but no 2-methylcholestane-l,3-dione.Evidently, fromrecent work in the lanostene series, the action of chromyl chloride on cyclicolefins does not always yield chlorohydrins.43Cupric acetate in tetrahydrofuran is a catalyst for the 1,4-addition ofGrignard reagents to A4-3-keto-steroidsY both in the normal and in thenor-series. The products have the cis-ring juncti0n.44~ Tropone analoguesof oestrone have been prepared 44b and several other steroids having ring Aexpanded have been made.45 The solvolysis of 4a-methylcholesteryl37 J. A. Marshall and W. S. Johnson, J. Org. Chem., 1963, 28, 421.38 J. Schmitt, J. J. Panouse, A. Hallot, P. J. Cornu, P. Comoy, and H. PIuchet,39 W. Reusch and R. Le Mahieu, J .Amer. Chem. Soc., 1963, 85, 1669; J. Org.40 S. Julia, B. Decouvelaere, J. P. Lavaux, C. Montonnier, and P. Simon, Bull.41 A. Nickon and W. L. Mendelson, J . Amer. Chem. SOC., 1963, 85, 1894.4 2 H. MLihle and Ch. T a m , Helv. Chim. Acta, 1963, 46, 268.43 D. H. R. Barton, P. J. L. Daniels, J. F. McGhie, and P. J. Palmer, J., 1963,44 (a) A. J . Birch and M. Smith, Proc. Chem. SOC., 1962, 356; ( b ) A. J. Birch,45 G. Snatzke, B. Zeeh, and Eu. Muller, Tetrahedron Letters, 1963, 1425; E. Muller,Bull. SOC. chin%. France, 1963, 807, 816, 1753.Chem., 1963, 28, 2443.SOC. chim. France, 1963, 1221, 1223, 1231, 1238.3675; S. J. Cristol and K. R. Eilar, J . Amer. Ckm. SOC., 1950, 72, 4353.J. M. H. Graves, and J. B. Siddall, J., 1963, 4234.B. Zeeh, R.Meischkeil, H. Fricke, and H. Suhr, Annalen, 1963, 682, 38420 ORGANICtoluene-p-sulphonate yields 46 the4p-methyl isomer gives 46, *' mainly @ ...... ( 2 9 )OHCHEMISTRYcyclosteroid (29). By contrast the4 -met hylcholest a -3,5 - diene and a littleMeof the alcohol (30). Reaction between 19-hydroxyandrost-4-ene-3,17-dione(31) and compound (32) affords48 a mixture of (33) and (34). The enolderivatives of (33) have the eucarvone structure (35).?HRing B. The isolation of cholest-6-en-3~-01 from the reaction of 7-dehy-drocholesterol with diborane was taken previously 49 as evidence of a 1,4-addition process. New work 5O has firmly established the reaction to be a1,2-addition, the 6-olefin arising by the protonation of the initial adduct (36),evidently through the carbanion (37).The structure of compound (36)OH46R. M. Moriarty and R. M. de DOUS&, J . Org. Chem., 1963, 28, 3072.47 S. Julia, J. P. Lavaux, S . R. Pathak, and G. H. Whitham, Compt. rend., 1962,48 L. H. Knox, E. Velarde, and A. D. Cross, J . Anzer. Chem. SOC., 1963, 85, 2533.O9 Y. Mazur, M. Nussim, and F. Sondheimer, Proc. Chem. Suc., 1959, 314.6 O L. Cagliotti, G. Cainelli, and G. Maina, Tetrahedron, 1963, 19, 1057.256, 1537WHITEHURST : STEROIDS 421rests on its oxidation by hydrogen peroxide-sodium hydroxide to the6a-hydroxy-compound (38) (75% yield).The dienone (39) reacts with aqueous methanolic potassium cyanide toyield 51 an interesting diadduct (40). Hydrolysis of the latter yields thealmost non-enolic diketone (41).The adduct (40) can be completelydehydrocyanated by potassium t-butoxide-t-butyl alcohol to regenerate thedienone (39).Ring c. The available evidence 52 indicates that 1 l-keto-steroids bearingan aromatic ring A are more stable in the gPH(B/C-CiS) form than in the9aH configuration and that the conversion is particularly rapid underalkaline conditions. Birch reduction of such compounds affords 52d accessto the 19-nor-steroids with the 9P, lOa(retro)-configurations. The 9PH, 10a-methyl-steroids are, of course, well Sodium-ethanol reduction ofthe 12-oximes of 5a- and 5p-steroids yields the 12cc(axial)-amines exclu-sively, and equilibration studies on the 12a- and 12~-alcohols have shown thegreater thermodynamic stability of the former.A novelty is the introduction 55 of a 17a-hydroxyl group by the scheme shown in Chart 1.Ring D and the side chain.AC {6Me1Me\ Me.CO * 0A C'CH2PhCHART 1. Reagents: 1, PhCH,*NH2. 2, Ac,O-C,H,N. 3, LiAlH,. 4, PhC03H5, AcOH-H2O. 6, Aq. NaOH.If the amide (42) is epoxidised and hydrolysed with hot dilute aceticacid the product is the 17/?-acetoxy-pregnane (43).6 1 R. G. Christiansen and W. S. Johnson, Steroids, 1963, 1, 620.52 (a) J. Elks, J. F. Oughton, and L. Stephenson, Proc. Chew. Soc., 1959, 6; (b) E.Caspi, E. Cullen, P. K. Grover, and N. Grover, J., 1963, 2166; (c) H. Hasegawa, S.Nozoe, and K. Tsuda, Chem. and Pharrn. Bull. (Japan), 1963, 11, 1027, 1037; (d) J. A.Edwards, P. Crabbe, and A. Bowers, J. Amer. Chem.SOC., 1963, 85, 3313.53 L. F. Fieser and H. Fieser, " Steroids," Reinhold Publ. Corp., New York, N.Y.,1959, 136; J. Castells, E. R. H. Jones, G. D. Meakins, and R. W. J. Williams, J., 1959,1159.5 4 M. Alauddin and H. Martin-Smith, J. Org. Chem., 1963, 28, 886.55 W. Fritsch, J. Schmidt Thom6, H. Ruschig, and W. Haede, Chem. Ber., 1963,96, 68; cf. T. H. Kritchevsky and T. F. Gallagher, J. Amer. Chem. SOC., 1951, 73, 184;J. Schmidt-Thorn6 and W. Fritsch, Amaten, 1963, 882, 27422 ORGANIC CHEMISTRYDeamination of the amine (44) gave 56 as the only isolated product ofMeIHO-CH(4 5)the cyclopropane (45). Decomposition of the N-nitroso-Iactam (46) gave 57the ester (47).H20-Oxopregn-16-enes react with acetone in alkaline solution to yieldcompounds such as (48), if a 12-oxo-group is pre~ent.~s Acrylonitrileattacks 21-formyl-pregn-l7(2O)-enes a t the 16-p0sition,~~ also with theformation of a new ring.17,17a-Dioxo-~-homo-steroids undergo benzilicacid ring contraction to give l7/3-hydroxy-l7a-~arboxylic acids stereo-specifically.60 17/?-Hydroxy-steroids possessing a 17-acetylenic substituent,on mild acid treatment,61 yield compounds with ring D aromatic. Thelithium aluminium hydride reduction of the toluene-p-sulphonylhydrazonesof 17-oxo-steroids is an excellent way of preparing A1s-compounds.62One (49) of the products obtained 63 by irradiating Photochemistry.OH1 -dehydrotestosterone acetate has been converted64 by six steps intol0a-methyltestosterone, which undergoes the simple conversion into thes6 J. Hora, V.Czerny, and F. sorm, Coll. Czech. Chem. Comm., 1962, 27, 2771.,57 A. Kasal, V. Czerny, and F. germ, Coll. Czech. Chem. Comm., 1963, 28, 411.,58 M. E. Wall, S. Serota, H. E. Kenney, and S. G. Abernethy, J. Amer. Chem. SOC.,5 g Ch. R. Engel and J. Lessard, J . Amer. Chem. SOC., 1963, 85, 638.sOV. Georgian and N. Kundu, Tetrahedron, 1963, 19, 1037.J. Cenceill, M. Dvolaitzky, and J. Jacques, Bull. SOC. chGn. France, 1963, 336;E. Hardegger and C. Scholz, Helv. Chim. Acta, 1945, 28, 1355.62 L. Cagliotti and M. Magi, Tetrahedron, 1963, 19, 1127.H. Dutler, C. Ganter, H. Ryf, E. C. Utzinger, K. Weinberg, K. Schaffner, D.Arigoni, and 0. Jeger, Helv. Chim. Acta, 1962, 45, 2346.64 R. Wenger, H. Dutler, H. Wehrli, K.Schaffner, and 0. Jeger, Helv. Chim. Acta,1962, 45, 2420.65 H. Wehrli, R. Wenger, K. Schaffner, and 0. Jeger, Helv. Chim. Acta, 1963,46, 678.1963, 85, 1844WHITEHURST : STEROIDS 423A5-isomer with U.V. light.(49; 3,4-&hydro) and the compound (50).Under similar conditions testosterone affordsPhotolysis of 1 l-oxo-steroids yields cyclobutanols 67 (51) by hydrogentransfer from the 19-methyl group. The conversion is enhanced in the4,4- dimet hyl compounds. 6816-Diazo-17-oxo-steroids (52) undergo ring contraction on irradiation tocompounds of type ( 5 3 ) . 6 9 Experimentation 69bs with the (2-13 lumi-compounds of (52) has rigorously established that the stereochemistry at thisposition is not inverted in the process. Most information is available forthe 16-diazodehydroepiandrosterone (52).Two acids are formed. Theirstereochemistry at C-16 has been determined.Photolysis of dehydroepiandrosterone involves 70 fission of ring D at the16(17)-bond and yields compound (54). In the presence of oxygen theproduct is (55). Compound (56) is smoothly decarbonylated on irradia-tion,'l and it has been shown by deuterium labelling that the hydrogenatom of the aldehyde group becomes fixed at position 19 in the nor-steroidproduced.Some 17a-hydroxyaldosterones have been synthesised by the photolysisof suitable 1116-nitrites.72 Because of nitrone formation it was necessary toprotect the side-chain as the bismethylenedioxy-derivative.66 B. Nann, D. Gravel, R. Schorta, H. Wehrli, K. Schaffner, and 0.Jeger, Helv.Chim. Acta, 1963, 46, 2473.6 7 M. S. Heller, H. Wehrli, K. Schaffner, and 0. Jeger, Helv. Chinz. Acta, 1962,45, 1261.6 8 J. Iriate, K. Schaffner, and 0. Jeger, HeEv. Ci~irn. Acta, 1963, 46, 1599.6 9 ( a ) J. L. Mateos, 0. Chao, and H. Flores, Tetrahedron, 1963, 19, 1051; idem,Bol. Inst. Quim. Univ. nac auton. Mexico, 1961, 13, 3; (b) M. P. Cava and E. Moroz,J. Amer. Chem. Soc., 1962, 84, 115; ( c ) J. Meinwald, G. G. Curtis, and P. G. Gassman,ibid., 1962, 84, 116; (d) G. Muller, C. Huynh, and J. Mathieu, Bull. SOC. chim. France,1962, 296; ( e ) A. Hassner, A. W. Coulter, and W. S. Seese, Tetrahedron Letters, 1962,759.'O G. Quinkert and H. G. Heine, Tetrahedron Letters, 1963, 1659.71 J. Iriate, J. Hill, K. Schaffner, and 0.Jeger, Proc. Chem. Xoc., 1963, 114.72 31. Akhtar, D. H. R. Barton, J. 31. Beaton, and A. G. Hortmann, J. Amer. Chern.Soc., 1963, 85, 1512424 ORGANIC CHEMISTRYLead tetra-acetate oxidation of hydroxy steroids. Most of the work hascome from Swiss laboratories. 73 Wettstein and his colleagues have developeda " hypoiodite " reaction involving the use of lead tetra-acetate and iodine(with illumination) as an intense and specific oxidising agent. So far, itsmain application has been to introduce an oxygen function into the 18- and19-methyl groups of steroids. The course of this reaction is suggested inChart Z.74Me OH Me 01 Me 0' eH OHAA -AA-AA-&,J (A) \ jICH OH ICHI 0' ICH2 OHc- - ,- - 1\1\ (B) IHC - 0JH2C -0 u (C)( E lHemiacetals,lactones(D)CHART 2.It is considered that the cyclisation (B) -+ (C) will proceed best by anSN2 mechanism but for this a linear arrangement (E) of the I, C, and 0atoms in (B) will be required.An SN1 mechanism for this step is notprecluded but it will be slower and the stereochemistry will be unimportant.The products (C) and (D) are referred to as " mono- " and " di-substitution "compounds, respectively.In conformity with this scheme, 6j%hydroxy-50c-steroids, where conforma-tion (E) is possible, yield 75 6P,l%ethers, whereas 2g- and 4P-hydroxy-5a-steroids, in which this conformation is made impossible by the presence ofring c, yield hemiacetals and lactones.74 The reaction with 1 lg-hydroxy-5a-compounds is complicated but yields 76 llg,l8- and 11/?,19-lactones, as wellc.../L .rY73 ( a ) G. Cainelli, M. Lj. Mihailovic, D. Arigoni, and 0. Jeger, Helv. Chim. Acta,1959, 42, 1124, and subsequent papers; ( b ) Ch. Meystre, K. Heusler, J. Kalvoda, P.Wieland, G. Anner, and A. Wettstein, Experientia, 1961,10,474, and subsequent papers.7 4 K. Heusler, J. Kalvoda, P. Wieland, G. Anner, and A. Wettstein, Helv. Chim.Acta, 1962, 45, 2575; ibid., Cfazzetta, 1963, 93, 140.7 5 Ref. 7 3 b ; J. F. Bagli, P. F. Morand, and R. Gaudry, J . Org. Chem., 1963,28,1207.76 J . Kalvoda, K. Heusler, G. h e r , and A. Wettstein, Helv. Chim. Acta, 1963,46, 618WHITEHURST : STEROIDS 425as 1 1pyl9-ethers, the latter arising presumably by an SN1 substitution.With 1 l~-hydroxy-5~-compounds, the l1pyl9-ethers are the chief products,73bas the conformational constraint of the 28- and 4p-hydrogen atoms on the19-iodomethyl group is no longer important.The use of lead tetra-acetate alone on 1 lp-hydroxyprogesterone 3'20-bisethylene ketal (57; llB-OH, R = H) gives the la,lla-ether (58; R = H).The 1 la-hydroxy-epimer behaves similarly.Deuterium was quantita-tively 77 retained at C-11 when the deuterio-compounds (57; R = D) wereemployed. Wettstein et aZ.78 have also investigated the 1 la-compound(57; lla-OH, R = H) and, as a second product, have isolated the ketal(59).Epimerisation a t C-11 is evidently due to the reversibility of the fragmenta-tion reactionI t I 1 -c-c-0' - -C' + c=ot i I ILead tetra-acetate oxidation 78 of the ester (60) gives, beside the 4pY19-ether,0 * COlEtIO.CO,EtIthe ester (61) evidently by epimerisation at both C-4 and C-5 positions.Oxidation of the tertiary alcohol 79 (62) yields the hemiacetal(63) by cleavageMeAcO FHIMeAcO - CHIof the 5,6-bondY hydrogen transfer from C-1 to C-5 (proved by deuteriumlabelling), rotation of ring A and recyclisation, this time a t (3-3.The action of Wettstein's reagent on compounds (64) and (66) yields thedisubstitution-type products (65) and (67), Oxidationsof this nature are making available a large number of novel compounds.7 7 G.B. Spero, J. L. Thompson, W. P. Schneider, and F. Kagan, J . Org. Chem.,1963, 28, 2225.7 8 K. Heusler, J. Kalvoda, G. h e r , and A. Wettstein, Helv. Chim. Acta, 1963,46, 352; 1961, 44, 186.7B K.Heusler and J. Kalvoda, Helv. Chim. Acta, 1963, 46, 2732.* O K. Heusler and J. Kalvoda, Helv. Chim. Acta, 1963, 46, 2020.81 Ch. Meystre, J. Kalvoda, G. Anner, and A. Wettstein, Helv. Chirn. Acta, 1963,46, 2844426 0 R G A N I C CHEMISTRY@ *@: H (64) 1 . H j (65) H (66)0' HOVery recently, 82 the lead tetra-acetate-iodine reaction has been appliedto amides. Compound (68) gave the 16/?-lactone (69) in 55% yield.@ &C**N*?&OAcO AcOH (67) H (6 8) H (6 9)0 :Synthesis.-A spate of synthetical work has been reported. Oestronehas been synthesised by alkylation of (70 ; R = /?-O-tetrahydropyranyl,a-H) s3 and (70; R = 0) with m-methoxyphenethyl toluene-p-sulphonate 83and the corresponding bromide.84 The dione (71) undergoes acid cyclisa-tion to the bisdehydro-oestrone (72), which has been reduced 85 to oestrone.Compound (71) is also available by the base-catalysed cyclisation of theadduct (73).Alkylation of 2-rnethylcyclopentane-ly3-dione with either s6b 2-(6-82 D.H. R. Barton and A. J. L. Beckwith, Proc. Chem. SOC., 1963, 335.s3 D. J. Crispin and J. S. Whitehurst, Proc. Chem. SOC., 1962, 366.a4 H. Smith, G. A. Hughes, and B. J. McLoughlin, Experientia, 1963, 19, 177.s5 (2. A. Hughes and H. Smith, Chem. and Id., 1960, 1022.86 (a) I. V. Torgov, Pure Appl. Chem., 1963, 6, 525; S. N. Ananchenko and I. V.Torgov, Tetrahedron Letters, 1963, 1553; ( b ) D. J. Crispin and J. S. Whitehurst, Prcc.Chem. SOC., 1963, 22; ( c ) T. B. Windholz, J. H. Fried, and A.A. Patchett, J . Org. Chenz.,1963, 28, 1092; ( d ) T. Miki, K. Hiraga, and T. Asako, Proc. Chem. SOC., 1963, 139;( e ) H. Smith, G. A. Hughes, G. H. Douglas, D. Hartley, B. J. McLoughlin, J. B. Siddall,G. R. Wendt, G. C. Buzby, D. R. Herbst, K. W. Ledig, J. R. McMenamin, T. W. Pattison,J. Suida, J. Tokolies, R. A. Edgren, A. B. A. Jansen, B. Gadsby, D. H. R. Watson,and P. C . Phillips, Experientia, 1963, 19, 394; G. H. Douglas, J. M. H. Graves, D.Hartley, G. A. Hughes, B. J. McLoughlin, J. Siddal, and H. Smith, J., 1963, 5072WHITEHURST : STEROIDS 427methoxy-1 -naphthylidene)ethyl bromide or 86 6-methoxy-1 -vinyl-1 -tetra101yields the compound (74). The latter method of alkylation (probably (75))constitutes a new rea~tion.~’ In the presence of acid, the dione (74) under-goes cyclisation to the bisdehydro-oestrone (72) in over 40% yield 86a from6-methoxy-l-tetralone and this seems to be the best available route tooest rone .Velluz and his associates have published a new total synthesis of steroids 88beginning with 2-methylcyclopentane-1,3-dione (Chart 3).The initial0 6 ___) ‘ , 2 , 3 0 p4 __f p(77)H02C(76) Me0 ZC 5 H OZC5 pL *e - { Testosterone Oestrone0 Cortisone(78) MeCHART 3. Reagents: 1, Toluene-pyridine. 2, ~N-HC~. 2, NrtBH,. 5, Ac,O-NaOAc.6, CH,-C-CH,=CH,-CH,.MgBr.oAoCHART 4. Reagents : 1, Furfuraldehyde, CH,.OH, KOH. 2, CH,*O*CH,*CHa*CN,CH,-OH, tetrahydrofuran, NaO-CH,. 3, 0,. 4, NaBH,. 5, NaIO,. 6, CH,*OH-H+.7, Ac,O-C,H,N. 8, AcOH. 9, Cr0,-C5H,N. 10, aq.KOH. 11, CH,N,.12, Ac,O-C,H,W. 13, PhLi. 14, Ac,O-C H N. 15, SOCl,-C5H,N.16, 0,. 17, Zn-AcOH. 18, Pipe~id&e-AcOH-C&f,.87 S. N. Anachenko and I. V. Torgov, Doklady Akad. Nauk S.S.S.R., 1959,127,553.L. Velluz, G. Nomin6, G. Amiard, V. Torelli, and J. C6&de, Compt. rend., 1963,257, 3086428 ORGANIC CHEMISTRYstages are similar to those of the well-known Ciba route.s9 The course ofthe catalytic reduction step (76 + 77) is of interest because the analogue(76 ; no CH,*CH,*CO,H) gives,g0 stereospecifically, the cis-ring junction.A full account has appearedg1 of the total synthesis of aldosteroneannounced earlier. New work is cited for the construction of ring D, someof which is outlined in Chart 4. Some unusual features were encounteredin the chemistry of the intermediates.For example, oxidation of the dieneto the dialdehyde could only be achieved with ozone. In connexion withaldersterone synthesis, it has been found 92 that di-isobutylaluminiumhydride has advantages over lithium aluminium hydride in the reduction ofCHART 5. Reagents: 1, MeLi. 2, Ac20-C,H,N. 3, POC1,-C,H,N. 4, 0,.5, KOH-EtOH. 6, KCN-NH,Cl-Me,N.CHO. 7, C2H,( OH),-H+. 8, LiAlH,-tetra-hydrofuran. 9, Wolff-Kishner. 10, (30,-C,H,N. 11, Br,-AcOH. 12, Tetramethyl-ammonium mesitoate-ace tone.HCHART 6. Reagents: 1, C,H,(OH),-H+. 2, LiAlH,. 3, H+. 4, H2-Pt.5, CH,O-HC0,H. 6, (30,. 7, Br,-dehydrobromination. 8, Me,NH.9, NaBH,-MeOH-AcOH.89 P. Wieland, H. Uberwasser, G. Anner, and K. Miescher, Helv. Chirn. Acta,9oC.B. C. Boyce and J. S. Whitehurst, J., 1960, 4547.9 1 W. S. Johnson, J. C. Collins, R. Pappo, M. B. Rubin, P. J. Kropp, W. F. Johns,92 J. Schmidlin and A. Wettstein, Helv. Chirn. Acta, 1963, 46, 2799.1953, 38, 376, 646, 1231.J. E. Pike, and W. Bartmann, J. Arner. Chern. SOC., 1963, 85, 1409WHITEHURST : STEROIDS 42911,18-lactones to the hemiacetals. Aldosterone has also been obtained 93from 3/3-acetoxy-l1 -oxo-5a-conanine by a seventeen-stage synthesis.Conversion of compound (79) into (81) has permitted elegant synthesesof progesterone (82; Chart 5) g4 and conessine (83; Chart 6).95Nagata and his colleagues 96 have published (Chart 7) total synthesesof 38-hydroxy-5a-pregnane-20-one (87) and of conessine, starting from the3/?,5a-isomer (85) of Johnson's compound (80).Nagata's compound wasobtained via the tricyclic intermediate (84). The addition of hydrogencyanide to the enone system in (85) was highly stereospecific, yielding thedesired 138-cyano-derivative (86) in over 80% yield. The lithium aluminiumhydride reduction of the ethylene ketal of this compound was reported to do flC, H AHO HO -H (84) HAc v HCHART 7. 1, HCN-tetrahydrofuran-AlEt3, 2, C,H,(OH),-H+. 3, LiAlH4.4, NaOAc-AcOH (20-ethylene ketd group intact). 5, Wolff-Gshner. 6, H+.7, LiAlH, (95").give, in one step (59%), the compound (88) which was further elaborated toconessine.Conessine has also been synthesised by Stork and his colleague^.^^ Theapproach was to fashion the nitrogen system of this alkaloid in a tricycliccompound and then to add ring A as the ultimate step. The principalstages are shown in Chart 8.Details have now appeared 98 of the synthesis of equilin announcedearlier.,4 preliminary communication 99 has appeared on the synthesis of 3-tachy-sterol (92) by the Wittig reaction between the unstable aldehyde (90) andhalide (91).The aldehyde was obtained initially from cholesterol but was93 J. I?. Kerwin, M. E. Wolff, F. F. Owings, B. B. Lewis, B. B. Blank, A. Magnani,C. Kharasch, and V. Georgian, J. Org. Chem., 1962, 2'9, 3628.94 W. S. Johnson, J. F. W. Keana, and J. A. Marshall, Tetrahedron Letters, 1963, 193.95 J. A. Marshall and W. S. Johnson, J. Amer. Chem. SOC., 1962, 84, 1485.96 W. Nagata, T. Teresawa, and T. Aoki, Tetrahedron Letters, 1963, 865, 869.9 7 G.Stork, S. D. Darling, I. T. Harrison, and P. S. Wharton, J. Amer. Chem. SOC.,g* J. A. Zderic, H. Carpio, A. Bowers, and C. Djerassi, Steroids, 1963, 1, 233;R. S. Davidson, P. S. Littlewood, T. Medcalfe, S. M. Waddington-Feather,1962, 84, 2018.idem, J . Amer. Chem. SOC., 1958, 80, 2596.D. H. Williams, and B. Lythgoe, Tetrahedron Letters, 1963, 1413430 ORGANIC CHEMISTRYCOzMe@o ' - 3 , pi - 4 - 6?- Me0 / Me0 /Me0 ZC T8-10,4\H'sO*H2C COMe {j-y aH Ac0 Me{B HI 5 - 17___fHOlC 0CHART 8. Reagents : 1, Me,C0,-NaH-C6H,. 2, CH,=CMe.COMe-KOBu-t -BuOH.3. H+. 4, H,-Pd. 5, POC13-C,H5N. 6, NaOMe-MeOH. 7, 0,. 8, C,H,(OH),-H+.9, LiAIH,. 10, C7H,*S0,C1-C5H,N. 11, NH,*OH-C,H,N. 12, H,-Rh. 13, HBr-AcOH.14, Ac,O-KOH.15, H,-RuO,. 16, Cr0,-H+. 17, CHFCHCN-Triton B, hydrolysis.18, Br,, hydrolysis, oxidation. 19, Me,S04. 20, NaOH aq. Pd(SrC0,)-H,,Ca-HN,,Ac,O. 2 1, CrO,-C,H,N. 22, Ac,O-NaOAc, MeMgI. 23, Me,NH, NaBH4-NaOAc-later synthesised totally from the readily prepared dione (89). The halidewas made in six steps from the Diels-Alder adduct of citraconic anhydrideand but>adiene.ACOH-EtOH, Ca-NH,, HCHO-HCO,H.0 fyJ OHC fl H M e ( y H( 8 9 ) (90) ( 9 ' )Representatives of two of the three classes of solanum alkaloids havebeen synthesised. Demissidine was obtained 100 from the compound (93)by addition of 2-lithio-5-methylpyridine followed by acetylation, dehydra-loo G. Adam and I(. Schreiber, Tetrahedron Letters, 1963, 913WHITEHURST : STEROIDS 431tion, and reduction.A mixture of stereoisomers (94) was produced, fromwhich one compound (10% of the mixture) by the Hofmann-Loffler-Freyttagreaction on the N-chloro-compound gave demissidine (95). Starting from>H &OAcAcO HO(95) H (96)H3B,16/Ldiacetoxy-5cc-pregnan-20-one (96) the same authors lol have syn-thesised soladulcidine (97) and tomatidine (98).Preliminary accounts 102 have appeared of work directed towards asynthesis of veratramine. In particular the compound (99) has beenOHC OMeOHC 'AOMeAcO-"H (I 0'3)OMeIo1 K. Schreiber and G. Adam, Annulen, 1963, 666, 155.l o 2 R. W. Franck and W. S. Johnson, Tetrahedron Letters, 1963, 545; P. W. Schiess,D. M. Baily, and W. S. Johnson, ibid., 1963, 549; D.M. Bailey, D. P. G. Hamon, andW. S. Johnson, &id., 1963, 555432 ORGANIC CHEMISTRYconverted into the compound (101) (via (100)) which is a likely intermedi-ate for this purpose. The S~-H(B/C trans)-stereochemistry for the alkaloiditself and for ll-oxoveratramine has been confirmed. The synthetic ketone(102) has been isolated in two forms, stereoisomeric at C-9.Natural Products.-Ecdysone, an insect metamorphosis hormone, is asteroid.103 250 mg. of the crystalline hormone have been isolated from1000 kg. of the pups of Bombyx m r i , and work so far suggests a cholest-9(11)-en-12-one structure bearing five hydroxyl groups, one of which issituated at position 25.Macdougallin, from Peniocereus mucdougaZZi Cut., has structure (103).The existence of a methyl group a t C-14 but none at C-4 raises lo4 doubtsabout the generality of the currently accepted scheme for the order in whichthe methyl groups of lanosterol are removed in its conversion into chole-sterol .The structure of sarcostin is (104),105, 106 the stereochemistry at C-20only, being uncertain.The compounds cynanchogenin, lo6 lineolone, log, 107and taylorone lo5 are similarly constituted. Diginigenin, the Czl aglyconeof diginin, has the formula (105; R = H) lo* and digifologenin log has thestructure (105; R = OH). Canarigenin, obtained from the leaves ofDigitalis cunariensis L., is compound (106) l10 and is thus the A4-isomer ofxysmalogenin. Antiarigenin, the genin of IX- and #l-antiarins, has beenlo3 P. Karlson and H.Hofmeister, Annalen, 1963, 682, 1.lo4 C. Djerassi, J. C. Knight, and D. I. Wilkinson, J . Arner. Chem. SOC., 1963, 85,835; for the synthesis of 14a-methyl-steroids, see G. R. Petit, P. Hofer, W. J. Bomyer,T. R. Kasturi, R. C. Bansal, R. E. Kadunce, and B. Green, Tetrahedron, 1963,19, 1143.Io5 K. A. Jaeggi, E. K. Weiss, and T. Reichstein, Helv. Chim. Acta, 1963, 46, 694.lo6 H. Mitsuhashi and Y. Shimizu, Steroids, 1963, 2, 373.lo7 I. Takemori and T. Nomura, Chem. and Pharm. Bull. (Japan), 1962, 10, 805.lo* C. W. Shoppee, R. E. Lack, and A. V. Robertson, J., 1962, 3610.loo C. W. Shoppee, R. E. Lack, and S. Sternhell, J., 1963, 3281.110 P. Studer, S. K. Pavanarum, C. R. Gavilanes, H. Linde, and K. Meyer, Helv.Chim. Acta, 1963, 48, 23WHITEHURST : STEROIDS 433related A miscellany of sapogeninsbearing hydroxyl substituents in ring F have been isolated.l12Confirmation of the p-configuration for the 24-methyl group of brassi-casterol has been obtained by a synthesis 113 employing the Wittig reaction.The ethyl group in 0-sitosterol is biosynthesised 11* from two C1 units.Cyclobuxine (isolated from Buxus sempervirens) has constitution (107).115Some new C21 nitrogen bases have been discovered.116 Fusidic acid 117 isnow known 116 to have structure (108). Of interest was the use made duringto antiogenin, the genin of antioside.MeHC-NHMe @ --OH('07) M e NHCH2this study 118 of optically active compounds derived initially by totalsynthesis .A number of useful examples of chemical modification of steroids bymicro-organisms have been reported.Il9 -129C.JuslBn, W. Wehrli, and T. Reichstein, Helv. Chim. Acta, 1962, 45, 2285.112 (a) K. Takeda, T. Okanishi, H. Minato, and Shimaoka, Tetrahedron, 1963, 19,759; (b) H. Minato and A. Shimaoka, Chem. and Pharm. Bull. (Japan), 1963, 11, 877;(c) K. Takeda, H. Minato, A. Shimaoka, and Y. Matsui, J., 1963, 4815.113 K. S3kai and K. Tsuda, Chem. and P h r m . Bull. (Japan), 1963, 11, 650.11* M. Castle, G. Blondin, and W. R. Nes, J . Amer. Chem. SOC., 1963, 85, 3306.115 K. S. Brown and S. M. Kupchan, J . Amer. Chem. Soc., 1962, 84, 4590, 4592.116 M. M. Janor, F. K.-H. Laine, and R. Goutarel, Bull. SOC. chirn. Prance, 1962,117 W. 0. Godtfredsen and S. Vangedal, Tetrahedron, 1962, 18, 1029.648, and subsequent papers.R.Bucourt, M. Legrand, M. Vignau, J. Tessier, and V. Delaroff, Compt. rend.,llD C. G. Bergstrom, R. T. Nicholson, and R. M. Dodson, J . Org. Chem., 1963, 28,120 C. H. Robinson, N. F. Bruce, and E. P. Oliveto, J . Org. Chem., 1963, 28, 975.121 W. J. Wechter and H. C. Murray, J . Org. Chem., 1963, 28, 755.122 C. J. Sih, S. M. Kupchan, N. Katsui, and 0. El Tayeb, J . Org. Chem., 1963,28,854.123 K. Tori and E. Kondo, Tetrahedron Letters, 1963, 645.12* S. M. Kupchan, C. J. Sih, S. Kubota, and A. M. Rahim, Tetrahedron Letters,125 Y. Sato and S. Hayakawa, J . Org. Chem., 1963, 28, 2739.126 H. Ishui, Y. Nozaki, T. Okumura, and D. Satoh, Chem. and Pharm. Bulb. (Japan),12' J. de Flines, W. F. van der Waard, W. J. Mijs, and S.A. Szpilfogel, Rec. Trav.128 E. Weiss-Berg and Ch. T a m , HeEw. Chim. Acta, 1963, 46, 1166.129 S. Baba, H. J. Brodie, M. Hayans, D. H. Petersen, and 0. K. Sebek, Steroids,1963, 257, 2679.2633.1963, 1767.1963, 11, 156.c?&n., 1963, 82, 121, and subsequent papers.1963, 1, 15112. CARBOHYDRATESBy D. J. MannersSINCE the previous Report dealt mainly with monosaccharide chemistry,only selected topics will be considered here and emphasis given to recentdevelopments in the structural analysis of polysaccharides, particularlythose of plant and microbial origin. Mucopolysaccharides and glycoproteinsare reviewed elsewhere in this volume. Attention is drawn to recentreviews of higher-carbon sugars, the carbohydrate components of the cardiacglyco~ides,~ the selective oxidation of carbohydrates by using platinumcatalystsY5 dicarbonyl carbohydrates,6 purine nucleosides, and the chem-istry of branched-chain, deoxy- and amino-sugars.* A general survey ofcarbohydrate chemistry9 and a revised edition of a standard text-bookhave also been published.10General Methods.-New or improved methods for the separation ofvarious carbohydrates by thin-layer,ll paperY12 column (carbon,l3 ion-exchange resin,l* or Sephadex 15), and g.l.c.16 have been described.Thelatter has been used for the separation of sugars ranging from glycolaldehydeto stachyose, as their trimethylsilyl derivati~es,~’ and for the preliminaryidentification 18 and estimation l9 of the methanolysis products from methy-lated polysaccharides.However, less-stable carbohydrates may undergostructural modification during g.1.c. *OColorimetric reactions have been used for the differential analysis ofglucuronate, glucosiduronate, and hyaluronate, 21 the determination of3,6-anhydrogala~tose,~~ and of D-galactosamine in the presence of D-glucosa-1 J. Honeyman, Ann. Reports, 1962, 59, 359.2 D. W. Russell and R. Sturgeon, Ann. Reports, 1963, 60, 486.4 T. Reichstein and E. Weiss, Adv. Carbohydrate Chem., 1962, 17, 65.5 K. Heyns and H. Paulsen, Adv. Carbohydrate Chem., 1962, 17, 169.6 0. Theander, Adw. Carbohydrate Chem., 1962, 17, 223.7 J. A. Montgomery and H. J. Thomas, Adv. Carbohydrate Chem., 1962, 17, 301.8 W. G. Overend, “ Jubilee Memorial Lecture,” Chem. and Ind., 1963, 342.9 “ Comprehensive Biochemistry,” Vol.5, ed. M. Florkin and E. H. Stotz, Elsevier,1 0 E. G. V. Percival, revised by E. Percival, “ Structural Carbohydrate Chemistry,”11 C. E. Weill and P. Hanke, Analyt. Chem., 1962, 34, 1736; M. Gee, ibid., 1963,1 2 E. J. Bourne, E. M. Lees, and H. Weigel, J. Chromatog., 1963, 11, 253; R. Piras13 W. A, L. Evans and D. W. Payne, Analyst, 1963, 88, 204.1 4 S. Adachi and H. Sugawara, Arch. Biochem. Biophys., 1963, 100, 468.15 P. Nordin, Arch. Biochenz. Biophys., 1962, 99, 101.16 E. C. Horning and W. J. A. VandenHeuvel, Ann. Rev. Biochenz.., 1963, 32, 709.1 7 C. C. Sweeley, R. Bentley, M. Makita, and W. W. Wells, J . Amer. Chem. Soc.,1 8 G. 0. Aspinall, J., 1963, 1676.1 9 K. Wallenfels, G. Bechtler, R.Kuhn, H. Trischmann, and H. Egge, Angew.20 C. T. Bishop, F. P. Cooper, and R. K. Murray, Canad. J . Chem., 1963, 41, 2245.2 1 H. Yuki and W. H. Fishman, Biochem. Biophys. Acta, 1963, 69, 576.22 W. Yaphe, Nature, 1963, 197, 488.J. M. Webber, Adv. Carbohydrate Chem., 1962, 17, 15.New York, 1963.J. Garnet Miller, London, 1962.35, 350; 0. W. Hay, B. A. Lewis, and F. Smith, J . Chromatog., 1963, 11, 479.and E. Cabib, Analyt. Chem., 1963, 35, 755; J. A. Thoma, ibid., p. 214.1963, 85, 2497.Chenz., Internat. Edn., 1963, 2, 515MANNERS : CARBOHYDRATES 435mine,23 the microanalysis of blood galactose,24 and the degree of polymerisa-tion (DP) of oligosaccharides.25 For polysaccharides, methods for determin-ation of sulphate,26 uronic acid,27, 28 and alkoxyl 28 groups, and the mech-anism of decarboxylation of uronic acids 29 have been examined.Experimental conditions for the methylation,19 and benzylation 30 ofcarbohydrates, and for the complete 31 or partial 32 deacetylation of sugaracetates have been improved.The products of sulphation of D-galactose andD-glucose have been characterised;33 the rates of acid hydrolysis of many ofthese sulphates are sufficiently different as to have diagnostic value.34Certain carbohydrate secondary sulphonates on treatment with sodiumbenzoate in dimethylformamide yield the corresponding benzoate, but withinversion of configuration.35 This reaction has been used to locate theposition of free hydroxyl groups in the isopropylidene derivatives of L-rham-nitol, L-arabitol, and ribitol,36 and to convert D-erythro-derivatives into thethreo-isomers .37Periodate-oxidation methods continue to be widely used, e.g., in structuralstudies on polysaccharides (heparin 26 and yeast phosphomannan 38), in thestepwise degradation of 14C sugars, 39 and for preparative procedure^.^^The mechanism of the oxidation of malonaldehydes, and amino- and aceta-mido-sugars,41 has been studied, and new nitrogen-containing derivatives ofperiodate-oxidised methyl 4,6-0-benzylidene-a-~-glucoside prepared.42 Thestructural signi6cance of the presence of small amounts of glucose,43glyceraldehyde, and glycolaldehyde 44 in hydrolysates of periodate-oxidisedborohydride-reduced polysaccharides has been discussed.An increasing number of physical methods have been applied to stereo-chemical and conformational problems, including mass spectrometry (for23 C.Cessi and F. Serafini-Cessi, Biochem. J., 1963, 88, 132.2 4 D. Watson, Analyt. Biochem., 1963, 5, 260.25 L. Stewart and P. Nordin, Analyt. Biochem., 1963, 5, 175.26 A. B. Foster, R. Harrison, T. D. Inch, M. Stacey, and J. M. Webber, J., 1963,27 D. M. W. Anderson and S. Garbutt, Analyt. Chim. Acta, 1963, 29, 31.28 D. M. W. Anderson, S. Garbutt, and S . S . H. Zaidi, Analyt. Chim. Acta, 1963,2 9 D. M. W. Anderson and S. Garbutt, J . , 1963, 3204.31 J. Stanirk and J. CernQ, Tetrahedron Letters, 1963, 35.32 Y. Z . Frohwein and J. Leibowitz, Bull. Res. Council Israel, 1963, 11A, 330.83 J. R. Turvey and T. P. Williams, J ., 1963, 2242.3 4 D. A. Rees, Biochem. J., 1963, 88, 343.55E. J. Reist, R. R. Spencer, and B. R. Baker, J . Org. Chem., 1959, 24, 1618;M. A. Bukhari, A. B. Foster, J. Lehmann, M. €1. Randall, and J. M. Webber, J., 1963,4167.38 M. A. Bukhari, A. B. Foster, J. Lehmann, and J. M. Webber, J., 1963, 2287;31. A. Bukhari, A. B. Foster, J. Lehmann, J. M. Webber, and J. H. Westwood, J.,1963, 2291.37 A. B. Foster, R. Harrison, J. Lehmann, and J. M. Webber, J., 1963, 4471.38 31. E. Slodki, Biochim. Biophys. Acta., 1963, 69, 96.39 A. M. Unrau and D. T. Canvin, Canad. J . Chem., 1963, 41, 607.40 D. L. Mitchell, Canad. J . Chem., 1963, 41, 214.O1 M. Cantley, L. Mough, and A. 0. Pittet, J., 1963, 2527; M. Cantley and L.4 2 G. J. F. Chittenden and R. D.Guthrie, J., 1963, 2358, 3658.O3 D. J. Manners and G. A. Mercer, J . , 1963, 4317.4 4 A. Bl. Unrau, Canad. J . Chem., 1963, 41, 2394.2279.29, 39.M. E. Tate and C. T. Bishop, Canad. J . Chevt., 1963, 41, 1801.Hough, J., 1963, 2711436 ORGANIC CHEMISTRYstudies on various acetates 45) and n.m.r. spectro~copy.~~ The latter sup-ports the generally accepted assignment at C1 of /l-~-glucose,~~ in contrastto other evidence,48 and has also provided new information on carbohydrateor tho acetate^,^^ lac tone^,^^ and the conformations of methyl a- and P-D-xylothiapyranosides, 51 methyl 3-O-carbamoyl-a- and -#?-L-novioside 52 and1,3 : 2,4-di-O-methylene-~-threitol. 53 1.r. spectroscopy has been used, interaZ., to determine the configuration of branched-chain sugars and to study thedeuteration of cellulose-type polysaccharides.54The experimental methods of carbohydrate chemistry have been des-cribed in detai1.55MonosaccWdes.--Higher sugars.The aldo heptose D -gZycero- D -gaZacto-heptose has been isolated for the first time from a plant (avocado), togetherwith a second octulose-D-glycero-L-galacto-octulose, and the first nonulose-D -erythro-L-gluco-nonulose. 56 D -gZuco-~-gZycero -3 - 0 ctulose was prepared byan aldol condensation from D-erythrose. 57 New synthetical methods involvethe addition of two carbon atoms (as malonic acid) in a single step, and anapplication of the Wittig reaction.58Derivatives of various oxo-sugars have beenconverted into 6-deoxy-~-talose and 2-amino-2,6-dideoxy-~-talose,~~ andinto 2-amino-2,6-dideoxy-~-mannose (L-rhamnosamine).60 The D-xylo-con-figuration of desosamine, a 3,4,6-trideoxy-3-dimethylaminohexose, has beenconfirmed by stereospecific synthesis.61 Pneumosamine, a constituent ofthe Pneumococcus type V polysaccharide has been characterised as 2-amino-2,6-dideoxy-~- t alop yranose. Stereospecific syntheses of 5 -amino - 5,6-di-deoxy-DL-allonic and -gulonic acid have been reported,63 and the reductionof hydrazine derivatives was used in the synthesis of 5-amino-3,6-anhydro-5-deoxy-L-idose and derivatives. 64 The hydrochloride of 6-amino-6-deoxy-~-Amino- and deoxy-sugars.46 K. Biemann, D. C. DeJongh, and H. K. Schnoes, J . Arner. Chem. SOC., 1963,46 R. U. Lemieux and D. R. Lineback, Ann.Rev. Biochem., 1963, 32, 155.47 S. Furberg and B. Pedersen, Acta Chem. Scand., 1963, 17, 1160.48 J. Blom, Acta Chem. Scand., 1963, 17, 73.4OA. S. Perlin, Canad. J . Chem., 1963, 41, 399, 555.50 R. J. Abraham, L. D. Hall. L. Hough. K. A. McLauchlan, and H. J. Miller, J..85, 1763; D. C. DeJongh and K. Biemann, ibid., p. 2289.~~ V r 1963, 748.1730.51 V. S. R. Rao, J. F. Foster, and R. L. Whistler, J . Org. Chem., 1963, 28,52 S . A. Ba.rker, J. Homer, M. C. Keith, and L. F. Thomas, J . , 1963, 1538.53 R. U. Lemieux and J. Howard, Canad. J . Chem., 1963, 41, 393.64 R. J. Ferrier, W. G. Overend, G. A. Rafferty, H. M. Wall, and N. R. Williams,56 “ Methods in Carbohydrate Chemistry,” Vol. 1 and 2, ed. R. L. Whistler and56H. H. Sephton and N.K. Richtmyer, J . Org. Chem., 1963, 28, 1691, 2388.57 R. Schaffer and A. Cohen, J . Org. Chem., 1963, 28, 1929.58N. K. Kochetkov and B. A. Dmitriev, Chem. and I n d . , 1963, 115, 864.M. Collins and W. G. Overend, Chem. and I n d . , 1963, 375.6o J. S. Brimacombe and M. C. Cook, Chem. and Ind., 1963, 1281.61 A. C. Richardson, Proc. Chem. SOC., 1963, 131; see also H. Newman, Chem.62 J. S . Brimacombe and M. J. How, J . , 1962, 5037.63 B. Belleau and Y . K. Au-Young, J . Amer. Chem. SOC., 1963, 85, 64.64 M. L. Wolfrom, J. Bernsmann, and D. Horton, J . Org. Chem., 1962, 2’7,Proc. Chem. SOC., 1963, 133; R. Jeffries, Polymer, 1963, 4, 375.M. L. Wolfrom, Academic Press, New York and London, 1962-63.and I n d . , 1963, 372.4505MANNERS : CARBOHYDRATES 437glucose, a constituent of the antibiotic kanamycin, has been preparedcrystalline. 65The first known 4-amino-sugar, amosamine, from the antibiotic amicetin,was shown by synthesis to be 4,6-dideoxy-P-dirnethylamino-~-glucose.~~Mycosamine, from the antibiotic nyst atin, is 3-amino - 3,6-dideoxy-~ - man-nose, the position of the amino-group being located by periodate oxidation. 67N-Acetyl-D-talosamine was prepared by epimerisation of N-acetyl-D-galactosamine at pH 10-1 1 .68 D-Chalcose, 4,6-dideoxy-3-0-methyl-~-glucose, a degradation product of the antibiotic chalcomycin acid, wass ynthesised from methyl 4,6 - 0- benzylidene-3 - O-methyl-2- 0- tosyl- a-D - ghco-side,6Q and also prepared from desosamine, thus confirming the configura-tional assignment .70 1 -Deoxy-~-arubo-3-hexulose, a possible intermediate inthe synthesis of L-streptose and other branched-chain sugars, has beenprepared from L-rhamnitol.71 The preparation of S-deoxy-~-ribohexo-pyranose and 4-deoxy-~-xy~ohexopyranose has been improved. 72Thio-sugars have been reviewed in detail. 73The conversion of thioglycosides into glycosyl halides has been developed 74375and in the D-glucose and D-galactose series yields the more unusual p-halo-geno-sugar. 74 Several nitrogen-containing derivatives of thio-sugars weresynthesised by use of complex neighbouring-group reactions. 76 Syntheses ofderivatives of l-thio-~-galactose,~~ 3-thio-~-glucose,~~ 2- and 3-thio-pento-furanoses 79 and l-deoxy-1-seleno-D-glucose have been described; some ofthese are intermediates in the preparation of deoxy-sugars.New hetero-sugars include derivatives of D-fructose 81 and various pentoses 82 containing,respectively, sulphur and nitrogen in the ring structure.These compounds include, or are related to, bio-chemical intermediates and D-glucosamine 3-~hosphate,~~ L-glycero-tetrulose1 -phosphate,84 D-glycero-tetrulose 1,4-diphosphate,85 and the 6-phosphates of65 E. Hardegger, G. Zanetti, and K. Shiner, Helv. Chim. Acta, 1963, 46, 282.66 C. L. Stevens, P. Blumbergs, and F. A. Daniher, J . Amer. Chem. SOC., 1963,87 J. D. Dutcher, D. R. Walters, and 0. Wintersteiner, J . Org. Chem., 1963, 28,6 8 S. Fujii and H. Kushida, Biochim. Biophys. Acta, 1963, 69, 572.6 s N. K. Kochetkov and A.I. Usov, Tetrahedron Letters, 1963, 519.70 A. B. Foster, M. Stacey, J. M. Webber, and J. H. Westwood, Proc. Chern. Soc.,71 J. W. Bird and J. K. N. Jones, Canad. J . Chem., 1963, 41, 1877.72 E. J. Hedgley, W. G. Overend, and R. A. C. Rennie, J., 1963, 4701.73 D. Horton and D. H. Hutson, Adv. Carbohydrate Chern., 1963, 18, 123.7 4 M. L. Wolfrom and W. Groebke, J . Org. Chem., 1963, 28, 2986.75 M. L. Wolfrom, H. G. Garg, and D. Horton, J . Org. Chem., 1963, %, 2989, 2992.76 L. Goodman and J. E. Christensen, J . Org. Chem., 1963, 28, 158, 2610, 2995;7 7 M. Cerny, J. Stanek, and J. Pacak, Monatsh., 1963, 94, 290.78 M. Cerny, J. Pacak, and V. Jina, Monatsh., 1963, 94, 632.7 9 G. Casini and L. Goodman, J . Amer. Chein. SOC., 1963, 85, 236.8o J. Kocourek, J.Klenha, and V. Jiracek, Chem. and Ind., 1963, 1397.81 M. S. Feather and R. L. Whistler, J. Org. Chem., 1963, 28, 1567.82 J. K. N. Jones and W. A. Szarek, Canad. J . Chem., 1963, 41, 636; S. Hanessian83 0. Westphal and R. Stadler, Angew. Chem., 1963, 75, 452; R. Lamhert and F.84 J. W. Gillett and C. E. Ballou, Biochemistry, 1963, 2, 547.G. A. Taylor and C . E. Ballou, Biochemistry, 1963, 2, 553.Thio- and hetero-sugars.Sugar phosphates.85, 1552.995; M. von Saltza, J. D. Dutcher, J. Reid, and 0. Wintersteiner, ibid., p. 999.1963, 279.M. L. Wolfrom, D. Horton, and D. H. Hutson, ibid., p. 845.and T. H. Haskell, J . Org. Chem., 1963, 28, 2604.Zilliken, Chem. Ber., 1963, 96, 2350438 ORGANIC CHEMISTRY2-0- and 3-O-methyl-~-glucose, S-deoxy-~-glucose, D-allOSe, and D-altrose,SGof D-g~ycero-~-ga~?actoheptose,*~ and of glucometasaccharinic acid 88 havebeen synthesised.Di- and O&o-saccharides.-Variations of the Koenigs-Knorr reactionbetween a tetra-0-acyl-a-D-hexopyranosyl halide and an alcohol, in presenceof various condensing reagents, have been used for the synthesis of 6 - 0 - a - ~ -glucopyranosyl-D-galactose 89 (a hydrolytic product of SaZmoneZZa poly-saccharides), 4-0-a- and 4-C)-B-D-glucosaminyl-D-ribitol (degradation pro-ducts of a ribitol teichoic acid), 5-O-~-~-glucopyranosyl-~-xylose and3,5-di- 0-/3- D -glucop yranos yl-D - xylose , mannos ylinosi t 01s ,9 a branchedtetrasac~haride,~~ and for 2-acetamido-2-deoxy-3-O-~-~-galactopyranosyl-a-D-glucose and a glucosaminylmuramic acid disaccharide,g* both of whichare degradation products of glycoproteins.The constitution of panose wasconfirmed by rnethylati~n.~~ New syntheses of kojibiose 96 and sophorose 97have been described; the rates of acid hydrolysisY98 and of alkaline degrada-t i ~ n , ~ ~ of these and six other glucose disaccharides have been compared.Dilute solutions of maltose are converted by acid into a mixture of sugars,including nigerose ; hence, the presence of the latter in partial hydrolysatesof amylopectin is of doubtful significance. lo0Galactosylinositol lol and 3-O-~-~-ce~obiosy~-~-glucose lo2 have beenprepared by enzymic methods ; 3-keto-glycosides, prepared by the bacterialoxidation of disaccharides, have been converted into gulosylglucose, allosyl-glucose , and allosylfructose.10Analysis of oligosaccharides isolated from partial acid or enzymic hydro-lysates of polysaccharides has yielded new structural information ; examplesinclude several di- and tri-saccharides from human blood group substances, lo4branched oligosaccharides from dextran, lo5 and disaccharides from carboxyl-reduced heparin.lo6a6 L.G. Egyiid and W. J. Whelan, Biochem. J., 1963, 86, 11P.8’D. R. Strobach and L. Szab6, J . , 1963, 3970.88 S. Lewak and L. Szab6, J., 1963, 3975.8 9 I. J. Goldstein and W. J. Whelan, J . , 1963, 4264.9 o F . E. Hardy, J. G. Buchanan, and J. Baddiley, J . , 1963, 3360.9 1 J. K. N. Jones and P. E. Reid, Canad. J . Chem., 1963, 41, 2382.9 2 S. J. Angyal and B. Shelton, Proc.Chent. SOC., 1963, 57.9 3 A. Blemer and F. Gundlach, Ber., 1963, 96, 1765.9 4 H. ill. Flowers and R. W. Jeanloz, J . Org. Chem., 1963, 28, 1377, 1564.95 E. E. Smith and W. J. Whelan, J., 1963, 3915.96 M. L. Wolfrom, A. Thompson, and D. R. Lineback, J . Org. Chew., 1963, 28, 860.9 7 P. A. Finan and C. D. Warren, J . , 1963, 5229.98 M. L. Wolfrom, A. Thompson, and C. E. Timberlake, Cereal Chem., 1963, 40, 82.9g T. J. Painter, Chent. and Ind., 1963, 36.loo D. J. ilIanners and G. A. Mercer, Biochem. J., 1963, 89, 34P; see also M. L.101 R. B. Frydman and E. F. Neufeld, Biochem. Biophys. Res. Comm., 1963,12, 121.1 0 2 E. T. Reese and A. S. Perlin, Biochem. Biophys. Res. Comm., 1963, 12, 191.103 M. J. Bernaerts, J. Fuenelle, and J. De Ley, Biochim.Biophys. Acta, 1963, 69,3 2 2 ; see also S. Fukui and R. M. Hochester, Canad. J. Biochem. Physiol., 1963, 41,2363.lo4 V. P. Rege, T. J. Painter, W. M. Watkins, and W. T. J. Morgan, Nature, 1963,200, 532.lo5 E. J. Bourne, D. H. Hutson, and H. Weigel, Biochem. J., 1963, 86, 555; D. H.Hutson and H. Weigel, ibid., 1963, 88, 588.106 M. L. Wolfrom, J. R. Vercellotti, and D. Horton, J. Org. Chem., 1963,28,278,279.Wolfrom, A. Thompson, and R. H. Moore, Cereal Chem., 1963, 40, 182MANNERS : CARBOHYDRATES 439Polysaccharides.-General. Substantial progress in the structuralanalysis of several polysaccharides, including details of fine structure, havebeen reported. Experimental work was facilitated by the improvements inthe methylation technique already discussed, by application of the Smithdegradation (periodate oxidation, borohydride reduction, and partial acidhydrolysis), and by enzymic methods of degradation, particularly of non-starchy polysaccharides.107 Many workers are indebted to E.T. Reese andhis co-workers 108 for generous supplies of various fungal polysaccharasepreparations. The sequential induction of polysaccharases by micro-organisms is a promising development .looPartial acid hydrolysis continues to be widely used as a method of linkageanalysis. Painter 110 has extended Kuhn's statistical treatment of randomdepolymerisation, and shown that when a polysaccharide is randomlydegraded so that liberated lower oligosaccharides are protected from furtherdegradation (e.g., by continuous dialysis), the overall yield of these oligo-saccharides is greatly increased, and may amount to 90% of the originalpolysaccharide. The method is independent of the degree of branching andmolecular size of the polysaccharide.GEucans.Current views on the structure of the starch components nowrequire some simplification. Periodate oxidation 43 and acid hydrolysis looexperiments show that, in contrast to earlier suggestions, amylopectin doesnot contain 1,3-glucosidic linkages. The small proportion of b-amylase-resistant linkages in amylose, discovered in 1950-1952 by Peat and his co-workers, has now been identified as a-lY6-inter-chain linkages since theyare hydrolysed by isoamylase, an or-1,6-glu~osidase.~~~ It is not thereforenecessary to postulate the existence of additional, and as yet unknown,starch-metabolising enzymes, or to express doubts as to the specificity ofthose already known.Structural analyses of starch-type polysaccharidesfrom various sources have continued. There are some differences in theproperties of the amylose components of starches from potato berries com-pared with those from tubers; the amylopectin fractions are, however, verysimilar.l12 Many green seaweeds contain small quantities (about 1 yo) ofstarch, and that from five species has been investigated.113 The reservepolysaccharide of the protozoan Entodinium caudutum has a typical amylo-pectin-type structure.114A proportion of the phosphate groups in the components of potato starchare attached to glucose residues in the vicinity of ar-1,6-inter-chain linkages.115The mode of incorporation of these phosphate groups is not known.lo' See, for example, T.E. Nelson, J. V. Scaletti, F. Smith, and S. Kirkwood, Canud.l08 E. T. Reese and M. Mandels, Canad. J. Microbiol., 1959, 5, 173; E. T. Reese,lo9 S. A. Barker, G. I. Pardoe, &I. Stacey, and J. W. Hopton, Nature, 1963,197, 231.ll1 0. Kjdberg and D. J. Manners, Biochem. J., 1963, 86, 258.lL2 C. T. Greenwood and S. Mackenzie, Starke, 1963, 15, 251.113 J. Love, W. Mackie, J. P. McKinnell, and E. Percival, J., 1963, 4177.114 J. M. Eadie, D. J. Manners, and J. R. Stark, Biochem. J., 1963, 89, 91P.115 M. W. Radomskj and M. D. Smith, Cereal Chem., 1963,40, 31; G. Harris and I. C.J .CJzem., 1963, 41, 1671.F. W. Parrish, and M. Mandels, ibid., 1961, '7, 309; 1962, 8, 327.T. J. Painter, J., 1963, 779.MacWilliarn, Sturke, 1963, 15, 98440 ORGANIC CHEMISTRYPhysicochemical measurements on solutions of amylose in varioussolvents have enabled the course of association, and the configuration of thepolysaccharide molecules to be examined. 116, 117 In certain solvents, e.g.,aqueous potassium chloride, the molecules behave as random coils,118 butthe coils are drained to varying extents in the various solvents used;119 inmixed solvents, the molecules may exist in at least two configurationsdepending on the solvent environment .l 2OForty different samples of glycogen, including specimens of liver glycogenfrom fed and starved animals, have been analysed; the majority had averagechain lengths of 12-15 glucose residues.121 The relationship betweenglycogen structure and the physiological state of pig muscle has beenexamined.122s 123 Liver glycogen from chicks fed toxic amounts of D-galac-tose contained about 0.2% of galactose, most of which was present as non-reducing end-groups. 124 Various methods for the extraction of glycogen ofhigh molecular weight have been suggested, phenol and water,125 dimethylsulphoxide,126 or glycine being used as solvent. The physicalstate of particulate glycogen, as isolated from liver, has been examined byelectron microscopy.128Methylation studies on cellulose polyalcohol have not confirmed anearlier report of the presence of about 0.2% of 1,3-linkage~.l~~ The majorityof recent studies deal with physicochemical measurements on cellulose or itsderivatives,l30 many of which are described in a symposium report.131 Themaximum weight-average DP’s of native cotton and bacterial (Acetobacterxylinum) cellulose are about 9000 132 and 6000,133 respectively ; the latterexists in elementary fibrils which have a diameter of about 35 A and containabout 36 chain molecules.134 Cadoxen (triethylenediaminecadmium hydro-xide) is a useful solvent for cellulosic polysaccharides , in which sodiummethoxycarbonylcellulose shows the configuration of a randomly coiled116 E. Husemann, B. Pfannemuller, and W. Burchard, Makromol. Chem., 1963,117 W. Burchard, Makromol. Chem., 1963, 59, 16.118 W. Banks and C.T. Greenwood, Makromol. Chem., 1963, 67, 49.119 W. Burchard, Makromol. Chem., 1963, 64, 110.120 J. M. G. Cowie, Makromol. Chem., 1963, 59, 189.l21 0. Kjdberg, D. J. Manners, and A. Wright, Comp. Biochem. Phgsiol., 1963, 8,122 0. Kjdberg, D. J. Manners, and R. A. Lawrie, Biochem. J., 1963, 87, 351.123 R. N. Sayre, E. J. Briskey, and W. G. Hoekstra, Proc. SOC. Exp. Biol. Med.,124 J. H. Nordin and R. G. Hansen, J . Biol. Chem., 1963, 238, 489.lZ5 R. Laskov and E. Margoliash, Bull. Res. Council Israel, 1963, 11A, 351.1~ R. L. Whistler and J. N. BeMiller, Arch. Biochem. Biophys., 1962, 98, 120.127 S. A. Orrell and E. Bueding, in “ Control of Glycogen Metabolism,” CIBA128 P. Drochmans, J . Ultrastructure Res., 1962, 6, 141.129 I. J. Goldstein, J.K. Hamilton, G. W. Huffman, and F. Smith, J . Org. Chem.,1962, 27, 3962.13O See, for example, W. Brown, D. Henley, and J. Ohman, Makromol. Chem.,1963, 64, 49; F. Friedberg, W. Brown, D. Henley, and J. Ohman, ibid., 1963, 66, 168.131 Proc. Fourth Cellulose Conf., ed. R. H. Marchessault, J . Polymer Sci., Part C,Polymer Xymp., 1963, 2.132 M. Marx-Figini and G. V. Schultz, Makromol. Chem., 1963, 62, 49.133 E. Husemann and R. Werner, Makromol. Chem., 1963, 59, 43.13* A. Frey-Wyssling and K. Muhlethaler, Makromol. Chem., 1963, 62, 25.59, 1.353.1963, 112, 223.Foundation Symp., J. and A. Churchill Ltd., London, 1964MANNERS : CARBOHYDRATES 441polymer.135 Many workers will welcome the publication of a book onmethods of cellulose chemistry.136The fungus Pullularia pulluktns produces a mixture of an a-glucan, a#?-glucan, and an acidic polysaccharide, in proportions dependent upon thenature of the carbohydrate in the culture medium.13‘ The a-glucan derivedfrom sucrose is a linear molecule of DP 280 containing maltotriose unitslinked by 1,6-linkages (1).In another laboratory,138 the fungus was grownon D-glucose to give a similar a-glucan, except that about 6% of a-1,3-linkages were also present.* * a-G1+ 6 x 4 1 -+ 4x-G1+ 4a-G1+ 6a-G1 * - (1)/I-Gl.16* #I-Gl+ 3/3-G1+ 3/l-G1+ 3/3-G1 * * * (2)During the past year the existence of a group of microbial polysaccharidesbased on structure (2) was reported. The individual a-glucans differ in DPand in proportion of 1,3- to 1,6-linkages.Examples have been isolatedfrom the culture media of Pullularia pullulans grown on ~ - x y l o s e , l ~ ~ of anunidentified fungi irnperfecta, 140 and of Cktwiceps purpurea.141 In theformer, for example, two out of every three glucose residues in the main-chain carry a lJ6-linked glucose residue. The #?-glucan of corn gum isclosely related to these p01ysaccharides.l~~Other #?-glucans examined include the reserve polysaccharides of theprotozoa Ochromonas malhamensis and Peranema trichophorum which con-tain /3-1,3-linkages and have DP’s of about 34 and 80, re~pectively,l~~ anda #?-glucan produced by Microsporum quinckeanum containing 57% of 1,6-and 24% of 1,3-linkages, which shows some resemblance to certain yeastglucans. 144 Structural studies on the cereal #?-glucans and cellulose havebeen ~ummar4sed.l~~Various aspects of the metabolism of starch, l46-8, glycogen,l46, 148, 149135 W.Brown, D. Henley, and J. Ohman, Malcromol. Chem., 1963, 62, 164.136 “ Methods in Carbohydrate Chemistry,” Vol. 3, ed. R. L. Whistler and M. L.137 H. 0. Bouveng, H. Kiessling, B. Lindberg, and J. McKay, Acta Chem. Scand.,138 W. Sowa, A. C. Blackwood, and G. A. Adams, Canad. J . Chern., 1963, 41, 2314.139 H. 0. Bouveng, H. Kiessling, B. Lindberg, and J. McKay, Acta Chem. Scand.,140 J. Johnson, S. Kirkwood, A. Misaki, T. E. Nelson, J. V. Scaletti, and F. Smith,Wolfrom, Academic Press, New York and London, 1963.1963, 17, 797.1963, 17, 1351.Chem. and Ind., 1963, p. 820.A. S. Perlin and W.A. Taber, Canad. J . Chem., 1963, 41, 2278.142 F. Smith, cited in ref. 139.143 A. R. Archibald, W. L. Cunningham, D. J. Manners, J. R. Stark, and J. F. Ryley,144 H. Alfes, C. T. Bishop, and F. Blank, Canad. J . Chem., 1963, 41, 2621.145 D. J. Manners, Recent Adv. Food Res., Vol. 3, ed. J. M. Leitch and D. N.146 J. S. Brimacombe and M. Stacey, “ Comparative Biochemistry,” Vol. 4, ed.14’ W. J. Whelan, Starke, 1963, 15, 247.148 D. J. Manners, Adv. Carbohydrate Chem., 1962, 17, 371.149 See, for example, papers by D. H. Brown, H. G. Hers, B. Illingworth, J. Lamer,D. J. Manners, E. Rosenfeld, and W. J. Whelan, in ref. 137.Biochem. J . , 1963, 88, 444.Rhodes, Butterworths, London, 1963, p. 291.M. Florkin and H. S. Mason, Academic Press, New York, 1962, p.27442 ORGANIC CHEMISTRYcellulose,146, 150, 151 and p-1,S-glucans 152 have been reviewed. Of particularinterest is the discovery of a new pathway in rabbit muscle for the enzymicdebranching of glycogen,153 and evidence that the amylose and amylopectincomponents of starch are synthesised by separate pathways.154HemiceZZuZoses. Studies on the fine structure of hemicelluloses con-taining a main chain of @-1,4-linked D-XylOpyranOSe residues, to whichvarious side-chains are attached, have continued. Using the principle ofoptical superposition, an equation relating the specific rotation of nativexylans with their content of 4-O-methylglucuronic acid and/or arabino-furanose residues has been de15ved.l~~ The equation gives values in goodagreement with literature data for 4-O-methylglucuronoxylans and arabi-noxylans (but not for 4-O-methylglucuronoarabinoxylans), and the resultsindicate an cc-linkage for the L-arabinofuranose residues.Enzymic hydro-lysis of a 4-O-methylglucuronoxylan from white birch 156 gave two seriesof oligosaccharides, one neutral and one acidic; the former were reducedto the corresponding alditols. The molecular rotations of the three seriesvary linearly with DP; the calculated and observed rotation values foresparto xylaii are in good agreement. The xylan from Mesta fibrelj' isgenerally similar to that from jute, roselle, or flax; it has a DP of 144, andthere is a small degree of branching in the main chain, where one-seventh ofthe xylose residues carry a 4-O-methylglucuronic acid residue linked throughC-2.The xylan from the roots of perennial rye-grass 158 resembles those ofother xylans from the Graminea in having side-chains of single L-arabino-furanose and 4-0-methylglucuronic acid residues, linked to C-3 and C-2,respectively, of main-chain xylose residues, together with more complex side-chains, e.g., 2-O-~-~-xy~opyranosy~-~-arabinofuranose and O-@-D-galacto-pyranosyl-( 1+4)-O-p-~-xylopyranosyl-( 1+2)-~-arabiiiose units ; however,the presence of terminal D-galactose residues is an unusual feature. Applica-tion of the Smith degradation to rye-flour arabinoxylan 159 has shown thatthe L-arabinofuranose side-chains are randomly attached along the mainxylan chain. With barley-husk arabinoxylan,15* the same procedureshowed that the 2 - 0-B- D - x ylop yranos yl - ~ - a r a binofuranose side - chains aredirectly linked to the main chain.Analysis of Rhodymenia palmata xylan 160by the Smith degradation, and by enzymic studies, showed that a smallproportion of adjacent p-l,3-linked D-xylopyranose residues are present inthe chain. Degradation of wheat arabinoxylan 161 with a XtreptomycesE. T. Reese, Pergamon - Press, Oxford, 1963.150 " Advances in Enzymic Hydrolysis of Cellulose and Related Materials," ed.151 J. A. Gascoigne, Chem. and Ind., 1963, 1580.152 A. E. Clarke and B. A. Stone, Rev. Pure Appl. Chem. (Australia), 1963, 13, 134.153 M. Abdullah and W. J. Whelan, hTature, 1963, 197, 979; D. H. Brown, B. Illing-164 0. E. Nelson and H.W. Rines, Biochern. Biophys. Res. Comm., 1962, 9, 297;165 R. H. Marchessault, H. Holava, and T. E. Timell, Canad. J . Chem., 1963,41, 1612.156 R. H. Marchessault and T. E. Timell, J. Polymer Sci., Part C, Polymer Symp.,15' S. K. Sen, Canad. J . Chem., 1963, 41, 2346.15* G. 0. Aspinall, I. M. Cairncross, and K. M. Ross, J., 1963, 1721.159 G. 0. Aspinall and K. M. Ross, J., 1963, 1681.l6O D. J. Manners and J. P. Mitchell, Biochem. J., 1963, 89, 92P.1 6 1 H . R. Goldschmid and A. S. P e r k , Canad. J . Chem., 1963, 41, 2272.worth, and C. F. Cori, ibid., p. 980.R. B. Frydman, Arch. Biochern. Biophys., 1963, 102, 242.1963, 2, 49MANNERS : CARBOHYDRATES 443xylanase preparation gave a mixture of oligosaccharides including a newtetrasaccharide (3), and the results indicated that the xylan molecules wereB-D-xyl~l-t4B-D-xyl~l~ 4p-D-xYlp3a-L-Arafl(3)constituted mainly of highly-branched regions in which isolated and pairedL-arabinosyl branches are separated by single D-XylOSJd residues.Diboranereduction of elm ( Ulmus americana) 4-O-methylglucuronoxylan followed bypartial acid hydrolysis gave 162 the neutral trisaccharide O-cc-4-O-methyl-~-glucopyranosyl -( 1+ 2) - 0 - - D - xylopyranosyl- (1+ 4) - D-xylopyranose. Theeffect of glucuronic acid side-chains on the stability of xylopyranosidiclinkages in the main chain is discussed. The solution properties of birchxylan have been examined,l63 and a weight-average and number-averageDP of 178 and 151 obtained, showing the low degree of polydispersity of theextracted pol y sa c c haride.The water-soluble arabinogalactans of European and mountain larchesare very similar,l64 and contain main-chains of 1,3-1inked D-galactoseresidues, each of which is substituted at C-6 by a side-chain of 1,6-linkedD-galactose residues, or by other residues ; however, mountain larch containsD-glucuronic acid as non-reducing terminal residues.The same residue hasnow been found lfj5 in tamarack “arabinogalactan” since a partial acidhydrolysate contained 6-O-(~-~-glucopyranosyluronic acid)-D-galactose. Itis suggested that “ arabinogalactoglucuronoglycans ” may OCCUT morewidely than is at present believed.Major problems of isolation and purification frequently arise, owing to thepresence of complex mixtures of polysaccharides in extracts of many planttissues.Examples of current fractionation methods are given in the follow-ing recent studies. The hemicellulose B fraction of corn stalk 166 contains amixture of a p-l,4-glucan, an arabinoxylan (comprising a main xylan chainand short linear side-chains terminated by L-arabinofuranose and D-xylo-pyranose residues), and an acidic polysaccharide containing D-xylose (57 yo),L-arabinose (23%), D-glucuronic acid (lo%), and D-galactose (9%). Aqueousextraction of Scots pine gave 16’ a partly acylated galactoglucomannan, anarabinogalactan, and traces of an acidic xylan. The former containedessentially linear chains of I ,4-linked 8-D-glucopyranose and P-D-manno-pyranose residues, in the ratio 1 : 3, to which D-galaCtOpy3XbnOSe residueswere attached, probably as side-chains.The arabinogalactan consisted ofmain chains of 1,3-linlced /?-D-galaCtOpyI’anOSe residues to which various side-chains (including L-arabinofuranose end-groups) were attached. From the162 S. C. McKee and E. E. Dickey, J . Org. Chem., 1963, 28, 1561.le3 R. G. LeBel, D. A. I. Goring, and T. E. Timell, J . Polymer Xci., Part C, Polymer164 J. K . N. Jones and P. E. Reid, J. Polymer Xci., Part C, Polymer Symp., 1963,166 B . Urbas, C. T. Bishop, and G. A. Adams, Canud. J . Chem., 1963, 41, 1522.166 R. E. Gramera and R. L. Whistler, Arch. Biochem. Biophys., 1963, 101, 7 5 .167 G. 0. Aspinall and T. M. Wood, J., 1963, 1686.tSyrnp., 1963, 2, 9; R. G. LeBel and D. A.I. Goring, ibid., p. 29.2, 63444 ORGANIC CHEMISTRYwood of Amubilis fir 168 a mixture of an arabino-4-O-methylglucuronoxylan,a water - solu ble galac t oglucomannan , and an a1 kali - solu ble gala ct oglu -comannan (of different composition) was isolated, the yields being 7, 4, andS%, respectively. A similar mixture of three hemicelluloses was extractedfrom Engelmann spruce WOO^,^^^ but the respective yields were 8, 1, and 8%.Hot-water extraction of certain varieties of pine wood 170 gavea mixture of apectic acid, a galactoglucomannan, an araban, and a glucuronoarabinoxylo-galactan. The terminal groups of the latter included a small proportion of/?-D-glucopyranosyluronic acid and a-D-xylopyranose residues, in addition tothe more usual D-galactopyranose end-groups.The presence of small quantities of the branched-chain pentose apiose inacid hydrolysates of certain plant polysaccharides will stimulate furtherinvestigation of their fine structure.171Diborane reduction of acetylated gumarabic converted D-glucuronic acid residues into D-ghCOSe.172 Acetolysisfollowed by deacetylation gave a mixture of oligosaccharides including4-O-a-~-rhamnopyranosyl-~-g~ucose.This observation, together with pre-vious work, shows that the sequence (4) is an important structural feature.Plant gums and polyuronides.or-~-Rhapl+4/l-~-GpAl+6~-Galpl (4)3The work emphasises the value of acetolysis as an alternative method forthe linkage analysis of polysaccharides.Fractionation of the water-soluble part of gum tragacanth gave traga-canthic acid and an arabinogala~tan.l7~ The former contains chains ofa-l,4-linked D-galacturonic acid residues, the majority of which carry xylose-containing side-chains through C-3 ; the latter include single xylopyranoseresidues, and disaccharide units of 2-O-a-L-fucopyranosyl-D-xylopyranose and2- O-B-D -galactop yranosyl-D -xylop yranose. The arabinogalactan consistsmainly of interior chains of 1,6-linked D-galactopyranose residues whichcarry highly branched exterior chains of 1,2-, 1,3-, and lY5-linked L-arabino-furanose residues.74Methylation studies of acid-degraded (i.e., arabinose-free) gum fromVirgiliu oroboides revealed a complex structure with 1,6-linked D-galacto-pyranose, lY2-linked D-mannopyranose, and a small proportion of 1,3-linkedD-galactopyranose residues, and various end-groups including D-glucuronicacid.l75 Application of the Smith degradation to mesquite gum showed 176the presence of both 1,6- and 1,4-linked D-galactopyranose residues in themain chain, and the probable presence of acids other than 4-O-methyl-168E.C. A. Schwarz and T. E. Timell, Canad. J . Chem., 1963, 41, 1381.1ssA. R. Mills and T. E. Timell, Canad. J . Chem., 1963, 41, 1389.17oA. J. Roudier and L. Eberhard, Bull. SOC. chim. France, 1963, 844.171 J. S. D. Bacon, Biochem. J., 1963, 89, 103P.1 7 2 G. 0. Aspinall, A. J. Charlson, E. L. Hirst, and R. Young, J., 1963, 1696.173 G. 0. Aspinall and J. Baillie, J . , 1963, 1702.174 G. 0. Aspinall and J. Baillie, J., 1963, 1714.176A. M.Stephen, J., 1963, 1974.176 G. G. S. Dutton and A. M. Unrau, Canad. J . Chem., 1963, 41, 1417MANNERS : CARBOHYDRATES 445glucuronic acid. Salrnaliu rnalabarica gum also has a branched structure, 17'with main chains of 1,3-linked D-galactopyranose residues and side-chainsattached a t C-4 ; the side-chains may include 6-O-#?-~-galacturonosyl-~-galactose units. However, caution is required in the deduction of details offine structure, as distinct from general structure, since significant variationin the composition of gum isolated from different nodules may occur. Forexample, the uronic anhydride content of nine nodules of Acacia seyal gumvaried from 12-1 to 16-8y0.178Developments in the chemistry of pectic substances were discussed a t arecent symposium.179 It is now clear that many purified pectic acidscontain varying proportions of neutral sugars (including L-arabinose,D-galactose, and L-rhamnose) and are not simply chains of ~-1~4-linkedD-galacturonic acid residues, which may be partly esterified.180 Other topicsincluded the chemical degradation of pectic substances under alkaline andneutral conditions, and degradation by microbial enzymes which produce,by trans-elimination mechanisms, unsaturated derivatives of galacturonicacid.181A general classification of plant polysaccharides, particularly plant gumsand pectic substances, in terms of the chemical structure has been suggested,and historical developments in the chemistry of protopectin have beenreviewed.l 8 2Algal polysaccharides. Partial acid hydrolysis of diborane-reducedalginic acid gave a mixture of sugars including a mannosylgulose disaccharide,thus confirming the presence of both mannuronic and guluronic acid inalginic acid.ls3 A study of the degradation of alginate at 68" over the pHrange 5-10 showed that the extent of the 8-elimination reaction variedmarkedly with pH, but was still significant in neutral s01ution.l~~ The rateof degradation was increased by various reducing agents.Methanolysis of fucoidan from Macrocystis pyrifera caused both depoly-merisation and removal of sulphate groups, and gave a high yield of methyla-~-fucoside.l~~ The polysaccharide also contained about 6% of D-galactosewhich is therefore a heteropolymer containing L-fucose and D-galactoseresidues in the ratio of 18 : 1.The 3 ~ - and A-components of carrageenan are structurally related.186The former contains an alternating sequence of lY3-linked D-ga,lactose and1,4 - linked 3 , 6 - anhydro - D - galactos e residues whereas in 1 -carrageenan , theanhydro-sugar residues are replaced by D-galactose 2,6-disulphate residues.In both components, some of the D-galaCtOSe residues are sulphated at (2-4.177 S.Bose and A. S. Dutta, J . I n d . Chem. Soc., 1963, 40, 257, 557.178 D. M. W. Anderson and M. A. Herbich, J., 1963, 1.179 Abs. 144th Amer. Chem. SOC. Meeting, 1963, pp. 9C-13C.I8O G. 0. Aspinall, ref. 179, p. 9C.181 See papers by H. Neukom, H. J. Phaff, C. W. Nagel, J. D. MacMillan, and W. W.182 G.0. Aspinall in ref. 145, p. 282; M. A. Joslyn, Adv. Food Res., 1962, 11, 2.lS3 E. L. Hirst, E. Percival, and J. K. Wold, Chem. and Ind., 1963, 257.184 A. Haug, B. Larsen, and 0. Smidsrod, Acta Chem. Xcand., 1963, 17, 1466; 0.lE5 R. G. Schweiger, J . Org. Chem., 1962, 27, 4267, 4270.186 D. A. Rees, J., 1963, 1821.Kilgore in ref. 179.Smidsrod, A. Haug, and B. Larsen, ibid., p. 1473446 ORGANIC CHEMISTRYThe interaction of carrageenan with gelatine l S 7 and with basic dyes 188 hasbeen examined.Water-soluble sulphated heteropolysaccharide from Ulva lactuca, likethat from Enteromorpha cmpressa and Acrosiphonia centralis, containsglucose, glucuronic acid, xylose, and rhamnose (a proportion of the last twosugars being 2-sulphated), a high proportion of 1,3-linkagesY and the aldo-biouronic acid 4-O-glucuronosyl-~-rhamnose, possibly as an end-group.189Studies on these polysaccharides pose addi-tional problems since many contain unusual monosaccharides 01' amino-acidor phospholipid constituents.For example, the C-polysaccharide from astrain of pneumococcus contains four aniino-acids and four amino-sugars,including 35% of D-galactosamine 6-phosphate (isolated for the first timefrom bacterial cell walls), llyo of D-glucosamine and muramic acid and4% of muramic acid phosphate. lS0 Other recently identified constituentsinclude N-acetylglucosamine-uronic acid from a polysaccharide fromHemophihs in$uenxa?, type d, lgl D-glycero-D-manno-heptose from an extra-cellular polysaccharide from Axotobacter indicum, lg2 D-fucosamine in alipopolysaccharide from the cell wall of Chromobacterium violaceum,l93mannose-containing derivatives of glycerol myoinositol phosphate from astrain of Mycobacterium tuberculosis, and the N-acetyl derivative of 2-amino-2 -deoxymannuronic acid from the cell walls of Micrococcus Zyso-diekticus, where this sugar alternates with 6-substituted glucose residues.195Many Xanthomonas species produce complex heteropolysaccharides com-posed of D-glucose, D-mannose, and D-glucuronic acid, but also containing1-7% of pyruvic acid.lQ6 I n Xanthomonas campestris, the latter is attachedto D-glucose side-chains as a 4,6-0-( l-carboxyethylidene) group. Hydro-lysis of these polysaccharides also gives the aldobiouronic acid, ~-O-(/?-D-glucopyranosyluronic acid) -D-mannose. Methylation studies show lg7 thepresence of 1,2-linked D-mannose residues in Xanthomonas hyacinthi.Otherspecies, e.g., Xanthmonus stewartii lg7 and X . v e ~ i c a t o r i a , ~ ~ ~ contain D-galactose instead of D-mannose.Methylation studies suggest that the acidic polysaccharide of Klebsiellapnezmoniz type A contains 1,3-linked D-glucose and L-fucose residues,with glucose also comprising the non-reducing terminal group ; D-glucuronicacid is also present.lg* Alkaline hydrolysis of the specific substance fromPneurnococcus type 34, followed by enzymic dephosphorylation, gave apentasaccharide repeating unit-O-D-galactofuranosyl- ( 1 +3)-o-a-D-gluco-Bacterial polysacchccrides.18'E. A.MacMullan and F. R. Eirich, J . Colloid Sci., 1963, 18, 526.188 A. L. Stone, L. G. Childers, and D. F. Bradley, BiopcZymers, 1963, 1, 111.l90 T. Y. Liu and E. C. Gotschlich, J . Biol. Chem., 1963, 238, 1928.lgl A. R. Williamson and S. Zamenhof, J . Biol. Chem., 1963, 238, 2255.lg2 J. K. X. Jones, M. B. Perry, and W. Sowa, Canad. J . Chem. 1963, 41, 2712.193 R. 'CV. Wheat, E. L. Rollins, J. M. Leatherwood, and R. L. Barnes, J . Biol.lg4 C. E. Ballou, E. Vilkas, and E. Lederer, J . Biol. Chem., 1963, 238, 69.lg5 H. R. Perkins, Biochem. J., 1963, 86, 475.ls6 D. G. Orentas, J. H. Sloneker, and A. Jeanes, Canad. J . Microbial., 1963, 9, 427.lg7 P. A. J. Gorin and J. F. T. Spencer, Canad. J . Chem., 1963, 41, 2357.lg8 S. A. Barker, J. S . Brimacornbe, J.L. Eriksen, and 11. Stacey, Nature, 1963,E. Percival and J. K. Wold, J., 1963, 5459.Chem., 1963, 238, 26.19'7, 899MANNERS : CARBOHYDRSTES 447pyranosyl- (1+2) -O-~-galactofuranosy1-( 1+3) -0-a-D-galactopyranosyl- (1-+2) -ribitol. lg9Studies on teichoic acids have been continued by Baddiley and his co-workers. The intracellular glycerol teichoic acids from two streptococcalstrains are glycerol phosphate polymers in which most of the glycerol unitspossess cc-l,2-linked glucose residues as either kojibiose (strain 39) orkojitriose (strain 8191 ) substituents. 201The chemical synthesis of polysaccharides isnow receiving increased attention. Acid polymerisation of D-glucose orD-xylose leads to the formation of highly branched polysaccharides contain-ing both pyranose and furanose residues joined together by several types ofglycosidic linkage.2oA further series of polysaccharides have been prepared from amylose bythe introduction of various side-chains. For example, mono- and di-saccharide units were attached by 1 ,6-linkagesY by treatment of 6-trityl-2,3-dicarbanilylamylose with cc-acetobromo-glucose, -maltose, or -cellobioseunder appropriate conditions. 203 Side-chains of 3-6 glucose residues havealso been attached to amylose, and these could be further lengthened by thesynthetical action of potato phosphorylase. Side-chains of single glucoseresidues have also been added to amylose by treatment with tetra-acetyl-l-isocyanato-glucose. 204Finally, linear polymers containing glucose residues have been pre-pared 205 by polperisation of the 3-O-methacryloyl ester of 1,2 : 5,6-di-O-isopropylidene-a-D-glucofuranose (6), followed by acid treatment (5), or ofthe 3-O-vinyl ether (6).Synthetic polysaccharides.cCHISOHHOCO OH- CMe - CH2- 1 '(5)1lQ9 W.K. Roberts, J. G. Buchanan, and J. Baddiley, Biochem. J., 1963, 88, 1.g o o J. Baddiley, J . Roy. Imt. Chem., 1962, 366.201 A. J. Wicken and J. Baddiley, Biochem. J., 1963, 87, 54.202 G. G. S. Dutton and A. M. Unrau, Cunad. J. Chem., 1962, 40, 1196, 1479, 2101,2 0 3 E . Husemann and M. Reinhardt, Mukyornol. Chem., 1962, 57, 109, 129.204 E. Husemann and A. P. 0. Schmidt, Makromol. Chem., 1963, 65, 114.205 W. A. P. Black, E. T. Dewar, and D. Rutherford, J., 1963, 4433.2105; 1963, 41, 243913.AMINO-ACIDS AND PEPTIDESBy R. C. SheppardTHIS year, aspects of the chemistry of peptides and proteins are reviewed inboth the Organic Chemistry and Biological Chemistry sections of theseReports. Readers are referred to the Biological Chemistry section fordiscussion of methods and results of sequence analysis of peptides andproteins, as well as biological aspects of peptide and protein structure.Proceedings 1 of the Fifth European Peptide Symposium (Oxford, 1962)include further suggestions for amino-acid and peptide nomenclature,revising and extending the I.U.P.A.C. " Tentative Rules." 3 These newsuggestions will be adopted throughout this Report.Amino-acids.-A number of new natural amino-acids have been identi-fied since the last Report.4 2-Amino-4-pyrimidylalanine (lathyrine) (1) hasbeen isolated from Luthyrus tingit~nus.~ Two related amino-acids, L-homo-arginine 6 (2; R = H), and y-hydroxy-L-homoarginine (2 ; R = OH) alsooccur in various Lathyrus species, and are probable biogenetic precursors oflathyrine.m-Carboxy-L-tyrosine (3) has been isolated from seeds of Resedaodorata.8 Together with m-carboxyphenylalanine and m-carboxyphenylgly-cine, it also occurs in Lunaria ~ n n u a . ~ Hydrolysis of the antibiotic thio-strepton has yielded a further thiazole amino-acid (4), lo presumably derivedbiogenetically from adjacent dihydroxyleucine and cysteine residues. l1CHc.co2- II(4)1 Peptides, Proc. Fifth European Peptide Symp., Oxford, Sept.1962, ed. G. T.2 R. Schwyzer, J. Rudinger, E. Wunsch, and G. T. Young, ref. 1, p. 261.3 " Tentative Rules for Abbreviations and Symbols for Chemical Names of Special4 Ann. Reports, 1961, 58, 300.ti R. A. Bell and R. G. Foster, Nature, 1962, 194, 91.Young, Pergamon Press, Oxford, 1963.Interest in Biological Chemistry," Bull. SOC. Chim. biol., 1960, 42, 731.S. L. N. Rao, L. K. Ramanchandran, and P. R. Adiga, Biochemistry, 1963,E. A. Bell, Nature, 1963, 199, 70.2, 298; E. A. Bell, Biochern. J., 1962, 85, 91.8 L. P. 0. Larsen and A. Kjzer, Acta Chem. Xcand., 1962, 16, 142.9 L. P. 0. Larsen, Acta Chem. ScanJd., 1962, 16, 1511.lo M. Bodanszky, J. Alicino, C. A. Birkhimer, and N. J. Williams, J . Amer. Chem.l1 D. F. W. Cross, G. W. Kenner, R. C.Sheppard, and C. E. Stehr, J., 1963, 2143.SOC., 1962, 84, 2003SHEPPARD : AMINO-ACIDS AND PEPTIDES 449Formation of the bisthiazole (5) on alkaline degradation of cystine has alsobeen noted.12 A new cysteine derivative (6) has been isolated from theurine of hypocholesterolemic patients. l3trans-3-Hydroxy-~-proline (8) has been isolated from Mediterraneansponge,14 and from collagen.14, l 5 Both the cis- and trans-isomers have beenfound in hydrolysates of the antibiotic telomycin,16, l7 but these do notarise by epimerisation during hydrolysis.17 Hydroboration of benzyloxy-carbonyl-3,4-dehydro-~~-proline methyl ester (9 ; R = OMe) provides astereospecific synthesis of racemic (8) ; after oxidation of the diborane adductand removal of protecting groups, 63% of (8) and 10% of the correspondingtrans-4-hydroxyproline (10) are obtained.1 4 Several other syntheses of (8)have also been described.15, 16, l8 Sodium borohydride reduction ofbenzyloxycarbonyl-3-oxoproline methyl ester yields 37 yo of the cis- and63% of the trans-3-hydroxyproline derivatives.17 This contrasts with the4-oxo-series where similar reduction yields exclusively the ~is-is0mer.l~The racemic form of 4-methyleneproline (11) has been isolated fromseeds of loquat (Eriobotrya japonica) ;20 hydrogenation yields mainly cis-4-methyl- DL- proline. Benz ylox y car bonyl- 4- met h ylene - ~ - p r oline has beensynthesised by Wittig reaction between benzyloxycarbonyl-4-oxo-~-prolineand trimethylphenyl phosphorane. 21 Hydroboration with di-isoamylboraneof the benzhydryl ester of the resulting benzyloxycarbonyl-4-methylene-~-proline has yielded 4-hydroxymethyl-~-proline, 22 identical with the naturalamino-acid.Since attack by the bulky borane is presumed to take placefrom the least-hindered side of the 4-methyleneproline derivative, supportis provided for the cis-configuration (12) of natural hydroxymethylproline.This is in agreement with the similarity in n.m.r. spectra of the hydroxy-methyl derivative and cis-4-methylproline7 23 although mass-spectral datahave been interpreted in favour of a trans-str~cture.~~ Full details haveappeared of the stereospecific syntheses of cis- and trans-4-methylprolineYboth isomers of which are of natural occ~rrence.~~The chemistry of 3,4-dehydroproline has been studied in detail.26, 27l 2 H.Zahn and E. Golsch, Chem. Ber., 1963, 96, 438.l3 S. Oomori and S. Mizuhara, Arch. Biochem. Biophys., 1962, 96, 179.l4 F. Irreverre, K. Morita, A. V. Robertson, and B. Witkop, J. Amer. Chem. SOC.,l5 H. D. Ogle, R. B. Arlinghaus, and M. A. Logan, J . Biol. Chem., 1962,237, 3667.l6 J. C. Sheehan and J. G. Whitney, J. Amer. Chem. SOC., 1962, 84, 3980.F. Irreverre, K. Morita, S. Ishii, and B. Witkop, Biochem. Biophys. Res. Comm.,K. Morita, F. Irreverre, F. Sakiyama, and B. Witkop, J. Amer. Chem. SOC.,A. A. Patchett and B. Witkop, J. Amer. Chern. SOC., 1957, 79, 185.1963, 85, 2824; Biochem. Biophys. Res. Comm., 1962, 8, 453.1962, 9, 69.1963, 85, 2832.2 o D. 0. Gray and L. Fowden, Nature, 1962, 193, 1285.21 M.Bethell, G. W. Kenner, and R. C. Sheppard, Nature, 1962, 194, 861.2 2 M. Bethell, D. Bigley, and G. W. Kenner, Chem. and Ind., 1963, 653; cf. A. W.23 R. J. Abraham, K. A. McLauchlan, S. Dalby, G. W. Kenner, R. C. Sheppard,2 4 K. Biemann, G. G. H. Deffner, and F. C. Steward, Nature, 1961, 191, 380.25 J. S. Dalby, G. W. Kenner, and R. C. Sheppard, J., 1962, 4387.*6 A. V. Robertson and B. Witkop, J. Amer. Chern. Soc., 1962, 84, 1697.2 7 A. IT. Robertson, J. E. Francis, and B. Witkop, J . Amer. Chern. SOC., 1962, 84,Burgstahler and C. E. Aiman, ibid., 1962, 1430.and L. F. Burroughs, Nature, 1961, 192, 1150.liO9.450 ORGANIC CHEMISTRYBecause of the allylic nature of the asymmetric carbon atom, derivatives of3,4-dehydroproline are optically labile, especially the amide derivative.Asymmetric hydrolysis of the DL-amide by the enzyme hog kidney amidaseyields more than 50% of the L-amino-acid, providing a first example ofenzymic resolution combined with simultaneous racemisation of an opticallylabile substrate. 26 With N - bromsuccinimide, benzyloxycarbonyl-3,4-de-hydroprolinamide (9 ; R = NH,) is converted into the remarkable carbinol-amine derivative ( 13).The polyfunctional amino-acid amide structure (14 ; R = NH,, R' = H)has a t last been established for the plant toxin, lycomarasmine.28 Itscyclisation product, anhydrolycomarasminic acid (1 6 ) has been synthesisedby the route S ~ O W ~ .~ ~ The related toxins aspergillomarasmines A and Bhave been identified as lycomarasminic acid (14; R = OH, R' = H) andits aminomethyl derivative (14; R = OH, R' = CH,*NH,), respe~tively.~OThe analogue (15) simply prepared 31 by reaction between ethylenediamineand monobenzyl maleate also has lycomarasmine-like activity.H02C .CHI C02H .H02C.CH CHz* CO2HH02C * CH -NH *CH2 * CH *NH*CHR'*CO.RI I I IHOZC. CH.NH.CH2.CHZ-NH *CH .C02H(1 4) (15)Et02CaCH2 COlEt EtOZC.CH2 7 0 2 E tEt02C * CH * NH2I 4- I - CH2 = C CI EtOl C * CH . NH CH2 * CH C INH1-CHl*CO,EtEtOZCmCH2 C02EtEt02C.CH *NH .CH2 * CH .NH *I ICH2 * COZEtA new approach to the asymmetric synthesis of optically active amino-acids involves catalytic reduction of or-keto-acids in the presence of D- or2 * E. Hardegger, P. Liechti, L. M. Jackman, A.Boller, and P. A. Plattner, Helv.Chim. Acta, 1963, 46, 60.2 9 E. Hardegger, J. Seres, R. Andreatta, F. Szabo, W. Zankowska-Jasinka, A.Romeo, Ch. Rostetter, and H. Kindler, Helv. Chim. Acta, 1963, 46, 1065.3O M. Robert, M. Barbier, E. Lederer, L. ROUX, K. Biemann, and W. Vetter,Bull. SOC. chinz. Frunce, 1962, 187; A.-L. Haenni, M. Barbier, and E. Lederer, Compt.rend., 1962, 255, 1476.M. Barbier, D. Bogdanovsky, W. Vetter, and E. Lederer, Annalen, 1963,668,132SHEPPARD : AMINO-ACIDS AND PEPTIDES 451~-ac-methylbenzylamine.32 Reduction takes place through the intermediateSchiff's base and is sterically controlled. Thus pyruvic acid hydrogenatedin the presence of L-a-methylbenzylamine yields alanine containing 91 yo ofthe L-isomer. cc-Methylbenzylamides of acetamidoacrylic acids are similarlyreduced, but less selectively and in the opposite sense, i.e., the L-a-methyl-benzylamide induces preferential formation of the D-amino-acid.33 Additionof benzylamine to a/l-epoxy-acids provides a versatile new stereospecificsynthesis of a-amino-p-hydroxy-acids. Thus (trans-) crotonic acid yieldsallothreonine free of threonine and a-hydroxy-@-amino-acids, after hydro-genolysis of the benzyl group.34 Maleic and fumaric acids similarly yieldthe theo- and erythro-isomers of p-hydroxyaspartic acid, and several otherexamples have been recorded.The need for optically pure N-methylamino-acids, especially for anti-biotic and depsipeptide synthesis, has led to the development of new pre-parative methods.Methylation of toluene-p-sulphonamido-acids frequentlyleads to partially racemised products. 35 However, methylation of benzyl-amino-acids (prepared by in situ reduction of benzylidene derivatives)yields fully active N-benzyl-N-methylamino-acids, from which the benzylgroup can be removed by hydrogenolysis.36 An entirely new methodillustrated by the preparation of N,-methyltryptophan makes use ofy-chlorobutyryl derivatives (17) which are cyclised by silver fluoroborate toimino-ethers ( 18). Methyl iodide then yields the quaternary monomethylderivative from which the protecting group is split by very mild alkalinetreatment. 37ClCH,*CH,*CH,CO*XHCHR*CO,Me CH ,CH ,.CH,*C = N-CHRCO ,Me-0-(17) (18)Importa& advances in instrumentat'ion now enable mass spectra ofamino-acids and their hydrochlorides to be rec0rded,~8 obviating the needfor the preparation of volatile deri~atives.3~ The characteristic fragmenta-tion patterns should greatly facilitate the rapid identification of new naturalamino-acids isolated on a micro-scale.The technique is also applicable tosuitable derivatives of short peptides, offering a promising new method ofsequence determination.*o 0.r.d. methods, used for the assignment of32 R. G. Hiskey and R. C. ru'orthrop, J. Amer. Chem. SOC., 1961, 83, 4798.3 3 J. C. Sheehan and R. E. Chandler, J. Anzer. Chem. SOC., 1961, 83, 4795.34 Y. Liwschitz, Y. Rabinsohn, and D. Perera, J., 1962, 1116; Y. Liwschitz, Y.35 cf. Yu. A. Ovchinnikov, V. T. Ivanov, and A. A. Kiryushkin, Izvest.Akad. Kauk36 P. Quitt, J. Hellerbach, and K. Vogler, Helv. Chirn. Acta, 1963, 46, 327.37 H. Peter, M. Brugger, J. Schreiber, and A. Eschenmoser, Helv. Chim. Acta,1963, 46, 577.3* K. Biemann and J. A. McCloskey, J. Amer. Chem. SOC., 1962, 84, 3192; G. Junkand H. Svec, J. Amer. Chem. SOC., 1963, 85, 839.39 e.g., K. Biemann, J. Seibl, and F. Gapp, J. Amer. Chem. SOC., 1961, 83, 3795;C. 0. Andersson, R. Ryhage, S. Stallberg-Stenhagen, and E. Stenhagen, Arkiv. Kern;,1962, 19, 405, 417.40 F. Weygand, A. Prox, W. Konig, and H. H. Fessell, Angew. Chem., 1963, 75,784; K. Heyns and H. F. Griitzmacher, Tetrahedron Letters, 1963, 1'161.Rabinsohn, and A. Haber, J., 1962, 3589.S.S.S.R., Otdel. khim. Nauk, 1962, 2046452 ORGANIC CHEMISTRYabsolute configuration to amino-acids and N-terminal amino-acids in pep-tides,41 have been extended to include phthaloyl derivative^.^^ Thiobenzoyland phenylthioacetyl derivatives are unreliable for this purpose, however.43Peptide Synthe~is.~~--Protectinq groups.45 The protection of side-chainand terminal amino and carboxyl groups by t-butyloxycarbonyl and t-butylester groups is now widespread, and has made possible the synthesis of manymajor peptides containing sensitive amino-acids.The distinctive feature ofthese protecting groups is their ease of removal under very mild acidic con-ditions, e.g., by dissolution in trifluoroacetic acid a t room temperature, con-ditions which do not affect the side-chains of amino-acids such as serine,methionine, and tryptophan.A new preparation of t-butyloxycarbonyl-azide, used for the introduction of t-butyloxycarbonyl groups, has beendescribed,46 and improvements have been effected in the preparation ofE-t-butyloxycarbonyl-lysine derivative^.^' Full details of Roeske’s methodfor the preparation of amino-acid t-butyl esters have now appeared.48Side-chain hydroxyl groups are not extensively etherified under these con-ditions. The /3- and y-t-butyl esters of benzyloxycarbonylaspartic 49 andglutamic 50 acids have been prepared via the a-alkyl esters, and by directtransesterification with t-butyl acetate.51 The /?-t-butyl ester of aspartylresidues in peptides shows greater lability towards alkali than is normal fort-butyl esters, doubtless due to participation of the adjacent amide groupwith the formation of succinimide derivative^.^^ The same effect is observedwith the a-t-butyl ester of asparagine derivative^.^^ Side-chain hydroxylgroups of serine, threonine, hydroxyproline, and tyrosine can be protected ast-butyl ethers if ne~essary.~3~, The ethers are cleaved under the usualacidic conditions. The t-butyl group is not suitable for the protection ofthe thiol group of cysteine, however, as the t-butyl sulphide requires drasticconditions for its cleavage.53b, 5 4 The selection removal of t-butyloxycar-Bony1 and t-butyl ester in combination with other protecting groups has41 C. Djerassi, K. Undheim, R. C. Sheppard, W. G. Terry, and B. Sjoberg, ActaChene. Scand., 1961, 15, 903; R. C.Sheppard, Coll. Czech. Chem. Comm., 1962, 27, 2251.4 2 C. Djerassi, E. Lund, E. Bunnenberg, and J. C. Sheehan, J . Org. Chem., 1961,26, 4509.43 B. Sjoberg, B. Karlen, and R. Dahlbom, Acta Chem. Scand., 1962, 16, 1071.4 4 For recent reviews see: N. F. Albertson, Org. Reactions, 1962,12,157; J. Rudinger,Record Chem. Progress, 1962, 23, 3; J. Meienhofer, Chirnia (Switz.), 1962, 16, 385;T. Wieland and H. Determann, Angew. Chem., 1963, 75, 539.4 5 For a, review of amino-protecting groups, see R. A. Boissonnas, Adv. Org. Chem.,1963, 3, 159.46 L. A. Carpino, J . Org. Chem., 1963, 28, 1909.4 7 K. Sturm, R. Geiger, and W. Seidel, Chem. Ber., 1963, 96, 609.4 8 R. Roeske, J . Org. Chem., 1963, 28, 1251.4 9 R. Schwyzer and H. Dietrich, Helv. Chim. Acta, 1961, 44, 2003; E.Wiinsch andA. Zwick, 2. physiol. Chem., 1962, 328, 235; 1963, 333, 108.R. Schwyzer and H. Kappeler, Helv. Chim. Acta, 1961, 44, 1991; E. Kleiger andH. Gibian, Annalen, 1962, 655, 195.51 E. Taschner, A. Chimiak, J. F. Biernat, C. Wasiellewski, and T. Sokolowska,Amden, 1963, 663, 188.5 2 R. Schwyzer, B. Iselin, H. Kappeler, B. Riniker, W. Rittel, and H. Zuber,Helv. Chim. Acta, 1963, 48, 1975.53 (a) H. C. Beyerman and J. S. Bontekoe, Rec. Truv. chinz., 1962, 81, 691;( b ) F. M. Callahan, G. W. Anderson, R. Paul, and J. E. Zimmerman, J . Amer. Chem.SOC., 1963, 85, 201.5 4 A. Chimiak, ref. 1, p. 37SHEPPARD : AMINO-ACIDS AND PEPTIDES 453been discussed by Schwyzer and Kappeler;55 a noteworthy feature is theselective cleavage of t-butyloxycarbonyl in the presence of a, #?, or y-t-butylesters.Several other acid-sensitive protecting groups (in addition to theimportant trityl derivatives) have been examined.Ring substituents fend-ing to stabilise the benzyl cation should make benzyloxycarbonyl derivativesmore easily cleaved by acid, and this is found to be the case with p-methoxy-deri~atives.~s Thus, p-methoxybenzyloxycarbonylamino-acids and -pep-tides (prepared via the crystalline azide) are cleaved by trifluoroacetic acida t O", preferably in the presence of an easily substituted aromatic compound,such as anisole, which prevents undesirable polymerisation or other side-reactions. These derivatives in combination with benzyl esters have foundapplication in the synthesis of extended y-glutamyl pep tide^.^' p-Methoxy-benzyl esters also show increased lability towards acid.56 Like benzyloxy-carbonyl derivatives and benzyl esters, the p-methoxy-derivatives are ofcourse also cleaved by hydrogenolysis.Two promising new protecting groups have been examined which con-tain acid-sensitive sulphur-nitrogen bonds. 58 Tritylsulphenyl derivatives,prepared from the corresponding sulphenyl chloride, Ph,-C=S*Cl, and amino-acid esters are free from the massive steric hindrance usually shown byN-tritylamino-acids, and couple well by the active ester method. o-Nitro-phenylsulphenyl derivatives have also been prepared. These have theadvantage of being accessible directly from the amino-acid and can becoupled to form peptide derivatives by several methods.Both groups arecleaved almost instantly by two equivalents of hydrogen chloride in ethylacetate, with the regeneration of the sulphenyl chloride. Schiff's basederivatives of o- hydroxy-aromatic aldehydes 59 and enolisable b-dicarbonylcompounds 6o have also been advocated as protecting groups. The arylideneor alkylidene derivatives are stabilised by hydrogen bonding, e.g., as in (19),although the aliphatic derivatives may exist in the enamine form (20).60Sensitivity to acid is extreme, and the derivatives of amino-acids appear tobe stable only as their esters or salts. Cleavage is immediate by one equi-valent of mineral acid or by acetic acid.5 5 R. Schwyzer and H. Kappeler, Helv. Chim. Acta, 1963, 46, 1550.56 F.Weygand and K. Hunger, Chem. Ber., 1962, 95, 1.5 7 F. Weygand and K. Hunger, Chem. Ber., 1962, 95, 7.5 8 L. Zervas, D. Borovas, and E. Gazis, J . Amer. Chem. SOC., 1963, 85, 3660.5 9 J. C. Sheehan and V. J. Grenda, J . Amer. Chew. SOC., 1962, 84, 2417.6 o E. Dane, F. Drees, P. Konrad, and T. Dockner, Angew. Chem., 1962, 74, 873454 ORGANIC CHEMISTRYOne alkali-labile N-protecting group has been suggested. Toluene-p-sulphonylethyloxycarbonyl derivatives of amino-acids (21) have been pre-pared from the corresponding chloroformate and used in peptide synthesisby the active ester method.61 This protecting group is removed by base-catalysed #?-elimination under very mild conditions, even in the presence ofalkyl esters. A potential, but as yet untried, protecting group is y-chloro-butyryl, derivatives of which are cleaved by silver perchlorate via the inter-mediate irnino-ether ( 18).37Improved methods for the preparation of amino-acid alkyl and benzylesters by using dialkyl sulphites,62 dimethylformamide acetals,63 andbenzenesulphonyl chloride,64 have been described.Methylthioethyl estershave been advocated for carboxyl pr~tection.~~ They are removed by verymild alkaline treatment after conversion into the sulphonium salt with methyliodide, but their preparation presents serious difficulties. Phenylhydrazideshave also been suggested as possible carboxyl protecting groups, beingcleaved by manganese dioxide oxidation.66 Neither of the above methodsis applicable to methionine-containing peptides.Methods for the differential protection of the sulphydryl groups ofcysteine residues have been discussed.S - T r i t ~ l , ~ ~ S-diphenylmethyl,67and various acyl groups 68 may be used in place of the more usual S-benzylderivatives, and selective removal is possible. A potentially importantfeature of 8-trityl and S-diphenylmethyl derivatives is their cleavage bythiocyanogen yielding sulphenyl thiocyanates. 69 These react with addedthiol forming disulphide~,6~, 7O providing a new method for the synthesis ofunsymmetrical cystine peptides. 8-Sulpho-derivatives may also be com-bined with thiols to yield unsymmetrical di~ulphides,~~ but the reactionappears to be less selective. Dehydrogenation of thiols with vicinal halides(e.g., 1,2-di-iodoethane) has been recommended as an alternative to aerialoxidation for the conversion of thiols into di~ulphides.7~ A high yield isclaimed in the preparation of oxytocin by this method.72Formation of the peptide bond.Two main coupling methods, the use ofp-nitrophenyl esters and of dicyclohexylcarbodi-imide, have found frequentapplication in recent major syntheses. In addition the mixed-anhydrideprocedure continues to serve well, and the azide route to be indispensable forapplications where racemisation is a serious danger. Several new methodsfor the preparation of activated (aryl) esters have been described, e.g., use61 A. J. Kader and C. J. M. Stirling, Proc. Chem. Soc., 1962, 363.62 J. M. Theobald, M. W. Williams, and G. T.Young, J., 1963, 1927.63 H. Brechbuhler, H. Riichi, E. Hatz, J. Schreiber, and A. Eschenmoser, Angew.6 4 G. Blotny, J. F. Biernat, and E. Taschner, Annalen, 1963, 663, 194.6 5 H. N. Rydon and J. E. Willett, ref. 1, p. 23.66 R. B. Kelly, J . Org. Chem., 1963, 28, 453.67 L. Zervas and I. P h o t i , J . Amer. Chem. SOC., 1962, 84, 3887; L. Zervas, I.6* L. Zervas, I. Photaki, and N. Ghelis, J . Avner. Chem. SOC., 1963, 85, 1337.6 0 R. G. Hiskey and W. P. Tucker, J . Amer. Chern.. SOC., 1962, 84, 4799.'OR. G. Hiskey and W. P. Tucker, J . Amer. Chem. SOC., 1962, 84, 4794.c1 I. W. Stapleton and J. M. Swan, Austral J . Chem., 1962, 15, 570; H. Zahn and'3 F. Weygand and G. Zumach, 2. Naturjorsch., 1962, 17b, 807.Chern., Internat. Edn., 1963, 2, 212; H.Vorbriiggen, ibid., 1963, 2, 211.Photaki, A. Cosmatos, and N. Ghelis, ref. 1, p. 27.H. G. Otten, Annalen, 1962, 653, 139SHEPPARD : AMINO-ACIDS AND PEPTIDES 455of ethoxyacetylene,73 diphenylketen, 74 and di-p-nitrophenyl carbonate. 75A number of new active esters have been suggested. Pless and Biossonnas 76have compared the rates of ammonolysis of a large number of substitutedaryl esters, and conclude that 2,4,5-trichlorophenyl esters are promising newderivatives for peptide synthesis. A number of coupling reactions in highyield have been rep0rted.~7 One adva.ntage over the customary p-nitro-phenyl esters is that traces of unremoved phenol are not reduced to the veryreactive p-aminophenol during subsequent hydrogenation steps. Weygandand Steglich 78 have described the use of vinyl esters, prepared from vinylacetate by transesterification.Coupling reactions are best carried out indiethyl malonate or ethyl cyanoacetate, preventing the formation of colouredproducts from the liberated acetaldehyde. Esters of selenophenol have alsobeen suggested as active ester component^.^^ Full details have appeared ofthe use of esters of N-hydroxyphthalimide ;SO some solubility advantage isclaimed for the alternative hydroxysuccinimide derivatives. 81 Severalpapers 8 2 p s3 have shown that like hydrolysis, ammonolysis of esters (includ-ing p-nitrophenyl esters s3) is accelerated by the presence of relatively largeamounts of imidazole. However, the risk of racemisation must be greaterunder these conditions.Use of amino-acid active esters as the amino-component in carbodi-imide coupling reactions has found occasional applica-t i ~ n , ~ ~ but with proline p-nitrophenyl ester, acyldioxopiperazine formationwas substantial. 85 O-Acylation of the phenolic hydroxyl group of tyrosinehas been encountered as a side reaction in the nitrophenyl ester 86 andcarbonyl(di-imidazole) 87 methods, but this may be due to the presence ofexcess of tertiary base during the coupling reaction. Since nitrophenylesters couple well with the acetate salts of amino-acid and peptide esters,ssthe use of tertiary base may now be avoided completely.Full details of the pivalic acid mixed-anhydride method89 have nowappeared, and this has found an important application in the coupling ofpeptides at proline residues.tis Side-reactions occurring in the azide methodi 3 M .Bodanszky and C. A. Birkhimer, Chern. and Ind., 1962, 1620.7 4 D. T. Elmore and J. Smyth, Proc. Cheni. SOC., 1963, 18.7 5 T. Wieland, B. Heinke, K. Vogeller, and H. Morimoto, Annalen, 1962, 855,i6 J. Pless and R. A. Boissonnas, Helv. Chinz. Acta, 1963, 48, 1609.i i E. Sandrin and R. A. Boissonnas, Helv. Chim. Acta, 1963, 48, 1637; S. Guttmannand R. A. Boissonnas, ibid., p. 1626.78 F. Weygand and W. Steglich, Angew. Clzem., 1961, 73, 757.i9H-D. Jakubke, 2. Chem., 1963, 3, 65.189.G. H. L. Kefkens, G. I. Tesser, and R. J. F. Nivard, Rec. Traa. china., 1962, 81,G. W. Anderson, J. E. Zimmerman, and F. M. Callahan, J. Amer. Chem. SOC.,85 T.Wieland and K. Vouler, Angew. Chem., 1962, 74, 904; T. Wieland, H. Deter-83 R. H. Mazur, J. Org. Chem., 1963, 28, 2498.e.g., B. Berde, R. Huguenin, and E. Stiirmer, Experientia, 1962, 18, 444; P.-A.683.1963, 85, 3039.menn, and W. Kahle, ibid., 1963, 75, 209.Jaquenoud and R. A. Boissonnas, Helv. Chim. Acta, 1962, 45, 1462.8 5 M. Goodman and K. C. Stuben, J. Arner. Chem. SOC., 1962, 84, 1279.86 J. Ramachandran and C. H. Li, J . Org. Chem., 1963, 28, 173.R. Paul, J. Org. Chem., 1963, 28, 236.8sR. Schwyzer end P. Sieber, Nature, 1963, 199, 172.M. Zaoral, Coll. Czech. Chew). Comm., 1962, 27, 1273456 ORGANIC CHEMISTRYhave been summari~ed.~~ A novel approach to peptide synthesis has beenthe use of a chloromethylated polystyrene polymer as an insoluble but poroussolid phase on which the coupling reactions are carried 0ut.~1 Attachmentto the polymer constitutes protection of the carboxyl group (as a modifiedbenzyl ester), and the peptide is lengthened from its amino-end by successivecarbodi-imide couplings.The method has been applied to the synthesis of atetrapeptide, but incomplete reactions lead to the accumulation of by-products.Studies of racemisation by the synthesis of benzoyl-I;-leucylglycine esterYg2 and by the separation of diastereoisomers by paper~hromatography,~3 and g.1.c. ,94 have appeared. Only the azide, cyano-methyl ester, and p-nitrophenyl ester methods gave optically pure benzoyl-L-leucylglycine ester.92 In the condensation of benzyloxycarbonyl-L-valinewith L-valine methyl ester,94 racemisation was detected in only the cyano-methyl ester and phenylthio ester methods, and this may have occurredduring the preparation of the active ester derivatives themselves (see below).A critical test for coupling methods is the preparation of trifluoroacetyl-I;-valyl-L-valine methyl ester.94 In this case only the products from the azideand vinyl ester routes were optically pure within the limits of the method.The influence of solvent, temperature, base, and salt concentration on thedegree of racemisation in the above coupling by the carbodi-imide methodhas been studied.The deleterious effect of added triethylamine or tri-ethylamine hydrochloride is especially notable, confirming the advantage ofusing free amino-acid esters rather than a mixture of the ester hydrochlorideand trieth~lamine.~~~ 94 Even added lithium bromide increases the degreeof racemisation.Added imidazole is also an effective catalyst for racemisa-tion,94 indicating that special caution is needed in the synthesis of histidinepeptides. G.1.c. showed the presence of small concentrations of trifluoro-methyloxazolone during syntheses of trifluoroacetyl-L-valyl-1;-valine methylester by the carbodi-imide method,94 further supporting the oxazolone theoryof racemisation.and phthaloyl-amino-acid active esters 96 has been studied by Liberek.Slow racemisation of benzyloxycarbonyl derivatives, especially of amino-acids containing electronegative p-substituents, is observed in the presenceof triethylamine, presumably by an ionisation mechanism.Phthaloylderivatives are much worse in this respect. Attention is drawn to thepossible racemisation of cyanomethyl esters under the conditions normallyused for their preparation.9'Further development of this interesting method is awaited.*Racemisation.The base-catalysed racemisation of benzyloxycarbonyl-E. Schnabel, Annalen, 1062, 859, 168.91 R. B. Merrifield, J . Arner. Chem. SOC., 1963, 85, 2149.92M. W. Williams and G. T. Young, J., 1963, 881.O 3 E. Taschner, T. Sokolowska, J. F. Biernat, A. Chimiak, C. Wasielewski, andO4 F. Weygand, A. Prox, L. Schmidhammer, and W. Konig, Angew. Chem., Internat.95 B. Liberek, Tetrahedron Letters, 1963, 925.96 B. Liberek, Tetrahedron Letters, 1963, 1103.9 7 B.Liberek, A. Nowicka, and Z . Grzonka, Tetrahedron Letters, 1963, 1479.B. Rzeszotarska, Annalen, 1963, 663, 197.Edn., 1963, 2, 183.* Added in proof. This method has now been further developed and used in asynthesis of bradykinin (R. B. Memifield, J . Amer. Chern. SOC., 1964, 86, 304)S H E P P A R D : A M I N O - A C I D S A N D P E P T I D E S 457Synthesis of Natural Peptides.-The space available precludes completecoverage of the tremendous activity in this field since the last Rep0rt.lMeienhofer 98 has reviewed the synthesis of biologically active peptides, in-cluding references appearing in the first half of 1962, and only later develop-ments will be discussed here. Foremost amongst these later developmentsare the syntheses of pituitary hormones by Schwyzer and his collabora-t o r ~ .~ ~ , 88, loo The general principles underlying these and many otherrecent syntheses are now clear. Side-chain amino and carboxyl groups aremost often protected as t-butyloxycarbonyl derivatives and t-butyl estersrespectively, as are the N - and C-termini of the final, fully protected peptide.Benzyloxycarbonylamino-acids are extensively used throughout the prepara-tion of intermediate peptides, although trityl derivatives find application indifficult cases, e.g., in the presence of methionine. Stepwise synthesis fromthe C-terminus, e.g., by the successive addition of benzyloxycarbonylamino-acids by the nitrophenyl ester or carbodi-imide methods, is increasinglyoften used for the preparation of intermediate peptides without risk ofracemisation. For the same reason, the coupling of intermediate peptidesis effected at proline or glycine residues wherever possible.The mixed-anhydride method seems to be favoured for coupling at proline residues, anddicyclohexylcarbodi-imide for glycine residues. However, formation ofacylurea is sometimes a problem in the latter case, and carbonyldi-imidazolehas been advocated as an alternative.101 Where coupling at glycine andproline residues is not feasible, the steric reliability of the azide procedure isoften preferred. Departure from these generalisations is frequently seen,but often some degree of racemisation is then encountered.1O2 Enzymicmethods, e.g., digestion by leucine aminopeptidase l o 3 or other enzymes, lo*are becoming widely used for testing the optical purity of synthetic peptides.Xchwyzer lo6 hasreported two new syntheses of a-MSH using, respectively, s-t- butyloxy-carbonyl- and s-phthaloyl-lysine derivatives.These new syntheses havemade the hormone available in sufficiently large quantity for the specificrotation, [aID = -58.5" -4 26", to be measured for the first time. p-MSH,[a]= = - 57-5" & lo, has also been synthesised.52 This octadecapeptidecontains nearly every '' difficult " protein amino-acid, i.e., those with func-tional and sensitive side-chains, and the synthesis shown in Fig. 1 is illu-strative of some of the methods developed over the past few years to solveMelanophore stimulating hormones, cc and p-MSH.10598 J.Meienhofer, Chimia (Switz.), 1962, 16, 385.g g cf. E. D. Nicolaides and H. A. DeWald, J . Org. Chem., 1963, 28, 1926.loo R. Schwyzer, A. Costopanagiotis, and P. Sieber, Helv. Chim. Acta, 1963, 46, 870.Iol K. Hofmann, in " Internat. Symp. Pharmaceutical Chem., Florence, September,1962," Butterworths, London, 1963, p. 248.lo2 e.g., W. Rittel, Helv. Chim. Acta, 1962, 45, 2465; R. Schwyzer, B. Riniker, andH. Kappeler, ibid., 1963, 46, 1541 ; E. D. Nicolaides, H. A. DeWald, and D. A. McCarthy,Biochem. Biophys Res. Comm., 1961, 6, 210.I o 3 e.g., D. Gillessen, E. Schnabel, and J. Meienhofer, Annalen, 1963, 667, 164;P. G. Katsoyannis, K. Suzuki, and A. Tometsko, J . Amer. Chem,. SOC., 1963, 85, 1139;W. Rittel, Helv. Chim. Acta, 1962, 45, 2465.lo* e.g., R.Schwyzer, B. Riniker, and H. Kappeler, Helv. Chim. Acta, 1963, 46, 1541.Io5 For a review see R. Schwyzer, A. Costopanagiotis, and P. Sieber, Chimia (Switz).,106 R. Schwyzer, A. Costopanagiotis, and P. Sieber, Helv. Chim. Acta, 1963, 46, 870.1962, 16, 295- ButB O C ~ O HOOutI Pro TTRI-.OHTRIO N B TRI.ONB TRI-H.-r L0 Me0 MeONB TRIarONB Tf?ImvOH Hm.s MBOCN3 HlOMeJ&e2:; H?OCBOCB OC IBOCG u tOButZ l O HFBU'OButOButOMe Z-OMe Z-OMe Z-OMe Z-OBut0 ButN.-, ;Bu'OBut0-.Ii OMe Z phs 0 2OHFIU. 1. Synthesis of fl-MSH.62 (Protecting group abbreviations:2 Z = benzyloxycarbonyl:OBut = t-butyl ester; ONB = p-nitrobenzylester.SHEPPARD : AMINO-ACIDS A N D PEPTIDES 459this type of problem.Dicyclohexylcarbodi-imide and the azide method wereused extensively for condensation reactions. Because of the difficulty ofremoving benzyloxycarbonyl groups in the presence of methionine, thetrityl group was used in building up this sequence. Also noteworthy is theuse of glycine p-nitrobenzyl ester in the synthesis of the N-terminal tri-peptide. This ester group has a lower sensitivity to acid than the customarybenzyl ester, and its use allows selective cleavage of benzyloxycarbonylderivatives. 107 Simultaneous acetylation of the serine side-chain hydroxylgroup99 was avoided by effecting this cleavage with hydrogen bromide inethyl acetate solution,l07 rather than in the more usual acetic acid. Thestepwise synthesis of the C-terminal pentapeptide foreshadowed the verymuch more extensive use of this type of approach in the later synthesis ofACTH (see later).Adrenocorticotrophic hormone (ACTH).l o 5 9 112 Full details have appearedof the major syntheses of adrenocorticotrophically active peptides containingthe first 19,108 2O,lo9 23,110 and 24,55 residues of the natural hormone, as wellas of a number of other substantial fragments.lll However, these out-standing achievements have been overshadowed by the total synthesis ofthe fully active ACTH molecule, having the amino-acid sequence (39 resi-dues) of the porcine horrnone.ll3 The synthesis includes preparation of theC-terminal pentadecapeptide sequence by a etepwise method using exclusivelybenzyloxycarbonylamino-acid p-nitrophenyl esters.This general procedurepioneered in Bodanszky's synthesis of oxytocin 11* is becoming very widelyused, and is clearly a very powerful approach to the synthesis of largepeptides. The presence of methionine residues may, however, be a limitingfactor. Further coupling with preformed peptide derivatives were carriedout at proline or glycine residues, or by the azide method.The spate of synthetic analogues continues.Meienhofer 98 lists 58 synthetic analogues of oxytocin and vasopressin, andadditional references are collected below. 115 A new natural hormoneOxytocin and vasopressin.10' B. Iselin and R. Schwyzer, Helv. Chint. Acta, 1962, 45, 1499.lo8 C. H. Li, J. Meienhofer, E. Schnabel, D. Chung, T.-B. Lo, and J.Ramanchandran,J . Amer. Chern. SOC., 1961, $3, 4449.log K. Hofmann, H. Yajima, T.-Y. Liu, N. Yanaihara, C. Yanaihara, and J. L.Humes, J . Amer. Chem. SOC., 1962, 84, 4481.K. Hofmann, H. Yajima, T.-Y. Liu, and N. Yanaihara, J . Amer. Chem. SOC.,1962, 84, 4475.ll1 R. Schwyzer, W. Rittel, and A. Costopanagiotis, Helv. Chim. Actcr, 1962, 45,2473; K. Medzihradsky, V. Bruckner, M. Kajtar, M. Low, S. Bajusz, and L. Kisfaludy,Acta Chim. Acad. Sci. Hungary, 1962, 30, 105, 239, 473; C. H. Li, J. Ramachandran,and D. Chung, J . Amer. Chem. SOC., 1963,$5, 1895; K. Stum, R. Geiger, and W. Siedel,Chem. Ber., 1963, 98, 609, 1080.112 For a review see ref. 101, p. 245.113 R. Schwyzer and P. Sieber, Nature, 1963, 199, 172.114 M. Bodanszky, J. Meienhofer, and V.du Vigneaud, J . Amer. Chena. SOC., 1960,82, 3195.115 P.-A. Jaquenoud and R. A. Boissonnas, Helv. Chim. Acta, 1962, 45, 1462, 1601;R. L. Huguenin and R. A. Boissonnas, ibid., 1963, 46, 1669; S. Guttmann and R. A.Boissonnas, ibid., 1962, 45, 2517; 1963, 4$, 1626; R. A. Boissonnas, S. Guttmann,R. L. Huguenin, P.-A. Jaquenoud, and E. Sandrin, ibid., p. 2347; M . Zaoral, V. Pliska,K. Rezabek, and F. Sorm, Coll. Czech. Clzem. Comm., 1963, 28, 746; H. Nesvadbs, J.Honzl, and J. Rudinger, ibid., p. 1691 ; K. Jost, J. Rudinger, and F. Sorm, ibid., p. 1706;C. H. Schneider and V. du Vigneaud, J . Amer. Chem. SOC., 1962, $4,3005; M. Bodanszk460 ORGANIC CHEMISTRY(isotocin) has structure (22), i.e., that of Ser4-Ile *-oxytocin, and has beensynthesised.116I -1 Cys-Tyr-Ile-Ser-Asp-Cys-Pro-Ile-Gly-NH, (22)Bradykinin and kallidin.lZ1 New syntheses of bradykinin,ll’ kallidin,ll8and a number of analogues 119 have been reported. An interesting featureof the bradykinin amino-acid sequence (23) is the high degree of end-$0-endsymmetry. This has prompted two syntheses of “ retro-bradykinin ” (24)having the reverse amino-acid sequence. 120 However, the synthetic producthad no biological activity or inhibitory effect. Perhaps it should have beensynthesised from D-amino-acids!Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg (23)Arg-Phe-Pro-Ser-Phe-Gly-Pro-Pro-Arg (24)This peptide,122 isolated from the salivary glands of molluscsbut which also has powerful physiological effects in mammals, has beensynthesised by Sandrin and Boissonnas (Fig.2). 23 Although possessing aterminal lactam rather than amino-group, protection of the pyroglutamylresidue was found necessary, at least in the initial stages of the synthesis.Also noteworthy is the use of tritylglycine in the synthesis of the C-terminalmethionine-containing tripeptide, and also the use of tritylserine. Thelatter allows differential protection of the lysine side-chain amino-group as itsbenzyloxycarbonyl derivative, although in the final stages this was ex-changed for t-butyloxycarbonyl. The benzyloxycarbonyl-protecting groupof aspartic acid was similarly exchanged. Azide couplings were usedwherever a possibility of racemisation existed. Progress in the synthesisof analogues has also been reported.’‘, lZ4Several groups have synthesised large fragments of the in-dividual A and B chains,lZ5 using extensively the stepwise nitrophenyl esterEledoisin.Insulin.and C.A. Birkhimer, ibid., p. 4943; R. D. Kimbrough, W. D. Cash, L. A. Branda,W. Y . Chan, and V. du Vigneaud, J . Biol. Chem., 1963,238, 1411; W. Siedel, K. Sturm,and R. Geiger, Chem. Ber., 1963, 96, 1436.116A. Johl, A. Hartman, and H. Rink, Biochim. Biophys. Acta, 1963, 69, 193;S . Guttmann, Helv. Chim. Acta, 1962, 45, 2622.1 1 7 S. Guttmann, J. Pless, and R. A. Boissonnns, Helv. Chim. Acta, 1962, 45, 170.11s J. Pless, E. Sturmer, S. Guttman, and R. A. Boissonnas, Helv. Chim. Acta,1962, 45, 394; E. D. Nicolaides, H. A. DeWald, and D. A. McCarthy, Biochem. Biophys.Res.Comm., 1961, 6, 210.119 M. A. Ondetti, J . Medicin. Chem., 1963, 6, 10; M. Bodanszky, J. T. Sheehan,M. A. Ondetti, and S. Lande, J . Amer. Chem. SOC., 1963, 85,991; D. Nicolajdes, M. K.Craft, and H. A. DeWald, J . Medicin. Chem., 1963, 6, 524.120 S. Lande, J . Org. Ghem., 1962, 27, 4558; K. Vogler, P. Lanz, and W. Lergier,Helv. Chim. Acta, 1962, 45, 561.12l “ Bradykinin and Vasodilating Polypeptides,” Biochem. Pharmacol., 1962,10, 1 ;“ Structure and function of biologically active peptides : bradykinin, kallidin, andcongeners,” Ann. New York Acad. Sci., 1963, 104, 1.122 V. Erspamer and A. Anstasi, Ezperisntia, 1962, 18, 58.123 33. Sandrin and R. A. Boissonnas, Experientia, 1962, 18, 59.12* B. Camerino, G. de Caro, R. A. Boissonnas, E. Sandrin, and E.Sturmer,Experientia, 1963, 19, 339; E. Sandrin and R. A. Boissonnas, Helv. Chim. Acta, 1963,46, 1637.125 P. G. Katosoyannis and K. Suzuki, J . Amer. Chem. SOC., 1963, 85, 2659, andprevious papers; H. Zahn, J. Kunde, and R. Zabel, Annalen, 1963,663,177, and previou2.-ONP H~~ HHHS H E P P A R D : AMINO-ACIDS AND P E P T I D E SOH TRIn-BOC 0-LNJ Ht’BOC OHI 1H: 0-IFIG. 2. Synthesis of e1ed0isin.l~~ (Pyr = pyroglutamic acid.)method. The outstanding achievement, however, is the total synthesis ofthe A chain and its oxidative recombination with natural B chain, regenerat-ing a small (0-5-1-2%) but real level of insulin activity (the individualchains are totally inactive).126 A brief report has also appeared of therecombination of totally synthetic A and B chains.127 * Further progress inthis field will presumably require differential protection of cysteine residuesand more selective recombination methods.Regeneration of insulin activityby combination of natural chains from different species has also beena’chieved, leading, for example, to “ cod-ox hybrid insulin.” 12*Ribonuclease activity has been regenerated from thepartially degraded enzyme and synthetic peptides.129 Cleavage of theRibonuclease.papers; Y. Wang, J.-J. Huang, W.-C. Chang, C.-T. Tu, C.-C. Wang, Y.-Y. Hsu, Y . 3 .Tang, Y.-H. Lu, Z. W. Kin, and Y.-T. Kuang, Acta China. Sinica, 1963, 29, 190, andprevious papers.lZ6 P. G. Katsoyannis, A. Tometsko, and K. Fukuda, J . Amer. Chem. Soc., 1963,85, 2863.127 Chem.Eng. News, 1963, Oct. 21, p. 45.128 S. Wilson, G. H. Dixon, and A. C. Wardlaw, Biochim. Biophys. Acta, 1962,62, 483.129 K. Hofmann, F. Finn, W. Ham., M. J. Smithers, Y. Wolman, and N. Yanaihara,J . Amer. Chenz. SOC., 1963, 85, 833.* Added in proof. A second total synthesis of insulin has now been described(J. Meiehhofer, E. Schnabel, H. Bremer, 0. Brinkhoff, R. Zabel, W. Sroka, H. Kloster-meyer, D. Brandenburg, T. Okuda, and H. Zahn, 2. Naturforsch., 1963, 18b, 1120)462 ORGANIC CHEMISTRYintact enzyme between the twentieth and twenty-first amino-acid residuesby subtilisin yields the S-peptide (residues 1-20), and the S-protein (residues21-124), both totally devoid of enzymic activity. However, full ribonu-clease activity can be obtained by mere mixing of the S-peptide and S-protein.A synthetic peptide containing the first thirteen residues of t.he S-peptideregenerates 50% of the activity when added at a concentration of 3 : 1.Thesequence Asp-Ser which occurs at positions 14-15 in ribonuclease is there-fore not essential for enzymic activity. However, the sequence Hisl2-Metl3is apparently essential since the synthetic peptide containing residues 1-1 1does not restore activity when added to the S-protein.129Cyclic Peptides.-Cyclic dipeptide structures have been advanced forechinulin 130 (25) and the antibiotic albonoursin 131 (26). The plant toxinmalformin, which produces grotesque malformations of bea.n plants, has thecyclic pentapeptide sequence, cyclo(Ile-Cys-Val-Cys-Leu-),13~ although thelinkage of the cysteine sulphur atoms is unknown. Thiol, disulphide, andthiazoline groups are not present, although malformin is rea.dily reduced to athiol compound.Advances in the chemistry of Amanita cyclic peptideshave been reviewed by Wieland.133 Structure (27) has been advanced forthe antibiotic telomycin.134 Alkaline degradation yielded the unsaturateddioxopiperazine (28), as well as indole-3-aldehyde, and this is taken asevidence for the presence of a dehydrotryptophan residue. However, theformation of tryptophan itself on alkaline hydrolysis of the antibiotic is noteasily explained on this structure.,--+ Ser -+ Thr -+ uThr -+ Ala -+ Gly -+ (trans-3-OH-Pro) -+ (fl-OH-Leu)--iI ' (57) ASPA large group of iron-containing microbial growth factors have beenshownto be cyclic peptide derivatives. Ferrichrome has structure ( 29),135, 136the iron atom being bound as its octahedral hydroxamate complex of threeresidues of N6-acetyl-N6-hydroxyornithine. The amino-acid sequence 135follows from reduction to a deferri-compound, identical in melting point andchromatographic behaviour to synthetic cyclo( Gly-Gly- Gly- Orn- Orn- Om-).Other members of the group have glycine partly replaced by serine, and1 1--(cis-3-OH-Pro) t (A-Try) + (P-Me-Try)+130 G.Casnati, A. Quilico, and A. Ricca, Guzzettu, 1963, 93, 349.lal A. S. Khokhlov and G. B. Lokshin, Tetrahedron Letters, 1963, 1881.Ia2 S. Marumo and R. W. Curtis, Phytochemistry, 1962, 1, 245.Ia3 T. Wieland, in ref. 101, p. 339.135 S. J. Rogers, R. A. J. Warren, and J. B. Neilands, Nature, 1963, 200, 167.J. C. Sheehan, P. E. Drummond, J. N. Gardner, K. Maeda, D. Mania, S. Naka-T. Emery and J. B. Neilands, J . Amer. Chena. SOC., 1961, 83, 1626.mura, A. K. Sen, and J. A. Stock, J . Amer. Chem. Soc., 1963, 85, 2867SHEPPARD : AMINO-ACIDS APU’D P E P T I D E S 463various acyl groups in place of a ~ e t y l . l ~ ~ - l ~ ~ The antibiotic albomycin alsoappears to be a closely related compound.138Several recent reviews 139 have dealt with the synthesis of cyclic depsi-peptides, and only the latest results are reported here. Synthetical studies,pre-eminently by Shemyalcir’s group, have led to revision of several structurespreviously suggested for natural cyclic depsipeptides. The highly sym-metrical nature of some of these substances underlines the need for accuratemolecular-weight measurement during structure determination. Synthesisof the cyclic tetradepsipeptide structure (30; n = 2 ) suggested for the anti-biotic enniatin B yielded a totally inactive product.140 Subsequent re-determination of the molecular weight suggested a more probable hexadepsi-peptide structure (30; n = 3), andthis has beenconfirmed bysynthesis.141, 142The cyclic octadepsipeptide (30; n = 4) has also been ~ynthesisedl~~and has comparable antibiotic activity. Enniatin A has the structure ofenniatin B with N-methyl-I;-isoleucine replacing N-methyl-~-valine.l43Cyclo-octadepsipeptide structures suggested for valinomycin and amido-mycin are also incorrect,144 the former being shown by synthesis to bethe duodecadepsipeptide (31).145 However, synthesis 147 has confirmed thesuggested structures 146 for sporidesmolide I and 11.P r i P r i P r i Me P r i P r iI I I I I IL D D L L D(NMe -CH.CO - 0 -CH ‘CO),, (NH .CH -c0 - 0 - C H - c0 - NH -CH -CO-O.CH .CQ,Full details have appeared of the brilliant total synthesis of ergotamine,which allows the full stereochemical expression (32) to be written for thisalkaloidal p e ~ t i d e . l ~ ~ The spontaneous formation of the cyclol (33 ;R = OEt) from the alcohol (34) is stereospe~ific,~~~, 149 yielding the anti-arrangement of the tertiary hydroxyl group and adjacent hydrogen atom.13’ TV. Keller-Schierlein and A. Deer, Helv. Chim. Acta, 1963, 48, 1907; W. Keller-Schierlein, ibid., p. 1920; V. Prelog, in ref. 101, p. 327.138N. A. Poddubnaya and E. P. Krysin, Zhur. obshchei Khim., 1962, 32, 1005;J. Turkova, 0. Mikes, and F. sorm, Coll. Czech. Chem. Comm., 1962, 27, 591.139 Ref. 1, pp ... 195, 207; ref. 101, p. 305; M. M. Shemyakin, Uspekhi Khim., 1962,31, 269; E. Schroder and K. Lubke, Experientia, 1963, 19, 57.140 M. M. Shemyakin, Yu. A. Ovchinnikov, A. A. Kiryushkin, and V. T. Ivanov,Tetrahedron Letters, 1962, 301.141 P. A. Plattner, K. Volger, R. 0. Studer, P. Quitt, and W. Keller-Schierlejn,Helv. China. Acta, 1963, 46, 927.142 M. M. Shemyakin, Yu. A. Ovchinnikov, A. A. Kiryushkin, and T’. T. Ivanov,Tetrahedron, Letters, 1963, 886.143 M. M. Shemyakin, Yu. A. Ovchinnikov, A. A. Kiryushkin, and V. T. Ivanov,Izvest. Akad. Nauk S.S.S.R., Otdel. khim. Nauk, 1963, 1148; P. Quitt, R. 0. Studer,and K. Vogler, Helv. Chim. Acta, 1963, 48, 1715.144 M. M. Shemyakin, E. I. Vinogradova, M. Yu. Feigina, and IT. A. Aldanova,Tetrahedron Letters, 1963, 351.145 M. M. Shemyakin, N. A. Aldanova, E. I. Vinogradova, and M. Yu. Feigina,Tetrahedron Letters, 1963, 1921.148 D. W. Russell, J . , 1962, 753.14’ M. M. Shemyakin, Yu. A. Ovchinnikov, V. T. Ivanov, and A. A. Kiryushkin,Tetrahedron, 1963, 19, 995; Tetrahedron Letters, 1963, 1927.148 A. Hofmann, H. Ott, R. Griot, P. A. Stadler, and A. J. Frey, Helu. Chim. Acta,1963, 46, 2306.14@ H. Ott, A. J. Frey, and A. Hofmann, Tetrahedron, 1963, 19, 1675464 ORGANIC CHEMISTRYThis was deduced from pK measurements on the acid (33; R = OH) and itsepimer, the absolute configuration of the carboxyl group in both compoundsbeing known.(3 4) H- 'CH2Ph (33) H- CH2PhGeneral studies of cyclol formation from N - (hydroxyacy1)-lactams haveshown that the equilibria between hydroxyacyl-lactam (35), cyclol (36), andlactone-lactam (37) are very delicately balanced in terms of the precisestructural features.150 Formation of stable cyclols is obtained only witha-hydroxyacyl-lactams where the lactam ring is six-membered or larger. Inone case the cyclol has also been obtained from the corresponding syntheticlactone.151 Cyclol formation is not observed with hydroxyalkyl-lactams,presumably because of the lower reactivity of the lactam carbonyl group,nor, rather unexpectedly, with N-hydroxyalkylglutarimides. With /3-hydro-xyacyl-lactams, the equilibrium is generally in favour of the lactone (37).152An analogous transformation occurs also with open chain diacylimides, bothin the a- and 8-hydroxyacyl series:152COCH,*N-PHT---+ PHT-NCH ,.CO*O*[ CH ,In-CO*NH.CH ,*CO ,Me/\HO*[CH 2In.CO.NCH,.CO,MelSo M. M. Shemyakin, V. K. Antonov, A. M. Shkrob, Yu. N. Sheinker, and L. B.Senyavina, Tetrahedron Letters, 1962, 701; R. G. Griot and A. J. Frey, Tetrahedron,1963, 19, 1661.151 R. C. Sheppard, Experientia, 1963, 19, 125.152 V. K. Antonov, A. M. Shkrob, V. I. Shchelokov, and M. M. Shemyakin, Tetra-hedron Letters, 1963, 1353S H E P P A R D : AMINO-ACIDS AND P E P T I D E S 465This constitutes a hydroxy-acid insertion reaction closely related to Brenner’samino-acid insertion.163 Impressed by the ease with which the di- @-hydro-xyacy1)diketopiperazine (38) underwent ring expansion to the cyclic depsi-peptide (39).152 Shemyakin suggests that this reaction may be operative inthe biosynthesis of natural cyclic depsipeptides containing #I-hydroxy-acidresidues, e.g., serratamolide.154 Similar reactions may also be involved inthe biosynthesis of the peptide-lactone rings of actinomycin and relatedantibiotics. 155The co-operative effects of functional amino-acid side-chains when heldin fairly rigid cyclic peptide structures continue to be investigated. Cata-lysis of the hydrolysis of p-nitrophenyl acetate by cyclo( Gly-Tyr-Gly-Gly-His-Gly-) results in acylation of the phenolic hydroxyl as with thepreviously reported cyclo(Tyr-Gly-Gly-Gly-His-Gly-) and cy~lo(Tyr-His-).l~~However, O-acylation occurs with only a fraction of the ester consumed, i.e.,hydrolysis of the intermediate acetylimidazole is faster than intramoleculartransfer to the tyrosine hydroxyl group. The intramolecular nature of thereaction has been confirmed by synthesis of diastereoisomeric D-L cyclicpeptides where the side-chains are effectively trans to one another. In thesecompounds acylation of tyrosine occurs, but at a very much slower rate.156An analogous, serine derivative, cyclo( Gly-His-Ser-Gly-His-Ser-), has alsobeen synthesised.158 It shows no greater catalytic effect on the hydrolysisof p-nitrophenyl acetate than does imidazole itself, and no evidence wasreported for acetyl transfer to the serine hydroxyl group. Of some interest,however, is the observation that the cyclic hexapeptide appears to catalyseits own hydrolysis. When kept in aqueous solution, free serine is liberatedtogether with the dioxopiperazine of glycine and histidine. A similar readycleavage of the tripeptide, His-Pro-Phe, has also been rep0rted.15~ Inthe open-chain peptide series, no significant lability of the y-benzyl ester ofZ-Glu(0BZL)-Ser-NH, is conferred by the adjacent serine amide residue.160This contrasts with the extreme lability shown by the analogous Z-Asp-(0BZL)-Ser-NH,, which is reported to hydrolyse some lo7 times faster thanbenzyl propionate.161153 M. Brenner, in “ Amino-acids and Peptides with Antimetabolic Activity,”15* H. H. Wasserman, J. J. Keggi, and J. E. McKean, J. Amer. Chem. Xoc., 1961,155 cf. A. W. Johnson, in “ Amino-acids and Peptides with Antimetabolic Activity,”156 K. D. Kopple, R. R. Jarabak, and P. L. Bhatia, Biochemistry, 1963, 2, 955.16’ K. D. Kopple and D. E. Nitecki, J. Amer. Chern. Xoc., 1962, 84, 4457.15* J. C. Sheehan and D. N. McGregor, J . Amer. Chem. SOC., 1962, 84, 3000.159 Pv. H. Mazur and J. M. Schlatter, J. Org. Chem., 1963, 28, 1025.160 A. P. Fosker, R. W. Hanson, and H. D. Law, Chem. and Ind., 1963, 569.161 S. A. Bernhard, A. Berger, J. H. Carter, E. Katchalski, M. Sela, and Y. Shalitin,Churchill, London, 1958, p. 157; M. Brenner, in ref. 1, p. 123.83, 4106.Churchill, London, 1958, p. 166.J . Amer. Chem. SOC., 1962, 84, 2421466 ORGANIC CHEMISTRYThe formation of cyclic peptides by doubling-up reactions may bestereospecific. The cyclic hexapeptide obtained from Gly-Gly-DL-Phe bythe active ester method has been shown by independent synthesis to beexclusively the meso-form, i.e., an L-tripeptide unit reacts preferentially witha D-unit and vice versa.l62 The yield of cyclic hexapeptide from linearhexapeptide azide is also lower for the L-L or D-D series than for the L - D . ~ ~ ZThis is in accord with results obtained for the cyclisation of diastereoisomericpentapeptides by the nitrobenzenethiol ester and carbodi-imide methods,163and which have been discussed in terms of preferred conformations of linearpeptide derivatives in solution. Dielectric-increment measurements alsosupport the hypothesis that short peptides adopt preferred conformations inaqueous s0lution.l6~lB2 R. Schwyzer and A. Tun-Kyi, Helv. Chim. Acta, 1962, 45, 859.163 P. M. Hardy, G. W. Kenner, and R. C. Sheppard, Tetrahedron, 1963, 19, 95

ISSN:0365-6217    

DOI:10.1039/AR9636000245

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

BIOLOGICAL CHEMISTRY1. INTRODUCTIONBy D. F. ElliottTHE ever-quickening pace of research in the fields of polypeptide and poly-saccharide chemistry calls for an allocation of space which can no longer beprovided within the confines of the organic section. The results of theseinvestigations are, nevertheless, of consequence both to the organic chemistand to the biological chemist, presenting to the one the challenge of synthesisand to the other clues to the understanding of biological action in terms ofmolecular structure. It seems appropriate, therefore, to make some spaceavailable in the biological section for reporting on these subjects.The advent of automation in protein chemistry has resulted in theaccumulation of a massive amount of data concerning amino-acid sequence,but the problem of conformational analysis, although brilliantly elucidatedin one or two cases, remains for the most part unsolved. It is the fieldin which further advances are now eagerly awaited because, one has t oa.ssume, the biological activity must somehow be bound up with the overallshape of the molecule.The heteropolymeric molecules which constitute some of the structuralelements of living matter have remained, until recently, almost intractableto chemical investigation.Several classes of compound, for examplecarbohydrates, peptides, and lipids, are herein found to be represented andsometimes combined with one another, thus calling forth a wide mnge oftechniques for the solution of structural problems. These highly complexmolecules are found not only in insoluble structural matter, but also influids such as serum, in the form of glycoproteins, and in tissues, such as brain,in the form of cerebrosides.The steady progress in the elucidation of thesedifficult problems promises that a whole new vista of stlructural organicchemistry will soon be revealed.Thyroid hormones have always aroused great interest, but the mech-anism by which they stimulate metabolic activity is still not understood.That they might act by direct stimulation of cellular enzymes is not supportedby the many investigations which have been carried out with this idea inmind. Recently, it has been shown that the actual synthesis of certainenzymes in the cytoplasm is stimulated by the hormones, this being a mani-festation of a stimulation of protein synthesis in general. Further studieshave shown that this effect on protein synthesis is a result of the stimulationof DNA-dependent RNA-polymerase in the cell nucleus.Such a mech-anism would provide a ready explanation of the manifold actions of thethyroid hormones.In view of this demonstration of a direct effect of the thyroid hormoneson the production of messenger RNA it is appropriate to conclude this year'sreport with an account of the advances recently made in the understandingof protein synthesis; these have stemmed, to a large extent, from investiga-tions on the ribosome and its interaction with messenger RNA2. PROTEINS AND PEPTIDESBy Derek G. SmythRECENT progress in this field has been extensive and some achievements havebeen outstanding.The syntheses of the A-chain (21 amino-acid residues)and the B-chain (30 residues) of insulin, and the total synthesis of adreno-corticotrophic hormone (39 residues) have been made possible by r e h e -ments in the methods of peptide synthesis. The further elucidation of thethree-dimensional structures of crystalline horse haemoglobin 4 and whalemyoglobin has followed the development of improved methods of X-rayanalysis ; molecular structures of insulin,s ribonuclease, chymotrypsinogen,*lysozyme,g ferritin,lO procarboxypeptidase,ll and lactoglobulin 1 2 are beinginvestigated. As a result of advances in chemical techniques for the deter-mination of structure, the number of different proteins of which the completeamino-acid sequence is firmly established has risen to six: insulin,l3 ribo-nuclease,14 hzemoglobin,15 cytochrome c, l6 tobacco mosaic virus protein,17and lysozyme ;18 the difficult elucidation of the sequences of chymotryp-P.G. Katsoyannis, A. Tometsko, and K. Fukuda, J . Amer. Chem. Soc., 1963,2 P. G. Katsoyrtnnis, Ann. Sci. Conf. Protein Foundation, Cambridge, Mass.,4 M. F. Perutz, Nature, 1962, 194, 914.85, 2863.U.S.A., 1963, to be published in Von: Sanguinis; personal communication.R. Schwyzer and P. Sieber, Nature, 1963, 199, 172.J. C. Kendrew, Brookhaven Symp. Biol., No. 15, 1962, 216.J. R. Einstein, A. S. McGavin, and B. W. Low, Proc. N u t . Acad. S c i . U.S.A.,7 C. H. Carlisle and R.A. Palmer, Acta Cryst., 1962, 15, 129; M. V. King, B. S.8 J. Kraut, L. C. Sieker, D. F. High, and S. T. Freer, Proc. Nat. Acad. S c i . U.S.A.,L. K. Steinrauf, J. M. Reddy, and R. E. Dickerson, Acta Cryst., 1962, 15, 423.1 0 P. M. Harrison, T. Hofmann, and W. I. P. Mainwaring, J . Mol. Biol., 1962,4, 251.11 M. L. Ludwig, I. C. Paul, G. S. Pawley, and W. N. Lipscomb, Proc. N u t . Acad.Sci. U.S.A., 1963, 50, 282.12 D. W. Green and R. Aschaffenburg, J . Mol. Biol., 1959, 1, 54.13 F. Sanger and H. Tuppy, Biochem. J . , 1951, 49, 463; F. Sanger and E. 0. P.Thompson, ibid., 1953, 53, 353; A. P. Ryle, F. Sanger, L. F. Smith, and R. Kitai,ibid., 1955, 60, 541.1 4 ( a ) C. H. W. Hirs, S. Moore, and W. H. Stein, J . Biol. Chem., 1960, 235, 633;( b ) D.H. Spackman, W. H. Stein, and S. Moore, ibid., p. 648; ( c ) D. G. Smyth, W. H.Stem, and S. Moors, ibid., 1962, 237, 1845; ( d ) D. G. Smyth, W. H. Stein, and S. Moore,ibid., 1963, 238, 227.(a) R. J . Hdl and W. Konigsberg, J . Biol. Chem., 1962, 237, 3151; W. Konigs-berg, J. Goldstein, and R. 5. Hill, ibid., 1963, 238, 2028; ( b ) G. Braunitzer, V. Rudloff,and N. Hilschmann, 2. physiol. Chem., 1963,331, 1 ; ( c ) W. A. Schroeder, J. R. Shelton,J. B. Shelton, J. Cormick, and R. T. Jones, Biochemistry, 1963, 2, 992, 1353.16 H. Tuppy and G. Kreil, Monatsh., 1962, 92, 780; E. Margoliash, J. R. Kimmel,R. L. Hill, and R. Schmidt, J . Bid. Chem., 1962, 23'7, 2148; E. Margoliash, and E. L.Smith, ibid., p. 2151 ; E. Margoliash, ibid., p. 2161.1 7 A.Tsugita, D. T. Gish, J. Young, H. Fraenkel-Conrat, C. A. Knight, andW. M. Stanley, Proc. N u t . Acad. Sci. U.S.A., 1960, 46, 1463; F. A. Anderer, H. Uhlig,E. Weber, and G. Schramm, Nature, 1960, 186, 922.1* R. E. Canfield, J . Biol. Chem., 1963, 238, 2698; J. Jolles and P. Jolles, Compt.rend., 1961, 253, 2773.1963, 49, 74.Magdoff, M. B. Adelman, and D. Harker, ibid., p. 144.1962, 48, 1417SMYTH: PROTEINS AND PEPTIDES 469sinogen 19 and myoglobin 20 are approaching completion, and papain 21 andtrypsinogen 22 are also being studied. The knowledge of these structuresprovides a firm foundation for further work towards an understanding oftheir biological activities at a molecular level. In this Report, emphasis isplaced on determination of structure by chemical methods, and on attemptsto relate structure to biological activity.Insulin.-The first chemical synthesis of a naturally occurring proteinhas been achieved.Following the synthesis of the A-chain, the synthesisof the B-chain has now been completed. Although a procedure for ensuringthe correct coupling of the disulphide bonds to give a high yield of an activemolecule is still not available, experiments designed to isolate the biologicallyactive component obtained by hybridization of the reduced chains are inprogress.2 It had previously been shown 23 that when the reduced forms ofthe A- and B-chains of natural insulin were mixed and the solution oxy-genated, the recovery of activity was only 1-2%, a result which correspondedwith the calculated value if hybridization were a random procedure.Thiscontrasts with the high recoveries obtained on reoxidation of reducedribonuclease 24 and other proteins.The action of insulin does not appear to involve a disulphide interchangewith a protein receptor because the binding of insulin by isolated diaphragmis reported to be unaffected by N-ethylmaleimide and iodoacetate.25 Otherreports, however, have described inhibition of insulin action by thesereagents. 26 Precise interpretation of such observations must await detailedinvestigations involving structural analysis of modified derivatives in orderto locate the sites of reaction; in addition, a possible r61e of co-factorspossessing thiol groups should be considered.An understanding of the relation between structure and activity ininsulin has been restricted by lack of knowledge concerning the nature ofits receptor and by difficulties inherent in quantitative assays based on theactivity of the hormone.Mild treatment with acid has selectively hydro-lysed the amide from the carboxyl-terminal asparagine residue of theA-chain; the product, which was fully active, was identified with a minorcomponent present in commercial preparations. 27 Complete removal ofJ. R. Brown and B. S. Hartley, Biochem. J., 1963, 89, 5 9 ~ ; B. S. Hartley,Brookhaven Symp. Biol., 1962, No. 15, 85; B. Keil, Z. Prusik, and F. Sorm, Biochim.Biophys. Acta, 1963, 78, 559; D. Van Hoang, M. Rovery, and P. Desnuelle, ibid.,1962, 58, 613.4o (a) A.B. Edmundson and C. H. W. Hirs, J. Mol. Biol., 1962, 5, 663, 683, 706;(b) A. B. Edmundson, Nature, 1963, 198, 354.21 J. R. Kimmel, 0. K. Kato, A. C. M. Paiva, and E. L. Smith, J. Biol. Chem.,1962, 237, 2525; A. Light and E. L. Smith, ibid., p. 2537.22 V. Tomask, 0. Mike;, V. Holeysovsky, B. Keil, and F. Sorm, Biochim. Biophys.Acta, 1963, 69, 186; K. A. Walsh, D. L. Kauffman, and H. Neurath, Biochemistry,1962, 1, 893:23 S. Wilson, G. H. Dixon, and A. C. Wardlaw, Biochim. Biophys. Acta, 1962,62, 483; D. Yu-Cang, Z. Yu-Shang, L. Zi-Nian, and T. Chen-Lu, Sci. Sinica, 1961,10, 84.2 4 F. H. White, J. Biol. Chem., 1961, 236, 1353.25H. Carlin and 0. Hechter, J. Bid. Chem., 1962, 237, PC 1371.26 I. A. Mirsky and G. Perisutti, Biochim. Biophys.Acta, 1962,62, 490; E. Cadenas,27 F. H. Carpenter and A. Chrambach, J. Biol. Chem., 1962, 237, 404.H. Ksji, C. R. Park, and H. Rasmussen, J. Biol. Chem., 1961, 236, PC 63470 BIOLOGICAL CHEMISTRYthe asparagine or of the aspartic acid residue by reaction with carboxy-peptidase, however, gave a product with very little activity. In contrast,the carboxyl-terminal alanine residue of the B-chain has been removedfrom deamidoinsulin with little alteration in activity."* The results wereexplained by changes in overall conformation of the hormones and a specialr61e of the aspartic acid residue in an " active centre " was not suggested.In comparison, similar experiments with hzemoglobin, which resulted inremoval of a histidine and a tyrosine residue, gave a molecule possessing aten-fold increase in oxygen affinit~.2~The action of tyrosinase on insulin,30 in contrast to earlier studies,31 hasbeen reported to take place at all of the four tyrosine residues.Differencesin rates of reaction with B-chain, amorphous insulin, A-chain, and zincinsulin were considered to reflect differences in conformation.Ribonuc1ease.-A convenient method for obtaining a salt-free homo-geneous preparation of bovine pancreatic ribonuclease A has been described. 32The amino-acid sequence of ribonuclease, reported in the classical studies ofHirs, Moore, and Stein,14a has undergone complete re-examination bySmyth, Stein, and The errors and uncertainties in the earlierwork had arisen from limitations inherent in the methods used, namely in theEdman degradation, in the use of leucine aminopeptidase, and in the methodof application of the fluorodinitrobenzene (DNFB) procedure for NH,-term-inal analysis.In the course of the Edman degradation, glacial acetic acid-hydrogen chloride had been used for the cyclization step, but the conditionshave been found to cause blockage of sequential degradation because ofthree unexpected reactions : (a) intramolecular condensation of glutamineresidues, on becoming NH2-terminal, to form residues of pyrrolidinone-carboxylic acid; ( b ) acetylation of the hydroxyl groups of serine and threonineresidues which undergo an 0 - N acyl shift when the residue becomesNH,-terminal ; ( c ) condensation of aspartyl and asparaginyl residues to formimides which open to give p-aspartyl peptides.Consecutive cycles of thedegradation had then been applied to peptides which were resistant tofurther cleavage. Artifactual losses of serine, threonine, or tyrosine, whichoccurred during acid hydrolysis of residual peptides, resulted in the incorrectassumption that one of these amino-acids had been removed as a phenyl-thiohydantoin. The difficulties were overcome by the use of anhydroustrifluoroacetic acid for cyclization, and by purification of the resultingpeptides by column chromatography. In the use of leucine aminopeptidase(LAP), the preparations employed possessed carboxypeptidase activity ;release of amino-acids from the COOH-terminus had been the predominantaction of LAP on peptides containing a residue of pyrrolidinonecarboxylicacid, aspartic acid, glutamic acid, cysteic acid, serine, threonine, or proline28 L.I. Slobin and F. H. Carpenter, Biochemistry, 1963, 2, 16, 22.2D E. Antonini, J. Wyman, R. Zito, A. Rossi-Fmelli, and A. Caputo, J . Biol.Chem., 1961, 236, PC 60.30 J. C. Cory, C. G. Bigelow, and E. Frieden, Biochemistry, 1962, 1, 419.3 1 K. T. Yasonobu, E. W. Peterson, and H. S. Mason, J . Biol. Chem., 1959, 234,3291; W. J. Haas, I. W. Sizer, and R. Loofburrow, Biochim. Biophys. Acta, 1951,6, 589.32 A. M. Crestfield, W. H. Stein, and S. Moore, J . Biol. Chem., 1963, 238, 618SMYTH: PROTEINS AND PEPTIDES 47 1at or near the NH,-terminus. In later studies,14d LAP was not employed;results obtained with carboxypeptidase proved consistently reliable. In theuse of the DNFB procedure, the presence of dinitrophenylserine had beenincorrectly deduced in a peptide lacking a free a-amino-group, probablybecause of artifacts resulting from incomplete removal of dinitrophenol ordinitroaniline derived from the reagent.Some workers have since used acolumn of silicic acid to overcome this d i f f i c ~ l t y . ~ ~ Details of these andother problems involved in determining the structure of proteins and peptideshave recently been reviewed.34 The sequence of amino-acids shown inFig. 1 has been established with the aid of improved methods. The sequence5 6 7 8 9 10 I1 12 13 I4 15 16 17 18 19 20212923242526 I2'128!a3031324 4? % 15 44 43 42 41 40 39 38 37 36 35 34 33ItFIG.1. The sequence of amino-acids i n bovine pancreatic ribonuclease A. From Smyth,Stein, and Moore.14d This structure is based on the experiments of Hirs Moore, andStein;14" Spackman, Stein, and Moore;14b and Smyth, Stein, and Moore.l4c9 d *[Reproduced, by permission, from D. G. Smyth, W. H. Stein, and S. Moore, J. Biol.Chem., 1963, 238, 228.1from residues 11-18 has been confirmed by two concurrent investigationsfrom other lab~ratories.~~ Because ribonuclease has been widely used as amodel for chemical studies, some data on the location of amino-acid residuesat individual sites has been 0btained,~6 and the results are all consistent withthe revised sequence.An enzymatically activemolecule has been obtained by physical aggregation of two inactive frag-ments, either from the same molecule or from different molecules.70% ofthe activity of the native molecule was present after adding the syntheticXtructure-activity relationships in ribonuclease.33 N. A. Matheson, Biochem. J., 1963, 88, 146.34 D. G. Smyth and D. F. Elliott, Analyst, 1964, 89, 81.35 J. T. Potts, A. Berger, J. Cooke, and C. B. Anfinsen, J. Biol. Chem., 1963,237, 1851; E. Gross and B. Witkop, ibid., p. 1856.36 ( a ) J. P. Cooke, C. B. Anfinsen, and M. Sela, J. Biol. Chem., 1963, 238, 2034;(b) C. Chul-Yung and H. A. Scheraga, J. Biol. Chern., 1963,238,2965; ( c ) L. G. Donovan,Biochim. Biophys. Acta, 1963, 78, 474; ( d ) J. G. Wilson and L. A. Cohen, J. Amer.Chern. ~Soc., 1963, 85, 564472 BIOLOGICAL CHEMISTRYpeptide containing residues 1-13 to the S-protein containing residues21-124.37 The absence of the aspartyl-serine sequence, positions 14 and15, excludes the possibility that these residues might perform a specialfunction in the activity of ribonuclease.In a different approach, digestionof the S-peptide, 1-20, with carboxypeptidase removed five amino-acidresidues from the COOH-terminus, and the full activity of ribonucleaseappeared on addition of S-pr~tein.~*The reaction of iodoacetate with ribonuclease has been thoroughlyexamined. At pH 3, the predominant reaction involved progressive modifi-cation of methionine residues;39 the concomitant loss of enzymic activity wasrelated to a suggested r61e of methionine in maintaining a catalyticallyactive configuration.Replacement of methionine' by oc-aminobutyric acida t position 13 of the synthetic peptide 1-13 resulted in no change in thepotential of the peptide to activate S-protein;40 an important r61e for thisone of the four methionine residues in ribonuclease is therefore precluded.At pH 5.5, a rapid reaction with iodoacetate occurs specifically with thehistidine residue at position 119 and results in a total loss of activity. Thepeculiar reactivity of this one histidine residue was abolished by procedureswhich caused disruption of the three-dimensional structure of the molecule. 41The presence near the susceptible histidine of a positively charged groupwhich could bind and orientate the iodoacetate anion was anticipated.Thus,no corresponding reaction with iodoacetamide was to be expected, and nonewas observed. Further studies 4 2 with iodoacetate at pH 5-5 have revealeda competitive reaction with the histidine residue at position 12 to give a.nalmost inactive derivative. The modification at position 119 was found tooccur exclusively at the l-position of the imidazole ring whereas modificationat position 12 occurred at the 3-position; alkylation of the one histidineprevented reaction at the other. When the two inactive carboxymethylderivatives were lyophilized together from 50 yo acetic acid, a procedureknown to produce aggregate^,^^ considerable activity was restored. Aplausible interpretation was that hybridization resulted in juxtaposition ofan unsubstituted histidine-12 contributed by the histidine- 119 derivative,and an unsubstituted histidine-119 contributed by the histidine-12 deriva-tive. The results are consistent with a hypothesis that two histidineresidues are required for enzymic activity of ribon~clease.~~? 44 Extensivekinetic evidence 45 has supported the hypothesis, and an alternative mech-37 K.Hofmann, F. Finn, W. Haas, M. J. Smithers, Y. Wolman, and N. Yanaihara,38 J. T. Potts, M. Young, and C. B. Anfhsen, J . Biol. Chem., 1963, 238, PC39 N. P. Neumann, S. Moore, and W. H. Stein, Biochemistry, 1962, 1, 68.4 O K. Hofmann, Symposium on Peptide Chemistry, London, 1963; Proc. Chein.41 G. R. Stark, W. H. Stein, and S. Moore, J . Biol. Chem., 1961, 236, 436.42 A. M. Crestfield, W.H. Stein, and S. Moore, J. Biol. Chem., 1963, 238, 2413,O3 A. M. Crestfield, W. H. Stein, and S. Moore, Arch. Biochern. Biophys., 1962,4 4 F. M. Richards, Proc. Nat. Acad. Sci. U.S.A., 1958, 44, 162.4 5 D. G. Herries, A. P. Matthias, and B. R. Rabin, Biochem. J., 1962, 85, 127;J . Amer. Chem. SOC., 1963, 85, 833.2593.SOC., 1963, 363.2421.1, 217.D. Findlay, A. P. Matthias, and B. R. Rabin, ibid., p. 139SMYTH: PROTEINS AND PEPTIDES 473anism of action of the enzyme also requires the participation of two histidineresidues.A detailed study of the modification of ribonuclease by DNFB at pH 8,in the presence of phosphate, has revealed an unusually high reactivity ofthe E-amino-group of lysine at position 41.47 This was attributed to theproximity of positively charged groups a t an anion binding site.Theaccompanying inactivation was considered to be caused by disruption of theactive conformation because, after the initial reaction, a hitherto unreactiveamino-group at position 7 became accessible to the reagent. Previousinactivations of ribonuclease by diphosphoimidazole, cyanate, and iodo-acetate under alkaline conditions may also have resulted from modificationof the amino-group at position 41. The coupling of amino-groups withresidues of polyalanine, on the other hand, has revealed that at pH 6-8 thelysine residues in positions 7, 31, and 41 were resistant to attack by N-car-boxyalanine anhydride.36a The surprising lack of reactivity at position 41under these conditions has been reversed by performing the reaction inhydrogen carbonate instead of in phosphate. Such observations call atten-tion to the necessity for rigorous definition of the reaction conditions duringstudies with proteins.The anomalous chromatographic and electrophoreticbehaviour of ribonuclease in the presence of phosphate 42, 48 has been ex-plained by the binding of polyvalent anions which confer a stabilizing effecton the molecule. That this binding involves the " catalytic site " of theenzyme has been affirmed by kinetic studies of its denaturation in thepresence of 8~-urea. 49A remarkable finding was that undiminished activity was maintainedby a polyalanyl ribonuclease in which eight of the eleven amino-groups hadbeen modified, each one being coupled to a tetra- or penta-alanyl ~ e p t i d e .~ ~The positive charges on the original amino-groups thus cannot perform aspecific r61e in the activity of the molecule, either chemically or by maintain-ing structure. In a derivative where activity is retained, as in this case, noambiguity exists concerning a possible r61e of the groups which undergomodification ; where activity has disappeared, unequivocal interpretationsare more difficult.Other modifications of ribonuclease have been performed specifically toobtain information on the configuration of the molecule without specialregard to its enzymic activity. The differential rates of iodination oftyrosine residues 36c9 51 indicated, in contrast to an earlier report,52 thatonly four of the six residues were accessible: those at positions 25 and 97were unreactive.Digestion of the native molecule with ~hymotrypsin,~~and also with trypsin, has been employed to obtain information concerningthe nature of conformational changes occurring at transitional temperatures.46 H. Witzel and E. A. Barnard, Biochim. Biophys. Res. Comm., 1962, 7 , 289, 295.47 C. H. W. Hirs, Brookhaven Symp. Biol., No. 15, 1962, 154.4 8 A. M. Crestfield and F. W. Allen, J . Biol. Chem., 1954, 211, 363.4s C. A. Nelson and J. P. Hummel, J . Biol. Chem., 1962,237, 1567; E. A. Barnard,50 C. B. Anfinsen, M. Sela, and J. P. Cooke, J . Biol. Chem., 1962, 237, 1825.51 C. Chul-Yung and H. A. Scheraga, J . Biol. Chew., 1963, 238, 2958, 2965.5 2 C. Chul-Yung and H.A. Scheraga, Biochim. Biophys. Res. Comm., 1961, 6, 369.63 T. Ooi, A. Rupley, and H. Scheraga, Biochemistry, 1963, 2, 421, 432.Biochem. J . , 1962, 83, 1 4 ~ 474 BIOLOGICAL CHEMISTRYA strong inhibition of the action of ribonuclease by the copolymer of glutamicacid and tyrosine has been interpreted by an interaction between aromaticamino-acid residues and complementary areas on the ribonuclease mole-cule, over and above the expected long-range electrostatic interactionbetween inhibitor and e ~ y m e . ~ 4Hremogoblin.-The pioneer studies of Perutz and Kendrew on the three-dimensional structures of hzemoglobin and myoglobin in the crystalline statehave been outstanding, and the information obtained concerning interactionsof amino-acid side-chains with each other and with the solvent will beinvaluable for an understanding of the problems of protein structure ;detailed accounts have a~peared.~, 5 3 55 The question of whether the con-formation of a protein in the crystalline state differs from that in solutionhas been discussed by Doscher and Richards 56 in a study on the enzymicactivity of suspensions of ribonuclease S: “ Those aspects of the structureof the enzyme that relate to an active site are not markedly changed whenit passes from dilute solution to the crystalline state, but it seems unwise atpresent to assume that the result applies to all crystalline enzymes.” Areview 55 by Richards on “ The Structure of Proteins ” is commended.The announcements of the total amino-acid sequences of the a- and the/?-chain of hzemoglobin A, as determined by chemical methods, have nowbeen substantiated by full details of the experimental data.lga The completeagreement reported between the two investigations is a reflection of recentadvances in methodology, and communication.Concurrently, the completesequence of HEmoglobin F has been firmly e~tab1ished.l~~ Two of its fourchains are identical with the a-chains of hzemoglobin A; the other two(y-chains) each possess 146 amino-acid residues :GLY -his-PHE-thr-GLU-glu-ASP-lys-ALA-THR-ILEU-leu-try-gly-lys-val-aspNH ,-val-GLU-ASP-ALA-gly-gly-glu-THR-leu-gly-arg-leu-leu-val-val-tyr-pro-try-thr-glu-NH,-arg-phe-phe-ASP-ser-phe-gly-ASPNH,-leu-ser-SER-ALA-SER-ala -1LEU -met -gly -aspNH ,-pro-lys-val-lys-ala-gly -1ys-val-leu-THR -SER -LEU-GLY -asp-ALA-ILEU-LY S -his -leu-asp-ASP-leu-lys-gly -thr-phe-ala-GLUNH,-leu-ser-glu-leu-his-cys-asp-lys-leu-val-asp-pro-glu-aspNH,-phe-LYS-leu-leu-gly -aspNH,-val-leu-val-THR -Val-leu-ala-ILEU-his-phe-gly -1ys-glu-phe-thr-pro-GLU-val-gluNH,-ala-SER-TRY -gluNH ,-lys-MET-val-THR-gly-val-ala-SER-ala-leu-SER-SER-ARG-tyr-hisThe residues in capitals are those which differ from the correspondingresidues of the /?-chain.The sequence of the a-chain shows surprising lackof correspondence with that of the /?-chain, especially in view of the abilityof either chain to aggregate physically with a-chain, and then exhibit similaroxygenation properties as haemoproteins. The question of whether theoxygen affinity of haemoglobin is determined by the specific sequence ofamino-acids is still in dispute.A report that isolated haemoglobin S exhibiteda lower oxygen affinity than haemoglobin A 57 is in contrast with the resultsof other investigators, who found identical oxygenation characteristics. 586 4 M. Sela, J. Biol. Chem., 1962, 237, 418.5 5 F. M. Richards, Ann. Rev. Biochem., 1963, 32, 269.66 M. S. Doscher and F. M. Richards, J. Biol. Chem., 1963, 238, 2399.57 A. Riggs and M. Wells, Biochim. Biophys. Acta, 1961, 50, 243.68 J. J. P. Schruefer, C. J. Heller, F. C. Battaglia, and A. E. Hellegers, Nature,1962, 196, 550; J. Wyman and D. W. Allen, J. Polymer. Sci., 1951, 7, 499SMYTH: PROTEINS AND PEPTIDES 475As noted before, the removal of only two residues from the COOH-terminusof the p-chain profoundly altered the oxygen affinity of hEmoglobin A,29a fact which stresses the importance of primary sequence ; on the other hand,the influence of inorganic salts on the oxygen affinity of hemoglobin A hasrecently been confirmed in detail,59 and this should emphasize the necessityfor performing measurements of physiological properties under standardconditions.In summary, the oxygen affinity of haemoglobin appears to bedirectly affected by the conformation of the molecule, and the latter isdetermined both by the primary structure and by the environment of theprotein.Considerable attention has been given to conformational features ofhaemoglobin and the reactivities of its thiol groups. Reduced hzemoglobinwas less reactive than oxyhemoglobin towards both N-ethylmaleimide(NEM) and iodoacetamide.60 The principal site of reaction of both iodo-acetamide 6l and of NEM 6Za with hzemoglobin has been shown to be thecysteine residue a t position 93 of the ,!?-chain, but a slower reaction can alsotake place a t the terminal amino-groups.6Zb, Configurational changeshave been invoked to account for changes in the Bohr effect resulting fromaddition of thiol reagents to haemoglobin;63 the results of a variety of similarstudies have recently been s~mmarized.~* Since hemoglobin H, whichpossesses only ,!?-chains,65 exhibited no Bohr effect, a mechanism involvinginteraction between dissimilar chains has been proposed.66 An examinationof the oxygenation characteristics of haemoglobin a A would be of interest.Elegant application of dialysis techniques has revealed that haemoglobin,considered to be a tetramer, diffuses a t about the rate expected for a dimer.67Association, and not dissociation, was favoured at high ionic strength andthis was taken to indicate that the forces controlling the association are notelectrostatic in character. A particularly interesting study of the simul-taneous action of iodoacetamide and NEM on carboxylhaemoglobin furthersupported a dynamic view of the hEmoglobin molecule in equilibrium withits sub-units.68 The results were consistent with a symmetrical dissociationinto dimers, and a partial dissociation of the dimers at low pH to individualDeDtide chains :5 0 E.Antonini, J.Wyman, A. Rossi-Fanelli, and A. Caputo, J . Biol. Chem., 1962,237, 2773.6o R. E. Benesch and R. Benesch, Biochemistry, 1962, 1, 735; A. Riggs, J . Biol.Chem., 1961, 236, PC 1948.61 J. Goldstein, G. Guidotti, W. Konigsberg, and R. J. Hill, J . Biol. Chem., 1961,236,62PC 77.( a ) G. Guidotti and W. Konigsberg, J . Biot. Chem., 1964, in the press; ( b ) D. G.Smyth, A. Nagametsu, and J. S. Fruton, J . Amer. Chem. SOC., 1960, 82, 4600; (c) D. G.Smyth, 0. 0. Blumenfeld, and W. Konigsberg, Biochern. J . , in the press.63 D. G. Smyth, G. Meschis, and F. C. Battaglia, J . Gen. Physiot., 1961, 44, 889.64 J. F. Taylor, E. Antonini, and J. Wyman, J . Biol. Chem., 1963, 238, 2660.6 5 R. T. Jones and W. A. Schroeder, Biochemistry, 1963, 2, 1357.66 R.E. Benesch, H. M. Ranney, R. Benesch, and G. M. Smith, J . Biot. Chem.,6 7 G. Guidotti and L. C. Craig, Proc. Nut. Acad. Sci. U.S.A., 1963, 50, 46.6 8 G. Guidotti, W. Konigsberg, and L. C. Craig, Proc. Nat. Acad. Sci. U.S.A.,1961, 236, 2926.1963, 50, 774476 BIOLOGICAL CHEMISTRYHybridization between different haemoglobin molecules was explained as afunction of the rate of monomer formation; each chain was considered tohave a greater affinity for a dissimilar than for a similar chain, The possi-bility, therefore, that a haemoglobin molecule might be formed from identicalchains, though not thermodynamically probable, was not ruled out. Therecent isolation of molecules containing only ar-chains,69 ,9-chainsY70 ory-chains 71 is consistent with the equilibria discussed above.Myog1obin.-The chemical studies on whale myoglobin have beenadvanced by the characterization of a large number of chymotryptic peptidesin addition to the tryptic peptides previously described.2oa The applicationof cyanogen bromide, which cleaves specifically at methionine residues, hasliberated three fragments for further study.2M The following sequence of153 amino-acid residues includes the most recent additions to the almostcomplete sequence published by Edmundson ; 20bVal. Leu. Ser . Glu. Gly . Glu .Try. (Glu ,Leu ,Val,Leu,His ,Val ,Try). Ala. Lys .Val.Glu. Ala. Asp .Val. Ala. Gly . (His, Gly , Glu) Asp.lleu .Leu .lleu . Arg . Leu. Phe.Lys .Ser.His.Pro.Glu .Thr.Leu.Glu.Lys.Phe.Asp.Arg.Phe.Lys.His.Leu.Lys,Thr.Glu.Ala.Glu.Met .Lys. Ala. Ser.Glu. Asp .Leu .Lys .Lys.His .Gly .Val.Thr.Val.Leu. T hr . Ala .Leu. G1 y . Ala.lleu .Leu .Lys .Lys. L ys . G1 y . His .His. Glu. Ala. Glu.Leu.Lys.Pro.Leu.Ala.Glu.Ser.His.Ala.Thr.Lys.His.Lys.1leu .Pro.lleu.Lys.Tyr.Leu.Glu.Phe.lleu.Ser.Glu.Ala.lleu.lleu.His.Va1.Leu.His.Ser.Arg.His.Pro.Gly.Asp.Phe.Gly.Ala.Asp,Ala.Glu.Gly.Ala.Met.Asp.Lys.Ala.Leu.Glu.Leu .Phe . Arg .Lys .Asp .lleu . Ala . Ala . Lys .T yr . Lys . Glu .Leu. G1 y .T yr ( Glu-NH, ,GlY).This sequence represents some revision over that given in a recentReview 7 2 based on the combined results of the early chemical studies andX-ray analysis at a resolution (2 A"), lower than that (1.4 A") currentlybeing obtained.Cytochromes.-The total amino-acid sequences of cytochrome c fromeight different sources are presented in the Table.It would appear a reason-able assumption that a feature which differs in one of the enzymes, e.g.,the absence of an acetylated NH,-terminal residue in yeast cytochrome c,cannot be essential to the function of any of the cytochromes. However,although the Pseudomonas enzyme possesses the same function as the other6 9 E. R. Huehns, N. Dance, E. M. Shooter, and G. H. Beaven, J . Mol. Biol.,70N. Dance, E. R. Huehns, and G. H. Beaven, Biochem. J., 1963, 87, 240.71N. Dance and E. R. Huehns, Biochem. J., 1962, 83, 4 0 ~ .72 W. A. Schroeder, Ann. Rev. Biochom., 1963, 32, 301.73 €€. Matsubara and E. L. Smith, J. Biol. Chem., 1963, 238, 2732.7 4 T. Nakashima, H.Higa, A. Benson, and K. T. Yasonobu, Pacific Slope Con-75 S. K. Chan, S. B. Needleman, J. W. Stewart, 0. F. Walasek, and E. Margoliash,76 E. Margoliash, E. L. Smith, G. Kreil, and H. Tuppy, Nature, 1961, 192, 1125.7 7 G. Kreil, 2. Physiol. Chem., in the press.7t3 K. Narita, K. Titani, Y. Yaoi, H. Murakami, M. Kimura, and J. Vanacek,7 9 R. P. Ambler, Biochem. J., 1963, 89, 349.1962, 5, 511; K. Satake and T. Take, J . Biochem. Japan, 1962, 52, 304.ference, Hawaii, Aug. 1963.Fed. PTOC., 1963, 22, 658.Biochim. Biophys. Acta, 1963, 73, 670TI, e sequence of amino-acids i n C?ytochrome C from varioits1 10( a ) Acetyl-Gly -Asp-Val-Glu-Lys-Gly-Lys-Lys-Ileu- Phe-Ileu-Met-Lys-Cys-( Ser,Acetyl- Gly -Asp -Val-Glu-Lys- Gly -Lys-Lys-Ileu- Phe-Val-GluN-Lys---Cys- Ala-Acetyl-Gly- Asp-Val-Glu-Lys-Gly-Lys-Lys-Ileu- Phe-Val-GluN-Lys---Cys-Ala-( b )( c )Acet yl - Gly -Asp -Val- Glu-L ys - Gly -L y s- Lys-Ileu - Phe -Val- GluN- Lys-Cys -AlaAcetyl- Gly -Asp-Ileu-Glu- Lys-Gly -Lys-Lys-Ileu- Phe-Val-GluN-Lys-Cys-Ser-(4(e) (f) Acetyl-Gly-Asp-Val-Ala-Ly.s-Gl~-~ys-Lys-Thr-Phe-Val-GluN-~y~~(9) Thr-Glu-Phe-Lys-Ala-Gl~-rSer-Ala-Lys-Lys-Gl~-Ala-Thr-Leu-Phe-Ly~-T~r-Arg--Cys-Glu-Leu-(h) Glu -Asp -Pro - Glu -Val-Leu - Phe-L ys- AspN-L ys- Gly -Cys-Val(a) -Lys-H~s-Lys-Thr-Gly-Pro-AspN-Leu-His-Gly-Leu-Phe-Gly-Arg-Lys-Thr-Gl~-GluN-Ala-( b ) -Lys-His-Lys-Thr--Gly-Pro-AspN-Leu-His-Gly-Leu-Phe-Gly-Arg-Lys-Thr-Gly-(c) -Lys-His-Lys-Thr-Gly-Pro-AspN-Leu-His-Gly-Leu-Phe-Gly-Arg-Lys-Thr-Gly-GluN-( d ) - Lys-His- Lys-Thr-GZy - Pro- AspN- Leu-His-Gly-Leu-Phe -Gly -Arg-Ly s-Thr-Gly -GluN - Ala-Pro-(e) -Lys-His-Lys-Thr-Gly-Pro-AspN-Leu-His-Gly-Leu-Phe-Gly-Arg-Lys-Thr-Gly-(f ) -Lys-His- Lys- (Val,Gly, Pro,AspN) Leu-Try -Gly -Leu- Phe- Gly -Arg -Lys-Thr -( Gly - GluN) -Ah-Glu-(9) -Pro -His- Lys-Val-Gly - Pro- AspN - Leu-His- Gly -1leu- Phe - Gly - Arg-His- Ser-Qly -GluN- A la- (GluN,( h ) -Val -Gly-Pro -Ala-Tyr-Lys- Asp-Val- Ala- Ala-Lys- Phe-Ala-Gly-GluN-Ala-Gly-Ala-Glu-( a ) -AspN- Lys-Gly-Ileu-Ileu-Try-Gly-Glu-Asp-Thr-Leu-~~-~Glu- Tyr- Leu-Glu-AspN-Pro-( b ) -AspN- Lys-Gly-Ileu-Thr-Try-Gly-Glu-Glu-Thr-Leu-Met--Glu- Tyr- Leu-Glu-AspN- Pro-( C ) -AspN-Lys-Gly-Ileu-Thr- Try-Gly-Glu-Glu-Thr-Leu-Met-Glu- Tyr- Leu-Glu-AspN- Pro-( d ) -AspN- Lys-Gly-Ileu -Thr-Try-Lys-Glu-Glu-Thr-Leu-Met-Glu- Tyr- Leu-Glu-AspN- Pro-(e) -AspN- Lys-Gly-Ileu-Thr-Try-Gly-Glu-Asp-Thr-Leu-Met-Glu- Tyr- Leu-Glu-AspN- Pro-( f ) - Ser- L ys- G1 y -1leu-Val- Try - ( AspN, AspN, Asp ) -Thr -Leu-Me t - Glu- Tyr - Leu- Glu-Asp N - Pro-( g ) -Lys-Lys-AspN-Val-Leu- Try-Asp-Glu-AspN-AspN-Met-Ser -Glu- Tyr- Leu-Thr-(AspN,Pro,(h) -Gly-Ser-GluN-Val-Try--Gly-Pro-ileu-Pro-Met-Pro-Pro---- AspN-Ala-Val-Ser-Asp-( a ) - Phe-Val - Gly -1leu- Lys- Lys-Lys-Glu -Glu-Arg- Ala-Asp- Leu-Ileu- Ala- Tyr -Leu- Lys-Lys- Ala-( b ) -Phe-Ala-Gly-Ileu-Lys-Lys-Lys-Gly-Glu-Arg-Glu-Asp-Leu-Ileu-Ala-Tyr-Leu-Lys-(c) - Phe-Ala-Gly-Ileu- Lys-Lys-Lys-Gly-Glu-Arg-Glu-Asp- Leu-Ileu-Ala-Tyr-Leu- Lys-Lys-Ala-( d ) - Phe- Ala -GZy-Ileu- Lys- Lys-Lys-Thr-Glu-Arg-Glu- Asp- Leu-Ileu-Ala-Tyr- Leu- Lys-Lys-Ala-(e) - Phe- Ala - Gly -1leu- Lys- Lys-Lys-Ser -Glu-Arg -Val-Asp- Leu-Ileu- Ala-Tyr - Leu- Lys-Lys- Ala-( f ) - Phe- Ala -Gly -1leu- Lys- Lys-Lys-Gly -Glu-Arg- GluN-Asp - Leu- (Va1,Ala) - Tyr- Leu- Lys- Ser -Thr(g) - Phe-Gly-Gly-Leu - Lys- Lys-Glu-Lys- Asp-Arg-AspN-Asp- Leu-Ileu-Thr-Tyr- Leu- Lys-Lys-Ala-(h) -Ser-GluN-Lys.residues in italics are common t o the cytochromes from all eight sources, (a) man,73 ( b ) cattle,74(9) (h) pseudomonas.7930 4060 7090The author is indebted to Professor Hans Tuppy of the Institut fur Biochemie, Vienna478 BIOLOGICAL CHEMISTRYcytochromes, its amino-acid sequence shows remarkably little similarity tothat of the other enzymes. Caution is therefore recommended in inter-pretation of coincident sequences in molecules exhibiting similar properties.The recent elucidation of the sequence of cytochrome c-551 serves todemonstrate an effective approach to determinations of protein structure.Small peptides were obtained by successive enzymic degradation of theprotein, and the compositions of these were determined by quantitativemethods.The sequence of *amino-acids within each peptide was thenderived by sensitive, qualitative methods, among which was a new procedurefor sequential degradation employing a fluorescent reagent -60Further Methods used in Studies of Structure.-The problem of studyinga very large protein has been facilitated by new procedures for fragmenta-tion. A novel approach for dissociation of aggregated sub-units 81 has beenachieved in hzmoerythrin by succinylation of amino-groups, to releaseeight polypeptide chains.Further studies on the use of sulphite as a reagentfor the cleavage of disulphide bonds have confirmed that intra-chain bondsare cleaved in preference to inter-chain bonds. 82 Reduction of disulphidebonds by 2-mercaptoethanol, and alkylation of the thiol groups by iodo-acetate has been achieved under conditions which ensure both specificityand high yield.83 Other reagents used for alkylation have included acry-lonitrile,8* and N-ethylmaleimide,62C the extent of these reactions has beenfollowed by acid hydrolysis and determination of carboxymethylcysteineand S-( 1,2-dicarboxyethyl)-cysteine respectively ; with NEM, a comparisonbetween the amounts of ethylamine and of X-( 1,2-dicarboxyethyl)-cysteinereleased on hydrolysis provided a direct measurement of t,he specificity ofthe alkylation.Caution should be observed in the use of NEM as a reagentfor modifying proteins since its reaction with the thiol group of cysteine hasbeen found to result in the formation of two diastereoisomers with differentphysical properties.fCH - CF> RS - CH -Cq11 NEt 4- RSH __.). I ,NEtCH - C 6 CH2-COReagents for effecting modification of amino-groups under mild conditionsinclude ethyl acetimidate hydrochl~ride,~~ and cyanate.86, 8' The latter reac-tion has been developed into a quantitative method for the determinationof NH,-terminal residues in proteins and pep tide^.^'Cyanate was coupled with amino-groups, and subsequent treatment of thecarbamoyl derivatives with acid resulted in the formation of hydantoinsderived from the NH,-terminal residues.After isolation, the hydantoins8o W. R. Gray and B. S. Hartley, Biochefn. J., 1963, 89, 5 9 ~ , 379.I. M. Klotz and S. K. Nagy, Nature, 1962, 195, 900; S. K. Nagy and I. M. Klotz,82 R. Cecil and R. G. Wake, Biochem. J., 1962, 82, 401.89 A. 35. Crestfield, S. Moore, and W. H. Stein, J . Biol. Chern., 1963, 238, 622.84 L. We3 and T. S. Seibles, Arch. Biochem., 1961, 95, 470.85 M. L. Ludwig and R. Byrne, J . Arner. Chem. SOC., 1962, 84, 4160.88 G. R. Stark, W. H. Stein, and S. Moore, J . Biol. Chem., 1960, 235, 3177.87 G R. Stark and D. G. Smyth, J . Biol. Chem., 1963, 238, 214.Biochemistry, 1963, 2, 445, 923SMYTH: PROTEINS AND PEPTIDES 479were hydrolysed to the corresponding amino-acids for estimation andidentification.With the exception of serine and threonine, high yields ofall NH,-terminal residues were obtained.HNCO + NH,*CHR*CO-NH*CH . * * . * * *R*CH*NH2*CO&IAn important advance in t,he techniques for the separa,tion of peptideshas been reported.42~ 88 Successful column chromatography was accom-plished using the standard resins and buffer solutions of an automatic amino-acid analyser; the results obtained were highly reproducible and are en-couraging for the future use of modified systems in the detection of smalldifferences in structure among closely related proteins.New procedures have appeared for the selective cleavage of peptides.Hydrogen fluoride has proved a suitable reagent for effecting the N+Oshift on dipeptides,*g and it appears to be free of the side-reactions associatedwith other reagents.The problem of blocking the liberated amino-groupsat low pH values, where the reversed acyl shift does not occur, has beenapproached by the use of acetic anhydride in formic acid sw following theearlier method of Elliott,gob or by the use of potassium cyanate at pH 5.91Subsequent hydrolysis under mild conditions should yield peptides withserine or theonine at the NH,-terminus, but successful application of theN-tO shift to a protein of known structure is still awaited.Ribonuclease has been used as a model for the development of othermethods of specific cleavage.The reaction of trifluoroacetic anhydride withthe amino-groups of lysine has been used to restrict cleavages by trypsin tothe carboxyl group of arginine residues ;92 the trifluoroacetyl substituentswere removed from the resulting peptides under mild conditions. N-Bromo-succinimide cleavage of reduced carboxymethylated ribonuclease, which con-tains no tryptophan, occurred specifically at the carboxyl group of tyrosineresidues, releasing the expected NH,-terminal residues in moderate yield.36d8 8 W. A. Schroeder, R. T. Jones, J. Cormick, and K . McCalla, Analyt. Chem., 1962,34, 1570.89 S . Sakakibara, K. H. Shin, and G. P. Hess, J. Amer. Chem. SOC., 1962, 84,492 1.(a) W. Schneider, Fed. Proc., 1960, 19, 334; (b) D.F. Elliott in “ The ChemicalStructure of Proteins,” eds. G. E. W. Wolsfenholme and M. P. Cameron, Churchill,London, 1953.91 G. R. Stark and D. G. Smyth, J. BioZ. Chem., in the press.B2 R. F. Goldberger and C. B. Anfinsen, Biochemistry, 1962, 1, 401480 BIOLOGICAL CHEMISTRYA procedure for the introduction of a thiol group into a protein wouldbe particularly important because of the possibility of attaching a heavymetal at a single, known position in the molecule. Such derivatives are indemand for their possible r61e as isomorphous replacements for use in thedetermination of protein structure by X-ray crystallography. Full detailsof the thiolation of amino-groups in ribonuclease by reaction with homo-cysteine thiolactone have revealed, disappointingly, that a mixture of pro-ducts was formed containing derivatives in which up to five sites had beenmodified.g3 After prolonged reaction, some disulphide interchange occurred ;evidence was also presented that an exchange with one disulphide bond hadlittle effect on enzymic activity. In this connexion, it is of interest that aribonuclease enzyme isolated from B.subtilis is reported to contain nodisulphide bonds, and this enzyme is immune to the action of iod0acetate.~4Antigenicity.-Three chemical approaches have been used in the study ofthe structural basis of immunological reactions. (1) Synthetic polypeptideshave been employed as antigens possessing determinants of well-definedand narrow specificity. Copolymers of glutamic acid and tyrosine, inparticular, have been used to probe the nature of the sites on antibodieswhich combine with these antigen~.~5 The smallest synthetic polypeptideantigen has been found 96 to have a molecular weight of about 4000. Overallshape did not seem to be a critical factor in antigenicity, but the immuno-logically important area needed to be readily acce~sible.~7 On the basis ofinhibition studies with diamines, the distance between negatively chargedgroups in the antibody has been estimated as 7-9 A", which corresponds tothe separation of adjacent amino-acid side-chains on the sa,me side of apolypeptide chain ; the separation of positively charged groups was estimatedto be greater, probably every other residue on the same side of the poly-peptide chain.95b An interesting observation was that, although neitherpoly(g1utamic acid) nor polylysine was antigenic, an insoluble, electrostaticaggregate of the two homopolymers did exhibit antigenicity; most of thespecificity was directed against the p~lylysine.~* The suggestion was madethat a poor antigen, or a small basic peptide, may become an effectiveantigen if given in admixture with poly( glutamic acid).This possibilitymay provide a means of obtaining antagonists to physiologically activehormones. (2) Antibodies have been prepared to antigens of known amino-acid sequence. For example, peptides from ribonuclease have been testedfor inhibition of the reaction between ribonuclease and its antiserum ;99 thebinding sites on the antigen were located at two well-defined regions, residues38-62 and 105-124 (see Fig.1). Hzemoglobin, known to be a very weakantigen, possesses antigenic sites in the interior of the folder molecule. Theisolated j3-chain has been found to be a more potent antigen,loO and antiserum93 F. H. White and A. Sandoval, Biochemistry, 1962, 1, 938.9 4 S. Nichimura and H. Ozawa, Biochim. Biophys. Acta, 1962, 55, 426.9 5 (a) S. Fuchs and M. Sela, Biochem. J., 1963, 87, 70; ( b ) T. J. Gill, H. W. Kunz,96 D. Givol, S. Fuchs, and M. Sela, Biochim. Biophys. Acta, 1962, 63, 222.9 7 M. Sela, S. Fuchs, and R. Amon, Biochem. J., 1962, 85, 223.9 8 T. J. Gill and P. Doty, Biochim. Biophys. Acta, 1962, 60, 450.99 R. K. Brown, J . Biol. Chem., 1962, 237, 1162.E. Friedman, and P.Doty, J. Biol. Chem., 1963, 238, 108.looA. Askonas and D. G. Smyth, Nature, 1964, 201, 496SMYTH: PROTEINS AND PEPTIDES 481prepared to the p-chain cross-reacted weakly with haemoglobin. Trypticpeptides from the ,&chain partially inhibited binding of the latter to itsantiserum. Similar studies have been reported with peptides from TMVprotein.lol (3) Chemical modifications of anti-hapten antibodies have beenperformed. In one case the presence of an important amino-group in anantibody site was inferred,102 but the conclusion contrasted with the findingthat guanidination of 75% of the amino-groups in the same antibody didnot change its ability to participate in specific precipitation. lo3 Interpreta-tions of studies in which chemical reagents are added to complex mixturesof proteins have rarely been unequivocal.Adrenocorticotrophic Hormone.-The total synthesis of a 39-residuepeptide with the same structure as the natural hormone (ACTH) has beenachieved by Schwyzer and Sieber.3 This great achievement follows less thanten years after the synthesis of the first peptide hormone by du Vigneaudand his colleagues.The reaction of periodate with the NH,-terminal serineresidue of ACTH to give a glyoxylyl residue, and modification of the latterto a glycine residue, resulted in no loss of extra-adrenal corticotrophica~tivity.10~ The r61e of methionine, on which some emphasis had beenplaced following isolation of an inactive sulphoxide derivative,1O5 has beenclarified by its replacement by a-aminobutyric acid in a synthetic analogue/ /!\CH-CH, .OHFIG.2.M. M. Marsh, Biochim. Biophys. Acta, 1962, 58, 556.1Diagrammatic representation of the suggested conformation of angiotensita 11.108[Reproduced, by permission, from R. R. Smeby, K. Arakawa, F. M. Bumpus, andlol J. D. Young, E. Benjamini, M. Shimizu, C. Y. Leung, and B. F. Feingold,lo2 C. C. Chen, A. L. Grossberg, and D. Pressman, Biochemistry, 1962, 1, 1025.lo3 A. F. S. A. Habeeb, H. G. Cassidy, P. Stelos, and S. J. Singer, Biochim. Biophys.lo4 H. B. F. Dixon and L. R. Weitkamp, Biochem. J., 1962, 84, 462.lo6 T. Lo, J. S. Dixon, and C. H. Li, Biochim. Biophys. Acta, 1961, 53, 584; M. L.Dedman, T. H. Farmer, and C. J. 0. R. Morris, Biochem. J., 1961, 78, 348.Nature, 1963, 199, 831.Acta, 1959, 34, 439.482 BIOLOGICAL CHEMISTBYwith retention of activity.lo6 Syntheses of other peptides related to ACTHhave revealed further relationships between structure and melanocyte-stimulating properties ,107Angiotensh-It has been suggested that the octapeptide, Angiotensin11, may possess a preferred configuration, even in the absence of receptor,and a proposed three-dimensional model has been based on an a-helix inwhich six amino-acid residues were involved.108The r61e ascribed to the aspartic acid and arginine residues at the NH,-terminus of angiotensin was that of stabilizing an active conformationof the molecule, but no specific interactions of these residues with others inthe hormone were proposed.It may be noted from the precise experimentsof Kennard and Walker lo9 that direct electrostatic interactions betweenamidine and carboxylate groups can endow considerable stability in certainmodel compounds in which these groups are suitably orientated.Somemeasurements of optical rotatory dispersion in angiotensin have been inter-preted as indicating a definite degree of order which was decreased by8M-UI?ea,los and some loss of biological activity of the hormone has also beenreported to occur in urea.ll0 Further studies, however, have failed to pro-vide solid support for the hypothesis involving a rigid conformation. Theliydroxyl group of the tyrosine residue has been found to possess a normalpKvalue,lfl and this makes its participation in hydrogen bonding improbable.Detailed experiments by Paiva, Paiva, and Scheraga, 112 including determina-tions of molecular weight, direct and spectrophotometric titrations, opticalrotatory dispersions, and hydrogen-deuterium exchange, strongly supportedthe view that the hormone exists in solution as a monomeric, random poly-peptide chain.It seems unlikely that a predetermined, ordered spatialarrangement of the molecule is necessary for biological activity.The synthesis of a large number of analogues by Schwyzer, and by Pageand Bumpus, has not provided any compounds with enhanced, prolonged,or antagonistic action, though some analogues have proved to be moreselective than the parent hormone with respect to their biological actions.Small modifications of angiotensin have resulted in loss of activity to a greateror lesser extent, and consequently certain residues in the molecule havebeen presumed to be particularly important for activity.These includephenylalanine as the C-terminal amino-acid, proline as the penultimateresidue, tyrosine in position 4, and histidine in position 6. In other positions,there is a greater degree of freedom. The high activity of @-aspartyl-,ll3and deaminoangiotensin,11* in which the NH,-terminus had been modified,106 K. Hofmann, R. D. WeIls, H. Yajima, and J. Rosenthaler, J . Amer. Chem. Soc.,1963, 85, 1546.lo' B. T. Pickering and C. H. Li, Biochim. Biophys. Acta, 1962, 62, 475.108 R. R. Smeby, K. Arakawa, F. M. Bumpus, and M. M. Marsh, Biochim. Biophys.Acta, 1962, 58, 550.lo9 0.Kennard and J. Walker, J . , 1963, 1046, 5513.F. M. Bumpus, P. A. Khairallah, K. Arakawa, I. H. Page, and R. R. Smeby,Biochim. Biophys. Acta, 1961, 46, 38.A. C. M. Paiva and T. B. Paiva, Biochirn. Biophys. Acta, 1962, 56, 339.112 T. B. Paiva, A. C. M. Paiva, and H. A. Scheraga, Biochemistry, 1963, 2, 1327.113 B. Riniker, H. Brunner, and R. Schwyzer, Angew. Chem., 1962, 74, 469.114 K. Arakawa, R. R. Smeby, and F. M. Bumpus, J . Amer. Chem. SOC., 1962,84, 1431SMYTH: PROTEINS AND PEPTIDES 483has confirmed the comparative unimportance of this section of the molecule.These latter derivatives were more stable than angiotensin to the action ofenzymes in serum and so it appears that one of the enzymes involved is anaminopeptidase. Angiotensin coupled at the NH,-terminus to poly-0-acetylserine was found to possess considerable activity ;114 it was thereforesuggested that the octapeptide exerts its biological action in vivo withoutpenetration of the cell wall.Angiotensinamide has been found to be chemically unstable under rathermild conditions, probably because of the ease of formation of an intermediateimide at the NH,-terminal asparagine residue.i13CH2- CO * NHIR IH2N * CH -CO;1HCH2-CONH2 CH2-C,O / CH 1 - CO2H-+- 1 ,NR --& IH2N.CH- CO H2N0CH-CCO*NHRIHzN *CH-CO *NHR\ CH2-C02H I $- RH -& NH,HZN *CH - COLHMultiple forms of analogous peptides from elastase, ribonuclease, 14' andcytochrome c-551 79 have also been reported. The rapid release of asparticacid on acid hydrolysis of proteins may occur by a similar mechanism.l16Bradykiuh-A report on a symposium on structure and function ofbiologically active peptides has appeared.117 Limited progress has beenmade toward an understanding of the mechanism of action of bradykininand of its precise mode of release from plasma proteins.The existence of two precursors has been inferred from some data onrates of appearance of kinin activity in serum treated with different activa-tors.ll* The quantitative assay of kinin activity in blood, however, iscomplicated by the presence of kinin-releasing and kinin-destroying enzymes;attempts have been made t o inactivate the latter by addition of chelatingagents and by treatment with acid.l19 Incubation at pH 7 of acid-treateda2-globulin fractions led to the formation of a number of compounds whichexhibited kinin activity, one of which has been isolated and identified asmethionyl-lysyl-bradykinin.l20 This analogue has been synthesized, andexhibited similar biological properties to the hendecapeptide isolated fromplasma.121A large number of synthetic analogues has now been prepared. Of115 M. A. Naughton, F. Sanger, B. S. Hartley, and D. C. Shaw, Biochem. J., 1960,116 J. Schultz, H. Allison, a,nd M. Grice, Biochemistry, 1962, 1, 694.117 " Structure and Function of biologically active peptides," Ann. New York Acad.118 J. Margolis and E. A. Bishop, Australian J . Exp. Biol. Med. Sci., 1963, 41, 293.ll0 G. P. Lewis and H. Edery, J. Physid., 1962, 160, 2 0 ~ .l 2 0 D.F. Elliott, G. P. Lewis, and D. G. Smyth, Biochem. J., 1963, 87, 2 1 ~ .lel E. Schroder, Experientia, 1964, 20, 39.7'7, 149.Sci., 1963, 104, 1484 BIOLOGICAL CHEMISTRYthese, the glycine-6-analogue deserves note because its equal biologicalactivity to bradykinin excludes the possibility of an important r61e for thehydroxyl group of serine in position 6.122 Retrobradykinin, a nonapeptidewith a sequence of amino-acids in the reverse order of bradykinin, may bementioned ;123 it was inactive.Eledoish-A new peptide hormone, the most potent vasodilator known,has been isolated from the salivary gland of molluscs. Degradation hasestablished the following sequence 124 which has been confirmed bysynthesis :125pyr -pro -ser -1ys -asp -&la-phe -ileu-gly -leu-met -NHOxytocin.-The number and variety of analogues of oxytocin that havebeen recently synthesized attests to advances in currently available methods.Some derivatives have been prepared in the hope that an analogue exhibitingprotracted action would be obtained.Thus, glycyloxytocin,126 leucy-loxytocin and leucyl-glycyl-glycyl-oxytocin,~27 which themselves are com-paratively inactive, offered the possibility of releasing oxytocin uponexposure to aminopeptidases present in serum. However, although pro-tracted effects have been seen, definite evidence of oxytocin release has notbeen obtained. Other derivatives, initially prepared for the study ofstructure-activity relationships, have been examined for antagonistic pro-perties against the natural hormone.Among these, the O-methyltyrosinederivative 12* has been found to exhibit variable inhibitory properties, andintrinsic activity was frequently seen at these concentrations. Carbamoyl-ated derivatives of oxytocin,l29 assayed on isolated rat uterus, act as specificinhibitors of oxytocin without intrinsic activity. 1 -Acetyl-8-argininevaso-pressin exerts a prolonged depressor effect on blood but givesno inhibition during in vitro assays.Investigations designed to elucidate features essential for the functionof oxytocin have led away from the concept of important reactive groupsper ~ f 3 . l ~ ~ The very low biological activity exhibited by glycyloxytocin,126carbamoyloxytocin,l32 and N-methylhemicystineoxytocin contrasts withthe high potency of de-amino-oxytocin 133 and may be explained by sterichindrance. Similarly, deoxyoxytocin was active l34 yet an analogue inwhich the tyrosine hydroxyl group has been modified exhibited little122 M.Bodanszky, J. J. Sheehan, M. A. Ondetti, and S. Lande, J. Amer. Chem.lZ3 S. Lande, J . Org. Chem., 1962, 27, 4558.124 V. Erspamer and A. Anstasi, Experientia, 1962, 18, 58.125 E. Sandrin and R. A, Biossonas, Experientia, 1962, 18, 59.126 V. du Vigneaud, P. S. Fitt, M. Bodanszky, and M. O’Connell, Proc. SOC. Exp.12’ K. Jost, J. Rudinger, and F. $om, CoZZ. Czech. Chem. Comm., 1963, 28, 2021.12* H. D. Law and V. du Vigneaud, J . Amer. Chem. SOC., 1960, 82, 4579.lZ9 D. G. Smyth, Biochem. J., 1964, in the press.130 R.0. Studer and W. D. Cash, J . BioZ. Chem., 1963, 238, 657.131 J. Rudinger and I. Krejci, Experientia, 1962, 18, 585.132G. W. Risset, A. M. Poisoner, and D. G. Smyth, Nature, 1963, 199, 69.133 D. B. Hope, V. V. S . Murti, and V. du Vigneaud, J . Biol. Chem., 1962, 237,ls4P. A. Jaquenod and R. A. Boissonnas, Helv. Chim. Acta, 1959, 42, 788; M.Soc., 1963, 85, 991.BioZ. Med., 1960, 104, 653.1563.Bodanszky and V. du Vigneaud, J . Amer. Chem. SOC., 1959, 81, 6072SMYTH: PROTEINS AND PEPTIDES 485activity. 128 Deaminodeoxyoxytocin, which possesses neither a chemicallyreactive group nor any group bearing a formal electric charge, was foundto be a~tive.13~ Its initial attachment to a receptor cannot involve anelectrovalent or a covalent bond ; the short-range hydrophobic forces pre-sumably involved appear to require precise complementarity betweenhormone and receptor only at certain regions of the peptide.du Vigneaudand his colleagues have replaced the chemical group under investigation byhydrogen in the synthesis of -4-a-aminobutyric oxytocin acid and 5-alanine-0 x y t o ~ i n ; l ~ ~ a critical requirement was found for the amide in position 5 ofthe natural hormone.A plausible hypothesis 40, 137 for the mode of action of peptide hormonesis that the combination of the peptide with a portein receptor results inconfigurational changes in the latter to produce an activated molecule. Anunderstanding of the underlying features required for such associations maylead to an understanding of the biological properties of oxytocin and itsanalogues.lS6D.B. Hope and V. du Vigneaud, J. Biol. Chem., 1962, 237, 3146.13* V. du Vigneaud, G. S. Denning, S. Drabarek, and W. Y. Chan, J. Biol. Chem.,1963, 238, PC 1560; P. A. Jaquenod and R. A. Boissonnas, Helv. Chirn. Acta, 1959,42, 788.l37 F. M. Richards and P. J. Vithayathil, “ Protein Structure and Function,”Brookhaven Symp. Biol., No. 13, 1960, 1153. HETEROMERIC SACCHARIDESBy D. W. Russell and R. J. SturgeonWE consider mainly those oligo- and poly-saccharides that are covalentlylinked to proteins or lipids, or that contain acidic residues. Many participatein important biological processes, the key to whose understanding lies inthe detailed structural chemistry with which this Report is chiefly con-cerned.Gbcoproteins.-Recent reviews have dealt with glycoproteinsl and theirbiological significance. The albumin fraction of egg white has three electro-phoretically distinct components, of which two, ovalbumin and ovomucoid,contain carbohydrate prosthetic groups. Crystalline ovalbumin as normallyisolated is probably inhomogeneous with respect to the prosthetic group.Fractions of a peptic digest had mannose: glucosamine ratios varyingbetween 1-7 and 3.2.3 This may explain why both glucosamine andmannose 5, have been found as non-reducing end-groups although chain-branching is not excluded.A glycopeptide from proteolytic enzymic digests of ovalbumin yieldedD-mannose, D-glucosamine, aspartic acid and ammonia in the ratio 5 : 3 : 1 : 1on acid hydrolysis.7-9 The saccharide-peptide link is between glucosamineand aspartic acid.Partial acid hydrolysis of an ovalbumin glycopeptideyielded a compound that, on an ion-exchange column, was not resolvedfrom synthetic ~-~-~-~-a~paTtylamin0-2-deoxy-~-g~ucose (1) .lo However,other workers showed by degradative studies and by chromatographic-electrophoretic, and infrared spectral comparison with synthetic 2 -ace tamido ,1 R. Bourrillon and R. Got, Expos. ann. Biochim. mid., 1963, 24, 25; W. Pigman,2 Z. Dische, Expos. ann. Bwchirn. mid., 1963, 24, 49; G. Biserte, R. Havez, andL. W. Cunningham, R. W. Clouse, and J. D. Ford, Biochim. Biophys. Acta,* J. R. Clamp and L. Hough, Chem. and Ind., 1963, 82.P. D. Bragg and L. Hough, Biochem.J., 1961, 78, 11.G. S. Marks, R. D. Marshall, and A. Neuberger, Biochem. J., 1962, 84,A. P. Fletcher, G. S. Marks, R. D. MarshaI1, and A. Neuberger, Biochem. J.,* E. D. Kaverzneva and V. P. Bogdanov, Biochem. (U.S.S.R.), 1962, 27, 233.l o F. Micheel, E. A. Ostmann, and G. Pielmeier, Tetrahedron Letters, 1963,i b a . , p. 67.R. Cuvelier, ibid., p. 85.1963, 78, 379.3 0 ~ .1963, 87, 265.I. Yamashina and M. Makino, J. Biochem. (Japan), 1962, 51, 359.115RUSSELL AND STURGEON : HETEROMERIC SACCHARIDES 487l-~-~g'-aspartamido-1,2-dideoxy-~-g~ucose (2), that the latter is liberatedby partial acid hydrolysis of the ovalbumin glycopeptide. 11-13The carbohydrate composition of ovomucoid was first studied more than20 years ago;l* recent studies on glycopeptides from the protein have givenconflicting results. A glycopeptide from proteolytic enzymic digests con-tained hexose and glucosamine in the molar ratio 5 : 8.The amino-acidsasp, thr, ser, ala, and gly were present (1 mole each), together with leu(0.5 mole), and N-terminal asp, ala, gly, and leu were detected, although thepreparation was electrophoreticaUy and chromatographically homogeneous. l5In pronase digests of the protein, two glycopeptides have been found, bothcontaining glucosamine, galactose, and mannose in 9 : 1 : 5 molar ratio.One was stable to alkali; on dinitrophenylation and acid hydrolysis it gaveDNP-asp and DNP-thr. The conclusion that both amino-acids are boundto the same oligosaccharide, which may thus form an inter- or intra-chainlink in the proteiriY16 is valid only if the glycopeptide is a single entity.Asimilar glycopeptide fragment, obtained by papain-pronase digestion, was amixture of asp-thr and thr-asp, in both of which carbohydrate was attachedto aspartic acid.17 A glycopeptide containing both cys and asp was alsoisolated from pronase.digests by one group 16 but not by the 0ther.l' Thepresent evidence favours the existence in ovomucoid of three differentoligosaccharide units, each containing D-galactose, D-mannose, and D-glucosamine in the same proportions and each linked to the protein " back-bone" through the amide group of asparagine. One oligosaccharide unitalso contains N-acetylneuraminic acid.17The heterogeneity of ovomucoid has been discussed in terms of possibleremoval of N-acetylneuraminic acid residues during isolation.l8 Results sofar obtained gre equally consistent with the presence in the isolated proteinof three molecular species, each with an identical protein backbone butbearing different prosthetic groups.Similar doubt surrounds the status of the a,-acid glycoproteins isolatedfrom mammalian plasma and so called because of their low isoelectric pH.In pooled human plasma, this protein fraction contains a t least seven electro-phoretically distinguishable component^.^^ Six or seven components werealso present in q-acid glycoproteins from single individuals. Part of thecomplexity may be due to differences in sialic acid content and/or com-position, for enzymic removal of the sialic acid residues decreased to two thenumber of resolvable components. 2o Fractionation was also obtained withSephadex G-25.21 Two acid glycoproteins of bovine plasma, orosomucoidl1 V. Bogdanov, E. Kaverzneva, and A. Andreyeva, Biochim. Biophys. Acta,G. S. Marks, R. D. Marshall, and A. Neuberger, Biochem. J., 1963, 87, 274.l3 I. Yamashins, K. Ban-i, and M. Makino, Biochinz. Biophys. Acta, 1963, 78, 382.l4 M. Stacey and J. M. Woolley, J., 1940, 184.l5 F. K. Hartley and F. R. Jevons, Biochem. J., 1962, 84, 134.l6 J. Montreuil, G. Biserte, and A. Chosson, C m p t . rend., 1963, 256, 3372.l7 R. Montgomery and Y . - C . Wu, J . Biol. Chem., 1963, 238, 3547.A. K. Chatterjee and R. Montgomery, Arch. Biochem. Biophys., 1962, 99, 426.lS K.Schmid, J. P. Binette, S. Kamayima, V. Pfister, and S . Takahashi,2oK. Tokita and K. Schmid, Nature, 1963, 200, 266.21 M. Ledvina, J . Chromatog., 1963, 11, 71.1962, 65, 168.Biochemistry, 1962, 1, 959488 BIOLOGICAL CHEMISTRYand M2, had similar carbohydrate compositions. Glucosamine, galactose,and mannose were present in 1 : 1 : 1 molar ratio, and three different sialicacids were found : N-acetyl- and N-glycolloyl-neuraminic acids, and a thirdthe acyl group of which was not identified.22 Pronase digestion yieldedfrom human a,-acid glycoprotein a glycopeptide, homogeneous in the ultra-centrifuge. Heterogeneity due to partial removal, or plurality, of sialicacids was avoided by previous digestion with sialidase. The glycopeptide onhydrolysis yielded hexose, fucose, and glucosamine (8 : 1 : 6) with asp, thr,and ammonia (1 : 1 : 2).As the amino-groups of both amino-acids werefree, and two moles of ammonia were liberated by hydrolysis, linkage ofboth amino-acids to carbohydrate by glycosylamide bonds was suggested.23As with ovomucoid, the presence of two amino-acids each linked to the sameoligosaccharide would suggest that the carbohydrate is an inter- or intra-chain bridge in the protein. By enzymicand partial acid hydrolysis, a glycopeptide with aspartic acid as the onlyamino-acid was isolated. 24 Enzymic removal of sialic acid and galactosehad little effect upon the optical rotation or solubilities of the protein.25This would be surprising if the conformation were partly determined bycarbohydrate bridges.Finally, an orosomucoid preparation was unchangedin electrophoretic mobility, and retained antibody-fixing properties to anenhanced degree, after periodate oxidation. 26 However, structures in whichan oligosaccharide bridge remains a bridge through such procedures can stillbe envisaged.A promising approach to sequence determination in carbohydratesdepends upon the sequential utilization of substrate components by agrowing culture of a micro-organism. When an a,-acid glycoprotein pre-paration from nephrotic urine was included in the growth medium ofRhodopseudomow palustris, the sugars of the prosthetic group were releasedsequentially. Only when one sugar was completely released did the nextsugar appear in the medium, and the enzymes responsible could therefore beisolated and their specificities determined.27 The results were in accordwith previous structural work on an a,-acid glycoprotein preparation that,however, was probably a mixture.28Glycopeptides have also been obtained from proteolytic enzymic digestsof pleuromucoid, an a,-acid glycoprotein from pleural fluid. 29 Amino-acidsaccounted for 12% of the glycopeptide mixture, which contained hexoses,hexosamines, sialic acid, and fucose. Zone electrophoresis and DEAE-cellulose chromatography gave only partial fractionation. A structure wassuggested in which the pleuromucoid protein bears 5-6 carbohydrategroups of average molecular weight ( M ) about 3000.Biochemistry, 1963, 2, 10.and I.Yamashina, ibid., p. 365.Some contrary evidence exists.28 A. Bezkorovainy, Arch. Biochem. Biophys., 1963, 101, 66; A. Bezkorovainy,23 N. Ui and 0. Tmutani, J . Biochem. (Jupum), 1962,51,370; K. Izumi, M. Makino,24 S. Kamayima and K. Schmid, Bwchim. Biophys. Acta, 1962, 63, 266.25 K. Schmid and S. Kamayima, Biochemistry, 1963, 2, 271.26 S. A. Barker and P. H. Whitehead, Clinica Chim. Acta, 1963, 8, 848.27 S. A. Barker, G. I. Pardoe, M. Stacey, and J. W. Hopton, Nature, 1963,197,231.28 E. H. Eylrtr and R. W. Jeanloz, J . Biol. Chem., 1962, 237, 622, 1021.29 R. Bourrillon, R. Got, and D. Meyer, Biochim. Biophys. Actu, 1963, 74, 255RUSSELL AND STURGEON : HETEROMERIC SACCHARIDES 489In the glycoproteins so far mentioned, the evidence favours a linkagebetween glucosamine and asparagine (2).A different situation exists forthe salivary glycoprotein of ovine submaxillary gland, which contains 40%of carbohydrate. Residues of N-acetylneuraminyl-(2 +6)-N-acetylgalactos-amine are distributed along the protein chain.30 Almost 90% of theseunits were rapidly removed by alkali, the rest much more slowly. Withlithium borohydride 90% of the dicarboxylic amino-acids disappeared fromthe protein. Hydroxylamine gave similar results; it seems that some 90%of the disaccharide groups esterify asp and glu residues. Since the glyco-protein did not reduce alkaline o-dinitrobenzene or Benedict's reagent, theesterified hydroxyl group is presumably that in the l-position of 2-acetamido-2-deoxygalactose (3).The resistant 10% of carbohydrate may be linked' NHAC (3)by O-glycoside bonds to hydroxyl groups of serine and threonine, for furthertreatment with hydrazine gave a glycopeptide, cont,aining only galactoeamine,gly, ser, ala, and ~ a l . ~ l The slow removal by alkali of the remaining 10% ofcarbohydrate may be by /3-elimination, a process a t one time suggested toaccount for the release of carbohydrate by alkali from ovom~coid.~~Reticulin, a glycoprotein from bovine spleen, gave after proteolysis anelectrophoretically homogeneous glycopeptide of M about 9000. Theglycopeptide was also released by 8M-urea. A structure of two nonadeca-peptide chains joined by three pairs of tetrasaccharide bridges was suggestedfor the glyc~peptide,~~ and its possible r61e in the biosynthesis of collagenwas discussed.33The carbohydrate of fibrinogen has been studied by controlled periodateoxidation of the glycoprotein.Mannose and N-acetylglucosamine were notattacked, so that the former is linked 1 : 3 and the latter 1 : 3 or 1 : 4.Galactose was attacked; it is thought to be linked 1 : 6, and to occupy thenon-reducing terminal position after removal of sialic a ~ i d . 3 ~ Normalclotting does not occur after removal of sialic acid. Clotting is accompaniedby release of sugars from fibrinogen by an enzyme (LLF) whose actionrequires the sialic acid end-groups. 35 Glycopeptides have been isolatedfrom pronase digests of the glycoprotein. 36The serine content of chondroitin sulphate (see below) was unaltered by30 A.Gottschalk, W. H. Murphy, and E. R. B. Graham, Nature, 1962, 194, 1051.31 E. R. B. Graham, W. H. Murphy, and A. Gottschalk, Biochirn. Biophys. Acta,32 0. Snellman, Acta Chern. Scand., 1963, 1'9, 1049.33 0. Snellmann, Acta Chem. Scand., 1963, 17, 1057, 1062.34 L. Mester, E. Moczar, and K. Laki, Compt. rend., 1963, 256, 307.35K. Laki and N. Chandrasekha, Nature, 1963, 197, 1267.36 L. Mester, E. Moczar, G. Medgyesi, and K. Lalci, Compt. rend., 1963, 256,1963, 74, 222.3210490 BIOLOGICAL CHEMISTRYextensive proteolysis so that this amino-acid may be directly linked to thepolysaccharide. 37 Alkali removed all amino-acids from chondroitin sul-phate ; two-thirds of the serine was destroyed, threonine being unaffected.This finding, and the results of hydrazine treatment, together exclude thepossibility of an ester bond linking protein to chondroitin sulphate; the linkmay be glycosidic through the serine hydroxyl group, alkaline degradationtaking place by p-elimination.38 Cartilage digested with hyaluronidase andproteolytic enzymes yielded a small glycopeptide containing uronic acid,galactosamine, galactose, and serine. The glycopeptide had no reducingend-group, 39 and linkage of the polysaccharide, through the galactose reduc-ing group, to serine was suggested. Galactose and serine were also obtainedfrom heparin.40The x-casein from cow’s milk is split by rennin into x-paracasein (free ofcarbohydrate) and x-caseino-gly~opeptide.~~ The former has C-terminalphenylalanine.Treatment of x-casein by lithium borohydride similarly gavetwo fragments; phenylalaninol was found in the hydrolysate of the para-casein-like fragment .42 Esterification of the phenylalanine carboxyl witha sugar or amino-acid hydroxyl of the glycopeptide is thus indicated.Glycopeptides have been isolated from other caseins including that fromhuman m i l k . 4 3 The carbohydrate composition of polar-bear casein hasbeen determined.44Fractionation of bovine colostrum gave a complex glycopeptide inwhich a heneicosapeptide ‘‘ backbone ” was believed to bear four identicalsialylgalactosylacetamidodeoxyhexose residues.45 Glycopeptides frompooled human colostrum were separated by chromatography on DEAE-cellulose into several fractions of M about 3500.Hexosamine, hexose, sialicacid, and 6-deoxyhexose were found in all fractions; the peptide contentranged from 2 to 50%.4* Fractionation by gel filtration through SephadexG-25, and column and paper chromatography, gave three glycopeptidefractions each of which contained, in different proportions, galactose,glucosamine, galactosamine, fucose, and sialic acid, with amino-acids. 47The interstitial cell-stimulating hormone from sheep pituitary, degradedwi€h pronase, gave a glycopeptide fraction, about half of which consisted ofhexoses and hexosamines. Ser, thr, asp, and glu were among ten amino-acids present, aspartic acid occupying the N-terminu~.~~ In glycopeptides87 A. A. Castellmi, B. Bonferoni, S. Ronchi, G. Ferri, and M. Mlcovati, ItaZ.J .BwoJtem., 1963, 11, 187.88 B. Anderson, P. Hoffman, and K. Meyer, Biochim. Biophys. Acta, 1963, 74,309.38 L. RodBn, J. D. Gregory, and T. C. Laurent, Fed. Proc., 1963, 22, 413.40 U. Lindahl, Fed. Proc., 1963, 22, 413.41 C. Alais, G. Mocquot, H. Nitschmann, and P. Zahler, Helv. China. Acta, 1953, 36,42 P. Jollbs, C. Alais, and J. Jollks, Biochim. Biophgs. Acta, 1963, 69, 511.43 C. Alais and P. Jollks, Nature, 1962, 196, 1098.44 B. E. Baker, F. Y. Y. Huang, and C. R. Harington, Biochem. Biophys. Res.45 R. Kuhn and D. Ekong, Chem. Ber., 1963, 96, 683.46 R. Got, J. Font, R. Bourrillon, and R. Cornillot, Biochirra. Biophys. Acta, 1963,4 7 R. Got, J., Font, and R. Bourrillon, Biochim. Biophys. Acta, 1963, 78, 367.48 H. Papkoff, Biochim.Biophys. Acta, 1963, 78, 384.1955.Comm., 1963, 13, 227.74, 247RUSSELL AND STURGEON : HETEROMERIC SACCHARIDES 491from papain digests of a human y-globulin fraction, galactose, fucose,mannose, and glucosamine were present.49 Periodate destroyed all thegalactose and fucose, and presumably the terminal sialic acid which is alsopresent, with part of the mannose and glucosamine. These results and thoseof borohydride reduction of the oxidized products showed that some of theglucosamine is terminal or 1: 6 linked; the other sugars destroyed areterminal, 1 : 6 linked or multiply linked 1 : 6 and 1 : 2. Four of five mannoseresidues were unaffected and, if in the pyranose form, are either 1 : 3 ormultiply linked. Mild acid hydrolysis of the oxidized and reduced glyco-peptides gave a small glycopeptide, hydrolysates of which contained asp,glu, and glucosamine in 1 : 1 : 2 molar ratio; the saccharide-peptide link waspresumed, from earlier results, to be between the hexosamine and asparticacid.60 An ester link was excluded by the method of preparation and byi.r.spectral examination.The presence in bovine pancreas of two ribonucleases was suggested manyyears ago? Ion-exchange chromatography of a fraction of pancreatic juicehas now been used to separate a second enzyme, ribonuclease B, from theknown ribonuclease A. The two enzymes have identical amino-acid com-positions and enzymic activities, but ribonuclease B is a glycoprotein con-taining five residues of mannose and two of glucosamine per mole.62Preliminary studies have been made of the carbohydrate compositions ofovine luteinizing hormone 53 and ceruloplasmin.64 I n sialic acids liberatedfrom glycoproteins of animal skin by mild acid hydrolysis the relative pro-portions of N-acetyl- and N-glycolloyl-neuraminic acids were determined.Neuraminidase also released most of the sialic acids from these proteins.The galactose content was diminished by periodate oxidation only after suchremoval; mannose, glucose, and fucose were in all cases unaffected.An0-glycoside bond between sialic acid and galactose is thus indi~ated.5~Several workers reported syntheses of 2-aminoacylamido-2-deoxy-gl~coses.~~ Glucose 6-esters of amino-acids have also been prepared andtheir stability studied as a function of P H .~ ~Glycolipids and Glycopeptidolipids. -Brain and other tissues containgangliosides, that yield on hydrolysis fatty acids, sphingosine, and carbo-hydrates. The four chief brain gangliosides, GI-N of Kuhn 58 have beencharacterized. Acetolytic removal of the acylsphingosine gave oligosac-~ h a r i d e s , ~ ~ that were studied by periodate oxidation with or without49 J. A. Rothfw and E. L. Smith, J . Biol. Chem., 1963, 238, 1402.J. W. Rosevear and E. L. Smith, J . Biol. Chem., 1961, 236, 425.s l A . J. P. Martin and R. R. Porter, Biochem. J., 1951, 49, 215.68 T. H. Plummer, jun., and C. H. W. Hirs, J . Biol. Chem., 1963, 238, 1396.63 E. F. Walborg and D. N. Ward, Biochim. Biophys. Acta, 1963, 78, 304.64 E. D. Kaverzneva and G.P. Gashko, Ukrain. biochim. Zhur., 1963, 35,6 5 S. M. Bose, Biochirn. Biophy8. Acta, 1963, 74, 265.J. K. N. Jones, J. P. Millington, and M. B. Perry, Canad. J . Chem., 1962, 40,2229; M. Liefliinder, Naturwiss., 1962,49,541; E. D. Kaverzneva and M. I. Konovalova,Izvest. Akad. Nauk S.S.S.R., Otdel. khirn. Nauk., 1963, 124.67 N. K. Kochetkov, V. A. Derevitakaya, and L. M. Likhoshertsov, Izvest. Akad.Nauk S.S.S.R., Otdel. khim. Nauk., 1963, 688.68R. Kuhn, H. Wiegandt, and H. Egge, Angew. Chem., 1961, 73, 580.69 R. Kuhn and H. Wiegandt, Chern. Ber., 1963, 96, 866.607492 BIOLOGICAL CHEMISTRYsubsequent borohydride reduction, and by partial acid hydrolysis. Thesetechniques, with previous data, showed that all four gangliosides arederivatives of the same acylsphingosine tetrahexoside (4).The differentRO-CH,I R’CO-NH-CHIH0CHCH:CH [CH 2] ,.CHB A(4); R = D-Galp l--S~-GalpNAc 1--4~-Galp 1--4~-Gp 1-(5); R = D-GalpNAc 1-3~-Galp 1-4~-Gp 1-4INANA(6); R = D-GalpNAc 1--6~-Galp 1-4~-Galp 1-4~-Gp 1-gangliosides are distinguished by the number and position of N-acetylneur-aminyl residues. Ganglioside GI 59 is a monosialoganglioside with N-acetyl-neuraminic acid linked 2+3 to galactose residue A, and bears a secondN-acetylneuraminyl residue similarly linked to galactose residue B. GnI isan isomer of GII in which galactose A bears an N-acetylneuraminyl-(2+8)-N-acetylneuraminyl-( 2-+ 3)-disaccharide residue, and the trisialogangliosideGIv is related to GIII as is GII to GI.60led to assignmentof a structure identical with that of GII except that galactosamine wasconsidered to be linked 1+3 to galactose A, which bore the N-acetylneuia-minyl residue at the 4-po~ition.~~ Such a structure for the tetrasaccharidebackbone of ganglioside A has been previously ~uggested.~~ The assignmentrests upon the absence of 2,3,6-tri-O-methylgalactose among the products ofmethylation and hydrolysis of the sialic-acid-free gangliosides , and ganglio-sides GII and B may be identical.Brain gangliosides of several other speciespossess the N-acylsphingosine-tetrahexoside ‘‘ backbone. ” 64In Tay-Sachs disease there is a great increase in the amount of braingangliosides,G5 some 90% of which were reported to lack the terminalgalactose residue ;66 other workers found a normal percentage of hexoses.67Two gangliosides lacking sialic acids were also found in brains from patientswith the disease, but not in those of “normal” patients.One was anMethylation studies of the brain disialoganglioside B6o L. Svennerholm, J . Neurochem., 1963, 10, 613.6lE. Klenk and W. Gielen, 2. physic2. Chem., 1961, 326, 144.e2 E. Klenk and W. Gielen, 2. phyaiob. Chem., 1963, 330, 218.g3 E. Klenk and W. Gielen, 2. physiob. Chem., 1960, 319, 283.64L. Svennerholm, Acta Chem. Scand., 1963, 17, 239.65 E. R. Berman and S. Gatt, in “ Cerebral Sphingolipidoses,” eds. S. M. Aronsonand B. Volk, Academic Press, New York, 1962, pp. 237-248.66 L. Svennerholm, J. Neurochem., 1963, 10, 613.67 S. Gatt and E.R. Berman, J . Neurochem., 1963, 10, 65RUSSELL AND STURGEON : HETEROMERIC SACCHARIDES 493acylsphingosine digalactoside , the other an acylsphingosine trihexoside con-taining glucose, galactose, and galactosamine ;6* the first was similar to aganglioside from the kidney lipids of a patient with Fabry's disease.69Thin-layer chromatography of gangliosides, from Tay-Sachs brains originallyinvestigated by Klenk, and preserved for 25 years, revealed a major com-ponent, an N-acylsphingosine-monosialotrihexoside. This is believed to be( 5 ) on the evidence of partial acid hydrolysis, periodate oxidation, andmethylation.The relativepositions of substitution of this and the galactosamine on galactose are inHuman erythrocyte stroma contains gangliosides.71 One of these,globoside, was studied by partial hydrolysis and methylation techniques.It contained no sialic acid and had structure (6).72Two glycolipids with blood group A specific activity from humanerythrocyte stroma, if homogeneous with respect to carbohydrate, areconsiderably more complex than the chief brain gangliosides. Each onhydrolysis yielded glucose, galactose, and their 2 -amino-2 - deou y -derivatives,with sialic acid, sphingosine, and fucose. One, in which the chief fatty acidwas lignoceric, was insoluble in cold methanol ; the other, soluble, glycolipidcontained mainly lower fatty acids. The insoluble glycolipid had hzmag-glutination activity one hundred times that of the soluble one; the latterhad full activity when mixed with serologically inactive lipid.A mixture ofthe two glycolipids had low activity. Sedimentation studies led to thesuggestion that serological activity depends upon a high degree of aggrega-tion in aqueous dispersions. Sedimentation, diffusion, and viscositymeasurements on ox-brain ganglioside aqueous sols led to the assignment ofa particle weight of 250,000450,000. In dimethylformamide only mono-mers were present.74 The chief ganglioside of human spleen is a mono-sialoganglioside containing N-acetylneuraminic acid, glucose, and galactosein equimolar ratio.75 Spleen, liver, and serum have all been shown tocontain N-acetylsphingosine hexosides, 76 including, from serum, an acyl-sphingosine glu~oside.'~ Thin-layer chromatography has been useful instudies of the heterogeneity of ganglioside fractions.78Neuraminidase specifically cleaves terminal N-acetylneuraminic acidresidues linked a-ketosidically a t position 2, but part of the N-acetylneur-aminic acid in mixed gangliosides of brain is not so cleaved. A brainmonosialoganglioside preparation resistant to neuraminidase was analysedThe N-acetylneuraminic acid was not removed by sialidase.6 8 S. Gatt and E. R. Berman, J . Neurochem., 1963, 10, 43.69 C. C. Sweeley and B. Klionsky, J . Biol. Chem., 1963, 238, PC3148.70 E. Klenk, U. Liedtke, and W. Gielen, 2. physiol. Chem., 1963, 334, 186.71 D. A. Booth, Biochim. Biophys. Acta, 1963, 70, 486.7 2 T. Yamakawa, S. Yokoyama, and H. Harda, J . Biochem. (Japan), 1963,53, 28.73 J.Kokcielak, Biochim. Biophys. Acta, 1963, 78, 313.7 4 D. B. Gammack, Biochem. J . , 1963, 88, 373.7 5 L. Svennerholm, Acta Chem. Scund., 1963, 17, 860.76 J. Polonovski and M. Petit, Bull. SOC. Chim. biol., 1963, 45, 11 1 ; E. Svennerholm77 E. Svennerholm and L. Svennerholm, Biochim. Biophys. Acta, 1963, 70, 432.7 8 J. R. Wherrett and J. N. Cumings, Biochem. J . , 1963, 86, 378; G. A. Johnsonand L. Svennerholm, Nature, 1963, 198, 688.and R. H. McCluer, Biochim. Biophys. Acta, 1963, 70, 487494 BIOLOGICAL CHEMISTRYfor N-acetylneuraminic acid before and after treatment with lithium boro-hydride which reduces non-ketosidically linked sialic acids. Such treatmentdestroyed the N-acetylneuraminic acid. This was therefore presumed tobe linked in some other manner, although the semicarbazide reaction wasalso negative.79Acylglycerol galactosides occur in green plants ; diacyl derivatives of1 -D-glycerol @-D-galactopyranoside and of l-D-glyCer01 a-D-gahCtOpYranOSyl-(1+ 6)~-~-galactopyranoside have been found in runner beans.8* Lipids ofox-brain also contain a monoacyl derivative of the former glycerol galacto-side.8l A glycolipid from Pseudomonas zruginosa is an L-rhamnosyl-L-rhamnosyl-/3-hydroxydecanoyl-@-hydroxydecanoic acid, and @-hydroxy-decanoyl-coenz yme A and thymidinediphosphate-L-rhamnose participate inits biosynthesis.82Mycosides are specific glycolipids of certain types of Mywbacteria.Mycoside B from bovine strains of M . tuberculosis is a mixture of homologues,in which 2-O-methyl-~-rhamnose is linked p-glycosidically to the phenolichydroxyl group of a phenolic trihydric long-chain alcohol.One alcoholichydroxyl is methylated while the other two bear long chain fatty acyl groups.83Other mycosides are peptidoglycolipids. Mycoside Cm, from M . marianum,contains a simple heptapeptide chain, -phe-allothr-ala-al~thr-ala-alZothr-ala-,the N-terminus of which is acylated by a long-chain (C4J diunsaturafedhydroxy-acid. Each of the two outer allothreonine residues bears 3,4-di-O-methyl-L-rhamnose, glycosidically linked through the amino-acid hydroxyls,while a third methylpentose, 6-deoxy-~-talose, is esterified a t the 1-hydroxylby the carboxyl group of the 0-terminal alanhe. One methylrhamnose ismonoacetylated, and the deoxytalose has two acetyl groups atta~hed.8~Mycosides CZa and CZb from M .avium are similar. A shorter peptide chain,-phe-allothr-ala-allt~-ala-, is acylated at its N-terminus, and the allo-threonine residue next to phenylalanine bears a monoacetylated 3,4-di-O-methyl-L-rhamnose. In Ceb the C-terminal alanine carboxyl group is esteri-fied by the l-hydroxyl of 3-0-methyl-6-deoxy-~-talose, that is, replaced by6-deoxytalose in CZa.The " Wax D " fraction of mycobacteria contains glycolipid, and hithertoit was thought that only human strains of M . tuberculosis gave wax Dfractions that also contained the peptide portion necessary for E'reund'sadjuvant activity.86 However, peptidoglycolipids with adjuvant activityhave now been demonstrated in wax D fractions of several non-humanmycobacteria.~7 The heterogeneity of wax D from M .tuberculosis has beendemonstrated by silicic acid chromatography of the acetylated material.88Synthetic wax D analogues, methyl 6-O-stearoyl-~-~-ga~actopyranosides70 J. N. Kaufer and R. 0. Brady, Biochem. Biophys. Res. Comm., 1963, 11, 267.8 0 P. S. Sastry and M. Kates, BiocJzim. Biophys. Acta, 1963, 70, 214.81 W. T. Norton and M. Brotz, Biochem. Biophys. Res. Cornm., 1963, 12, 198.83 M. M. Burger, L. Glaser, and R. M. Burton, J . Biol. Chem., 1963, 238, 2595.ss H. Demarteau-Ginsburg and E. Lederer, Biochim. Biophys. Acta, 1963, 70, 442.84 M. Chaput, G. Michel, and E. Lederer, Biochim. Biophys. Acta, 1962, 63, 310.M. Chaput, G. Michel, and E. Lederer, Biochiim. Biophys.Actu, 1963, 78, 329.86 E. Lederer, Adv. Carbohydrate Chem., 1961, 16, 207.a7 P. Joll&s, D. Samour, and E. Lederer, Biochim. Biophys. Acta, 1963, 78, 342.88A. Tanaka, Biochh. Biophys. Ada, 1963, YO, 483.In both cases the deoxytalose is dia~etylated.~RUSSELL AND STURGEON : HETEROMERIC SACCHARIDES 495esterified in the 2-position with the a-carboxyl group of either L- or D-glutamic acid, had no adjuvant activity.89Bacterial Cell Wall and Capsular Polysaccharides.-CeZZ wazls. Thechemistry of bacterial cell walls has recently been reviewed.90 All cellwalls investigated contain a peptidoglycan; the glycan “ backbone ” iscomposed of an N-acetylglucosaminyl-N-acetylmuramoyl repeating unit.Lysozyme digestion of Hicrococcus Zysodeikticus walls gives a disaccharide ofN-acet yl-D - glucosamine and N - acetylmuramic acid, previously thought tobe 6-0-(2-aceta~do-2-deoxy-~-~-glucopyranosyl)-2-acetam~do-3-~-~-boxyethyl-2-deoxy-~-glucose (7).91 Hoshino similarly obtained a disac-charide which he considered to be 2-acetamido-4-0-(2-acetamido-3-0-~-1 ’- carboxyethyl-2- deoxy- D -glucop yranos yl) -2 - deoxy -D - glucop yranoseSynthetic (7) differed only slightly from an isolated disaccharide in rotationand Rglucosamine values, but gave a clearly different colour value in both theMorgan-Elson and Elson-Morgan tests.93 A 1+ 6 linkage was thereforepresumed absent, the only possible structure being 2-acetamido-4-0-(2-acetamido - 2-deoxy-/?-~-g~ucopyranosy~) - 3-0- D- 1’- carboxyethyl-2-deoxy-~-glucopyranose (9).This structure differs from those suggested by Salton,Perkins, and Hoshino, but is compatible with the properties of the di-saccharides.The presence of O-acetyl groups in the glycan has been confirmed. Froman enzymic digest of Staphylococcus aureus walls an O-acetylated N-acetyl-N-acetylglucosaminyl-muramic acid was isolated that, hydrolysed with a#I-acetylglucosaminidase, gave an ON-diacetylmuramic acid. This gave 1mole of formaldehyde with periodate, evidence that the 6-position was un-substituted. The disaccharide would then be 2-acetamido-6-0-( 2-acetamido-2-deoxy-#?-~-glucopyranosyl) - 4 - 0-acetyl- 3 - 0 - D - l’-carboxyethyl-2-deoxy-~-glucose This result is not necessarily incompatible with that of( 8).C H ~ o R”R’O OHNH’COMe(7); R = D-l-carboxyethyl, R’ = H, R” = 2-acetamido-2-deoxy-~-~-gluco-(8) ; R = H, R’ = 2-acetam~do-3-O-~-l’-carboxyethyl-2-deoxy-~-glucopyran-pyranosyl.0 ~ ~ 1 , R” = H.(9) ; R-= D- 1 -carboxyethyl, R’ = 2-acetamido-2-deoxy-~-~-glucopyranosyl,R” = H.(10); R = D- l-carboxyethyl, R’ = acetyl, R” = 2-acetamido-~-~-ghcopyra,nosy~.M.Cerny, J. Moron, and E. Lederer, Bull. Xoc. Chim. biol., 1963, 45, 601.H. R. Perkins, Bacteriol. Rev., 1963, 27, 18; 0. Westphal and 0. Luderitz,Naturwiss., 1963, 50, 413.O1 M. R. J. Salton and J. M. Ghuyssn, Biochim. Biophys. Acta, 1960, 45, 355;H. R. Perkins, Biochem. J., 1960, 74, 182.g2 0. Hoshino, Chem. Pharm. Bull. (Tokyo), 1960, 8, 411.g3 R. W. Jeanloz, N. Sharon, and H. M. Flowers, Bwchem.Biophys. Res. Comm.,g4 J. RI. Ghuysen and J. L. Strorninger, Biochemistry, 1963, 2, 1119.1963, 13, 20496 BIOLOGICAL CHEMISTRYJeanloz and Fl0wers,~3 since different micro-organisms were used as cell-wall sources.From enzymic digests of walls of 8. uureus a teichoic acid-glycopeptidecomplex was isolated that contained all the teichoic acid of the wa11.95 Apeptide bond between the amino-group of the D-alanine which esterifies thepolyol in teichoic acids, and the peptide carboxyl group of the C-terminalamino-acid of the peptido-glycan, had been suggested as linking the twopolymers.96 This possibility is now excluded, for the complex could befreed from ester-linked D-alanine a t pH 8.1 without dissociating the twopolymer^.^' Also, all the D-alanine in walls of S. aureus and 8.fecalis wasrapidly released by O.l~-alkali.~* Since the teichoic acid-peptidoglycanhad no demonstrable phospho-monoester group, peptidoglycan may belinked to teichoic acid as a pho~pho-diester.~~ The peptidoglycan containsno aminohydroxy-acid so that the linkage may involve hydroxyls of theglycan.A preparation of Erysipelothrix rhusiopathiz has yielded an antigenicpolymer, M at least 40,000. Hydrolysates contained amino-acids, gluco-samine, and muramic acid.99The peptide has been thought of as linking adjacent glycan chains.Such links may not occur at every muramic acid residue; many muramicacid carboxyl groups in M . Zysodeikticus walls are free. Walls of Arthrobacterglobiformis have a high ratio of peptide to glucosamine and muramic acid;here, the peptide chains may be longer and the glycan chains potentiallyfurther apart than in M .Zysodeikticus. Alternatively, some peptide may belinked other than through the carboxyl of muramic acid.loOIn cell walls of rickettsiae and psittacosis-lymphogranuloma organismsthere was evidence for the presence of muramic acid. This work supportsthe view that these organisms are more closely related to bacteria than toanimal viruses, since only the former (and the related Cyanophycez) havebeen shown to contain muramic acid.lO1The peptidoglycan of 8. aureus walls is thought to be synthesized bytransglycosylations involving UDP-N-acetylglucosamine and UDP-N-acetyl-muramoyl-pentapeptide, accumulation of which is observed in culturescontaining antibiotics that inhibit cell-wall synthesis.UDP-muramoyl-L-alanine and UDP-muramic acid also accumulate. The time course ofaccumulation under conditions of lysine and nitrogen deprivation and inthe presence of oxamycin or penicillin is consistent with a, biosyntheticalpathway that requires the presence of nucleotides of N-acetylglucosamine,N-acetylmuramic acid, and N-acetylmuramoyl-pentapeptide. Lack of thetwo former nucleotides inhibits incorporation of the last .lo28 6 J. M. Ghuysen and J. L. Strominger, Biochmistry, 1963, 2, 1110.O 6 M. H. Mandelstam and J. L. Strominger, Biochem. Biophys. Res. Comm., 1961O 7 J. L. Strominger and J. M. Ghuysen, Biochem. Biophys. Res. Comm., 1963, 12,OS G. F. Kdf and T.G. White, Arch. Biochem. Biophys., 1963, 102, 39.5, 466.418.G. D. Shockman, Nature, 1963, 198, 997.l o o D. C. Gillespie, Canad. J . Microbiol., 1963, 9, 515.lol H. R. Perkins and A. C. Allison, J. Qen. Microbiol., 1963, 30, 469.lo2 E. Ito and M. Saito, Biochim. Biophys. Acta, 1963, 78, 237RUSSELL AXD STURGEOX : HETEROMERIC SACCHARIDES 497Antibiotics might bring about accumulation of nucleotides by inter-ference with the tranglycosylation reactions that form the peptidoglycan.However, antibiotics do not affect incorporation of nucleotides in a cell-freesystem from 8. aureus 103 so that some other mechanism must be sought.It has been suggested 90 that teichoic acids may act as a template for peptido-glycan synthesis. The accumulation of nucleotides in vivo in the presenceof antibiotics might thus reflect their interference with teichoic acid bio-synthesis.Inhibition of cell wall synthesis by 0-carbamoyl-D-serine is thought toresult from metabolic antagonism between this amino-acid and D-alanine.lo4Capsules. The antigenic specificity of some hzmolytic streptococcalcarbohydrates has been shown to depend on terminal N-acetylhexosaminideresidues on a rhamnan backbone. Group A streptococcus antigen containedrhamnose and N-acetylglucosamine lo5 and group C , rhamnose and N-acetyl-galactosamine residues 106 the antigenic specificity depending on terminalN-acetylglucosaminide and N-acetylgalactosaminide residues, respectively.A variant of Group A streptococcus gave a polymer of rhamnose with veryfew hexosamine residues ; immunological evidence suggested that therhamnose-rhamnose links conferred the immunological specificity.A poly-saccharide from a Group C variant also contained rhamnose and littlehexosamine with the rhamnose-rhamnose linkages immunologicallysimilar to those of the Group A variant. The carbohydrates of Groups Aand C had a similar rhamnan structure but the antigenic specificity dependedon the particular N-acetylhexosamine. Chemical studies on the groupspecific polysaccharide of Group A haemolytic streptococci confirmed theexistence of (1+3) linked rhamnose units. Branching at position 2 withN-acetylglucosaminylrhamnose non-reducing groups was found, 108 con-firming serological tests which had previously indicated ( b 3 ) linkedrhamnose residues.lo9An antigen from the culture filtrate of a mucoid strain of StctphyZococcusaureus strain Smith 110 contained an unknown amino-sugar, later char-acterized as 2-amino-2-deoxy-glucuronic acid. m Staphylococcus protectiveantigen (SPA) isolated from a similar mucoid S. aureus 112 may be identicalto Morse's antigen. For the antigen isolated by Fisher, methylation andhydrolysis of parent and reduced polysaccharide indicated a ( b 4 ) glycosidiclink between 2-~-acety~a~any~amino-2-deoxy-~-glucuro~c acid and 2-aceta-mido-2-deoxy-~-glucuronic acid. The active antigen contains unlocatedO-acetyl groups.The capsular polysaccharide of KZebsieZla pneumonk type A containedlo3A. N. Chatterjee and J. T. Park, Proc.Nat. Acad. Sci., 1964, 51, 9.Io4 N. Tanaka, Biochern. Biophys. Res. Cornm., 1963, 12, 68.lo5 M. McCarty, J. Exp. Med., 1956, 104, 629.Io6 R. M. Krause and M. McCarty, J . Exp. Med., 1962, 115, 49.lo' P. Araujo and R. M. Krause, J . Ezp. Med., 1963, 118, 1059.lo* H. Heyrnan, J. M. Manniello, and S . S. Barkulis, J . B i d . Chem., 1963, 238, 502.loQ S. Estrada-Parra, M. Heidelberger, and P. A. Rebers, J . Biol. Chem., 1963, 238,S. I. Morse, J . Exp. Med., 1962, 115, 295; S. I. Morse, Nature, 1963, 200, 1126.111 H. R. Perkins, Biochem. J., 1963, 88, 475.112 M. W. Fisher, H. B. Devlin, and A. L. Erlandson, Nature, 1963, 199, 1074.510498 BIOLOGICAL CHEMISTRYglucose, fucose, and glucuronic acid residues.l13 Alkaline degradation,periodate, and met hylation studies suggested the presence of glucose non-reducing end-groups, and of fucose and glucose in (1+3) links.In an attempt to study the combining regions of the polysaccharideand the homologous antibody, oligosaccharides have been isolated fromtype I11 (S 111) Pneumococcus poly~accharide,~~~ a linear polymer ofrepeating units of cellobiuronic acid (4-o-~-D-g~ucopyranosy~wonic acid-D-glucose) in /I( 1+ 3)-glycosidic links.l15 Precipitin and inhibition data in-dicated that the anti-SIII combining sites varied in size and that theantigenic determinant occurred at intervals along the chain.Initial studies on the capsular polysaccharide of Pneumococcus typeXVIII (SXVIII) showed the presence of D-glUCOSe, r,-rhamnose, galactose,and glycerol l-phosphate, the last removable by alkali without loss of thesugars.116 Oxidation of the original and alkali-degraded polysaccharideswith periodate, and identification of the products after reduction suggestedthat the rhamnose and galactose were (1+3) linked and that part of theglucose was bound (1+4) and (1+6). The galactose was identified as theD-enantiomorph by means of D-galactose oxidase. 117 This evidence togetherwith the cross reactions and tests for their inhibition have indicated one orother structure :-Galp1-4a-~- 313 - Galpl-4~ - Gpl-3~ -Rhamp1-4a -D - Gpl- 6~ -Gp-HOCH2*CH( OH)*CH2*OPO 2- [ Ac-lx Structures of several complex polysaccharides associated with typespecificity in strains of Hzmophilus injuenzg have been reported.Thetype specific substance of type d contained 2-acetamido-2-deoxy-~-glucuronicacid and D-glucosamine residues and was stable to periodate; the links aretherefore probably (1+3) or (1+4).llS Another esoteric type of polymer isassociated with H. injuenzz type f and contained 2 moles of N-acetyl-galactosamine per gram-atom of phosphorus.11g The chemical and physicalproperties of the intact and alkaline degraded materials suggested a polymerof 2-acetamido-2-deoxygalactosyl-2-acetamido-2-deoxygalactoside units con-nected by phospho-diester links in the 3 or 4 positions. A similar capsularsubstance reported from H. parasius contained galactose, glucosamine, andphosphorus.120 Stability to alkaline phosphatase suggested phospho-diester113 S.A. Barker, J. S . Brimacornbe, J. L. Eriksen, and IT. Stacey, Nature, 1963,197, 899.114R. G. Mage and E. A. Kabat, Biochemistry, 1963, 2, 1278.116 R. E. Reeves and W. F. Goebel, J . Biol. Chem., 1941, 139, 511.116 S. Estrada-Parra, P. A. Rebers, and M . Heidelberger, Biochemistry, 1962,1, 1175.117 S. Estrada-Parra and M . Heidelberger, Biochemistry, 1963, 2, 1288.118 A. R. Williamson and S . Zamenhof, J. Biol. Chern., 1963, 238, 2255.1l9 E. Rosenberg, G. Leidy, I. Jaffee, and S. Zamenhof, J . Biol. Chem., 1961, 236,2841.A. R. Williamson and S. Zamenhof, Fed. Proc., 1963, 22, 239RUSSELL AND STURGEON : HETEROMERIC SACCHARIDES 499links; alkaline treatment gave a disaccharide phosphate of glucosamine andgalactose.The chemical relationship between the teichoic acids and pneumococcalcapsule polymers became clearer with the demonstration that the specificsubstance from Pneumococcus type VI is a polymer with galactopyranosyl-glucosylrhamnosylribitol units joined through phosphodiester linkages.lZ1The similarity was further confirmed by the isolation and characterization ofa repeating unit from the specific substance of Pneumococcus type 34 (41)as O-D-galactofuranosyl- ( 1 +3) -0-a-D-glucopyranosyl- ( 1 +2)-0-~-galactofura-nosy~-(l+3)-O-~-~-ga~actop~anosy~-( 1+2)-ribitol (1 1).122Glycosaminoglycuronoglycans of Connective Tissue.-This subject hasrecently been extensively reviewed.123Heparin.This highly sulphated polysaccharide composed of D-glu-curonic acid and D-glucosamine residues is an anticoagulant present in humanconnective tissue.The presence of O-sulphate and N-sulphate linkagestogether with uronic acid residues has for years complicated structuralstudies on this polysaccharide. Isolation of a de-N-sulphated, de-0-sulphated, and carboxyl reduced polymer permitted study of the linkagesequence. Partial hydrolysis yielded a crystalline disaccharide identified as4 - 0 - (2 - amino - 2 - deoxy - a - D - g~ucopyranosy~) - a - D - glucopyranose hydro-chloride 124 together with a small amount of a second disaccharide, 4-0-a-D-g~ucopyranosy~-2-am~o-2-deoxy-a-~-g~ucopyranose hydrochloride. 125 Com-parison of the molecular rotations of these two oligosaccharides with that ofthe corresponding a-D-linked disaccharide alditols, suggested an a-D-linkagein both disa c c harides .I The disaccharide 4- 0 - (2 -a cetamido - 2 - deoxy- D -g1ucopyranosyl)-cc-D-ghcuronic acid was isolated from a partial hydrolysateof a desulphated N-acetylated heparin.lZ7 Sodium borohydride reductionshowed the acetylglucosamine to be at the non-reducing end bound to uronic121 P. A. Rebers and M. Heidelberger, J. Amer. Chem. Soc., 1961, 83, 3056.lea W. K. Roberts, J. G. Buchanan, and J. Baddiley, Biochem. J., 1963, 88, 1.123 R. W. Jeanloz, Expos. ann. Biochim. mu., 1963, 24, 1; R. W. Jeanloz, Adv.Enzyrnol., 1963, 25, 433; A. Dorfman, fled. Proc., 1962, 21, 1070; A. Dorfman, J.Histochem. Cytochem., 1963, 11, 2.12* M. L. Wolfrom, J. R. Vercellotti, and D. Horton, J. Org. Chem., 1963, 28, 278.lg6 M.L. Wolfrom, J. R. Vecellotti, and D. Horton, J. Org. Chem., 1963, 28, 279.lS6 M. L. Wolfrom, J. R. Vercellotti, H. Tomomatsu, and D. Horton, Biochm.1%' P. Hoffman, Fed. Proc., 1962, 21, 170; P. Hoff~nan and K. Meyer, ibid., p. 1064.Biophys. Res. Comm., 1963, 12, 8500 BIOLOGICAL CHEMISTRYacid. Rotation and i.r. spectral data suggested an a-glycosidic link. Methy-lation and periodate studies on a desulphated, carboxyl-reduced heparinhave also shown the glycosidic links to be to position 4 of each sugar residue.128Deaminative degradation of de-N-sulphated heparin gave a mixture ofsulphated derivatives of D-glUCOpyranOSylWOniC acid-2,5-anhydromannose,in which all the uronic acid is attacked by periodate. Reduction and acidhydrolysis of periodate-oxidized heparin showed that 90% of the uronic acidresidues are 2-sulphated.The rate of consumption of oxidant and ofdestruction of sugar residues during the oxidation of heparin and its de-N-sulphated derivative by periodate implied the presence of O-sulphate groupsat position 6 of the (1+4) linked hexosamine residues and the variability ofheparin samples may lie in the degree of de-iV-sulphation and the extent ofO-sulphation at position 2 of the ( l e a ) linked hexuronic acid units andposition 3 of hexosamine units.lZ9 A 1 : 1 correspondence between theappearance of free amino-groups and the release of sulphate during autolyticde-N-sulphation has been demonstrated. 130 No diester sulphate links werefound in heparinic acid.Hyaluronic acid.This substance, found in connective tissues, is chemi-cally the simplest known connective tissue glycosylaminoglycuronoglycan.Its structure, emerging from the results of acid and enzymic hydrolysis,periodate oxidation and methylation procedures, is of alternating units ofD-glucosamine and D-glucuronic acid linked at positions 3 and 4, respectively.When hyaluronic acid was permethylated, a disaccharide obtained from themethanolysis product was shown to be methyl 2-acetamido-2-deoxy-4,6-di-O-met hyl- 3- 0- (methyl 2,3 -di- O-met hyl-p- D -glucop yranuronate) -glucopyrano -side indicating, with other evidence, an unbranched molecule with the gluco-saminidic link to position 4 of the D-glUCUrOniC acid moiety.131 The linkageto position 3 of the D-glucosamine residues was known from methylationstudies.132 Hirano and Hoffman isolated a tetrasaccharide from hyaluronicacid after enzymic hydrolysis with testicular hyaluronidase.133 Reductionof the uronic acid residues followed by methylation and hydrolysis confirmedthe ( b 4 ) linkage of 2-acetamido-2-deoxy-~-glucose residues to glucuronicacid.Bee-venom hyaluronidase gave a similar breakdown pattern. l34 Thisenzyme, a p-hexosaminidase, also degraded chondroitin sulphates A and C,heparin and Blood Group substances A and B. Results of periodate oxida-tion of hyaluronic acid supported the results from methylation studies for90% of the hexuronic acid residues were de~tr0yed.l~~ Destruction of 10%of the hexosamine residues may indicate the possibility of other types oflinkage within a linear molecule, or of branching.188 I.Danishefsky, H. B. Eiber, and A. H. Williams, J . BioE. Chern., 1963, 238,2895; A. B. Foster, R. Harrison, T. D. Inch, M. Stacey, and J. M. Webber, J . , 1963,2279.G. J. Durant, H. R. Hendrickson, and R. Montgomery, Arch. Biochem. Biophys.,1962, 99, 418.lao J. R. Helbert and M. A. Marini, Biochemistry, 1963, 2, 1101.lal R. W. Jeanloz and P. J. Stoffp, Fed. Proc., 1962, 21, 81.132R. W. Jeanloz, Chimia (Switz.), 1953, 7, 292.la3 S. Hirano and P. Hoffman, J. Org. Chem., 1962, 27, 395.135 R. Montgomery and S . Nag, Biochim. Biophys. Acta, 1963, 74, 300.S. A. Barker, S. I. Baypk, J. S. Brimacombe, and D. J. Palmer, Nature, 1963,199, 6934.ACTION OF THYROID HORMONESBy J. R. TataTHERE are two principal ways of considering the regulation of metabolicactivity by thyroid hormones, ( a ) interaction with individual rate-limitingenzymes or cellular structural components, and ( b ) control of synthesis ofspecific enzymes or structural elements. The majority of work on theelucidation of mechanism of action of thyroid hormones is based on thefirst idea of their interaction with rate-limiting steps in metabolic pathwaysand many reviews have been written on this aspect in recent years.l-sLittle thought has been given to the second possibility of changes in amountsof cellular constituents. This aspect merits more thought, especially inview of the recent developments in our understanding of the control mech-anisms of protein ~ynthesie.~, 10Structural and Physicochemical Aspects.-The two thyroid hormones,L-thyroxine (3,3’,5,5’-tetraiodo-~-thyronine) and 3,3’,5-tri-iodo-~-thyronine,have the following steric disposition, as illustrated for their thyronineskeleton (1) :11, 1 2H,C” ’‘U, 0 - c , ‘COZH (1)An angle of 11 1 O of the diphenyl ether oxygen precludes certain substitutionsand introduces a spatial factor in the interaction between thyroid hormonesand enzymes. On the basis of this spatial consideration and the data nowavailable for the relative biological activities and protein-binding affinitiesof various structural analogues of thyroid hormones,l, Jorgensen et al. l1have suggested a mode of interaction between tri-iodothyronine and cellularreceptor sites (2), the latter being assumed to be protein molecules.Accord-ing to scheme (2), the proximal benzene ring adjacent to the alanine side-chain confers the protein binding properties whereas the distal phenolicS. B. Barker, Physiol. Rev., 1951, 31, 205.R. Pitt-Rivers and J. R. Tata, “ The Thyroid Hormones,” Pergamon Press,London, 1959.J. Tepperman and H. M. Tepperman, Pharmucol. Rev., 1960, 12, 301.0. Lindberg, H. Low, T. E. Conover, and L. Ernster, in “ Biological Structureand Function,” eds. T. W. Goodwin and 0. Lindberg, Academic Press Inc., New York,1961, Vol. 11, p. 3.R. E. Smith and D. J. Hoijer, Physiol. Rev., 1962, 42, 60.F. L. Hoch, Physiol. Rev., 1962, 42, 605.R. Trotter, Butterwortha, London, 1964, p 236.’ D.F. Tapley and W. B. Hatpld, Vitamins and Hormones, 1962, 20, 251. * E. C. WOW and J. WOW, in The Thyroid Gland,” eds. R. Pitt-Rivers andF. Jacob and J. Monod, J . MoZ. Bzol., 1961, 3, 318.lo S. Spiegelman, Fed. Proc., 1963, 22, 36.l1 E. C. Jorgensen, N. Zencker, and C. Greenberg, J . Biol. Chem., 1960, 235, 1732;E. C. Jorgensen, P. A. Lehrnan, C. Greenberg, and N. Zencker, J. Biol. Chem., 1962,237, 3832.l2 S. €3. Barker, Fed. Proc., 1962, 21, 635502 BIOLOGICAL CHEMISTRYbenzene ring interacts with an adjacent, functional site of the protein. Theobvious point of interest is to know whether this functional site is the initialcellular site triggering off the series of reactions constituting the biologicalactions of the hormones.[Reproduced, by permission, from E. C.Jorgensen, P. A. Lehmm, C. Greenberg,and N. Zencker, J. Biol. Chenz., 1962, 237, 3837.1Interrelation of chemical structures and biologicul activity. As a result ofstudies 1, 2, 11-15 on the relative potencies of a large number of chemicalanalogues of thyroid hormones, the following conclusions can be drawn aboutthe relationship between chemical structure and biological activity of thyroidhormones: (a) the diphenyl ether linkage is essential for biological activity.( b ) The asymmetric carbon of the alanine side-chain is important ; D-thyroxineexhibits less than 10% of the activity of L-thyroxine. Deaminated an-alogues such as the propionic, acetic, and formic acid derivatives have only3-1070 of the calorigenic activity of L-thyroxine but in the amphibianmetamorphosis test they appear to be several times as potent as the parentcompound.This discrepancy may be due to a very rapid diffusion of thedeaminated analogues into tadpole tissues.l* (c) There should be at leastone substitution in each benzene ring. The substitution should be in the3- or 5-positions and ortho to the phenolic hydroxyl which is also essentialfor biological activity. (d) Substitution with iodine generally yields com-pounds with higher biological activity than those with bromine and chlorineor with methyl, butyl, or isopropyl groups. An exception is 3,5-di-iodo-3’,5’-dimethylthyropropionic acid which has 30-+to~0 higher calorigenicactivity in the rat than the 3,3‘,5,5’-tetraiodo-analogue.l7 (e) The phenolichydroxyl must be freen2 It is important to bear in mind in such considera-tions that the relative biological potencies of thyroxine-like compounds mayl3 M.L. Sachs, ed., “ Derivatives and Isomers of Thyroid Hormones,” School ofMedicine of the University of Pennsylvania, Philadelphia, 1960.l* N. R. Stasilli, R. L. Kroc, and R. I. Meltzer, Endocrinology, 1959, 64, 62.lii W. L. Money, S. Kumaoka, R. W. Rawson, and R. L. Kroc, Ann. N . Y . Acad.Sci., 1960, 86, 512.l7 C. S. Pittman, H. Shida, and S. B. Barker, Endocrinology, 1961, 68, 248.E. Frieden and G. W. Westmark, Science, 1961, 133, 1487TATA: ACTION O F THYROID HORMONES 603vary according to the biological assay, i.e., calorigenesis, growth-promotion,goitre-prevention, lowering of blood cholesterol, or acceleration of amphibianmetamorphosis.Interrelation of redox properties and biological activity.The requirementof a free phenolic group for biological activity and the rBle of thyroidhormones in oxidative processes has focused attention on the redox pro-perties of these substances. Electrometric measurements show thatthyroxine has an E',,, a t pH = 0, of ~ 0 . 8 v, and thyroxine as well as manyanalogues reduce Cu2+ to Cu+ ions, although the nature of the oxidizedproducts of these substances remains ~ n k n 0 ~ n . l ~ Niemann 20, 21 had sug-gested that thyroxine could participate in redox processes by a reversiblequinone formation via a semiquinone intermediate (3,4).:Q(3)I(4)Il b RIThe lack of biological activity in the 3-hydroxy-" metathyroxine ", (5)which could not undergo quinone-formation, was cited in support of thebiological importance of a reversible quinonoid formation.22 The oxidizableisomer of thyroxine with the phenolic group in 2-position was found to havesome biological activity.2O There have been other suggestions based onindirect evidence of the formation of free radicals of oxidized forms ofthyroxine 23-25 but as yet there is no analytical data to support it. Oxidizedforms of iodotyrosines and some biologically inactive iodothyronines, formedby the action of peroxidases or polyphenol oxidases, have however beenidentified chromatographically. 26A recent approach to the relationship between structure and biologicalH.E. Evert, Fed. Proc., 1953, 12, 201.l9 E. Frieden and R. Flitman, Arch. Biochem. Biophys., 1956, 64, 513.20 C. Niemann and J. F. Mead, J . Amer. Chem. SOC., 1941, 63, 2685.21 C. Niemann, Fortschr. Chem. org. Natur., 1950, Y, 167.22 C. Niemann and C. E. Redemann, J. Amer. Chem. SOC., 1941, 63, 1549.s3 C. L. Gemmill, Amer. J . Physiol., 1953, 172, 286.e 4 J. H. Park, B. P. Meriwether, and C. R. Park, Biochim. Biophys. Acta, 1958,25 E. Frieden, K. Forsblad, and A. L. Ezell, Arch. Biochem. Biophys., 1962, 96,28, 662.423.26 S. Lissitzky and S. Bouchilloux, Bull. Xoc. Chim. biol., 1957, 39, 1215; S . Lis-sitzky and S. Bouchilloux, Ciba Foundation Colloquia on Endocrinology, 1957, 10, 135504 BIOLOGICAL CHEMISTRYactivity is based on a study of the electronic properties of thyroid hormones.Thyroxine has a reduction wave of E$ = -1.05 v as measured polaro-graphically in dimethyl sulphoxide.Thyroxine, tri-iodothyronine, andrelated compounds &re good electron accepters and the electron-acceptercapacity of the different substances agrees well with their relative biologicalpotencies.27, 28Biological effects of metal chelation. Thyroxine forms complexes withbivalent metal ions, such as Cuz+, Mg2+, and Mn-t2. It seems that boththe alanine side-chain and the diphenyl ether part of the molecule are in-volved.25, 29-32 In the case of CU(II) chelation, complex (6) has been sug-gested. The principal significance of metal chelation is in the explanation ofeffects such as the inhibition in vitro by thyroxine of certain enzymes, likethe Mg2+-containing creatine phosph~kinase,~~, 33 Cuz+-dependent mush-room tyrosinase 34 or the variety of Zn2+-containing dehydrogena~es.~5, 36However, it is not true that all metal-containing enzymes are inhibited bythyroxine, i.e., the lack of effect on Zn2+-containing carboxypeptidase 37 orMgz+-dependent hexokinase.38 In some cases, thyroxine may stimulateenzyme activity in vitro by complexing with inhibitory metal ions, as for27 A.C. Allison, M. E. Peover, and T. A. Gough, Life Sciences No. 12, 1962, 729.28 J. E. Lovelock, Nature, 1961, 189, 729.z9 E. Frieden and B. Naile, Arch. Biochem., 1954, 48, 448.30 H. A. Lardy, Brookhaven Symp. Biol., 1955, 7 , 90.31 C. L. Gemmill, J .Biol. Chem., 1957, 192, 749.32 S. Davis, J . Biol. Chem., 1957, 224, 759.33 S. A. Kuby, L. Noda, and H. A. Lardy, J . Biol. Chem., 1954, 210, 66.34 Y. Karkhanis and E. Frieden, Biochern. Biophys. Res. Comrra., 1961, 4, 303.35 B. L. Vallee and F. L. Hoch, Ergeb. Physiol. Biol. Chem. Exp. Pharrnakol.,36 J. Wolff and E. C. Wolff, Biochim. Biophys. Acta, 1957, 28, 387.37 J. Wolff, J . Biol. Chem., 1962, 237, 230.38 R. H. Smith and H. G. Willittms-Ashman, Biochim. Biophys. Acta, 1951, 7 , 295.1961, 51, 52TATA: ACTION O F THYROID HORMONES 505example the reversal of inhibition by Mg2f of ascorbic acid oxidase 39 orthe protection of spermatozoan respiration against Ca2+ ions.Interaction with Enzymes or Rate-limiting Metabolic Steps.-The mostaccepted view of the past two decades on the mechanism of action of thyroidhormones has been that the primary hormonal action involves the modifica-tion, by some form of direct interaction, of the rate a t which a key metabolicreaction proceeds.It has therefore led to a large number of experimentsin vitro in which the effect of addition of thyroxine and its analogues topurified enzymes or subcellular constituents is observed. The primary siteof action of thyroid hormones in the cells is unknown; it is therefore difficultto interpret the mechanism of action of thyroid hormones on the basis ofthe few physicochemical characteristics considered above and the results ofdirect hormone-enzyme interactions.Thyroid hormones elicit multiple biological actions which include calori-genesis, acceleration of growth and metamorphosis, changes in protein, lipid,and water metabolism, brain and bone development, etc.But for a varietyof arbitrary reasons, most work has been devoted to the elucidation of thecalorigenic effect (i.e., regulation of basal metabolic rate), with the assumptionthat it is the fundamental hormonal action. Since mitochondria play animportant r61e in cellular oxidation and energy metabolism, much work hasbeen done on the effect of thyroid hormones on mitochondria1 enzymes orprocesses. 2--8The first biochemical studies on the action of thyroidhormones concerned changes in respiration of various tissue preparationsfrom animals treated with the hormones, or when the latter were added totissue preparations in vitro.1,2 In general, the oxidation of a variety ofsubstrates by tissue slices, homogenates , isolated mitochondria, or individualdehydrogenases is enhanced after thyroid hormone is administered in vicobut depressed if added in vitro. The most intensely studied system is suc-cinoxidase.Interest in succinoxidase was heightened by the finding thatthyroxine and tri-iodothyronine stimulated it even in vitro in different tissuehomogenates and mito~hondria.~*~~ The stimulations after treatment invivo and in vitro may be mediated through different mechanisms. Wolffand Ball 4 1 showed that the stimulation of succinoxidase in vitro did notinvolve an interaction with succinic dehydrogenase but that thyroxine pre-vented the accumulation of oxaloacetate which is a potent inhibitor ofsuccinic dehydrogenase (7).Cellular oxidation.1 2 3Succinate + fumarate + malate --j.oxalacetate. (7)This protective action is unlikely to explain the stimulation of succinoxidasein v ~ v o . ~ ~ In the case of oxidation of glycerol l-phosphate, and probably39H. A. Lardy and G. Feldott, Ann. New York Acad. Sci., 1951, 54, 636.40 C. L. Gemill, Amer. J . Physiol., 1952, 170, 502; J. G. Wiswell, K. L. Zierler,M. B. Fasano, and S. P. Asper, jun., Johns Hopkins Hosp. Bull., 1954,94, 94; M. Suzuki,M. Inoue, Y. Sugisawa, and T. Takahashi, Endow:. jap., 1956, 3, 98; P. V. Tishler,Endocrinology, 1963, 72, 673.41 E. C. Wolff and E. G. Ball, J . Biol. Chem., 1957, 224, 1083.42 S. B. Barker, Endocrinology, 1957, 61, 534606 BIOLOGICAL CHEMISTRYof other substrates, the enhanced stimulation in wiwo is likely to be due toincreased levels of dehydrogenases or other mitochondrial constituents.4s-45Besides direct effects on mitochondrial oxidation^,^^ some workers havealso considered the possibility that thyroid hormones may control mito-chondrial oxidation through some extra-mitochondria1 sites.Two suchBites suggested are: (a) the transhydrogenase system catalysing a directtransfer of electrons between mitochondrial NAD and extramitochondrialNADPH and which is inhibited in vitro by thyroxine.47 ( b ) The microsomalNADPH-cytochrome c reductase which is stimulated in experimental hyper-thyroidism or thyrotoxic~sis.~~~ 499 459 The net effect of the two actions,according to scheme (8),5, 49 would be t o lower the overall yield of high-energy phosphorus compounds produced by the oxidation of substrates(P/O ratio of 1 against P/O ratio of 3 for mitochondrial electron transport).Substrate Substrate- - - _ _ - - - _ _ NADH + Transhydrogenase + NADPH - - - - - - - - - - I I t 1 NADPH-cytochrome creductase.1 NADH-cytochrome c 7 reductase J cytochrome cIThis mechanism has been suggested to explain the stimulation of respirationand uncoupling of oxidative phosphorylation by thyroid hormones.Thephysiological significance of the above scheme is doubtful ; the inhibitionof transhydrogenase has not been demonstrated in vivo.Since the initial observations in 1951 fromthe laboratories of Liprna~m,~O lard^,^^ and M a r t i ~ s , ~ ~ the property of highconcentrations of thyroxine to uncouple mitochondrial oxidative phos-Oxidative phosphorylation.43 H.A. h d y , Y.-P. Lee, and A. Takemori, Ann. New York Acad. Sci., 1960, 86,44 J. R. Tata, L. Ernster, and 0. Lindberg, Nature, 1962, 193, 1058.45 J. R. Tata, L. Ernster, 0. Lindberg, E. Arrhenius, S. Pedersen, and R. Hedman,Biochern. J., 1963, 86, 408.46 a. E. Gloclr and P. McLean, Biochem. J., 1955,61,390; 1956,63,520; N. Bargoni,A. Luzzati, M. T. Rinaudo, L. Rossini, and E. Strumitl, 2. phpiol. Chern., 1961,326, 65.E. G. Ball and 0. Cooper, Proo. Nat. A d . Sci., Washington, 1957, 43,357.506.a8A. H. Phillips and R. G. Ltmgdon, Biochim. Biopziys. Acta, 1956, 19, 380.O D R.E. Smith, Fed. Proc., 1960, 19, 64.6 0 M. Niemeyer, R. K. Crane, E. P. Kennedy, and F. Lipmann, Fed. Proc., 1951,S1 C. Martius and B. Hess, Arch. Biochem. Biophys., 1951, 33, 480.10, 229TATA: ACTION O F THYROID HORMONES 507phorylation in vitro has been repeatedly demonstrated under a variety ofdifferent conditions.62-55 Mitochondria isolated from animals treated withlarge or toxic amounts of thyroid hormones also show a lowered P/Oratio.39, 63, 56 The degree of uncoupling obtained in vivo or in vitrovaries amording to a large number of conditions which include substrate,pre-incubation and washing of mitochondria, the presence of Mg2 + ions,concentration and nature of hormone derivative, species of animal andtissue from which mitochondria were prepared.These have all been ex-haustively catalogued in recentThe physiological significance of uncoupling of oxidative phosphorylationwas based on the argument that the increase in basal metabolic rate of theanimal would be due to a compensatory increase in oxidation of substratescaused by lowered phosphorylative efficiency. However, uncoupling bythyroxine in vitro is not accompanied by an increased mitochondria1 respira-tion. Also no increase in the net synthesis of ATP can be demonstratedunder these conditions, which is incompatible with the anabolic action ofthyroid hormones accompanying calorigenesis under physiological conditions.It is to overcome such objections that the concept of respiratory controlindex or the tightness of coupling has been invoked.Mitochondria fromhyperthyroid or thyrotoxic subjects may exhibit a state of " loose " couplingunder certain conditions.53, 499Exactly how high concentrations or toxic doses of thyroid hormonesuncouple phosphorylation or release mitochondria from tight coupling, invivo or in vitro, still remains to be defined. Most effort in this field has beendirected towards the inhibition of ZY4-dinitrophenol- or Mg2 +-dependentATPase and ATP-inorganic phosphate and ATP-ADP exchange reac-tions. All these reactions represent the terminal phosphorylation site.*, 69The NAD-linked first phosphorylative site may also be sensitive tot h~~oxine.4, 60Some workers have not only failed to confirm the uncoupling of oxidativephosphorylation by thyroxine but shown a stimulation of phosphorylationin vitro under certain conditions.619 62 In a recent systematic study of theaction of thyroid hormones a t the cell 45 it was found that theuncoupling of phosphorylation can only explain the toxic effects of un-physiological amounts of the hormones. Under conditions that were closeto the physiological mechanism itself, the coupling or the degree of tightness3, % ', 83 575% C.Martius and B. Hem, Arch. exp. Path. Phamak., 1952, 216, 42; G. F. MaIeyand H. A. Lardy, J . Biol. Chem., 1953, 204, 435; J. H. Park, B. P. Meriwether, C. P.Park, S. H. Mudd, and F. Lipmann, Biochim. Biophys. Acta, 1956, 22, 403; F. Dickensand D. Salmony, Biochem. J., 1956, 64, 645.5 3 F. L. Hoch and F.Lipmann, Proc. Nut. Acad. Sci., Wash., 1954, 40, 909.54 H. Q. Klemperer, Biochm. J., 1955, 60, 122.5 5 G. F. Maley J. Biol. Chem., 1957, 224, 1029.56 C. Martius and B. Hess, Biochem. Z., 1955, 326, 191.57 H. A. Lardy and G. F. Maley, Recent Progr. Hormone Res., 1954, 10, 129.68 L. Ernster, D. Ikkos, and R. Luft, Nature, 1959, 184, 1851.5 @ J. R. Bronk, Biochim. Biophys. Acta, 1963, 69, 375.6 o B. Chance and G. Hollunger, Nature, 1960, 185, 666.6 1 J. R. Bronk, Ann. New York Acad. Sci., 1960, 86, 494; J. R. Bronk and M. S.6 q R. D. Dallam and J. M. Reed, J . Biol. Chem., 1960, 235, 1183.Bronk, J . Biol. Chem., 1962, 237, 897608 BIOLOGICAL CHEMISTRYof coupling were unaffected in the hormonal stimulation of mitochondrialor whole-body respiration.The concomitant increase in phosphorylationwas compatible with the conclusion that, under physiological conditions,thyroid hormones stimulate respiration by a selective increase in thesynthesis of some mitochondrial constituents. This was later supported byelectron-microscopic studies 6 3 and by a sequential analysis of mitochondrialprotein synthesis and oxidative phosphorylation.64Egects of changes of permeability of mitochondrial membranes. It is nowwell established that thyroxine and related compounds are potent swellingagents in vitro when added to liver mitochondria in high concentrations(5 x 10-6-10-4~).7, 65--68 Mitochondria1 swelling involves active uptakeof water and electrolytes and it is not clear as to whether thyroid hormonesact directly on the energy-dependent " mechanoenzyme " elements ofmito~hondria.~~ Work from Lehninger's laboratory has suggested thatthyroxine may act indirectly by releasing a mitochondrial fatty acid, termed" factor U," which is a potent swelling agent. 699 7O Mitochondria previouslyswollen by thyroxine can be made to contract by the addition of ATPand Mg2+.67, 69, 7 1 Mitochondria from all tissues are not susceptible tothe swelling action of thyroid hormones ; liver mitochondria are the mostsensitive and mitochondria from muscle, brain, and testis do not undergoswelling.Liver mitochondria isolated from thyrotoxic animals have a swollenappearance and at the same time are more sensitive to swelling agents thanparticles from normal or hypothyroid animals.72, 73 Moderate hyper-thyroidism however does not affect the structural stability of liver mito-chondria.45 On the other hand, mitochondria from skeletal muscle fromthe same animals were larger in size than normal, which however does notrepresent the same phenomenon as swelling.63It has been suggested that mitochondrial swelling may explain the un-coupling of oxidative phosphorylation by thyroxine without invoking aninteraction with any specific rate-limiting step of electron transport orphosphorylation.', 66 There may be a common mechanism such as " factor63 R. Gustafsson and J. R. Tata, J. Ultrastructure Res., 1963, 9, 396.6 4 K. B. Freeman, D. B. Roodyn, and J. R. Tata, Biochirn. Biophys. Acta, 1963,72, 129.65 H. G.Klemperer, Biochem. J., 1955, 60, 128; D. F. Tapley, C. Cooper, andA. L. Lehninger, Biochim. Biophys. Acta, 1955, 18, 597; R. E. Beyer, H. Low, andL. Ernster, Acta Chem. Scand., 1956, 10, 1039.66D. F. Tapley, J . Biol. Chem., 1956, 222, 325; D. F. Tapley and C. Cooper,J . Bid. Chem., 1956, 222, 341; C. Cooper and D. F. Tapley, Biochim. Biophys. Acta,1957, 25, 426.67A. L. Lehninger, B. L. Ray, and M. Schneider, J. Biophys. Biochem. Cytol.,1959, 5, 97.6 8 J. E. Rall, J. Roche, R. Michel, 0. Michel, and S. Varrone, Biochiim. Biophys.Acta, 1962, 62, 622.a9A. L. Lehninger, Ann. New Yorlc Acad. Sci., 1960, 86, 484; A. L. Lehninger,Physiol. Rev., 1962, 42, 467.7 O L. Wojtczak and A. L. Lehninger, Biochim. Biophys. Acta, 1961, 51, 442.71 A. L.Lehninger, J . Biol. Chem., 1959, 234, 2187.'4 D. F. Tapley and C. Cooper, Nature, 1956, 178, 1119.73 M. Schulz, H. Low, L. Ernster, and F. S. Sjostrand, " Electron Microscopy,"eds. F. S. Sjostrand and J. Rodin, Academic Press Inc., New York, 1957, p. 134;R. Poche, Arch. Pathol. Anat. Physiol., 1962, 335, 292TATA: ACTION O F THYROID HORMONES 509U " which is both a potent swelling agent 70 and an uncoupler of oxidativephosphorylation.69 Mitochondria1 swelling is also accompanied by a re-distribution of pyridine nucleotides and proteins, and an alteration in theoxidoreduction states of respiratory chain carriers.69 However, there is noevidence to indicate that mitochondria represent the primary site of thephysiological action of thyroid hormones.The only possible physiologicalsignificance of thyroxine-induced mitochondria1 swelling is that it re-presents a hypothetical model system which can be extrapolated to thecontrol of permeability of all types of cellular membranes by thyroidhormones.With the increasing availability ofpurified enzymes in recent years, the effect of thyroxine and its derivativeshas been tested on enzymes catalysing almost every type of biologicalreaction. Taken as a whole, the results of these studies are often mutuallycontradictory and disappointing in terms of the mechanism of action ofthyroid hormones. They have been exhaustively reviewed.l, 2, 67 Thesystematic studies of Wolf€ 36, 37, 74 on the interaction between purifieddehydrogenases and thyroid hormones however merit brief mention.Thyroxine inhibits both NAD- and NADPH-dependent dehydrogenases invitro, many of which contain Zn2+.The inhibition is reversible, complex,neither fully competitive nor non-competitive, and cannot be explained bymetal-chelation or oxidation of sulphydryl groups. With glutamic dehydro-genase, the inhibition by thyroxine was accompanied by a disaggregationof the enzyme to four times smaller units and an activation of alaninedehydrogenase activity. This type of inhibition has been cited by Monodet as a model of " allosteric " or conformational changes produced bybiologically active substances in the regulation of metabolic activity ofthe cell.Regulation of Protein Synthesis by Thyroid Hormones.-Recent studieson the cellular action of thyroid hormones supports the view that the multiplebiological hormonal actions may be mediated via a subtle control of proteinsynthesis. The cytochrome c and glycerol 1 -phosphate dehydrogenasecontent of mitochondria is lowered after thyroidectomy and elevatedafter mild hyperthyroidism or feeding of large amounts of thyroid hor-m o n e ~ .~ ~ , 43, 44, 45 The increase in the levels of these constituents wasfound to be part of a general increase in the cytoplasmic capacity to synthe-size protein. Administration of thyroid hormone to man and rat is followedby an overall increase in incorporation of radioactive amino-acids intoprotein in v ~ v o . ~ ~ ~ 78 Cell-free preparations from thyroid-hormone-treatedanimals also exhibit a stimulation of amino-acid incorporation intoInteractions with puriJied enzymes.i4 J.Wolff, J. Bid. Chem., 1962, 237, 236.i5 J. Monod, J.-P. Changeux, and F. Jacob, J. Mol. Biol., 1963, 6, 306.i6 S. R. Tipton, M. J. Leath, I. H. Tipton, and W. L. Nixon, Amer. J. Physiol.,1946, 145, 693; A. Tissieres, Arch. Int. Physiol., 1948, 55, 252; D. L. Drabkin, J. Bid.Chem., 1950, 182, 335." K. R. Crispell, W. Parson, and G. Hollifield, J. Clin,. Invest., 1956, 35, 164;K. R. Crispell, G. A. Williams, and W. Parson, J. Clin. Endocrin., 1957, 17,221. '* R. Michels, J. Cason, and L. Sokoloff, Science, 1963, 140, 1417610 BIOLOGICAL CHEMISTRYprotein.44, 45, 7~1-8~ Sokoloff and his colleagues further found that thyroxinecan stimulate microsomal protein synthesis in vitro 79, but there is dis-agreement about the conditions in which this effect can occw.45,81,82Sokoloff et al.suggested that thyroid hormones acted at the step involvingthe transfer of soluble-RNA-bound amino-acid to microsomal protein.However, as mentioned below, the physiological control of protein synthesisby thyroid hormones does not involve action at this step.I n work carried out in the author's laboratories during the last threeyears, the study of protein synthesis was co-ordinated with other major bio-chemical effects of thyroid hormones under physiological conditions. Thelatent period of action was taken into account for the first time in bio-chemical studies by recording changes in different cellular function as afunction of time following a single administration of thyroid hormones.Inthis way, it was found that oxidative phosphorylation or mitochondrialstructural properties were unaffected during the stimulation of basal meta-bolic rate.44, 45 On the other hand, the peak stimulation of mitochondrialQ (oxygen) and phosphorylation was preceded by a peak stimulation ofprotein synthetic capacity of mitochondria and microsomes from the samesample of tissues.44~ 45, 64The following two observations 45 suggested that the stimulatory actionof thyroxine and tri-iodothyronine was not at the cytoplasmic level ofassembly of peptide chains : (a) the amount of ribosomal RNA was increasedbefore peak stimulation of amino-acid incorporation ; (b) the stimulation wasabolished by starvation. Furthermore, the enhancement of cytoplasmicprotein synthesis still required a long latent period (about 24 hours in therat 443 45, 64) which was longer than the biological half-lives of the twohormones.2? 86 Attention was therefore focused on the synthesis of nucleicacids, and our recent results show that activity of DNA-dependent RNApolymerase in the cell nucleus is stimulated about 16 hours before an increasein cytoplasmic protein synthesis could be observed following a single ad-ministration of thyroid hormone.8' This enzyme is believed to synthesize" messenger RNA," and accordingly it was later found that the synthesisof nuclear RNA was stimulated at an early time-interval following hormonetreatment.88 Inhibitors of nucleic acid and protein synthesis, such asactinomycin D, 6-fhorouraci1, and puromycin, not only inhibit the growth-promoting action of thyroid hormones but also their calorigenic action.89Mechanism of action of thyroid hormones.Work on enzyme-hormoneinteractions has failed to account for the multiple physiological actions of79L. Sokoloff and 8. Kaufman, J. Bwl. Chem., 1961, 238, 795.S O L . Sokoloff, S. Kaufktan, P. L. Campbell, C. M. Francis, and H. V. Gelboin,81 0. Stein and J. Gross, Proc. SOC. Exp. Biol. Med., N.Y., 1962, 109, 817.83 J. Roche, R. Michel, and T. Kamei, Biochim. Biophys. Acta, 1962, 61, 647.E3 J. R. Bronk, Science, 1963, 141, 816. ** E. Frieden, A. E. Herner, L. Fish, and E. J. C. Lewis, Science, 1957, 126, 559.85 R.L. Metzenberg, M. Marshall, W. K. Pa&, and P. P. Cohen, J . Biol. Chem.,86 J. R. Tata, Mem. SOC. Endocrinol., 1961, 11, 90.87 C. C. Widnell and J. R. Tata, Biochim. Biophys. Ada, 1963, 72, 506.88 J. R. Tata, unpublished results.J . Biol. Chem., 1963, 238, 1432.1961, 236, 162.J. R. Tata, Nature, 1963, 197, 1167TATA: ACTION OF THYROID HORMONES 51 1thyroid hormones. Uncoupling of oxidative phosphorylation or mito-chondrial swelling can only account for the toxic or catabolic action of verylarge amounts of the hormones. Under physiological conditions, the regula-tion of B.M.R. appears to be secondary to a selective control of the synthesisof certain mitochondria1 enzymes. Action at the level of genetic regulationof protein synthesis may Bimilarly account for the other biological actionsof the hormones.The r8le of thyroid hormones as.regulators of proteinsynthesis focuses attention on their growth-promoting and developmentalproperties. Thus, induction of metamorphosis by thyroid hormones notonly involves the stimulation of protein synthetic activity 8 4 7 8 5 , but alsothe appearance of new proteins.91 It is of some interest that other anabolichormones, such as growth hormone,gz test~sterone,~~ oestrogen~,~~ also exerttheir action through genetically controlled mechanisms regulating proteinsynthesis. The exact mechanisms of action however remain unknown.For this, it will be important to identify the primary sites with which thehormones interact in the cell and which trigger off a series of secondarychanges.In the case of thyroid hormones, the chronological study of thelatent period of action appears to be a promising approach for detecting theinitial stages of action.F. J. Finamore and E. Frieden, J. BioZ. Chem., 1960, 235, 1751.91 E. Frieden, Amer. ZooZ., 1961, 1, 115.s2 A. Korner, Mem. SOC. Endocrin., 1961, 11, 60.KG S. Liao and H. G. Williams-Ashman, Proc. Nut. Acad. Sci., Wmhington, 1962,94 G. C. Mueller, J. Gorski, and Y. Aizawa, Proc. Nut. Acud. Sci., Washington,40, 1956.1961, 47, 1645. THE STRUCTURE AND FUNCTION OF RIBOSOMES I NPROTEIN BIOSYNTHESISBy R. R. V. ArnsteinIntroduction. The importance of ribosomes in protein biosynthesis has beenrecognized for many years. Both in animal and bacterial cells incorporationin vivo of amino-acids into peptide linkage takes place on ribosomes withsubsequent release of the newly synthesized protein into the cytoplasm.1, 2In cell-free systems from a variety of organisms this process has been shownto involve at least four different steps. First, ATP reacts with the carboxylgroup of an amino-acid to form an’ aminoacyl adenylate, the reaction beingcatalysed by amino-acid-activating enzymes, each specific for one of the20 amino-acids which commonly occur in p r ~ t e i n .~ The activated amino-acid residues are then transferred to the C,’-hydroxyl group of the terminaladenosine residue of the appropriate soluble (or transfer) ribonucleic acid(s-RNA). s-RNA’s belong to a group of polynucleotides of similar mole-cular weight (approx.25,000) and an identical base sequence (-pCpCpA) inthe terminal triplet.5 Most, if not all, of the remaining structure of eachs-RNA differs and evidently confers specificity for the appropriate amino-acyl adenylate-activating enzyme complex.The matching of activating enzymes from one species with the s-RNAfrom another indicates only a partial overlap and there are species differencesin many S-RNA’s.79 8 Moreover, three different leucine s-RNA’s have beenfound in Escherichia COWThe s-RNA’s are arranged sequentially on the ribosome-messenger RNAcomplex, the order being determined by an interaction which is believed toinvolve base-pairing between a triplet of nucleotides of s-RNA and thecomplementary sequence of the messenger RNA.l o Polypeptide synthesisstarts with the formation of a peptide bond between the N-terminal amino-acid and the next residue by displacement of the terminal s-RNA by theamino-group of the adjacent aminoacyl s-RNA. The peptide chain thusgrows from the N-terminal end by stepwise addition of amino-acidresidues,ll, 1 2 the C-terminal residue remaining covalently linked to the1 H. Chantrenne, “ The Biosynthesis of Proteins,” Pergamon Press, Oxford, 1961.2 P. C. Zamecnick, Biochem. J., 1962, 85, 257.3 M. B. Hoagland, E. B. Keller, and P. C. Zamecnick, J . BioZ. Chem., 1956,218,345. * J. Sonnenbichler, H. Feldmann, and H. G. Zachau, 2. physiol. Chem., 1963,334,5 L. I. Hecht. M. L. SteDhenson, and P. C. Zamecnick, Proc. Nut. Acad. Sci.283.U.S.A., 1959, 45, ‘505.2002.6 R.K. Ralph, R. J. Young, and H. G. Khorana, J . Amer. Chem. SOC., 1963,85,_.7 T. P. Bennett, J. Goldstein, and F. Lipmann, Proc. Nut. Acad. Sci. U.S.A.,* B. P. Doctor and J. A. Mudd, J . Biol. Chem., 1963, 238, 3677.G. von Ehrenstein and D. Dais, Proc. Nut. Acad. Sci. U.S.A., 1963, 50, 81.l o J. D. Watson, Science, 1963, 140, 17.11 H. M. Dintzis, Proc. Nut. Acad. Sci. U.S.A., 1961, 47, 247.l2 J. Bishop, J. Leahy, and R. S. Schweet, Proc. Nat. Acad. Sci. U.S.A., 1960, 46,1963, 49, 850.1030ARNSTEIN : STRUCTURE AND FUNCTION OF RIBOSOMES 513appropriate s-RNA until addition of the next residue.l3, l4 After comple-tion of the polypeptide chain, the final step of protein synthesis involvesremoval of the terminal s-RNA and release of soluble protein, but themechanism of these steps is a t present not well understood.I n view of the complexity of the topic, the present report deals mainlywith the structure of ribosomes in relation to their function in proteinsynthesis.Other aspects, such as the enzymes involved in this process,will not be discussed in detail.The Occurrence of Ribosomes.-Ribosomes contain most of the cellularRNA. I n cells such as Escherichia coli they may constitute as much as30% of the dry weight.l5 In bacteria, the amount of ribosomes is closelyrelated to the growth rate of the organism, the rate of protein synthesisbeing proportional to the cellular concentration of ribosomes.16, l7Ribosomes may occur either as free ribonucleoprotein particles orattached to the endoplasmic reticulum in animal cells 18 and to the cyto-plasmic membrane in bacteria.lg, 2O Isolation procedures thus frequentlyyield a microsome fraction, consisting of ribosomes attached to fragmentsof membranes.I n such cases, free ribosomes may be obtained by treatmentwith deoxycholate 21-23 or other detergents. 24Some of the properties of ribosomesfrom different cells are summarized in Table 1. The fundamental ribosomalGeneral properties of ribosomes.TABLE 1 General properties of ribosomesSedimentation MSource coeff. ( x 10-8)Animal cellsRat liver 80 s(subunits: 60 s, 45 s)(subunits: 57 s, 33 s )85 sOx pancreas 75 s-80 sGuinea-pigp am c r e a sCompositionRNA Pro- RNA:(%) tein Pro-(%) tein Ref.40 0.9 25,26,2724-3339-45 55-67 0.8 28,2935-45 30l3 M.S. Bretscher, J. Mol. Biol., 1963, 7, 446.l4 W. Gilbert, J . Mol. Biol., 1963, 6, 389.l5 A. TissiGres, J. D. Watson, D. Schlessinger, and B. R. Hollingworth, J. Mol.l7 N. 0. Kjeidgaard and C. G. Kurland, J . MoZ. Biol., 1963, 6, 341.l8 P. Siekevitz and G. E. Palade, J. Biochern. Biophys., 1960, 7, 619.l9 J. A. V. Butler, A. R. Crathorn, and G. D. Hunter, Biochem. J., 1958, 69, 544.2o K. McQuillen, R. B. Roberts, and R. J. Britten, Proc. N u t . Acad. Sci. U.S.A.,21 J. W. Littlefield, E. B. Keller, J. Gross, and P. C. Zamecnick, J. Biol. Chem.,2 2 G. E. Palade and P. Siekevitz, J . Biochem. Biophys., 1956, 2, 171.2 3 M. L. Petermann and M. G. Hamilton, J.Biol. Chew,., 1957, 224, 725.2 4 R. Rendi and T. Hultin, E x p . Cell Res., 1960, 19, 253.25M. G. Hamilton and M. L. Petermann, J. Biol. Chem., 1959, 234, 1441.26 A. Korner, Biochem. J., 1961, 81, 171.27 J. Chauveau, Y. MoulB, C. Rouiller, and J. Schneebeli, J. Cell. Biol., 1962, 12, 17.28 P. J. Keller, E. Cohen, and R. D. Wade, Biochemistry, 1963, 2, 315.29 J. T. Madison and S. R. Dickman, Biochemistry, 1963, 2, 321.ao P. Siekevitz and G. E. Palade, J. Biochem. Biophys., 1960, 7, 631.Biol., 1959, 1, 221.R. E. Ecker and M. Schaechter, Biochim. Biophys. Acta, 1963, 7$, 275.1959, 45, 1437.1955, 217, 111.514SourceAnimal cellsNovikoffhepatomaRat JensensarcomaRabbitreticulocytesCalf-thymusnucleiEggs. of Mellitaquznquzeqm-forataPlant cellsPea seedlingsSpinachchloroplastsBIO L 0 GI C -4 L CH E MI S TRYTABLE 1 General properties of ribosomes (contd.)ProtozoaTetrahymenap yrif ormisEuglena(a) chloroplasts(b) microsomesPungiNeurospora crassaYeastsBakers’ yeastSchizosaccharo-myces pombeSedimentationcoeff.81 s(subunits: 56 s, 46 s)80 s(subunits: 62 s, 50 s)78 s(subunits: 58 s, 40 s)72 s(subunits: 63 s, 45 s)85 s80 8(subunits: 60 s, 41 s)80 s(subunits: 71 s, 50 s)66 s(subunits: 47 s, 33 s)75 s(subunit: 50 s)44 s*(subunits: 30 s, 24 s)49 s*(subunits: 36 s, 27 s)81 s(subunits: 60 s, 40 s)80 s(subunits: 60 s, 40 s)83 s(subunits: 60 s, 38 s)* Particles may be degraded.CompositionRNA Pro- RNA:M (yo) tein Pro-( x 10-6) ( %)4.6 37504.0503.34.0-4.5 35-4040-44 53-6042-4567 434.1-4-5 47 5340 603.8tein1.00-81-30.7Ref.313233,3435,363738394041424344,45464731 E.L. Kuff and R. F. Zeigel, J . Biochem. Biophys., 1960, 7, 465.32 M. L. Petermann and A. Pavlovec, J. Biol. Chem., 1963, 238, 318.33 P. 0. P. Ts’o rand J. Vinograd, Biochim. Biophys. Acta, 1961, 49, 113.34 W. E. Dribble and H. M. Dintzis, Biochim. Biophys. Acta, 1960, 37, 152.36 T.-Y. Wang, Biochim. Biophys. Acta, 1961, 51, 180.36 T.-Y. Wang, Biochim. Biophys. Acta, 1961, 53, 158.3 7 R. E. Ecker and J. W. Brookbank, Biochim. Biophys. Acta, 1963, 72, 490.38 P. 0. P. Ts’o, J. Bonner, and J. Vinograd, Biochim. Biophys. Acta, 1958,30,570.30A.A. App and A. T. Jagendorf, Biochim. Biophys. Acta, 1963, 76, 286.40 J. W. Lyttleton, Exp. Cell Res., 1962, 26, 312.41 J. W. Lyttleton, Exp. Cell Res., 1963, 31, 385.4 2 G. Braweman, Biochim. Biophys. Acta, 1963, 72, 317.43 R. Storck, Biophys. J., 1963, 3, 1.44 R. S. Morgan, C. Greenspan, and B. Cunningham, Biochim. Biophys. Acta,46 F.-C. Chao, Arch. Biochem. Biophys., 1957, ‘SO, 426.48 Y. Ohtaka and K. Uchida, Biochim. Biophys. Acta, 1963, 76, 94.4? S. Lederberg and J. M. Mitchison, Biochim. Biophys. Acta, 1962, 55, 104.1963, 68, 642ARNSTEIY : STRUCTURE AND FUNCTION O F RIBOSOMES 515TABLE 1 General properties of ribosomes (contd.)CompositionRNA Pro- RSA:Sedimentation M (yo) tein Pro-Source coeff. ( x 10-6) (yo) tein Ref.BacteriaEscherichia coli ‘70 s 2.6-3.1 63 37 15Sarcina lutea 70 s 48Salmonella 70 s 16units are strongly negatively charged, highly hydrated particles of uniformsize characterized by sedimentation coefficients of 70-85 S, depending ontheir cellular origin.These sedimentation coefficients correspond to mole-cular weights of approximately 3 - 4 x 106. The most detailed studieshave been made with ribosomes from Escherichia cobi, which are mainly70 s particles. As visualized by electron microscopy 4 9 9 50 these particlesare almost spherical with diameters of approx. 200 and 170 8. The mole-cular weight has been calculated l5 from sedimentation, partial specificvolume, and diffusion or viscosity data to be approximately 3 x lo6.Ribosomes from other bacteria are similar in size to those from E.cobi,but those from yeasts and animal or plant cells are larger (diameters about240 x 180 A), with sedimentation coefficients of 80-85 s, corresponding toa molecular weight of approximately 4 x 106. The chemical compositionof ribosomes also depends somewhat on their cellular origin. Bacterialribosomes usually contain more than 60% of RNA and less than 400/6 ofprotein, whereas some animal ribosomes contain about equal amounts ofRNA and protein and those from other animal cells and plants appear tocontain somewhat more protein than RNA. Lipids are absent, but ribo-somes contain also appreciable amounts of d i a m i n e ~ , ~ ~ ~ 5l9 52 such asspermidine, spermine , agmatine , cadaverine, and putrescine, which maycontribute to their stability.53, 54Ribosomes dissociate into twosubunits of unequal size and different properties when the ratio of mono-valent cation (usually K+ or Na+) to bivalent cation (usually Mg2+) in thesuspending medium is mfficiently increased by lowering the bivalent-cationconcentration.Thus, E. coZi ribosomes give rise 15 to 50 s and 30 s sub-units of molecular weight 1.8 x lo6 and 0.7 x lo6, respectively, when Mg2-is decreased from lov2 M to 2-5 x lo-* M. The 50 s particles are dome-shaped; the 30 s particles are flatter and fit on to the 50 s particles like acap.50 The dissociation of ribosomes from many other cells, e.g., baker’s(subunits: 50 s, 30 s)(subunits: 50 s, 33 s)(subunits: 55 S, 35 S) typhimzzriumDissociation of ribosomes into subunits.4 8 J.W. Brown and C. F. Rosenberg, Biochim. Biophys. Acta, 1962, 61, 657.49 C. E. Hall and H. S. Slayer, J. MoZ. Biol., 1959, 1, 329.61 W. Zillig, W. Krone, and 31. Albers, 2. physiol. Chem., 1959, 317, 131.5 2 S. S. Cohen and J. Lichtenstein, ‘J. BioE. Chem., 1960, 235, 2112.b 3 R. G. Martin and B. N. Arnes, Proc. Nut. Acad. Sci. U.S.A., 1962, 48,6 4 A. Hershko, S. Amoz, and J. Mager, Biochem. Biophys. Res. Commn., 1961,H. Huxley and G. Zubay, J . Mol. Biol., 1960, 2, 10.2171.5, 46516 BIOLOGICAL CHEMISTRYyeast,45, 55 pea seedlings,38 rat liver,56 calf liver,57 and reticulocytes 33 ofvarious animal species has also been observed, but the precise conditionsvary in each case.Pancreatic ribosomes, for example, seem to be particu-larly resistant to disso~iation.~~ In the case of the 50 s subunit fromE. mli, a further change has been observed when the sodium chlorideconcentration was increased from 50 to 100 mM at a constant calciumconcentration of 1 mM. These conditions result 58 in the formation ofeither a 47 s or a 43 s particle and release of 5 s material containings - R N A . ~ ~ ~ 6o A 4.5 s component which may be identical with this materialis also released on dissociation of E. coli ribosomes by dialysis against tris-buffer containing 2.5 x 10 -4 M magnesium.61 Rat-liver ribosomes alsocontain bound s-RNA.G2 This treatment also releases nascent proteinchains from 50s ribosomes and it is likely that each of these chains isterminated by s-RNA.l3, l4 The 30 s ribosomal subunit is stable underthese conditions.58In many cases it has been found that dissociation into subunits is rever-sible and ribosomes are re-formed when the magnesium-ion concentrationDissociation of yeast ribosomes by papain digestion also gives 60 s and40 s ribosomes which, however, do not re-aggregate to 80 s particles in highconcentrations of magnesium, indicating that the linkage of subunits mayinvolve to some extent bonds other than RNA-Mg2+-RNA bonds.44Physical re-aggregation of subunits from different bacterial species canoccur,63 but mixtures of subunits from E.coZi and the yeast Schizosaccharo-myces pombe combine in a species-specific manner.47 In the absence of30 s subunits, aggregation of the 50 s particle from E.coli in high magnesiumconcentration has been observed to give an 80 s dimer.50Early work concerning the activity of ribosomes in protein biosynthesisafter dissociation and re-aggregation gave conflicting results. Re-associa-tion of 60 s and 40 s subunits from pea seedlings to fully active 80 s ribo-somes has been reported,64 but in other systems the re-aggregated particleswere not active.65, 66 Failure to obtain active ribosomes from subunitsmay have been due to destruction of messenger RNA, since a latent ribo-nuclease is present in ribosomes from E. coli 583 67 and yeast.46 The E. coZienzyme is present on the 30 s It is activated by Na' and K+and inhibited by Mg2+ 69 and thus conditions used for dissociating ribosomesis increased.15, 2 5 , 33, 38, 45, 56, 576956 R.S. Morgan, J. Mol. Biol., 1962, 4, 115.66 M. Takanami, Biochim. Biophys. Acta, 1960, 39, 318.67 B. D. Hall and P. Doty, J. Mol. Biol., 1959, 1, 111.5 8 D. Elson, Biochim. Biophys. Acta, 1961, 53, 232.69 D. Elson, Biochim. Biophys. Acta, 1962, 61, 460.6 o R. Rosset and R. Monier, Biocl~im. Biophgs. Acta, 1963, 68, 653.6 1 R. G. Hart, Biochim. Biophys. Acta, 1963, 72, 662.62 A, Hicklin and F. Leuthardt, Helv. China. Acta, 1963, 48, 1143.63 S. Lederberg and V. Lederberg, Exp. Cell Res., 1961, 25, 198.64 B. Abdul-Nour and G. C. Webster, Exp. Cell Res., 1960, 20, 226.6 5 A. Tissikres, D. Schlessinger, and F. Gros, Proc. Nut. Acad. Sci. U.X.A., 1960,66 H. Lamfrom and E.R. Glowacki, J. Mot. Biol., 1962, 5, 97.67 H. E. Wade, Biochem. J., 1961, 78, 457.D. Elson and M. Tal, Biochim. Biophys. Acta, 1959, 38, 281.46, 1450.F. Spahr and B. R. Hollingworth, J. Biol. Chem., 1961, 236, 831ARNSTEIN : STRUCTURE AND FUNCTION OF RIBOSOMES 517would be expected to activate the enzyme. Other ribosomes, e.g., thosefrom pea seedlings 38, 70 or liver,71 also contain various ribonucleases.Recent work, however, shows clearly that reconstitution of ribosomal sub-units from E. coli gives ribosomes active in protein synthesis.72, 73Ribosomal RNA’s from a wide variety ofcells have similar nucleotide compositions,74~ 75 characterized by a relativelyhigh guanine content. RNA from ribosomes of animal and plant cells, suchas calf liver,57 rat l i ~ e r , ~ 6 reticulocytes,76 pea seedlings,77 or consistsof two major components, which have sedimentation coefficients of about17 and 30 s, corresponding to molecular weights of approximately 0.5 x lo6and 1.5 x 106, respectively.In the best preparations of RNA from reticu-locyte ribosomes, the two components were present in approx. equimolaramounts. 76 Bacterial ribosomal RNA 79, has sedimentation coefficientsof approximately 16 s and 23 s ( M 0.6 x lo6 and 1.1 x lo6). The 23 scomponent has been isolated only from the 50 s ribosome subunit.s0The optical and hydrodynamic properties 81 and electrometric andspectrophotometric titrations 76 of RNA indicate that ribosomal RNA con-sists mostly of helical regions separated by non- hydrogen-bonded regions.The thermal stability of the secondary structure of ribosomal RNA is some-what greater than that of nuclear RNA or viral RNA.82Considerations of the composition of the ribosomal subunits and theirmolecular weight lead to the conclusion that one molecule of the RNA ofM = 0.5 x lo6 is present in the smaller subunit and one of the RNA ofM = 1.5 x lo6 (or 1.1 x lo6 in the case of bacteria) in the large subunit.Although the two ribosomal RNA components of E.coli have similarbase compositions and physicochemical properties, 83 differences have beendemonstrated in the nucleotide fragments obtained by digestion with pan-creatic ribon~clease.~~ Differences in base composition of the 28 s and 16 sribosomal RNA components of HeLa cells have been reported.85 Structuraldifferences are also indicated by the additive hybrid formation betweenDNA and 16 s or 23 s RNA from E.coli and absence of competitive inter-action between the two RNA components for the same DNA site.86The ribosomal proteins, other thanRibosomal ribonucleic acid.The structural protein of ribosomes.7 0 S. Matsushita and F. Ibuki, Biochim. Biophys. Acta, 1960, 40, 358.71 Y. Tashiro, H. Shimidzu, S. Honde, and A. Inouge, J . Biochem., Tokyo, 1960,72 W. Gilbert, J . Mol. Biol., 1963, 6, 374.73 D. Schlessinger and F. Gros, J . Mol. Biol., 1963, 7, 350.7 4 J. M. Wallace and P. 0. P. Ts’o, Biochem. Biophys. Res. Commn., 1961, 5, 125.7 5 J. E. M. Midgley, Biochim. Biophys. Acta, 1962, 61, 513.7 8 R. A. Cox and H.R. V. Arnstein, Biochem. J., 1963, 89, 574.7 7 G. K. Helmkamp and P. 0. P. Ts’o, J . Amer. Chem. SOC., 1961, 83, 138.7 8 A. Maeda, J . Biochem., Tokyo, 1960, 48, 363.7 9 U. Z. Littauer and H. Eisenberg, Biochim. Biophys. Acta, 1959, 32, 320.g o C. G. Kurland, J . Mol. Biol., 1960, 2, 83.81 R. A. Cox and U. Z. Littauer, Biochim. Biophys. Acta, 1962, 61, 197.82 W. Dingman and M. B. Sporn, Biochim. Biophys. Acta, 1962, 61, 164.83 P. F. Spahr and A. Tissi&res, J. Mol. Biol., 1959, 1, 237.84 A. I. Aronson, J . Mol. Biol., 1962, 4, 453.85 S . Penman, K. Schemer, Y . Becker, and J. E. Darnell, Proc. Nat. Acad. Sci.86 C. Yankofsky and S. Spiegelman, Proc. Nut. Acad. Sci. U.S.A., 1963, 49, 538.47, 37.U.S.A., 1963, 49, 65451 8 BIOLOGICAL CHEMISTRYthe polypeptide precursors involved in protein synthesis, are a complexmixture of basic proteins of relatively uniform molecular weight.Theprotein of E. coli ribosomes has a molecular weight of about 25,000,87 buta somewhat lower figure has also been reported.51 The molecular weightof calf-liver ribosomal protein is similar,ss but that of a fraction of basicproteins extracted from rat-liver ribosomes by dilute acid has been re-ported 89 to be 36,00040,000. Chemically, ribosomal proteins appear tobe very heterogeneo~s.~~ The acid-soluble protein from pea-seedling ribo-somes has been separated by starch-gel electrophoresis into at least 16components.9f The proteins from ribosomes of reticul~cytes,~~ pea seed-l i n g ~ , ~ ~ rat liver,93 and calf thymus n ~ c l e i , ~ ~ ~ have similar amiao-acid com-positions, but different N-terminal groups : alanine and methionine inE.C O E ~ , * ~ alanine and valine in pea seedling^,^^ and alanine, proline, serine,and glycine in rabbit reticulocytes 95 and in rat liver.@ I n E. coli, the sameN-terminal amino-acids were present in the protein from the 50 s and 30 ssubunits as in the 70 s rib0somes.8~The configuration of the RNA inthe ribosome appears t o be similar to that in solution, as shown by thesimilarity in the hy-pochromicity of ribosomes and isolated RNA.96 TheX-ray diffraction patterns of concentrated gels of ribosomes from E. coZi,97Drosophila l a r v ~ e , ~ ~ rat liver,98 and rabbit reticulocytes 98 show reflectionsat 45 and 50 8, which are believed to arise from the internal structure of theribosome, the RNA being present as an array of four or five parallel helicalregions, approximately 45-50 apart.The ribosomal protein might fulfila structural function in preserving this spacing, perhaps by interacting withthe RNA in the non-helical regions.98 Small-angle X-ray scattering ofribosomal RNA from ascites tumour cells, yeast, or E. coli indicates that theRNA is composed of short rigid rods, 50-150 8 in length, joined by smallflexible regions.99 Electro-optical birefrigence and ultraviolet dichroismmeasurements on 80 s yeast ribosomes are also consistent with a regulararrangement of RNA in ribosomes, the plane of the purine and pyrimidinebases being orientated predominantly parallel to the electrical axis of theribosome.loo These observations are compatible with ribosomes consistingof layers of disks in which the ribosomal RNA forms a regular structuralframework. Since the ribosomal RNA appears to be a single strand, itwould connect the different layers, but other components such as the protein,The internal structure of ribosomes.8 7 J.-P. Waller and J. I. Harris, Proc. Nut. Acad. Sci. U.S.A., 1961, 47, 18.J. B. Curry and R. T. Hersh, Biochem. Biophys. Res. Commn., 1962, 8, 415.8 9 P. Cohn and P. Simpson, Biochem. J., 1963, 88, 206.90 P. Spitnick-Elson, Biochim. Biophys. Acta, 1962, 55, 741.91 G. Setterfield, J. M. Neelin, E. M. Neelin, and S. T. Bayley, J. MoZ. Biol., 1960,92 P. 0. P. Ts'o, J.Bonner, and H. Dintzis, Arch. Biochem. Biaphys., 1958, 76, 225.93 C. F. Crampton and M. L. Petermann, J. Biol. Chern., 1960, 234, 2642.94 T.-Y. Wang, Arch. Biochem. Biophys., 1962, 97, 387.95 P. Cohn, Biochem,. J., 1962, 84, 1 6 ~ .g6 D. Schlessinger, J. Mol. Biol., 1960, 2, 92.97 R. Langridge and K. C. Holmes, J . MoZ. Biol., 1962, 5, 611.98 R. Langridge, Science, 1963, 140, 1000.g9 S . N. Timasheff, J. Witz, and V. Luzzati, Biophys. J., 1961, 1, 525.loo R. S. Morgan, Biophys. J., 1963, 3, 253.2, 416ARNSTEIN : STRUCTURE AND FUNCTION O F RIBOSOMES 519diamines, and magnesium would contribute to the stability of the structure.The RNA is not completely buried in the ribosomal protein, since some ofit is accessible to ribonuclease action.lO1 Experiments on the binding ofmagnesium by rabbit -reticulocyte ribosomes show that almost all the bind-ing sites are located on the RNA moiety; about 70% are accessible in theintact ribosome and the remainder are uncovered when the protein isremoved.lo2Polyribosomes: The Ribosomal Structure active in Protein Synthesis.-The existence of aggregates of ribosomes with sedimentation coefficientslarger than 70-85 s was &st noted in E.coli l5 and in rat liver.25 Rabbit-reticulocyte ribosomes were also reported to consist of a mixture of 78 s and113 s particles.33 Subsequently, it was shown that E. coli ribosomes active inprotein biosynthesis have a higher sedimentation coefficient than the bulk ofthe ribosome particles.103 In cell-free preparations from rabbit reticulocytesaggregated ribosomes, with sedimentation coefficients of up to 155 s, werefound to be particularly sensitive to attack by ribonuclease and simultane-ously to lose the capacity to incorporate labelled amino-a~ids.~04 Thelarge-particle fraction of yeast, which has been reported lo5 to be more activethan free ribosomes in protein synthesis, may also have contained suchaggregates.Recent work on the characterization of these aggregates, termed eitherpolyribosomes (polysomes) or ergosomes, has resulted in the elucidation oftheir function in protein biosynthesis both in mammalian 106-1** and bac-terial ~ells.7~9 73 As a result, the concept has now become widely accepted logthat the structure active in protein synthesis (Fig.1) consists of severalribosomes attached to a molecule of messenger RNA (m-RNA). Theribosomes are metabolically relatively stable, whereas m-RNA has a fastturnover rate. During protein synthesis, each ribosome moves along them-RNA. Each nucleotide triplet of the m-RNA determines which amino-acyl s-RNA is added to the growing peptide chain and hence the amino-acidsequence of the protein. Peptide-bond synthesis takes place whilst theamino-acyl-sRNA is attached temporarily to a binding site on the ribosome.The most detailed studies of polyribosomes have been made with pre-parations from animal cells. When rabbit reticulocytes were incubatedbriefly with 14C-labelled amino-acids and the cell lysate was then examinedby zone centrifugation in a sucrose density gradient, the bulk of the ribo-somal radioactivity was found to be associated with the 170 s peak, corres-ponding to the region of tetra-, penta-, and hexa-meric particles.107~ 108lol M.Santer, Science, 1963, 141, 1049.102 I. S. Edelman, P. 0. P. Ts'o, and J. Vinogrsd, Biochim. Biephys. Acta, 1960,l o 3 R. W. Risebrough, A. Tissikres, and J. D. Watson, Proc. Nut. A d . Sci. U.S.A.,1O4 H. R. V. Amstein, Biochern. J., 1961, 81, 24~.lo5 J. G. Hauge and H. 0. Halvorson, Biochim. Biophys. Acta, 1962, 61, 101.lo8 F. 0. Wettstein, T. Staehelin, and H. Noll, Nature, 1963, 197, 430.lo' J. R. Warner, A. Rich, and C. E. Hall, Science, 1962, 138, 1399.lo* J. R. Warner, P. M. Knopf, and A. Rich, Proc. Nat. Acad. Sci. U.S.A., 1963,109 A.Gierer, J. Mol. Biol., 1963, 6, 148.43, 393.1962, 48, 430.49, 122520 BIOLOGICAL CHEMISTRYGrowing peptide chainI, Mov em ent ofribosomes I , Growing peptide chain7S-RNA\Diagram illustrating the function of polyribosomes in protein biosynthesis.Ribosomes attach to messenger RNA at point a and move along the RNA moleculefrom a to f during polypeptide synthesis. s-RNA functions as an adaptor in the codingfor amino-acids by interaction of part of the molecule (probably 3 bases) with the com-plementary nucleotides of m-RNA. The carboxyl group of the growing peptide chainis always attached to s-RNA. When ribosomes reach the end of the m-RNA molecule( f ) , they become detached and the completed peptide chain is released. Emptyribosomes are then available for re-attachment t o m-RNA.I n HeLa cells, labelled leucine was similarly incorporated into aggregatedribosomes of about 250 s sedimentation coefficient.On examination oflysed reticulocytes by electron microscopy, over 75% of the ribosomes werefound to be present as pentamers and it was concluded that haemoglobinbiosynthesis is carried out by the pentaribosomes. The polyribosornestructure has been shown l11 to consist of either a tightly clustered groupor a linear array of particles, connected by a strand lOA in width, withgaps of 100-150 A between ribosomes. The linear structure predominatedin positive contrast, whereas in negative contrast clusters were present. Itis considered that the linear configuration represents the in vivo structure.I n HeLa cells infected with poliovirus new polyribosomes appear.85Electron microscopy 112 and zone centrifugation show these polysomes to belarger (400 s) than those present in uninfected cells (250 s), each polysomecontaining up to 60 ribosomes.85 The new polysome fraction has been foundto contain nascent virus protein by specific precipitation with antiserum. 113The functional significance of polyribosomes in protein biosynthesis hasIloE. F. Zimmerman, Biochern. Biophys. Res. Commn., 1963, 11, 301ll1 H. S. Slayter, J. R. Warner, A. Rich, and C. E. Hall, J . Mol. Biol., 1963, 7 , 652.112 A. Rich, S . Penman, Y. Becker, J. E. Darnell, and C . E. Hall, Science, 1963,113 M. D. Scharff, A. J. Shatkin, and L. Levintow, Proc.Nat. Acad. Sci. U.S.A.,142, 1658.1963, 50, 686ARNSTEIN: STRUCTURE AND FUNCTION O F RIBOSOMES 521been demonstrated also with various cell-free preparations capable of in-corporating labelled amino-acids into protein.lO6, 114 Isolation of rat-liverribosomes at low temperature gave preparations containing more than 50%of particles with sedimentation coefficients ranging from 100 s to 600 S,corresponding to aggregates of from 2 to 20 particles, and incorporation of[ 14Clleucine by fractionated particles showed that the monomeric ribosomeswere inactive.106 The amino-acid incorporating activity per ribosome in-creased up to the pentamers and thereafter stayed constant. This evidencesuggests that the active unit consists of a t least five ribosomes, althoughlarger structures are as active as the pentamers.Essentially similarresults have been obtained in cell-free experiments with ribosome prepara-tions from rabbit reticulo~ytes,~0~, 114 except that no aggregates with sedi-mentation coefficients larger than 220 s (corresponding to hexamers) appearto be present. The polysome fraction is much more active in protein syn-thesis than the monomeric 80 s particles, but the latter fraction respondsto the addition of polyuridylic acid as a messenger by a greater increase inthe incorporation of phenylalanine.lOg The ribosomes of 8. coZi which havethe capacity to synthesize protein in cell-free preparations are also presentin the form of rapidly sedimenting complexes with sedimentation coefficientsof 100-200 s .7 2The relation between polyribosome breakdown and protein synthesishas been studied with cell-free systems from rat liver,l15 HeLa andrabbit reticul~cytes.~~~, 118 Under conditions of protein synthesis, thereis a stepwise breakdown of polysomes by the sequential release of monomerseach containing a completed peptide chain. 115--118 This process differsfrom the random degradation of polysomes by ribon~clease.1~~ There isalso good correlation between protein biosynthesis and the polysome contentof rabbit reticulocytes during maturation of the intact cells in vitr0.1~~Size of messenger RNA. From electron-microscopic measurements, thecontour length of reticulocyte polysomes containing five ribosomes has beencomputed to be about 1500 8.On the assumption that the coding ratio is3 nucleotides per amino-acid 120 and that the nucleotides in m-RNA arestacked with a translation of 3.4 A per nucleotide, this figure is in goodagreement with the length of messenger required for the synthesis of ahaemoglobin chain of approximately 150 amino-acids.1O6, 111 Polysomesfrom HeLa cells infected with poliovirus consist of about 60 ribosomes andsince the virus RNA ( M 2 x lo6) contains about 6000 nucleotides,l12 thenumber of ribosomes in polysomes from reticulocytes and polio infected114 P. A. Marks, E. R. Burka, and D. Schlessinger, Proc. Nut. Acad. Sci. U.S.A.,115 H. Noll, T. Staehelin, and F. 0. Wettstein, Nature, 1963, 198, 632.116 H. M. Goodman and A. Rich, Nature, 1963, 199, 318.117 B. Hardesty, R.Miller, and R. Schweet, Proc. Nut. Acad. Sci. U.S.A., 1963,118 B. Hardesty, J. J. Hutton, R. Arlinghaus, and R. Schweet, Proc. Nat. Acad.119 P. A. Marks, R. A. Rifkind, and D. Danon, Proc. h7at. Acad. Sci. U.S.A., 1963,I2O F. H. C. Crick, L. Barnett, S. Brenner, and R. J. Watts-Tobin, Nature, 19611962, 48, 2163.50, 924.Sci. U.S.A., 1963, 50, 1078.50, 336.192, 1227522 BIOLOGICAL CHEMISTRYHeLa cells appears to be proportional to the length of messenger RNA.Analysis of the length of messenger RNA attached to liver polysomes ofdifferent aggregate size by zone centrifugation in sucrose gradients indi-cates 121 that the length of messenger RNA per ribosome (unit length) isconstant and corresponds to 90 nucleotides (& 10%).This figure is similarto the unit length of polyuridylic acid (about 80 nucleotides per ribosome)which can be derived from the ratio of l*C-labelled polyuridylic acid toribosomes in the case of polysomes formed by E. coli ribosomes.72 In theexperiments with liver polysomes,121 messenger RNA was isolated fromribosomes and polysomes containing 3, 5, 7, 10, or 14 ribosomes after pulse-labelling in vivo with phosphorus-32, and the size of the piece of m-RNAconnecting the ribosomes was computed from the sedimentation coefficientsof the RNA. Incorporation of labelled amino-acids indicated that thelength of polypeptide chain synthesized per ribosome is 2 0 4 0 amino-acids,giving a coding ratio of 3 (i.e., between 2 and 4) nucleotides per amino-acid.Ribosomes can interactwith s-RNA, messenger RNA, synthetic polyribonucleotides, and poly-deoxyribonucleotides. In the case of s-RNA and polyribonucleotides bothenzymic and non-enzymic reactions have been demonstrated.Only arelatively small proportion of ribosomes in E. coli (usually of the order of10%) are, however, capable of interaction with polynucleotides such asturnip yellow mosaic virus RNA 1 2 2 or polyuridylic acid.72 Since it isknown also that, in E. wli, only B small fraction of the total ribosomes con-tains messenger RNA, the majority of the isolated ribosomes seem neitherto contain messenger RNA nor to be competent to accept messenger poly-nucleotides. These observations indicate that most of the ribosomes maybe damaged during isolation, possibly by the latent ribonuclease present inribo~ornes,~*~ 67 by polynucleotide phosphorylase 123 or by the potassium-activated phosphodiesterase.124 Alternatively, inactive particles may bepresent already in the intact cell.By contrast, ribosomes in animal cellssuch as reticulocytes 119 or liver 106 appear to be present mainly in the formof relatively stable polysomes. As in E. coli, the reticulocyte ribosomeswhich interact with polyuridylic acid lo9 or with messenger RNA from rabbitreticulocytes 125 appear to be the 78 s particles. A mixture of the ribosomesubunits may, however, be the active forrn,lO9 particularly since 50 s and30 s subunits of E. coli can form an active complex with polyuridylic acid.14The site of attachment of messenger RNA to ribosomes is still in doubt.There have been reports that both 50 s and 30 s subunits of E.coli containsites which interact with m-RNA 126 or turnip yellow mosaic virus RNA,122but other work indicates that only the 30 s subunit of E. coli ribosomesinteracts with synthetic polynucleotides, such as polyuridylic orT. Staehelin, F. 0. Wettstein, H. Oura, and H. Noll, Nature, 1964, 201, 264.122 R. Haselkorn, V. A. Fried, and J. E. Dahlberg, Proc. Nat. Accld. Sci. U.X.A.,123 J. T. Andoh, S. Natori, and D. Mizuno, J . Biochem. Tokyo, 1963, 54, 339.lfL4 P. F. Spahr and D. Schlessinger, J . Biol. Chem., 1963, 238, PO 2251.125 H. R. V. Arnstein and R. A. Cox, Biochem. J., 1963, 88, 2 7 ~ .126 A. Ishihama, N. Mizuno, M.Takai, E. Otaka, and S. Osawa, J . Mol. Biol.,12' T. Okamoto and M. Takanami, Biochirn. Biophys. Acta, 1963, 68, 325.Interaction of polynucleotides with ribosomes.1963, 49, 511.1962, 5, 251ARNSTEIN : STRUCTURE AND FUNCI'ION O F RIBOSOMES 523natural polyribonucleotides.128 Polydeoxyribonucleotides also interact withthe 30 s subunit, as well as with 70 s ribosomes.129In the absence of soluble enzymes, interaction between ribosomes andpolynucleotides can take place without phosphate-linked energy. 130 Thereis no interaction of E. coEi ribosomes with polyuridylic acid at low concen-trations of magnesium (0-25 mM), but at 5 mM a polyribosome complex isformed.127 Polyadenylic acid apparently does not combine with ribosomesunder these conditions.129 The optimum attachment of messenger RNA toE.coZi ribosomes 73 requires about 0 . 0 1 ~ of magnesium ions. A similarmagnesium requirement for the enzymic synthesis of polyphenylalanine byrabbit-reticulocyte ribosomes in the presence of polyuridylic acid has beennoted.l31The enzymic interaction of polynucleotides with ribosomes requiresphosphate-linked energy, but the reaction appears to take place even at lowtemperatures.132 Synthetic polynucleotides which are capable of function-ing as messengers in polypeptide synthesis form poly~omes.~~s 132 -134 Underthese conditions, polyadenylic acid, which is apparently not bound by ribo-somes in the absence of enzymes,129 also gives rise to p01ysomes.l~~ Theaffinity of some polynucleotides, e.g., polycytidylic acid, for ribosomes islow, and high concentrations may be required for intera~ti0n.l~~ Thechain-length of the polynucleotide may also be important, at least in thecell-free system from E.C O Z ~ . ~ ~ ~ 136 I n a yeast ribosome system short-chainpolyuridylic acid containing only about 20 nucleotide residues, whichare insuflicient for polysome formation, can induce polyphenylalaninesynthesis. 13' Polyuridylic acid-directed incorporation of phenylalanine byEhrlich ascites tumour ribosomes also does not require the obligatoryformation of polyribos~mes.~~~Attachment of new 80 s ribosomes to polysomes has been demonstratedin a cell-free system, but the rate of this process is much less than the rateof polysome breakdown.116-118 The reaction may be enzymic and itsrelative inefficiency is probably an important limiting factor for proteinsynthesis in cell-free systems.ll*The attachment of polynucleotide messenger involves a specific site onthe ribosomal RNA, situated on the surface of the ribosome, since treatmentof ribosomes with ribonuclease TI, which does not degrade polyuridylic acid,inhibits the polyuridylic acid-stimulated synthesis of polyphenylalanine.139128 T. Okamoto and M. Takanami, Biochim. Biophys. Acta, 1963, 76, 266.119 M. Takanami and T. Okamoto, Biochem. Biophys. Res. Commn., 1963, 13, 297.1 3 0 S. Pedersen and T. Hultin, Biochim. Biophys. Acta, 1963, 68, 328.lslH. R. V. Amstein, R. A. Cox, and J. A. Hunt, Nature, 1962, 194, 1042.ls2 A. Kaji and H.Kaji, Biochem. Biophys. Res. Commn., 1963, 13, 186.ls3 G. J. Spyrides and F. Lipmann, Proc. Nut. Acad. Sci. U.S.A., 1962, 48, 1977.lS4 S. H. Barondes and M. W. Nirenberg, Science, 1963, 6, 374.lS5 A. J. Wahba, R. S. Gardner, C. Basilio, R. S. Miller, J. F. Speyer, and P. Lengyel,136 J. H. Matthaei, 0. W. Jones, R. G. Martin, and M. W. Nirenberg, Proc. Nat.13' L. Marcus, R. K. Bretthauer, R. M. Bock, and H. 0. Halvorsen, Proc. Nut.ls8 S . Pedersen, A. M. White, and T. Hultin, Biochern. Biophys. Res. Commn.,139 D. 'CV. Allen and P. C. Zamecnick, Biochem. Biophys. Res. Commn., 1963,11, 294.Proc. Nut. Acud. Sci. U.S.A., 1963, 49, 116.A d . Sci. U.S.A., 1962, 48, 666.Acad. Sci. U.S.A., 1963, 50, 782.1963, 12, 374524 BIOLOGICAL CHEMISTRYThe interaction of ribosomes with different polynucleotides is independentof their cellular origin.Thus, the cell-free system from E. coli responds toRNA from rat-liver nuclei Ig0, lgl or yeast,136, 142 as well as to syntheticpolynucleotides and bacteriophage RNA. Poliovirus RNA interacts withribosomes from either E. coli or reticulocytes.143Interaction between messenger RNA and ribosomes may be inhibitedby homopolyribonucleotides. The phage RNA-induced synthesis of virusprotein by E. coEi ribosomes is inhibited by polyinosinic, polyadenylic, poly-cytidylic, and polyuridylic acids. 144 Polyadenylic and polyuridylic acidsinhibit hzmoglobin synthesis by reticulocyte ribosomes and polyadenylicacid also increases the rate of polysome breakdown, apparently by prevent-ing the re-attachment of 80 s ribosomes to messenger RNA.118 Chloram-phenicol inhibits the polyuridylic acid-induced incorporation of phenyl-alanine by reticulocyte ribosomes,145 and, in bacteria, tetracycline may alsointerfere with the attachment of messenger to ribosomes.146An interaction between s-RNA and ribosomes was first demonstratedsome years ago with ribosomes from Ehrlich ascites ~e1ls.l~' It has beensuggested that the number of ribosomal binding sites for s-RNA may be alimiting factor in protein synthesis.148 The non-enzymic binding of s-RNA,labelled with [14C]uracil or phosphorus-32, to E.coli ribosomes has beenshown to involve mainly a single site, which is located on the 50 s ribosomesubunit, and to be stabilized by magnesium ions.lg9 The s-RNA bindsequally well whether or not it is loaded with amino-acid~,~~~ but the terminalpCpCpA sequence must be present intact.149-152 The terminal phosphategroup at the other end of the s-RNA molecule may be removed withoutaltering its capacity to incorporate amino-acids into protein,153 and inter-action with ribosomes is thus probably not impaired by this treatment. Thepresence of messenger RNA on the ribosome is required for the enzymicinteraction with s-RNA, as shown by the observation that amino-acyl-s-RNA's are bound almost exclusively to the polysome fraction.132, 154Moreover, in experiments with polysomes containing polyuridylic acid orpolyadenylic acid as messenger only the appropriate s-RNA, i.e., phenyl-alanyl-s-RNA and lysyl-s-RNA, respectively, was bound.132 The messenger140 S.H. Barondes, C. W. Dingman, and M. B. Sporn, Nature, 1962, 198, 145.141 G. Braweman, L. Gold, and J. Eisenstadt, Proc. Nat. Acad. Xci. U.S.A., 1963,142 M. W. Nirenberg and J. H. Matthaei, Proc. Nut. Acad. Sci. U.S.A., 1961,47, 1588.143 J. Warner, M. J. Madden, and J. E. Darnell, Virology, 1963, 19, 393.144 W. J. Moller and G. von Ehrenstein, Biochem. Biophys. Res. Commn., 1963,145 A. S. Weisberger, S. Armentrout, and S. Wolfe, Proc. Nat. Acad. Sci. U.S.A.,146 A. I. Laskin and W. M. Chan, Biochem. Biophys. Res. Commn., 1964, 14, 137.147 M. B. Hoagland and L. T. Comly, Proc. Nat. Acad. Sci. U.S.A., 1960, 46, 1554.148 C. L. Robinson and G. D. Novelli, Arch. Biochem. Biophys., 1962, 96, 459.14D M.Cannon, R. Krug, and W. Gilbert, J. Mol. Biol., 1963, 7, 360.160 M. Takanami, Biochim. Bwphys. Acta, 1962, 55, 132.161 L. Bosch, F. Huizinga, and H. Bloemendal, Biochim. Biophys. Acta, 1962,61,220.1 5 2 H. Bloemendal, F. Huizinga, M. de Vries, and L. Bosch, Biochim. Biophys. Acta,lS3 D. R. Harkness and R. J. Hilmoe, Biochem. Biophys. Res. Commn., 1962, 9, 393.154 P. Cammarano, G. Giudice, and G. D. Novelli, Biochem. Biophys. Res. Commn.,50, 630.11, 325.1963, 50, 86.1962, 61, 209.1963, 12, 498ARNSTEIN : STRUCTURE AND FUNCTION O F RIBOSOMES 525polynucleotide thus controls the specificity of the interaction between s-RNAand ribosomes, but there is no interaction between polynucleotides ands-RNA in the absence of ribosomes.132 Interaction between s-RNA andmessenger on the ribosome does not necessarily require that both moleculesmust be attached to the ribosome surface in close proximity.The s-RNAmolecule is a double helix 100 in length 155 and could stretch across about1/.6th of the circumference of the ribosome. Attachment of the CCA endof a s-RNA to the 50 s subunit therefore does not preclude location of themessenger on the 30 s particle or between the two subunits.Under conditions of cell-free protein synthesis, there is an enzymicattachment of s-RNA to ribosomes which appears to differ from the non-enzymic interaction of ribosomes with s-RNA in being dependent on GTPand a nucleoside triphosphate-generating system 1 4 ' 3 156--159 and on messen-ger polynucleotides.~5~ The extent of this enzymic attachment of s-RNAhas not been calculated, but appears to be considerably greater than thenon-enzymic interaction and may thus amount to several molecules perribosome.Polynucleotides with a high degree of ordered secondary structure, suchas poly-UG containing relatively large amounts of G, have low messengeractivityY16O which may be due to poor interaction with s-RNA.The interaction between s-RNA and messenger RNA or polynucleotideson the ribosome is independent of the amino-acid attached to the s-RNA.Thus, alanine attached to cysteine-specific s-RNA, prepared by desulphuriza-tion of cysteinyl-s-RNA with Raney nickel, is incorporated into polypep-tides when poly-UG is added to the E.coZi cell-free system.161 Poly-UGcodes for cysteine but not for alanine, and this result is therefore a convincingdemonstration of the adaptor function of s-RNA in coding for amino-acids.When hzemoglobin is synthesized in a cell-free system from rabbitreticulocytes, alanine attached to the cysteine-specific s-RNA is incorporatedinto cysteine positions of the a-chain, showing that s-RNA functions as anadaptor with a natural messenger 162 as well as with the synthetic poly-nucleotide, poly-UG.Similar experiments have been carried out 163 with3,4- di h ydr ox y [ I4C]p henylalanine - s - RNAg:& prepared by incubation of[ 14C]tyrosine-s-RNA~Y',,i with polyphenoloxidase. Incubation of the newamino-acyl-s-RNA with a cell-free system from reticulocytes resulted in theincorporation of 3,4-dihydroxyphenylalanine into haemoglobin.155 M.Spencer, W. Fuller, M. F. Wilkins, and G. L. Brown, Nature, 1962, 194, 1014.156 A. von der Decken, Biochem. Biophys. Res. Commn., 1963, 11, 483.15' W. S. Bont, L. Bosch, H. Bloemendal, H. Hilders, and F. Huizinga, Biochim.158 T. Hultin and A. von der Decken, Exp. Cell Res., 1959, 16, 444.R. Arlinghaus, G. Favelukes, and R. Schweet, Biochem. Biophys. Res. Commn.,160 M. F. Singer, 0. W. Jones, and M. W. Nirenberg, Proc. Nut. Acad. Xci. U.S.A.,F. Chpeville, F. Lipmann, G. von Ehrenstein, B. Weisblum, W. J. Ray, jun.,l62 G. von Ehrenstein, B. Weisblum, and S. Benzer, Proc. Nut. Acad. Sci. U.S.A.,1 1 3 ~ F. Chapeville, G. Cartouzou, and S. Lissitzky, Biochim. Biophys.Acta, 1963,Biophys. Acta, 1963, 68, 487.1963, 11, 92.1963, 49, 392.and S. Benzer, Proc. Nut. Acad. Sci. U.S.A., 1962, 48, 1086.1963, 49, 669.68, 496526 BIOLOGICAL CHEMISTRYControl of polysome function in protein synthesis. There itre two differentmechanisms, one involving regulation of messenger RNA synthesis, the othertranslation of the encoded information from messenger RNA to protein.The first mechanism operates, for example, in the induction and repressionof enzyme synthesis in bacteria 164 and in higher organisms may play a partin the stimulation of protein synthesis after fertilization lG59 166 or byhormones. 167Secondly, synthesis of different proteins may be controlled by regulationof the activity of polysomes containing a polycistronic messenger RNA,i.e., a messenger which codes for several proteins. Thus, RNA from thebacteriophage, MS@2 induces the synthesis of at least three different proteinswhen added to a cell-free system from E . coli, but synthesis of one proteinprecedes that of the other two by several minutes.168 Since the phageRNA consists of one single-stranded molecule, it is likely that only onespecies of polysome is formed.There is evidence that in the polyuridylic acid-induced synthesis of poly-(phenylalanine) the number of active centres at which peptide synthesisoccurs in the polysomes increases with time,l4 suggesting that ribosomesstart to synthesize polypeptide only at the beginning of the messengerpolynucleotide strand. In this case, delay in translation of a polycistronicmessenger RNA after the first protein is read could arise by the presence atcertain points on the messenger of triplets controlling the movement ofribosomes. Alternatively, ribosomes may attach at the appropriate startingpoint of the messenger for each protein,l12 the rate of synthesis being deter-mined either by the facility with which attachment occurs a t differentpoints or by factors controlling the rate at which different portions ofmessenger RNA are read.Recent Work on the Polynucleotide Code for Amino-Acids.-Since lastyear’s Report l 6 9 several reviews of the polynucleotide-directed proteinsynthesis in cell-free systems have been published. l7O-l74 An importantdevelopment has been the discovery that polyadenylic acid codes forlysine.175 Recent work has also confirmed earlier results 176 indicating thatpolynucleotides other than copolymers of U are also active in directing poly-peptide synthesis. Of the 64 theoretically possible combinations more than40 coding triplets (codons) have now been assigned to the 20 amino-acids164 T. Kano-Sueka and S. Spiegelman, Proc. Nat. Acad. Sci. U.S.A., 1962, 48, 1942.1 6 5 M. Nemer and S. G. Baird, Science, 1963, 140, 664.166 A. Monroy and A. Tyler, Arch. Biochem. Biophys., 1963, 103, 431.16’ D. A. Silverman, S. Liao, and H. G. Williams-Ashman, Nature, 1963, 199, 808.16* Y. Ohtaka and S. Spiegelman, Science, 1963, 142, 493.169 T. L. V. Ulbricht, Ann. Reports, 1962, 59, 379.1 7 0 F. H. C. Crick in “ Progress in Nucleic Acid Research,” eds. J. N. Davidson1 7 1 M. W. Nirenberg, J. H. Matthaei, 0. W. Jones, R. G. Martin, and S. H. Barondes,17% S. Ochoa, Fed. Proc., 1963, 22, 62.1 7 3 R. V. Eck, Science, 1963, 140, 477.T. H. Jukes, American Scientist, 1963, 51, 227.1 7 5 R. S. Gardner, A. J. Wahba, C. Basilio, It. S. Miller, P. Lengyel, and J. F. Spyer,Proc. Nat. Acad. Sci. U.S.A., 1962, 48, 2087.176 31. S. Bretscher and M. Grunberg-Manago, Nature, 1962, 195, 283.and W. E. Cohn, Vol. 1, Academic Press, New York, 1963, p. 164.Fed. Proc., 1963, 22, 55ARNSTEIN : STRUCTURE AND FUNCTION OF RIBOSOMES 527which commonly occur in proteins.135 There is thus convincing evidencefor the degeneracy of the code, i.e., for coding of some amino-acids by morethan one codon. The activation of N-acetyltyrosine by calf-liver extractsand its transfer to s-RNA have been dem0nstrated.l'' It is possible there-fore that the acetylated N-terminal amino-acid residues in certain proteinsmay be derived by biosynthesis from acetamido-acids. In this case,messenger RNA would presumably have to code for acetamido-acids bytriplets different from those used for free amino-acids.At least one example of ambiguity, i.e., coding for more than one amino-acid by the same codon, has been detected in experiments with poly-uridylic acid, which stimulated the incorporation of leucine as well asphenylalanine.136, 176, 17* This ambiguity appears to be restricted to oneof the three leucyl s-RNA's, since after separation of the leucine-transferRNA's by counter-current distribution, one responded to poly-UC, thesecond to poly-UG and only the third to polynucleotides rich in U, includingpolyuridylic acid.g It is possible, however, that the degeneracy detected bypolynucleotide-directed amino-acid incorporation may not be related to themessenger RNA code, as synthesis of f2 bacteriophage protein by the cell-freeE. coli system following addition of phage RNA takes place equally wellfrom leucine attached to either s-RNA~",~ (which responds to poly-UC) ors-RNA~",~ (which responds to p~ly-UG).~It has been suggested 179 that messenger polynucleotides are read fromthe free 3'-hydroxyl end, since a polynucleotide prepared by priming poly-uridylic acid synthesis with ApU and ApApU and therefore believed to beApUpUp. . . . UpU incorporated phenylalanine and tyrosine, the latterbeing apparently in the C-terminal position. tobe coded by the triplet U,A and it has therefore been assigned the sequenceAUU. Apart from the homopolynucleotides, this is the first coding tripletwhich has been assigned a definite sequence, but it should be noted thatonly a very small stimulation of tyrosine incorporation was obtained inthese experiments and the evidence is therefore not conclusive.The products synthesized by the cell-free E. coli system in the presenceof certain polynucleotide messengers have been identified. Polyadenylicacid containing more than 200 residues synthesizes polylysine, but theaverage peptide length was only 14-17 residues.ls2 The chain length ofthe polypeptide is thus much shorter than would be expected from the sizeof the polynucleotide messenger. Other workers 183 have found only dilysineas the main product, with small amounts of oligopeptides. It is clear,therefore, that either the messenger polynucleotides or the products (or both)Tyrosine is known l80,177 R. Pearlman and K. Bloch, Proc. Nat. Acad. Sci. U.S.A., 1963, 50, 533.178 B. Weisblum, S. Benzer, and R. W. Holley, Proc. Nat. Acad. Sci. U.S.A., 1962,A. J. Wahba, C. Basilio, J. F. Speyer, P. Lengyel, R. S. Miller, and S. Ochoa,l S o R. J. Martin, J. H. Matthmi, 0. W. Jones, and M. W. Nirenberg, Biochem.J. F. Speyer, P. Lengyel, C. Basilio, and S . Ochoa, Proc. Nat. A d . Sci. U.S.A.,182 Y. Kaziro, A. Grossman, and S. Ochoa, Proc. Nut, Acad. Sci. U.S.A., 1963,50,64.18s M. A. Smith and M. A. Stahmann, Biochem. Biophys. Res. Commn., 1963,13,251.48, 1449.Proc. Nat. Acad. Sci. U.S.A., 1962, 48, 1683.Biophys. Res. Commn., 1962, 8, 410.1962, 48, 63528 BIOLOGICAL CHEMISTRYmay be extensively degraded in the cell-free system. Poly-AU (6 : 1)directs the synthesis of lysine-containing co-polypeptides with asparagineand isoleucine.182Ultraviolet irradiation of polyuridylic acid gives a product which hasless activity as a messenger for phenylalanine incorporation, but stimulatesthe incorporation of serine into p0lypeptides.~*4 The change in coding isdue to formation of a water adduct across the 4,5 double bond of uracil, theother irradiation product, uracil dimer, being inactive as a messenger foreither phenylalanine or serine incorporation. lS518* L. Grossman, Proc. Nat. Acad. Sci. U.S.A, 1962, 48, 1609.lS5 L. Grossman, Proc. Nut. Acad. Sci. U.S.A., 1963, 50, 657

ISSN:0365-6217    

DOI:10.1039/AR9636000467

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRYA. Doason, C. II. Hughes, and G. Ingram1. INTRODUCTIONANALYTICAL chemistry is now very concerned with the characterisation ofcomplex inorganic and organic structures. In consequence every techniqueof science, which may involve a chemical, physical-chemical, or physicalprocedure, is being utilised by the analyst to resolve the many problemsprovided by the diverse materials submitted for analysis. The continuedexpansion of the industries on a more scientific basis is reflected in the vastamount of literature published during 1963 concerning the analysis ofindustrial products. Whereas Continental and American publications wereprevalent prior to the present decade, Russian and other Eastern countriesare now providing a vast amount of literature on analytical topics makingthe task of any reviewer more difKcult.Further evidence of the enormous expansion of analytical chemistry isthe period of time which now elapses between publication of an article andits reporting in abstract form in the various English-language abstractjournals, e.g., Chemical Abstracts and Analytical Abstracts.This interval isnow more than 6 months and in many instances, in the case of Russianarticles, up to 1 year elapses before an English abstract appears. It ishoped that this state of affairs will right itself in the not too distant future,though the present trend is for the interval to increase. Previous reviewers 1have commented on the extent of the numerical coverage of analyticalchemistry papers in the literature and the help that such abstracts give tothe analytical chemist, and in particular to the reviewer.It is the opinionof the present reviewers that it is no longer possible to cover the whole fieldand give a balanced picture of progress made during any one year, unlesssome selection is made. It is acknowledged that individual reviews ofspecialised topics, which appear too infrequently in some journals, providea valuable service and should be encouraged by editors. Such reviews, inthe light of the increasing magnitude of literature, are perhaps the bestmeans of giving a balanced coverage of any branch of analytical chemistry.In such an article it is not the number of references which counts, but thekind of information it contains, coupled with an unbiased appreciation ofthe topic under review.Some fields of chemistry are covered by suchreviews, e.g., Quarterly Reviews,2 but as yet a similar type of review has notbeen promoted to serve the needs of the analytical chemist. Perhaps thisis now the time to consider such a project.Papers published during 1963 have covered a diversity of methods.These range from a simple spot test to the near-automation of carbon andhydrogen; from a method employing filtration as the simple means ofD. W. Wilson, J. V. Westwood, and P. F. S. Cartmight, Ann. Reports, 1962,59, 436.2 Quart. Rev., published by The Chemical Society530 ANALYTICAL CHEMISTRYseparation to the use of vapour phase chromatography to separate com-ponents of a complex organic liquid; and from a macro- to an ultramicro-method using only a few micrograms of material for analysis.It is difficult to write an introduction to the progress in analyticalchemistry without echoing the words of last year’s reporters. There is nodoubt that the trends indicated by them, i.e., the increased use of instru-mental techniques and complexometric analysis, are still apparent. Therehas been talk in recent years of analysis reaching the extreme of full automa-tion, and one wonders whether a reactionary school is being established bythose opposing this end.It is difficult to express this without appearingcynical but it seems that more and more use is now being made of knowledgeand materials which have been available for many years.Certainly anumber of analytical applications of well-known but hitherto unusedmaterials have been reported.It is also evident that papers are sometimes being published at greatlength when a short communication would suffice. Whilst one dare not saythat research should go unreported, a great deal of the 1963 literature couldhardly be called a record of progress. Your reporters hope that they havebeen able to make the distinction. It is also hoped that those worthyauthors whose papers have been omitted for other reasons will forgive usand not assume that we thought their papers without merit.Automation continues to expand, particularly in the control of in-dustrial products, where indeed it finds its most useful application. Thisbeing the current trend, it is assumed that it should function in all cases andfind its place in laboratories less concerned with industrial practice.Thus,there is the tendency to think that classical methods of analysis, in-corporating as they do less complex techniques, are obsolete. Equallycostly instrumental methods are also dominating the analytical scene as aservice to technical research laboratories, as shown by the number of paperspublished on this aspect. As typical examples, vapour phase chromato-graphy and differential thermal techniques find useful application in theanalysis of plastic materials, hitherto difficult to cope with by classicalmethods. It is therefore refreshing to note that simple thin-layer chroma-tography is finding pride of place in the analysis of materials derived frommany sources.One of the arguments in favour of automation is the need for the rapidreporting of analytical data.Another equally important reason is the needto conserve valuable samples, often available in extremely small amounts.The determination of carbon and hydrogen simultaneously with nitrogen, inorganic compounds, is a typical example of the current trend towardssatisfying these needs. In the past few years developments have takenplace in which samples of the order of 0.5 mg. can be analysed within 15minutes in this way. Within the space of one year a commercial apparatushas become available which, though costly, has revolutionised elementalanalysis, and may oust the gravimetric method that has withstood the testof time for about 100 years.Nevertheless, some reserve is necessary beforerejecting a well-tested procedure. Thought must be given to the chancethat a sample derived from a large bulk of material, such as an industriaIXORGANIC QUALITATIVE ANSLYSIS 531product, may not be homogeneous, and the few hundred micrograms takenmay not be truly representative of the whole.Milligram analysis has continued to form a fair proportion of publishedwork, particularly on the determination of the elements in organic corn-pounds. The simultaneous determination of more than two elements usingone sample weight continues to attract attention.Reporters in the past have presented their review under various tech-nique headings. We have preferred to adopt the opposite approach andarrange the subjects according to inorganic and organic classes.Thearrangement is as follows : (1) Introduction. (2) Inorganic QualitativeAnalysis. (3) Inorganic Quantitative Analysis. (4) Organic Analysisthrough Functional Groups. ( 5 ) Organic Elemental Analysis. In thisway, we present our Report under the theme of application, and only ina few cases have we resorted to a discussion under the heading of atechnique.2. INORGANIC QUALITATIVE ANALYSISComplexometric Analysis.-Complexometric determinations continue tobe widely used, As expected, therefore, the year’s literature was wellsprinkled with articles of a general nature on this subject. There have beenpapers on the analytical significance of co-ordination ~hemistry,~ and theanalytical approach to chelating resins.4 The use of Schiff bases as indi-cators in complexometric titrations has been discussed.An account hasbeen given of the effect of pH on selectivity in complexometric analysk6Apart from these more general discussions, a great deal has been writtenon the use of specific organic materials for inorganic analysis. The analyticalproperties of anthranilic acid 7 and ascorbic acid 8 have been described.The applications of mercaptoquinol qualitative analysis of 8 inorganic ionswere also reported in the first of a series of papers on mercaptodiphenols ininorganic analy~is.~ Cinnamic acid has been used as an analytical reagentfor indium and gallium.1°Spot Tests.-Several new spot tests were reported, some of which canbe developed into colorimetric quantitative determinations.Antipyrine inthe presence of potassium chromate has been given as a new reagent for thedetection of nitrite.ll The test is very sensitive and has the advantage thatother anions do not interfere, although iodides require a modified technique.Another interference-free test, requiring spot paper impregnated withbrucine, benzidine, and phosphoric acid, was reported by Gressmann. l23 P. W. West, Acta Chim. Acad. Sci. Hung., 1962, 34, 143.G. Schmuckler, Takcnta, 1963, 10, 745.S. N. Poddar, N. R. Sengupta, and A. K. Dey, S ~ i e ~ e and Czcltzcre, 1963, 29,V. G. Sochevanov, Zavodskaya Lab., 1963, 29, 531.D. L. Dinsel, Diss. Abs., 1963, 24, 51.F. Buscarons and J.Alsina, A& red SOC. e q a k Pis. Quim., 1963, 59, B, 101.257.8 L. Erdey and G. Svehla, Chemi&-Analyst, 1963, 52, 24.lo E. A. Ostroumov and J. I. Volkov, Zlzur. analit. Khim., 1963, 18, 52.l1 U. Bogs and W. Gothe, 2. analyt. Chem., 1963, 196, 87.12 K. Gressmann, Mikrochim. Ichnoanalyt. Acta, 1963, 782532 ANALYTICAL CHEMISTRYA further paper by this author gives a spot test for oxidant anions includingnitrite, hypochlorite, chromate, bromate, hexacyanoferrate(m), peroxodi-sulphate, iodate, chlorate, and nitrate.13Feigl and Pollak l4 described a spot test for phosphate and bromateusing the familiar Molybdenum Blue colour reaction. Phosphate requiresalkali, molybdate, and iodide, whilst bromate is identified with phospho-molybdate and sulphosalicylic acid.Sulphosalicylic acid has also been used in the detection of ferricyanidesince this latter catalyses its reaction with cerium(~rr).l~ The same authorshave reported spot tests for cerium and cobalt.16 Cerium(Iv) has been usedfor the quantitative titrimetric analysis of ferrocyanide using nickel phthalo-cyaninesulphonic acid as indicat0r.l' A spot test for beryllium, usingEriochrome Cyanine R, was reported.lsNew Techniques applied to Qualitative Analysis.-The ring-oven techniquehas again received attention.A separation of anions by this means waspublished late in 1962 l9 and further work has been reported this year.20The ring oven has been applied to the study of air pollution. A method forthe determination of sulphur dioxide and sulphate in air by the coprecipita-tion of barium sulphate with permanganate was also described.21 Anotherscheme, for inorganic microanalysis, based on circular paper chromatographyhas been detailed.22 Two workers in this field, Biswas and D e ~ , ~ 3 alsoproduced a separation scheme for cations by filter-paper-strip chromato-graphy.They also have applied the ring-oven method to the identificationof less-familiar cations. 24New methods of separating cations have been outlined 25, 26and techniques have been described for the separation of bivalent rare earthsfrom tervalent rare earths, aluminium, and yttrium.27 Cationic resins havebeen used to remove interfering anions prior to nitrate determination. 28Analytical separations have also been discussed by Donaldson, 29 whilstBabko and Zharorskii 30 have treated the subject of extraction in analyticalchemistry.Associated work has been carried out on qualitative paperXeparations.13 K. Gressmann, Milcrochim. Ichnoanalyt. Acta, 1963, 784.14F. Feigl and M. M. Pollak, Mikrochim. Ichnoanalyt. Acta, 1963, 696.15V. P. Ranga Rao and D. Satyanarayana, Z. analyt. Chem., 1963, 195,16V. P. Ranga Rao and D. Satyanarayana, Z. analyt. Chem., 1963, 197, 409.1 7 G. Gopala Rao and N. V. Rao, 2. analyt. Chem., 1963, 196, 102.lap. R. Mohilner, Analyt. Chem., 1963, 35, 1103.19 A. Musil, W. Haas, and J. Drabner, Mikrochim. Acta, 1962, 1121.20 S. D. Biswas, K. Nath Nunshi, and A. K. Dey, Mikrochim. Ichnoanalyt. Acta,21 C. Huygen, Milcrochim.Ichnoanalyt. Acta, 1963, 6.22 I. I. M. Elbeth and G. G. Gabra, Chemist-Analyst, 1963, 52, 36.2 3 S. D. Biswas and A. K. Dey, Z. analyt. Chem., 1963, 192, 376.2 4 S. D. Biswas and A. K. Dey, Milcrochim. Ichnoanalyt. Acta, 1963, 10.25E. Popper, Rev. Chim. (Acad. R.P.R.), 1962, 7, 381.28 E. Popper, L. Roman, R. Craciuneanu, and E. Florian, Bull. SOC. chim. France,2 7 J. S. Fritz and B. B. Garralda, Talanta, 1963, 10, 91.I. K. Tsitovich and T. A. Lapina, Zhur. Vsesoyuz. Khim. obshch. im. D.I.2 * D. L. Donaldson, Diss. Abs., 1963, 23, 4082.30A. K. Babko and F. G. Zharovskii, Zavodskaya Lab., 1962, 28, 1287.256.1963, 40.1963, 991.Mendeleeva, 1962, 7, 579INORGANIC QUALITATIVE ANALYSIS 533electrophoresis.31 There has been some work on microdiffusion analysis 32and a rapid method of microanalysis by the moving boundary techniquehas been described.33The thin-layer chromatography of condensed phosphates is described ina series of papers.34 Schafer 35 has written on the application of ion ex-change in the analysis of phosphate rocks.Further papers on phosphateanalysis are discussed under other sections.Detection of Cations.-Several recommendations have been made for thedetection of traces of copper. Variamine Blue has been used36 for copper(I1)and a highly selective test for copper(1) as the acetylide has been given.37Cupric ions are reduced with hydroxylamine and a red colour is developedwith acetylene. Many other cations do not interfere, but anions such aschloride, sulphate, nitrate, and carbonate cause some interference.A newmicrocrystallographic detection of silver as diamminesilver thiocyanate hasbeen reported, in which the limit of detection is 1 : 17,000. Nickel, cobalt,manganese, and mercury were found to impair this sen~itivity.~~A test for beryllium in the qualitative scheme, in which it separates inthe ammonia group, has been described.39 The reagent is hexamino-cobalt(m), and the test is not subject to the usual interferences. Berylliumhas also been detected by coprecipitation with thorium using MethyleneBlue and tannic acid at pH 8-10, and ammonium chloride as the coagu-lating agent.40A new reagent for magnesium has been reported,41 5-chloro-2-hydroxy-3-sulphophenylazobarbituric acid, called for short, Lumomagneson Irea.Cadmium has been detected using a simple technique of ascending~hromatography.~~ Ion-exchange resin particles have been used 43 for themicrochemical detection of mercury( II), and a colorimetric method, dependingon the reduction of by mercury in hydrochloric acid, has been givenas a means of identifying mercury(I), mercury(II), and molybdenun~~~Methyl Violet has been described as a reagent for the detection of bor0n.~5Several new colour reactions of elements in the boron group have beenapplied quantitatively.These will be dealt with in the appropriate section.A spectrophotometric study has been made of the colour reactions31 S. Elias, M. Elias, I. Vintila, A. Popescu, and I. Szathmary, Studii si Cercetari32 0.Ishizaka, Japan Analyst, 1962, 11, 1064.33 B. P. Kanstantinov and 0. V. Oshurkova, Doklady Akad. Nauk X.X.S.R., 1963,34 T. Rossel, Z . analyt. Chem., 1963, 197, 333.35 H. N. S. Schafer, Analyt. Chem., 1963, 35, 53.36 F. Buhl and Z. Gregorowicz, Chem. Analit., 1963, 8, 511.37 T. H. Whitehead and G. Hatcher, Chemist-Analyst, 1963, 52, 109.38 K. R. Manolov, Mikrochim. Ichnoanalyt. Acta, 1963, 239.ss J. W. L. Van Ligten and W. Cool, Analyt. Chim. Acta, 1963, 29, 89.40 K. Sudhalatha, Talanta, 1963, 10, 934.41 G. V. Serebryakova, A. M. Lukin, and E. A. Bozhevolnov, Zhur. analit. Khim.,42 M.-E. Cohen-Nordmann, Bull. SOC. chim. France, 1963, 320.43 K. Kato and H. Kakihana, J. Chem. SOC. Japan, 1963, 84, 405.4 4 A. Alexandroff and P. Vassileva-Alexandrova, Mikrcchim.Ichnoanalyt. Acta,46 M. P. Babkin and R. D. Sechan, Izvest. V.U.Z.M.V.O. S.S.S.R.. Khim. i Lhim.Sti., Chim. (Baza Cercetari Sti., Timisoara), 1962, 9, 47.148, 1110.1963, 18, 706.1963, 23.Tekhnol., 1962, 5, 847534 ANALYTICAL CHEMISTRYbetween germanium and compounds of the o-diphenol type,4s 3,4-dihy-droxyazo benzene -4-sulphonic acid and 3,4- dih ydrox ynap ht h yldip henyl car -binol have been investigated. These form coloured complexes in strong acidby tautomerism to the o-hydroxyquinone structure.The reaction of bismuth ions with salicylic acid and cyanide has beenemployed as a spot test for the element, the conditions of the test allowbismuth to be detected without interference from silver, tin, or lead.47Further work on the detection of selenium and tellurium has been carriedout.The reaction between selenium( N) and 3,3'-diaminobenzidine hasbeen studied further.48, 49 It has been shown that, as a test for selenium, itis less specific than previously believed. It can be made specific after separa-tion of the selenium as the tetrabromide. The procedure is described.49Lakin and Thompson have reported a new, very sensitive test for tell~rium.~0The use of p-thiocresol as a reagent for technetium and rhenium has beeninvestigated. 51 Technetium can be preferentially reduced. The influenceof other elements on the test is given. Iron(m) has been detected by acompound Ferricon 5 2 which is claimed to be specific for the element. Therehave been several new reagents for cobalt and nickel.l-Phenylthiosemi-carbazide has been used both qualitatively and quantitatively as a reagentfor cobalt.53 A 1 : 3 cobalt : organic compound is formed in the presence ofnickel, zinc, or iron(m) in an ammoniacal medium. Cobalt and nickel havebeen detected in the presence of one another by ~entane-2~4-dione.~~ Thenickel complex is preferentially extracted into chloroform a t pH 7-8.Iron, copper, and chromium, however, interfere and must be removed.Other work on these elements which should be mentioned has been carriedout by Nishida.55A selective test with phosphomolybdic acid has been developed foreuropium in the presence of other rare earths.56 The rare earths in generalwere among the many compounds whose reaction with Xylenol Orange wasstudied .3.INORGANIC QUANTITATIVE ANALYSISMANY papers of interest on the colorimetric, gravimetric, and titrimetricdetermination of elements have been published. Classical methods foranions have also received some attention with regard to improvement ofexisting procedures.Colorimetric Analysis.-A review has been written on new colorimetricreagents for the determination of metals.58 The determination of copper46 V. A. Nazarenko and G. V. Flyantikova, Zhur. analit. Khim., 1963, 18, 172.4 7 M. R. T'erma and K. C. Agrawal, Mikrochirn. Ichnoanalyt. Ada, 1963, 395.4 8 L. Barcza, Magyar Ke'rn. Polydirat, 1963, 69, 248.4 9 L. Barcza and L. Sommer, 2. analyt. Chin., 1963, 192, 304.6 o H. W. Lakin and C. E. Thompson, Science, 1963, 141, 42.61 M.Al-Kayssi and R. J. Magee, Talanta, 1963, 10, 1047.6 2 S. N. Sinha and A. K. Dey, Ghim. analyt., 1963, 45, 224.5 3 N. V. Koshkin and N. M. Shreiner, Zhur. analit. Khim., 1963, 18, 767.5 4 A. H. I. Ben-Bassat and I. Bineboym, Chernist-Analyst, 1963, 52, 103.65 H. Nishida, Japan Analyst, 1963, 12, 567.66 E. Jungreis and E. Levy, Talanta, 1963, 10, 708.6 7 D. Prajsnar, Chem. Analit., 1963, 8, 71.6* T. S . West, I n d . Chemist, 1963, 379INORGANIC QUANTITATIVE A N A L Y S I S 535with diethyldithiocarbamate has been discussed, particularly with respectto interference from porcelain crucibles. 59 The colorimetric determinationof silver has also received attention.60A new reagent, the product of self-coupling of H-acid, has beenrecom-mended for the determination of calcium.It has been given the short nameof Calcion Irea.61 The co-extraction of calcium and strontium with oxy-quinolinates has also been the subject of a paper.e2 There have beenseveral communications on boron determination by means of curcuminreagent, I n one, boron was separated by distillation as methyl borate.63Aluminium has been determined colorirnetrically in some minerals usingPyrocatechol Violet as reagent.64 Optimum pH values are given as 6-1-6-2.The effect of other ions is discussed and it is recommended that iron isremoved with o-phenanthroline prior to the determination. The reaction ofaluminium with Xylenol Orange was studied. This reaction was used todetermine aluminium and molybdenum in uranium. The composition ofthe complexes and their association constants were calculated. 65In a series of communications on the use of formazans in analyticalchemistry, S-cyano-l,5-di-(2-hydroxyphenyl)- formazan was given as a re-agent for gallium.66 The authors report two blue compounds of the reagentwith gallium, and suggest its use for the determination in the presence ofaluminium, zinc, lead, cadmium, manganese, indium, germanium, copper, ornickel.It is necessary to extract the last two metal complexes from thegallium compound with benzene. The spectrophotometric determination ofgallium has also been achieved using 1 -(2,4-dihydroxyphenylazo)-2-hydroxy-naphthalene-4-sulphonic acid.67 The coloured complex obeys Beer's Lawup to 2.8 p.p.m.of gallium. Rhodamine G as a fluorescence reagent forindium as its bromide has been reported.68Small amounts of tin in common salt have been determined using 9-phenylfluorene G9 in contrast to its determination colorimetrically usingXylenol Orange. 70A study has been made of the extraction of selenium and telluriumchloride and bromide with diantipyrilpropylmethane. 71 A spectrophoto-metric method has been devised, based on this separation, for the analysisof selenium and tellurium in lead dusts. In contrast, tellurium has beendetermined colorirnetrically with tetraethylthiurarn di~ulphide.~~59 L. De Roo, J. F. M. Tertoolen, and C. Buijze, Analyt. Chirn. Acta, 1963, 29, 82.61 A. M. Lukin, K. A. Xmirnova, and G. B. Zavarikhina, Zhur.analit. Khim.,6zN. V. Shakhova, I. P. Alimarin, and Iu. A. Zolotov, Doklady Akad. NaukssM. Miyamoto, Japan Anccylst, 1963, 12, 115.64A. D. Wilson and G. A. Sergeant, Analyst, 1963, 88, 109.6 5 B. Budesinsky, Zhur. analit. Khim., 1963, 18, 1071.66 N. L. Vasilieva and M. I. Ermakova, Zhur. analit. Khim., 1963, 18, 43.6 7 T.-L. Chang and J. H. Yoe, Analyt. Chim. Acta, 1963, 29, 344.6 8 A. K. Babko and Z. I. Chalaya, Zhur. analit. Khim., 1963, 18, 570.6 9 K. Shimizu and N. Ogate, Japan Analyst, 1963, 12, 526.70V. N. Danilova, Zavodskaya Lab., 1963, 29, 407.71 A. I. Busev, X. L. Babenko, and Hoang Minh, Zhw. andit. Khim., 1963, 18,'4 H. Yoshida, Japan Analyst, 1962, 11, 549.F. Vyelra and V. Markova, Chem. Zisty, 1963, 57, 958.1963, 18, 444.S.S.S.R., 1963, 152, 884.1094536 ANALYTICAL CHEMISTRYColorimetric analysis has, as usual, been widely used for the trans-ition elements.Xylenol Orange has been used for scandium,73 and thecolour reaction of scandium with quercetin studied for analytical appli-cation.74 A 1 : 1 complex is formed a t pH 4.4 with maximum absorp-tion a t 435 mp. The scandium needs to be separated from interferingelements by ion exchange. Hydroximic acids as analytical reagents havebeen reported, benzohydroximic acid has been used for titanium determina-tions. 75 Factors influencing the optical density and optimum conditionsare discussed. Thiophen-2-hydroxamic acid has been shown to react with iron, cobalt, manganese,molybdenum, and niobium. The violet colour produced on reaction withvanadium&) has been used for the determination of this element.76 Colori-metric studies have been carried out on the reaction of vanadium(v) withorganic acids not previously used for its analysis.Intense yellow coloursare produced on reacting ammonium metavanadate with acetic, succinic,malonic, benzoic, and phthalic acids. The decrease in the colour of theacetic acid-metavanadate complex brought about by oxalic and citric acidcan be used for the indirect determination of these acids.77The determination of traces of iron in zinc and cadmium has beenaccomplished. 78 New colorimetric methods for iron analysis have beencritically st~died.~B Interferences in the determination with 4,7-diphenyl-1 ,lo-phenanthroline have been overcome.The use of syn-phenyl-2-pyridylketoxime was thoroughly investigated by the authors. Iron has also beendetermined photometrically in ethyl acetate as its thiocyanate.sOA large number of papers have been written on colour reactions of cobaltand nickel. Among these are the reaction with diphenylcarbazone-hydrogenperoxide,S1 1 -phenylthiosemicarbazide mentioned previously, and 1,2’-pyridylazo-2-naphthol for nickel in the presence of cobalt .82A fluorescent determination of niobium with Lumogallion Irea, Ei-chloro-2,2’,4’-triliydroxyazobenzene-3-sulphonic acid, has been described.83 Nio-bium has also been determined colorirnetrically with 4-(2-pyridylazo)-resorcinol in a buffer of acetate-tartrate which yields a purple complex.84In the presence of EDTA only vanadium, uranium, and phosphate interfere.However, vanadium can be masked by zinc, and uranium by ammoniumoxalat e .The rare earths have also received attention and methods based on aspectrophotometric determination have been reported.The reagent 1,2’-The sensitivity is 1-2 x lo-’ g./ml. of titanium.7 3 M.-L. Gong, Acta Chim. Sinica, 1963, 29, 223.74H. Hamaguchi, R. Kuroda, R. Sugista, N. Onuma, and T. Shimizu, AnaZyt.7 5 I. P. Alimarin, N. P. Borzenkova, and R. I. Shmatko. Zhur. analit. Khim.,76 J. Minczewski and Z. Skorko-Trybula, Talanta, 1963, 10, 1063.7’R. K. Mittal and R. C. Mehrotra, 2. analyt. Chem., 1963, 198, 92.78F. Vydra and V. Makkova, 2. analyt. Chem., 1963, 192, 347.7 9 H. J. Culley and E.J. Newrnan, Analyst, 1963, 88, 3.Y . Okura, Japan Analyst, 1963, 12, 279.J. Bognar and 0. Jellinek, Acta Chim. Acad. Xci. Hung., 1963, 35, 13.82C. Nakagawa and H. Wada, J . Chem. Xoc. Japan, 1963, 84, 636.83 V. V. Klimov and 0. S. Didkovskaya, Zavodskaya Lab., 1963, 29, 147.s4 R. Belcher, T. V. Ramakrishna, and T. S. West, TaZanta, 1963, 10, 1013.Chim. Acta, 1963, 28, 62.1963, 18, 342INORGANIC QUANTITATIVE ANALYSIS 537pyridylazo-2-naphthol, for example, has been used to determine the rareearths,85 the red insoluble complex formed in an alkaline solution is extractedwith ether and the ether extract measured at 530 and 560 mp. The complexformation and valency effects in rare earth analysis have been discussed byPajakoff.86 Yttrium and lanthanum have been determined spectrophoto-metrically using Methylthymol Blue as reagent.87Gravimetric Analysis.-The thermogravimetric examination of pre-cipitates has continued, indicating that classical methods of analysis involv-ing the weighing of reaction products still find application in this age ofinstrumental procedures. The subject has been reviewed by Coats andRedfern.88 The use of organic reagents for the precipitation of elementsincludes the determination of silver in thorium with 1,4’-dimethylamino-benzylidene-rhodanine as a carrier precipitation reagent. 89Several communications have appeared on homogeneous precipitation.Attention should be drawn to two reviews on the precipitation of metalchelates from homogeneous s o l u t i ~ n .~ ~ ~ 91 In the gravimetric determinationof barium, tracer work has shown that pure precipitates are obtained by insitu reagents. Coprecipitation of calcium, for example, is negligible.g2Nickel has been determined by precipitation as its dimethylglyoximate fromhomogeneous sol~tion.~3 Thioacetamide in perchloric acid was used for theprecipitation from homogeneous sdution of molybdenum as s~lphide.~*The 8- hydroxyquinoline complexes of niobium and tantalum have beenseparated by extraction from solutions of hydroxy-a~ids.~~ Niobium stan-nide, a super-conducting alloy, has been a n a l y ~ e d . ~ ~ The niobium wasdetermined gravimetrically as the pentoxide after volatilisation of tin as thebromide.Traces of uranium have been determined in water by coprecipitationwith aluminium hydroxide, reduction to uranium( IV) and subsequentreaction with Arsenazo 111.The coloured soluble complex formed ismeasured spectrop hot ometricall y. 97Titrimetric Analysis.-Questions on the theory of titration have beendiscussed, including titration curves and the possibility of titrimetricdetermination~.~S Thermometric analysis, which utilises the heat liberatedor absorbed during a chemical reaction to determine by titration the con-centration of a substance in solution, has been reviewed by Bark.99 OtherThe tin content was obtained by iodometric analysis.85 S. Shibata, Analyt. China. Acta, 1963, 28, 388.86 S. Pajakoff, Monatsh., 1963, 94, 400.H. Okada, K. Kaneko, and S. Goseki, Japan Analyst, 1963, 12, 822.88A. W.Coats and J. P. Redfern, Analyst, 1963, 88, 906.8 9 S. Hirano, A. Mizuike, and Y. Ujijira, Japan Analyst, 1963, 12, 160.F. H. Firsching, Talanta, 1963, 10, 1169.O1 K. Takiyama, S. Hikime, and L. Gordon, Japan Analyst, 1963, 12, 985.O 2 P. Terentiev, K. I. Litvin, and E. G. Rukhadze, Zhur. analit. Khim., 1963,18,406.O3 E. D. Salesin, Diss. Abs., 1962, 23, 1898.O 4 F. Burriel-Marti and A. Maceira Vidan, Anales real SOC. espafi. Pis. Quim.,9 5 I . P. Alimarin, G. N. Bilimovich, and Ts’ui Hsien-Hang, Zhur. neorg. Khina.,O6 K. L. Cheng, Chemist-Analyst, 1963, 52, 115.O 7 E. Singer and J. Marecek, 2. analyt. Chem., 1963, 196, 321.g8 E. A. Polyak, Zhur. analit. Khirn., 1963, 18, 687.1963, 58, By 777.1962, 7, 2725.L. S.Bark, Ind. Chemist, 1963, 39, 545538 AKALYTICAL CHEMISTRYworkers loo have discussed the usefulness and applications of thermometricmethods, with particular reference to automated routine analysis.Complexometric Titrations. Copper has been analysed complexometric-ally using chromotropic acid dioxime indicator. l01 The complex is purplea t pH 5-82-6.45 and 7.25-8-05. It is less stable than copper(I1)-EDTA,and solutions turn yellow at the end-point of the titration with EDTA. Inacid solution magnesium and the alkaline earths do not interfere, but zinc,cadmium, nickel, cobalt, aluminium, and iron( 111) do. In alkaline solutionthese elements and all the alkaline earths interfere. A study has been madeof the effect of polyvalent silver ions on argentometry with absorptionindicators. l o 2Alizarin acid Black SN has been used as a metallochromic indicator forcalcium.103 The nature of its calcium chelates was discussed and also theirstability.An optical aid to the end-point determination in the calcium-EDTA titration has been described.lo4 A method for the selective titrationof calcium in the presence of magnesium has been reported,lo5 while screenedEriockrome indicator has been used in the magnesium-EDTA titration.106Vanadium as V02+ has been used as a back-titrant for indirect ampero-metric titrations with EDTA. An excess of the EDTA is added to anycation which will form a chelate having a stability constant of 10-'6 atpH 4. The vanadyl back-titration was used to determine aluminium(m),zirconium(Iv), and thallium(rv) in fluoride-bearing materials.lo7 The directchelometric titration of aluminium( 111) has also been reported. l08Some new indicators for use in the determination of iron(m) withEDTA have been described. rn-Cresotic acid log and 1 -hydroxy-2-naphthoicacid 110 are typical examples. Iron and copper have been separated fromnickel using the C,-Cg fatty acids.lll Finally, the stepwise titration ofiron(m) and iron(n) with EDTA and ferricyanide has been carried out usingsquare-wave titrimetric end-point detection. 112The nickel determination with EDTA and Eriochrome Black as indicatorsuffers from the usual disadvantages arising from the very strong metal-indicator complex. In the analysis of cobalt(n), iron, and copper thesehave been overcome by adding ethanol to the reaction mixture.It hasbeen reported 113 that the nickel determination can be treated analogously.The titration can then be performed slowly, as there is no interferencefrom the indicator.100 P. T. Priestley, W. S. Sebborn, and R. F. N. Selman, Analyst, 1963, 88, 797.l 0 1 A. B. Sen and T. S. Srivastava, 2. analyt. Chem., 1963, 193, 412.102 F. Sierra and C. Sanchex-Pedreno, Anales real SOC. espafi. Pis. Quim., 1963,103 GI. Ross, D. A. Aikens, and C. N. Reilley, Analyt. Chem., 1962, 34, 1766.104 R. J. Toft, H. W. Wastman, and D. B. McKenney, Chem. and Ind., 1963, 1030.105 Y. Date and K. Toei, Bull. Chem. SOC. Japan, 1963, 36, 518.106 T. W. Bloxam, Analyst, 1962, 87, 907.1°7 G. Goldstein, D.L. Manning, and H. E. Zittel, Analyt. Chem., 1963, 35, 17.188 G. Asensi Mora, Anales real SOC. espafi. Pis. Quim., 1962, 58, B, 525.1oSA. B. Sen and V. B. S. Chauhan, Indian J . Appl. Chem., 1963, 25, 127.11oA. B. Sen and V. B. S. Chauhan, Indian J . Appl. Chem., 1963, 25, L30.111 S. E. Kreimer, N. V. Tuzhilina, and A. S. Lomekhov, Zhur. analit. Khim.,112 D. A. Flanigan, Diss. Ah., 1962, 23, 1181.113 V. D. Canic and T. A. Kiss, Chemist-Analyst, 1963, 52, 111.59, B, 263.1963, 18, 1080INORGANIC QUANTITATIVE ANALYSIS 539The potentiometric work of Rao and co-workers, mentioned in thisreview of last year,ll4 on the use of iron in strong phosphoric acid as areducing agent has been continued. The reagent has been applied to theestimation of molybdenum(rv) 115 and to the simultaneous determinationof vanadium( v) and uranium( v) [or molybdenum( VI)] in mixtures.ll8Vanadium, iron, and chromium mixtures have also been ana1y~ed.l~~There has also been further work on cerimetry carried over from lastyear. Perrocyanide, quinol, and arsenic( rn) have been determined usingnickel phthalocyaninesulphonic acid as indicator. llSA direct hypohalite titration of selenite has been described in which thereaction is carried out in 2-5-3*5~-sodium hydroxide with osmium tetroxideas the catalyst. The end-point can be determined potentiometrically, orcolorimetrically with diphenylaminesulphonic acid indicator. 119The use of sulphur trioxide in acetic acid as an acid titrant has beenoutlined,120 and the determination of tellurium in refined tellurium products,using a differential potentiometric procedure has been reported.121The determination of halide ionsin mercury(n) compounds has been described by Shub.122 Procedures havealso been reported for very small quantities of fluoride,123 and micro-amountsof iodine have been analysed by means of its catalytic action on thiocyanateoxidations.124 Chloride in low concentration has been determined in poly-carbonates 125 and a colorimetric method has been used to determinechlorine dioxide in the presence of chloride in water.126Improvements in Classical Analysis of Anions.-In the barium perchloratedetermination of sulphate, interference from phosphate can be eliminated byits removal as the insoluble silver salt.Silver sulphate must be decomposedon an ion-exchange column. 127 Another novel method for sulphate reportedthis year involves precipitation with barium chromate labelled withchromium-51. The excess of 51Cr is determined in the filtrate.128 Sulphatehas also been precipitated using radioactive barium.129 The titrimetricdetermination of sulphate, phosphate, and chromate was detailed byPo1ak,l3O and sulphate, phosphate, and arsenate solutions have been de-termined without difliculty. 131 Kirsten and his associates have discussedDetermination of Traces of Halogens.114 Ann. Reports, 1962, 59, 468.115 G. Gopala Rao and S. R. Sagi, Talanta, 1963, 10, 169.116 G. Gopala Rao and L. S. A. Dikshitulu, Talanta, 1963, 10, 1023.117 0. Gopala Rao and L.S. A. Dikshitulu, Talanta, 1963, 10, 295.118 G. Gopala Rao and N. V. Rao, Z. analyt. Chem., 1963, 196, 102.llD F. Solymosi, Chemist-Analyst, 1963, 52, 42.120 R. C. Paul, K. R. Kapoor, and S. S . Pahil, J. Sci. Ind. Res., India, 1962, 21,121P. W. Bennett and S. Barabas, Analyt. Chem., 1963, 35, 139.122 N. S. Shub, Zhur. analit. Khim., 1963, 18, 141.123 W. Oelschlager, 2. analyt. Chern., 1962, 191, 408.124 K. B. Yatsimirsky, L. I. Budarin, N. A. Blagoveshchenskaya, R. V. Smirnova,125 J. Urbanski and S. Iwanska, Chem. analit., 1962, 7, 1129.126 P. Kerenyi and P. Kuba, Chem. Zvesti, 1963, 17, 146.127 A. F. Colson, Analyst, 1963, 88, 26.128 W. J. Armento and C . E. Larson, Analyt. Chem., 1963, 35, 918.129 D. Picou and J. C. Waterlow, Nature, 1963, 197, 1103.130 H.L. Polak, Chem. Weekblad, 1963, 438.131 L. Szekeres and E. Kardos, Ann. Chim. (Italy), 1962, 52, 844.B, 533.A. P. Fedorova, and V. K. Yatsimirsky, Zhur. analit. Khirn., 1963, 18, 103540 ANALYTICAL CHEMISTRYsulphate and sulphur determination in both organic and inorganic com-p o u n d ~ . ~ ~ ~Raney nickel has been employed for the estimation of low concentrationsof nitric acid in sulphuric acid.133 It was found that Raney nickel workedwell when aluminium or Devarda’s alloy failed. Poor results were obtainedat concentrations greater than about 10% nitric acid.Bark and Higson 134 published a comprehensive review of methodsavailable for cyanide detection and determination. Titrimetric methodsinvolving visual and instrumental end-points, polarographic, gas-chromato-graphic, and colorimetric procedures are all discussed.The authors quote122 references.Po1arography.-The amount of work published appeared to be less thanin recent years although it still occupied a considerable section of theelectroanalytical field.The concentrations of substances in polarographic analysis was dis-cussed 135 and methods for several cations have been presented. A methodfor the determination of NH4+ was published,136 and verified in anotherpaper.137 The silver oxide method of salt analysis by polarography was thesubject of another paper.138 Procedures for copper in the presence ofiron 139 and as the diethyldithiocarbamate 140 have been given, and anindirect method for silver was reported.141Methods have beenreported for zinc determination in cuproaluminium 142 and in zinc teara ate.^^^Cadmium in aluminium was analysed 144 and also in br0nze.14~ Galliumanalysis was described 146 and also indium in lead and zinc.147 Among thetransition elements communications were published on the polarography oftitanium in the presence of iron,l4* nickel in molybdenum,149 manganese iniron and steel,l50 and molybdenum in uranium al10y.l~~ The polarographyof manganese-(I), -(II), and -(III) was discussed 152 in some detail. Ripan andZinc and cadmium received the usual attention.132 W.J. Kirsten, K. A. Hansson, and S. I<. Nilsson, Analyt. Chim. Acta, 1963,133 C. Wankat, D. A. Keyworth, and V. A. Brand, Analyt.Chem., 1963, 35, 1090.134 L. S. Bark and H. G. Higson, Analyst, 1963, 88, 751.135 K. Z. Brainina, Zhur. analit. Khim., 1963, 18, 1169.136 Ya. I. Tur’yan and B. P. Zhantalai, Zawodslcuya. Lab., 1962, 28, 1431.1 3 7 P. Ya. Yakovlev and R. D. Malinina, Zavodskaya. Lab., 1962, 28, 1434.138 Annon, Chemistry (Quart. Chinese Chem. SOC., Formosa), 1963, 41.139 E. Troncoso, L. Balabanoff, and S. Burkhard, Bol. SOC. Childna Quim., 1962,l 4 0 J. Fuginaga, M. Isibasi, and K. Yamasita, Japan Analyst, 1962, 11, 1122.141 M. Kopanica and R. Pribil, TaZunta, 1963, 10, 37.142 N. Fleury, Chim. analyt., 1963, 45, 462.144 M. Fleury and R. Capelle, Chim. analyt., 1963, 45, 357.145 M. Fleury and R. Capelle, Chim. analyt., 1963, 45, 193.146 G. W. Latimer, jun., Analyt.Chim. Acta, 1963, 29, 480.147 R. J. Hofer, R. Z. Bachman, and C. V. Banks, Analyt. Chim. Acta, 1963, 29, 61.14* G. S. Deshmukh and J. P. Srivastava, Indian J . Chem., 1963, 1, 12.149 Z. Zlobowska, Chem. analit., 1963, 8, 405.150 H. Asaoka, Japan Analyst, 1963, 12, 156.151 V. T. Athavaole, R. Kalyanaraman, and K. A. Khaogiwall, AnaZyt. Chim. Actca,152 S. Moros and L. Keites, J . Electroanalyt. Chem., 1963 5, 90.28, 101.12, 17.W . U. Malik, R. Haque, and S. P. Verma, Bull. Chem. SOC. Japan, 1963, 38,746.1963, 29, 280INORGANIC Q U A N T I T A T I V E ANALYSIS 541Pop l53 have described details for the determination of bismuth in lead, inwhich the test solution was polarographed in complexone I11 medium.The indirect determination of acids by polarography was also reported.lS4Other Electroanalytical Techniques.-Controlled potential coulometry hasbeen used for the determination of s 0 d i ~ m .l ~ ~ Copper was analysedamperometrically with dipentyldithiocarbamidohydrazine 156 and silver withthiourea.157 Zinc has been examined in a ferrocyanide-ferricyanidesystem,15* and mercury has been studied from several aspects. Mercury(@was determined potentiometrically using a mercury electrode, 159 it has beendetermined with Reinecke salt,l60 and in bismuth by means of potassiumethyl xanthate.lsl Tin was determined with dichromate.162 Biswas andDey i63 have determined arsenic(rr1) and antimony(m), and the chloro-complexes of bismuth have been studied potentiometri~ally.~~~The transition elements have also received attention.An assay ofvanadium in vanadium metal was carried 0 ~ t , 1 6 5 vanadium steel was alsoanalysed,l66 and vanadium has been determined in titanium tetrach10ride.l~’8-Mercaptoquinoline has been used for the amperometric determination ofpalladium and iridium,l68 and for palladium together with iron and ~ 0 p p e r . l ~ ~Zirconyl chloride has been estimated with potassium ferrocyanide l70 andcupferron was used to titrate zirconium in radioactive s01utions.l~~ Anacidimetric determination of zirconium was also carried out ,172 whilst leadtetra-acetate was used for the titration of ruthenium. 173A method of high-speed controlled potential coulometry was reported. 174It was tested on silver and other ions.Bromine numbers have also beendetermined coulometrically.175Other miscellaneous analyses include the coulometric determination of153 R. Ripan and G. Pop, Rev. Chim. (Roumania), 1963, 14, 464.15* J. C. Abbott and J. W. Collat, Analyt. Chem., 1963, 35, 859.155 E. J. Cokal and E. N. Wise, Analyt. Chem., 1963, 35, 914.156 E. Jaeobsen and C. Hansteen, Analyt. Chim. Acta, 1963, 28, 249.157 G. S. Deshmukh, S. V. Tatwawadi, and M. Surendranath, Current Xci., 1963,l5* J. D, Winefordner and G. A. Davison, Analyt. Chim. Acta, 1963, 28, 480.159 A. I. Mogilyanski, 0. N. Temkin, R. M. Flid, and R. V. Burina, Zhur. analit.160 J . L. Bagbarly, A. J. Illexperoro, and K. N. Nadzhafova, Azerb. Khim. Zhur.,161 Y. I. Usatenko and F. M. Tulyupa, Ukrairt. khim.Zhur., 1963, 29, 747.162 G. S . Oeshmuth and S. V. S. S . Murty, Z. analyt. Chem., 1963, 198, 328.163 S. D. Biswas and A. K. Dey, J . prakt. Chern., 1963, 21, 147.16* V. E. Mironor, F. Ya Kul’ba, V. A. Fedorov, and J. F. Nikitenko, Zhur. neorg.165 R. A. Lannogl, Analyt. Chem., 1963, 35, 588.166 G. Roland, Analyt. Chim. Acta, 1963, 28, 93.l a 7 I. V. Pyatintsky and V. Y. Verisor, Ukrain. khim. Zhur., 1963, 29, 1088.16* Yu. I. Usatenko and V. I. Suprunovieh, Izvest. Akad. Nauk Latv. S.S.R., Ser.169 Yu. I . Usatenko and V. I. Suprunovich, Izvest. Akad. Nauk Latv. S.S.R., Ser.170 J. N. Gaur, 2. analyt. Chem., 1963, 194, 47.171H. Kubota and J. G. Surak, Analyt. Chem., 1963, 35, 1715.172 D. Singh and V. S . Agarawala, Z. anorg Chem., 1963, 321, 81.173 J.Xemee, A. Berka, and J. Zyka, Microchem. J., 1962, 6, 525.174 A. J. Bard, Analyt. Chem., 1963, 35, 1125.176 F. Baumann and D. D. Gilbert, Analyt. Chem., 1963, 35, 1133.32, 69.Khim., 1963, 18, 1211.1963, 1, 51.Khim., 1963, 8, 1852.Khim., 1963, 18.Khim., 1963, 25542 AN AL Y T I C 9 L C HE MI S TRYsea-water alkalinity, 176 weak acids have been determined potentiometricallyusing a t,ungsten electrode,l77 and carboxylic acid-modified solutions ofnitrobenzene in benzene were employed as solvents for the potentiometrictitration of basic materials.178 Salts and acids have also been estimated innon-aqueous media. 179 Sulphuric and lactic acids have been determined inthe presence of one another.l8*SeveraJ electroanalytical methods for anions have been reported, notablythe determination of nitrite with chloramine T , ~ ~ ~ the potentiometric estima-tion of cyanide 182 and of fluorine as lanthanum fluoride.1834.ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPSIN order to give a compIehensive picture of developments in the analysisof organic compounds we have adopted the Ma184 classification scheme.Thus, our Review is presented according to the functional group of thecompound, namely the oxygen, nitrogen, sulphur, and miscellaneousfunctions.Oxygen Functional Group.-The literature concerning the analysis ofcompounds containing oxygen has had a wide coverage. Chromatography,gas chromatography, potentiometric titrations, and colorimetric methodshave been employed to determine and characterise organic structures.Chromatography has been used extensively for thedetection and determination of organic acids.Pyridine has been used as areagent for their determination on paper chromatograms ;lS5 the reagentgives fluorescent da’rk-blue spots with acids when subjected to ultravioletradiation. Centrifugal paper chromatography has been used to separate2,4-dinitrobenzyl esters,l86 and Riddle lS7 has described a procedure for thedetermination of traces of organic acids in small samples by gas chromato-graphy of the total concentrate. A novel method for the preparation ofmethyl esters by pyrolysis of their tetramethylammonium salts has beenreported.ls8 The tetramethylammonium salt is prepared either by titrationof the acid with tetramethylammonium hydroxide or by ion exchange on ananion-exchange column.The salts are converted to the correspondingmethyl esters in high yield when injected into a gas-chromatography unita t a vaporiser temperature of 330-365 ’. Thin-layer chromatography hasbeen used for the separation of cis-trans isomers. lS9Carboxylic acids.176 K. Parke, M. Oliphant, and H. Freund, Analyt. Chem., 1963, 35, 1549.Ii7 M. Ito and S. Musha, Japan Analyst, 1963, u, 439.17* J. Xlinczlwskii and S. Kiciak, Chem. Analit., 1963, 8, 239.179 A. P. Kreshkov, A. K. Yarovenko, and I. Ya Zel’manova, Zavodskaya. Lab.,180 M. Fedorouko, K. Linelr, and C. Peciar, Chem. Zwesti, 1963, 17, 191.181 G. S. Deshmuklv and S. V. S. S. Murty, Indian J. Chem., 1963, 1, 316.lS2 F.Shinoznka, Diss. Abs., 1962, 23, 1503.1963, 29, 295.A. Chambionnat and G. Montel, Bull. SOC. chim. France, 1963, 362.T. S. Ma, Ajzalyt. Chem., 1958, 30, 760; “ Proceedings of the InternationalSymposium on Microchemistry 1958,” Pergamon, London, 1959, p. 151.l a 5 J. Cerbulis and M. W. Taylor, Analyt. Chem., 1963, 35, 114.186 Z . Cejkova, Z. Deyl, and J. Rosmus, 2. analyt. Chem., 1963, 195, 1.l S i V. M. Riddle, Analyt. Chem., 1963, 35, 853.1 8 8 E. W. Robb and J. J. Westbrook, tert., AnaZyt. Chem., 1963, 35, 1644.lS9 G. Pastuska and H. J. Petrowitz, J . Chromatog., 1963, 10, 517ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPS 543The potentiometric titration of acids in an NN-dimethyl fatty acidamide has been des~ribed.1~~ A conventional glass indicating electrode isused with a saturated calomel reference electrode modified by replacing thesaturated potassium chloride with a saturated aqueous solution of lithiumchloride. The equivalent weights of some organic acids have been deter-mined by titration of the benzylthiuronium salts with a solution of the sodiumsalt of o-hydroxybenzoic acid.lglA benzidine-copper reagent (5% solution of benzidine in 5% acetic acidand 0-%-copper acetate) has been used for the spectrophotometric determina-tion of some organic acids.lg2A new reagent, tetra-p-tolylstilbonium sulphate, has been reported forthe qualitative analysis of various aromatic sulphonic acids.lS3AZiphutic carboxyZic acids. The violet colour produced when formic acidis mixed with anisole in the presence of 0 .1 ~ lead nitrate solution has beenused as a specific test for the acid,lg4 and Deshmukh and Rao lg5 havedetermined formates by oxidation with alkaline ferricyanide in the presenceof osmium tetroxide catalyst at room temperature.Oxalic acid and mandelic acid have been determined 196 potentio-metrically using ammonium hexanitratocerate( rv) .The stable Krebs-cycle acids have been separated and identified by gaschromatography of their methyl esters.197Blundstone 19* has reported the separation of tartaric, citric, oxalic,succinic, and lactic acids by paper chromatography using an n-butyl formate-formic acid-water (10 : 4 : 1) solvent. Detection was effected by additionof Bromophenol Blue and sodium formate to the solvent.A large number of hydroxy-acids have been separated by anion-exchangechromatography using Dowex 1 -X8 anion-exchange resin and sodium acetateeluent.lg9 Citric acid, in the presence of carboxylic acids and lactic acid,has been determined by Choy et U Z .* ~ ~ using a non-aqueous spectrophoto-metric method.Aromatic acids. A sensitive method for the detection of some aromaticacids based on the formation of fluorescent hydroxyl derivatives *01 has beendescribed. The derivatives are formed by means of hydroxyl radicalsphotochemically generated in dilute aqueous hydrogen peroxide solution.Several methods have been proposed for the separation and/or determina-tion of mixtures of benzoic, isophthalic, terephthalic, and toluic acids, theirmethyl esters, and their potassium salts.Gas chromatography, for example,lgo C. A. Reynolds, J. Little, and M. Pattengill, ,4naZyt. Chem., 1963, 35, 973.lgl M. Wronski, Chem. Analit., 1963, 8, 113.lg2 Z. D. Draganie, Analyt. Chim. Acta, 1963, 28, 394.193 H. E. Affstrung and A. B. Gainer, Analyt. Chim. Acta, 1962, 27, 578.l94M. Quereshi, W. Husain, and J. P. Rawat, Analyt. Chem., 1963, 35, 1592.lg5 G. S. Deshmukh and A. L. J. Rao, 2. analyt. Chem., 1963, 194, 110.G. Gopala Rao, K. S . Murty, and P. V. Kriskna Reo, Talanta, 1963, 10, 657.lg7 H. H. Luke, T. E. Freeman, and L. B. Kier, Analyt. Chem., 1963, 35, 1916.19* H. A. W. Blundstone, Nature, 1963, 197, 377.lg9 B. Alfredsson, S . Bergdahl, and 0. Samuelson, Analyt. Chim. Acta, 1963, 28,*I71 3 1 1 .200 T.K. Choy, J. J. Quattrone, jun., and BE Elefant, Analyt. Chim. Acta, 1963,2O1 D. W. Grant, J. Chromatog., 1963, 10, 511.29, 114544 ANALYTICAL CHEMISTRYhas been used to separate methyl benzoate and methyl phthalates,202 andphthalic acid has been determined by gas chromatography using a silica gelc0lumn.~03 A hot methanol extraction procedure has been reported for theseparation of terephthalic and isophthalic acids, 204 and Bellen and Kochel 205have proposed a method for the polarographic determination of terephthalicacid and its potassium salts in the presence of phthalic, toluic, and benzoicacids and their potassium salts.A thin-layer-chromatographic method for the separation of the 2,4-dinitrophenylhydrazones of a number of keto-acids has been reported.206Aromatic a-keto-acids have been determined by paper chromatography byNiel~en,~~' the acids, protected against oxidation by means of sodiumhydrogen sulphide, react with o-phenylenediamine to form S-alkylquinoxal-inols.The latter reaction products are separated by paper chromatography,eluted from the paper, and determined by ultraviolet spectrophotometry.The analysis of these acids has aroused considerableinterest. James 208 has reviewed the methods of separation of long-chainunsaturated fatty acids, and numerous papers have been published on theirseparation and determination by gas and other forms of chromatography.The colorimetric microdetermination of saturated acids of high molecularweight, after separation by paper chromatography, has been described.209The acids are converted to their lead salts and developed on the paper withammonium sulphide solution. Each of the lead salts is eluted from thechromatogram with dilute nitric acid (1 : 10) and determined with dithizone.Aqueous solutions of volatile fatty acids have been estimated by gas chroma-tography,210 in which formic acid vapour was added to the carrier gas toimprove resolution. Silicone, polyester, and Tween stationary phases onChromosorb W support material were found to be satisfactory using aflame-ionisation detector. A diethyleneglycol succinate stationary phasehas been used to separate the methyl esters of fatty acids and resin acidsfound in wood and wood products.211 The chromatographic analysis ofseed oils, in particular the fatty acid composition of castor oil, has beenreported.212 Quantitative separation of the higher fatty acid methyl estershas been achieved by absorption chromatography on silica impregnatedwith silver nitrate.2i3 Short-chain fatty acids have been analysed bygas chr~matography,~~~ and a technique for the quantitative estimationof unsaturated higher fatty acids by paper chromatography has beenFatty Acids.202 R. Komers, Coll. Czech. Chem. Comm., 1963, 28, 1549.203A. L. Kamneva and E. S. Panfilova, Zavodskaya Lab., 1963, 29, 666.204 G. N. Freidlin and V. N. Davydov, Zhur. priklad. Khim., 1962, 35, 2520.205 Z. Bellen and I. Kochel, Chem. Analit., 1963, 8, 411.206P. Ronkainen, J . Chromatog., 1963, 10, 228.207 K.H. Nielsen, J . Chromatog., 1963, 10, 463.208 A. T. James, Analyst., 1963, 88, 572.209 E. K. Alimova, A. T. Astvatsaturian, E. A. Endakova, and V. A. Stepanova,210 R. G. Ackman and R. D. Burgher, Analyt. Chem., 1963, 35, 647.211 F. H. M. Nestler and D. F. Zinkel, Analyt. Chem., 1963, 35, 1747.212 R. G. Binder, T. H. Applewhite, G. 0. Kohler, and L. A. Goldblatt, J . Amer.213 B. De Vries, J . Amer. Oil Chemists' SOC., 1963, 40, 184.214 B. M. Craig, A. P. Tullock, and N. L. Murty, J . Amer. Oil Chemists' SOC., 1963,Zhur. analit. Khim., 1963, 18, 767.Oil Chemists' SOC., 1962, 39, 513.40, 61ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPS 545de~cribed.2~5 The separation of isomeric mono-unsaturated fatty acids bythin-layer chromatography has been achieved.216 Column chromatographyusing a silica gel column, with subsequent regeneration, has been used for theanalysis of volatile fatty acids.2f7 A quantitative method for the prepara-tion of methyl esters of carboxylic acids in biological materials has beenreported.21s The esterification procedure involves the reaction of iodo-methane with the silver salts of the acids. The procedure is claimed t oproduce esters in quantitative yields with little or no undesirable sidereactions or loss of the more volatile methyl esters. The 2-methylalkanoicacids have been suggested as suitable internal standards in the gas-chromato-graphic assay of fatty acidsY2l9 and a procedure for the microdeterminationof long-chain carboxylic acids in materials containing acetyl groups has beenThe method is based on quantitative transesterification withboron trifluoride in methanol.The methyl esters are extracted into hexane,and the methyl acetate removed from the hexane extract by warming at67". This treatment is claimed not to influence the amount of C8 or higherfatty acid esters. The residual methyl esters are determined by the hydro-xylamine-ferric perchlorate method of Snyder and Stephens. Two colori-metric methods for the estimation of long-chain acids have been reported.Duncombe 221 has described a procedure for the microdetermination ofthese acids, and Pilz reports on a procedure for the determination of theiresters using ferric chloride-hydroxylamine hydrochloride. 22The determination of alkoxyl groups has continuedto receive attention, and attempts to extend the Zeisel method to theanalysis of more difficult types of organic compounds have been described.Anderson et have continued their study of applications of infraredspectroscopy to the microdetermination of t-butoxyl groups and report onthe anomalous reactions of t-butylphenols.The simultaneous identificationand determination of methoxyl, ethoxyl, propoxyl, and butoxyl groups bygas-chromatographic analysis of the corresponding iodides has been des-~ r i b e d . ~ ~ * Alkoxyl groups in alkoxysilanes have been determined byperchloric acid-catalysed cleavage with acetic anhydride in ethyl acetatesolvent, 225 and alkoxyl groups in organometallic compounds have beendetermined by Bondarevskaya et aZ.226 A method for the determination ofmethoxyl by the Zeisel method for use with small quantities of sample hasAEkoxyZ compounds.2151.G. Borisova and E. V. Budnitskaya, Biokhimiya, 1963, 28, 497.216 L. D. Bergelson, E. V. Dyatlovitskaya, and V. V. Voronkova, Izvest. Akad.XauL S.S.S.R., Otdel. khirn. Nauk, 1963, 954.%17 V. W. Ulitko, I. I. Koronko, and V. M. Chertov, Ukrain. biochim. ZJzzcr., 1963,35, 606.218 C. W. Gehrke and D. F. Goerlitz, Analyt. Chem., 1963, 35, 76.219 E. A. Napier, jun., Analyt. Chem., 1963, 35, 1294.220 0. S. Duron and A. Nowotry, Analyt. Chem., 1963, 35, 370.221 W. G. Duncombe, Biochem. J., 1963, 88, 7.222 W. Pilz, 2. analyt. Chern., 1963, 193, 338.223 D. M. W. Anderson, J. L. Duncan, M.A. Herbich, and S. S. H. Zaidi, Analyst,224 T. Mitsui and Y. Kitamiera, Microchem. J., 1963, 7, 141.225 J. A. Magnuson, Analyt. Chenz., 1963, 35, 1487.2 2 6 E. A. Bondarevskaya, S. V. Syavtsillo, and R. N. Potsepkins, Trudy Kom.1963, 88, 353.analit. Khirn., Akad. Nauk S.S.S.R., 1963, 13, 178.546 ANALYTICAL CHEMISTRYbeen described.227 The methyl iodide is absorbed in or-picoline and theresulting N-methyl-a-picolinium iodide is determined colorimetrically. Achange in the cleavage reagent for the determination of alkoxyl has beenproposed,228 in which a mixture of potassium iodide and orthophosphoricacid is used in place of the less stable hydriodic acid.Peroxides. Reduction of several alkylhydroperoxides and dialkyl-peroxides at the dropping-mercury electrode has been investigated.229 Theinfluence of solvents on half-wave potential and shape of wave has beenstudied, and the polarographic characteristics of different groups of per-oxides determined.A method of separating hydroperoxides and peroxidesbased on extraction has been developed. Ledaal and Bernatek 230 havereported a method for the determination of per-acids and hydrogen peroxidein mixtures. The method is based on the instantaneous reaction of per-acids with neutral potassium iodide solution, and on the formation of a stablecomplex between hydrogen peroxide and titanyl ions. This complex isdecomposed with sodium fluoride and the ensuing reaction with iodine isaccelerated with molybdic acid. The influence of the different additives onthe analytical results has also been studied.The decrease in absorption at260 mp when triphenylphosphine is oxidised to the corresponding oxide by ahydroperoxide has been used for the spectrophotometric determination ofthe latter,231 and the method compared with the iodometric and ferricthiocyanate methods. A photometric method for the determination ofperoxides in tetrahydrofuran, based on the reaction of tetrahydrofuranperoxide with NN- die t hyl -p - phen ylenediamine sulp hat e , has been reported. 32Aldehydes and Ketones,-The differences in spectral properties betweenaldehydes and their corresponding dimethyl acetals has been used for thecharacterisation and determination of aldehydes. 233 The qualitative appli-cation has been demonstrated on 49 aldehydes of various molecular composi-tion, whilst the quantitative aspects were demonstrated by the analysis offurfural and cinnamaldehyde in the presence of compounds which wouldnormally seriously interfere with direct ultraviolet determinations.The fluorescence observed when methanol solutions of normally non-fluorescent substituted aldehydes are acidified, has been studied by Crowelland Varsel. 234 These workers found that the fluorescence results fromelimination of the quenching effect of the aldehyde group in the acid-catalysed reaction between the aldehyde and methanol to form the corres-ponding acetal.Formaldehyde and acetaldehyde have been determinedspectrophoto-fluorometrically with J-acid (6-amino-l-naphthol-3-sulphonica ~ i d ) .~ ~ 5 The method has been critically compared with other methods ofanalysis, as have the spectrophotometric and spectrophoto-fluorometric227 J. Schole, 2. analyt. Chem., 1963, 193, 321.2 z S V . A. Klimova and K. S. Zabrodina, Zhur. analit. Khim., 1963, 18, 109.2Ss M. F. Romantsev and E. S. Levin, Zhur. analit. Khim., 1963, 18, 1109.230 T. Ledaal and E. Bernatek, Analyt. Chim. Acta, 1963, 28, 322.B31R. A. Stein and V. Slawson, Analyt. Chem., 1963, 35, 1008.332A. P. Zozulya and E. V. Novikova, Zhur. analit. Khim., 1963, 18, 1105.233 E. P. Crowell, W. A. Powell, and C. J. Varsel, Analyt. Chem., 1963, 35,234 E. P. Crowell and C. J. Varsel, Analyt. Chem., 1963, 35, 189.235 E. Sawicki, T. W. Stanley, and J. Pfaff, Analyt.Ch+n. Acta, 1963, 28, 156.184ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPS 547methods for the determination of mal~naldehyde.~~~ A second method forthe fluorometric determination of formaldehyde has been described byBelman.237 The method, which is claimed to measure 0.01 pg. of formalde-hyde, is based on the Hantzsch reaction between acetylacetone, ammonia,and formaldehyde. The product, 3,5-diacetyl-I ,4-dihydrolutidine, is yellowand fluoresces yellow-green. The reaction may be extended for the assay ofother aldehydes, amines, and b-diketones.Infrared spectrometry has been used for the differentiation of saturatedaliphatic aldehydes as their 2,4-dinitrophenylhydrazones. 238A spot test for the detection of aromatic aldehydes with NN-dimethyl-p-phenylenediamine has been described,239 as also has a new colour reaction ofanthrone with malonaldehyde and other aliphatic aldehydes.240 Sawickiet ~1.241 have made a comparative study of some of the more recent methodsfor the detection of malonaldehyde. They concluded that, of the colourtests available, the 4’-aminoacetophenone and p-nitroaniline tests are themost sensitive.The colorimetric determination of acetaldehyde by measuring at 575 mp,the pink colour produced when acetaldehyde is reacted with sodium nitro-prusside and a secondary aliphatic amine in the presence of acetic acid, hasbeen reported. 242 Interference from other aldehydes is discussed. Inter-ference is less when p-dimethylaminoaniline oxalate is used for the colori-metric estimation of aldehydes and oxosteroids.243Polarographic methods have been used to determine certain aldehydes.Benzaldehyde, furfural, and methyl furfural have been determined in thepresence of sulphite by a pulse-polarographic procedure.244 A 0-1M-solutionof tetraethylammonium iodide has been used as supporting electrolyte forthe estimation of acetaldehyde in the presence of acrylonitrile by Klyaevet uZ.245 Other workers have studied the behaviour of acrolein, formalde-hyde, and acetaldehyde at the dropping-mercury electrode and a method forthe analysis of these aldehydes in mixtures was suggested. 246Thin-layer chromatography has been employed for the separation ofaromatic aldehydes, 247 and of the 2,4-dinitrophenylhydazones of aliphaticcarbonyl compounds.248, 24gPetrova et ~ 1 .~ ~ ~ have used the reaction between aldehydes and a d s , t o236 E. Sawicki, T. W. Stanley, and H. Johnson, Analyt. Chem., 1963, 35, 199.237 S. Belman, Analyt. Chim. Acta, 1963, 29, 120.239 F. Feigl, L. Ben-Dor, and E. Jungreis, Chemist-Anatyst, 1963, 52, 113.240 B. M. Watts, Analyt. Chem., 1963, 35, 733.241 E. Sawicki, T. W. Stanley, and H. Johnson, Chemist-Analyst, 1963, 52, 4.242 D. J. Clancy and D. E. Kramm, Analyt. Chem., 1963, 35, 1987.243 M. Pesez and J. Bartos, Talanta, 1963, 10, 69.244 V. I. Bodyu and Yu S. Lyalikov, Zhur. analit. Kkim., 1963, 18, 1003.245 V. I. Klyaev, F. A. Slisarenko, and A. V. Finkelstein, Zhur. analit. Khim.,246 Shao-Chuntung and Er-Kank Wang, Acta Chim.Sinica, 1963, 29, 1.247 M. H. Klouwen, R. Terheide, and J. G. J. Kok, Pette u. Seqen, 1963, 65,248 G. M. Nan0 and P. Sancin, Experientia, 1963, 19, 323.250 L. N. Petrova, A. B. Skvortsova, and E. N. Novikova, Zhur. analit. Khim.,H. G. Lento and J. A. Ford, Analyt. Chem., 1963, 35, 1418.1963, 18, 999.414.C. Bordet and G. Michel, Compt. rend., 1963, 258, 3482.1963, 18, 131548 ANAL Y TI C A L C H E MI S TRYyield Schiffs bases and water, to determine aldehydes in the presence ofketones. The water liberated during the reaction is determined by theKarl Fischer method. Ketones are reported not to interfere.Alcohols.-Chromatography ha.s been used extensively for the estimationof alcohols and diols. Procedures have been proposed for the determinationby gas chromatography of traces of methanol in ethanolY25l and vice versa.252The triterpene alcohols have been separated by gas chromatography using a1% SE 30 (methyl silicone polymer) stationary phase, on silonised 100-120mesh acid-washed Gaschrom P A mixed stationary phase ofsorbitol-di-( 2-ethylhexyl)-sebacate, has been used for the analysis of butanolin aqueous solution,254 the sorbitol acting as a retardant for water.n-Pro-panol is used as internal standard. Gas chromatography has also been usedfor the separation of the stereoisomeric alkylhexanols, 255 and the analysis ofpolyhydric organic compounds as their trimethylsilyl ethers. 256The separation and identification of the acetates of polyols and glucosidesby thin-layer chromatography has been described,257 while Kucera 258 hasemployed a thin-layer technique using alumina for the separation of aliphaticalcohols, glycols, and diketones.Patterson 259 has described a procedure for the detection and determina-tion of glycerol in tobacco. The glycerol is separated from sugars on acolumn of cellulose; a layer of activated charcoal at the top of the columnremoves other tobacco materials. The glycerol is determined by oxidationwith periodate.The separation of aliphatic alcohols as 2,4-dinitrophenylsulphenylderivatives, 260 and the analysis of Clo-C,, alcohols as monoalkylsulphates, 261by paper chromatography have been reported.Vincent 262 has described atest for the detection of diols on paper chromatograms. cis-Diols havingadjacent hydroxyl groups can be detected by spraying with saturated boraxsolution adjusted to pH 6.9 with hydrochloric acid, after first revealing anyacidic substances by spraying with a solution of 0.1% Bromocresol Purplein 0.5% sodium carbonate which has been adjusted to pH 6.8 with hydro-chloric acid.All acidic substances show as yellow spots on a purple back-ground.The specfrophotometric behaviour of potassium &chromate in sul-phuric acid has been studied and used for the indirect colorimetric deter-mination of alcohols. 263Phenols.-The separation and identification of some phenols by paper2 5 l 0. Mlejnek and V. Adamee, Chem. Zwesti., 1963, 17, 118.252K. J. Bombaugh and W. E. Thomason, Analyt. Chem., 1963, 35, 1452.253 P.Capella, E. Fedeli, and M. Cirimele, Chem. and Ind., 1963, 1590.z54M. Rogozinski, L. M. Shorr, and A. Warshawsky, J . Chromatog., 1963, 10,2 5 5 R. Komers and K. Kochloefl, Coll. Czech. Chem. Comm., 1963, 28, 46.256 B. Smith and 0. Carlsson, Acta Chem. Xcand., 1963, 17, 455.257 C. Dumatzert, C. Chiglione, and T. Pugnet, Bull. SOC. chim. France, 1963, 475.z 5 8 J. Kucerat, Coll. Czech. Chem. Comm., 1963, 28, 1341.259 S. J. Patterson, Analyst, 1963, 88, 387.260 M. R. Tulus and A. Guran, Arch. Pharm., 1963, 296, 623.261 J. Borecty, Coll. Czech. Chem. Comm., 1962, 27, 2761.262 W. A. Vincent, Nature, 1962, 198, 771.263 J. Mosse, P. Guyon, and M. Sallantin, Compt. rend., 1963, 257, 148.114ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPS 549chromatography has been described.264 The phenols, coupled with diazo-tised aromatic amines to form soluble stable azo-dyes, are separated intosingle components on paper impregnated with formamide. A cyclohexane-benzene-dipropyleneglycol mixture is employed as developing solvent. Theazo-dyes are further characterised by the colour reactions they give inalkaline solution.Duvall and Tulley 265 have reported the separation of phenol and fiveof its t-butyl derivatives by gas chromatography using a stationary phaseconsisting of 3 parts Silicone Oil 550 to 2 parts Carbowax 4000.A specific colour reaction for the detection of l-naphthol has beendescribed by Feigl and Anger.266 The compound couples on warming withpotassium p-nitrophenyldiazonium salt in 2 yo sodium hydroxide to producea blue dye in alcohol solution. l-Naph-tho1 has also been determined by a spectrophotometric method by P e a r ~ e , ~ ~ 'who measured the coloured product obtained by shaking l-naphthol withiodine, sodium hydroxide, and a water-immiscible solvent.Carbohydrates.-Several procedures for the thin-layer-chromatographicseparation of carbohydrates have been proposed.homers and isomers ofmethylated sugar glycosides 268 have been separated on silica gel, and thespots are developed by spraying with dilute sulphuric acid and charring at110". The quantitative separation and estimation of O-methyl sugars hasbeen accomplished using silicic acid-coated plates, 269 and the separation ofsugars and sugar alcohols has been described.270The separation of sugar acetates by column chromatography using asynthetic magnesium silicate, Magnesol , has been r e p ~ r t e d .~ ' ~ The tech-nique can also be applied to the separation of methylated sugars.Paper chromatography has been applied to the separation and detec-tion of substituted sugar hydra zone^,^^^ and to the determination of sucrosewith triphenyltetrazolium chloride. 2 iThe gas chromatography of methylated and partially methylated methylglycosides has been studied, and is reported to provide a highly selectivemethod for the analysis of individual methylated sugars and of the cleavageproducts from methylated oligo- and poly-saccharides. 274The stable fluorescent intensities of several carbohydrates after reactionwith o-phenylenediamine has been studied.275 A linear relationship betweenthe fluorescence produced by the reaction and carbohydrate concentrationin the range 0.2-2.0 pg./ml. holds for several sugars.Reducing sugars have been determined by oxidation in alkaline264 G. B. Crump, J. Chronzatog., 1963, 10, 21.265 A. H. Duvall and W. F. Tully, J . Chromatog., 1963, 11, 38.266 F. Feigl and V. Anger, 2. analyt. Chem., 1963, 193, 274.267 G. A. Pearse, Analyt. Chem., 1963, 35, 1954.z6* M. Gee, Analyt. Chem., 1963, 35, 350.270L. Wassermann and H. Hanus, Naturwiss., 1963, 50, 351.271M. L. Wolfram, R. M. DeLederkremer, and L. E. Anderson, Analyt. Chem.,Z72H. H. Stroh, E. Domann, and E. Haschke, 2. Chem., 1962, 2, 338.27s F. Fric and 0. Kubaniova, J .Chromatog., 1963, 11, 127.274 G. 0. Aspinall, J., 1963, 1676.275 J. C. Tome and J. E. Spikner, Analyt. Chem., 1963, 35, 211.The dye is extracted into pentanol.G. W. Hay, B. A. Lewis, and F. Smith, J . Chrowzatog., 1963, 11, 479.1963, 35, 1357550 ANALYTICAL CHEMISTRYferricyanide solution, 276 and the colorimetric determination of fructoseand fructofuranosides with thiobarbituric acid has been reported.277Nitrogen Functional Groups.4ompounds containing nitrogen linked tocarbon or hydrogen have been determined in various ways. The micro-heterometric titration of large organic nitrogen-containing compounds hasbeen suggested.278 Nitron, quinine, strychnine, and other alkaloids weretitrated with silicotungstic, phosphotungstic, or phosphomolybdic acids atpH 1-7.Application of differ-ential kinetics to mixtures of diazonium compounds is an example of a newattempt to analyse mixtures of compounds containing nitrogen linked in asimilar manner.279 The study involved following the rates of decompositionof the compounds with cuprous chloride by measurement of the nitrogenliberated. The decomposition follows a first-order rate process and thestudy shows that the kinetic approach can be applied to the analysis ofmixtures of diazonium compounds.Amines. p - Aminosalicylic acid is decarboxylated on boiling in aqueousacid and this forms the basis of a method for its analysis.280 The carbondioxide formed can be measured by a simple distillation procedure, Asdecarboxylation also yields m-aminophenol, bromination produces tri-bromoresorcinal and ammonia, and further confirnation can be obtained bydistilling off the ammonia and determining it in the normal way. Thebromination can also be used as a means of estimation.Amino-groups ininsoluble materials have been determined by Kendall 281 by application ofthe ninhydrin reaction. The purple colour obtained on oxidising p-amino-phenol with cerium(Iv) perchlorate in perchloric acid has been utilised byGuilbault 2s2 to determine the compound spectrophotometrically. Themethod is claimed to be specific for p-aminophenol. Other aromatic amineshave also been determined spectrophotometrically, based on colour reactionswith stabilised diazonium s a l t ~ . ~ S ~ The reactions of 24 toxic amines andphenols with 25 diazo-salts have been examined to develop reagents forthe determination of the toxic materials in the atmosphere.Mixtures of brominated salicylanilides or of benzoic acid and hydroxy-benzoic acids have been separated by adsorption on Dowex 2-X8 acetate-form resin, and selective desorption with acetic acid-methanol, their concen-trations being determined by ultraviolet spectrophotometry.284p-Phenylenediamine has been determined chemically by its oxidationwith sodium metavanadate in N-sulphuric acid at room temperature, theexcess of reagent being titrated with ferrous sulphate Thepotentiometric titration of primary aromatic amines with sodium nitriteThe reverse titrations were also studied.a76 T.E. Friedenmann, C. W.Weber, and N. F . Witt, Analyt. Biochem., 1962, 4,277F. Percheron, Compt. rend., 1962, 255, 2521.278 M. Bobtelsky and I. Barzily, Analyt. Chim. Acta, 1963, 28, 82.270 S. Siggia, J. G. Hanna, and N. M. Sereneha, Analyt. Chem., 1963, 35, 575.281 P. A. Kendall, Nature, 1963, 197, 1305.as2 G. G. Guilbault, Analyt. Chem., 1963, 35, 828.283 G. A. Lugg, Analyt. Chem., 1963, 35, 899.2s4 N. E. Skelly and W. B. Crummett, Analyt. Chem., 1963, 35, 1680.286 T. P. Sastry, 2. analyt. Chem., 1963, 196, 349.358.E. Schulek, L. Maroz, and I. Molnar-Perl, Talanta, 1963, 10, 561ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPS 551was reported to be more rapid and accurate than the conventional starch-iodide method.286 Oxidation at a platinum anode in dimethylsulphoxidewith a Pb-Pbn reference electrode has been employed for the determinationof triethylamine.287 Under optimum conditions quantitative analysis canbe performed with a relative standard deviation of 2%.Use has been madeof anodic depolarisation of a dropping-mercury electrode by an excess ofsodium tetraborate, followed by electrochemical oxidation of the tetraborateion a t a graphite electrode, for the amperometric determination of amines.2ssIt was considered by the authors that the two procedures, which were usedfor the determination of sympathomimetric amines, were more convenient,rapid, and precise than other methods in current use.Analysis of aliphatic tertiary amines and mose aromatic tertiary aminesin mixtures containing primary and secondary amines can be carried out byreacting the primary and secondary amines with phenylisothiocyanate.289The tertiary amine can then be titrated potentiometrically with anhydroushydrogen chloride in methyl isobutyl ketone. The colorimetric determina-tion of tertiary amines has been accomplished by Pesez and Bartos 290 usingchlorop henyldiaz onium fluoro borat es .According to Silverstein,291 primary, secondary, and tertiary fatty aminesin aqueous media in the p.p.m. range can be determined spectrophoto-metrically by virtue of the fact that amines react with Methyl Orange a tpH 3 4 to form a yellow complex, soluble in organic solvents. Thisreaction, however, is by no means specific for fatty amines, but it providesa satisfactory method of determining mixtures of the three classes of amines.The colour intensity, measured a t 430 mp, gives the total amine concentra-tion in all cases.Primary amines in the presence of salicylaldehyde do notreact with Methyl Orange, and tertiary amines only react in the presenceof acetic acid. The accuracy claimed is h0.l p.p.m. in the 0-2 p.p.m.range.Aziridinyl compounds have been assayed by reacting them with anexcess of thiocyanic acid, generated in situ from the potassium salt andtoluene-p-sulphonic acid. 292 The excess of reagent is determined by back-titration with methanolic potassium hydroxide, the indicator used dependingon the aziridinyl compound under examination. N-Aryl-substituted amidescan be identified by hydrolysis with solid potassium or sodium hydroxide,according to Owen.293 A simple cleavage is effected by heating the samplewith alkali, and the boiling or melting point of the distillate and the con-stitution of the residue are used to identify the compounds.Amino-acids.Amino-acids have been determined using a micro-method 294 and some compounds have been determined by Hamilton.295286 D. Trokowicz, Chem. Analit., 1963, 8, 107.287 R. F. Dapo and C. K. Mann, Analyt. Chem., 1963, 35, 677.288 E. D. Smith, L. F. Worrell, and J. E. Sinsheimer, Amlyt. Chcm., 1963, 35, 58.28oM. Miller and D. A. Keyworth, Talanta, 1963, 10, 1131.2ooM. Pesez and J. Bartos, Bull. SOC. chim. France, 1963, 2333.291 R. M. Silverstein, Analyt. Chem., 1963, 35, 154.*o* R. C. Schlitt, Analyt. Chem., 1963, 35, 1063.298 W.S. Owen, Milcrochim. Ichnoanalyt. Acta, 1963, 19.294 S. Blackburn a d G. R. Lee, Bwchsm. J., 1963, 87, 1.2ga P. B. Hamilton, Analyt. Chem., 1963, 35, 2055552 ANALYTICAL CHEMISTRYDetails of an improved method for the separation of amino-acids as theirN-2,4-dinitrophenyl derivatives has been described by Matheson, 296 andthe use of the mass spectrometer for the quantitative analysis of mixtureshas been described by Junk and Svec.”’The difliculty of determining mixtures of e-aminocaproic acid andor-e-diaminocaproic acid by a simple procedure has been overcome byCzerepko and Wolo~owicz.~~~ Their method is based on the differentialcolorimetric reactions given with ninhydrin at pH 1 and 6.4 for cc-e-diamino-caproic acid and E-aminocaproic acid, respectively.Oxidative decarboxyla-tion of cc-amino-acids and many other acids has formed the basis of ananalytical method,299 the carbon dioxide evolved being collected anddetermined.Hydrazim functional group. It has been shown by Feigl and Ben-Dor 3OOthat the spot-test detection of phenylhydrazine, some phenylhydrazones,and osazones can be carried out using the colour produced with pyridine-2-aldehyde. Some work on the analysis of hydrazine and its derivatives hasbeen reported. The chronopotentiometric oxidation of hydrazine at aplatinum electrode has been studied by Bard.301 The effect of electrodepretreatment on the anodic oxidation of the compound in sulphuric acidmedia was investigated, and led to various conclusions as to the best con-ditions.In contrast, hydrazine was determined by the oxidation of thecompound in a moderately alkaline solution with hexacyanoferrate( n ~ ) , theexcess of ferrate reagent being titrated with ascorbic a ~ i d . ~ O ~ The oxida-tion of hydrazine derivatives has been studied by Vulterin 3 O 3 who determinedisonicotinic acid hydrazide, semicarbazide, and benzoylhydrazine by directpotentiometric or visual titration with potassium bromate using platinum-calomel electrodes and Methyl Orange or Methyl Red, respectively. Mix-tures of hydrazine and 1 ,l-dimethylhydrazine have been determined usinga non-aqueous titration procedure by Burns and La~ler.~O~ Their methodis based on determination of the alkalinity of the mixture by titration withperchloric acid in glacial acetic acid, before and after treatment withsalicylaldehyde, using a potentiometric or spectrophotometric detection ofthe end-point.The latter method, using Crystal Violet as indicator, issaid to be more sensitive than the former.Microgram amounts of hydrazine and some primary hydrazides havebeen determined 305 by oxidation of the hydrazide with ferric ion at 85” inan acetate-buffered 2,2’-bipyridyl solution, and determination of the ferrous-bipyridyl complex spectrophotometrically at 510 mp. An ion-exchangeprocedure to separate mixtures containing substances that might interfereN. A. Matheson, Biochem. J., 1963, 88, 146.297 G. Junk and H. Suec, Anal. Chim. Acta, 1963, 28, 164.29* K. Czerepko and N.Wolosowicz, Talanta, 1963, 10, 813.299 L. Maros, I. Molnar-Perl, M. Vajda, and E. Schulek, Analyt. Chim. Acta, 1963,300 F. Feigl and L. Ben-Dor, Talanta, 1963, 10, 1111.301A. J. Bard, Analyt. Chem., 1963, 35, 1602.ao2 L. Erdey, G. Svehla, and L. Koltai, Analyt. Chim. Acta, 1963, 28, 398.303 J. Vulterin, Coll. Czech. Chem. Comm., 1963, 28, 1393.304E. A. Burns and E. A. Lawler, Analyt. Chem., 1963, 35, 802.305 F. B. Weakley, M. L. Ashby, and C. L. Mehltretter, Michrochem. J., 1963,7, 185.28, 179ORGANIC ANALYSIS THROUGH FGNCTIONAL GROUPS 553in the analysis of the hydrazides was also described. Coulometric bromina-tion of carboxylic acid hydrazides has been proved a more versatile andreliable means of determining these compounds. 306 The more conventionalmethods, the iodate, potentiometric acid-base titration, and chloramine Tmethods, were found to have their limitations.The microdetermination of hydrazine salts and some derivatives havebeen studied by Barakat and Shaker,307 who conclude that the accuracy ofthe generally accepted potassium iodate method depends largely on con-centration factors.Their examination of the method using phenylhydrazinesand hydrazine sulphate gave results in which the error appeared to increaseas the concentration of determinate increased. Moreover, it was found thatthe end-point was difficult to detect when the amount of sample in solutionwas less than 30 mg. The investigators recommended instead oxidationwith N-bromosuccinimide in dilute sulphuric acid.The reaction was foundto take place a t room temperature and the reagent was irreversibly reducedto succinimide. The methods of analysis are presented by the two workersand comparative results with the potassium iodate method given. Theexperimental error of the new method was &2%, or less. The behaviourof hydrazine and its derivatives towards various oxidants has also beenstudied by Marzadro and de Car0lis.30~ These investigators preferredoxidation with 0-0%-bromate for the microdetermination of mono- anddi-substituted organic derivatives and 0*02~-iodine solution in alkalinemedia for monosubstituted hydrazine derivatives.The titration of weak bases in acetic anhy-dride with perchloric acid has been accomplished successfully with thesemicarbazones, phenylhydrazones, 4-nitrophenyl- and 2,4-dinitrophenyl-hydrazones of several aldehydes and ket0nes.3~~ The titrations were carriedout potentiometrically with a glass electrode and a modified calomel electrodecontaining an 0-lM-solution of anhydrous lithium perchlorate in aceticanhydride, in place of the usual aqueous solution.The results obtainedshowed a divergence of not more than 2% when millimolar amounts wereused. A better accuracy and precision was obtained when the titrationvessel was maintained at 0 O. 0-005~-Toluene-p-sulphonic acid in chloroformhas been employed for the titration of similar weak bases, up to KB(HIO)= 10-l1, with dichloromethane or chlorobenzene as the titration mediumusing Dimethyl Yellow as indicator.310 In contrast , infrared spectrometryhas been employed for the analysis of N-alkanal 2,4-dinitrophenylhydra-The absorbance ratio of the CH, and NH bands is calculated fromthe measured absorbances. The method has been applied t,o the differentia-tion of N-alkalans from C3-C16.Aromatic azo-compounds can be determined bytheir oxidation with chromic-sulphuric acid in a closed apparatus. TheHydrazo functional group.Axo functional group.306 A. F. Krivis, E. S. Gazda, G. R. Supp, and P. Kippur, Analyt. Chem., 1963,307 M. Z . Barakat and M. Shaker, Analyst, 1963, 88, 59.300 D. B. Cowell and B. D. Selby, Analyst, 1963, 88, 974.310 L. Xafarik, Mikrochim. Ichnoanalyt. Acta, 1963, 26.311H. G. Lento and J. A. Ford, Analyt. Chem., 1963, 35, 1418.35, 1965.M.Marzadro and A. de Carolis, Mikrochim. Ichnoanalyt. Acta, 1963, 726554 ANALYTICAL CHEMISTRYnitrogen split off is measured in a nitrometer. Kozak et d 3 1 2 have analysed25 azo-compounds in this way using 15-50 mg. samples. Alternatively, theacid number of the azo-compound can be obtained by determining theamount of the unconsumed chromic acid.313 Terentev and Luskina 314have also applied the chromic acid oxidation method to the determination ofWerent forms of nitrogen in organic compounds.Sulphur Functional Group.-Much of the published work has been con-cerned with the analysis of thio-compounds and the determination of com-pounds containing SH groups. Aromatic thioureas, being particularlyinsoluble in water, are difficult to analyse.Accordingly, it is not surprisingthat there is a lack of suitable methods for such compounds. It has nowbeen found 315 that some aryl-substituted thioureas can be determinedtitrimetrically with bromine-bromate solution in an acid medium, and withiodine in the presence of sodium hydrogen carbonate. Satisfactory resultswere reported with N-phenyl-, NN’-diphenyl-, NN‘-methylphenyl-, andNN’-ethylphenyl-thiourea. Thiourea and some of its alkyl and arylderivatives have been determined by titration procedures using diethylenetetra-ammonium sulphatocerate as a redox reagent.316 With ferroinindicator, results were satisfactory for thiourea and alkyl derivatives only.Alkyl and aryl derivatives were best titrated using amylose indicator andmaintaining the acid strength at 2~ for alkyl compounds and at 2-5--3.5~for aryl compounds.Alkyl and aryl derivatives have also been determinedby the same investigators potentiometrically with platinum vs. an S.C.E.system. Singh and Verma 317 have continued their study of the oxidationof organic compounds with an investigation of the use of potassium dichro-mate and of chloramine T 3l* as oxidimetric reagents for the determination ofthiourea and its organic derivatives.Technical thiourea has also been determined by amperometric titra-tion,319 and in copper-plating solution in a similar manner.32o Mentionshould also be made of a method given for the analysis of thiourea 321 (thefirst part of an investigation on the determination of thiocarbamides), theanalysis of mixtures of dithiocarbamic derivatives,322 and the spectrophoto-metric study of xanthates and dixanthogen solutions.323The mercapto functional group.Methods for the determination of themercapto-group have been reviewed by Pelleri~~.~~* One of the drawbacks319 P. Kozak, V1. Novak, Zd. Bohackova, and M. Jurecek, Milcrochirn. Ichnoanalyt.Acta, 1963, 643.813 V. Novak, P. Kozak, P. Matouselr, and M. Jurecek, Coll. Czech,. Chem. Comm.,1963, 28, 487.s14A. P. Terentev and B. M. Luskina, Trudy Kom. analit. Khirn., Akad. NaukS.S.S.R., 1963, 13, 20.315 P. C. Cupts, Analyst, 1963, 88, 896.316 B. Singh and B. C. Verma, J . Indian Chern. SOC., 1963, 40, 39.317 B. Singh and B. C. Verrna, 2. analyt. Chern., 1963, 196, 432.B. Singh, B.C. Verma, and Y . K. Kalia, J. Indian Chem. SOC., 1963, 40, 697.319 M. S . Rovinskii, A. E. Kretov, and S. I. Zlotchenko, Zavodskaya Lab., 1963,320N. N. Kuz’mins, Zavodskaya Lab., 1963, 29, 152.321 P. C. Cupta, 2. analyt. Chern., 1963, 196, 412.322 C. Bighi and L. Penzo, Ann. Chim. (Italy), 1963, 53, 1068.3Z3A. Pomianowski and L. Leja, Canad. J . Chern., 1963, 41, 2219.3a4 F. Pellerin, Bull. SOC. Chim. Prance, 1962, 2319.29, 154ORGANIC ANALYSIS THROUGH FUNCTIONAL GROUPS 555in the mercuri- and argenti-metric amperometric titration method is thetime taken. This, according to B o r r e ~ e n , ~ ~ ~ is due to the sluggish nature ofthe reaction near the end of the titration when the concentration of SHgroups falls. Some improvement is claimed if the mode of titration isreversed and the cation solution is titrated with the thiol test solution.Other workers 326 have preferred to titrate their solutions with lead tetra-acetate and detect the end-point potentiometrically, or visually with quina-lizarin as the indicator.Thiobarbituric and barbituric acids give, respectively, a blue and areddish-blue colour with pyridylpyridinium dichloride and thus provides anew spot test for these substances.327 The limit of identification is 0.5 pgin each case.The extent of oxidation of the SH group in thiomalic acid byiodine, potassium iodate or bromate, potassium periodate, and chloramine Tdepends on alkalinity, temperature, and duration of the reaction. Applica-tion of these oxidants has not proved satisfactory, as reported by Arava-mundan and Ra0.328 Further examination by Chromy and S v ~ b o d a , ~ ~ however, revealed that Wronski’s method for SH groups can be applied tothe determination of thiomalic acid with an accuracy of &O*lyo.The100-200 mg. sample is dissolved in water containing 0.2% sodium sulphiteas a stabiliser, ammonia is added and the solution titrated with O-O~M-O-hydroxymercuribenzoate using thiofluorescein as the indicator. At theend-point the solution changes from sky-blue to colourless.Cysteine, thioglycollic acid, and other similar compounds have beenanalysed successfully by Wr0n~k.i.~~~ A method for mixtures of the abovesubstances is based on the fact that cysteine reacts readily with formaldehyde,and that the product of the reaction does not react with o-hydrouymercuri-benzoic acid.Thioglycollic acid and other mercaptans having no primaryor secondary amino-group can be determined by titration with o-hydroxg-mercuribenzoic acid. This allows the determination of cysteine andthioglycollic acid in the presence of each other, since formaldehyde has noeffect on the reagent. Wronski has also described a suitable analyticalprocedure for the determination of dithioglycollic acid and for cyanide inthe presence of a mercaptan. For the cyanide ion analysis, provided themercaptan does not contain an amino-group, the SH group is complexedby reaction with acrylonitrile and the cyahide then determined by titrationwith silver nitrate solution. The mercaptan may be determined, using asecond sample, by addition of formaldehyde and titration with o-hydroxy-mercuribenzoic acid.Analytical procedures havebeen described by Porter et ~ 1 .~ ~ ~ for mixtures of alk(en)yl mono-, di-, andpoly-sulphides. The general reaction is based on reduction of RS,R’ withlithium aluminium hydride, followed by hydrolysis. Hydrogen sulphideMiscellaneous Sulphur Functional Groups.325 H. Chr. Borresen, Analyt. Chern., 1963, 35, 1096.326 L. Suchomelova and J. Zyka, J . Electroanalyt. Chem., 1963, 5, 57.327 V. Anger and S. Ofri, Talanta, 1963, 10, 1302.328G. Aravamundan and C. R. Rao, Talanta, 1963, 10, 231.saOV. Chromy and V. Svoboda, Talanta, 1963, 10, 1109.330 M. Wronrki, Analyst, 1963, 88, 562.331 M. Porter, B.Saville, and A. A. Watson, J., 1963, 346556 ANALYTICAL CHEMISTRYformed on acidification is determined iodimetrically as cadmium sulphide,giving the '' polysulphide " sulphur content; the thiols are determined bygas chromatography. Limitations of the methods are discussed. Othersulphur-containing compounds, for example, iodothiophens have beendetermined by polarographic analysis, 332 mercaptides, thioacetamide, etc.,by amperometric t i t r a t i ~ n , ~ ~ ~ and carbon disulphide in hydrocarbons hasbeen determined spectrophotometrically. 334 Infrared spectrometry hasbeen employed for the analysis of alkylbenzene sulphonates in aqueoussolution,335 and the three isomeric toluenesulphonic acids have been deter-mined by ultraviolet spectrometry.336 A spectrophotometric method for thedetermination of low concentrations of sodium dodecylbenzenesulphonatehas been described by Cropton and Joy.337 A new method for the detectionof sulphoxides has been described by Safronov.338Phosphorus Compounds.-The tributyl- and tricyclohexyl-phosphineshave been determined by gas chromatography using Reoplex 400 (poly-oxyalkylene adipate) stationary phase.339 A gas-chromatographic separa-tion and identification of aliphatic and aromatic diesters and phosphorictriesters has also been described.340Klement and Wild 341 have discussed the various solvent systems avail-able for the separation of alkyl and aryl phosphates and phosphites by thin-layer chromatography. The paper-chromatographic separation of alkyl andalkyl-aryl phosphites and esters of phosphoric acid has also been describedby Mode and Greenfield,342 who give details of suitable stationary andmobile phases, as well as spray reagents for development of the spots.Miscellaneous Classes of Compounds.-Chromatographic techniques havebeen used for the determination of aromatic hydrocarbons by Khin andSzasz,343 who separated the spots, exposed them to bromine vapour,removed the excess of reagent by setting aside in air, and identified thehydrobromic acid formed in the bromination by application of a DimefhylYellow spray.Gas chromatography has been employed for the determina-tion of naphthalene and alkylnaphthalenes, 344 propyl- and butyl-benzenes 345and for the separation and isolation of p - and m-xylene from crude ~ y l e n e .~ ~ The analysis of o-xylene oxidation products was achieved by combined gas-chromatographic and spectroscopic techniques by Brown and Q ~ i r a m . ~ ~ 'The polarographic determination of benzene in toluene involved nitration,332L. W. Brown and E. Krupski, J . Phurm. Sci., 1963, 52, 55.333 M. Nedic and I. Berkes, Actu Pharna. Jugosluv, 1963, 13, 13.334 S. Ciborowski, Z. Przybylowicz, and E. Maciejewska, Chem. Analit., 1963, 8,335 S. D. Kullbom and H. F. Smith, Analyt. Chem., 1963, 35, 912.336 H. Cerfontain, H. G. J. Duin, and L. Vollbracht, Analyt. Chem., 1963, 35, 1005.337 R. W. G. Coopton and A. S. Joy, Analyst, 1963, 88, 516.33* A. P. Safronov, Zhur. analit. Khirn., 1963, 18, 584.339 R. Feinland, J.Sass, and S. A. Buckler, Analyt. Chem., 1963, 35, 920.340 J. Zulaica and G. Guiochon, Bull. SOC. chim. France, 1963, 1242.341 R. Klement and A. Wild, Z . analyt. Chern., 1963, 195, 180.342 H. A. Moule and S. Greenfield, J . Chromatog., 1963, 11, 77.343L. Khin and G. Szasz, J . Chromatog., 1963, 11, 416.344 F. Garjlli, G. Lombardo, and G. Zerbo, Ann. Ch%m. (Italy), 1962, 52, 849.346 B. V. Ioffe and B. V. Stolyarov, Neftekhim., 1962, 2, 911.346 J. Swiderski, A. Marczewski, and A. Uliasz, Rocxniki Chem., 1962, 38, 1787.347 R. A. Brown and E. R. Quiram, AppE. Spectroscopy, 1963, 17, 33.75ORGANIC ELEMENTAL ANALYSIS 557separation, and polarographic estimation of the product. 348 The problemof water determination in benzene and related solvents has been studied bySwensen and Keyworth349 who have described a method for determiningwater below 10 p.p.m., using coulometrically generated iodine, whichincludes details of special techniques for handling samples.Archer et ~1.350 have combined gas chromatography withnuclear magnetic resonance spectrometry for the separation and identifica-tions of alkene isomers.Infrared spectrometry has been applied to thequantitative analysis of diketenes 351 and for the analysis of allene isopro-pane-propene fractions. 352The ultraviolet spectrophotometric determination of acety-lenic compounds as t,heir mercuric acetate complexes has been described bySiggia and Stahl.353 Their method, which is claimed to be specific foracetylenic compounds and sensitive to low concentrations, is based on theformation of mercuric acetate addition products of the acetylenic compoundsand measurement of the ultraviolet absorption.A second ultravioletspectrometric procedure for the determination of C4-C5 acetylenes has beenreported.354 The acetylenes are hydrated to their respective carbonylcompounds with mercuric sulphate-sulphuric acid catalyst. The mercuricions are then removed by the addition of sodium chloride, and the carbonylcompounds reacted with 2,4-dinitrophenylhydrazine in sulphuric acidsolution. The resulting 2,4-dinitrophenylhydrazones are selectively ex-tracted and measured spectrophotometrically at 340 mp.AZkenes.AZkynes.5. ORGANIC ELEMENTAL ANALYSISTHE examination of methods for the determination of elements in organiccompounds was continued with the same vigour as in previous years.Themajority of the literatuie published was concerned with methods of analysison the milligram scale. Perhaps the most important contributions wereconcerned with finishes for the carbon and hydrogen determination, toreplace the slower gravimetric procedure. The subject of quantitativeorganic microelemental analysis was reviewed by Schoniger, 355 who coveredthe period from 1959-1961.Carbon and Hydrogen.-The microdetermination of carbon and hydrogeninvolving combustion of the sample, removal of interfering combustionproducts, and determination of the carbon dioxide and water has receivedmuch attention. The introduction of combustion fillings capable of increas-ing the oxidation rate and thus permitting the use of faster oxygen flowrates has continued.A mixture of equal weights of magnesium oxide and348 G. F. Reynolds and J. Wild, J . Polarog. SOC., 1963, 8, 62.349 R. F. Swensen and D. A. Keyworth, Analyt. Chem., 1963, 35, 863.350 S. A. Francis and E. D. Archer, Analyt. Chem., 1963, 35, 1363; E. D. Archer,3 5 1 V . V. Zharkov, Zavodskaya Lab., 1963, 29, 701.352V. M. Mamedova, A. N. Shnulin, and A. E. Portyanskii, Neftekhim., 1963, 3,353 S. Siggia and C. R. Stshl, Analyt. Chem., 1963, 35, 1740.354 M. W. Scoggins and H. A. Price, Analyt. Chem., 1963, 35, 48.355 W. Schoniger, Mikroroshirn. Ichnoanalyt. Acta, 1963, 52.J. H. Shively, and S. A. Francis, ibid., 1369.620558 ANALYTICAL CHEMISTRYcopper oxide at 900-1000", and an oxygen flow rate of 100 ml./min.hasbeen proposed by Kakabadse and Manohin 356 for use in horizontal com-bustion tube systems or in the commercial Coleman train. Silver vanadate,h t advocated as an oxidation filling by Ingram,357 has been applied in theColeman train for the removal of halogen and sulphur oxidation products.358It has also been employed as an absorbent for fluorine, the halide beingextracted and determined afterwards by titrating the extract with a solutionof thorium nitrate, using Alizarin Red S as indicator.359 It is known thatusing silver as the absorbent for halogens can cause trouble by corrodingthe silica combustion tube. For this reason, strontium silicate has beenproposed for the retention of chlorine combustion products and is claimedto be superior to silver.360A new universal tube filling composed of 1 part silver tungstate and 4parts zirconium dioxide, mixed together in pellet form, and then mixed(9 parts) with magnesium oxide pellets (1 part) has been described.361 Thisfilling acts as an absorbent for all interfering oxidation products it is claimed,operating at 850 '.The combustion period is 12 minutes and one determina-tion can be completed in less than 25 minutes.Kainz and Mayer 362 have made a study of the absorption of nitrogenoxides on lead dioxide, and conclude that the extent of absorption dependson (a) the temperature and length of the lead dioxide layer, the velocity ofthe gas flow, and the amount of gas already absorbed; and ( b ) the methodof preparation.The same workers have also studied preparations ofmanganese dioxide and lead dioxide for carbon dioxide retention.363 Theexamination also included the absorption of nitrogen oxides. The efficiencyof the manganese dioxide was said to depend on the availability of OHgroups in the preparations. It was recommended in another paper 364 thatthe dioxide should be dried below 120°, since the activity was much less ifdried at 150", the temperature used by Belcher and Ingram, and laterworkers. Kainz and Mayer, in a later paper,365 have described theirexamination of errors ascribed to the Pregl method of combustion concerningthe retention of the carbon dioxide and water by the lead dioxide filling.This work was carried out with the aid of gas chromatography.The combustion train has received attention by Clifford and F r i b b i n ~ , ~ ~ ~who report a compact unit for the Vecera method, and Macdonald 367 hasreviewed automation in the carbon and hydrogen determination.Rapid microgram methods of analysis which determine carbon, hydrogen,and nitrogen on one sample have continued to appear in the literature.856 G.J. K. Kakabadse and B. M. Manohin, Analyst, 1963, 88, 816.357 G. Ingram, J. SOC. Chem. Ind., 1943, 62, 175.358 M. Ebaling and L. Malter, Microchem. J., 1963, 7, 179.359 A. I. Lebedevct, N. A. Nikolaeva, and V. A. Orestova, Zhur. analit. Khinb.,380 E. I. Margolis and G. C. Lyamina, Vestnik. Moskow Univ., 1963, No. 1, 66.361 C.S. Yeh, Microchem. J., 1963, 7, 303.36a G. Kainz and J. Mayer, Mikrochim. Ichnoanalyt. Acta, 1963, 481.s63 G. Kainz and J. Mayer, Mikrochim. Ichnoanalyt. Acta, 1963, 542.364 G. Kainz and J. Mayer, Mikrochim. Ichnoanalyt. Acta, 1963, 628.s65 G. Kainz and J. Mayer, Mikrochim. Ichnoanalyt. Acta, 1963, 601.s66 D. R. Clifford and E. A. Fribbins, Analyst, 1963, 88, 68.367 A. M. G. Macdonald, I n d . Chemist, 1963, 39, 265.1962, 17, 993ORGANIC ELEMENTAL ANALYSIS 559Walisch 368 has described an apparatus for the rapid determination of theseelements, with which 4 analyses can be completed in an hour, using 0.3 gm.of sample. The combustion is carried out in a continuous helium-oxygenstream, the excess of oxygen being retained by hot copper which alsoreduces nitrogen oxides.Water is absorbed by means of silica gel, andcarbon dioxide and nitrogen are passed into the cell of a Katharometer.The resulting bridge current is integrated to give a digital reading proportionalto the sum of the carbon and nitrogen contents of the sample. After carbondioxide has been absorbed, the nitrogen content is obtained by the passageof the gases through a second cell unit. Finally, the water is liberated fromthe silica gel and passed through the first cell to give a third reading pro-portional to the hydrogen content of the sample. The precision is said toequal or better that obtained by the classical methods.Clerc et aZ.3'39 in their method for the simultaneous determination ofcarbon, hydrogen, and nitrogen, using 2-0.5 mg.samples adopt a somewhatsimpler thermal conductivity method. The method is virtually automaticin that 16 previously weighed samples are analysed without manual help,each analysis being completed in 7-13 minutes. This method may wellbecome the standard method in future years as more experience is gained,but the price of the commercial counterpart might prohibit its generaladoption. There is still the need for a method of analysis requiring relativelysimple and less costly apparatus. However, there is a trend towards simul-taneous procedures. Frazer and Crawford, 370 for example, have improvedtheir original manometric method which has resulted in an improvement inaccuracy, and Koch and Jones 371 have scaled down the previous method ofPrazer to the microgram level (1-0.1 mg.) with no apparent serious loss ofaccuracy.These manometric methods are generally more time-consumingthan procedures employing other methods of finish, up to 18 hours beingtaken for a determination. Investigation of simultaneous methods ofanalysis coupled with the carbon and hydrogen determination has continuedwith a procedure including the analysis of silicon.372The search for a satisfactory method to replace the gravimetric determina-tion of the carbon dioxide and water has been continued by Greenfield andSmith,373 who determine the combustion products conductimetrically.Each determination, which is conducted with a modified Vecera combustiontrain, is completed in 15-20 minutes. On the microgram scale, Hozumiand Kirsten 374 have developed their sealed tube technique into a simple,fast, and reliable method for the simultaneous determination of carbon,hydrogen, and nitrogen.The accuracy is as good as that obtained at themilligram level with conventional methods. The standard deviations were0.21% C, 0.2% H, and 0.12% N.368 W. W. Walisch, Trans. New York Acad. Sci., 1963, 25, 693.360 J. T. Clerc, R. Dohner, W. Sauhr, and W. Simon, Helv. Chin%. Acta, 1963,370 J. W. Frazer and R. Crawford, Mikrochim. Ichnoanalyt. Acta, 1963, 561.371 C. W. Koch and E. E. Jones, Mikrochiim. Ichnoanalyt. Acta, 1963, 734.37a Yu. N. Platonov, Trudy Kom. analit. Khim., Akad. Nauk X.S.S.R., 1963, 13, 15.373 S. Greenfield and R. A. D. Smith, Analyst, 1963, 88, 886.3 7 4 K.Hozumi and W. J. Kirsten, Analyt. Chem., 1963, 35, 1522.46, 149560 ANALYTICAL CHEMISTRYThe determination of carbon dioxide by non-aqueous titrimetry has beenaccomplished by Grant et aZ.375 These workers have proposed dimethyl-formamide as an absorbent for the carbon dioxide. The absorbed gas issimply titrated with potassium methoxide in benzene-methanol, usingthymolphthalein as indicator. White,376 on the other hand, absorbed thecarbon dioxide in acetone and continuously titrated the solution withO.OOS~-sodium hydroxide solution. For amounts of carbon up to 100 pg.the accuracy is within ,t0.002%, absolute. White has also described aprocedure for internal coulometric generation of the titrant , which has been.used to determine up to 800 pg.of carbon.Organic matter in aqueous solutions is normally determined by a wetcombustion procedure. Details of a method have been given in which thesample is injected into a combustion tube and the organic constituentoxidised in the normal ~ a y . 3 ~ ' The resulting carbon dioxide is determinedby an infrared analyser, giving a rapid method of analysis (about 2 minutes).Another interesting departure from current procedure in the determinationof carbon has been described by M l i n k ~ , ~ ~ ~ who has studied the pyrolysisof organic compounds in streaming ammonia. Hydrogen cyanide is pro-duced, absorbed in cold water, and estimated. The conversion is rapid,and pyrolysis products such as methane and carbon monoxide are readilyconverted to hydrogen cyanide.The behaviour of some elements, C, H, N,etc., on the destructive chlorination of organic compounds has been studiedby Korbl379 to see if it could be used as a means of determining elements.The method appears to have promise for at least hydrogen and oxygen, andfurther work is being carried out.Oxygen.-In a study of the determination of oxygen in organic com-pounds Vecera et aZ.380 have examined the conductimetric finish for thecarbon dioxide produced, and the relationship between the temperature andthe percentage conversion of oxygen to carbon dioxide. Other workershave described modifications in procedure, 381 9 382 and Ehrenberger et aZ. 383have extended the method for the analysis of fluorine- and phosphorus-containing compounds.Nitrogen.-Nitrogen has been detected in organic compounds by theoxygen-flask combustion procedure, absorbing the oxides of nitrogen formedin alkali, and detecting the resultant nitrite ions by the Griess reaction.384Differential reaction rate studies on the micro-Dumas method have beencarried out 385 and applied to the determination of mixtures of nitrogen-containing substances.Colson 386 has combined electrolytic generation of375 J. A. Grant, J. A. Hunter, and W. H. S. Massie, Analyst, 1963, 88, 134.376 D. C. White, Talanta, 1963, 10, 727.377 C. E. Van Hall, J. Safranko, and V. A. Stenger, Analyt. Chem., 1963, 35, 315.378 S. Mlinko, Mikrochim. Ichnoanalyt. Acta, 1963, 759.3 7 9 J. Korbl and D. Mansfeldova, Talanta, 1963, 10, 816.380 M.Vecera, J. Lakomy, and L. Lehar, Talanta, 1963, 10, 801.381E. A. Bondarevskaya and M. 0. Korshun, Zhur. analit. Khim., 1963, 18,382A. I. Lebedeva and N. A. Nikolaeva, Zhur. analit. Khim., 1963, 18, 984.383 F. Ehrenberger, S. Gorbach, and W. Mann, 2. analyt. Chenz., 1963, 198, 242.3t34 A. D. Campbell and M. H. G. Munro, Analyt. Chin?,. Acta, 1963, 28, 574.385 J. Block, S. Morgan, and S. Siggia, Analyt. Chew%., 1963, 35, 573.386 A. F. Colson, Analyst, 1963, 88, 243.641ORGAXIC ELEMENTAL ANALYSIS 561oxygen into the Kipps apparatus, giving a mixture of carbon dioxide andoxygen. Precipitated copper oxide has been recommended as a more activeoxygen donor.387 An improved nitrometer for the Dumas determinationhas been described by M i t z ~ i .~ ~ *Nitrogen on the microgram scale has been determined 389 by combustionof the sample in a sealed tube at 750", in the presence of metallic copperand a mixture of magnesium and barium oxides to absorb water and carbondioxide, oxides of nitrogen being reduced to nitrogen by the copper. Thenitrogen volume is determined by weighing the amount of mercury it dis-places. A small correction must be applied to allow for nitrogen occludedby the reagents. The method is considered an improvement over existingones as it is simple and rapid, requiring no special equipment.The Kjeldahl determination of nitrogen has been the subject of somepapers. An ion-exchange procedure has been employed for the micro-determinati0n.3~0 After digestion in sealed tubes, the acid digests arepassed through two columns of anion-exchange resin, placed one above theother.The upper column contains Amberlite IRA-400 resin in the hydrox-ide form, and the lower column the same resin in the iodide form. Ammon-ium sulphate is therefore converted to ammonium iodide, which is thendetermined by the Leipert amplification method.The reduction of nitro-groups so that the nitrogen can be quantitativelydetermined by the Kjeldahl method involves the use of an acid medium.Lunt,391 however, has shown that certain nitrophenols can be rapidly andquantitatively reduced by an alkaline stannate solution, prior to normal aciddigestion. Lithium aluminium hydride has been used for the same purposeby Bezinger et In this case the azo-compound produced is furtherreduced by treatment with sodium thiosulphate.Simple methods for the determination of nitrogen on the microgram scalehave been reported,3g3 Belcher et aZ.394 have described procedures for nitro-gen bound in any form, and Mann 395 has reported the application of thephenol-hypochlorite reaction to microgram amounts of ammonia in totaldigest of biological material.Sulphur.-Investigations have continued, as in previous years, to developa simple and fast method of analysis.Of such methods, combustion bythe oxygen-flask procedure to give sulphuric acid has proved the mostfruitful and versatile. Reduction methods yielding sulphides have alsobeen proposed, but are prone to errors and have not been generally adopted.However, a simple and accurate method has now been proposed 396 fornon-volatile compounds.The sample is fused with sodium in the presence387 E. Pella, 2. analyt. Chem., 1963, 192, 397.388 T. Mitzui, Microchem. J., 1963, 7, 277.389 K. Hozumi, Analyt. Chem., 1963, 35, 666.390 R. A. Shah and A. A. Qadri, Tala.nta, 1963, 10, 1083.391 T. G. Lunt, Analyst, 1963, 88, 466.392 N. N. Bezinger, T, I, Ovechkina, and G. D. Gal'pern, Zhur. andit. Khinz.,393 G. H. Soane-Stanley and G. R. N. Jones, Biochem. J., 1963, SQ, 16.394 R. Belcher, A. D. Campbell, and P. Gouverneur, J., 1963, 531.395 L. T. Mann, Analyt. Chem., 1963, 35, 2179.396 M. H. Hashimi, M. Elahi, and E. Ali, Analyst, 1963, 88, 140.1962, 17, 1027562 ANALYTICAL CHEMISTRYof sodium chloride, sodium carbonate, and glucose.These ingredients aresaid to provide a smoother reaction, particularly in the fusion of nitrogen-containing compounds. The fusion of 20-50 mg. of sample is carried outin an open glass fusion tube, and the sulphide is determined by oxidationwith hypochlorite solution, the excess of reagent being determined iodo-metrically. Details of an improved type of alkali-metal fusion bomb havebeenA departure from the standard practice of sulphur determination hasbeen made by Ackermann and P i t ~ l e r . ~ ~ ~ In their method the sample isoxidised, and the sulphate produced is reacted with metaphosphoric acid bya distillation procedure. The sulphuric acid collected in the distillate ispassed through an ion-exchange column to remove interfering cations, anddetermined by titration with barium perchlorate solution using thorinindicator. Oxidation of sulphur-containing substances with potassium per-manganate has been reported,399 the sulphate being titrated.Traces of theelement have been determined by a combustion method carried out with ahigh-frequency condenser electrode of the submersion t~pe,~OO and Gorskiand Grabczak 401 have made a comparative investigation of methods ofsulphur determination by use of X - and y-radiation.Pell et ~ 1 . ~ ~ 2 have extended the conductimetric finish to the micro-determination. The sample is burned at 1400" in pure oxygen, and thesulphur oxides are led into sulphuric acid containing hydrogen peroxide.The sulphur dioxide is converted into sulphuric acid and the change inconductivity measured, giving the concentration of sulphur in the sample.The sodium peroxide fusion-ion exchange method of Inglis has been re-examined by Colson,403 since he found that certain steps in the procedureneeded improving. Phosphate removal, necessary in the barium perchloratetitration of sulphate, was also examined by C01son,~~7 who found thatremoval by means of the silver salt was more efficient than with magnesiumcarbonate to precipitate the phosphate ions.A study of available methodsfor the determination of sulphate ion and investigation of the various aspectsconnected with the determination of sulphur in organic compounds hasbeen carried out by Kirsten et aL132 This work led to the recommendationof a method for sulphur estimation after decomposition by the oxygen-flaskprocedure.Compounds containing up to 70% of sulphur have been com-busted in the oxygen-flask, sulphate precipitated with an excess of bariumchloride solution, and the excess of reagent determined by an EDTA titra-tion.404 For the titrimetric determination of sulphate, the use of a new897 H. J . Francis, jun., Microchem. J., 1963, 7, 150.398 G. Ackermann and L. G. Pitzler, Milcrochim. Ichnoanalyt. Acta, 1963,*9g A. A. Abramyan and R. S. Saxkisyan, Ixvest. Akad. Nauk Armyan. S.S.R.,4001. Fujishima and T. Takeuchi, J . Chem. SOC. Japan, Ind. Chem. Sect., 1963,40lL. Gorski and J. Grabczak, Chem. Analit., 1963, 8, 415.402 E. Pell, L.Machherndl, and H. Malissa, Milcrochim. Ichnoanalyt. Acta, 1963,404 G. Vetter, Chem. Tech. (Leipzig), 1963, 15, 43.636.Khim. l'Va.uk, 1963, 16, 131.66, 775.615.A. F. Colson, Analyst, 1963, 88, 791ORGANIC ELEMENTAL ANALYSIS 563indicator, a carboxy-arsenazo-compound, has been reported for applicationon the micro-~cale.~~~The simultaneous determination of sulphur and halogens has beendescribed by Dirscherl and Eme.406 A sample weighing between 0-1-1.5mg. is combusted at 1000" and the products are absorbed in hydrogenperoxide solution. Sulphate ion is determined by titration with bariumperchlorate, then the solution is titrated with mercuric perchlorate solutionto obtain the chlorine or bromine content. Thorin and diphenylcarbazoneindicators are used, respectively, for sulphate and halide ions.Halogens.-The determination of highly halogenated organic compoundsoften proves troublesome, particularly when the oxygen-flask procedure isemployed, Mazor et aL407 have described a modified decomposition pro-cedure in which the flask combustion is encouraged by the addition ofpowdered sugar to the sample.The halogen combustion products areabsorbed by an ammonia solution, which is said to reduce the time of absorp-tion. It was recommended that the halide solution should be titrated withsilver nitrate solution using Variamine Blue redox indicator. The end-point was improved if the ammonia was first removed. The oxygen-flaskprocedure has been used, modifications as regards the finish of the analysishave been des~ribed,~*~, 409 and a study of the method has been carriedKirsten 411 has employed the Ingram 412 ignition combustion pro-cedure, in a modifiedform, for the determination of halogens onthe microgramscale.Certain organic halides have been found to react quantitatively withsodium thiosulphate to form Bunte salts, suggesting a method for theiranalysis.413 Titration of the excess of thiosulphate is readily accomplishedand is very accurate. A method for the determination of chlorine in2-chloroethyl derivatives of organic phosphates has been reported,414 othermethods for the halogen have been describedy4l52 416 and a method on themicrogram scale has been reported.417Methods for the determination of fluorine have been reviewed,418 andone using a complexometric titration has been reported 419 involving deter-mination of the excess of lead ions with EDTA.Carbonate ions were found405 K. F. Novikova and N. N. Basargin, Trudy Kom. analit. Khim., Akad. Nauk406 A. Dirscherl and F. Erne, Milcrochim. Ichnoanalyt. Acta, 1963, 242.40* Analytical Methods Committee, Analyst, 1963, 88, 415.409 J. M. Corliss and J. B. Miller, Microchem. J., 1963, 7, 5.410 C. E. Childs, E. E. Meyers, J. Cheng, E. Laframboise, and R. B. Balodis,411 W. J. Kirsten, Microchem. J., 1963, 7, 34.412 G. Ingram, " Proceedings of the International Symposium on Microchemical413 M. R. F. Ashworth and M. Winter, Anal. Ghirn. Acta, 1963, 29, 75.414 E. L. Gefter, Zavodskaya Lab., 1963, 29, 419.a6 R.A. Shah, S. A. Janbar, and M. K. Bhatty, Pakistan J . Sci. Ind. Rea., 1962,416 A. Wielopolski and J. Krajewski, Chem. Analit., 1962, 7, 1139.417 A. Stier, 2. analyt. Chem., 1963, 193, 197.41* W. Funasaka, J . SOC. Org. Synth. Chem. Japan, 1962, 20, 947.419 M. A. Leonard, Analyst, 1963, 88, 404.S.S.S.R., 1963, 13, 27.L. Mazor, K. M. Papay, and P. Hlatsmanyi, Talanta, 1963, 10, 557.Microchem. J., 1963, 7, 266.Techniques, 1961," Wiley (Interscience), New York, 1962, pp. 495-526.5, 162564 ANALYTICAL CHEMISTRYt o seriously interfere. The sample was decomposed by the oxygen-flaskprocedure using a silica flask. An accuracy of &O.Z% has been claimed fora titration method following an oxygen-flask comb~stion.~~O The fluorideion was titrated with O.O05~-cerium(111) solution in the presence of murexide-Naphthol Green B indicator.' Procedures were described for when phos-phorus or arsenic was present. Other publications have described methodsfor the determination of fluorine in fluorop~lymers,~~~ for microgram amountsof relatively involatile compounds, 422 and a colorimetric method for samplescontaining both fluorine and phosphor~s.4~~Determination of the Less-common Elements.-The trend of simultaneousdetermination of elements other than carbon and hydrogen in organiccompounds is apparent by the number of papers in the literature. A methodfor the microdetermination of both silicon and phosphorus,424 nitrogen andphosphorus,425 germanium and hal~gens,~~s mercury and halogens,427 andcarbon and halogen in organo-oxyhalogenosillanes by wet combustion, 28have been reported, as has a method for fluorine and nitrogen.429Methods for the determination of the less-common elements, bothmetallic and non-metallic, have also been the subject of publications.Methods have been reported for the analysis of organosilicon compoundscontaining flu0rine,4~* and halogen bound to silic0n,~3l and for the chroma-tographic determination of chlorosilanes.432 Methods for the micro-determination of vanadium-containing compounds have been described. 433Aluminium has been determined by X-ray fl~orescence,4~~ arsenic gravi-metrically as the triuranium octaoxide after flask-combustion using analuminium or steel gauze support for the sample and boron by aflame spectrophotometric method in which the sample was decomposed in asealed ampoule with nitric acid a t S0°.436 Methods have also been reportedfor boron alone, or simultaneously with nitrogen and/or phosphorus inorgan~boranes.~~' The microdetermination of calcium by photometrictitration with complexone(m) after decomposition of the organic material420 M. Trutnovsky, Mikrochim. Ichnoanalyt. Acta, 1963, 499.421 A. I. Filina, G. P. Shcherbachev, and V. A. Zarinsky, Zhur. analit. Khint.,4s2 G. Tolg, 2. analyt. Chem., 1963, 194, 20.423 E. Debal, Chim. analyt., 1963, 45, 66.424 35. N. Chumachenko and V. P. Burlaka, Izvest. Alcad. Nauk S.S.S.R., Otdel.425 B. Filipowicz, M. Gross, and B. Skoczylas, Analyt. Biochem., 1963, 5, 187.426 M. D. Vitalina and V. A. Klimova, Zhur. analit. Khirra., 1962, 1'7, 1105.427 V. Pechance, Coll. Czech. Chem. Comm., 1962, 27, 2976.428 A. Radecki, Chem. Analit., 1963, 8, 607.4g9 N. E. Gel'man and N. I. Larina, Zhur. unaZit. Khim., 1963, 18, 1100.430 E. A. Bondarevskaye, A. P. Kreshkov, S. V. Syavtsillo, and V. M. Kuznetsova,43lV. A. Bork and L. A. Shvyrkove, Trudy Kom. analzt. Khim., Akad. Nauk432 N. A. Palamarchuk, S. V. Syavtsillo, N. M. Tarkel'taub, and V. T. Shemyaten-433 M. K. Dzhanaletdinove and L. V. Ivanova, Izvest. Akad. Nauk L?.S.S.R., Otdel.434 H. F. Smith and R. A. Royer, Analyt. Chenz., 1963, 35, 1098.435A. D. Wilson and D. T. Lewis, Analyst, 1963, 88, 510.436 T. Yoshizaki, Analyt. Chem., 1963, 35, 2177.4 3 7 R. C. Rittner and R. Culmo, Analyt. Chmvz., 1963, 35, 1268.1962, 17, 990.Khim. Nauk, 1963, 5.Trudy Korn. analit. Khim., Akad. Nauk S.S.S.R., 1963, 13, 24.S.S.S.R., 1963, 13, 148.kova, Trudy Korn. analit. Khim., Akad. Nauk S.S.S.R., 1963, 13, 277.Khim. Nauk, 1962, 112ORGANIC E L E M E N T A L -4NALYSIS 565has been rep0rted,4~8 and the determination of traces of copper suitable forapplication to many organic materials has been reported on by the AnalyticalMethods C0rnmittee.4~~ The difficulty experienced with the mineralisationof manganese-containing compounds has been overcome and a suitablemethod of analysis has been ad~anced.4~~ Mercury in organic substanceshas been determined by the well-known combustion procedure, but the tubefilling has been modified to contain an oxygen donor, absorbents for theretention of halogens and sulphur, and metallic copper to reduce oxides ofnitrogen.441 The mercury formed is retained on silver, and the combustioncarried out in a stream of nitrogen-containing electrolytic oxygen. Aspectrophotometric method for the determination of phosphorus has beenproposed for application on the micro-scale. 442 The sample is decomposedby an oxygen-flask combustion and the phosphorus converted to MolybdenumBlue. Zinc in many organicmaterials has been determined by a rapid selective one-colour dithizonemethod, suitable for trace amounts.443 It is applicable in the presence ofmany other cations, the zinc dithizone being extracted and determined byspectrophotometric measurement at 535 mp.An accuracy of k0-274, absolute, is claimed.438 B. G. Belenky and L. Ya Severinets, Zhur. analit. Khim., 1963, 18, 950.4sB Analytical Methods Committee, Analyst, 1963, 88, 253.4 4 0 R. Riemschneider and K. Petzoldt, 2. analyt. Chern., 1963, 193, 193.441 T. Mitsui, K. Yoshikawa, and Y. Sakai, Microchem. J., 1963, 7, 160.442 N. E. Gel’man and T. M. Shanina, Zhur. analit. Khim., 1962, 17, 998.4 4 3 G. Westao, Analyst, 1963, 88, 287

ISSN:0365-6217    

DOI:10.1039/AR9636000529

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

CRYSTALLOGRAPHYBy €I. M. Powell, G. K. Prout, and S. C. Wallwork1. INTRODUCTIONOUTPUT of crystal structures certainly does not diminish and for this Reportit was necessary to consider many more than 1000 papers covering theperiod 1961-1963. Selection is inevitable and some topics are deferred.Information on current work is available in the abstracts of communicationsto the Sixth International Congress of the International Union of Crystallo-graphy, held in Rome in September, 1963. These have been published asa special number of Acta Crystallographica. In the present Report, detailsof methods of structure analysis are curtailed in favour of structures ofchemical interest, though current technical developments are briefly noted.It has often been mentioned that, as an approximate truth, determinationof a crystal structure is, in principle, not dependent on complexity.Themore complicated the molecule or group of atoms, the larger the unit cell,and therefore the larger the number of independent quantities observablein diffraction experiments carried out with radiation of a given wavelength.The number of positional or other parameters required to define a structureis matched by the number of observations from which they must be deduced.The practical difficulties change with time.Computers dealing with thousands rather than hundreds of observationshave had several effects. Systems of greater complexity are accessible,less complex structures are determinable with higher accuracy, and it is nownormal to expect three-dimensional analysis if results are to be used fordetailed discussion of bond lengths and angles.Temporarily, the collectionof diffraction information rather than the problem of calculation may haveseemed the greater obstacle ; automation of the data collection process,including computer control of dfiactometers, is therefore developing.Structural details that are intractable to X-ray diffraction, or capable ofonly limited solution by this method, are attacked by electron or neutronbeams. There seems to be no immediate prospect of any of the crystalanalysis methods exhausting their usefulness.One result of widening of the field of investigation can be seen in anumber of seemingly unrelated crystal structures , which illustrate degreesof complexity which chemists may increasingly have to consider.Atoms,molecules, or other aggregates that would not be distinguishable in a liquidphase may in the crystal occupy positions which are, in it formal geometricalway, recognisable as Werent, and which in some instances clearly correspondto different function or chemical state. Substances having little chemicalrelationship to each other may crystallise together to form either ordered orpartly ordered structures, related or unrelated to the structures of the purecomponents. These two complications are not in themselves new but theyare being found in increasing number and variety. A common result insuch cases is that certain simple questions, which perhaps motivated th568 CRY STALLOCRAPHYexamination, prove to be meaningless in the light of the structures found.Thus, an enquiry as to the state of co-ordination of the metal atom ina-plutonium cannot be answered simply, as could the correspondingquestion about metallic copper.There are eight crystallographically differ-ent kinds of plutonium atom. Six of the eight different kinds have fourshort, though not identical, bonds of lengths 2.57-2-78A, and ten longbonds in the range 3.19-3-71 A. The seventh plutonium has five shortand seven long bonds, but the eighth has 3 short and 13 long bonds. Inb-plutonium there are 7 different kinds of plutonium atom, having co-ordination numbers 12, 13, or 14, with a mixture of short and long bondswhich are not so sharply classifiable as those in a-plutonium.In the system tantalum-sulphur, TaS, has its tantalum atoms 6-co-ordinated in layer lattices.One form has an octahedral and another atrigonal prism of sulphur atoms around tantalum. Both stereochemicalkinds can co-exist, the layers being in various regular stacking orders, andthere is also a form with random layer order.3In octamethylcyclotetrasilazane (1) two conformations, chair and cradle,MeMe I H')Si-N, ,MeSi-MeNHH \'MeI HY Me-SiMe' 'N-Si'Meoccur in the same c r y ~ t a l . ~ The molecular symmetry is I for one isomerand 2 for the other.The /%form of dithiosemicarbazidenickel( 11) sulphate has been found tocontain equal numbers of cis- and trans-i~omers.~Bis( benz yldiphenylphosphine)dibromonickel( rr) crystallises from the samesolution in red diamagnetic and green paramagnetic forms.These mightbe supposed to be isomeric, differing essentially only in the square-planarnickel bonds for the diamagnetic and tetrahedral nickel bonds for theparamagnetic form. The crystals of the green form prove to oontain threemolecules per unit cell, one with square-planar and the other two withtetrahedral nickel bonds.Some structures contain groups which might have been expected to bealike but which differ in less radical ways. Thus, in KH,F3 there are twonon-equivalent forms of the FHFHF- ion.' In one set ,/(F-F-F) = 130"and in the other, 139".Disorder, another complicating factor in structures, appears in varied1 W. H. Zachariasen and F.H. Ellinger, Acta Cryst., 1963, 16, 777.2 W. H. Zachariasen and F. H. Ellinger, Acta Cryst., 1963, 16, 369.F. Jellinek, J . Lms-Common Metals, 1962, 4, 9.G. S. Smith and L. E. Alexander, Actu Cryst., 1963, 16, 1015.R. Gronbaek, Acta Cryst., 1963, Rome Conference Abstracts, A, 65.13 B. T. Kilbourn, H. M. Powell, and J. A. C. Darbyshire, PTOC. Chem. Xcc., 1963,J. D. Forrester, M. E. Senko, A. Zalkin, and D. H. Templeton, Actu Cryst.,207.1963, 18, 58INTRODUCTION 569forms. Trimethyloxosulphonium perchlorate, [Me,SO] +C104 -, has per-chlorate groups which are crystallographically of two types. One type hasthe symmetry 3 and is ordered. The space group position for the otherwould require this perchlorate ion to have symmetry mm2, but each ionutilises only the single mirror plane rn and the higher symmetry is achievedonly in a statistical way by a disordered set of these perchlorate ions.8 Inthe analogous but not isomorphous trimethyloxosulphonium fiu~borate,~the BF4- ions are crystallographically also of two kinds.Both, by apparentspace group, are required to have symmetry 2, but both are disordered andachieve the symmetry statistically .The fine structural detail that may be derived for suitably chosen mater-ials is illustrated in the following two cases.An X-ray and neutron-diffraction study of the magnetic phaseAlo.&h,.ll shows that in this small tetragonal unit cell, a = 2.77, c = 3.54 a,the distribution of atoms is Alo.03Mno.97 at 000 and Alo.8sMno.le at ;;&.The manganese magnetic moments of 1.94B.M.are along the c-axis pointingin opposite directions for the two positions.1°A very thorough examination l1 has been made of the previously well-known structure of hexamethylenetetramine, which has a body-centredarrangement of the highly symmetrical molecules. In this, the h a 1 dis-crepancy factors for one set of X-ray observations were reduced to 2.3%(at 298"~), 4.6% (at 100'~), and 3.4% (at 3 4 " ~ ) , and several different sets ofboth X-ray and neutron diffraction results were used. There are few inde-pendent positional parameters and the components of the mean-squarevibration tensor were determined for the carbon, nitrogen, and hydrogenatoms. The atomic co-ordinates were corrected for the rotational-oscillationerror by use of derived values of the mean square amplitude of the molecularangular oscillation.The weighted mean estimate of the C-N bond lengthis 1.476 & 0.002 8, one of the most accurate bond lengths ever determinedby crystal diffraction methods other than those which depend only onmeasurement of unit cell dimensions. 0-lo, close to107.3 0.2" found for L(H-N-H) in ammonia. The N-C-N angle(113.6 & 0.2") is close to 112" 9' & 9' for L(C-C-C) in n-butane. Sincethe C,N, skeleton is a closed framework, L(C-N-C) and (N-C-N) cannotbe varied independently, and since the angles at both atoms are found to betypical, there must be negligible angular strain in the framework. TheC-H distance is 1.11 A. The great detail now available shows that eachmolecule makes contacts not only to its eight neighbours of the body-centred lattice but also that contacts through hydrogen atoms at van derWaals distances occur between a molecule and its six neighbours in adjacentcells in the directions of the cube axes.The cohesion of the crystal musttherefore be described in terms of contact between one molecule and 14neighbours. Because of the very favourable molecular arrangement, thereis no narrowing of the nuclear magnetic resonance (n.m.r.) spectrum, dueL(C-N-C) = 107.2* C. L. Coulter, P. K. Gantzel, and J. D. McCullough, Acta Cryst., 1963, 16, 676.9 I. C. Zimmermann, M. Barlow, and J. D. McCullough, Acta Cryst., 1963, 16, 883.lo P. B. Braun and J. A. Goedkoop, Acta Cryst., 1963, 16, 737.11 L.N. Becka and D. W. J. Cruickshank, Proc. Roy. SOC., 1963, A , 273, 435, 455570 CRYSTALLOGRAPHYto molecular rotations, up to a t least 2 9 8 " ~ and there is no phase transitionup to at least 510"~. It had previously been suggested that the absence ofrotational phase change might be due to weak CH-N bonds, but since theH--N distance is no shorter than the van der Waals value this view isrejected. Purely thermodynamic reasoning can explain why the meltingpoint is high (263"~) compared with those of many substances of similarmolecular weight. The temperature of fusion TF = AHF/MF. The heatof fusion AH, will not be less than normal since there are so many inter-molecular contacts in the crystal. On account of the high molecularsymmetry, the entropy of fusion ASF will be small owing to the reducednumber of complexions in the liquid phase.Adamantane, (CH,),(CH),,with a similar molecular structure and the same molecular symmetry ashexamethylenetetramine, has long been known to have a quite differentcrystal structure. This arises from the van der Waals radius of the CHgroup which is about 0.75 A greater than that of nitrogen. If adamantanewere to adopt the hexamethylenetetramine type of crystal structure therewould have to be a considerable expansion along the cube diagonal direc-tions, where these groups lie. The contacts along the cube axes betweenCH, groups would then be lost and the structure would become very open2. INORGANIC AND ORGANOMETALLIC STRUCTURESElements.-Americium is already known to have a dense hexagonal close-packed form.A face-centred cubic structure has now been noted, but noothers.1, It thus seems to conform more closely to the " normal " typesof elementary metal structures than its immediate predecessors in theperiodic table.One of two newforms of silicon is denser and much more highly conducting than the normalform.14The /?-rhombohedra1 form of boron, a phase obtained between 1500"and the melting point, contains a complex unit, in which the familiaricosahedral groups of twelve boron atoms occur, with a new en~ir0nment.l~One B,, icosahedron is radially linked t o twelve others, each pair sharinga common five-fold axis, and being relatively rotated through 2n/10 aboutthis axis.These 13B1, condensed groups are joined through single boronatoms which are octahedrally co-ordinated.Intermetallic Systems.-Among many systems investigated, a few onlycan be mentioned. Some are very complex and lead to very detailed dis-cussion about networks and atomic co-ordination as in the 6-Mo-Ni phase.16In Pu,Co the plutonium atom has three cobalt and twelve plutonium neigh-bows which form a convex polyhedron with 22 three-sided faces and 2 four-sided faces.17 Cobalt has nine plutonium neighbours, six of which form atrigonal prism. The remaining three are displaced outward from the four-sided faces of the prism. There are also two cobalt atoms not so far out-wards from the ends of the trigonal prism. ReBe,, illustrates the kind ofcomposition that may result when a particular binary system is examined.l8In this phase there are several structurally different types of beryllium.The rhenium atom has sixteen beryllium neighbours at distances 2.50-2.53 8. Ru,Be,, is cubic with eight formula units per cell.19 One set ofberyllium atoms occurs in pairs with d(Be-Be) = 2.118 A, a distance whichis rather short compared to some Be-Be contacts. At the unit cell originthere is a hole. It is bounded by twelve beryllium atoms a t a distance of2.81 8, and is similar to the hole in the CoAs, structure.Some Small Molecules.-Dinitrogen tetroxide is shown 2o to exist in anA dense form of solid germanium has been obtained.13l2 D. B. McWhan, B. B. Cunningham, and J. C. WalImann, J . Inorg.Nuclear Chem.,l3 F. P. Bundy and J. S. Kasper, Science, 1963, 139, 340.l4 R. H. Wentorf, jun., and J. S . Kaspor, Science, 1963, 139, 338.l5 R. E. Hughes, C. H. L. Kennard, D. B. Sullenger, H. A. Weakliem, D. E. Sands,113 C. B. Shoemaker and D. P. Shoemaker, Acta Cryst., 1963, 16, 997.l7 A. C. Larson, D. T. Cromer, and R. B. Roof, jun., Acta Cryst., 1963, 16,l8 D. E. Sands, Q. C. J o h o n , A. Zalkin, 0. H. Krikorian, and K. L. Kromholtz,l9 D. E. Sands, Q. C. Johnson, 0. H. Krikorian, and K. L. Kromholtz, Acta Cry&.,1962, 24, 1025.and J. L. Hoard, J . Amer. Chem. Soc., 1963, 85, 361.835.A d a Cryst., 1962, 15, 832.1962, 15, 1191.P. Groth, Nature, 1963, 198, 1081572 CRYSTALLOGRAPHYunstable monoclinic form. The molecular dimensions found are close tothose determined by electron diffraction and from the crystal structure 21of the addition compound which the substance forms with 1,4-dioxan.Thelong bond, N-N = 1.75 8, is confirmed; d(N-0) = 1.21 8, L(0-N-0 =135". These values differ somewhat from those found in the more stablecubic modification.22A neutron diffraction study of solid deuteroammonia 23 givesd(N-D) = 1.0058 and L(D-N-D) = 164". Between molecules there are" hydrogen " bonds of length 2-374 8 and L(N-D--N) = 110".I n /3-ICl,24 as in the a-form, the molecules are arranged in zigzag chains.There are two different types of molecule. The atomic sequence isas in a-IC1, but the chlorine atoms branching from the chain are trans (cis inthe a-form). The distance I-C1 is2-35A in the branches and 2-448 in the chain; d(1-I) = 3.06 A andd(C1-I) = 2.94 8.The bond lengths in the u- and ,&structures agree well.The distances shown as broken lines represent weak bonds. They areabout 1 A shorter than van der Waals distances and the angles are reason-able for bonding interactions. Also, the IC1 molecule included in the chainis significantly longer than the other, corresponding to a lowered bond order.Suggestions as to the bonding mechanism include one involving a nearlylinear three-centre bond.At -95"c, cyanogen has a fairly simple orthorhombic structure 25containing linear molecules in which d(C-C) = 1-37 5 0-02, d(C-N)= 1.13 & 0.015 8, and ,/(C-N-N) = 179" 38' & 18'. The four moleculesper unit cell are so arranged that all the nitrogen atoms lie in a hexagonalclose-packed array.This is possible because of the unique circumstancethat in the molecule the distance between the two nitrogen atoms closelyapproximates the van der Waals diameter for nitrogen. Selenium andsulphur dicyanides are isomorphous. There are conflicting reports 26, 27which may arise from polymorphism. For selenium dicyanide 26 a structureof relatively low accuracy reveals a V-shaped molecule of symmetry m withL(C-Se-C) about 120". No conclusion is possible concerning the natureof the bonding. betweenselenium and a nitrogen atom of a neighbouring molecule.Arsenic tricyanide 28 forms pyramidal molecules of symmetry approxi-mately CSv, with C-As-C angles not significantly different from 90".Oneof the cyanide groups is involved in a weak bond to the arsenic atomAlso the chains are nearly planar.There appears to be a short distance of only 2-352 1 P. Groth and 0. Hassel, Proc. Chem. SOC., 1962, 379.22 J. S. Broadley and J. M. Robertson, Nature, 1949, 164, 915.23 J. W. Reed and P. M. Harris, J. Chem. Phys., 1961, 35, 1730.24 G. B. Carpenter and S. M. Richards, Acta Cryst., 1962, 15, 360.2sA. S. Parkes and R. E. Hughes, Acta Cryst., 1963, 16, 734.28 A. C. Hazell, Acta C y s t . , 1963, 16, 843.27 F. FehBr, D. Hirschfeld, and K. H. Linke, Acta Cryst., 1963, 16, 154.28 K. Emerson and D. Britton, Acta Cryst., 1963, 16, 113INORGANIC AND ORGANOMETALLIC STRUCTURES 573of an adjacent molecule. This results in infinite, nearly linear chainsAsCN.-AsCN-, which presumably account for the low volatility of the com-pound.This interaction is indicated by the short distance, 2.85 8, betweena nitrogen atom and the arsenic of a neighbouring molecule, and is possiblyassociated with small differences between the chain-forming cyanide groupand the other two. A special type of structural argument was used t oeliminate the possibility of isocyanide groups. Values for the residual dis-crepancies obtained in the refinement process do not provide a distinction.In the cyanide structures, the outer atoms (with respect to As) have largertemperature factors than the inner atoms and all the factors are about thesame. In the isocyanide structure the inner atoms have the larger tempera-ture factors, about twice those for the outer atoms.This seems contrary toreason and so an isocyaniqe form is rejected.Di-iodomethylarsine 29 is pyramidal, d(As-I) = 2-54 & 0.01 8,Xenon trioxide has the form of a trigonal pyramid.30 Its dimensionsand crystal diffraction pattern resemble those of HIO, with which it isisoelectronic, d(Xe-0) = 1.76 Xenon di-fluoride has been examined by X-ray 313 32 and neutron 33 diffraction. Ithas a simple tetragonal structure with the symmetric linear molecule lyingalong the direction of the tetragonal symmetry axis. The parametersfound in the neutron diffraction studies might be taken to imply d(Xe-F)= 1.983 8, but the anisotropic temperature factors suggest that there is aprecession of the molecule about the symmetry axis with half-angle about7 '.The interatomic distance therefore appears foreshortened and, on theassumption that the fluorine " rides " on the xenon, the corrected Xe-Fdistance is given as 2.00 & 8. Xenon tetrafluoride 3* is monoclinic andthe molecule is planar by space-group symmetry. Xe-F distances, correctedfor thermal movements in which fluorine is assumed to " ride " on xenon,have the average value 1.938, and the four xenon bonds are very closeto the square-planar configuration. The two stereochemical forms foundin these fluorides are those expected on the basis of a semi-empiricalLCAO molecular orbital treatment,35 or by simple chemical analogy tothe IC1,- and IC1,- ions. What was a t first thought to be a secondpolymorphic form of xenon tetrafluoride 36 proves 37 to be a molecularaddition compound, XeF,,XeF,.The molecules have the same formsand dimensions as in the simple compounds and there is no structuralevidence of anything other than van der Waals interaction between the,/(I-AS-I) = 104 & 0.4".0-03 8, L(0-Xe-0) = 103".%@N. Camerman and J. Trotter, Acta Cryst., 1963, 16, 922.31D. F. Smith, J . Chem. Phys., 1963, 38, 270.32 S. Siege1 and E. Gebert, J . Arner. Chem. Soc., 1963, 85, 240.33H. A. Levy and P. A. Agron, J . Amr. Chem. Soc., 1963, 85, 241.34 D. H. Templeton, A. Zalkin, J. D. Forrester, and S. M. Williamson, J. Arner.35 L. L. Lohr, jun., and W. N. Lipscomb, J . Amer. Chem. Soc., 1963, 85, 240.37 J. H. Burns, R. D.Ellison, and H. A. Levy, J . Phys. Chem., 1963, 87,D. H. Templeton, A. Zalkin, J. D. Forrester, and S. M. Williamson, J . Amer.Chem. Soc., 1963, 85, 817.Chem. SOC., 1963, 05, 242.J. H. Burns, J. Phys. Chem., 1963, 87, 536.1569574 CRYSTALLOGRAPHYcomponents. The structure may be likened to that of Cs,[AuCl,][AuCl,]in that the geometrical forms of the complex groups are similar, and bothare examples of the multitudinous ways in which an AX, component mayappear in the empirical formula for reasons other than the existence of afinite complex of that composition.Small Ring or Framework Molecules.-In tetrathiazyl fluoride, (NSP),,the molecule 38 has symmetry 3 and the nitrogen-sulphur bonds alternatein an eight-membered ring with distances 1.66 and 1-54 8.A three-dimen-sional structure analysis 39 confkms the bisphenoidal (2a) form of the S4N,molecule found by Clark. The molecular symmetry is very close to z2m.The average S-N distance is 1-616 & 0.01 8. This corresponds to aboutone-third double-bond character, though the bond angles do not imply this.The nature of the bond remains in doubt." Methyl metadithiophosphonate '' has the form (2b)*O with a, planarring, ,/(S-P-S) = 958", L(P-S-P) = 84*2", and d(S-P) = 2.144 A. Planarphosphorus-nitrogen ring systems are found in both the trimeric 41 andtetrameric 42 phosphonitrilic fluoride (PNF,),. In the trimer, the P-Ndistance (average 1-57 8) agrees with that in the corresponding chloride,but in the tetramer the (equal) P-N distances are shorter, (1.51 A). Inthe metastable form 43 of phosphonitrilic chloride (PNCl,), the eight-membered ring of alternate nitrogen and phosphorus atoms is puckered,and the two sets of P-N bonds, although crystallographically non-equivalent,have the same length, 1.57 8.The phosphorus bonds point to the apicesof a distorted tetrahedron, with L(N-P-N) = 121" and <(CI-P-CI) = 103",differing appreciably from the tetrahedral. The configuration of the mole-cule is compatible with theories in which delocalisation of the pn and d,electrons is assumed.Octamethylcyclotetraphosphonitrile (3) has molecular symmetry z, with38 G. A. Wiegers and A. Vos, Acta Cryst., 1963, 16, 152.3a B. D. Sharma and J. Donohue, Acta Cryst., 1963, 16, 891.40 P.J. W'heatley, J., 1962, 300.*l M. W. Dougill, J., 1963, 3211.42 H. McD. McGeachin and F. R. Tromans, J., 1961, 4777.43 R. Hazekamp, T. Migchelsel, and A. Vos, Acta Cryst., 1962, 15, 539INORGANIC AND ORQANOMETALLIC STRUCTURES 575d(P-N) = 1.60 and 1.59A. L(P-N-P) and L(N-P-N), 132" and 119*8'"respectively, show the puckering of the ring.44A four-membered ring system is present in the structure of (PCF,),.An accurate structure deterrninati~n,~~ with corrections for libration, showsthe molecular form (4) with the ring folded; d(P-P) = 2.213, d(P-C) = 14367,d(C-F) = 1.326 and 1.313A.Dimethylphosphinoborine tetramer 46 has a puckered eight -memberedring, symmetry D2d, of alternating phosphorus and boron atoms ;d(P-C) = 1-84, d(P-B) = 2.08 8. The angles in the ring are 104" at Band 125" at P.Tetramethyl-27"-bistrimethylsilylcyclodisilazane (5)*' contains theplanar four-membeied ring with ,/(Si-N-Si) = 91.7 O and L(??-Si-N)= 88.3". d(Si-N) in the ring is 1.724A, slightly larger than that outsidethe ring (1.707 A).An almost planar ring (6) with slight chair characteroccurs in bis (t etramet hyldisilan yl ) dioxide, (Me,Si,O ) ,. 48 The distanced(Si-Si) = 2-35 8, as in the element,. Isola,ted Si, tetrahedra are reported 49in BaSi,.Monomeric (C6H,),Sn polymerises to form (C,H,),,Sn, containing tetra-valent tin. A preliminary communication 50 shows that the moleculecontains the new six-membered ring of tin atoms. The Sn-Sn bond length(2.78 8) agrees with that in grey tin and corresponds to normal tetrahedralcovalent bonding.The ring has the chair form with angles Sn-SnSnfairly close t o the tetrahedral. The observations were made on a crystalwhich contains xyleiie molecules. These are not involved in the bonding.A new type of aluminium compound [Ph.Al.N.Ar], has a cubic alumin-ium-nitrogen framework with aluminium and nitrogen at alternate cornerseach bonded to an aryl group.51 All the A1-N bonds are essentiallyequivalent. The hydride AlH,,ZN(CH,), has a linear N-A1-N system, andthe three hydrogens are believed to complete a trigonal bi~yramid.~,Forms of Some Complexes.-In fetramethylammonium-mercury tri-bromide, NMe,HgBr,, the mercury atom has three bonds which are notcoplanar. 53 There are two crystallographically independent anions inwhich the mercury atoms are 0.3 A out of the plane of the attached bromineatoms.d(Hg-Br) = 2.52 A, and each mercury atom has a further bromineneighbour at 2.9 8. The arrangement is intermediate between discreteanions and infinite anion chains. A ferroelectric reversal a t room tempera.-ture is explained by relative movement of the mercury to correspondingpositions on opposite sides of the triangle of bromine atoms. In RbBe,F5,the Be,F,- unit consists of extended pseudohexagonal sheet networks of44M. W. Dougill, J., 1961, 5471.45 G. J. Palenik and J. Donohue, Actu Cryst., 1962, 15, 564.48 P. Goldstein and R. A. Jacobson, J . Amer. Chem. Xoc., 1962, 84, 2457.47P. J. Wheatley, J., 1962, 1721.4 8 T. Takano, N. Kasai, and M.Kakudo, Bull. Chem. SOC. Japan, 1963, 36,4sH. Schlifer, K. H. Janzon, and A. Weiss, Angew. Chem., 1963, 75, 451.6 o D. H. Olson and R. E..Rundle, Inorg. Chem., 1963, 2, 1310.61 T. R. R. McDonald and W. S. McDonald, Proc. Chem. Soc., 1963, 382.52 C. W. Heitsch, C. E. Nordman, and R. W. Parry, Inorg. Chem., 1963, 2, 508.63 J. G. White, Actu Cryst., 1963, 16, 397.585576 CRYSTALLOGRAPHYthat comp~sition.~~ Polymer sheets of composition [Cu,(CN),] - are foundin P(CU,(CN)~,~H,O.~~ They are made up of two kinds of CuCN chain,one a zigzag and the other a spiral similar to that found in ICCu(CN),. Thecopper atoms in these two chains are linked by a third CN group. Theresulting polymer sheet has the form of a network of rather irregular puckeredhexagons. Copper atoms are at the junctions of the hexagons which haveCN groups along their sides.Thestructure would be a rather open one because the sides of the hexagons arecomparatively long, but water molecules lie within the hexagons and helpto fill the space. A similar networkoccurs in Hg,S,C1,.56 Here sulphur atoms form the junctions of the hexa-gons, and mercury atoms lie on the sides, so producing the extended cationof composition [Hg,S,],2n +. Chloride ions complete the structure.A New Type of Clathrate Hydrate.-Quaternary n-butyl- and 3-methyl-butyl-ammonium salt hydrates and some analogues have crystal struc-tures 5 7 9 6% s9 related to those of the gas clathrate hydrates. They arestable in air and have melting points above 0'0. The structures containpolyhedra of hydrogen- bonded water molecules similar in many respectsto those of the gas hydrates.In the alkylammonium salt hydrates, thecentral Nf atom lies at a common vertex of four large polyhedra and each ofthe four alkyl legs extends into one of the hydrogen-bonded cages. Thewater and anions together form the clathrate structure which encloses thecations. A condition of formation is therefore that the anions shouldhydrogen-bond strongly with the water. Acetates, nitrates, carbonates,oxalates, tungstates, and benzoates form such hydrates and, among thehalides, the fluoride is the most readily formed. The cations, since theyplay the same rdle as gas molecules in the gas hydrates, must be non-hydrogen-bonding ionic species. This group of compounds is reviewed inref.60. The compositions and general structural classification are shownin the Figure on facing page.Oxides, Oxyacids, and Related Compounds.--Simple and mixed oxides.A resurgence of interest in this field has come from applications in solid-state physics, and has resulted in many cases in the use of powerful crystallo-graphic methods, in the past reserved for complex molecular crystals. Thereseems to be scope for greater use of neutron diffraction methods for thelocation of oxygen atoms in the way illustrated by investigations of thelead,61 tellurium,62 and uranium dioxides.63A redetermination of the structure of tellurium dioxide by neutronmethods demonstrated that the tellurium atom is at the apex of a squarePotassium ions bind the sheets together.They apparently play no other rdle.54 V.V. Ilyukhin and K. V. Belov, Doklady Akad. Nauk S.S.S.R, 1961, 140, 1066.5 5 D. T. Cromer and A. C. Larson, Acta Cryst., 1962, 15, 397.58 H. Puff and H. Kuster, Naturwiss., 1962, 49, 299.5 7 D. Feil and G. A. Jeffrey, J. Chem. Phys., 1961, 35, 1863.58 M. Bonamico, G. A. Jeffrey, and R. K. McMullan, J. Chem. Phys., 1962, 37,5aG. A. Jeffrey and R. K. McMullan, J. Chem. Phys., 1962, 37, 2231.6o G. A. Jeffrey, Dechema Monograph., 1962, 47, 849.61 J. Leciejeewicz and I. Padlo, Naturwiss., 1962, 49, 373.62 J. Leciejeewicz, 2. Krist., 1961, 116, 345.63 B. T. M. Willis, Proc. Roy. SOC., 1963, A, 2'44, 122, 134.2219Class I. Dodecahedra corner-linked,forming tetrakaidecahedral voids.(a) Cubic, a, = 12 A.(Bu~)~S+F-, 20H,OCl,, 7.67H20 gas hydrate, alsoBr2, CCl,, CCl, + H,S, C,H,Cl, etc.[(Bun) 4N+]z-W0 42-, 6OH,O(b) Cubic, a, = 24 A.(second form).Class 111.Dodecahedra sharing facesthree -dimensionally, forming hexakaideca-hedral voids.C,H,, 17H,O, gas hydratealso CH,Cl,, CF,BrCl, (CH,),O + A, etc.Corresponding quaternary ammoniumsalt hydrate unknown.Cubic, a, = 17 8.Class 11. Dodecahedra sharing facesin infinite sheets, forming tetrakaideca-hedral and pentakaidecahedral voids.Orthorhombic,a = 12.1,c = 12.8 A.b = 21.6,(isopentyl),N+F-, 3SH,Oalso C1-, CrO,-, W0,2-, etc.Corresponding gas hydrate structure,X,lOH,O, unknown.Class IV. Dodecahedra sharing facesin 5(H,,02,) units which are corner-linkedforming tetrakaidecahedral and penta -kaidecahedral voids. Tetragonol, a = 24,c = 12 A.(Bun) ,N+X-, 32H,Owhere X is C1-, Br-, CH,CO,-, i(C2042-),+(WOP2-), PhCO,-, nx-Cl.C,H,.CO,-,HCO,-, H,PO,-.X,8*4H20, ~nknown.Corresponding gas hydrate structure,Structural classification of clathrate hydrates.[Reproduced, by permission, from G.A. Jeffrey, Dechema Monograph, 1962, 47, 849.1578 CRYSTALLOGRAPHYpyramid with four oxygen atoms, d(Te-0) = 2.09 and 1.91 A, at the base.The next nearest oxygen atoms are a t 2.89 A. This structure, althoughrelated to that of rutile is quite different from an earlier structure based onX-ray data and showing a distorted octahedral co-ordination of telluriumatoms.A new X-ray analysis of tetragonal zirconium dioxide 64 revealsthat the metal atom has eight neighbouring oxygens, four a t 2-065A atthe corners of a flattened tetrahedron and four a t 2.455 A a t the corners ofan elongated tetrahedron. This form of co-ordination polyhedron has beenobserved in zirconium silicate, and the whole structure closely resemblesthat of red mercuric iodide. One modification of UO,,y-UO, appears tobe uranyl rana ate.^^ Two crystallographically different uranium atomsboth have distorted octahedral co-ordination but one is more closely associ-ated with two oxygen atoms and the other with four. The uranium mineralsbillietite, Ba0,6U03, 10-1 1H,O, and becquerelite, CaO,GUO,, 10-1 1H,O,have been examined 6 6 and the barium and uranium positions determined.There is a similarity to Pb0,,2U03,2H,0.LiFeO,,LiInO,, LiScO, (tetragonal s~perlattices),~~s 68 NaInO,, NaFeO,, andLiA10, (rhombohedra1 superlattice~)6~s 70 are of the sodium chloride type.SrZnO,, is more remarkable.71 The ZnO, system is related to p-crystobalitebut has the form of crinkled layers with the strontium atoms lying betweenthe layers.BaCdO, is related to it;72 the two-dimensional ZnO, system isreplaced by a three-dimensional CdO, system in which the cadmium acquiresa fifth nearest neighbour.BaMnO, is a new ABO, structure 73 related to perovskite but with theclose packed BaO, layer sequence ABACABAC . . . Many more perovskiteshave been reported, including a large number of osmium and rhenium com-pounds A,BB’O, where B’ is Re or Os, A is Ba, Sr, or Cu, and B is one of awide variety of metal ions.74 NaNbO, and Na,.97,Ko.o,,Nb0, have twodifferent distorted perovskite forms,Y5 the former changing to the latter inan electric field, Also of the perovskite class are Ba(M,.,3+Nb,.55+)0, whereM 3 + is a rare earth, indium, or iron.76 Some manganese(m) rare-earthtrioxides have unusual structures 77 with 5- and 7-co-ordination polyhedraabout the manganese and rare earth respectively.Unacceptable oxygenthermal parameters for two oxygens throw doubt on the exact determinationof atomic positions.A number of mixed oxides, ABO,, have been examined.6 4 G. Teufer, Acta Cryst., 1962, 15, 1187.6 5 R. Engmann and P. M. de WOW, Acta Cryst., 1963, 16, 993.6 6 J.Protas and C. RQrat, Compt. rend., 1962, 255, 1959.6 7 C . J. M. Rooymans, 2. anorg. Chem., 1961, 313, 234.6 8 R. Hoppe and H.-J. Rohrborn, Naturwiss., 1961, 48, 452.6 0 H.-A. Lehmann and H. Hesselbarth, 2. anorg. Chem., 1961, 313, 117.7 0 H . Hesselbarth and H.-A. Lehrnann, 2. Chem., 1961, 1, 306.71 H. G. Schnering and R. Hoppe, 2. anorg. Chem., 1961, 312, 87.72H. G. Schnering, 2. anorg. Chem., 1962, 314, 144.73 A. Hardy, Acta Cryst., 1962, 15, 179.7 4 A . W. Sleight, J. Longo, and R. Ward, Inorg. Chem., 1962, 1, 245.7 5 M . Wells and H. D. Megaw, Proc. Phys. Soc., 1961, 78, 1258.7 6 F. Galasso and W. Darby, J . Phys. Chem., 1962, 66, 131.77 H. L. Yakel, W. C. Koehlcr, E. F. Bertaut, and E. F. Forrat, Acta Cryat., 1963,16, 957I N O R G A N I C AND ORGANOMETALLIC STRUCTURES 579The scheelite (CaWO,) structure is reported 789 79 for ammonium, sodium,potassium, cEsium, and silver pertechnetates, and the distorted YTaO,variant is found for synthetic compounds, ABO,, where A is a rare earthand B is niobium or tantalum.80 Europium tungstate, Eu,(WO,),, has ascheelite superlattice with ordered vacancies in the cation positions andthe atoms considerably displaced from the scheelite " locations." Inaluminium niobium oxide, AINbO4,82 distorted oxygen octahedra shareedges and corners to give an infinite three-dimensional net.The aluminiumand niobium atoms are located on octahedral sites, d(Nb-0) = 1-74-2.38 8,d(Al-0) = 1.77-2-17 A.The monoclinic form of BiOHCrO, contains pairs of Bi20,2+ orBi2(OH),4+ anions each connected by a chromate group to four other pairs.83Simple oxyacids and their derivatives.Recent developments in the ideasof d,-p, bonding in oxyacids and related compounds of the second-rowelements have led to some interesting, accurate structure determinations.In potassium imidodisulphite K,[NH(S03),],84 the two N-S bonds,1.662 & 0.005 8, at an angle of 124.5", are very similar to the S-0 linkagesin the pyrosulphate ion but contrast with the C-S bond in Na,[CH,(SO,),],d(S-C) = 1.77 A, L(C-S-C) = 119~7O.8~ I n the latter case the carbon atomhas no electrons available for partial double bonding according to theCruickshank theory.86 The long carbon-sulphur linkage was also observed 87in sodium hydroxymethylenesulphinate dihydrate ; d( S-C) has the samevalue (1.83 A) as the C-S single bond in organic molecules.Similar carbon-sulphur distances were also observed in two determinations *, on thetrimethylsulphonium cation, d(S-C) = 1.76-1.78 A in [ (CH,),SO]BF, andin [(CH,),SO]ClO,. In the cation the S-0 bond is rather short (1.45 A)as might be expected on the Cruickshank model. Thortveitite, Sc,Si,O,,a rare mineral containing an isolated Si2076- anion, has been re-examined 88and the Si-0-Si system shown to be truly linear after a very careful con-sideration of refinement methods and possible space groups. The systemis in marked contrast to most other A207"- anions and the Si-0-Si linkagein most structures.91 of the thiosulphate anion give S-S distancesof between 1.96 and 2.01 8.The longer, from anhydrous Na,S,O,, is prob-ably the best measurement and still shows some shortening from the expectedsingle-bond value of 2-08 A. Potassium O-dimethylphosphorodithioateThree examinations 89,7 8 K. Schwochau, 2. Naturforsclz., 1962, Ira, 630.7 9 B. J. McDonald and G. J. Tyson, Actu Cryst., 1962, 15, 87.So H. P. Rooksby and E. A. D. White, Acta Cryst., 1963, 16, 888.81 D. H. Templeton and A. Zalkin, Acta Cryst., 1963, 16, 762.82 13. F. Pedersen, Acta Chem. Scand., 1962, 16, 421.83 B. Aurivillius and I. Jonsson, Arlciv Kemi, 1962, 19, 271.8* D. W. J. Cruickshank and D. W. Jones, Acta Cryst., 1963, 16, 877.8 6 M. R. Truter, J., 1962, 3400.86 D. W. J. Cruickshank, J., 1961, 6486.8'M.R. Truter, J., 1962, 3393.88D. W. J. Cruickshank, H. Lynton, and (in part) G. A. Barclay, Acta Cryst.,8 9 M. Nardelli, G. Fava, and G. Giraldi, Acta Cryst., 1962, 15, 227.M. Nardelli and G. Fava, Acta Cryst., 1962, 15, 477.91 E. Ssndor and L. Csordas, Acta Cryst., 1961, 14, 237.1962, 15, 491580 CRYSTALLOGRAPHYK[ S,P( OCH,),] has phosphorus-sulphur distances of 1.96 A and apparentlyrather long phosphorus-oxygen (1-64 A) and oxygen-carbon (1.58 A)bonds.9Details of the hydrogen bond systems have been discussed in recent workon sodium sulphate decahydrate 93 and sodium hydrogen carb0nate.~4 Itwas observed that, as in potassium sesquicarbonate, one of the C-0 linkages(1.264 8) was considerably shorter than the others (1.346 A). However, inthe hydrogen carbonate, the oxygen involved in the short contact is alsohydrogen-bonded, but in the sesquicarbonate it is not.The structures ofminerals vaterite CaC0,,95 anhydrite CaS0,,96, 97 and huntite Mg,Ca(CO,), 913have been determined, the latter being a good example, along with y-UO,mentioned earlier, of high-quality powder work.An interesting group of iodate and tellurate structures has appeared.The 10,- and TeOS2- anions in Zr(10,),,99 CuIO,(OH) (salesite),lOO, lo1 andCuTeO,,ZH,O lo2 are pyramidal, d(1-0) = 1-78-1-85, d(Te-0) = 1.88 A.The angles of the pyramids, 10,-(96.7") and Te0,2-( loo"), are considerablyless than the tetrahedral angle. In the zircohium compound the metal hasa square antiprism co-ordination polyhedron and in salesite the copper hasa distorted octahedron.In CuTe03,2H,0 the copper has tetragonalpyramidal co-ordination. Compounds of the form MCrIO, where M is analkali metal have been reported lo3 as containing the CrIO,- anion formedby a CrOd tetrahedron sharing a corner with an 10, trigonal pyramid.Octahedral iodine in the form of the anion (7) occurs in N~,KH,[CU(IO,),].~~~/O\ /:\ OJ -0-cu - - 10, \o/ \ o /(7)OHI'-OH 0-09HO-g //*-OI (8)OHComplex poZyoxyacids and anions. The structures of 18- and y-metaboricacid are now known in detail. Monoclinic p-HBO, has endless zigzagchains of composition [ B,O,( OH)( OH,)] with hydrogen bonds betweenchains.lo5 Two-thirds of the boron atoms have trigonal planar bonds and92 Ph. Coppens, C. H.MacGillavry, S. G. Hovenkamp, and H. Douwes, Acta Cryst.,93 H. W. Ruben, D. H. Templeton, R. D. Rosenstern, and I. Olovsson, J . Amer.9 4 R. L. Sass and R. F. Scheuerman, Acta Cryst., 1962, 15, 77.O 5 S. R. Kamhi, Acta Cryst., 1963, 16, 770.96 E. Khene, Kristallograftya, 1962, 7 , 690.97 G. C. H. Cheng and J. Zussman, Actu Cryst., 1963, 16, 767.98 D. I,. Graf and W. F. Bradley, Actu Cryst., 1962, 15, 238.9 9 A. C. Larson and D. T. Cromer, Actu Cryst., 1961, 14, 128.loo S. Ghose, Actu Cryst., 1962, 15, 1105.lol S. Ghose, Naturwiss., 1962, 49, 102.Io2 A. Zemann and J. Zemann, Actu Cryst., 1962, 15, 698.l o 3 K.-A. Wilhelmi and P. Lofgren, Actu Chern. Xcand., 1961, 15, 1413.Io4 I. Hadinec, L. Jensovsky, A. Linek, and V. Synecek, Naturwiss., 1960, 47, 377.lo5 W.H. Zachariasen, Acta Cryst., 1963, 16, 385.1962, 15, 765.Chem. SOC., 1961, 83, 820INORGANIC AND ORGANOMETALLIC STRUCTURES 581one-third tetrahedral bonds. The water oxygen is at an unshared corner ofa BO, group, and the hydroxyl at an unshared corner of a BO, triangle inwhich the other oxygens are shared by two borons. The cubic y-form lo6is a three-dimensional network of B04 tetrahedra. Strong 0-H-0 hydrogenbonds of 2.487 A total length are found.In lithium diborate, Li,0,2B,0,,107 the borate anion consists of twointerlocking three-dimensional networks extending throughout the crystal.In the basic group, two boron atoms are co-ordinated tetrahedrally and twotriangularly with oxygen atoms. These boron atoms form part of a doubletwisted ring resembling the isolated ion in borax and K2B,0,,4H,0.Infinitesheets of composition [B305( OH)In2"- formed by crosslinking of calimanite-like chains are found in CaB,O,(OH).lO~ The sheets, containing two tetra-hedral and two triangular planar boron atoms per repeat unit, are heldtogether by calcium-oxygen interactions. The centrosymmetric ion (8) logis found in sodium peroxoborate, Na,[B,( 02)2( OH),JY6H,O and isolatedBOS3- planar ions occur in a new group of transition metal boratesFe,,,M,BO, (M = Ga, Cr, or Ti) with a calcite type structure.l1° Thestructures of calcium metaborate,lll potassium pentaborate tetrahydrate,llsodium metaborate,113 and potassium tetraborate 114 have been carefullyrefined by Zachariasen and his co-workers.The B-0 distance in tetrahedra is in general about 1.45-1.50 A and inplanar groups 1.32-1.38 8.Zachariasen discusses the relationship betweenbond length and bond strength in some detail.Some highly complex silicate minerals have been investigated, includingthe well-known anorthite, CaAl,Si,O,.ll~ Chemically, the following featuresare important ; silicon and aluminium tetrahedra alternate, each oxygenhaving one silicon and one aluminium neighbour; the Si-0 and A1-0 bondlengths show real variation in the same tetrahedron; most of the bondangles at oxygen are between 125" and 145" but some are exceptionallylarge, 165-170 O ; the calcium atom positions are ordered. Other mineralsreported include mullite,116, 117 yoderite, llS monderite,l19 phillipsite,l*Ohydrated 121 and dehydrated chabazite, harrnat~ne,~,~ a,mesite,l24la6 W.H. Zachariasen, Acta Cryst., 1963, 16, 380.lo7 J. Krogh-Moe, Actu Cryst., 1962, 15, 190.l o 8 J. R. Clark, C. L. Christ, and D. E. Appleman, Acta Cryst., 1962, 15, 207.log A. Hansson, Acta Chern. Xcand., 1961, 15, 934.1I0 I. Bernal, C. W. Struck, and J. G. White, Acta Cryst., 1963, 16, 849.M. Marezio, H. A. Plettinger, and W. H. Zachariasen, Acta Cryst., 1963, 16, 390W. H. Zachariasen and H. A. Plettinger, Acta Cyyst., 1963, 16, 376.113 M. Marezio, H. A. Plettinger, and W. H. Zachariasen, Acta Cryst., 1963, 16, 594.114 W. H. Zachariasen, Acta Cryst., 1963, 16, 975.115 C. J. E. Kempster, H. D. Megaw, and E. W. Radoslovich, Acta Cryst., 1962,116 S.Dyurovich, Kristallograftya, 1962, 7, 339.1 1 7 R. Sadanaga, M. Tokonami, and Y. Takeuchi, Acta Cryst., 1962, 15, 65.118 S. G. Fleet and H. D. Megaw, Acta Cryst., 1962, 15, 721.119 W. M. Meier, 2. Krist., 1961, 115, 439.120 H. Steinfink, Acta Cryst., 1962, 15, 644.121 J. V. Smith, F. Rinaldi, and L. S. D. Glasser, Acta Cryst., 1963, 16, 45.122 J. V. Smith, Acta Cryst., 1962, 15, 835.123 R. Sadanaga, F. Marumo, and Y. TakBuchi, Acta Cryst., 1961, 14, 1153.124 R, Steadman and P. M. Nuttall, Acta Cryst., 1962, 15, 510.15, 1005, 1017582 CRYSTALLOGRAPHYrosenb~schite,~~~ zunyite,12, inderite,l27 bultfonteinite,128 cronstedtite,l29lesserite,130 beryllonite, 131 and gagarinite (approximate formula Na,Ca@,F15, where M is a rare earth element).The hydrated and dehydratedchabazites Cal.95A13.9Si8.1024, 13( ?)H,O are of considerable chemical interest.In the structure determination, great difKculty was encountered in locat-ing the calcium atoms and water molecules. It is certain that during hy-dration the distribution of the calcium atoms changes greatly. In thehydrated form some water molecules are not bound directly to the frame-work and the cations are separated from the framework by other watermolecules.The phosphate mineral v&yrynenite,133 (Mn,Fe)Be(PO,)OH, and thesilicate euclase, AlBe(SiO,)OH, are related. In the former BeO,(HO), andPO, tetrahedra are linked by Mn-0 contacts and in the latter BeO,( OH) andSiO, are linked by A1-0 bonds. The main differences in structure can beexplained in terms of different electrostatic charge distributions.The metaphosphates [Kpo,],,134 Kurrol’s sodium salt [NaP03]n,135Maddrell ’s salt [NaPO,],, 36 and [ Na,H (PO,),] , contain polyphosp hat echains which in [KPO,], are like the silicate chains in diopside.A screwchain with four tetrahedra per period is found in Kurrol’s salt and a screwchain with three PO, tetrahedra per period occurs in the last two compounds.Kierkegaard has examined a number of molybdenyl phosphates. InNaWO,PO, and NaMoO,PO,, Mo(W)O, octahedra are coupled by PO,groups so that each MOO, is sharing edges with four PO, tetrahedra and eachPO, with four MOO, The pyrophosphate (MoOJ,P,O, is builtup of zigzag chains of fairly regular MOO, octahedra with corners in common,and these chains are connected by P,O, groups to give a three-dimensionaln e t ~ 0 r k .l ~ ~ The metaphosphate Mo0,(P03), 140 has layers of MOO, octa-hedra in the xy plane coupled by continuous chain anions with thechain axes parallel to x. The structures of “ crystalline oxide compoundsof phosphorus and molybdenum and tungsten ” have been reviewed.141are un- The phosphates Zn2Fe[(POp),,]4H,0 14, and Zn3(P0,),,4H,O126 R. P. Shibaeva, V. I. Simonov, and N. V. Belov, Kristallografiya, 1963, 8,126 Yu. G. Zagal’skaya and N. V. Belov, Kristallografiya, 1963, 8, 533.127 I. M. Rumanova and A. Ashirov, KristalZogra$ya, 1963, 8, 617.128 E. J. McIver, Acta Cryst., 1963, 16, 651.129 R. Steadman and P. M. Nuttall, Acta Cryst., 1963, 16, 1.130 A.Ashirov, I. M. Rumanov, and N. V. Belov, DokEady Akad. Nauk S.S.S.R,13l N. I. Golovastikov, DoEZady Akad. Nauk S.S.X.R, 1962, 142, 1301.1 3 2 A . A. Voronkov, N. G. Shumyatskaya, and Yu. A. Pyatenko, Zhur. strukt.133 M. E. Mrose and D. E. Appleman, 2. Krist., 1962, 117, 16.134 K.-H. Jost, Naturwiss., 1962, 49, 229.135 K.-H. Jost, Acta Cryst., 1963, 16, 640.13* K.-H. Jost, Acta Cryst., 1963, 16, 428.13* P. Kierkegaard, ArEiv Kemi, 1962, 18, 553.139 P. Kierkegaard, Arkiv Kemi, 1962, 19, 1.140P. Kierkegaard, Arkiv Kemi, 1962, 18, 521.141 P. Kierkegaard, Arkiv Kemi, 1962, 19, 51.142 W. Kleber, F. Liebau, and E. Piatkowiak, Acta Cryst., 1961, 14, 795.143 Kh. S. Mamedov, R. Gamidov, and N. V. Belov, Kristallografiya, 1961, 6, 114.606.1962, 143, 331.Khim., 1962, 3, 691.137 K.-H.Jost, Actct Cryst., 1963, 16, 623INORGANIC AND ORGANOMETALLIC STRUCTURES 583related, the former containing tetrahedral zinc and octahedral iron and thelatter octahedral zinc, both with isolated anions. Fe3(P04),,4H20is said not to be isostructural with either. InP0,,2H20 is unusual in thatone set of water molecules lies in otherwise unoccupied channels in a frame-work built up from indium atoms, phosphate ions, and another set of watermolecules.144 It is suggested that one “water” is OH- and the secondH30 +. Zirconium pyrophosphate 145 is said, from space-group considera-tions, to contain a linear P-0-P system.Wadsley and Anderson find some unusual titanates.146, 147, 148 Nao.2Ti02has distorted TiO, octahedra joined by sharing edges to give a double-sheet.Interstitial positions are partially occupied at random by sodium atoms.K0.13Ti02 is related to the mineral hollandite and contains continuous linearinterstices or tunnels which enclose varying numbers of ions such as barium,potassium, or lead.In K2Ti05 the anions are layers, of composition(Ti205)2-, in which the titanium is five-co-ordinated. The arrangement is adistorted trigonal pyramid. The anion layers are separated by potassiumcations. Na2Ti,07 contains layers of (Ti307)n3n- built of blocks of six TiO,octahedra sharing edges which are gained by having octahedral corners incommon. The layers are again joined by cations on two sites, one seven-and one nine-co-ordinated.The high-temperature form of barium germanate 149 contains infinitechains of GeO, tetrahedra.Oxyacid salts of heavy metals.A number of oxyacid salts, mainly sul-phates, have been investigated with the object of studying the metal atomenvironment and, in some cases, the hydrogen bond systems.In the anhydrous sulphates there is some confusion, high-temperatureP-MgSO, is reported 150 as isostructural with ZnSO,, CuSO,, and @-CoSO,;&C0S04 as isostructural with NiSO,, MgSO,, %SO,, and FeSO,; a-CoSO,as isostructural with CuSO, and ZnSO,. l 5 1 Two detailed examina-tions 152, 153 of anhydrous copper sulphate disagree in the details of thecopper co-ordination. It is agreed that the co-ordination is distortedoctahedral with six oxygens from six sulphate groups, but whereas the earlierdetermination suggests three pairs of different Cu-0 approach -distances of2.37, 2.15, and 1.89 8, the second determination, probably more correct,suggests four shorter and two longer distances d(Cu-0) = 2.37, 2.00,1.89 8.The mineral dolerophanite,l54 Cu,0S04, contains two types ofcopper atom, one with distorted octahedral co-ordination d(Cu-0) = 2.53,1-86, and 2.068, and the other with trigonal bipyramidal co-ordination,d(Cu-0) = 1-85, 2.00, 1.95, and 2.16 8. N~,CU(SO),)~,~H,O has the144 R. C. L. Mooney-Slater, Actu Cryst., 1961, 14, 1140.145 H. McD. McGeachin, Actu Cryst., 1961, 14, 1286.146 A. D. Wadsley and S . Anderson, Nature, 1961, 192, 551.14’S. Anderson and A. D. Wadsley, Actu Chem. Scund., 1961, 15, 663.148 S.Anderson and A. D. Wadsley, Acta Cryst., 1961, 14, 1245.14* W. Hilmer, Actu Cryst., 1962, 15, 1101.150 J. Coing-Boyat, Compt. rend., 1962, 255, 1962.151 P. J. Rentzeperis, Acta Cryst., 1961, 14, 1305.152 B. R. Rao, Actu Cryst., 1961, 14, 321.153 P. A. Kokkoros and P. J. Rentzeperis, Actu Cryst., 1958, 11, 361.154 E. Kahler, Naturwiss., 1962, 49, 298584 CRYSTALLOGRAPHYinteresting system (9) in which copper is distorted octahedral with a pair oflong contacts to two of the sulphate 0 ~ y g e n s . l ~ ~0 0' H i 0I \0 0An exactly similar system has been reported lS6 in ZnS04(N,H5),S04, inwhich the water molecules of (9) are replaced by -NH,NH3+ groups, makingthe polymer electrically neutral. Dizinc dihydroxide sulphate l57 containsboth tetrahedral and octahedral zinc, but the basic indium sulphate,JnOHSO,(H,O),, contains only In06 octahedra joined at the corners to givechains.158 The (Hg302),2n + cation, as an undulating two-dimensional in-finite layer, is found in HgS0,,2Hg0.159 0-Hg-0 is nearly linear.Theanions are enmeshed in the cation lattice. HgSe04,2Hg0 is isomorphouswith it.The three hydrated sulphates FeS0,,7H20, 16* CoS04,6H,0,161 and(NH,),Ni(S04),,6H,0 162 contain the [M(H,0)6]2 + octahedral cation. Thehydrogen bond systems are discussed in detail for each compound. Inthe cobalt salt there are twelve hydrogen bonds, eleven H,O-sulphate andone H,O-H,O, of an average length of 2.8A. The hydrogen atoms areassigned an ordered configuration that would not contribute to the residualentropy a t low temperatures. A new examination of nickel ammoniumsulphate shows slight differences from the early structure proposed byHoffmann.andNiS0,,6H,0,166 the metal co-ordination polyhedron is an octahedron of fourwater oxygens and two sulphate (or sulphite) oxygens, forming, forK2MnS04,4H,0, discrete molecules and, for Fe,(S04),,8H,0, rings of thisformula.The work on CuS04,5H,0 by neutron diffraction deals in themain with the water molecules. ,/(H-O-H) is shown to be within a degreeor two of the tetrahedral value and the system 0-H-0 to be bent by as muchas 26". Measurements between 20" and 90"c indicate that the water mole-cules rotate before dehydration takes place.In CuSO 4, 5H,O, K,Mn( SO 4 ) ,,4H,O, (Fe or Mg),( SO 4) 2, 8H,O155 B.R. Rao, Acta Cryst., 1961, 14, 738.156 C. K. Prout and H. M. Powell, J., 1961, 4177.1 5 7 Y. Iitaka, H. R. Oswald, and S. Locchi, Acta Cryst., 1962, 15, 559.158 G. Johansson, Acta Chem. Xcand., 1961, 15, 1437.159 G. Nagorsen, S. Lyng, and A. Weiss, Angew. Chem., 1962, 74, 119.16* W. H. Baur, Naturwiss., 1962, 49, 464.161 A. Zalkin, H. Ruben, and D. H. Templeton, Acta Cryst., 1962, 15, 1219.162 N. W. Grimes, H. F. Kay, and M. W. Webb, Acta Cryst., 1963, 16, 823.1e3 G. E. Bacon and N. A. Curry, Proc. Roy. Xoc., 1962, A, 266, 95.164 W. Schneider, Acta Cryst., 1961, 14, 784.165 W. H. Baur, Actil Cryst., 1962, 15, 815.166 D. Grand-Jean, R. Weiss, and R. K0m, Compt. rend., 1962, 255, 964INORGANIC AND ORGANOMETALLIC STRUCTURES 585Two silver salts have been re-investigated. Silver nitrate 167 has beenfound to be as reported by Ketelaar 168 in 1936, but d(Ag-N) is given as2.47 8.The earlier structure determination on the chlorite, AgClO,, appearsto be in The structure was said to have a short Ag-C1 distance of2.28, an intramolecular O-.O separation of 2-28, and an unusual silverenvironment. In the later structure,170 the silver is at the centre of adistorted triangular prism of oxygen atoms, with d(Ag-0) = 2*4--2*6 A.The shortest intramolecular 0-0 distance is 3-25 8, and there is no directAg-Cl contact.In [AgPO3],171 the PO, tetrahedra are joined at corners, and spiral, onetetrahedron to a quarter turn, round a 2-fold axis. The P-0 bonds involv-ing shared oxygens have d = 1.58 and 1.62 8, and those with unsharedoxygens d = 1.45 and 1.46 A.There are two sorts of distorted squarepyramidal co-ordination of the silver atoms. In one a silver atom is 0.58 Aabove the base of the pyramid, and in the other 0.94 8 above it. The shortestAg-Ag contact is 3-15A.So-caEZed peroxy-compounds. A tetragonal oxide of empirical formulaAgo has been prepared by the action of ozonised oxygen on hot silverpowder. It is distinct from the monoclinic Ago found in charged silverelectrodes. It contains silver atoms in two sets of crystallographic positionsand pairs of oxygen atoms apparently doubly bound. Part of the structureconsists of layers of empirical formula Ago,. The other half of the silveris present in inter-layer positions as Ag+.The silver in the layers is divalentand forms square-planar (dsp2) bonds. The formula of the oxides is ex-panded as4Ag0 =Ag2+[ (Ag2+) 2022-( 0 2-) 2]The same investigation gives results for some '' peroxy-compounds "of formulae Ag7SOl, and Ag,NO,,. The crystal structure of the second ofthese compounds has also been determined by Chou.173 It contains aframework of composition Ag,O, which is formulated as [AgI1,AgdI1O8ln.Each silver is co-ordinated to four oxygens in a rectangular arrangement.AgII and AglI1 occupy the same set of equivalent positions so the averagevalency is 8/3. The angles at the silver atom (84" and 96') differ slightlyfrom 90". In the three-dimensional framework there are two types ofcavity.Thesmaller cavity is a cube which contains an Ag+ ion with eight (framework)oxygen atoms at a distance of 2.6 8. The compound, which contains silverin three valency states, has a high electrical conductivity. The two reportsdiffer in some details. Ag7S01, is a similar compound with SO,z- groupssimilarly contained in the larger cavities. The name " peroxy-compound "is inappropriate to these and possibly other members of the series. TheThe larger is cubo-octahedral and contains an NO3- group.18' R. E. Long and R. E. Marsh, Acta Cryst., 1962, 15, 448.168 J. A. A. Ketelaar, 2. Krist., 1936, 95, 383.169 R. Curti, V. Riganti, and S. Locchi, Acta Cryst., 1957, 10, 687.170 J. Cooper and R. E. Marsh, Acta Cryst., 1961, 14, 202.171 K.H. Jost, Acta Cryst., 1961, 14, 779.172 A. 5. McKie and D. Clark, Third International Battery Symposium, 1964.173 Chou Kung-Du, Xci. Sinica, 1963, 12, 139586 CRY STALLOQRAPHYdegree of ionic interaction between the Ag+ ions and their immediate frame-work surroundings appears to be variable according to the nature of theanion. The anions are disordered or capable of considerable movement.The whole structure may be regarded as an approximation to a clathrate inwhich anions and cations occupy their own sets of different and unconnectedcavities in a neutral framework. It is possible that some of the cavities areempty and, as with clathrates, there should be an upper limit to the size ofenclosable group, in this case the anion.Metal Carbonyls and 0rganometaUics.-Many workers are now active inthis field.The structures elucidated present a great variety in both com-plexity and novelty.The structures of iron penta~arbonyl,~~~ distorted trigonal bipyramid,Mn,(CO),,( lO),175 Fe5(C0)1,C,176 and Os,(CO),, (11) 177 have been reported.In (ll), d(0s-0s) = 2.88 8. The iron carbonyl carbide has five iron atomsat the corners of a square pyramid, d(Fe-Fe) = 2.64 A, with the carbidecarbon atom in the centre of the base. Each iron atom is attached to threeterminal carbonyl groups.' Ioc g / \oc coOCOC00c,? ,co\ g //; \?, cO0 s \ ,os -I C ' co0C0In (lo), d(Mn--Mn) = 2.923 A, 0-5 A longer than twice the normal covalentradius, and this is attributed to localisation of negative charge on the metalatoms through co-ordination with the CO groups.In the bromide[BrMn(CO),],, two octahedra are joined by an edge with bridging bromineatoms equidistant from both metal atoms 178 and I,Ru(CO), is an octahedralmonomer, the iodines being in cis-p0sitions.17~Hexacarbonylbiphenyldichromium [ (CO),CrC,H,-], has the trans-form,and no alternation of d(C-C) was observed in the aromatic system.180Tricarbonylcyclopentadienylmanganese is monomeric. Dibenzene-chro-mium has been investigated at room temperature by Cotton et aZ.,ls2 whoobserved a molecular symmetry D,,,d(C-C) = 1-387 &- 0.017 A, and byJellinek,l83 who finds molecular symmetry D,,,d(C-C) = 1.366 & 0.012and 1.436 Jellinek claims that the discrepancy is due to orienta- 0.012 A.A.W. Hanson, Acta Cryst., 1962, 15, 930.1 7 5 L. F. Dahl and R. E. Rundle, Acta Cryst., 1963, 16, 419.178 E. H. Braye, L. F. Dahl, W. Hubel, and D. L. Wampler, J. Amer. Chem. Xoc.,1 7 7 E. R. Corsy and L. F. Dahl, Inorg. Chem., 1962, 1, 521.178 L. F. Dahl and Chin-Hsuan Wei, Acta Cryst., 1963, 16, 611.1 7 9 L. F. Dahl and D. L. Wampler, Acta Cryst., 1962, 15, 946.180 G. Allegra, Atti Accad. naz. Lincei, Rend. Clmse Sci. 3 s . mat. nut., 1961, 31, 399.18lA. F. Bernot and R. E. Marsh, Acta Cryst., 1963, 16, 118.182 F. A. Cotton, W. A. Dollase, and J. S. Wood, J. Amer. Chew%. Soc., 1963, 85, 1543.1962, 84, 4633.F. Jellinek, J . Organometallic Chem., 1963, 1, 43I N 0 R G AN I C AN D 0 RG AN 0 MET ALL1 C S T R U C T U R E S 587tional disorder in Cotton's crystals.A low-temperature study may settlethis.A new chain structure has been found in the monocyclopentadienyl-indium and the similar thallium compound.l8* Each metal has two cyclo-pentadiene neighbours with normals to the aromatic planes making anoblique angle a t the metal. Each aromatic group has two metal atomneighbours, one on either side, so that the metal-organic molecule-metalsystem is linear.Dicyclopentadienylberyllium has been found to be a " ferrocene-type "sandwich complex,l85 as also is n-cyclopentadienyl-n-cycloheptatrienyl-vanadium.186 Diacetylruthenocene, like other ruthenocenes and unlikeferrocenes, has an eclipsed configuration with the substituents cis.187 Thesubstituted cyclopentadiene system in cyclopentadienyl- 1 -phenylcyclo-pentadienecobalt 188 is non-planar, with the saturated carbon atom, whichcarries the phenyl group, bent away from the metal atom.The plane ofthe cyclopentadiene is approximately parallel to the four coplanar atoms ofthe 1-phenylcyclopentadiene molecule, which is presumed to be bonded tothe metal by two cr- and two n-bonds. The hydrogen atoms in dihydridodi-n-cyclopentadienylmolybdenum lS9 lie in the median plane between thecyclopentadienyl planes. These ring systems, which are somewhat inclinedto each other, are in the eclipsed orientation. The hydrogen atoms are atthe wider end of the partly opened sandwich. The Mo-H distance is 1.1 Aand ,/- (H-Mo-H) is close to 90". In tricarbonyl-n-cyclopentadienylethyl-molybdenum lgo the stereochemical arrangement approximates that of the[Nb0FJ3- ion.Six bonding orbitals to the metal of the cyclopentadienyland carbonyl ligands form a distorted octahedron and the metal-ethyl bondlies approximately along a three-fold axis of the octahedron. The metal-carbon bond of the ethyl group is 0.4 A longer than the metal-carbonyl-carbon distance (1.97 A).Tricarbonylcyclo-octa-l,3,5,-trienylchromium 191 is a near-planar com-plex analogous to tricarbonylcycloheptatrienylmolybdenum, but tricar-bonylcyclo-octatetraenyliron lg2 has a different, dihedral geometry (12) ;alternation of double and single bonds is observed only in the section of themolecule farthest from the metal atom. Tricarbonylbutadienyliron 193 isvery similar, the butadiene being in the cisoid form and the n-electrons de-localised ; d(C-C) = 1.45 and 1.46 A.Tricarbonyl-S,3-dimethylbutadienyl-osmium,194 in contrast, is a dimer (13) resembling (Me*CiCMe)H,Fe(C0)8,the major difference being that the Os(CO), group co-ordinated to thelE4 C. Panattoni, Nature, 1963, 199, 1087.lS6 R. Schneider and E. 0. Fischer, Naturwiss., 1963, 50, 349.1E8 G. Engebretson and R. E. Rundle, J . Amer. Chem. SOC., 1963, 85, 481.J. Trotter, Actu Cryst., 1963, 16, 571.lE* M. R. Churchill and R. Mason, Proc. Chem. SOC., 1963, 112.M. J. Bennett, M. Gerloch, J. A. McCleverty, and R. Mason, Proc. Chem. Soc.,lS0 M. J. Bennett and R. Mason, Proc. Chem. Soc., 1963, 273.lS1 V. S. Armstrong and C. K. Prout, J., 1962, 3770.lS2 B.Dickens and W. N. Lipscomb, J. Amer. Ohem. SOC., 1961, 83, 4862.lS3 0. S. Mills and G. Robinson, Actu Cryst., 1963, 16, 758.ls4 R. P. Dodge, 0. S. Milla, and V. Schomaker, Proc. Chem. SOC., 1963, 380.1962, 357588 CRYSTALLOGRAPHYheterocyclic ring is rotated through 60” relative to the iron complex, givingan octahedra’l co-ordination polyhedron. The Os-0s distance is 2.74 8.Fe*c’; ‘co00 sC’l \0 c co0The butadiene system may again be in evidence in the remarkablecyclopentadienylhexakistrifluoromethylbenzenerhodium ( 14), lg5 in whichonly four atoms of the benzene nucleus are associated with the metal atom.The double bond not associated with the metal atoms has a length of 1.32 8,0.13 shorter than the other.Herethe squarc-planar, chlorine-bridged rhodium atoms form olefhic p-bondswith the hydrocarbon. The benzene adduct of 1,2,3,4-tetramefhylcyclo-butadienylnickel( n) chloride 197 is also dimeric, two nickel tetrahedra sharingan edge, so bridging through chlorine atoms.One chlorine and one planarapproximately square cyclobutadiene ring complete the tetrahedron ; themethyl groups are displaced outwards from the metal, and the benzenemolecules lie between the cyclobutadiene planes. TiCl,( C,H,) and[TiCl,(C5H,)]20 are z-complexes, the latter being an oxygen-bridgedThe structure of three complex metal acetylenes have been reported,CO,(CO)~~C,H,*C~C*C~H~ ( 15),200 Fe,(CO),[C,H,C,H], ( 16),201 and biscyclo-pentadienylbisdimethylacetylenedicarboxylatenickel( a).802 In the last thereare discrete molecules in which the nickel is covalently bound to a n-cyclo-pentadiene anion and to a norbornadienyl anion which co-ordinates to themetal through a a-bond to the bridge carbon atom and a p-bond to theolefinic group to which the methyl carboxylate substituents are attached.Trimethyltin fluoride contains planar [Sn(CH,),] + ions connected intochains by bridging fluorine. The Sn-F-Sn system is non-linear and theSn-F bonds non-equivalent. 203The dimer 1,5-cyclo-octadienerhodiurn is of yet anotherdimer.198, 1991 9 5 M. R. Churchill and R. Mason, Proc. Chem. SOC., 1963, 365.196 J. A. Ibers and R. G. Snyder, Acta Cryst., 1962, 15, 923.197 J. D. Dunitz, H. C. Mez, 0. S. Mills, and H. M. M. Shearer, Helv. Chirn.Acta,198 P. Ganis and G. Allegra, Atti. Accad. nax. Lincei, Rend. Sci. fis. mat. nat., 1962,199 G. Allegra and P. Ganis, Atti. Accad. naz. Lincei, Rend. Xci. 3 s . noat. nat., 1962,200 L. F. Dahl and D. L. Smith, J. Amer. Chem. SOC., 1962, 84, 2450.201 G. S. D. King, Acta Cryst., 1962, 15, 243.202L. F. Dahl and Chin-Hsuan Wei, Inorg. Chem., 1963, 2, 713.203 H. C. Clark, R. J. O’Brien, and J. Trotter, Proc. Chem. Soc., 1963, 85.1962, 45, 647.33, 303.33, 438INORGANIC AND ORGANOMETALLIC STRUCTURES 589Co-ordination Complexes.-Three-dimensional heavy-atom methods arespecially suited for work on the structure of co-ordination compounds.Results obtained by two-dimensional methods must be regarded as lessreliable. Much of the structural work is still confined to the stereochemicaland related problems in compounds formed by the elements of the firsttransition series.In the structure of trisdimethylformaniidesodium iodide, the sodium hasa distorted octahedral environment of six oxygen atoms and the iodine isionic, Discrete [Al,( OH),( H20)8]4 f cations have been observed 204 as thesulphste and selenate dihydrates ; the aluminium is octahedrally co-ordinated,and the octahedra share edges by means of common hydroxyl groups.Themetal atoms in cerium(1v) ,05 and zirconium(rv) 206 acetylacetonates areeight-co-ordinated through oxygen atoms at the corners of an Archimedeanantiprism, d(Ce-0) = 2.40 -J= 0.03 A, d(Zr-0) = 2.198 8, in contrast withthe trigonal dodecahedra1 form of the 8-co-ordinate tetradibenzoylmethane-cerium(1v) and tet'rasodium tetrabisoxalatozirconate(1v) trihydrate.207Pu,(C,O,),,lOH,O is isostructural with La,(C,04),,10H,0.208204 G. Johansson, Actu Chem. Xcand., 1962, 16, 403.Z o 5 B. Matkovic and D. Grdeni6, Acta Cryst., 1963, 16, 456.206 J. V. Silverton and J. L. Hoard, Inorg. Chem., 1963, 2, 243.207 G. L. Glen, J. V. Silverton, and J. L. Hoard, Inorg. Chem., 1963, 2, 250.20* T). M. Chackraburtty, Actu Cryst., 1963, 16, 834590 CRYSTALLOGRAPHYThe peroxochromate Cr05,C,H5N (17) 209 has been reported t o haved(0-0) = 1.30 A in the peroxide group, d(Cr-0) = 1-78-1.85 8 to peroxideoxygens, and 1.72 to the remaining oxygen, but a second group ofN -NHHLN-C I1 \;i/’\C-NH2‘s’ \NH2-& ,Cu-N 0-0 0 1 O ’ - t - N 3 (18) 0(19) uc ..0,:G(17)workers 210 suggests a position for 0’ that gives an essentially pentagonalpyramidal co-ordination.Complexes of cobalt, nickel, copper, and zinc have been very popularsubjects for investigation.The crystal structures and absolute configurations of mtris(ethy1enedia-mine)cobalt(m) bromide monohydrateYz11 d(Co-N) = 1-98-2-03 8, andtrans-dichlorobis- l-propylenediaminecobalt (m) chloride dihydrate [chelatering puckered, d(Co-N) = 1.94-2.02, d(Co-C1 = 2-29 A] have been deter-mined 212 and two workers have independently 2139 214 determined thestructure of di-p-hydroxobistetramminedicobalt (m) chloride tetrahydrate,both finding the expected dimeric hydroxyl-bridged cation and an 0-H-C1hydrogen bond system.In [(NH,),CONH,CO(NH,)~](NO,), the dimericcation 215 is bridged by the single NH, group [d(Co-NH2) = 2.2 A andThe existence of square-planar cobalt( ZI) in the complex trans-dimesityl-bisdiethylphenylphosphinecobalt( II) has been reliably established. 216Four paramagnetic nickel complexes trans-bisethylenediaminedi-iso-thiocyanatonickel( n), 217 nitritobisethylenediaminenickel( n) perchlorate,21abis-a-aminoisobutyratonickel(n) tetrahydrate,219 and nickel formate,Ni(HC02),,2H20 220 have been shown to be octahedral. In the first,d(Ni-N) is 2.10 to ethylenediamine and 2-15 A to the NCS group. Thesecond compound is most unusual; the nickel is square-planar with respectt o the nitrogen of the amine, d(Ni-N) = 2.17 and 2.13 8, and a distortedoctahedron is completed by a nitrito-group oxygen which is co-ordinated totwo nickel atoms linking the octahedra by their apices to give a kind ofL(Co-NH2-Co) = 144’1.209 R.Stomberg, Nature, 1962, 196, 570.2I0 B. F. Pederson and B. Pederson, Acta Chem. Scand., 1963, 17, 557.211 K. Nakstsu, Bull. Chem. SOC. Japan, 1962, 35, 832.112 Y. Saito and H. Iwasaki, Bull. Chem. SOC. Japan, 1962, 35, 1131.21* N.-G. Vannerberg, Acta Chem. Scand., 1963, 17, 85.216 N.-G. Vannerberg, Acta Chem. Scand., 1963, 17, 79.216 P. G. Owston and J. M. Rowe, J., 1963, 3411.217 B. W. Brown and E. C. Lingafelter, Acta Cryst., 1963, 16, 753.218 F. J. Llewsllyn and J. M. Waters, J., 1962, 3845.219 T. Noguchi, Bull. Chew. SOC. Japan, 1962, 35, 99.220 K. K r o g m m and R.Mattes, 2. Krist., 1963, 118, 291.C. K. Prout, J., 1962, 4429INORGANIC AND ORGANOMETALLIC STRUCTURES 591chain polymer, d(Ni-0) = 2.58 8. The third contains the cis-bisaquobisa-minobutyratonickel(I1) group in which the chelate ring is not planar.Other paramagnetic nickel complexes contain dimeric complex ions.221Nien2C1, and Nien2Br2 (en = ethylenediamine) should be written in theform [Nien,C12]2+C1,2-. The co-ordination of the nickel is octahedral andthe nickel atoms are joined through two chlorine-atom bridges.In the paramagnetic complexes, bis-N-isopropylsalicyla.ldoximina.to-nickel( 11) 2 z 2 and dichlorobistriphenylphosphinenickel( n) , 223 the nickel bondsare, however, tetrahedral, but distorted. In the latter, L(P-Ni-P) = 117 *and L(C1-Ni-Cl) = 123”; d(Ni-P) and d(Ni-C1) are 2.27 and 2.28 8, res-pectively, very near the sum of covalent radii.Bisthiosemicarbazidatonickel(II) (red crystals) 224 (18) is a planarmolecule, d(Ni-N) = 1-91 and d(Ni-S) = 2.155 8.The shortest inter-molecular nickel contact is to a nitrogen atom at 3.67 8. The nickel in abis-5-chlorosalicylaldimine complex 255 and the palladium in a bis-N-butylsalicylaldoxime complex 26 have square-planar bonds, and the mole-cules are chair-shaped.In tetrakisthioacetamidecopper(1) chloride the copper bonds to foursulphur atoms at 2.34 A form a distorted tetrahedr~n.~~’ The anglesS-Cu-S bisected by the crystal 4 axes are 103” 40’.The search for unusual co-ordinations of copper(1r) has continued. Adistorted tetrahedral complex, 2,2’-biphenylbis-(2-iminomethylenephen-olato)copper(II) (19), 228 has been reported in which the copper atom has itsco-ordination polyhedron forced upon it by the geometry of the ligand.The cc-form of bis-(N-methylsalicyla1diminato)copper 229 is square-planarwith a short copper-copper contact of 3.33 8, d(Cu-N = 1.99 and d(Cu-0)= 1-90 8.The plane-to-plane arrangement in the square-planar NN’-ethylenebisacetylacetoneiminatocopper( DC) 230 and in the two reportedstructures of bis-( 8-hydroxyquinolinato)copper(rr) 231, 232 according to theauthors are reminiscent of donor-acceptor polarisation bonding.Further 5-co-ordinate complexes, both trigonal bipyramidal and square-pyramidal, have been reported. The iodobis-(2,2’-bipyridyl)copper( 11) ion(20) 233 is of the former type and bis(NN-di-n-propy1dithiocarbonato)-copper(@ (21) 234 is of the latter type, dimeric, with the copper atom 0.40 A221 A.S. Antsyshkina and M. A. Perai-Koshits, Doklady Akad. Nauk, S.S.S.R.,222 M. R. Fox, E. C. Lingafelter, P. I. Orioli, and L. Sacconi, Nature, 1963, 197,223 G. Garton, D. E. Henn, H. M. Powell, and L. M. Venanzi, J . , 1963, 3625.224 L. Cavalca, M. Nardelli, and G. Fava, Acta Cryst., 1962, 15, 1139.225 C. J. Brown, jun., Diss. Abs., 1962, 23, 84.226 E. Frasson, C. Panattoni, and L. Sacconi, Caxxetta, 1962, 92, 1470.22’M. R. Truter and I<, W. Rutherford, J . , 1962, 1748.2 2 8 T. P. Cheeseman, D. Hall, and T. N. Waters, Proc. Chem. Soc., 1963, 379.22* E. C. Lingafelter, G.L. Simmons, B. Morosin, C. Scheringer, and C. Freiburg,230 D. Hall, A. D. Rae, and T. N. Waters, Proc. Chem. SOC., 1962, 143.231 J. A. Bevan, D. P. Graddon, and J. F. McConnell, Nature, 1963, 199, 373.232 F. Kanamaru, K. Ogawa, and I. Nitta, Bull. Chew. SOC. Japan, 1963, 36,233 G. A. Barclay and C. H. L. Kennard, Nature, 1961, 192, 425.2 3 4 A. Pignedoli and G. Peyronel, Gazzetta, 1962, 92, 745.1962, 143, 105.1104.Acta Cryst., 1961, 14, 1222.422592 CRYSTALLOGRAPHYabove the base of the pyramid.the other Cu-S distances are 2.32 8.The copper-apex-sulphur distance is 2.7 1 A,I$ N /- -/Three copper complexes have been investigated as models of metal-protein interaction. They are glycylglycylglycinocopper( n) chloride 1.5hydrate (a),235 sodium glycylglycylglycinocuprate monohydrate (b),235 andmonoglycylglycinocopper(n) trihydrate (c).236 In compound (c) the copperatom achieves a square-planar configuration through a tridentate glycyl-glycine anion and a water molecule; a second much more loosely boundwater molecule completes a square pyramid. The metal ions in (a) and ( b )are also five-co-ordinated, but the relationship to the various ligands is morecomplex. I n (a) the chloride ion is found in the base of the pyramid and awater molecule is a t the apex, but in ( b ) the metal atom is co-ordinated onlyto the organic ligands. The authors discuss in detail the important complexhydrogen bond systems and molecular arrangements of the crystal structure.Copper atoms in bis-P-aminobutyratocopper(rr) dihydrate (22) , 237 copperammonium oxalate dihydrate, 238 diamminecopper( rr) carbonate (23) , 239 andcopper(rr) thiocyanate 240 have distorted octahedral co-ordination....-,o ....0-cI ‘*-.--HjN, I 0 Icu’ ‘ c - 0H~N’ I ‘0’(23)Copper ammonium oxalate dihydrate contains two types of copper atoms,one co-ordinated to six oxalate oxygens and one to four oxalate oxygensand two water molecules.In thediammine carbonate chain-polymer (23) , the carbonate forms a four-membered chelate ring similar to that observed in the carbonatotetra-amminecobalt(m) cation. 241The chelate rings are five-membered.z35 T. Cooper, H. C. Freeman, G. Robinson, and J. C. Schoone, Nature, 1962, 194,236 B. Strandberg, I. Lindqvist, and R.Rosenstein, 2. Krist., 1061, 116, 266.237 R. F. Bryan, R. J. Poljak, and K. Tomita, Actn Cryst., 1961, 14, 1125.238 M. A. Viswamitra, J. Chem. Phys., 1962, 37, 1408.239 F. Hanic, Acta Chim. Acad. Sci. Hung., 1962, 32, 305.240 B. W. Brown, Diss. Ah., 1961, 22, 1417.241 G. A. Barclay and B. F. Hoskins, J., 1962, 586.1237INORGANIC AND ORGANOMETALLIC STRUCTURES 593RiIonopyridinecopper(n) acetate 242 appears not to have a larger copper-copper distance than the corresponding hydrate, as was reported earlier.In KCuCl, and NH,CuCl,, discrete planar Cu,ClS2- dimers are found,with long Cu-Cl contacts (3.11, 2-94: A) between d i r n e r ~ . ~ ~ ~ The antiferro-magnetism and single- crystal polarised spectra are discussed.The salt Na[Zn(OH),] contains 244 an unusual %(OH), trigonal planaranion, d(Zn-0) = 1.96, 1.98, and 2.00 A.Two further hydroxyl ions at2-63 A complete a trigonal bipyramidal group. KZnCl,,ZH,O howevercontains only tetrahedral ZnC1,,H20 anions. 245 Slight corrections havebeen made 246 to Truter and Lippert's structure of monoaquobisacety-lacetonatozinc(m).In bisbiuretzinc chloride the zinc is octahedrally co-ordinated to twopairs of biuret oxygen atoms in the cis-configuration with nearly parallelC-0 These oxygen atoms are at the corners of an approximatelysquare plane, d(Zn-0) = 2-05 and 2.03 A. Bishydrazinezinc chloride(24) 248 crystals contain linear polymers ; co-ordination around t'he zincatom is octahedral.CI ciCI CI CIPotassium tetracyanodioxorhenate 249 contains octahedral rhenium withK,Re20Cl,,H20 is analogous to the the oxygen atoms cis to each other.ruthenium salt.250The Re,Cl,23- ion, Re atoms shaded.242 G.A. Barclay and C. H. L. Kennard, J., 1961, 5244.2 4 3 R. D. Willett, C. Dwiggins, jm., R. F. Kruh, and R. E. Rundle, J. Cheiit. Php.,2 4 4 H. G. Schnering, Naturwiss., 1961, 48, 665.245 B. Brehler and P. Susse, Naturwiss., 1963, 50, 517.246 H. Montgomery and E. C. Lingafelter, Acta Cryst., 1963, 16, 748.2 4 7 M. Nardelli, G. Fava, and G. Giraldi, Acta Cryst., 1963, 16, 343.3 4 * A. Ferrari, A. Braibanti, and G. Bigliardi, Acta Cryst., 1963, 16, 498.2 4 9 K. Lukaszewicz and T. Glowiak, Bull. Acad. pclon. Sci., Ser. Xci. chim., 19612 5 3 J. C. Morrow, Acta Cryst., 1962, 15, 851.1963, a, 2429.9, 613594 CRYSTALLOGRAPHYCsReCl, has a complex chloride anion of a new type (25) 2 5 1 p 252 containingthree rhenium atoms.Each of these has a pentagonal bipyramidal co-ordination including two metal-metal bonds. Bond lengths are 2.50 A(Re%), 2-43 A (Cl-Re bridging), 2.35 A (terminal off-plane C1-Re), and2.60 A (terminal in-plane C1-Re).Two platinum acetylacetonate complexes (26) 253 and (27) 254 have beenreported containing bonds between platinum and “ active methylene ”groups. In (26) d(Pt-CH) = 2.13 AY much shorter than in (27), d = 2-36 8.Distances between platinum and carbon atoms of methyl groups in (27) are2*03-2*07 A.Me0 ,CI MeM;tMeTwo interesting complexes with sulphur-containing ligands are bis-(thi0urea)cadmium formate (28) 255 and AgSCN,P(C,H,), (29),256 bothribbon-like.C-H 4 40’ C-H O/C-H 0’O‘C-H O\ ,C-H 9 C-H0’ C 0’(28)c y IN CI P II IN CI I (29)Ag- s// /251 J.A. Bertrand, F. A. Cotton, and W. A. Dollase, J. Amer. Chem. SOC., 1963,252 W. T. Robinson, J. E. Fergusson, and B. R. Penf‘old, Proc. Chew. SOC., 1963, 116.2s3 B. N. Figgis, J. Lewis, R. F. Long, R. Mason, R. S. Nyholm, P. J. Pauling, and254 A. G. Swallow and M. R. Truter, Proc. Roy. Soc., 1962, A , 266, 527.255 33. Nardelli, G. Fava, and P. Boldrini, CTazzettcc, 1962, 92, 1392.256 C. Panattoni and E. Frasson, Gazzetta, 1963, 93, 601.85, 1349.G. B. Robertson, Nature, 1962, 195, 1278.3. ORGANIC STRUCTURESCarboxylic Acids.-An X-ray study of liquid formic acid 257 indicates thatthe molecules form hydrogen-bonded chains, as in the solid, rather thandimers as in the gaseous phase, but both inter- and intra-molecular dimen-sions are larger in the liquid than in the solid.Two investigations of pro-pionic one a t -95" and the other a t -136", give substantially thesame result. The molecules are linked by hydrogen bonds of length 2.64 8to form centrosymmetric and nearly planar dimers. Butyric acid has beenstudied 259 in the form which is stable down to -55" and has been shownto be very similar in structure to propionic acid. Bond distances wereshorter than expected until they were corrected to allow for the effects ofthe thermal motion of the molecules. Valeric acid,260 because of its lowmelting point, was expected to have a different molecular arrangement, butits structure also was found to be similar to that of propionic acid.Thecarboxyl group and the first two carbon atoms of the chain are coplanarto within 0.01 A but the other two carbon atoms of the chain deviatefrom this plane by 0.026 and 0.159 8, respectively, and the planes of thetwo carboxyl groups hydrogen-bonded across the centre of symmetryare separated by 0.12 8. In fact, a survey 2 6 l of 12 recent analyses ofcarboxylic acid centrosymmetric dimers shows that coplanarity of the twocarboxyl groups is the exception rather than the rule. Separations of thetwo planes of up to 0.5 A have been found and it is suggested that the packingrequirements of the rest of the molecule may be responsible for this effect.Accurate structure determinations 262 of ammonium oxamate and lithiumoxalate from diffractometer data revealed central C-C bond lengths of1.564 & 0.002 and 1-561 & 0-004 A respectively (cf.1.517 for the longestC-C bond between trigonally hybridised carbon atoms previously reported).Spherical regions of particularly high electron density are found in thecentres of these bonds.Some low-molecular-weight compounds possess structural features similarto those of stereoregular polymers. ( -J- )-cccc'-Dimethylglutaric acid is onesuch compound, and a preliminary report 263 compares its conformation withthat of isotactic polypropylene where the planes of successive groups are at60" to each other.A number of papers on long-chain compounds have appeared during theyear, including several on carboxylic acids and related compounds.The forms D and E of ll-bromoundecanoic acid (30; n = 9, R = CH2Br)both show unusual features in addition to the remarkably small tilt of the257 G.Geisenfelder and H. Zimmermm, Ber. Bunsen Gesellschaft Phys. Chem.,1963, 67, 480.258 F. J. Strieter, D. H. Templeton, R. F. Scheuerman, and R. L. Sass, Acta Cryst.,1962, 15, 1233.2 5 9 F. J. Strieter and D. H. Templeton, Acta Cryst., 1962, 15, 1240.2soR. F. Scheuerman and R. L. Sass, Acta Cryst., 1962, 15, 1244.261 G. A. Jeffrey and M. Sax, Acta Cryst., 1963, 16, 430.282 B. Beagley and R. W. H. Small, Nature, 1963, 198, 1297.268 P. Corrandini, G. Diana, P. Ganis, and C.Pedone, Makromol. Chem., 1963, 61,242596 CRYSTALLOGRAPHYmolecules (41 ", and 40" respectively) towards the end-group planes.Adjacent double( i.e.dimer)-layers tilt in opposite directions in the D form 264and within each centrosymmetric dimer the parallel planes of the two car-boxyl groups are as much as 1.17 A apart. The E form, to which all otherstransform at their melting points, does not occur as a dimer, but in anunusual head-to-tail arrangement.265 The A , form of lauric acid 266 (30;n = 10, R = CH,) has a more normal molecular tilt of 67" 20' but the planeof the carboxyl group is rotated through 16" from the plane of the chain,and the carboxyl groups of each dimer are adjacent to the methyl group ofneighbouring dimers. The bent form characteristic of branched fatty acidsnow seems to be common also in unbranched long-chain molecules wheneverthe chain packing is disturbed by the presence of a group other than CH,.This effect is found, for example, in both 3-thiadodecanoic acid 26' (31 ;n = 1, R = S, m = 8) and its 1,3-digly~eride.~~* The former compoundprovides a further example of the separation of the carboxyl group planesacross a centre of symmetry, this time by 0-16 8.The diglyceride has twohydrocarbon chains pointing in opposite directions and the chain-tilt of 55"alternates in direction in successive layers of parallel chains. Another bent(30) (3 1 )molecule is ~Z~-~~-8,9-rnethyleneheptadecanoic acid 269 (31; n = 6, R = cy-clopropyl, m = 7). The difficulty of packing both cyclopropyl rings andcarboxyl dimer groups is shown by the increase in the average cross-sectionalarea occupied by each chain from the usual 18.5 A2 to 19.7 A2.The meand(C-C) is 1.508 A in the cyclopropyl ring and 1.507 A exo to the ring. Thelong chains in ethyl stearate 270 (ethyl ester of 30; n = 16, R = CH,) arepacked in the usual orthorhombic manner and are tilted at 64" towards theend-group planes. Each molecule is bent at the carboxyl group and theester groups appear to be either disordered or oscillating.Acrylic acid has a melting point 30" higher than that of the correspondingsaturated acid(propionic), but a determinat'ion of the crystal structure 271at -115" shows that this cannot be accounted for by the mode of hydrogenbonding, which is of the usual centrosymmetric dimer type with d(0-0)= 2.66 8.The carboxyl group dimensions, d(C-0) = 1-28 and 1.25 8,agree well with average values of 1.28 and 1.25 A for unsaturated dimericacids, contrasted with averages of 1.35 and 1.24 A for the two d(C-0) insaturated dimers. A preliminary account 272 of an independent structure2G4 K. Larsson, Acta Chem. &and., 1963, 17, 199.2135 K. Larsson, Acta Chew,. Scmd., 1963, 17, 215.266 T. R. Lomer, Acta Cryst., 1963, 16, 984.267 S. Abrahamsson and A. Westerdahl, Acta Cryst., 1963, 16, 404.z 6 * K. Larsson, Acta Cryst., 1963, 16, 741.269 G. A. Jeffrey and M. Sax, Acta Cryst., 1963, 16, 1196.z i O S. Aleby, Acta Cryst., 1962, 15, 1248.271 M. A. Higgs and R. L. Sass, Acta Cryst., 1963, 16, 657.$72 Y.Chatani, Y. Sakata, and I. Nitta, J. Polymer Bci., Part B, Polymer Letters,1963, 1, 419ORGANIC STRUCTURES 597determination a t -70" shows a greater discrepancy in the molecular dimen-sions than might be expected, with d(C-0) of 1-32 and 1.23 A, i.e., nearer tothe averages for saturated dimers. However, no indication is given of theaccuracy of these dimensions. I n crystals of oleic acid 273 the two parts ofthe chain adopt a cis-arrangement about the double bond, and both partsare tilted 56.5" towards the end-group planes. The planes of the twocarboxyl groups in each centrosymmetric dimer are separated by 0.35 Aand each makes an angle of 26" with the plane of its carbon chain. Thepacking of the chains is of a new orthorhornbic-parallel type.Two independent sets of three-dimensional visual data, estimated fromthe same photographs, were refined separately 274 to obtain accurate dimen-sions for the 2-amino-3-methylbenzoic acid molecule.The results did notdiffer significantly, the average differences in atomic positions other thanhydrogen being about 0.0036 8. The molecule is approximately planar,apart from two of the hydrogen atoms of the methyl group, and the dimen-sions can be interpreted in terms of resonance and hybridisation.Two further examples of short hydrogen bonds in acid salts have beenreported. In ammonium hydrogen dicinnamate d(0-0) = 2.51 0.03 Aand the carboxylate group is almost coplanar with the H-C=C-H group butthere is an angle of 17" between this plane and that of the benzene ring.275In potassium hydrogen di-p-chlorobenzoate d(0-0) = 2-457 & 0.013 A andthe carboxylate group is twisted 9" from the plane of the benzene ring.276The chlorine atom is also 0.13 A out of the plane of the ring but only packingforces can be causing these effects of non-planarity.A structure determina-tion in two projections 277 of sodium a-oxobutyrate indicates infinite doublelayers of anions due to strong Na+-O- bonding, but some unusual bondlengths indicate that a three-dimensional study is needed.A study 27* of the potassium and rubidium salts of the lactone of thenaturally occurring isocitric acid shows the configuration to be (32) with acis-arrangement of carboxyl groups. This confirms the configurationalready determined chemically for (+)-isocitric acid.Arabonic acid isshown,279 from the structures of its calcium and strontium salts, to have analmost planar zigzag carbon chain with the oxygen atoms above and belowthe plane, as in the gluconate ion. It is inferred that this is the preferredconformation for all open-chain sugars. The carboxylate group is roughlycoplanar with the a-C(0H) group.Acyclic Compounds.-Oxalyl bromide and chloride form rather differentcrystal structures : 280 the bromide is planar and intermolecular Br-0 charge-transfer interaction (see final section) links the molecule into sheets, whereasthe chloride is not quite planar, the molecules are not arranged in sheets,and there is no evidence for charge-transfer interaction.A redetermination273 S. Abrahamsson and I. Ryderstedt-Nahringbauer, A c t a Cryst., 1962, 15, 1261.2 i 4 G. M. Brown and R. E. Marsh, A c t a Cryst., 1963, 16, 191.2 i 5 $3. F. Bryan, H. H. Mills, and J. C. Speakman, J., 1963, 4350.276 H. H. Mills and J. C. Speakman, J., 1963, 4355.2 i 7 S. S. Tavale, L. 11. Pant, and A. B. Biswas, A c t a Cryst., 1963, 16, 566.278 J. P. Xlusker, A. L. Patterson, W. E. Love, and M. L. Dornbrg, Acta Cryst.,2 i 9 S. Furberg and S. Helland, A c t a Chern. Scand., 1962, 18, 2373.P. Groth and 0. Hassel, A c t a Chem. Scand., 1962, 18, 2311.1963, 18, 1102598 CRY STALL0 GRAPHYof the structure of chloral hydrate 281 shows the molecules to be of the gem-dihydroxyl type with two hydroxyl groups in staggered gauche positionsrelative to the CCI, group.Taurine, NH,*CH,*CH,*SO,H, has bond lengths in the N-C-C groupsimilar to those in the zwitterion form of amino-acids, but all the hydrogenatoms were located in the structure determination 282 and their positionsdid not correspond to the zwitterion. The compound previously assumedto have the closed-ring form, t-butylazetidine, has been proved, by a crystal-structure analysis of its hydr~chloride,~~~ to be the open-chain compound,N-propyl-t-butylamine.Ethylenediammonium chloride and tetramethylene-diammonium chloride have similar structures 284 with both molecules in theplanar trans-configuration. So it is now known that both these cations canexist in either the trans- or the gauche-configuration, whereas only thegauche-configuration has been found previously for the tetramethylenediammonium ion.Doubt has been cast 285 on a previous report of two molecular forms ofacetylcholine bromide in crystals of space-group P2,. If it is assumed thatthe crystals were twinned and have the space-group P2,/a, some reflectionspreviously not accounted for can be explained.The new space-group wouldimply identical or enantiomorphic molecules and the structure is beingredetermined. Quaternary bis( methylammonium) cations act as a blockingsubstance for ganglion nervous transmission because they resemble acetyl-c holine but cannot be hy drol ysed . Crystalline pent amet hylene bis ( trime t hyl-ammonium) di-iodide, [ (CH,),N +*(CH,) 5*N +(CH3),]21-, has fully extendedplanar chains with non-rotating methyl groups.286 Alternate layers ofcation chains and iodide ions cause each of the latter to be co-ordinated in anirregular manner by six quaternary nitrogen groups.Tri( aminoethy1)amineacts as a quadridentate ligand in many complexes and the crystal structureanalysis of its trihydrochloride 28' shows the ion to be roughly tetrahedral inshape with nitrogen atoms at the corners of a trigonal pyramid. However,it is pointed out that this ligand could more easily span the four corners ofan octahedron than form a tetrahedral complex because, in the latter, thecentral atom would be too close to the tertiary nitrogen atom unless themolecule were distorted, As a contribution to the study of the lack ofinternal rotation in a-sulphonyl carbanions, an accurate structure determina-tion 288 has been carried out for dimethylaminosulphonyldimethylamine,(CH3),N*S02*N(CH,),. The molecule departs slightly from C,, symmetrybecause each CNC plane is not quite perpendicular to the NSN plane, butthis is thought to be due to molecular packing.The barrier to internalrotation arises from the interactions between sulphur d-orbitals and nitrogenp-orbitals indicated by the molecular dimensions.181 K. Ogawa, Bull. Chem. Soc. Japan, 1963, 36, 610.282 H. H. Sutherland and D. W. Young, Acta Cryst., 1963, 16, 897.283 L. M. Trefonas and J. Couvillion, Acta Cryst., 1963, 16, 576.284 T. Ashida and S . Hirokawa, Acta Cryst., 1963, 16, 841.285 J. D. Dunitz, Acta Chem.Scand., 1963, 17, 1471.286 F. G. Canepa, Acta Cryst., 1963, 16, 145.2s7 S. E. Rasmussen and R. Grranbaek, Acta Chem. Scand., 1963, 17, 832.288 T. Jordan, H. Warren Smith, L. L. Lohr, jun., and W. N. Lipscomb, J . Amer.Chem. SOC., 1963, 85, 846ORGANIC STRUCTURES 599Irradiation of t-butyl nitrite by ultraviolet light produces k s t trans- andthen cis-dinitrosomethane, CH,NO:NOCH,. The structure of the cis-isomer has now been determined289 and compared with a previous, lessaccurate, determination of the trans-structure. The differences in themolecular dimensions between the two isomers are regarded as being prob-ably significant. Some unusual bond lengths which were noted 290 in thestructure of pentaerythritol tetranitrate, C(CH,ONO,),, have now beenfound,291 by further refinement of the same data, to be normal.The polymorphism of long-chain alcohols has been discussed 292 from astructural point of view.The p-form has vertical chains and a fairly com-pact end-group packing, but the chains pack more closely when they aretilted, as in the yl- and y,-forms found in even and odd carbon chains,respectively. The ,%form is, therefore, more stable for the lower members(up to C,, for the even series and up to C,, for the odd series) where the end-group packing is more important. Two triglycerides, tricaprin z93 andt r i l a ~ r i n , ~ ~ * have been studied in their $-forms and shown to have moleculesin a " tuning-fork " configuration, with the chains in the 1- and 3-positionspointing in the opposite direction from the chain in the %position.Aromatic and Other Homocyclic Molecules.--In the structure of m-bro-monitroben~ene,2~j planar molecules are arranged so that the bromine atomattached to C-1 of each molecule lies over the centre of the C-1-C-6 bond ofthe adjacent molecule, 3.30 A away.This suggests charge-transfer inter-action and is discussed in the last section. A studyzg6 of the monoclinicform of p-dichlorobenzene at room temperature is compared with a previouslow-temperature study of this form and with the structure of the triclinicform, stable above 30.8", in order to throw light on the mechanism of thetransformation. The anisotropic thermal motion of the atoms a t roomtemperature corresponds to rotation of the molecule in its own plane.Ifthis becomes sufficiently exaggerated it would cause the large swing requiredto transform the structure to the triclinic form. The structure of 2,5-dichloroaniline has been determined 297 by a combination of nuclear quad-rupole resonance and X-ray diffraction techniques. The molecule is planarexcept for a small deviation (0.06 A) of the nitrogen atom. The benzenering is not quite a regular hexagon, but the bond lengths agree well withsimple Huckel molecular orbital calculations. There is apparently nohydrogen-bonding and the molecular packing is probably determined byC1.-C1 interactions (3.37 A).Crystals of sulphanilic acid monohydrate 298 consist of parallel layers,3.41 A apart, of molecules in the zwitterion form.The NH,+ and SO,-groups and the water molecules are connected by hydrogen bonds, both289 G. Germain, P. Piret, and M. van Meerssche, Acta Cqst., 1963, 16, 109.2Q0 A. D. Booth and F. J. Llewellyn, J . , 1947, 837.291 J. Trotter, Acta Cryst., 1963, 16, 698.292 A. Watanabe, Bull. Chem. SOC. Japan, 1963, 36, 336.293 L. H. Jensen and A. J. Mabis, ATature, 1963, 197, 681.2 9 4 K. Larsson, Proc. Chem. Soc., 1963, 87.295 T. L. Charlton and J. Trotter, Acta Cyst., 1963, 16, 313.296 C. Panattoni, E. Frasson, and S. Bezzi, Gazzetta, 1963, 93, 813.297 T. Sakurai, 3%. Sundaralingam, and G. A. Jeffrey, Acta Cryst., 1963, 16, 364.298 A. I. M. Rae and E. N. Mash, Acta Cryst., 1962, 15, 1285600 CRYSTALLOGRAPHYwithin layers and between layers.Molecules of m-toluamide 299 have theamide group twisted 28.7" out of the plane of the ring because of sterichindrance between the ortho-hydrogen atom and the NH, group. Hydrogenbonds from NH, to CO link the molecules into dimers and then the dimersinto chains. The packing of the ions in benzenediazonium chloride 300 issuch that there are planes in which C1- ions and - (NiN) + groups occur in anapproximately square face-centred arrangement with the N-N axis per-pendicular to the square and the two nitrogens almost equidistant from theplane. This suggests that the positive charge on (NiN)+ is almost equallyshared by the two nitrogen atoms. This three-dimensional refinement con-firms that the benzene ring is no longer a regular hexagon after replacementof H by N,+.Benzenediazonium tribromide has been shown 301 to be a truediazonium salt with a Br,- anion and not the alternative possibilityArNBrONBr,. The Br3- ions lie on centres of symmetry with d(Br-Br)= 2.543 & 0.004 A, and the dimensions of the benzenediazonium ion aresimilar to those found more accurately in the structure of the chloride.with new data, of the structure of4,4'-dinitrobiphenyl shows that the approximately planar benzene ringsare twisted about the central C-C bond so that the angle between them is33". Previously, this structure was thought to provide an example ofcentrosymmetric molecules in a non-centrosymmetric space-group (Pc) butthe molecules now prove to be non-centrosymmetric. The central C-Cbond length of 1.50 A agrees with that in biphenyl itself.A preliminaryreport 303 of the structure of di-m-chlorobenzoylmethane concludes that themolecule has the resonance enol form (33) with a short, symmetric, intra-molecular hydrogen bond of length 2.47 A. The whole molecule is planarand the central C-C bond lengths correspond to 50% double-bond charactereach.A three-dimensional(32: X = COZH)The structures of three crystalline forms of naphthazarin (34) have beendetermined.304 In each case the molecules appear to be centrosymmetricand lacking in planes of symmetry perpendicular to the molecular plane. Itis therefore presumed that the intramolecular hydrogen bond is not sym-metrical and that the C=O and C-OH groups retain their identity, in spiteof the equality of the C-0 bond lengths.This seems to require further study.299 S. Orii, T. Nakamura, Y. Takaki, Y. Sasada, and M. Kakudo, Bull. Chem. SOC.Japan, 1963, 36, 788.300 C. Romming, Acta Chem. Scand., 1963, 17, 1444.301 0. Andresen and C. Romming, Acta Chem. Scand., 1962, 16, 1882.302 E. G. Boonstra, Acta Cryst., 1963, 16, 816.303 G. R. Engebretson, Diss. Abs., 1963, 23, 3645.304 C. Pascard-Billy, Bull. SOC. chim. France, 1962, 2282, 2293, 2299ORGANIC STRUCTURES 601In all three forms the molecules are stacked parallel to each other with aseparation of about 3-4 8, and the differences are mainly in the mode ofstacking. The suggestion, from infrared evidence, that there is an intra-molecular hydrogen bond in cis-acenaphthene-l,2-diol (35) has been dis-proved for the crystalline phase by an X-ray structure analy~is.~05 Thehydrogen-bonding is intermolecular, forming infinite zigzags.The carbonskeleton is planar and the C-1-C-2 bond length of 1.60 & 0.014 8 is accountedfor by ring strain and steric repulsion of the oxygen atoms. In the cor-responding quinone 306 the C-1-C-2 distance is 1.53 8. The planar molecnlesare stacked parallel to each other with a perpendicular separation of 3-37 A.Dibromoacenaphthene was thought to have the bromine atoms in positions5 and 6, where they would be rather close, but an X-ray study 307 shows thatthey are in positions 3 and 5. A preliminary report 308 of the structure of10,lO-dibromoanthrone (36 ; X = Br) shows an approximately planar ringsystem with the Br-C-Br plane approximately perpendicular to it.Theformally single bonds in the central ring are rather long, but are subject tofurther refinement. The packing of the molecules in parallel planes leavesinfinite channels in the structure. Anthrone itself 309 (36; X = H) has onlytwo molecules in each unit cell of space-group P2,/u, implying that theyshould be centrosymmetric. They cannot, in fact, be centrosymmetric, sothe molecules must be arranged fairly randomly in two orientations (0 takingthe place of HJ, and this gives rise to diffuse intermediate layer lines onb axis photographs. A similar situation arises in the case of 2-phenyl-azulene. 310 Here, attempts to refine a disordered structure of space-groupP2Ju and an ordered structure of space-group Pa both gave plausibleresults for the h0Z projection.It is not possible to decide, from the evidenceof this projection alone, which is the correct structure. This reinforces theview that structures based on incomplete data should be accepted withcaution.Certain aspects of the chemistry of 5-halogeno-2-phthalimidobenzoicacids cast doubt on the accepted structure and suggest either the cor-responding zwitterion form (37a) or the closed-ring form (37b). The struc-tures of the isomorphous bromo- and iodo-compounds have been deter-mined 311 and the ring-closure is found not to occur, but the structures are305 J. Trotter and T. C. W. Mak, Actu Cryst., 1963, 16, 1032.306 T. C. W. Mak and J. Trotter, Actu Cryst., 1963, 16, 811.307 R. L.Avoyan and Yu. T. Struchkov, Zhur. strukt. Khim., 1962, 3, 605.308 J. Silverman and N. F. Yannoni, Nature, 1963, 200, 64.309 S. N. Srivastava, 2. Krist., 1962, 117, 386.310 J. Donohue and B. D. Sharma, Nature, 1963, 198, 878.311 R. M. Mayer and M. R. A. Pratt, Acta Cryst., 1963, 16, 1086602 CRYSTALLOGRAPHYconsistent with the zwitterion form (37a). The two planar ring systems aretwisted about the C-N bond through 88” relative to each other. Anunexpected water molecule (for each acid molecule) was found on the electrondensity maps.n( 3 7 4 0The structures of phenanthrene 312 and triphenylene 313 have beenrefined with three-dimensional data. In both cases there are slight devia-tions from planarity, probably owing to intramolecular overcrowding, andthe bond lengths agree well, apart from two exceptions in phenanthrene, withthose predicted by valence-bond and molecular-orbital methods.Benzo[c]-phenanthrene and 1,12-dimethylbenzo[c]phenanthrene both have over-crowded m o l e ~ u l e s . ~ ~ ~ ~ 315 The strain is relieved by distortion from plan-arity and also, in the case of the dimethyl compound, by an increase in theangle which each C-Me bond makes with the “internal” side of the ringto which it is joined. The molecular deformations confirm a theoreticalpotential function but improvements are suggested. The near equality ofthe bond lengths in the two molecules and their agreement with theoreticalbond orders demonstrate that overcrowding has little effect on bond lengths.Part of the interest in the structures of the Ei-methyl- and the 2’-methyl-benz[a]anthraquinones, (as 38),316~ 317 is that the parent hydrocarbon in the2’former case is an active carcinogen but in the latter case it is not.Thedifferences in bond lengths are found mainly in the formally single bonds ofthe quinone ring but also in the C-C bond between this ring and the l-posi-tion. Overcrowding again causes deviations from planarity of up to about0-18 8, which take the form of a slight twist of each molecule to separatethe adjacent oxygen atom and benzene ring. Another structure of bio-logical interest is that of the estrogen, 5,6,11,12,4b,lOb-hexahydr0-2,8-dihydroxychrysene (39) .318 The molecule is centrosymmetric and the bondwhich is common to both the benzene nucleus and the reduced ring in each313 J.Trotter, Acta Cryst., 1963, 16, 605.313 F. R. A b e d and J. Trotter, Acta Cryst., 1963, 16, 503.314 F. L. Hirschfeld, S. Sandler, and G. M. J. Schmidt, J., 1963, 2108.315 F. L. Hirschfeld, J., 1963, 2126.316 R. P. Ferrier and J. Iball, Acta Cryst., 1963, 16, 269.317 R. P. Ferrier and J. Iball, Acta Cryst., 1963, 16, 513.318 M. Ehrenberg, Acta Cryst., 1963, 16, 215ORGANIC STRUCTURES 603half of the molecule is remarkably short (1.34 A). It forms one side of the"seat " of the chair form of the reduced ring. The rest of each benzenering is planar, together with the attached OH group.The strain in the dioleh of [2,2]paracyclophane (40) 319 is relieved bybending the aromatic rings about 14" at each end into a boat form and bybending the a-carbon atoms a further 15".The exocyclic C-C bonds arerather long (1.51 A), and this is attributed partly to the orthogonality of then-electron systems of the rings and the olefinic bonds and partly to theintramolecular strain.Preliminary results are reported 320 for the structure of the cyclic trimerof butadiene, cyclododeca-tr~ns-l-trans-5-trans-9-triene (41). The moleculeadopts the form of highest symmetry, D,, with planar -C-W-C- groups,gauche CH,-CH, groups, and 120" rotation between each CW, and its adjacentCH group. This conformation differs from that of the correspondingcrystalline high polymer.' C mc4 iIH ' c k E / c - HH2C - CH2/ \HC CH//\CH HCEach molecule in the metastable, monoclinic form of 9-phenyl-9-arsa-fluorene (42) has been shown 321 to have a planar arsafluorene group withd(As-C) = 1-98 A and ,/(C-As-C) = 88", and the pyramidal arrangementround the arsenic atom is completed by a bond to the phenyl nucleus oflength 2-02 making an angle of 98" with each of the other two As-C bonds.The molecule has a plane of symmetry passing through the arsenic atom andthe phenyl nucleus, and it is suggested that the orientation of the phenylnucleus necessary to produce this is maintained by p>,-dn bonding with thearsenic atom.The carbon ring in the polyoxocroconate ion C,O,,- is a regular penta-g0n,322 but that of the hydrogen croconate ion does not even possess a planeof symmetry coincident with the C-OH: bond.This is probably becauseonly one of the two C-0 groups adjacent to the C-OH group is involvedin the strong hydrogen-bonding of ions into chains, with d ( 0 - 0 ) = 2.48 A.Molecules of cyclohexane-1,4-dione have a twisted boat form 323 with anangle of about 152" between the two C=O bonds. The twist results inmore acceptable distances between neighbouring hydrogen atoms but it isnot clear why this form is more favourable than the centrosymmetric chairform. By contrast, the hexahydroxycyclohexane, myo-inositol, has the31D C. L. Coulter and K. N. Trueblood, Acta Cryst., 1963, 16, 667.320 G. Allegra and I. W. Bassi, Atti Accad. naz. Lincei, Rend. Clusse Sci. $s. mat-321 D. Sartain and M. R. Truter, J., 1963, 4414.322 N.C. Baenziger, J. J. Hegenbarth, and D. G. Williams, J . Amer. Chem. Xoc.,s2s P. Groth and 0. Hassel, Proc. Chem. Xoc., 1963, 218.nat., 1962, 33, 72.1963, 85, 1539604 CRYSTALLOGRAPHYchair form in the crystal structure of its dih~drate.~,* One hydroxyl groupis axial and the other five are equatorial. All the hydrogen atoms attachedto oxygen atoms are involved in hydrogen bonding which links the organicmolecules into chains and then links the chains sideways, partly throughwater molecules which are themselves hydrogen- bonded to form dimers.The cyclo-octane ring in 9,9-dirnethyl-9-azoniabicyclo[6,1 ,O]nonane iodide 325(43) has a conformation intermediate between a boat and a chair form becauseof the dissymmetry of the two CH, groups opposite the three-memberedring.However, a disordered arrangement of the two enantiomorphs causesthe structure as a whole to have a plane of symmetry which passes betweenthese CH, groups and is coincident with the NMe, group and perpendicularto the three-membered ring.C H 2- C,H 2 HO, ,Me -H2C' 1 CH2 ,c = c, N=N, q - y - y- +c-c,co H2C, CH2 H2C, o, c+o HN, HN\ ? C,H+ H HC'N:+ I' (43)' M k "Me(44) (4 5)Heterocyclic Compounds.-A preliminary report 326 of the crystalstructure of imidazole describes how the molecules are hydrogen-bonded byNH-N bonds of length 2.7 A to form chains in which adjacent molecules aretwisted 64" relative to each other. The formation of these chains explainsthe fibrous appearance of the crystals. Approximate bond lengths (fromtwo projections) 327 indicate that there is resonance in the molecule ofcc-methyltetronic acid (44) across the conjugated double bond systemHO-C=C-C=O with structures which include those involving H-0 +=.Tetrazole (45) is a weak organic acid which contains no oxygen and owesits acidic character to resonance stabilisation of the tetrazolate ion.Anaccurate X-ray analysis 3,* of the structure of sodium tetrazolate mono-hydrate has been carried out to determine the contributions to the resonanceform of the molecule. It also shows that the anions are linked into chainsby N...HOH...N hydrogen bonds and that these chains form layers with sodiumions between the layers. Resonance in the meso-ionic compound N-p-bromophenylsydnone (46) has been investigated in another accurate structurectetermination.329 The two planar rings are twisted 27.6" relative to eachother.The 0-Br and possible CH-0 interactions which link the moleculestogether are discussed in the final section. The crystal structure of rho-danine (47) 330 consists of planar molecules forming centrosymmetric dimersby N-H-*O hydrogen bonding. It is predicted that the silver rhodaninecomplex might be bimolecular with two linear N-Ag-S bonds. An inter-molecular S.-S distance of 3.47 provides further evidence that the van der324 T. R. Lomer, A. Miller, and C. A. Beevers, Acta Cryst., 1963, 16, 264.325 L. M. Trefonas and R. Majeste, Tetrahedron, 1963, 19, 929.32t3 G. Will, Nature, 1963, 198, 575.32's. G.G. MacDonald and A. B. Alleyne, Acta Cryst., 1963, 16, 520.328 G. J. Palenik, Acta Cryst., 1963, 16, 596.329 H. Biirnig-Hausen, F. Jellinek, J. Munnik, and A. Vos, Acta Cryst., 1963,16, 471.330 D. von der Helm, H. E. Lessor, and L. L. Merritt, Acta Cryst., 1962, 15, 1227ORGANIC STRUCTURES 605Wads radius of sulphur is less than Pauling’s value of 1.85 A. Xanthanehydride (48) is found 331 to have both its hydrogen atoms attached t o thenon-ring nitrogen atoms and the planar molecules exhibit effects of resonancemainly in the H,N-C=N-C=S part of the ring. Hydrogen bonds NH*.*Nand NH--S, of lengths 2.98 and 3.35 A, link the molecules together in thecrystal.Two structures of metal porphyrin derivatives have been reported, viz.,nickel etioporphyrin-I 332 and copper tetraphenylporphyrin 333 and bothindicate non-planar molecules.In the nickel compound alternate pyrrolerings are bent up and down from the mean plane and in the copper com-pound the phenyl groups are twisted approximately normal to the por-phyrin mean plane. They are also bent alternately up and down and thepyrrole groups become twisted, presumably to minimise the distortion ofbond angles a t each atom.The structure of crystalline trioxan has been studied 334 as an aid to theunderstanding of its polymerisation in the solid phase. The 1,4-dioxan ringhas the chair form in both its tram-Zy5-dichloro- 335 and cis-2,3-dichloro-derivatives.336 In the former compound both chlorine atoms are in axialAgain intermolecular S.*S distances are about 3.4 8.,CH2 - CH2Me H5OZC/ N , ysoH2N’ ( 4 9 ) (50) (5‘)HC-N, H2N, ,,N-N\H0 $=CHH< ,CH $-c, ,c=o H2C: I I :NHH2C-C\C=0 0Me H/NHC ‘C’*IIHC11 IRC, ,NH HC, +A(52) 5 $ (53)0 N H2positions, but, in the latter, one is axial and one is equatorial with a shorterC-C1 bond than the axial C-Cl bonds in either compound.The bond froman oxygen atom to the carbon atom bearing the axial chlorine atom is alsoshort in each compound. Each single crystal of the cis-compound containseither right-handed or left-handed molecules but solutions of the compoundare optically inactive because of the interchange of axial and equatorialpositions.The structure determination of dihydro-N-propylnicotinamide 337 proves331 R.H. Stanford, Acta Cryst., 1963, 16, 1157.332 E. B. Fleischer, J . Amer. Chem. Soc., 1963, 85, 146.333 E. B. Fleischer, J. Amer. Chem. SOC., 1963, 85, 1353.334 V. Busetti, G. Carazzolo, and M. Mammi, Guzzetta, 1962, 92, 1362.335 C. Altona, C. Knobler, and C. Romers, Acta Cryst., 1963, 16, 1217.336 C. Altona and C. Romers, Acta Cryst., 1963, 16, 1225.337 H. Koyama, 2. Krist., 1963, 118, 51606 CRYSTALLOGRAPHYthat it has the 1,4-dihydro-structure (49), in which the ring is planar butthe amide group is twisted 22" out of the plane. HN-0 hydrogen bondslink the molecules to form dimers and join the dimers into infinite lattices.A further refinement 338 of the structure of 6-amido-2,3-dihydro-3-oxopyri-dazine, using the original data, indicates clearly that the molecule has theketo-form (50).The ring is planar but the amido-group and the oxygenatom deviate slightly from the plane.The structures of a number of pyrimidines have been reported. Wherethe molecules have keto-forms, as in barbituric acid (51) 339 and potassiumviolurate dihydrate (51; with CH, replaced by C=N-OK),340 the rings arenon-planar but where there are formal double bonds in the ring, they seemto impose approximate planarity. Thus, in N-methyluracil341(52 ; R = H),which by its N-substitution is a simple analogue of a nucleotide, there areplanar molecules hydrogen-bonded in pairs in a similar manner to the linkingof adenine and thymine in DNA. The molecular dimensions comparefavourably with Spencer's " most probable " dimensions.342 1-Methyl-thymine (52; R = Me) 343 is almost planar and again hydrogen-bonded intodimers by NH-.O bonds of length 24330 8.Changes in the bond lengthsfrom those of thymine can be explained in terms of decreased contributionst o the resonance form by structures involving double bonds in the ring toN-1. Cytosine 344 (53) is almost planar in crystals of its monohydrate, andthe main differences in dimensions from those predicted by Spencer's modelare the C-C-C bonds of 1.432 and 1.348 A (predicted 1.40 and 1.40A).Anhydrous crystals of dilituric acid (5-nitrobarbituric acid) do not exist inthe trioxo-form (cf. 51) but in the 5-nitro-2,6-dioxo-4-hydroxy-form.346 Inspite of this, the NH-CO-NH part of the molecule is very similar in dimen-sions to barbituric acid, but the molecule is planar.The C-NO, bond isshort (1.406 A) and there is an intramolecular OH-.O,N hydrogen bond aswell as the intermolecular NH-OC hydrogen bonds which link the moleculesinto dimers and connect the diwers spirally.The purine ring system is planar in both guanine hydrochloride di-hydrate 346 and 1,3,7,9-tetramethyluic a~id,~4' but in the latter case, wherethe basic nitrogen atoms are fully substituted, the methyl groups deviateslightly from the plane. In this case, the bond lengths in the five-memberedring differ slightly from those found in purines without methyl and oxygensubstituents. The guanine dimensions, while indicating significant reson-ance contributions from structures other than the normal formula, neverthe-less agree well with Spencer's model.A two-dimensional crystal-structure determination of phenazine 5,lO-338 P.Cucka, Acta Cryst., 1963, 16, 318.33s W. Bolton, Acta Cryst., 1963, 16, 166.340 H. Gillier, Cornpt. rend., 1963, 257, 427.341 13. W. Green, F. S. Mathews, and A. Rich, J. Biol. Chem., 1962, 237,342 M. Spencer, Acta Cryst., 1959, 12, 59.343 K. Hoogsteen, Acta Cryst., 1963, 18, 28.344 G. A. Jeffrey and Y. Kinoshita, Acta Cryst., 1963, 16, 20.345 W. Bolton, Acta Cryst., 1963, 18, 950.346 J. Iball and H. R. Wilson, Nature, 1963, 198, 1194.347 D. J . Sutor, Acta Cryst., 1963, 16, 97.3573ORGANIC STRUCTURES 607dioxide 348sho~s moleculesof normal dimensions, except for d(N-0) = 1.33 A,which indicates some double-bond character.The molecules pack plane-to-plane like phenazine itself, with a separation of 3 . 5 k Two polymor-phic forms of 9,9'-bixanthenylidene (54), the blue-green cc- and the yellow$-form, are both shown 3*9 to contain molecules in the same '' doubly bent "conformation, Le., with each of the two centrosymmetrically related hetero-cyclic rings bent into a boat form. In spite of this, the distance between theclose non-bonded carbon atoms is only increased to 3-0 A in each case. Thecentral bond is longer than expected with a mean d(C-C) = 1.385 A. Thedifferences in colour are believed to be due to the differences in molecularpacking but there are similarities even here, and there are no short contacts.The explosive, HMX (octahydro-l,3,5,7-tetranitro- 1,3,5,7-tetrazocine) (55),has also been studied in two polymorphic forms (a and j3).350 Again, themolecules are very similar in the two forms, having a basket shape with allfour planar N-NO, groups tilted up out of the plane of the four carbon atoms.Natural Products and Related Compounds.-The crystal structure of,&D-glucose 351 shows the molecule to have a pyranose ring in the chairform with all the substituents in equatorial positions. The C-1-OH bondis short (1.404 A) as in a-D-glucose, but the C-6-OH bond, which is alsoshort in a-D-glucose, does not differ significantly from the mean C-OH bondlength.The same conformation, with all the substituents equatorial, isfound in the isomorphous dihydrated potassium and rubidium salts ofp-D-glucuronic acid 352 and in the thioglucoside, sinigrin 353 (56), in whichthere is a syn-configuration, between the sulphate group and the thioglucosering, about the C:N bond.The non-isomorphous hydrobromide 354 and hydrochloride 355 of (-&I-prodine both have the molecule in the configuration (57) in whichPh = phenyl, Pr = propionoxy.These two groups are equatorial and axialrespectively, as in the a-isomer, but the methyl group on C-3 is axial instead348 Y. Namba, T. Oda, and T. Watanabe, Bull. Chem. Soc. Japan, 1963, 36, 79.349 J. F. D. Mills and S. C. Nyburg, J., 1963, 308.350 H. H. Cady, A. C. Larson, and D. T. Cromer, Ada Cryst., 1963, 16, 617.351 W. G. Ferrier, Acta Cryst., 1963, 16, 1023.352 G. E. Gum, Acta Cryst., 1963, 16, 690.353 J. Waser and W.H. Watson, Nature, 1963, 198, 1297.364 F. R. Ahmed, W. H. Barnes, and L. di Marc0 Masironi, Acta Cryst., 1963,16,237.355 F. R. Ahmed and W. H. Barnes, Aeta Cryst., 1963, 18, 1249608 CRYSTALLOGRAPHYof equatorial, and is cis to the phenyl ring. A new direct phase-determina-tion procedure was used in the structure analysis 356 of the hemihydrate ofthe synthetic polypeptide, cyclo(hexaglycy1). The molecules are in theform of 18-membered rings which adopt four different codgurations in theunit cell. All the peptide groups are planar with dihedral angles betweenadjacent groups ranging from 90" to 116". Form I of poly(L-proline) has aright-handed helical containing ten residues in three turns, andwith the peptide bonds in the usual cis-configuration. The synthetic poly-nucleotide poly(cytidy1ic acid) is found 358 to form a two-strand helix withthe bases in the centre tightly hydrogen-bonded. It is suggested that,besides the usual pair of N-H-0 bonds, there is a central +N-H-.N bondfrom a protonated to an unprotonated base.The adenine ring system in thestructure of adenosine-5' phosphate 359 is found to be almost planar, andessentially the same as in the adenine hydrochloride structure. The N -glycosidic bond is bent about 8" out of the plane, and the adenine and ribosegroups adopt an anti-orientation about this bond, as is common in pyrami-dine nucleosides and nucleotides.The full account has now appeared 360 of the structure of casimidine, afragment of casimiroedine, the essential features of which have already beenrep0rted.36~ The stereochemistry found 362 in the structure of ( -)-cocainehydrochloride agrees with that deduced from chemical evidence.Thepiperidine ring of the tropone nucleus has the chair form, with the benzoyland carbomethoxyl side-chains equatorial and axial, respectively, so thatthey are cis to each other and to the nitrogen atom. The structures of boththe bromohydrin 363 and the bromo-dilactone 364 of jacobine have beendetermined. The absolute configuration of the bromohydrin (58) wasestablished by use of the anomalous dispersion of Cu K,-radiation by thebromine atoms, and, although the structure was not fully refined, thedimensions reported are thought to have a maximum error of 0.08 sinceH I nthey are averaged from two independent molecules in the asymmetric unit.A molecule of ethyl alcohol of crystallisation is hydrogen-bonded to thenitrogen atom of one of the molecules.A related structure is that ofthelopogine methiodide (59) which contains a very similar pyrrolizidine ring356 I. L. Karle and J. Karle, Acta Cryst., 1963, 16, 969.3 5 7 W. Traub and U. Shmueli, Nature, 1963, 198, 1165.35*R. Langridge and A. Rich, Nature, 1963, 198, 725.359 J. Kraut and L. H. Jensen, Acta Cryst., 1963, 16, 79.360 S. Raman, J. Reddy, and W. N. Lipscomb, Acta Cryst., 1963, 16, 364.361 Ann. Reports, 1962, 59, 512.362E. J. Gabe and W. H. Barnes, Acta Cryst., 1963, 16, 796.s63 J. Fridrichsons, A. McL. Mathieson, and D.J. Sutor, Acta Cryst., 1963, 16, 1075.364 A. McL. Mathieson and J. C. Taylor, Acta Cryst., 1963, 16, 524ORGANIC STRUCTURES 609system.365 The relative and absolute configurations of dihydro-p-erythro-idine hydrobromide have been determined 3669 367 and are represented by(60). Some short intermolecular distances in this structure are mentionedin a later section.Macusine-A iodide (61) 368 and akuammidine methiodide 369 have beenfound to differ only by interchange of the positions of the ester and carbinolgroups. In the akuammidine methiodide structure the ester group adopts,in a disordered manner, two orientations related to each other by approxim-ately 180" rotation about the C-C bond. In each compound the absolutestereochemistry has been defined chemically.Two unusual alkaloid struc-tures are reported. That of echitamine iodide 370 contains in its pentacyclicstructure two five-membered rings fused, along a common bond, to a boat-shaped substituted cyclohexane ring, and that of ( +)-hetisine hydrobrom-ide 371 provides the first example of an unusual heptacyclic structure anddiffers, mainly in the positions of its OH groups, from previous structuressuggested on chemical grounds.Confirmation of structures deduced from previous chemical and X-raywork has been obtained for the two sesquiterpene derivatives, (&)-cadinenedihydrochloride 372 and caryophyllene chlorohydrin.373 The recently deter-mined configurations of rosololactone and cascarillin are amongst thoseillustrated in a general account of the X-ray analysis of natural products.374nThe constitution and stereochemistry (except for the absolute configuration)have been established for the heartwood extractive ~ e d r e l o n e , ~ ~ ~ by theX-ray analysis of its iodoacetate.Ring c (62) is locked in a boat con-formation by the p-epoxide group, and ring A adopts a half-boat conforma-tion, probably because of steric interaction between its methyl groups andthe OH or iodoacetate group on ring B. There is also steric repulsionbetween the two axial methyl groups because they are only separatedby 3.04 8.365 J. Fridrichsons and A. McL. Mathieson, Actu Cryst., 1963, 16, 206.366 A. W. Hanson, Proc. Chem. SOC., 1963, 52.367 A. W. Hanson, Actu Cryst., 1963, 16, 939.368 A.T. McPhail, J. M. Robertson, and G. A. Sim, J., 1963, 1832.369 6. Silvers and A. Tulinsky, Actu Cryst., 1963, 16, 579.370H. Manohar and S. Ramaseshan, 2. Krist., 1962, 11'7, 273.371 M. Przybylska, Actu Cryst., 1963, 16, 871.373 N. V. Mani, 2. Krist., 1963, 118, 103.373 D. Rogers and Mazhar-ul-Haque, Proc. Chem. SOC., 1963, 371.374 J. M. Robertson, Proc. Chem. Soc., 1963, 229.375 I. J. %rant, J. A. Hamilton, T. A. Hamor, J. M. Robertson, and G. A. Sim,J., 1963, 2506.610 CRYSTALLOGRAPHYA structure determination of bromo-oestrone 376 (63) confirms that thebromine atom is attached at the 4-position and shows that the methyl groupa t position 18 has an axial conformation. Calculation of the " best " planesfor the atoms shows that ring A is planar, B and c have the chair form, andD exhibits an envelope effect. Similar conformations are found when suchcalculations are performed for cholesteryl iodide.377 The stereochemistryof calciferol has been established 378 by the determination of the structureof the 4-iodo-5-nitrobenzoate (64) and, although the arrangement is oppositeto that proposed originally,379 it is the same as that given in a more recentnote 380 and in other stereochemical studies. Rings c and D are trans-fusedand the two atoms a t their junction are on opposite sides of the plane of theother three atoms of ring D. Rings A and c both have the chair form,and the conjugated diene system, though approximately planar, is betterregarded as two planar halves at 9" to each other.The cis-diene system isnon-planar and the ester and nitro-groups are twisted at angles of 12" and60°, respectively, to the plane of the benzene ring.The structure and configuration of the hormone, prostaglandin F, (65),have been elucidated by the direct crystal structure determination 3 ~ 1 ofthe tri-p-bromobenzoate of its methyl ester. It is a trihydroxy-acid withtwo side-chains attached to a 5-membered ring, one containing a trans-double bond and the other being saturated and terminating in the carboxylgroup. Phenoxymethylpenicillin is found 382 to have a similar conformationfor the thiazolidine-p-lactam nucleus to that in benzylpenicillin salts, butthe benzene rings in the two molecules have very different orientations. Aclose contact of 2.58 A between the side-chain amide nitrogen atom and theoxygen atom of the phenoxymethyl group indicates a non-linear intra-molecular hydrogen bond which may explain the extra stability of thismolecule.The stereochemistry of griseofulvin (66) has been confirmed bythe X-ray analysis of its 5-bromo-derivative; 383 that of gibberellic acid (67)376 D. A. Norton, G. Kartha, and Chia Tang Lu, Acta Cryst., 1963, 16, 89.3 7 7 D. A. Norton and J. M. Ohrt, Nature, 1963, 197, 450.378 D. C. Hodgkin, B. M. Rimmer, J. D. Dunitz, and K. N. Trueblood, J., 1963,4945.379 D. C. Crowfoot and J. D. Dunitz, Nature, 1948, 162, 608.380 D. C. Crowfoot, M. Webster, and J. D. Dunitz, Chem. and Ind., 1957, 1148.381 S. Abrahamsson, Acta Cryst., 1963, 16, 409.382 S.Abrahamsson, D. C. Hodgkin, and E. N. Maslen, Biochem. J., 1963, 86, 514.383 W. A. C. Brown and G. A. Sim, J., 1963, 1050ORGANIC STRUCTURES 61 1has been established by the structure determination 384 of the di-p-bromo-benzoate of its methyl ester, the absolute configuration being determinedchemically. The The lactone ring is trans to the two-carbon bridge.OH! ( 6 9 )structure of byssochlamic acid, determined as the bis-p-bromophenyl-hydrazide (68),385 shows a close biogenetic relationship to glauconic andglaucanic acids. The stereochemistry of aureomycin 386 is that indicatedby (69). There is an unexpected eclipsed conformation about theC4-C4a bond.Preliminary reports have appeared of the structures of two plant pig-ments, morellin 387 and har~nganin,~88 the latter indicating the unusualgem-di-isopentenyl substitution.In the structure of the triclinic modification of vitamin A acid,389 theall-trans conjugated side-chain is approximately planar and markedlycurved because of the methyl group repulsions.The ring has a chair form,and the conformation about the bond joining the ring to the rest of the side-chain is opposite to that in trans-/3-ionylidine y-crotonic acid where thedouble bond of the ring continues, roughly in the same plane, the zigzag ofthe side-chain.Molecular Complexes and Molecular Interactions.-The interest inattractive forces between molecules has developed considerably in recentyears so this section not only describes examples of specific complex forma-tion, but also draws attention to unusual interactions discovered in crystalstructures.Hydrogen bonding of the more conventional type has generallybeen referred to in the previous sections.A full and detailed account 390 of the r81e of water molecules in hydratedorganic crystals confirms the view that there is a strong tendency for struc-tures containing hydrogen atoms attached to oxygen or nitrogen to be so3 8 4 J. A. Hartruck and W. N. Lipscomb, J . Amer. Chem. SOC., 1963, 85, 3414.385 I. C. Paul, G. A. Sim, T. A. Hamor, and J. M. Robertson, J., 1963, 5502.386 J. D. Dunitz, J. Donohue, K. N. Trueblood, and M. S. Webster, J . Amer. Chew.387 G. Kartha, G. N. Ramachandran, H. B. Bhat, P. Madhavan, Y . K. V. Raghavan,388 R. A. Alden, Diss.Abs., 1963, 24, 67.38g C. H. Stam and C. H. MacGillawy, Acta Cryst., 1963, 16, 62.390 J. R. Clark, Rev. Pure Appl. Chem., 1963, 13, 60.SOC., 1963, 85, 851.and K. Venkataraman, Tetrahedron Letters, 1963, 459612 CRYSTALLOGRAPHYarranged that these hydrogen atoms are fully utilised in hydrogen bonding.The review also draws attention to the tendency for halogen atoms, andespecially halide ions, to be chosen as hydrogen-bond receptors in preferenceto nitrogen atoms in structures where a choice is possible, thus indicatingthat halide anions are more electronegative than nitrogen in organic mole-cules. Another interesting point which emerges is that, although watermolecules are usually hydrogen-bonded in a roughly tetrahedral manner,about a quarter of the cases studied have an approximately planar three-fold arrangement.The formation of the complex NaCl, urea, H20 391 explains the modi-fication of the crystal habit of sodium chloride grown from aqueous solutionscontaining urea and the modification of the habit of urea by sodium chloride.The ions and molecules are linked by hydrogen bonds and electrostaticforces.The complex of urea with ammonium bromide 392 is held togetherby NH,+-O=C hydrogen bonds of lengths 2.76 and 2-91 8, and by electro-static forces (or possibly NH-Br- hydrogen bonds) between nitrogen atomsof urea and bromide ions at distances of 3-46-3453 8. There are furtherelectrostatic interactions between ammonium and bromide ions. A 1 : 1complex formed by cooling solutions of D-glUCOSe and urea is found 393 tohave the glucose in the a-D-pyranose form, irrespective of whether cc- orP-D-glUCOSe is used as the starting material.A complex between l-methyl-thymine and 9-methyladenine is found 394 to be hydrogen-bonded in amanner different from that proposed for the hydrogen-bonding of thymineand adenine in DNA. The bonds are from NH, of 9-methyladenine toO=C4 of l-methylthymine, with d(N-.O) = 24346 8, and from HN-3 ofl-methylthymine to N-7 of 9-methyladenine, with d(N-N) = 2.924 8,instead of to N-1 as in DNA. It would be possible for the same form ofhydrogen bonding to occur in DNA as is found in this complex but, if so,the cytosine-guanine pair would have to be in a zwitterion form to obtaina unit of similar size.The other interesting feature of the complex is thatthe perpendicular separation between parallel layers of molecules is only3.276 8, causing the shortest intermolecular C-C distance to be 3-285 8.A re-evaluation 3g5 of the hydrogen-bonding possibilities in (+)-de-methanoaconinone hydroiodide trihydrate suggests that a proton remainsattached to the iodine atom and forms hydrogen bonds to an oxygen atomwith d(1-0) = 3.52 A. The importance of hydrogen bonds from watermolecules to halogen atoms in this and other halogeno-alkaloid hydratestructures is also emphasised. The O-He-I- type of hydrogen bond withthe shortest d(O-I-) = 3.43 8, is also found in the structure of macusine-Aiodide.368 Pairs of strong hydrogen bonds of the NH+-O type with lengths2.794 and 2.771 A are reported 396 in the structure of 8-methylthiouroniump-chlorobenzoate, and it is suggested that this formation of coplanaramidinium carboxylate bridges might be important in many structures of3~31 J.H. Palm and C. H. MacGillavry, Acta Cryst., 1963, 16, 963.392 C. G. C. Catesby, Acta Cryst., 1963, 16, 392.393 H. H. Hatt and A. C. K. Triffett, J . , 1963, 2079.394 K. Hoogsteen, Acta Cryst., 1963, 16, 907.395 J. R. Clark, Acta Cryst., 1963, 16, 702.396 0. Kennard and J. Walker, J., 1963, 5513ORGANIC STRUCTURES 613biological interest. As an extension to the series of studies on short hydrogenbonds in acid salts, an example has now been confirmed of a short hydrogenbond in a basic salt, 2-picoline l-oxide hemihydrobromide. An X-raystudy 397 indicates the presence in the crystal structure of symmetricalunits C6H7*N0...H...0NoC6H7. The cytosine monohydrate structure 344 pro-vides a further example of planar three-fold hydrogen bonding of watermolecules and also an unusual formation of three hydrogen bonds to theoxygen atom of a C=O group. It is suggested that this may be the reasonwhy the C=O bond is slightly longer (1.260 A) than average, but in adenosine-5’ phosphate,359 where a similar situation occurs a t a phosphate oxygenatom, the P-0 bond is shorter (1-495 8) than another in the same group,d(P-0) = 1.514& where the oxygen accepts only two hydrogen bonds.Following an earlier note 398 on the possibility of explaining certain shortCH-0 distances in crystals as hydrogen bonds, a fuller account by thesame author 399 has presented further evidence for the existence of suchbonds. The angular requirements for hydrogen bonding are fulfUed for CHgroups and probably also for CH, and CH, groups showing similar closeapproaches to oxygen atoms of about 3.1 8, but it is interesting that there isno tendency for CH, and CH, groups to form more than one hydrogenbond. Several further examples of short CH-0 contacts varying from 3.0to about 3.3 A have been reported 289, 302, S29, 33% 343, 3479 367 during theyear under review but they have not all been interpreted as hydrogen bondsby the authors. Strong interaction between CH and C1- in benzenediazon-ium chloride, with d(H-Cl-) = 2.5 A, has been reported.300The crystal structure of the complex 2MeOH,Br, 40° provides a furtherexample of the 0-0 type of charge-transfer complex formed by interactionbetween oxygen or nitrogen atoms as donors and halogen molecules asacceptors. Chains of hydrogen-bonded methanol molecules with d( 0-0)= 2.61 8 are cross-linked by nearly linear O.-Br-Br-O bridges, with amean d(O-Br) of 2.80 A and d(Br-Br) = 2-28 8, resulting in a tetrahedralarrangement of all the bonds round each oxygen atom.Similar charge-transfer interactions have been found to be significantin the structures of certain single substances. In oxalyl bromide 280 thesecharge-transfer forces completely determine the crystal structure by linkingthe molecules into sheets, with Br-0 distances of 3-27 8. Oxalyl chloridehas a different arrangement of molecules in the unit cell and there is noevidence of charge-transfer interaction. In the structure of N-p-bromo-phenylsydnone 329 Br-0 charge-transfer bonds of length 3-16 8 link themolecules into chains. Similar interactions occur between Br and positively-charged nitrogen atoms at distances of about 3.3 A and between Br and theplane of the benzene ring at a distance of 3-68 in the structure of benzene-diazonium tribromide. 301 Interactions between bromine atoms and benzenerings in crystals of m-bromonitrobenzene, 295 and ascribed to charge-transfereffects, result in two Br-C contacts of 3-35 and 3-40A.397 H. H. Mills and J. C. Speakman, Proc. Chem. SOC., 1963, 216.398 D. J. Sutor, Nature, 1962, 195, 68.399 D. J. Sutor, J . , 1963, 1105.400 P. Groth and 0. Hassell, MoZ. Phys., 1963, 6, 543614 CRYSTALLOGRAPHYThe 1 : 1 complex between perylene and fluoranil (tetra.fluoro-p-benzo-quinone) 401 exhibits charge-transfer interaction of the n-z type. Thefluoranil molecules are planar and those of perylene are nearly so. Theyform layers which contain equal numbers of molecules of each type, soarranged that fluoranil and perylene molecules overlap and are, therefore,stacked in columns parallel to the c-axis of the crystal. The slightly differentangles (21.9" and 20.1") between the planes of the molecules and the c-axisindicate that the perylene molecules are attracted by the carbon atoms ofthe fluoranil molecules but not by the fluorine atoms.A type of interaction which has been found recently, and which may berelated to charge-transfer effects, is that resulting in close contacts betweenthe oxygen of one C=O group and the carbon atom of a similar group on anadjacent molecule. Special attention was first drawn to this type of inter-action in the report of the crystal structure of chloranil 402 where d(0-C)is 2.85 8. Further examples have now been reported in the crystal struc-tures of barbituric 339 and dilituric 345 acids where d(0-C) has the values2-90 and 2-99 hi respectively. In each case, the two C=O groups involvedare approximately at 90" to each other. In two further cases of short inter-molecular 0 4 distances, 3.14 and 3-22 A in cis-2,3-dichlor0-1,4-dioxan,~~~and 3.09 hi in dihydro-p-erythroidie hydrobromide,367 the oxygen atomsinvolved are not those of C=O groups, and it is possible that these distancesrepresent van der Waals contacts somewhat reduced by less specific polareffects.401 A. W. Hanson, Acta Cryst., 1963, 16, 1147.402 S. S. C. Chu, G. A. Jeffrey, and T. Sakurai, Acta Cryst., 1962, 15, 661

ISSN:0365-6217    

DOI:10.1039/AR9636000567

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

ERRATAVOL. 58, 1981.Page 201, line 27. For naphthylamine read naphthalene.Page 207, line 19. Insert after (14; R = R’ = H), the ketone(13’) with. [Formula (13’) has a double bond between thering-carbon carrying R‘ and the adjacent valley position of(131.1Page 209, formula 17.Page 282, line 7.Add Me0 group in the 4’-position,For dihydrobenzofuran, read hydroxybenzyl-coumarone.VOL. 59, 1962.Page 76, equation (1) shouZd read d2 = A,U/V.Page 78, ref. 24. For in the press, read 916.Page 93, ref. 119. For in the press, read 1963, 198, 683.Page 97, ref. 169. For Canad. J . Chem., 1963, in the press, readJ . Phys. Chem., 1963, 67, 858.Page 298, formula (185). The dotted line to the OR should bereplaced by a heavy one.Page 298, Zmt Eine should read: Their stereochemistry has been thesubject of two publications,l619 162 the expression (185) 161being the more complete assignment.Page 300, line 6. For position 12, read position 11.61

ISSN:0365-6217    

DOI:10.1039/AR9636000615

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

INDEXAaron, H. S., 416.Abbott, J. C., 541.Abdullah, M., 442.Abdul-Nour, B., 516.Abedini, M., 191.Abel, E. W., 232, 233.Abell, P. I., 269.Abernethy, S. G., 422.Abkin, A. D., 98.Aboderin, A., 57, 259, 357.Abraham, B. M., 133.Abraham, D. J., 292.Abraham, R. J., 311, 415,Abrahamsson, S., 596, 597,Abramovitch, R. A., 280,Abramyan, A. A., 562.Acheson, R. M., 381, 382,Achmad, S. A,, 258, 365.Ackermann, G., 562.Ackermann, T., 16.Ackman, R. G., 544.Adachi, S., 434.Adam, G., 413, 430, 431.Adam, M., 315.Adamee, V., 548.Adams, D. M., 139, 200,Adams, G. A., 441, 443.Adams, K. A. H., 327.Adams, R. E., 138.Adams, R. M., 185.Adams, R. N., 61.Adamson, A. W., 226.Addison, C. C., 181.Addy, J. K., 258.Adelman, M. B., 468.Adiga, P.R., 448.Aditya, S., 11.Affstrung, H. E., 543.Aftandilian, V. D., 182,183.Agar, D., 122.Agar, J. N., 23.Agarawala, V. S., 541.Ager, J. H., 407.Ageta, H., 375, 376.Aggarwal, R. C., 192.Aggarwal, S. L., 275.AgnBs, G., 340.Agnew, J. T., 146.Agrawal, K. C., 534.Agron, P. A., 179, 573.Ahern, A. J., 151.Ahmad, M., 272.Ahmed, A. K., 265.Ahmed, M. T., 78.436, 449.610345, 390.383, 392.211.O F AUTHORS’ NAMESAihara, A., 307.Aikens, D. A., 538.Aiman, C. E., 449.Aizawa, Y., 511.Ajello, T., 371.Akagi, M., 260.h e r l o f , G., 30.Akhmanova, M. V., 132.Akhtar, M., 423.Akiyoshi, S., 372.Akriche, J., 79.Alais, C., 490.Alauddin, M., 421.Albers, M., 515.Albert, A., 117.Alberts, G. S., 60.Albertson, N.F., 452.Albery, W. J., 54.Alcock, N. W., 203.Aldanova, N. A., 463.Alden, K. I., 136.Alden, R. A., 611.Aldous, J., 140.Aleby, S., 596.Alekseev, A. V., 125.Alemagna, A., 299.Alexakos, L. G., 203.Alexander, L. E., 568.Alexandroff, A., 533.Alfes, H., 441.Alfredsson, B., 543.Alfrey, T., 101.Alhojiirvi, J., 332.Ali, E., 561.Alicino, J., 448.Alimarin, I. P., 535, 536,Alimova, E. K., 544.Al-Kayssi, M., 534.Allan, E. A., 296.Allard, M. J., 71.Allbutt, M., 208.Allegra, G., 586, 588.Allen, A. O., 98.Allen, D. W., 474, 523.Allen, E. A., 212.Allen, F. W., 473.Allen, G., 111, 197, 267.Allen, G. F., 12, 294.Allen, H. C., 121.Allen, H. C., jun., 122.Allen, J. D., 310.Allen, J. K., 96, 104.Allen, K.W., 203.Allen, L. C., 179.Allen, P. E. M., 38, 104.Allen, W. F., 87.Allenstein, E., 196.Allerhand, A., 17.537.617Alleston, D., 192.Allgood, R. W., 38.Allin, E. J., 128.Allinger, J., 307.Allinger, N. L., 306, 307,308, 309, 358, 360, 362,415.Allison, A. C., 496, 504.Allison, H., 483.Allred, A. L., 59.Allred, E. L., 249.Almgren, M., 74.Alrash, H. I., 290.Alsina, J., 531.Amagi, Y., 99.Amat, G., 123, 164, 168.Amberg, C. H., 124.Amberger, E., 193, 195,Ambler, R. P., 476.Ames, B. N., 515.Ames, D. E., 333.Amiard, G., 427.Amin, J. H., 343.Amis, E. S., 20, 48.Amoz, S., 515.Amster, R. L., 132.Anachenko, S. N., 426, 427.Anacreon, R., 132.Anacreon, R. E., 139. .Anantaraman, R., 259.Anbar, M., 13, 49, 282.Anchel, M., 356.Anderer, F.A., 468.Andersen, F. A., 123.Anderson, A. G., 351, 396.Anderson, B., 490.Anderson, C. B., 252, 318.Anderson, D. B., 97.Anderson, D. M. W., 435,Anderson, D. W., 38.Anderson, E. W., 108, 248,Anderson, G. R., 145.Anderson, G. W., 452, 455.Anderson, L. E., 549.Anderson, R. G., 351, 396Anderson, R. S., 67.Anderson, S., 583.Anderson, W. S., 100.Andersson, C. O., 451.Andoh, J. T., 522.Andrade e Silva, M. H., 123.Andraschek, H.-J., 190.Andre, M. L., 150.Andreades, S., 305.Andreatta, R., 450.Andreev, S. N., 17.199.445, 545.364618 INDEX OF AUTHORS’ NAMESAndresen, H. G., 142.Andrews, J. M., 198.Andrews, L. J., 260.Andrews, S. L., 388.Andreyeva, A., 487.Andrussow, K., 8.Anet, F., 297.Anet, F.A. L., 308, 362,383, 385.Anfinsen, C. B., 471, 472,Angelici, R. J., 234.Angell, C. L., 146.Anger, V., 549, 555.Angoletta, M., 236.Angstadt, R. L., 208.Angyal, S. J., 334, 438.Anjaneyulu, B., 402.h e r , G., 424, 425, 428.Ansell, M. F., 267, 272, 309,Anselme, J.-P., 312.Anstasi, A., 460, 484.Antikainen, P. J., 31.Antipova Karataeva, I. I.,Antonaccio, L. D., 410.Antonni, E., 470, 475.Antonov, V. K., 464.Antsyshkina, A. S., 591.Aniur, A., 179.Aoki, T., 412, 429.Aplin, R. T., 374.App, A. A., 514.Appelbaum, A., 331.Appleman, D. E., 581, 582.Applequist, J., 297.Applewhite, T. H., 544.Ap Simon, J. W., 396.Apt, C. M., 38.Arai, S., 67, 86.Arakawa, K., 482.Arapakos, P. G., 146.Araujo, P., 497.Aravamundan, G., 555.Archer, E.D., 557.Archibald, A. R., 441.Arcus, C. L., 268.Arden, H., 46.h e n s , J. F., 326, 332.Argabright, P. A., 265,Argersinger, W. J., 29.Arigoni, D., 367, 374, 422,Ariyan, Z. S., 201.Ariyaratne, J. K. P., 237.Arlinghaus, R., 521, 525.Arlinghaus, R. B., 449.Armento, W. J., 539.Armentrout, S., 524.Armstrong, V. S., 587.Arndt, C., 328, 378.Arnett, E. M., 225, 256,Arnold, R. L., 263.473, 479.323.209.320.424.294.Arnold, Z., 322.Arnon, R., 480.Arnstein, H. R. V., 519,Aroney, M. J., 305, 310.Arons, H. L., 403.Aronson, A. I., 517.Arrhenius, E., 506.Arro, L., 267.Artemova, V. M., 208.Arthur, N. L., 83.Arvia, A. J., 31, 135, 137,Arya, V. P., 360.Asako, T., 426.Asami, R., 112.Asaoka, H., 540.Aschaffenburg, R., 468.Asensi Mora, G., 538.Ashby, E.C., 188.Ashby, M. L., 552.Asher, J. D. M., 396.Ashirov, A., 582.Ashworth, M. R. F., 563.Askonas, A., 480.Asper, S. P., jun., 505.Aspinall, G. O., 434, 442,Aspray, M. J., 47.Asprey, L. B., 139.Asscher, M., 94, 269.Astvatsaturian, A. T., 544.Athavaole, V. T., 540.Atherton, J. N., 106.Atkins, P. W., 83.Atkins, V. M., 21.Atkinson, C. M., 383.Atkinson, G., 19, 22, 228.Atkinson, J. G., 344.Atkinson, J. R., 266.Atkinson, R. S., 382.Audier, H., 415.Auerbach, J., 359.Augl, J. M., 238.Augustijn, G. J. P., 276,296.Augustine, R. L., 313, 321,Aurivillius, B., 579.Ausloos, P., 69, 73, 74, 75.Austin, J. M., 35.Austin, M. W., 277, 391.Austin, T.A., 196.Au-Young, Y. K., 436.Averbock, H. S., 58.Aver’ianov, S. V., 100.Avrahami, M., 86, 87.Axelrod, M., 359.Axelrod, N. N., 64.Ayer, D. E., 344.Ayer, W. A., 371, 413.Aymonino, P. J., 137, 203.Aynsley, E. E., 138, 202,Ayres, W. M., 227.Ayrey, G., 263.Ayscough, P. B., 348.522, 523.203.443, 444, 445, 549.323.203.Ayyangar, N. R., 267, 315.Azarova, M. T., 393.Baba, S., 433.Babad, H., 314, 322.Babaeva, A. V., 139, 219.Babbe, D. A., 250.Babenko, N. L., 535.Babkin, A., 533.Babko, A. K., 532, 535.Bacciarelli, S., 240.Bachman, G. B., 318.Bachman, R. Z., 540.Baciocchi, E., 263.Back, R. A., 66, 74, 80, 86.Bacon, G. E., 584.Bacon, J. S. D., 444.Badami, R. C., 332.Baddiley, J., 438, 447, 499.Baddley, W.H., 221.Bader, A. R., 318.Badger, G. M., 340.Badiger, V. V., 336.Baechle, H., 184.Biichmann, K., 25, 44.Baenziger, N. C., 603.Baer, W. K., 133, 136.Barnig-Hausen, H., 604.Baes, C. F., 28, 206.Baganz, H., 331.Bagbarly, J. L., 541.Bagby, M. O., 332.Bagdassarian, K. S., 99.Bagli, J. F., 424.Bagratishvili, G. D., 125.Bailar, J. C., 224.Bailey, D. M., 413, 431.Bailey, G. F., 139, 332.Bailey, N. A., 352.Bailey, R. T., 132, 141.Bailey, V. J., 380.Bailey, W. J., 314, 385.Bailin, L. J., 211.Baillie, J., 444.Bain, R., 139.Baird, J. C., 169.Baird, R., 250, 345.Baird, R. L., 57, 259, 357.Baird, S. G., 526.Baizer, M. M., 317.Bajusz, S., 459.Bak, B., 171, 173, 174, 311.Bak, G., 120.Bak, T.A., 84.Bakalo, L. A., 378.Baker, A. J., 414.Baker, A. W., 266, 283.Baker, B. E., 490.Baker, B. R., 435.Baker, C. D., 333.Baker, E. B., 252.Baker, F. B., 45.Baker, J. G., 168, 169.Baker, R., 275.Baker, R. H., 391.Baker, T. N., 266INDEX OF AUTHORS’ NAMES 619Baker, T. N., tert., 364.Bakule, R., 287, 296.Balabanoff, L., 540.Balasubramanian, M., 312,Balasubramanian, S. K.,Baldeschwieler, J. D., 81,Baldwin, J. E., 271.Balicheva, T. G., 17.Ball, D. F., 128, 145.Ball, E. G., 505, 506.Ballantine, D. S., 97.Ballhausen, C. J., 223.Balliah, V., 305.Ballou, C. E., 437, 446.Balodis, R. B., 563.Baltazzi, E., 378.Balueva, G. A., 181.Balzani, V., 47.Bambole, T. D., 278.Bamford, C. H., 93, 94, 95,96, 97, 102, 103, 106, 107,Ban, Y., 359.Banerjea, D., 46.Banerjee, A.K., 353, 355.Banerjee, P., 296.Banerji, K., 23.Bangert, A. F., 363.Ban-i, K., 487.Bank, S., 275.Banks, C. V., 540.Banks, W., 440.Bannerjee, A. K., 85.Bannerjee, K., 23.Bansal, R. C., 432.Banthorpe, D. V., 263.Barabas, S., 539.Barakat, M. Z., 553.Barbeau, C., 84, 235.Barber, M. S., 331.Barbier, M., 450.Barchewitz, P., 99, 120Barchukov, A. I., 167.Barclay, G. A., 220, 374579, 591, 592, 593.Barcza, L., 534.Bard, A. J., 541, 552.Barger, R. L., 126.Bargoni, N., 506.Bark, L. S., 537, 540.Barker, M. W., 392.Barker, R., 77.Barker, S. A., 436, 439Barker, S. B., 501, 502Barkhash, V. A., 324.Barlow, M., 569.Barltrop, J. A., 79, 362.Barnard, E. A,, 473.Barnard, M., 197.Barner, R., 283.Barnes, C.S., 396.359.370.299.123, 129.446, 488, 498, 500.505.3arnes, J. C., 11, 220.3arnes, R. L., 188, 446.3arnes, W. H., 607, 608.3arnett, J. E. G., 315.3arnett, L., 521.3arnett, M. P., 163.3arnum, D. W., 223.3arondes, S. H., 523, 524,3arrett, A. H., 165.3arrett, G. C., 281.3arrett, J., 84.3arrow, G. M., 120.3arte1, E. T., 53.Bartell, L. S., 142, 165.Bartlett, M. F., 408.Bartlett, N., 203, 219.Bartlett, P. D., 249.Bartman, S., 362.Bartmann, W., 428.Bartocha, B., 187.Bartok, W., 294.Barton, D. H. R., 66, 323,370, 373, 374, 376, 399,400,406, 419, 423, 426.Barton, G. W., jun., 162.Bartos, J., 547, 551.Bartram, S. F., 210.Bartsch, R. A., 259.Barua, A. B., 332.Barua, R.K., 332.Barzily, I., 550.Basargin, N. N., 563.Basco, N., 80, 81, 82, 83.Bascombe, K. N., 48.Rasi, J. S., 211.Basila, M. R., 125.Basilio, C., 523, 526, 527.Basolo, F., 216, 221, 224,229, 231, 234.Bass, A. M., 145.Bassham, J. A., 62.Bassi, D., 133.Bassi, I. W., 603.Bastien, I. J., 252.Bast6s, J. B., 325.Bates, R. B., 339, 365, 367,Bates, R. G., 27, 28, 30, 31.Bates, T. H., 100.Bath, S. S., 243.Batha, H. D., 183.Battacharyya, D. N., 111.Battaglia, A., 162.Battaglia, F. C., 474, 475.Batterham, T. J., 355.Battersby, A. R., 159, 399,Bauder, A., 172, 306, 359.Baudler, M., 198.Bauer, D. J., 383.Bauer, L., 282, 391.Bauer, R., 181.Bauer, W. H., 186.Baughan, E. C., 22.Baughman, G., 33.526.368.400, 410.Baum, S.J., 293.Baumann, C. G., 100.Baumann, F., 541.Baumann, J. E., 228.Baumgarten, H. E., 379.Baun, W. L., 151.Baur, W. H., 584.Bautista, R. G., 359.Bawn, C. E. H., 108, 118.Baxendale, J. H., 48.Bayer, R. P., 337.Bayer, R. W., 146.Bayes, K. D., 80.Bayles, J. W., 13.Bayley, S. T., 518.Bayyuk, S. I., 500.Bazhulin, P. A., 143.Beach, N. A., 232.Beagley, B., 595.Beak, P., 395.Beam, J. E., 163.Beaman, A. G., 394.Bean, G. P., 261, 382.Bearman, R. J., 23.Beaton, J. M., 423.Beattie, I. R., 134, 136, 192,194, 195, 198.Beaudet, R., 163.Beaudet, R. A., 174, 303.Beaven, G. H., 120, 476.Becher, H. J., 182, 184.Bechtler, G., 434.Beck, P. E., 325.Beck, W., 133, 146, 232,Beck, W. H., 28.Becka, L.N., 569.Becke-Goohring, M., 197,Becker, D. A., 66.Becker, E. I., 194, 289, 316,Becker, H., 334.Becker, K. A., 199.Becker, K. H., 80.Becker, W. E., 187.Becker, Y., 517, 520.Beckett, A., 89.Beckett, A. H., 391, 408.Beckey, H. D., 150.Beckman, T. A., 135.Beckwith, A. J. L., 323,Beckwith, A. L. J., 354.Bedford, A. F., 389.Beers, Y., 160, 161.Beeson, E. L., 172.Beevers, C. A., 604.Beezer, A. E., 389.Begun, G. M., 131.Behr, B., 24.Behrens, H., 233, 234.Beirne, P. D., 263.Beke, D., 391.Belardini, M., 373.Belcher, R., 536, 561.236.198, 394.327.426620 INDEX OF AUTHORS’ NAMESBelenky, B. G., 565.Beletskaya, I. P., 275.Belford, R. L., 136, 209.Belikov, V. M., 57.Bell, C. L., 391.Bell, E. A., 448.Bell, H.M., 247, 364.Bell, R. A., 413, 448.Bell, R. M., 118.Bell, R. P., 12, 19, 22, 34,48,49, 52, 54, 56,57, 266,287, 294.Bell, T. N., 83, 199, 202.Bellanato, J., 146.Bellas, M., 390.Bellas, T. E., 418.Bellasio, E., 381.Belleau, B., 342, 436.Bellen, Z., 544.Belli, M. L., 279.Belman, S., 547.Belov, N. V., 576, 582.Bel’skii, I. F., 313, 381.BeMiller, J. N., 440.Ben-Bassat, A. H. I., 534.Bench, R., 31.Bencker, K., 200.Bender, M. L., 289, 290,Ben-Dory L., 547, 552.Benedict, W. S., 122, 123.Benedikt, G., 389.Ben-Efraim, D. A., 252,Benerito, R. R., 227.Benesch, R., 475.Benesch, R. E., 475.Benesch, W., 128.Benesovsky. F., 208.Benghiat, I., 327.Benjamin, B. M., 254.Benjamin, L., 36.Benjamin, L. E., 182.Benjamini, E., 481.Benkeser, R.A., 146, 316,317, 339, 349.Benlian, D., 235.Bennett, C., 355.Bennett, J. E., 297.Bennett, J. F., 257.Bennett, J. M., 163.Bennett, L. E., 43.Bennett, M. A., 225.Bennett, M. J., 242, 587.Bennett, P. W., 539.Bennett, R. M., 213.Bennett, T. P., 512.Ben-Reuven, A., 127.Bensasson, R., 99.Benson, A., 476.Benson, R. E., 274, 348,350, 363, 380.Benson, S. W., 36, 37, 38,71, 104, 296.Bent, H. A., 126, 195.Bent, R., 137.291, 293.340.Bentley, K. W., 399, 402,Bentley, R., 434.Bentrude, W. G., 293.Benz, R., 205.Benzer, S., 525, 527.Beraud, J., 387.Berde, B., 455.Berezin, G. H., 293, 416.Berezina, N. P., 61.Berg, H., 60.Berg, R. A., 65.Bergdahl, S., 543.Bergelson, L. D., 320, 333,Berger, A., 465, 471.Bergman, E., 260.Bergson, G., 381.Bergstrom, C.G., 433.Berka, A., 541.Berkes, I., 556.Berkowitz, J., 153, 154,Berkowitz-Mattuck, J. B.,Berman, E. R., 492.Bernaerts, M. J., 438.Bernal, I., 209, 212, 581.Bernas, A. P., 99.Bernatek, E., 546.Bernauer, K., 406.Bernhard, S. A., 465.Berni, R. J., 227.Bernot, A. F., 586.Berns, D. S., 18.Bernsmann, J., 436.Bernstein, S., 418.Beroza, M., 358.Berrigan, P. J., 260.Berry, R. S., 76, 280.Berson, J. A., 247, 252.Bertaut, E. F., 578.Berthold, H., 336.Berthold, H. J., 242.Berti, G., 375.Bertoluzza, A., 47.Bertrand, J. A., 213, 238,Besch, E., 407.Bessho, K., 403.Best, J. V. F., 100.Bestian, H., 335.Bestmann, H. J., 320, 329.Bethell, D., 258.Bethell, M., 449.Bett, J. A.S., 285.Betts, J., 96.Betz, W., 115.Beugelmans, R., 412.Beutner, H., 236.Bevan, C. W. L., 278.Bevan, J. A., 591.Bevington, J. C., 91, 95, 96,97, 104, 106.Bewick, A., 40.Beyer, H., 184, 185.406.545.155.154.594.Beyer, R. E., 508.Beyerman, H. C., 325, 452.Beynon, J. H., 149, 155,157, 158, 311.Bezinger, N. N., 561.Bezkorovainy, A., 488.Bezman, I. I., 197.Bezzi, S., 599.Bezzubov, A. A., 333.Biarge, J. F., 145.Bickel, A. F., 329.Bidinosti, D. R., 185.Bidnyak, N. A., 46.Biedermann, G., 27, 31,Bielski, B. H., 47.Biemann, K., 149, 159,299,392, 408, 410, 436, 449,450, 451.Bienvenue, A., 302.Bier, G., 97.Bierl, B. A., 145.Biermann, W. J., 208.Biernat, J.F., 452, 454,Bierwirth, E., 333.Bigelow, C. G., 470.Biggs, A. I., 12.Bighi, C., 554.Bigley, D., 449.Bigliardi, G., 593.Biglino, G., 374.Bigorgne, M., 234, 235.Bikales, N. M., 289.Bilbo, A. J., 187.Bilimovich, G. N., 537.Billig, E., 215, 227, 233.Billmeyer, F. W., 91.Bills, C. W., 394.Binder, R. G., 544.Binebaym, I., 534.Binette, J. P., 487.Binger, P., 187.Binks, R., 399.Biossonas, R. A., 484.Biradar, N. S., 42.Biranouski, J. B., 263.Birch, A. J., 370, 372, 375,Birchall, T., 304.Bird, C. W., 266, 380, 383.Bird, G. R., 169.Bird, J. W., 437.Birkhimer, C. A., 448, 455,Birkofer, L., 394.Birks, J. B., 65.Birnkraut, W. H., 181.Biserte, G., 486, 487.Bishop, C. T., 289,434,435,Bishop, E. A., 483.Bishop, J., 512.Bishop, R.R., 277.Bisnette, M. B., 236, 353.Bissing, D. E., 289.221.456.384, 419.460.441, 443INDEX OF AUTHORS’ NAMES 621Biswas, A. B., 597.Biswas, S. D., 532, 541.Bittler, K., 240.Bhacca, N. S., 372.Bhat, H. B., 611.Bhate, D. S., 384.Bhatia, P. L., 464.Bhatnagar, S. S., 128.Bhattacharya, B. N., 161.Bhattacharyya, D. N., 113.Bhattacharyya, S. C., 365,Bhatty, M. K., 563.Blacet, F. E., 72, 81.Black, D. K., 329.Black, D. R., 150.Black, W. A. P., 447.Blackburn, S., 551.Blackie, M. S., 107.Blackwell, J., 277.Blackwood, A. C., 441.Bladen, P., 414.Blagoveshchenskaya, N. A. ,Blair, R. P., 230.Blake, A. B., 223.Blake, M. I., 286.Blaker, J. W., 163.Blanchard, E. P., jun., 322.Blanchard, K.R., 364.Blandamer, M. J., 9, 11, 36.Blank, B. B., 429.Blank, F., 355, 441.Blankenship, F. A., 209.Blaschke, G., 403.Blau, E. J., 135,Bloch, K., 527.Block, B. P., 224.Block, J., 560.Blocher, K. H., 347.Bloemendal, H., 524, 525.Blom, J., 436.Blomstrom, D. C., 397.Blondin, G., 433.Bloomfield, J. J., 292, 327.Blotny, G., 454.Bloxam, T. W., 538.Blues, E. T., 316.Blukis, U., 175, 301.Blum, S. C., 21.Blumbergs, P., 437.Blume, H., 68.Blumenfeld, 0. O., 475.Blundstone, H. A. W., 543.Blunt, J. W., 252.Blyholder, G., 124, 139.Boag, J., 11.Boag, J. W., 48.Boatman, J. C., 209.Bobbit, J. M., 403.Bobotelsky, M., 49, 550.Bobovich, Ya. S., 130, 137,Bobrov, A. V., 144.Bock, R. M., 523.Bocks, S. M., 355.367.539.145.3odansky, A., 37.3odanszky, M., 448, 455,3odyu, V.I., 547.Sohland, H., 212.Boekelheide, V., 63, 352,Boll, W., 75, 357.Boelrijk, N., 156.Boer, F. P., 184.Borresen, H. Chr., 555.Boeters, H., 199.Boeters, H. D., 193.Bogdanov, V. P., 486, 487.Bogdanovsky, D., 450.Bognar, J., 536.Bogs, U., 531.Bohackova, Zd., 554.Bohlmann, F., 327, 328,Bohm, B. A., 269.Bohrer, J. J., 101.Boikess, R. S., 350, 363Boissonnas, R. A., 455, 460,Boitsov, E. N., 378.Boldrini, P., 594.Bolesova, I. N., 353.Bolfa, L., 140.Boller, A., 450.Bollinger, J., 251.Bolton, P. D., 292.Bolton, R., 279.Bolton, W., 606.Bolzan, J. A., 31.Bombaugh, K. J., 548.Bonamico, M., 576.Bond, C. H., 314.Bondarevskaya, E. A., 545,Bonferoni, B., 490.Bonham, R.A., 303.Bonino, G. B., 15, 124.Bonnemay, M., 60.Bonner, J., 514, 518.Bonner, N. A., 42.Bonner, 0. D., 32.Bonner, T. G., 292.Bonner, W. A., 386.Bonnett, M., 295.Bonoli, L., 253.Bont, W. S., 525.Bontekoe, J. S., 452.Boonstra, E. G., 600.Booth, A. D., 599.Booth, D., 65.Booth, D. A., 493.Boppel, B., 197.Bor, G., 139, 234.Borden, G. W., 68, 362.Bordet, C., 547.Bordwell, F. G., 259, 263,265, 266, 288.Borecty, J., 545.Borgulyan, J., 283.Borisova, I. G., 545.459, 484.363, 384.378.484, 485.560, 564.Bork, V. A., 564.Borkowski, R. P., 69.Borla, A., 272.Born, H. J., 24.Bornengo, M., 335.Bornmann, P., 202.Bornowski, H., 328, 378.Borovas, D., 453.Borrell, P., 67, 69.Bortfeld, D.P., 148.Boryta, D. A., 198.Borzenkova, N. P., 536.Bosch, L., 524, 525.Bose, A. K., 360, 370, 408.Bose, A. N., 296.Bose, X., 445.Bose, S. M., 491.Bosnich, B., 232.Bosson, J. A., 401.Bostick, E. E., 108, 110,Boston, J. L., 238.Boswell, G. A., 416, 417.Bott, R. W., 193, 275.Bottari, F., 375.Bottei, R. S., 193.Bouchilloux, S., 503.Bourne, E. J., 434, 438.Bourns, A. N., 263, 276.Bourrillon, R., 486, 488,Bouveng, H. O., 441.Bovey, F. A., 107, 108.Bowden, K., 292.Bowen, D. M., 386.Bowen, D. O., 124.Bowen, E. J., 68, 77, 341.Bower, V. E., 12, 29, 30, 32,Bowers, A., 421, 429.Bowles, R., 73.Bowyer, W. J., 432.Boyce, C. B. C., 428.Boyd, G. E., 36.Boyd, G. V., 391.Boyd, R. H., 22.Boyer, E. W., 158.Bozhevolnov, E.A., 533.Bracken, R. C., 167.Brackman, W., 323.Bradbury, E. M., 304.Bradley, D. C., 205,207,211.Bradley, D. F., 446.Bradley, J. N., 337.Bradley, W. F., 580.Bradsell, R. H., 161.Bradshaw, J. S., 274.Brady, J., 230.Brady, P. R., 177.Brady, R. O., 494.Bragg, P. D., 486.Braibanti, A., 593.Brainina, K. Z., 540.Branch, R. F., 391.Brand, J. C. D., 299.Brand, V. A,, 540.115.490.294622 INDEX OF AUTHORS’ NAMESBranda, L. A., 460.Branden, C.-L., 194.Brandmuller, J., 121.Brandon, R. L., 68, 330.Brandsma, L., 326.Brandstiitter, O., 191.Brannan, J. R., 31.Brannock, K. C., 336.Brannon, D. R., 367.Brasen, W. R., 397.Braterman, P. S., 220.Brauer, G., 210.Brauman, J. I., 275.Braun, D., 115.Braun, P. B., 568.Braun, R., 355.Braun, R.A., 398.Braunitzer, G., 468.Brawerman, G., 514, 524.Braye, E. H., 233, 586.Brdidka, R., 53.Brechbiihler, H., 454.Breed, L. W., 191.Brehler, B., 593.BrGi6, B., 179.Breig, E. L., 173.Breisacher, P., 206.Breitbeil, F. W., 258.Breiter, M., 53Breitschaft, S., 242, 353.Bremer, H., 461.Brendel, G. J., 188.Brenna, G. L., 129.Brennen, J. F., 59, 276.Brenner, M., 465.Brenner, S., 521.Breslow, R., 253, 275, 340,Bretscher, M. S., 513, 526.Bretthauer, R. K., 523.Breuer, E., 292.Brewer, F. M., 189.Brewster, J. H., 333.Brey, W. A., jun., 184.Brey, W. S., 108, 201.Brey, W. S., jun., 357.Bricker, C. E., 64.Bridge, N. J., 127.Bridger, R. F., 345,Briegleb, G., 10, 295.Brieskorn, C.H., 371.Briggs, E. R., 101.Brim, W., 64.Brim, W. W., 123.Brimacombe, J. S., 436,441, 446, 498, 500.Brinckman, F. E., 207.Brinckman, F. E., jun., 187.Brinkhoff, O., 461.Brinton, R. K., 71.Briody, R. G., 254.Brisbin, D. A., 228.Brisdon, R. J., 212.Briskey, E. J., 440.Brissolese, J. A,, 159, 408,348, 359.410.Britten, A. Z., 409.Britten, R. J., 513.Britton, D., 572.Brizzolara, A., 323.Broadley, J. S., 572.Brodersen, S., 121.Brodie, H. J., 433.Broida, H. P., 126.Brois, S. J., 379.Bronk, J. R., 507, 510.Bronk, M. S., 507.Bronsted, J. N., 49.Brook, A. G., 193.Brookbank, J. W., 514.Brooke, G. M., 342.Brookes, D., 333.Brooks, T. W., 320.Brooks, W. V. F., 143.Bross, R., 259.Brotherton, R. J., 185,Brotz, M., 494.Brower, K.R., 271.Brown, A. G., 414.Brown, B. R., 314, 355.Brown, B. W., 590, 592.Brown, C. J., jun., 591.Brown, D., 205.Brown, D. F., 292.Brown, D. H., 217, 441,Brown, D. J., 285.Brown, D. M., 293, 325.Brown, F. B., 304.Brown, G. H., 21.Brown, G. L., 525.Brown, G. M., 597.Brown, H. B., 285.Brown, H. C., 247, 248,267, 275, 277, 315, 344,364.Brown, J. J., 418.Brown, J. M., 316.Brown, J. R., 469.Brown, J. W., 515.Brown, K. S., 410, 412,Brown, K. S., jun., 375.Brown, L. C., 44.Brown, L. W., 556.Brown, M. P.: 185.Brown, M. S., 314.Brown, P. E., 314.Brown, P. K., 89.Brown, R., 150.Brown, R. A., 556.Brown, R. F., 298.Brown, R. K., 311, 383,Brown, R. N., 208.Brown, R. T., 407.Brown, T.L., 146, 193,200,Brown, W., 440, 441.Brown, W. A. C., 610.Brown, W. B., 142.187.442.433.480.302.Brownstein, S., 108, 115,Brubaker, C. H., 33, 209.Bruce, N. F., 433.Bruckenstein, S., 11, 13.Bruckner, V., 459.Bruegel, W., 120.Brufani, M., 388.Brugger, M., 451.Bruice, T. C., 286, 291.Brummer, S. B., 38.Brune, H. A., 134, 139, 362.Brunet, P. C. J., 355.Brunet, V., 69.Brunie, J.-C., 322.Brunner, H., 482.Bruno, J. J., 291, 333.Brussct, H., 21.Bryan, R. F., 592, 597.Bryant, J. I., 128.Bryant, W. M. D., 296.Bryce, W. A., 89.Bryce-Smith, D., 79, 316,Bryvnak, D. A., 133.Bublitz, D. E., 353.Buchanan, J. G., 438, 447,Buchanan, R. A., 130.Buchert, H., 133.Buchler, A., 134.Buchman, O., 275.Buck, R.P., 55, 60.Buckingham, A. D., 127.Buckler, S. A., 556.Buckley, A., 292.Buckley, J., 200.Bucourt, R., 433.Buczkowski, Z., 305.Budarin, L. I., 539.Budenstein, P. P., 161.Budesinsky, B., 535.Budhiraja, R. P., 376.Budnitskaya, E. V., 545.Budzikiewicz, H., 159, 404,Buchi, G., 322, 344, 368,Buchi, H., 451.Buechler, A., 131, 154.Buchner, W., 181.Bueding, E., 440.Buehler, C. A., 344.Biirer, T., 224.Burger, H., 191, 207, 208.Bufalini, J., 17.Buffagni, S., 10.Buhl, F., 533.Buijs, K., 16, 125, 146.Buijze, C., 535.Bukhari, M. A., 435.Bulanin, M. O., 126, 128.Bulgakova, G. P., 10.Bull, W. E., 226.Bullock, E., 382.Bumpus, F. M., 482.309.343, 351.499.408, 409, 410, 415.369, 389INDEX OF AUTHORS’ NAMES 623Bunce, S.C., 253.Buncel, E., 350.Bundy, F. P., 190, 571.Bunnenberg, E., 299, 416,Bunnett, J. F., 48,263,278,Bunton, C. A., 58, 257,Burak, I., 10.Burch, D. E., 133, 145.Burchard, W., 440.Burchkhardt, U., 281, 346.Burg, A. B., 182, 234.Burger, M. M., 494.Burgher, R. D., 544.Burgstahler, A. W., 283,Burina, R. V., 541.Burka, E. R., 521.Burke, J. J., 256.Burkhard, S., 540.Burkhart, R. D., 103.Burlaka, V. P., 564.Burlant, W. J., 91, 99.Burleigh, P. H., 108.Burlingame, :A. L., 408,Burlington, A. L., 159.Burmeister, J. L., 224.Burn, D., 418.Burnett, G. M., 105.Burns, E. A., 552.Burns, G., 84.Burns, J. H., 179, 573.Burpitt, R. D., 336.Burr, M., 385.Burrett, G. M., 97.Burriel-Marti, F., 537.Burroughs, L.F., 449.Burrous, M. L., 316.Burrus, C. A., 161, 166.Burton, P. E., 259.Burton, R. E., 117.Burton, R. M., 494.Burwell, R. L., 267.Busby, R. E., 21.Buscarons, F., 531.Busch, D. H., 229.Buschmann, L., 394.Busetti, V., 605.Busev, A. I., 535.Busing, W. R., 13.Buslaev, Yu. A., 138.Buss, H., 221.Butcher, S., 168.Butcher, S. S., 175, 300.Butler, G. B., 108, 320.Butler, I. S., 233.Butler, J. A. V., 513.Butler, J. N., 72.Buttimore, D., 387.Buzby, G. C., 426.Bydalek, T. J., 231.Byers, G. W., 89.Byme, R., 478.452.285, 293, 383.267, 291, 321.316, 449.409Bywater, S., 108, 109, 110,113, 114, 115.Cabani, S., 229.Cabib, E., 434.Cabiddu, S., 320.Cadenas, E., 469.Cady, G. H., 180, 196, 201.Cady, H. H., 607.Cafferata, L.F. R., 135.Caffrey, J. M., 98.Cagliotti, L., 420, 422.Cahill, P., 168.Cainelli, G., 420, 424.Cairncross, I. M., 442.Cairns, T. L., 267, 397.Calder, I. C., 387.Calderazzo, F., 240.Calderon, N., 110.Caldwell, A., 70.Caldwell, D. J., 218.Califano, S., 137, 141, 142,Callahan, F. M., 452, 455.Callear, A. B., 79, 81, 84,Callis, J. W., 73.Callister, J. D., 258.Calvert, J. G., 66, 75.Calvin, M., 62, 296, 394.Cambie, R. C., 328, 355.Camerino, B., 460.Camerman, N., 573.Cameron, D. W., 370.Cammarano, P., 524.Campaigne, E., 262.Campbell, A. D., 560, 561.Campbell, A. N., 19.Campbell, P. L., 510.Campion, R., 45.Campos, M. de M., 202.Canady, W. T., 35.Canale, A. J., 95.Canceill, J., 422.Candela, G.A,, 214.Candlin, J. P., 42, 43.Canepa, F. G., 598.Canfield, R. E., 468.Canic, V. D., 538.Cannon, M., 524.Cantley, M., 435.Cantrell, T. S., 259, 350.Canvin, D. T., 435.Capella, P., 548.Capelle, R., 540.Capon, B., 289.Caputo, A., 470, 475.Carassiti, V., 47.Carazzolo, G., 605.Carboni, R. A., 327.Cardenas, C. G., 259.Cardwell, H. M. E., 399.Carell, B., 31, 36.Carlin, H., 469.Carlin, R. L., 216.Carlisle, C. H., 468.145.85.Carlson, E. G., 150.Carlson, G. L., 133, 136.Carlson, R. L., 295.Carlson, T. A., 156.Carlsson, O., 548.Carlton, D. M., 259.Carman, R. M., 373.Carnall, W. T., 206.Carnighan, R. H., 339.Carpenter, F. H., 469, 470.Carpenter, G. B., 572.Carpenter, W. R., 305.Carpino, L. A., 452.Carpio, H., 429.Carr, M.D., 267, 321.Carrington, A., 204, 299.Carrington, R. A. G., 133.Carroll, D. F., 197.Carruthers, W., 386.Carter, C. C., 190.Carter, J. H., 465.Carter, R. P., 198.Cartier, G. E., 253.Cartouzou, G., 525.Cartwright, P. F. S., 529.Casals, P.-F., 316.Casanova, J., 252.Casanova, J., jun., 364.Casapieri, P., 256.Casey, C., 267.Cash, W. D., 460, 484.Cashion, J. K., 129.Casini, J., 437.Casnati, G., 462.Cason, J., 509.Caspar, M. L., 259.Caspers, H. H., 130.Caspi, E., 417, 421.Cassady, D. R., 391.Cassata, A., 115.Cassidy, H. G., 481.Cassimatis, D., 134.Castellani, A. A., 490.Castellano, E., 83.Castells, J., 421,Castle, C. G., 418.Castle, M., 433.Castleman, H., 290.Castro, C. E., 282.Catalano, E., 126.Catchpole, K.W., 227.Catesby, C. G. C., 612.Caudle, J., 28.Caughey, W. S., 311.Cauzzo, G., 71, 76.Cava, M. P., 341, 383, 410,Cavalca, L., 591.Cavalieri, L., 297.Cavell, E. A. S., 277.Cavell, R. G., 209.Cavill, G. W. K., 258, 365.Ceccon, A., 256.Cecil, R., 478.Cedergren, I., 267.Cefola, M., 30.423624 INDEX OF AUTHORS’ NAMESCejkova, Z., 542.cekan, Z., 367, 368.Celiano, A. V., 30.Cerbulis, J., 542.Cbr&de, J., 427.Ceresa, R. J., 91.Cerfontain, H., 275, 277,285, 556.CerniL, J., 435.Cerny, M., 437, 495.Cervone, E., 214.Cessac, G., 209.Cessi, C., 435.Cetina, R., 146.Chackraburtty, D. M., 589.Chadde, F. E., 260.Chadwick, J. R., 189.Chakravarti, K. K., 367.Chalaya, Z. I., 535.Challis, B.C., 277.Chalvet, O., 294, 298, 310,Chamberlin, J. W., 415.Chambers, R. D., 194, 342.Chambionnet, A., 542.Chamness, J. T., 283.Chan, S. C., 231, 232.Chan, S. I., 82, 173.Chan, S. K., 476.Chan, W. M., 524.Chan, W. Y., 460, 485.Chance, B., 507.Chandler, R E: ., 451.Chandrasekha, N., 489.Chandross, E. A., 347.Chang, G., 241, 354.Chang, H. W., 253, 348.Chang, T.-L., 535.Chang, W.-C., 461.Changeux, J.-P., 509.Chang Hee Chin, 46.Chantooni, M. K., 13.Chantooni, M. L., 22.Chantrenne, H., 512.Chantry, G. W., 144.Chao, F. C., 514.Chao, O., 423.Chapeville, F., 525.Chapiro, A., 91, 98, 99, 103.Chapman, A. C., 136, 137,Chapman, D., 197.Chapman, N. B., 258, 277,278, 292.Chapman, 0. L., 66, 68,306, 351, 361, 362, 365,414.Chappell, S.F., 68.Chaput, M., 494.Charalambous, J., 186.Charles, S. W., 81.Charlesby, A., 91, 98.Charlson, A. J., 444.Charlton, T. L., 599.Charman, H. B., 57.Charters, P. E., 129.340.197.Chatani, Y., 596.Chatt, J., 139, 200, 207,211, 217, 238, 242.Chatterjee, A. K., 487.Chatterjee, A. N., 497.Chatterjee, K. K., 286.Chau, J. Y. H., 141.Chauhan, V. B. S., 538.Chauveau, J., 513.Chaventon, J., 123.Cheema, Z. K., 181.Cheeseman, T. P., 591.Cheesman, L. E., 147.Cheetham, N. F., 387.Chen, C. C., 481.Chen, C. S. H., 99.Chen, C.-Y., 360.Chen, D. T. Y., 12, 294.Chen, J. C., 72.Chen, M. C., 291.Cheng, G. C. H., 580.Cheng, J., 563.Cheng, K. L., 537.Chen-Lu, T., 469.Chernick, C.L., 130, 150,179, 180, 214.Chertov, V. M., 545.Chesick, J. P., 86, 259.Chesnokova, N. N., 113.Cheung, H. T., 374.Chia-Chen, Ni., 219.Chiang, Y., 58, 59, 310, 381.Chia Tang Lu, 610.Chiglione, C., 548.Chi-Hua Wang, 325.Childers, L. G., 446.Childs, C. E., 563.Chiltz, G., 337.Chimiak, A., 452, 456.Chin-Hsuan Wei, 586, 588.Chin-Yong Wu, 251, 261.Chiorboli, P., 15.Chisholm, M. J., 332.Chitoku, K., 307.Chittenden, G. J. F., 435.Chiurdoglhu, G., 307, 351.Chiusoli, G. P., 340.Chivers, T., 194.Chloupek, F. J., 248, 364.Cho, J. S., 129.Chodowski, J., 50.Choi, S. S., 221.Cholnoky, L., 331.Chopin, F., 187.Choppin, G. R., 16, 146.Chopra, C. S., 373.Chosson, A., 487.Chou Kung-Du, 585.Chow, N., 65.Choy, T.K., 543.Chrambach, A., 469.Christ, C. L., 581.Christe, K. O., 192.Christensen, B. W., 337.Christensen, D., 170, 171,174.Christensen, J. E., 437.Christensen, J. J., 31, 35.Christiansen, J., 174.Christiansen, R. G., 418,Christmann, A., 293, 335.Chromy, V., 555.Chu, S. S., 614.Chujo, R., 108.Chul-Yung, C., 471, 473.Chumachenko, M. N., 564.Chung, D., 459.Chung Ho Park, 249, 25 1.Chupka, W. A., 152, 153,154, 155, 157.Church, R. F., 370.Churchill, M. R., 239, 587,Ciampolini, M., 36, 218.Ciavatta, L., 31, 221.Ciborowski, S., 556.Cieciuch, R. F. W., 287.Cihla, Z., 142.CinnBide, F. O., 394.Cirimele, M., 548.Claassen, K. H., 130, 138,Clamp, J. R., 486.Clampitt, B. H., 73.Clancy, D. J., 155, 547.Clark, C. T., 344.Clark, D., 585.Clark, G.W., 358.Clark, H. C., 134, 177, 193,194, 209, 588.Clark, J. R., 581, 611, 612.Clark, R. D., 379.Clark, R. F., 68.Clark, R. J., 205.Clark, R. J. H., 139, 206,Clark, V. M., 293.Clarke, A. E., 442.Clarke, G. A., 25.Clarke, J. F. G., 231.Clarke, R. G., 115.Clarke, R. L., 359, 418.Clarke, R. T., 401.Clauder, O., 408.Claverie, N., 310.Clayton, E., 159.Clayton, J. W., 259.Clayton, L., 170.Clearfisld, A., 10, 208.Clement, G. E., 290.Clerc, J. T., 559.Clerc, R. J., 150.Zlever, H. L., 28.Clifford, A. F., 235.Clifford, D. R., 558.Zlifton, P., 230.Zloss, G. L., 75, 293, 357,Gloss, I;. E., 357, 363.Closson, W. D., 305.Elough, S. A., 145.421.588.179, 214.207, 209, 222, 225.363INDEX OF AUTHORS’ NAMES 625Clouse, R.W., 486.Clouston, J. G., 152.Cloutier, G. C., 151.Coates, E., 11.Coates, G. E., 139, 181,188, 189, 219.Coats, A. W., 537.Cobble, J. W., 36.Coblentz, W. W., 120.Cochran, J. C., 25.Cocivera, M., 262.Cocker, W., 332.Coe, G. R., 275.Coetzee, J. F., 22.Coffey, C. E., 241.Cogan, H. L., 9.Cohen, A., 436.Cohen, B., 201.Cohen, E., 513.Cohen, H. M., 193.Cohen, L. A., 346, 471.Cohen, P., 356.Cohen, P. P., 510.Cohen, S., 318, 334.Cohen, S. G., 290.Cohen, S. S., 515.Cohen, T., 406.Cohen-Xordmann, M.-E.,Cohin, J., 372.Cohn, P., 518.Coillet, D. W., 277.Coing-Bayat, J., 583.Cokal, E. J., 541.Coker, E. H., 129.Colburn, C. B., 135, 195,Colchester, J. E., 200.Cole, R.S., 345.Coleman, B. D., 107.Coleman, J. S., 48,205, 206.Coleman, L. F., 230.Colin, A., 188.Collat, J. W., 541.Collie, C. H., 31.Collin, J., 152, 299.Collins, C. H., 331.Collins, C. J., 254.Collins, D. J., 375, 416.Collins, J. C., 428.Collins, P. M., 436.Collinson, E., 97, 98, 100.Collman, J. P., 230, 349.Colonge, J., 322.Colson, A. F., 539, 560, 562.Colter, A. K., 257.Colthup, E. C., 94.Colthup, N., 99.Colwell, J. H., 137.Combs, C. M., 260.Comeford, J. J., 135.Comin, J., 356, 395.Comly, L. T., 524.Comoy, P., 315, 419.Conia, J. M., 306, 358, 359.Conley, R. T., 289.533.196.Conner, R. L., 373.Connick, R. E., 17.Connor, T. M., 51.Connor, W. A., 293.Conover, T. E., 501.Conroy, H., 272.Convert, G., 161.Cook, B.M., 18.Cook, C. D., 301, 310.Cook, C. M., 210.Cook, D., 304, 395.Cook, M. C., 436.Cooke, J. P., 471, 473.Cookson, R. C., 258, 259,266, 284, 393, 418.Cool, w., 533.Cooley, G., 418.Cooper, A. G., 290.Cooper, C., 508.Cooper, F. P., 289, 434.Cooper, J., 585.Cooper, J. N., 184.Cooper, O., 506.Cooper, R. D. G., 331.Cooper, T., 592.Cooper, W., 108.Coopton, R. W. G., 556.Cope, A. C., 249, 251, 259,Cope, K. C., 363.Copeland, C. S., 36, 37, 38.Copier, H., 355.Coppens, G., 279.Coppens, G. A., 265.Coppens, Ph., 580.Corbett, J., 393.Corbett, J. D., 199, 204,Corbin, J. L., 251, 261.Cordes, E. H., 286.Corey, E. J., 252, 253, 320,361, 364, 369.Corey, E. R., 232, 586.Cori, C. F., 442.Corliss, J.M., 563.Cormick, J., 468, 479.Cornell, D., 76.Cornforth, J. W., 333, 377.Cornforth, R. H., 333,Cornillot, R., 490.Cornu, P.-J., 315, 419.Cornwell, C. D., 174, 203.Corran, J. A., 396.Corrandini, P., 595.Corrodi, H., 356.Cortez, H. V., 323.Cory, J. C., 470.Cosmatos, A., 454.Costain, C. C., 164, 168,170, 171, 173.Costopanagiotis, A., 457,459.Cottam, B. J., 113.Cotter, J. L., 260.Cotterill, W. D., 288.264.205.377.Cotton, F. A., 139,213,222,223, 228, 232, 241, 586,594.Cotton, R., 213.Couch, J. P., 32.Coulson, C. A., 340.Coulter, A. W., 423.Coulter, C. L., 569, 603.Courtoy, C. P., 123.Cousins, M., 238.Couvillion, J., 598.Covington, A. K., 23, 26,Covitz, F., 57, 287.Cowan, M., 160.Cowdell, R. T., 206.Cowell, D.B., 391, 553.Cowie, G. R., 256.Cowie, J. M. G., 440.Cox, A. P., 162, 167, 170.Cox, D. A., 414.Cox, J. J., 242.Cox, J. R., 342.Cox, M., 74.Cox, R. A., 517, 522, 523.Coyle, J. J., 293.Cozzi, D., 61.Crabbe, P., 421.Craciuneanu, R., 532.Craft, M. K., 460.Craig, B. M., 544.Craig, D. P., 232.Craig, J. C., 320.Craig, L. C., 475.Craig, R. A., 17, 18.Craig, R. D., 150, 299.Craig, W. G., 259.Craig Taylor, R., 139.Cram, D. J., 106, 251, 262,265, 271, 273, 345, 345,349, 359.28, 29.Crampton, C. F., 518.Crane, R. K., 506.Crane-Robinson, C., 128.Crathorn, A. R., 513.Crawford, B., 143.Crawford, B., jun., 141, 142.Crawford, R., 559.Crawford, V. A., 134.Crayton, P. H., 209.Crean, P. J., 331.Creasey, N.G., 396.Creighton, J. A., 16, 134,Cressey, T., 26.Crestfield, A. M., 470, 472,Crick, F. H. C., 521, 526.Criegee, R., 318, 334, 362.Crispell, K. R., 509.Crispin, D. J., 426.Cristol, S. J., 263, 266, 419.Crombie, L., 333, 365, 396.Cromer, D. T., 571, 576,Cromwell, N. H., 265.136.473, 478.580, 607626 INDEX OF AUTHORS’ NAMESCronin, D. A., 259.Crook, J. R., 192.Crooks, J. E., 294.Cross, A. D., 416, 420.Cross, B. E., 371.Cross, D., 388.Cross, D. F. W., 448.Cross, P. C., 121, 137.Crossley, J., 290, 365.Crowell, E. P., 546.Crowell, T. I., 265, 268.Crowfoot, D. C., 610.Crowley, K. J., 68, 320, 329.Crowley, P. J., 228.Crowston, R. M., 372.hickshank, D. W. J., 569,Crummett, W. B., 550.Crump, G.B., 549.Crump, J. W., 285.Csordas, L., 579.Cubbon, R. C. P., 108.Cucka, P., 606.Cullen, E., 421.Cullen, W. R., 199.Culley, H. J., 536.Culmo, R., 564.Culvenor, C. C. J., 400.Cumings, J. N., 493.Cummins, B., 394.Cumper, C. W. N., 311.Cundall, R. B., 65, 89, 114.Cunningham, B., 514.Cunningham, B. B., 205,Cunningham, L. W., 486.Cunningham, W. L., 441.Cupta, P. C., 554.Cureton, P. H., 312.Curl, A. L., 332.Curl, R. F., jun., 163, 169,170, 174, 175.Current, J. H., 153.Currie, C. L., 66, 76.Curry, J. B., 518.Curry, N. A., 584.Curti, R., 585.Curtin, D. Y., 259.Curtis, C. G., 423.Curtis, N. F., 219, 221.Curtis, R. W., 462.Cuvelier, R., 486.Cvetanovic, R. J., 65, 81,579.571.87.Cymerman Craig, J., 326,Cwin, B.N., 142.327, 329.C+; S. J.,-142, 143.Czapski, G., 47.Czerepko, K., 552.Czerlinski, C., 50.Czerny, V., 415, 422.Dachille, F., 230.Diihne, W., 179.Dahl, A. J., 138.Dahl, L. F., 222, 232, 233,234, 239, 586, 588.Dahl, T., 332.Dahlberg, J. E., 522.Dahlbom, R., 452.Dahn, H., 258.Daignault, R. A., 314.Dailey, B. P., 172, 307, 309.Dainton, F. S., 91, 92, 96,97, 98, 100.Dais, D., 512.Dalby, J. S., 449.Dale, J., 340.Dallam, R. D., 507.Dalton, C. K., 251,271,348.Dalton, F. L., 98.Daly, J. W., 311.Dance, N., 476.Danckwerts, P. V., 57.Dandegaonker, S., 257.Dane, E., 453.Danielisz, M., 351.Danielli, N., 353.Daniels, P. J. L., 374, 419.Daniher, F. A., 437.Danilova, V. N., 535.Danil’tseva, G. E., 147.Danishefsky, I., 500.Dann, O., 396.Dannley, R.L., 118.Danon, D., 521.Danti, A., 299.Danyluk, S. S., 301, 302.Dapo, R. F., 551.D’Aprano, A., 20.Darby, W., 578.Darbyshire, J. A. C., 222,Darling, S. D., 429.Darnell, J. E., 517, 520,DaRooge, M. A., 307, 308,Dartnall, H. J. A., 89.Darwent, B. de B., 71, 76.Darwish, D., 260.Das, P. B., 21.Das, S. N., 17,27.Dasent, W. E., 203.da Silva, J. J. R. F., 180,Date, Y., 538.Datta, S. P., 30, 31.Dauben, H. J., 274, 350.Dauben, H. J., jun., 361.Dauben, W. G., 293, 361,414, 416, 417.Daudel, R., 294, 298.Daugherty, N. A., 44.Dautel, R., 132.David, J., 188.Davidson, A. W., 29.Davidson, E. B., 317.Davidson, J. M., 139, 200,Davidson, R. S., 429.568.524.362, 415.227.211.Davidson, T.A., 373, 414.Davidson, W. E., 193.Davies, A. G., 22, 193.Davies, C. W., 8, 22, 221.Davies, J. E., 376.Davies, J. S., 346.Davies, M., 309.Davies, W. G., 38.Davis, H. L., 163.Davis, M. M., 12, 13.Davis, S., 504.Davison, A., 215, 233, 237.Davison, G. A., 541.Davison, W. H. T., 98.Davydov, V. N., 544.Davydov, V. Ya., 125.Davydova, S. L., 184.Dawson, J. W., 184.Dawson, L. R., 21, 30.Dawson, R. L., 252, 361.Daxenbichler, M. E., 337.Day, A. C., 414.Day, J. C., 150.Day, M. C., 30.Day, W. C., 355.Deacon, G. B., 190, 221.Dean, F. M., 378.Dean, J. W., 418.Dear, R. E. A., 326.Debal, E., 564.De Boer, Th. J., 345.de Caro, G., 460.de Carolis, A., 553.Decius, J. C., 129, 142,Deck, J.C., 309.Deckert, H., 221.Declerck, F., 279.Decouvelaere, B., 419.Dedman, A. J., 226.Dedman, M. L., 481.de Dousa, R. M., 420.Deeds, W. E., 123.Deer, A., 463.Deffner, G. G. H., 449.de Flines, J., 412, 433.Defoe, J. D., 314.Degen, V., 128.De Graw, J. I., 386.de Hepche, S., 170.Dehnicke, K., 136, 199,Deichert, W., 99.De Jongh, D. C., 436.Delahay, P., 53.de la Mare, P. B. D., 251,De Lap, J. H., 26.Delaroff, V., 433.DeLederkremer, R. M.,De Ley, J., 438.Delfs, D., 118.de Lima, 0. G., 395.Della, E. W., 360.Delorme, P., 299.145.206.266, 275, 278, 312.549INDEX OF AUTHORS’ NAMES 627de Maeyer, L., 24, 40.de Mayo, P., 66, 72, 78, 79,343, 362, 369, 373.Dembitskii, I. A., 134.Demchenko, N. P., 387.de More, W.B., 83.DeNet, R. W., 260.de Neui, J. R., 165.den Hertog, H. J., 390.Denney, D. B., 331.Denney, D. Z., 331.Denning, R. G., 237.Dennison, D. M., 123, 142.Deno, N. C., 34, 251.de Nordwall, H. J., 39.DePamphilis, M. L., 323.de Pape, R., 181.De Puy, C. H., 258.Derbyshire, H., 73.Derevitskaya, V. A., 491.Dermarteau-Guisburg, H.,Derning, G. S., 485.De Roo, L., 535.Derr, V. E., 165.de Ruyter, H., 308.Desai. N. B.. 293.494.Dickens, F., 507.Dickerson, D. R., 390.Dickerson, R. E., 468.Dickey, E. E., 396, 443.Dickman, S. R., 513.Didkovskaya, 0. S., 536.Diebler, H., 46.Diebold, R., 190.Diekmann, J., 337, 348.Dietrich, H., 452.Dietrich, M. W., 44.Dijkerman, H. A., 162.Dikshitulu, L. S. A., 539.Dillon, J.F., 225.Dillon, R. L., 57.Di Maio, G., 381.di Marco Masironi, L., 607.Dimroth, K., 347, 394.Dinan, F. J., 283.Ding Djung H. Yang,Dingman, C. W., 524.Dingman, W., 517.Dinsel, D. L., 531.Dintzis, H., 518.Dintzis, H. M., 512, 514.Diorio, A. F., 130.358.nDoering, W. von E., 275,283, 329, 350, 357, 361,362.Dotzer, R., 189.Dogea, C., 394.Doggett, G., 232.Dogonadze, R. R., 41.Dohner, A. S., 82.Dohner, R., 559.Dohrmann, I., 328.Dolby, L. J., 259.Dolejs, L., 415.Dolfini, J. E., 410.Dollase, W. A., 213, 241,Dollimore, D., 225.Domann, E., 549.Domiguesdos Santos, J.,Dominy, B., 73.Donaldson, D. L., 532.Donaldson, J. D., 195.Donatti, M., 115.Donbrow, M., 19.Donnelly, D. M. X., 394.Donoghue, E., 340.Donoghue, J.T., 217, 226,586, 594.310.c22DiCi&, N., 168.Dickens, B., 587.DoeGing, J. P., 81.Doering, J. W., 85.DOWS, D. A,, 145.Doyle, L. C., 87628 INDEX OF AUTHORS’ NAMESDoyle, P., 370.Drabarck, S., 485.Drabkin, D. L., 509.Drabner, J., 532.Draganie, Z. D., 543.Dra.go, R. S., 195, 217, 226,228, 295.Drake, A. T., 72.Drees, F., 453.Dreiding, A. S., 385.Dreizler, H., 163, 164, 175.Drenth, W., 267.Dresdner, R. D., 196.Dribble, W. E., 514.Drochmans, P., 440.Drummond, P. E., 462.Dubeck, M., 240.Dubois, J. E., 11, 302.Dubois, J. T., 74.DGbravkova, L., 410.Dudek, G. O., 296.Dudley, F. B., 180, 201.Dudolph, H. D., 161.Dudykina, N. V., 395.Duecker, H. C., 22.Duggelby, P. M., 256.Dugger, H.A., 324.Duin, H. G. J., 556.Duke, F. R., 46.Dulz, G., 45.Dumazert, C., 548.Duncan, G. L., 105.Duncan, J. F., 177, 214.Duncan, J. L., 545.Duncanson, L. A., 238.Duncombe, W. G., 545.Dunitz, J. D., 368, 588, 598,Dunkelberger, D. L., 112.Dunkelman, L., 64.Dunn, M. F., 342.Dunn, M. G., 146.Dunn, T. M., 10, 139, 225.Dunsmore, H. S., 19.Dupeyrat, R., 148.Duphorn, I., 373.Durant, G. J., 500.Durham, L. J., 159, 409.Durig, J. R., 123, 310.Duron, 0. S., 545.Dutcher, J. D., 437.Dutler, H., 422.Dutta, N. L., 396, 445.Dutton, G. G. S., 444, 447.Duval, C., 138.Duvall, A. H., 549.du Vigneaud, V., 459, 460,Dvolaitzky, M., 422.Dwiggins, C., 220.Dwiggins, C., jun., 593.Dyatlovitskaya, E. V., 320,Dyck, R. H., 68.Dye, J.L., 29.Dyke, R., 43, 230.610, 611.484, 485.545.Dyke, S. F., 396.Dymanus, A., 161, 162.Dyrssen, D., 33, 221.Dyson, D. J., 65.Dyurovich, S., 581.Dzhagatkhezan, S., 144.Dzhanaletdinova, M. K.,564.Eaborn, C., 193, 275, 276.Eade, R. A., 374.Eades, J. F., 394.Eadie, J. M., 439.Eargle, D. H., jun., 312.Earle, F. R., 333.Earley, J. E., 42.Earnshaw, A., 216.Earnshaw, E., 210.East, G. C., 109.Eastham, J. F., 181, 324.Eastman, D. P., 122.Eastman, R. H., 365.Eastmond, G. C., 93, 95.Eastston, N. R., 391.Eaton, D. R., 218.Eaton, P. E., 72.Eaves, D. E., 106.Ebel, H. F., 250.Ebeling, M., 558.Eberhard, L., 444.Eberle, L., 30.Ebermann, R., 403.Ebke, K., 342.Ebsworth, E. A. V., 131,133, 167, 190, 202, 380.Eck, R.V., 526.Ecker, R. E., 513, 514.Eckhardt, G., 148.Eckstrom, H. C., 21, 30.Edelman, I. S., 519.Edelsten, N., 215.Edery, H., 483.Edgell, W. F., 134, 139, 142,Edgington, D. N., 257.Edgren, R. A., 426.Edmundson, A. B., 469.Edward, J. T., 294.Edwards, A. J., 180, 211.Edwards, D. A., 211, 212.Edwards, J. A., 421.Edwards, J. O., 31, 184.Edwards, L. J., 183.Edwards, 0. E., 254, 411.Edwards, P. N., 409.Efros, L. S., 378.Egan, E. P., 36.Egge, H., 434, 491.Eggensperger, E., 358.Eggensperger, H., 251.Eggers, D. F., 137, 201.Eggers, D. F., jun., 137,145, 172.Egli, Ch., 356.Eglinton, G., 326.Egyiid, L. G., 438.146.Ehrenberg, M., 602.Eluenberger, F., 560.Ehrenson, S., 298.Ehrhart, G., 346.Ehrlich, R., 132, 187.Eiber, H.B., 500.Eichelsdorfer, D., 200.Eichler, E., 46.Eichler, S., 94.Eiding, D., 191.Eiger, M., 24, 49, 50, 54.Eilar, K. R., 419.Eilingafeld, H., 325.Einstein, J. R., 468.Eirich, F. R., 446.Eisch, J. J., 276, 324.Eisen, B. M., 265.Eisenberg, A., 112.Eisenberg, H., 517.Eisenbraum, E. J., 318.Eisenstadt, J., 524.Ekong, D., 490.Elad, D., 323, 343.Elahi, M., 561.Eland, J. H. D., 77, 341.Elbeth, I. I. M., 532.Elder, F. A., 152.Elefant, M., 543.Eley, D. D., 114.Elias, L., 21.Elias, M., 533.Elias, S., 533.Eliassaf, J., 21.Eliel, E., 307.Eliel, E. L., 158, 296, 360.Elina, A. S., 393.Elison, C., 407.Elks, J., 421.Ellerman, J., 233, 234, 235.Ellestad, G. A., 373.Ellinger, F. H., 568.Elliott, A., 304.Elliott, D.F., 471, 479,483.Elliott, H. W., 407.Elliott, R. L., 191.Elliott, R. M., 150.Ellis, A. J., 38.Ellis, B., 418.Ellis, R. C., jun., 196.Ellis, R. L., 384.Ellison, F. O., 146.Ellison, R. D., 179, 573.Ells, F. R., 113.Elmore, D. T., 455.Elomaa, E., 332.Eloranta, J., 79.El-Sayed, M. A., 139, 232.Elson, D., 516.El Taylb, O., 433.Elving, P. J., 213.Embree, N. D., 22.Emelhus, H. J., 131, 138,200, 201, 202.Emerson, K., 572.Emerson, M. T., 51, 145.Emery, T., 462INDEX OF AUTHORS’ NAMES 629Emery, W. M., 314.Emmons, W. D., 261.Emons, H.-H., 181.Empedocles, P. B., 339.Emsley, J., 197.Emslie, A. G., 131.Endakova, E. A., 544.Endo, K., 366.Engebretson, G., 239, 587.Engebretson, G.R., 600.Engel, C. R., 422.Engel, W., 362.Engelbrecht, A., 166.Engelhard, N., 388.Engewald, W., 277.England, B. D., 13, 294.Englman, R., 127.Engmann, R., 578.Enzell, C., 366.Epikhjn, Yu. A., 32.Epstem, M., 196.Ercolani, C., 125.Erdey, L., 531, 552.Erdos, E., 92.Eriksen, J. L., 446, 498.Eriksen, S. P., 290.Er-Kank Wang, 547.Erlandson, A. L., 497.Erlandsson, G., 163.Erlanger, B. F., 290.Ermakova, M. I., 535.Erman, W. F., 308.Ermolaev, N. P., 205.Erne, F., 563.Emst, Z. L., 11, 12.Emster, L., 506, 507, 508.Erspamer, V., 460, 484.Ervasti, A., 291.Esbitt, A. S., 162, 170.Eschenmoser, A., 451, 454.Essyian, M., 11 8.Estrada-Parra, S., 497, 498.Esval, 0. E., 32.Etemadi, A. H., 356.Ettinger, R., 135, 305.Eudy, N.H., 418.Evans, A. G., 109,112,297.Evans, D. D., 323.Evans, D. E., 323.Evans, D. E. M., 314.Evans, D. F., 65, 139, 189,Evans, D. M., 92.Evans, J. C., 112, 136, 142,Evans, R. A., 338.Evans, R. J. D., 329.Evans, W. A. L., 434.Everest, D. A., 181.Everhard, M. E., 33.Evers, E. C., 21.Evert, H. E., 503.Evstaf’eva, 0. N., 139.Evstigneeva, R. P., 335.Ewing, G. E., 133.Exner, O., 292.303.209, 297.gylar, E. H., 488.$ r e , D. H., 372.{yring, E. M., 54, 153.Zyring, H., 153.hell, A. L., 503.Fabbri, G., 124.Fackler, J. P., 215, 223.Fahey, R. C., 265, 309,Fahrney, D. E., 290.Fairbrother, F., 189.Fajkos, J., 416.Falbe, J., 323.Fales, H. M., 365, 400.Falius, H., 198.Falk, M., 16.Falls, C. P., 292.Farina, M., 115.Farkag, J., 358.Farmer, T.H., 481.Farnum, D. G., 252, 385.Farona, M., 233.Farrar, K. R., 384.Farrell, P. G., 276.Farrier, N., 286.Farthing, E. C., 418.Fasano, M. B., 505.Fasella, P., 286.Fateley, W. G., 173, 299.Fatiadi, A., 181.Fattorusso, E., 385.Faust, J., 389.Faust, J. P., 183.Fava, A., 256, 278.Fava, G., 579, 591, 593,Favelukes, G., 525.Favero, P. G., 165,166,169,Favre, H., 254.Fay, R. C., 210, 224.Feairheller, S., 369.Feakins, D., 23, 30, 197.Feast, W. J., 314.Feates, F. S., 64.Feather, J. A., 57, 287.Feather, M. S., 437.Featherstone, W., 256.Fechtig, B., 356.Fedeli, E., 548.Fedeli, W., 388.Fedorouko, M., 542.Fedorov, V. A., 541.Fedorova, A. P., 539.FehBr, F., 202, 572.Fehlhaber, H.-W., 377.Fehlner, T.P., 154.Feigina, M. Yu., 463.Feigl, F., 532, 547, 549,Feingold, B. F., 481.Feinland, R., 556.Feitknecht, W., 33, 215.Feld, M., 269.Feldbauer, H., 52.331594.170.552, 576.Feldkimel-Gorodetsky, M.,Feldmann, H., 512.Feldott, G., 505.Fellmann, R. P., 114.Felten, E. J., 210.Feltz, A., 207.Fendler, J. H., 291.Feniak, G., 411.Fenoglio, R., 249, 363.Fensham, P. J., 98.Ferguson, J., 225.Fergusson, J. E., 198, 213,Fernandez, J., 173.Fernandez, V. P., 188.Fernando, M. J., 27.Fernelius, W. C., 35.Ferrari, A., 593.Ferri, C., 490.Ferrier, R. J., 436.Ferrier, R. P., 602.Ferrier, W. G., 607.Ferstandig, L. L., 106, 282.Fessell, H. H., 451.Fessenden, R. W., 307.FAtezon, M., 370, 415.Fetter, N.R., 187.Fetters, L. J., 110.Fiat, D. N., 17.Fichtner, K., 198.Fickweiler, E., 289.Fiedler, G., 315.Field, A. B., 217.Field, B. O., 180, 206, 210.Field, F. H., 151, 155.Fielden, E. M., 48.Fields, P. R., 179.Fieser, H., 421.Fieser, L. F., 416, 421.Figgis, B. N., 206, 594.Fike, C. T., 163.Filimonov, V. N., 125.Filina, A. I., 564.Filipovich, G., 108.Filipowicz, B., 564.Filler, R., 319.Finamore, F. J., 511.Finan, P. A., 438.Finch, C. A., 93, 107.Finch, N., 159, 408.Findlay, D., 472.Fine, N., 33.Finger, G. C., 390.Finholt, A. E., 187.Fink, W., 191.Finke, H. L., 297.Finkel’shtein, A. I., 378.Finkelshtein, A. V., 547.Finkelstein, M., 277.Finlayson, A. J., 259.Finn, F., 461, 472.Finnegan, R.A., 335, 343.Firl, J., 272.Firsching, E’. H., 537.Firsova, T. P., 181.343.594630 INDEX OF AUTHORS’ NAMESFischer, A., 38, 88,259,287.Fischer, D. W., 151.Fischer, E., 68, 290.Fischer, E. O., 236, 237,240, 242, 353, 587.Fischer, F., 378.Fischer, F. R., 322.Fischer, H., 208.Fischer, H. P., 259.Fish, L., 510.Fish, R. W., 353.Fisher, A. G., 399.Fisher, F. H., 38.Fisher, H. D., 190.Fisher, I. P., 281.Fisher, L. R., 305.Fisher, M. W., 497.Fishman, D. H., 324.Fishman, J., 321.Fishman, W. H., 434.Fitches, H. J. M., 256.Fitt, P. S., 484.Fitton, P., 351.Fitzi, K. O., 356.Fitzky, H. G., 165.Fitzwater, D. R., 220.Fiutak, J., 128.Flanagan, C., 173, 302.Flanigan, D. A., 538.Flate, J., 389.Flautt, T.J., 308.Fleet, S. G., 581.Fleischer, E. B., 605.Fleischmann, M., 40.Fleming, I., 265.Fleming, J. S., 304.Fletcher, A. P., 486.Fletcher, F. J., 89.Fletcher, H., 394.Fletcher, J. M., 214.Fletcher, W. H., 131, 133,Flett, M. St. C., 129, 299.Fleury, N., 540.Flid, R. M., 541.Fliszar, S., 289.Flitcroft, N., 189.Flitman, R., 503.Flood, P., 226.Flores, H., 423.Florian, E., 532.Florkin, M., 434.Flotow, H. E., 133.Flowers, H. M., 438, 495.Fluck, E., 177, 197, 198.Fluendy, M. A. D., 57,287.Flyantikova, G. V., 534.Flygare, W. H., 163, 171,Flynn, J., jun., 336.Flynn, R. R., 383.Foffani, A., 71, 76.Folting, K., 182.Fonken, G. J., 68.Font, J., 490.Forbes, W. F., 387.304.172.Ford, C. T., 197.Ford, J.A., 547, 553.Ford, J. D., 486.Ford, H. T., 158.Ford, H. W., 81.Fordhan, J. W. L., 106.Ford-Smith, M. H., 44.Forman, R. A., 170.Formen, L. E., 109.Forneris, R., 138.Forrat, E. F., 578.Forrester, A. R., 382.Forrester, J. D., 179, 180,Forsblad, K., 503.Forstner, J. A., 198.Fort, A. W., 258.Fosker, A. P., 465.Foss, O., 202.Foss, R. P., 65.Foster, A. B., 435, 437, 500.Foster, J. F., 436.Foster, P. W., 265.Foster, R., 280, 295.Foster, R. G., 448.Foulkes, D. M., 399.Fouquey, C., 373.Fowden, L., 449.Fowler, W. B., 64.Fowles, G. W. A., 206, 208,211, 212.Fox, J. R., 254.Fox, K., 123.Fox, M. E., 239.Fox, M. F., 84.Fox, M. R., 218, 591.Fox, R. E., 151.Fox, T. G., 107, 114.Fozard, A., 392.Fraenkel, G., 396.Fraenkel, G.K., 308.Fraenkel-Conrat, H., 468.Fraley, P. E., 123.Francis, C. M., 510.Francis, H. J., jun., 562.Francis, J. E., 449.Francis, R. J., 399.Francis, S. A,, 557.Franck, B., 403, 405.Franck, E. U., 37.Franck, R., 138.Franck, R. W., 259, 431.Frank, C. G., 111.Frank, H. S., 27.Frankiss, S. G., 190.Franklin, J. L., 151, 155.Franzus, B., 307.Fraser, M., 351, 384.Fraser, G. W., 132, 187.Fraser, R. R., 249, 364.Fraas, W., 341.Frasson, E., 219, 591, 594,Fratiello, A., 18.Frazer, J. W., 126, 559.Frazer, M. J., 186.568, 573.599.Frazer, R. T. M., 40, 41,Freedman, H. H., 275.Freeman, F., 290, 306.Freeman, H. C., 592.Freeman, J. P., 305.Freeman, K. B., 508.Freeman, T. E., 543.Freeman, W., 401.Freer, S.T., 468.Freiberg, L. A., 309.Freidlin, G. N., 544.French, C. M., 21.Freund, H., 542.Frey, A. J., 463, 464.Frey, H. M., 75.Frey-Wyssling, A., 440.Fribbins, E. A., .558.Fric, F., 549.Fricke, G., 198.Fricke, H., 341, 361, 385,Fridrichson, J., 388.Fridrichsons, J., 411, 608,Fried, J. H., 426.Fried, V. A., 522.Friedberg, F., 440.Friedel, R. A., 301.Frieden, E., 470, 502, 503,504, 510, 511.Friedenmann, T. E., 550.Friedlander, S. K., 59.Friedman, C., 282.Friedman, E., 480.Friedman, H. L., 26, 34.Friedman, J. P., 277, 344.Friedman, L., 156.Friedman, L. B., 182.Friedman, N., 251.Friedman, N. J., 10.Friedmann, H., 127.Friedmann, L., 346.Friedmann-Spiteller, M.,Friedrich, E. C., 252.Friedrich, H.B., 145.Friedrich, K., 342.Friend, J. P., 172.Frisch, M. A., 359.Fritsch, W., 421.Fritz, G., 188, 192.Fritz, H., 407.Fritz, H. P., 138.Fritz, J. S., 532.Fritz, P., 184, 186.Frlec, B., 179, 180.Frohlich, H.-O., 213.Frohwein, Y. Z., 435.Frommeld, H. D., 322.Froome. K. D., 161.Frost, D. C., 151.Fruton, J. S., 475.Fry, E. M., 391.Frydman, R. B., 438, 442.Fuchs, A., 371.230.419.609.401INDEX OF AUTHORS’ NAMES 631Fuchs, G., 195.Fuchs, R., 259, 292, 357.Fuchs, S., 480.Fuenelle, J., 438.Fuerholzer, J. F., 379.Fuginaga, J., 540.Fujii, S., 437.Fujimoto, S., 92.Fujishima, I., 562.Fujita, T. S., 351.Fujiwara, K., 320.Fukegawa, K., 405.Fuks, R., 351.Fukuda, K., 461, 468.Fukui, H., 394.Fukui, S., 438.Fukumoto, K., 405.Fukushima, S., 44.Fuller, E.J., 290.Fuller, M. E., jun., 184.Fuller, M. W., 289, 373.Fuller, N. A., 291.Fuller, W., 525.Funakubo, E., 293.Funasaka, W., 563.Fu Nhuan, N., 30.Funk, H., 212.Funk, K. F., 380.FUOSS, R. M., 18, 19, 20, 21,Furata, S., 308.Furberg, S., 436, 597.Furlani, C., 214.Furnival, S. G., 193.Furst, A., 308.Furukawa, H., 319, 405.FUPUbawa, J., 103.Futami, S., 98, 99.Futrell, J. H., 75, 100.Fyfe, W. S., 11.Gabb, E. G., 292.Gabe, E. J., 608.Gabra, G. G., 532.Gabrilova, L. A., 394. . Gadsby, B., 426.Giiumann, T., 150, 163.Gagan, J. M. F., 392.Gaglioti, L., 314.Gailar, N. M., 123.Gainer, A. B., 543.Gaines, D. F., 182, 183,Gaivoronskii, V. I., 134.Galasso, F., 678.Galinker, I.S., 37.Galkin, 0. A., 124.Gallagher, J. J., 165.Gallagher, P. K., 10.Gallagher, T. F., 421.Gallagher, W. P., 198.Galli, R., 387.Gal’pern, G. D., 561.Galt, R. H. B., 371.Galus, Z., 61.Gambini, M., 115.26, 38.185.Games, M. L., 239.Gamidov, R., 582.Gammack, D. B., 493.Ganis, P., 588, 595.Gans, P., 205.Ganter, C., 422.Ganter, K.-W., 199.Gantmakher; A. R., 113.Gantzel, P. K., 569.Gaoni, Y., 352.Gapp, F., 451.Garbisch, E. W., 263, 266.Garbisch, E. W., jun., 296,Garbutt, S., 435.Garcia- Fernandez, H., 178.Gard, G., 180.Gardella, L. A., 282.Gardi, R., 418.Gardner, D. M., 196.Gardner, E. R., 39.Gardner, J. N., 328, 462.Gardner, P. D., 259, 315,Gardner, R. S., 523, 626.Gardner, W.E., 214.Garg, H. G., 43;.Garilli, F., 556.Garland, C. W., 124, 139.Gar Lok Woo, 249.Garmire, E., 148.Garralda, B. B., 532.Garratt, P. H., 363.Garratt, P. J., 274, 350.Garratt, S., 389.Garrett, A. B., 183.Garrett, A. G., 187.Garrett, B. I., 114.Garrigou-Labrange, C., 310.Garst, J. F., 345.Garton, G., 189,217, 591.Garvin, D., 146.Gascoigne, J. A., 442.Gashko, G. P., 491.Gaspar, P. P., 275, 350,Gassman, P. G., 249, 423.Gaston, L. K., 266.Gatt, S., 492.Gatti, R., 84, 201.Gaudemer, A,, 373.Gaudry, R., 424.Gaur, J. N., 541.Gavilanes, C. R., 432.Gavrilenko, V. V., 188.Gaydon, A. G., 152.Gaylord, N. G., 91.Gazda, E. S., 553.Gazis, E., 453.Geacintov, G., 111.Gear, J. R., 399.Gebbie, H. A., 123, 127,128, 139, 299.Gebert, E., 179, 573.Gebura, S.E., 394.Gee, M., 549.306, 307.316.361.Geels, E. J., 348.Gefter, E. L., 563.Gehrke, C. W., 545.Geichmann, J. R., 212.Geier, G., 31.Geiger, F., 389.Geiger, R., 459, 460.Geisenfelder, G., 595.Geisler, K., 188.Geissman, T. A., 373, 394,Gelboin, H. V., 510.Geldard, J. F., 228.Geldern, K., 336.Geller, M., 148.Gellerman, J. L., 332.Gel’man, A. D., 205.Gel’man, N. E., 564, 565.Gemenden, C. W., 408.Gemmill, C. L., 503, 504,Gensler, W. J., 333.Gentile, P. S., 30.Genusa, V. A., 163.George, D. B., 109.George, J. H. B., 34.George, T. D., 215.Georgian, V., 422, 429.Gerber, A., 115.Gerber, F. W., 115.Gereste, J.-M., 321, 331.Gerhart, F. J., 184.Gerhart, F. S., 183.Gerig, J.T., 25.Gerloch, M., 587.Germain, G., 599.Gernert, F., 21.Gerngross, O., 286.Gerrard, W., 186.Gerratt, J., 139, 200, 211.Gerson, F., 384.Gestblom, B., 385.Geszetes, K., 408.Ghelis, N., 454.Ghersetti, S., 272.Ghosal, S., 399.Ghose, S., 580.Ghuysen, J. M., 495, 496.Giacomello, G., 388.Giacometti, G., 73.Giannini, u., 115.Gibbons, I. R., 89.Gibbons, L. K., 283.Gibbons, W. A., 87.Giber, J., 23.Gibert, R., 66.Gibian, H., 452.Gibson, C. W., 324.Gibson, F., 355.Gibson, G., 192.Gibson, G. W., 181.Giddings, W. P., 249.Giedt, D. C., 11.Gielen, M., 275.Gielen, W., 492, 493.Gieren, A., 191.400.505632 INDEX OF AUTHORS’ NAMESGierer, A., 519.Gierst, L., 53.Giese, C. F., 67, 152, 156,Giese, R.F., 217.Giguere, P. A., 16, 137, 138,139, 335.Gilbert, A., 79.Gilbert, B., 159, 374, 408,Gilbert, D. D., 541.Gilbert, G., 139.Gilbert, W., 513, 517, 524.Gilbreath, W. P., 201.Gilham, P. T., 334.Gilkerson, W. R., 21, 37.Gilks, S., 24.Gill, T. J., 480.Gillard, R. D., 216, 220,Gillespie, D. C., 496.Gillespie, J. F., 108.Gillespie, R. J., 15, 132,137, 138, 178, 201, 203,304.Gillessen, D., 457.Gillet, C., 279.Gillett, J. W., 437.Gillier, H., 606.Gillis, B. T., 325.Gillis, H. A., 98.Gilman, H., 324.Ginman, R. F. A., 311.Ginn, S. G. W., 299.Ginsberg, A. P., 214, 243.Giraldi, G., 579, 593.Gish, D. T., 468.Giudice, G., 524.Givol, D., 480.Givon, M., 34, 214.Gliiser, H., 199.Glarum, S. H., 197.Glaser, L., 494.Glass, D.S., 285, 361.Glass, I. I., 152.Glasser, L. S. D., 581.Glawitsch, G., 98.Glaze, W. H., 130.Glazier, E. R., 325.Gleinig, H., 328.Glemser, O., 199, 200, 201,Glen, G. L., 223, 589.Glick, R. E., 376.Glinka, J., 391.Glock, G. E., 506.Glockling, F., 193.Glowacki, E. R., 516.Glowiak, T., 593.Glueckauf, E., 26.Glusker, D. L., 114.Gnanadickam, C., 325.Godbole, E. W., 156.Godfrey, J. C., 388.Godtfredsen, W. O., 374,157.410.243.211.433.Goebel, W. F., 498.Goedertier, R. E., 170.Goedkoop, J. A., 569.Golitz, D., 201.Goerdeler, J., 388.Goering, H. L., 249, 254.Goerlitz, D. F., 545.Goetz, H., 289.Goetz, R. W., 259, 334.Goggin, P. L., 16, 131, 137.Gohlke, R. H., 150.Gohlke, R. S., 158.Gokhale, S.D., 29.Gold, A. M., 290.Gold, H., 258.Gold, L., 524.Gold, L. P., 165.Gold, M., 135.Gold, V., 57, 59, 275, 287.Goldberger, R. F., 479.Goldblatt, L. A,, 544.Golden, D. M., 143.Goldfarb, T. D., 134.Goldfinger, P., 337.Goldmann, F. L., 198.Goldring, H., 128.Goldschmid, H. R., 442.Goldsmith, N., 189.Goldstein, G., 538.Goldstein, H. W., 154.Goldstein, I. J., 438, 440.Goldstein, J., 468, 475, 512.Goldstein, J. H., 301.Goldstein, M., 251, 345.Goldstein, M. J., 270, 293.Goldstein, P., 575.Golfier, M., 370.Golovastikov, N. I., 582.Golsch, E., 449.Golubeva, G. A., 387.Gomel, M., 295.Gonqalves de Lima, O.,Gong, M.-L., 536.Gonzales, E. J., 220.Good, C. D., 184.Good, W. D., 297.Goode, W. E., 107,112,114.Goodgame, D.M. L., 217.Goodgame, M., 217.Goodgame, M. D. L., 189.Goodlett, V. W., 336.Goodman, H. M., 521.Goodman, L., 437.Goodman, M., 455.Goodrich, F. C., 106.Goodspeed, F. C., 72.Goodwin, T. W., 332.Goosen, A., 382.Gopal, R., 34, 37.Gopala Rao, G., 532, 539,Gopinath, K. W., 402.Gorbach, S., 560.Gorbachev, S. V., 37.Gorbitz, J. H., 42.356, 372.543.Gordon, A. R., 38.Gordon, A. S., 71.Gordon, B. M., 46.Gordon, J., 196.Gordon, J. E., 294.Gordon, J. T., 68, 373.Gordon, L., 537.Gordon, M., 323.Gordon, R., 73.Gordon, S., 48.Gordy, W., 160, 161, 165,Gorin, G., 216.Gorin, P. A. J., 446.Goring, D. A. I., 443.Gormann, M., 409.Gornowicz, G. A., 285.Gorokhov, L. N., 155.Gorski, J., 511.Gorski, L., 562.Gorvin, J.H., 268.Goschke, R., 411.Goseki, S., 537.Gosselck, J., 202.Gosser, L., 273.Got, R., 486, 488, 490.Gothe, W., 531.Goto, T., 394, 416.Gotschlich, E. C., 446.Gott, C. T., 123.Gott, P. G., 381.Gottschalk, A., 489.Goubeau, J., 135, 136, 184,Gough, T. A., 504.Gough, T. E., 9, 11.Gould, R. O., 217, 221.Goutarel, R., 412, 415, 433.Gouverneur, P., 561.Govindachari, T. R., 402.Gowan, A. C., 97.Gozzini, A., 162.Grabczak, J., 562.Grabowski, Z. R., 53.Graddon, D. P., 223, 591.Graf, D. L., 580.Graham, C. L., 324.Graham. E. R. B., 489.166, 168, 302.192, 195, 196, 202.Graham; J., 189. .Graham, J. F., 193.Graham, R. K., 112.Gramera, R. E., 443.Grandberg, I. I., 386.Grand-Jean, D., 584.Granito, C., 322.Grant, D.M., 301.Grant, D. W., 543.Grant, H. N., 356,Grant, I. J., 609.Grant, J. A., 560.Grant, R. F., 302.Grasley, M. €I., 357.Grasselli, J. G., 234.Gratch, S., 107, 114.Gravel, D., 254, 423.395.37 2INDEX OF AUTHORS’ NAMES 633Gravenor, R. B., 133, 140,Graves, J. M. H., 426.Gray, D. O., 449.Gray, H. B., 179, 203, 212,215, 221, 223, 227, 232,233, 305.Gray, P., 297, 304.Gray, W. R., 478.Graybeal, J. D., 166, 172,Graybill, B. M., 261.Grdeni6, D., 190, 195, 589.Greeley, R. S., 28.Green, B., 432.Green, B. N., 299.Green, D. H., 99.Green, D. W., 468, 606.Green, J. H., 344.Green, J. H. S., 299.Green, L. G., 36.Green, M., 196, 231, 293.Green, M. L. H., 237, 238,Green, R. W., 227.Greenberg, C., 501.Greenberg, S., 307.Greenfield, H., 313.Greedeld, S., 556, 559.Greenspan, C., 514.Greenwood, C.T., 439, 440.Greenwood, F. L., 334.Greenwood, N. N., 132,182, 187, 189, 203.Gregor, H. P., 29, 33.Gregorowicz, Z., 533.Gregory, H., 410.Gregory, J. D., 490.Gregory, J. E., 71.Grekov, A. P., 387.Grellmann, K. H., 383.Grenda, V. J., 453.Grenier-Besson, M.-L., 164,Gresham, J. T., 401.Gressmann, K., 531, 532.Grey, T. F., 332.Gribov, L. A., 145.Grice, M., 483.Griesbaum, K., 269, 321,Griffin, C. E., 323, 358, 381.Griffith, W. P., 226, 236.Griffiths, D. L., 225.Griffiths, J. E., 134, 192.Griffiths, T. R., 9.GrifXths, V. S., 21.Grigoryan, K. A., 321.Grim, S. O., 238.Grimes, N. W., 584.Grimley, T.B., 123.Grimm, D., 289.Grimmelikhuysen, J. C.,Grimshaw, J., 372.Grineva, N. I., 384.141, 143.303.241.168.329.334.X o t , R., 463, 464.kipenberg, J., 394.Jrisdale, P. J., 309.Jritter, R. J., 289.Jrob, C. A., 251, 259,Jroebke, W., 437.Jroeneveld, A., 33.Jroh, G., 242.Jronbaek, R., 568, 598.Gronowitz, S., 385, 386.Gros, F., 516, 517.Grosjean, M., 275.Grosmagin, J., 100.Gross, D., 391.Gross, E., 471.Gross, H., 342.Gross, J., 510, 513.Gross, M., 564.Gross, P. M., 33.Grossberg, A. L., 481.Grosse, A. V., 179, 180.Grossman, A., 527.Grossman, L., 528.Grossman, R. F., 349.Grossweiner, L. I., 79.Groth, P., 360, 571, 572,597, 603, 613.Grove, D. J., 151.Grove, J. F., 378.Grovenstein, E., 275.Grover, N., 421.Grover, P.K., 417, 421.Grubb, E. L., 136, 209.Grubb, H. M., 158.Gruen, L. C., 287, 297.Grutzmacher, H. F., 159,Grunberg-Manago, M., 526.Grundon, M. F., 315, 384,Grunwald, E., 31, 51, 52,Grunwald, R., 33.Grunze, H., 196, 198.Gryaznov, V. M., 124.Gryder, J. W., 25, 47. ,Grzonka, Z., 456.Grzybowski, A. K., 30, 31.Guarnieri, A., 169, 170.Gubler, B., 368.Guiebe, R., 144.Gunthard, H. H., 163, 172,Gunther, D., 335.Giinther, P., 318.Guertin, J. P., 192.Guggenheim, E. A., 25, 26,Guglielmetti, L., 376.Guidotti, G., 475.Guilbault, G. G., 550.Guiochon, G., 556.Gulik-Krzywicki, T., 14.Gundermann, K. D., 293.Gundlach, F., 438.364.451.401.53, 297.306, 359.27, 28.k n n , S. R., 36.Junning, G.E., 64.Junning, H. E., 85, 86, 87,Junstone, F. D., 332, 333.Junther, H., 346.Gupta, S. K., 132, 186.Jupta, S. R., 27, 28.Juran, A., 548.Jurliand, I. S., 100.Jurr, G. E., 607.Jush, H. P., 128.Justafson, D. H., 353.Justafson, E., 157.Zustafsson, E., 156.Gustafsson, R., 508.Elusten, H., 68.Guthie, G. B., 297.Guthrie, R. D., 435.Gutowsky, H. S., 390.Guttenberger, J. F., 84.Guttman, A., 145.Guttmann, S., 282, 455,Gutzwiller, J., 368.Guy, R. G., 238.Guyon, P., 548.Gwik, H., 321.Gwinn, W. D., 161, 169,88.459, 460.170, 172, 173, 302.Haag, A., 320, 346.Haake, P., 85.Haas, A., 138, 200, 201.Haas, H., 309.Haas, J. W., 287.Haas, T. E., 33.Haas, W., 461, 472, 532.Haas, W. J., 470.Haase, R., 28, 33.Habeeb, A.F. S. A., 481.Haberfield, P., 260, 342.Hackeng, W. H. L., 355.Hadinec, I., 580.Haeberle, H., 136.Haede, W., 421.HBfner, K. H., 350, 351.Haendler, H. M., 228.Haenni, A.-L., 450.Haeusler, C., 123.Hafer, K., 251.Hafner, K., 341, 398.Haga, M., 260.Hage, S. M., 347.Hagemann, R., 154.Hagen, A. W., 343.Hagenmuller, P., 182, 187,Haigh, C. W., 340.Haim, A., 231.Haiss, H. S., 207.Hai Won Chang, 359.Hakeem, M. A., 29.Hakka, L., 259.Hale, J. D., 35.Halevi, E. A., 294.188634 INDEX OF AUTHORS’ NAMESHall, B. D., 516.Hall, C. E., 515, 519, 520.Hall, D., 221, 591.Hall, D. M., 323.Hall, F. R., 185.Hall, G. E., 277.Hall, H. K., 292.Hall, J. R., 220, 312.Hall, L. D., 436.Hall, L. H., 182.Hall, R., 227.Hall, R.T., 82.Hall, S. R., 373.Hall, T. C., 81.Hall, W. L., 262.Hallada, C., 181.Hallam, H. E., 120.Haller, W., 22.Hallgren, B., 333.Halliwell, H. F., 36.Hallot, A., 315, 419.Halpern, J., 40, 42, 43, 45,Halsall, T. G., 374.Halsey, G. D., jun., 137.Halvorson, H. O., 519, 523.Ham, N. S., 133.Ham, Y. W., 285.Hamaguchi, H., 536.Hamann, S. D., 39,277.Hameed, A., 373.Hamer, J., 272, 390.Hamer, N. K., 139.Hamet, R., 407.Hamill, W. H., 156, 157.Hamilton, G. A., 277, 289,Hamilton, J. A., 609.Hamilton, J. K., 440.Hamilton, M. G., 513.Hamilton, P. B., 551.Hamilton, W. C., 236.Haming, M. C., 158.Hamlet, M. J., 287.Hammer, G., 337.Hammes, G. C., 230, 286.Hammond, G. S., 62, 65,88,89, 261, 293, 331.Hammond, P.R., 295.Hamon, D. P. G., 259, 413,Hamor, T. A., 609, 611.Hanack, M., 251, 358.Hancock, C. K., 292.Hand, E. S., 393.Hands, A. R., 392.Hmessian, S., 437.Hanic, F., 592.Hanna, 3. G., 550.Hanns, V., 415.Hansen, B., 290, 292, 293.Hansen, H. J., 283.Hansen, R. G., 440.Hansen, R. L., 58.Hansen-Nygaard, L., 171,46.344.418, 431.173, 174.Hanson, A. W., 586, 609,Hanson, J. R., 371.Hanson, R. W., 465.Hansson, A., 581.Hansson, H. G., 12.Hansson, K. A., 540.Hansteen, C., 541.Hantzsch, A., 57.Hanus, H., 549.Hanus, V., 54.Haque, R., 540.Hara, A., 99.Harda, H., 493.Hardegger, E., 356, 422,Hardesty, B., 521.Hardy, A., 578.Hardy, C. J., 180, 206, 210.Hardy, D. G., 406.Hardy, F. E., 438.Hardy, P. M., 466.Hare, C.R., 212.Harington, C. R., 490.Harker, D., 468.Harker, J. L., 336.Harkness, D. R., 524.Harley, J. D., 259.Harley-Mason, J., 265, 335,Harmon, D. F., 15.Harmony, M. D., 135.Harned, H. S., 22, 28.Harnisch, H., 177.Harper, J. S., 285.Harrington, W. F., 296.Harris, A. D., 214.Harris, C. M., 216, 220.Harris, G., 439.Harris, J. F., 269.Harris, J. I., 518.Harris, M., 375.Harris, P. M., 572.Harris, R. A., 65.Harris, R. K., 303.Harris, S. W., 183.Harris, T. M., 268.Harrison, C. R., 395.Harrison, I. T., 374, 429.Harrison, J. W., 372.Harrison, P. M., 468.Harrison, R., 435, 500.Harrison, S., 370.Harrison, W. F., 361, 396.Harsiinyi, K., 391.Hart, E. J., 11, 48.Hart, H., 251, 252, 261,290, 306, 344.Hart, P.B., 132.Hart, R. G., 516.Hartenstein, J. H., 68, 198,Hartley, B. S., 469, 478,Hartley, D., 426.Hartley, F. K., 487.614.437, 450.382, 395.361.483.Hartman, A., 460.Hartman, J. S., 308.Hartman, M. F., 71.Hartmann, H., 309.Hartmann, W., 331.Hartruck, J. A., 611.Hartshorn, M. P., 252.Hartung, H., 329.Harvey, G. J., 292.Harvey, K. B., 126.Harvey, R. G., 324.Haschke, E., 549.Hasegawa, H., 421.Hasegawa, M., 418.Hasek, R. H., 358, 381.Haselkorn, R., 522.Hashimi, M. H., 561.Haskell, T. H., 437.Hass, D., 199.Hassall, C. H., 346.Hassel, O., 360, 572, 597,603, 613.Hasserodt, U., 320.Hassner, A., 423.Hasted, J. B., 31.Hatch, L. F., 259.Hatchard, C. G., 64.Hatchard, W. R., 387.Hatcher, G., 533.Hatfield, W.B., 501.Hatfield, W. E., 210.Hathaway, B. J., 131, 134,Hathaway, C. E., 301.Haft, H. H., 612.Hatz, E., 454.Haubenstock, H., 317.Haug, A., 445.Hauge, J. G., 519.Haugen, G. R., 34.Hauke, P., 434.Hauser, C. F., 320.Hauser, C. R., 268, 382.Hautecloque, S., 78.Hauth, H., 258.Havez, R., 486.Havinga, E., 360.Havsteen, B. H., 290.Hawes, L. L., 202.Hawkins, C. J., 220.Haworth, R. D., 402.Hawthorne, M. F., 261,277.Kay, G. W., 434, 649.Hayakawa, S., 433.Hayase, Y., 371, 414.Kayashi, M., 164, 175.Hayans, M., 433.Hayden, P., 105.Hayes, M. J., 116.Haylock, J. C., 294.Haynes, L. J., 405,406.Haynes, N. B., 319.Hayter, R. G., 207, 218,219, 235, 243.Hazdra, 6. A,, 316.Hazekamp, R., 574.194, 226INDEX OF AUTHORS’ NAMES 635Hazell, A.C., 190,202, 572.Heacock, R. A., 311.Head, H. N., 155.Heal, A. R., 418.Heal, H. G., 186, 200.Hecht, H. G., 300.Hecht, J. K., 249, 363.Hecht, K. T., 123, 142.Hecht, L. I., 512.Hechter, O., 469.Heck, R. F., 234, 330.Hedgley, E. J., 437.Hedman, R., 506.Hegarty, A. F., 259.Hegenbarth, J. J., 603.Heicklen, J., 74, 142.Heidelberg, R. F., 169.Heidelberger, M., 497, 498,Heilbronner, E., 384.Hein, G. E., 290.Heine, H. G., 423.Heinemann, G., 256.Heinert, D., 391.Heinke, B., 455.Heintz, E. A., 206.Heischkeil, R., 419.Heistand, R. N., 10.Heiszwolf, G. J., 325.Heitler, C., 289.Heitman, P., 347.Heitsch, C. W., 132, 187,Heitzer, H., 89.Hekkert, G. L., 267.Helbert, J.R., 500.Helgren, P. F., 292.Helgstrand, E., 277.Helland, S., 597.Hellberg, K.-H., 211.Hellegers, A. E., 474.Heller, C. J., 474.Heller, M. S., 423.Hellerbach, J., 451.Helling, C., 187.Hellwarth, R. W., 147, 148.Helm, C. C., 139.Helsley, G. C., 268.Helvenston, E. P., 215.Henbest, H. B., 315, 365.Henderson, R., 375.Henderson, R. B., 257.Henderson, W. A., jun.,Hendley, E. C., 259.Hendrickson, J. B., 368,389, 408, 411, 500.Hendrikx, Y., 23.Hendry, D. G., 293.Hengge, E., 192.Henley, D., 440, 441.Hem, D. E., 217, 591.Henneberg, G., 192.Hennes, J., 64.Hennis, H. E., 272.Henrici-Olive, G., 104.499.575.196.Benry, J. P., 68, 269, 330.Henry, M. C., 193.Hensel, W., 297.Hepfinger, N. F., 358, 381.Hepler, L.G., 35, 36, 294.Heranz, J., 300.Herber, R. H., 214, 233.Herbert, E. J., 414.Herbich, M. A., 445, 545.Herbig, J. A., 258, 259.Herbst, D. R., 426.Kerbst, P., 328.Kerendeen, R., 148.Herget, W. F., 123.Herk, L., 330.Herman, R., 123.Herman, R. M., 127.Hermann, R. B., 309.Hermans, J., jun., 297.Hermes, M. E., 314.Herndon, J. A., 123.Herner, A. E., 510.HBrold, A., 190.Herold, R. J., 275.Herout, V., 366, 367, 368.Herr, W., 213.Herranz, J., 145.Heme, W., 10.Herries, D. G., 472.Herrmann, H., 415.Hers, H. G., 441.Herschbach, D. R., 142,164, 175, 300.Hersh, R. T., 518.Hershaft, A., 199.Hershko, A., 515.Hertler, W. R., 348.Hertz, H. G., 17, 18.Herz, W., 368.Herzberg, G., 64.Herzog, H., 11.Herzog, S., 188, 192, 208,Hess, B., 506, 507.Hess, G.P., 290, 479.Hesse, R. €I., 399.Hesselbarth, H., 578.Hessler, E. J., 365.Hester, R. E., 15, 144, 189,Hetnarski, B., 195.Hetzer, H. B., 28, 30, 31.Heusler, K., 424, 425.Heussner, W.-D., 201.Heuther, C. H., 193.Hewett, W. A., 95.Hewlett, P. C., 216.Hexter, R. M., 126, 130.Hey, D. H., 345, 346, 347.Hey, H. D., 78.Heydweiler, A., 22.Heyes, J., 342.Heying, T. L., 183.Heyman, H., 497.Heyns, H., 317.Heyns, K., 159, 434, 451.210.349.Zckam, C. W., 185.&ham, W. M., 151.3ickinbottom, W. J., 277.3icklin, A., 516.3iebor, W., 233, 234, 236,aiga, H., 476.Higashimma, T., 98, 99,117, 119.Bigasi, K.-I., 307.Higginson, W. C. E., 43,46,Higgs, M. A., 596.High, D.F., 468.Higson, H. G., 540.Hijikata, K., 166, 169.Kikime, S., 537.Hildenbrand, D. L., 154.Bilders, H., 525.Hileman, J. C., 232.Hill, D. A. W., 207.Hill, D. G., 268.Kill, E. A., 358.Hill, H. C., 155.Kill, J., 423.Hill, J. H. M., 387.Hill, R. J., 468.Kill, R. L., 468.Hiller, G., 336.Hills, G. J., 27, 28, 38.Hilmer, W., 583.Hilmoe, R. J., 524.Hilschmann, N., 468.Himmelblau, D. M., 22.Hindman, J. C., 17.Hine, J., 337.Hinman, R. L., 381.Hino, T., 411.Hinze, J., 223.Hiraga, K., 426.Hirai, H., 367.Hirai, S., 324.Hirakawa, H., 169.Hirano, S., 500, 537.Hirata, Y., 369.Hirokawa, S., 598.Hiroshi Tanida, 249.Hirota, E., 168, 172, 175,176, 303, 304.Hirota, K., 100.Hirs, C. H. W., 468, 469,Hirsch, H., 219.Hirschfeld, D., 202, 572.Hirschfeld, F.L., 602.Hirschfeld, M. A., 127.Hirst, E. L., 444, 445.Hirst, J., 278.Hirst, M., 399.Hisao Okada, 292.Hisashi Uda, 253.Hisatsune, I. C., 128, 135.Hiskey, R. G., 451, 454.Ho, L., 236.Hoagland, M. B., 512, 624.Hoang Minh, 535.236.230.473, 491636 INDEX OF AUTHORS’ NAMESHoard, J. L., 222, 223, 571,Hoare, D. E., 70.Hoare, F. E., 92.Hobbs, J. J., 416.Hobgood, R. T., jun., 301.Hobrock, B. G., 306.Hoch, F. L., 501, 504, 507.Hochester, R. M., 438.Hochheimer, B. F., 135.Ho Dac An, 372.Hodge, J. D., 251.Hodge, P., 382.Hodgeson, J. A., 174.Hodgkin, D. C., 610.Hodgkins, J. F., 89.Hodgson, F. N., 151.Hoekstra, H. R., 206.Hoekstra, W. G., 440.Horfeldt, A. B., 386.Hofer, P., 432.Hofer, R.J., 540.Hoffman, A. S., 91.Hoffman, J. M., 123.Hoffman, P., 490,499, 500.Hoffmann, H., 134.Hoffmann, R. A., 385.Hoffmann, R. W., 281,346.Hoffmann, W., 109.Hoffmeister, E., 78.Hofmann, A., 463.Hofmann, J. E., 265, 275,320.Hofmann, K., 457, 459,461, 472, 482.Hofmann, T., 468.Hofmeister, H., 432.Hogeveen, H., 267, 272.Hoijer, D. J., 501.Hoijtink, G. J., 65.Holah, D. G., 226.Holava, H., 442.Holdrege, C. T., 388.Holeysovsky, V., 469.Holker, J. S. E., 415.Holland, R. V., 221.Hollands, T. R., 373.Hollas, J. M., 302, 311.Holleck, H., 208.Hollenberg, L., 145.Holley, R. W., 527.Holliday, R. E., 272.Hollifield, G., 509.Hollinger, G., 507.Hollingworth, B. R., 513,Holloway, J. H., 179, 180,Holly, F.W., 384Holm, R. H., 215, 218, 241,Holman, R. T., 333.Holmes, J. M., 194.Holmes, J. R., 351.Holmes, K. C., 518.Holmes, L. H., 209.589.516.214.296.Holmes, 0. G., 213.Holmes, R. R., 198.Holroyd, R. A., 86.Holt, P. F., 393.Holt, S. L., 216.Holtz, W. J., 384.Holubek, J., 408.Holzapfel, C. W., 370.Homberg, O., 111.Homer, J., 436.Homer, J. B., 156.Honde, S., 517.Honeycutt, J. B., jun., 187.Honeyman, J., 434.Honour, R. J., 145.Honzl, J., 459.Hood, A., 150.Hoodless, R. A., 206.Hoogsteen, K., 606, 612.Hooper, E. W., 214.Hooton, F. A., 193.Hoover, F. W., 336.Hope, D. B., 484, 485.Hopff, H., 272.Hopkins, C. Y., 332.Hopmann, H., 396.Hoppe, R., 179, 578.Hopton, J. W., 439, 488.Hora, J., 422.Horak, M., 358.Hori, M., 397.Horne, R.A., 38, 44.Homer, L., 78, 293, 335.Homer, S. M., 209, 211,Hornig, D. F., 13, 129, 144.Homing, E. C., 434.Horrobin, S., 280.Horrock, W. de W., jun.,Horrocks, W. D., jun., 139,Horsfield, A., 299.Hortmann, A. G., 423.Horton, D., 436, 437, 438,Hoshino, O., 371,495.Hoskins, B. F., 592.Hossenlopp, I. A., 297.Hosterman, E. F., 269.Hostynek, J., 251, 364.Hoty, A., 322.Hougen, J. T., 142, 164.Hough, L., 435, 436, 486.Hough, W. V., 183.House, D. A., 13, 221,294.House, H. O., 258, 314, 316,322, 338, 340.Houser, J. J., 251.Hovenkamp, S. G., 580.Hovorka, F., 50.How, M. J., 436.Howard, J.,, 301, 333, 436.Howarth, M., 186.Howden, M. E. H., 251.212.179.146, 236.499.Howden, M.E. W., 358.Howe, J. A., 163, 171.Howe, J. P., 67.Howe, L. H., 16.Howells, W. G., 277, 354,Hoyer, H., 282, 297.Hozumi, K., 559, 561.Hseu, T.-M., 230.Hsia Chen, C. S., 269.Hsieh, H., 115.Hsiu, H. C., 376.Hsiu-Chu Hsu, I., 408.Huang, F. Y. Y., 490.Huang, J.-J., 461.Hubbard, R. L., 145.Hubbard, W. N., 297.Hubel, M., 239.Hubele, K. W., 290.Huber, H., 80, 315.Huber, J. E., 249, 364.Hubert, A. J., 340.Hudec, J., 266.Hudson, B. E., jun., 307.Hudson, M., 226.Hudson, R. F., 196, 289,Hubel, W., 233, 586.Huebner, C. F., 340.Hubner, G., 391.Hiickel, W., 249, 254, 259,Huehns, E. R., 476.Hiinig, S., 336.Hiittner, W., 168.Huff, T., 102.Huffman, G. W., 440.Huffman, J. W., 366.Hugel, G., 372.Huggett, C.M., 107.Huggins, D. K., 232.Huggins, M. L., 106.Hughes, G. A., 426.Hughes, R. E., 571, 572.Huguenin, R., 455.Huheey, J. E., 196.Huisgen, R., 250, 273, 277,281, 337, 344, 378.Huitric, A. C., 308.Huizinga, F., 524, 525.Hulett, J. R., 287.Hultin, T., 513, 523, 525.Hume, D. N., 11, 220.Humiec, F. S., 219.Hummel, J. P., 473.Humphrey, J. P., 256.Hunger, K., 453.Hunt, H. R., 216.Hunt, J. A., 523.Hunt, J. P., 8, 42, 230.Hunter, G. D., 513.Hunter, J. A., 560.Burst, G. L., 380.Kurwitz, H., 53, 152.355.HSU, Y.-Y., 461.HsU, H.-Y., 376.293.264, 359INDEX OF AUTHORS’ NAMES 637Husain, M. M., 34.Husain, W., 543.Husebye, S., 202.Husemann, E., 103, 440,Hush, N. S., 41.Hussain, D., 80, 82, 85.Hussek, H., 192.Hutchison, D.A., 151.Hutson, D. H., 437, 438.Hutton, H. M., 306.Hutton, J. J., 521.Hutzinger, O., 311.Huxley, H., 515.Huybrechts, G., 337.Huyffer, P. S., 390.Huygen, C., 532.Huynh, C., 423.Huyser, E. S., 269.Hwang A m Kim, 46.Hyde, K. R., 214.Hylton, T. A., 85.Hymers, W. A., 280, 345.Hyne, J. B., 17, 20, 255.Iawai, I., 327.Iball, J., 602, 606.Iber, P. K., 311.Ibers, J. A., 208, 243, 588.Ibne-Rasa, K. M., 264, 277,Ibuki, F., 517.Ide, J., 327.Ignat’eva, L. A., 125.Iitaka, Y., 584.Ikekawa, N., 371.Ikkes, D., 507.Iliceto, A., 256.Illingworth, B., 441, 442.Illingworth, G. E., 269.Illingworth, G. E., jun., 329.Illsley, R., 123.Illuminati, G., 279.Ilyukhin, V. V., 576.Imhof, V., 187.Impastato, F.J., 274.Inamoto, N., 310.Inatome, M., 186.Inayama, S., 368.Inch, T. D., 435, 500.Indelli, A., 13, 25, 48.Inghram, M. G., 152, 157.Ingold, C. K., 381.Ingraham, M. C., 67.Ingram, D. J. E., 146.Ingram, G., 558, 563.Inoue, M., 505.Inoue, T., 342.Inouge, A., 517.Insole, J. M., 280.Inubushi, Y., 402, 403.Ioan, V., 277.Ioffe, B. V., 556.Ioffe, D. V., 378.Ioffe, S. T., 181, 296.Ippolitov, E. G., 213.447.345.Ireeverre, F., 449.Ireland, R. E., 370, 413.Iriate, J., 423.Irving, H., 180, 227, 228,Isaacs, N. S., 393.Isagulyants, V. I., 321.Iseeva, F. A., 324.Iselin, B., 452, 459.Ish’iama, A., 522.Ish i, S., 449.Ishii, T., 374.Ishiwata, Y., 317.Ishizaka, O., 533.Ishui, H., 433.Isibasi, M., 540.Isler, E.O., 396.Isler, O., 396.Islip, P. J., 330.Issa, R., 125.Isslieb, K., 213.Itatani, H., 313.Ito, E., 496.Ito, H., 367.Ito, M., 542.Ito, S., 366.Itoh, K., 308.Ivanoff, C., 316.Ivanov, V. S., 100.Ivanov, V. T., 451, 463.Ivanova, L. V., 564.Ivanovov, Yu. B., 61.Iverach, G. G., 371, 413.Ives, D. J. G., 17, 27, 28.Ives, E. K., 186.Ivin, K. J., 91, 92, 96.Iwamoto, R. T., 17.Iwanska, S., 539.Iwasaki, H., 346, 590.Iwasaki, S., 417.Iwata, K., 375, 376.Izatt, R. M., 31, 35.Izmailov, N. A., 30, 294.Izumi, K., 488.Jache, A., 167.Jackman, L. M., 331, 352,355, 356, 370, 372, 391,395, 450.242.Jackson, A. H., 311.Jackson, B. G., 388.Jackson, E., 256.Jackson, H. L., 190.Jackson, J. A., 224.Jackson, R.H., 168, 169,Jacob, F., 501, 509.Jacobi, N., 146.Jacobs, A. M., 324.Jacobs, G. D., 173, 174.Jacobs, T. L., 269, 329.Jacobs, W. A., 413.Jacobsen, E., 541.Jacobsen, M., 358.Jacobson, E., 187.Jacobson, H. C., 127.172, 302.Jacobson, R. A., 575.Jacox, M. D., 126.Jacox, M. E., 81, 126, 129.Jacques, J., 422.Jiiger, L., 92.Jaeggi, K. A., 432.Jaff6, H. H., 223, 294, 310,Jaff6, J. H., 127, 146.Jaffe, S., 81.Jaffee, I., 498.Jagendorf, A. T., 514.Jahn, A., 417.Jain, D. V. S., 85.Jain, S. C., 134, 207.Jakubke, H.-D., 455.James, A. T., 544.James, D. M., 398.James, D. W., 221.James, E. L., 277.James, F. C., 67.Jameson, R. F., 217, 221.Janbar, S. A., 563.Jander, G., 21.Jann, K., 379.Jannuzzi, N., 163.Janor, M.M., 433.Janot, M. M., 159,409,414.Jansen, A. B. A., 426.Janssen, M. J., 193, 194.Janz, G. J., 28, 120, 133,Janzon, K. H., 575.Jaquenoud, P.-A., 455,459,Jarabak, R. R., 465.Jardetzky, O., 312.Jardine, R. V., 311, 383.Jart, A., 332.Jarvie, A. W., 191.Jaseja, T. S., 166.Jaselskis, B., 276.Javan, A., 166.Jayaraman, P., 368.Jeanes, A., 446.Jeanloz, R. W., 438, 488,495, 499, 500.Jefferies, P. R., 372.Jeffers, W., 183.Jeffery, E. A., 268.Jefford, C. W., 360.Jeffrey, G. A., 203,218,576,595, 596, 599, 606, 614.Jeffries, R., 436.Jeger, O., 69, 358, 367, 422,Jellinek, F., 586, 604.Jellinek, O., 536.Jen, M., 168, 302.Jencks, W. P., 286, 293.Jenkins, A. D., 94, 96, 97,Jenkins, D. R., 167, 169,Jenne, H., 185.Jensen, E.V., 324.340.221.484, 485.423, 424.102, 103, 106.171, 190638 INDEX OF AUTHORS’ NAMESJensen, F. R., 250, 307.Jensen, J. H., 255.Jensen, J. L., 292.Jensen, K. A., 218.Jensen, L. H., 252, 599,Jensen, S. L., 332.Jensovsky, L., 580.Jentzsch, J., 336.Jerschkewitz, H.-G,, 202.Jesse, N., 156.Jesson, J. P., 142, 144.Jevons, F. R., 487.Jezowska-Trzebiatowska,B., 47, 222, 236.Jicha, D. C., 229.Jina, V., 437.Jindal, S. P., 308, 362.Jiracek, V., 437.Joachim, E., 418.Job, B. E., 172.Jochims, J. C., 289.Johl, A., 460.Jorg, J., 318.Jost, K., 484.Joesten, M. D., 226, 228,Johannesen, R. B., 214.Johansson, G., 584, 589.Johari, G. P., 21.Johncock, P., 324.Johns, J. W. C., 166.Johns, W.F.. 428.Johnsen, R. H., 88.Johnson, A. W., 389, 465.Johnson, B. C., 356.Johnson, C. K., 73.Johnson, D. W., 266.Johnson, E. A., 275.Johnson, F., 391.Johnson, F. A., 135, 196.Johnson, G. A., 493.Johnson, H., 547.Johnson, H. W., 381, 383.Johnson, J., 441.Johnson, J. N., 37.Johnson, J. S., 11.Johnson, L. F., 308.Johnson, Q. C., 571.Johnson, S. A., 216, 231.Johnson, 8. L., 291.Johnson, T. A., 283.Johnson, U., 108.Johnson, W. A., 153.Johnson, W. S., 259, 315,359, 413, 419, 421, 428,429, 431.Johnston, R., 94, 96, 97,103, 106.Johnston, 8. L., 294.Johnstone, R. A. W., 330.Jolles, J., 468.Joll&s, L., 490.Jolles, P., 468, 490, 494.Jolley, H. R., 37.Jolly, J. E., 69.608.295.Jolly, W. L., 181, 195.Jonas, J., 360.Jonassen, H.B., 211, 214,220, 227, 238.Jonathan, N., 135.Jones, A. C., 144.Jones, D., 139.Jones, D. A. K., 292.Jones, D. H., 387.Jones, D. W., 579.Jones, E. A., 15.Jones, E. E., 559.Jones, E. R. H., 328, 421.Jones, F. R., 35.Jones, G., 365, 392, 400.Jones, G. C., 382.Jones, G. R. N., 56.Jones, J. B., 290.Jones, J. K. N., 437, 438,Jones, L. H., 17, 123, 139,Jones, M., jun., 357.Jones, M. M., 15, 27, 199,Jones, M. T., 48, 297.Jones, 0. W., 523, 525, 526,Jones, P. J., 39.Jones, P. R., 296, 378.Jones, R. H., 11, 145.Jones, R. T., 468, 475, 479.Jones, W. D., 141.Jones, W. M., 329, 357.Jonsson, I., 579.Joop, N., 384.Jordan, S. J. P., 86.Jordan, T., 598.Jrargensen, C. K., 205, 216,Jorgensen, E.C., 501.Jorgenson, M. J., 71, 321,Jortner, J., 79, 84, 179.Josefowitz, D., 103.Joshi, B. S., 384, 407.Joshi, R. M., 91.Joska, J., 416.Joslyn, M. A., 445.Jost, K., 459.Jost, K. H., 582, 585.Joule, J. A., 409.Joy, A. S., 556.Jucker, E., 378.Jucker, H., 79.Juenke, E. F., 210.Jukes, T. H., 526.Julg, A., 295.Julia, S., 419, 420.Jumper, C. F., 52, 53.Jung, L., 356.Jung, W., 10.Jungreis, E., 534, 547.Junji Maekawa, 292.Junk, G., 159, 451, 552.Jurd, L., 394.443, 446.206, 226.224, 277, 293.527.223, 229.357, 395.Jurecek, M., 554.JusIBn, C., 433.Just, G., 355.Justice, J. C., 20.Juza, R., 181.Kaandorp, A. W., 275,277.Kabachnik, M. I., 296.Kabanov, V. A., 92, 115.Kabaskalian, P., 76.Kabat, E.A., 498.Kader, A. J., 454.Kadunce, R. E., 287, 432.Kaediag, W. W., 318.Kaesz, H. D., 139,232,234.Kagan, F., 425.Kahle, W., 455.Kahler, E., 583.Kahlweit, M., 19.Kainz, G., 558.Kaiser, E. M., 316, 317,339.Kaiser, E. T., 293, 312.Kaji, H., 469, 523.Kajtar, M., 459.Kakabadse, G. J. K., 558.Kakihana, H., 533.Kakisawa, H., 376.Kakudo, M., 575, 600.Kalf, G. F., 496.Kalia, Y. K., 554.Kallos, G., 402.Kalman, 0. F., 145.Kalsi, P. S., 367.Kalvoda, J., 424, 425.Kalyanaramrtn, R., 540.Kamayima, S., 487, 488.Kamei, T., 510.Kamenar, B., 190, 195.Kamenskaya, S., 103.Kametani, T., 405,Kamhi, S. R., 580.Kamneva, A. L., 544.Kampf, M. J., 112.Kampmeier, J. A., 78.Kan, C., 412.Kanai, K., 394.Kanamura, F., 591.Kanbayashi, U., 301.Kane, A.A., 123.Kaneko, K., 537.Kang, J. W., 313.Kang, S., 358.Kangro, W., 33.Kano, H., 312.Kanoh, N., 117.Kano-Sueka, T., 526.Kapadia, V. H., 369.Kaplan, F., 272, 275, 303.Kaplan, M. L., 51.Kapoor, K. R., 539.Kapoor, R. N., 205.Kappeler, H., 452,453,457.Karabasheva, V., 128.Karabatsos, G. J., 251,304.Karabatsos, P. J., 51.Karabinos, J. V., 336INDEX OF AUTHORS’ NAMES 639Karagounis, G., 125.Karanka, S., 85.Kardos, E., 539.Karger, E. R., 263.Kargin, V. A., 92, 115.Karkhanis, Y., 504.Karl, D. J., 29.Karl, G., 85.Karle, I. L., 608.Karle, J., 608.Karlen, B., 452.Karlson, P., 432.Karmarkar, S. S., 384.Karplus, M., 300.Karrer, P., 407.Kartha, C. C., 367.Kartha, G., 610, 611.Kartunark, E.M., 19.Kasai, N., 575.Kasai, P. H., 172, 175,Kasper, J. S., 571.Kasturi, T. R., 432.Kasuya, T., 173, 174.Katchalski, E., 465.Kates, M., 494.Kato, G. K., 469.Kato, K., 533.Kato, T., 383.Kato, Y., 108.Katovic, V., 210.Katritzky, A. R., 277, 296,299, 391, 393.Katsoyannis, P. G., 457,460, 461, 468.Katti, M. R., 142.Katz, J. J., 286.Katz, T. J., 270, 271, 274,308, 350, 354, 363.Kaufer, J.-N., 494.Kauffman, D. L., 469.Kauffmann, T., 316, 347.Kaufman, J. J., 132.Kaufman, S., 510.Kaufmann, H. P., 371.Kaufmann, J. J., 154.Kauunann, W., 37.Kaverzueva, E. D., 486,Kavtaradze, N. N., 124.Kawabata, N., 103.Kawai, K., 139.Kawamura, S., 336.Kawazoe, Y., 312.Kay, H. F., 584.Kay, R. L., 9, 21.Kaye, I.A., 313.Ka,zda, A., 119.Kaziro, Y., 527.Keana, J. F. W., 429.Keane, F. M., 195.Kebarle, P., 86, 87, 156.Keck, J., 84.Kecki, Z., 14, 131, 144.Keefer, R. M., 260.Keely, H. C., 184.301.487, 491.Keenan, T. K., 206.Keene, J. P., 48.Keggi, J. J., 465.Keil, B., 296, 469.Keilin, B., 184.Keites, L., 540.Keith, M. C., 436.Kelkar, G. R., 365.Keller, E. B., 512, 513.Keller, H. E., 60.Keller, J., 23.Keller, K. H., 59.Keller, 0. L., 210.Keller, 0. L., jun., 136.Keller, P. J., 513.Keller, R., 170, 302.Keller, W., 356.Keller-Schierlein, W., 372,Kelley, D. J., 113, 115.Kelly, D. H., 202.Kelly, F. J., 32.Kelly, J. T., 344.Kelly, R. B., 454.Kelly, T. R., 19.Kemmitt, R. D. W., 186,Kemp, R. T., 265.Kempe, C.H., 383.Kempster, C. J. E., 581.Kemula, W., 53.Kenausis, L. C., 21.Kendall, F. H., 277.Kendall, P. A., 550.Kende, A. S., 350, 357.Kendrew, J. C., 468.Kenji Okano, 292.Kennard, C. H. L., 571,Kennard, O., 482, 612.Kennedy, C. D., 211.Kennedy, E. P., 506.Kennedy, J. P., 119.Kenner, G. W., 311, 382,Kennerly, G. W., 94.Kenney, C. N., 169.Kenney, H. E., 422.Kenney, T. E., 301.Kent, G. J., 389.Kent, P. W., 315.Kenyon, J., 292.Kenyon, W. O., 91.Kepert, D. L., 212, 222.Kerenyi, P., 539.Kergomard, A., 321, 331.Kerker, M., 23, 32.Kerkow, A., 334.Kerler, W., 177.Kern, R., 584.Kern, R. J., 115, 206.Kern, S., 148.Kern, W., 115.Kerr, J. A., 73, 75.Kerridge, ID. H., 221.Kershaw, J. W., 383.395, 463.225.591, 593.448, 449, 466.Kerwin, J.P., 429.Kerwin, L., 151.Kessler, H., 361, 385.Ketchum, M., 88.Ketelaar, J. A. A., 585.Kevill, D. K., 265.Kevill, D. N., 265.Kew, D. J., 387.Kewley, R., 165, 167, 170,Keyworth, D. A., 540, 551,Kezdy, F. J., 289, 290.Khachkuruzov, G. A., 163.Khairallah, P. A., 482.Khalafalla, S. E., 216.Khaleeluddin, K., 257.Khan, M. A., 386.Khananova, E. Ya., 196.Khaogiwall, K. A., 540.Kharasch, C., 429.Khare, B. N., 129.Kharitonov, Yu. Ya., 130,138, 139, 219.Khastgir, H. N., 373.Khedouri, E., 290.Khene, E., 580.Khin, L., 556.Khokhlov, A. S., 462.Khorana, H. G., 512.Khorlina, I. M., 317.Khromov-Borisov, N. V.,Khuong-Huu, Q., 412, 415.Khuong-Huu-Laine, F.,Kiang, A. K., 409.Kice, J.L., 259.Kiciak, S., 642.Kidder, G. W., 355.Kido, H., 35.Kiefer, H., 361.Kieffer, W. F., 67.Kielczewski, M. A., 415.Kielley, W. W., 296.Kier, L. B., 402, 543.Kierkegaard, P., 582.Kiessling, H., 441.Kikindai, M., 21.Kikkawa, S., 326.Kikuchi, K., 89.Kikuchi, T., 330, 403.Kikuchi, Y., 172.Kilbourn, B. T., 222, 568.Kilgore, W. W., 445.Kilpatrick, M., 285, 286,Kilpatrick, M. L., 285.Kflpi, S., 31.Kilroe, J. G., 106.Kim, H., 170, 302.Kimbrough, R. D., 460.Kimel, S., 127.Kimla, K., 61.Kimmel, J. R., 468, 469.Kimura, M., 476.306.557.394.412, 415.289640 INDEX OF AUTHORS’ NAMESKin, Z. W., 461.Kincaid, J. F., 107, 114.Kindler, H., 450.Kinell, P. O., 139.King, E. L., 10.King, G. S. D., 340, 588.King, H.C. A., 229.King, J. A., 89.King, J. F., 78, 260.King, J. R., 344.King, L. C., 227.King, M. V., 468.King, P. A., 58.King, R. B., 193, 212,233, 235, 236, 237, 240,241.King, R. N., 353.King, R. W., 414.King, W. T., 142, 145.Kingston, W. R., 233.Kinoshita, Y., 606.Kinsey, E. L., 130.Kinsey, J. L., 163, 169.Kippur, P., 553.Kirby, A. J., 293.Kirby, F. B., 58.Kirby, G. W., 399,400,406,Kirchhoff, W. H., 167, 169.Kirdani, R., 418.Kirk, D. N., 252.Kirkwood, S., 439, 441.Kirschenbaum, A. D., 179,Kirsten, W. J., 540, 559,Kirtman, B., 164.Kirwin, J. B., 47, 219.Kiryushkin, A. A., 451,Kiselev, A. V., 124, 125.Kiser, R. W., 306.Kisfaludy, L., 459.Kishimoto, Y., 332.Kishita, M., 220.Kiss, T. A., 538.Kitai, R., 468.Kitamiera, Y., 545.Kitano, H., 394.Kitao, T., 336.Kitaoka, Y., 336.Kitchener, J.A., 297.Kittila, A., 139.Kivelson, D., 170.Kjaer, A., 337, 448.Kjeldass, T., 151.Kjeldgaard, N. O., 513.Kjdberg, O., 439, 440.Klanberg, F., 230.Klatsmenyi, P,, 563.Kleber, W., 582.Klee, L. H., 290.Kleen, R. H., 162.Kleiger, E., 452.Kleiman, J. P., 240.Klein, E., 319.414.180.563.463.Klein, G. W., 86, 259.Klein, M. P., 162.Kleinberg, J., 216.Kleine, K.-M., 327, 328.Kleinerman, M., 53.Kleinfelter, D. C., 252, 308,Klejnot, 0. J., 192.Klement, R., 556.Klemer, A., 438.Klemperer, H. G., 507,508.Klemperer, W., 130, 131,165, 173, 299.Klenha, J., 437.Klenk, E., 492, 493.Klestermeyer, H., 461.Klett, D.S., 213.Klyaev, V. I., 547.Klyne, W., 278, 415.Klimentova, N. V., 184.Klimov, V. V., 536.Klimova, A. I., 183.Klimova, V. A., 546, 564.Klingsberg, E., 389.Klinke, H., 388.Kliowsky, B., 492.Kloosterziel, H., 78, 337,Klose, G., 380.Klots, R. R., 88.Klotz, I. M., 478.Klouwen, M. H., 547.Kneubuhl, F., 163.Knight, A. R., 64, 87, 88.Knight, B., 64.Knight, C. A., 468.Knight, H. M., 344.Knight, J. C., 375, 432.Knights, B. A., 416.Knipe, W. W., 196.Kniseley, R. N., 132.Knobler, C., 126, 605.Knopf, P. M., 519.Knorr, R., 281.Knoth, W. H., jun., 131.Knowles, T. A., 183.Knox, G. R., 271.Knox, K., 225, 243.Knox, L. H., 420.Knutson, G., 250.Kobayashi, H., 372.Kobetz, P., 187.Koch, C. W., 180, 559.Koch, F.W., 339.Koch, K., 361.Kochel, I., 544.Kocheshkov, K. A., 130.Kochetkov, N. K., 436,437,Kochi, J. K., 316, 331.Kochloefl, K., 548.Kocourek, J., 437.Kobrich, G., 346.Kohl, H., 238.Koehler, W. C., 578.364.361.491.Konig, C., 341, 350, 351,Koenig, E., 139.Konig, E., 208.Konig, W., 471.Kopf, H., 194.Koepfli, J. B., 402.Korbl, J., 560.KO&, E., 229.Koster, R., 389.Kofstad, P., 208.Kogan, V. A., 208.Kogelnik, H., 147.Kohle, H., 105.Kohler, G. O., 544.Kohlrausch, F., 22.Kohlschutter, H. W., 221.Kohnstam, G., 33, 254, 256.Kojima, T., 171, 173.Kok, J. G. J., 547.Kokalis, S. G., 197.Kokkoris, P. A., 583.Kolesnikov, G. S., 184.Kolker, P. L., 348.Kolonites, P., 391.Koltai, L., 552.Kolthoff, I.M., 13, 22, 216,Komers, R., 544, 548.Komitsky, F., 396.Kompig, I., 410.Kon, H., 211.Konasiewiez, A., 257.Kondo, E., 433.Kondo, K., 169.Kondrat’ev, V. P., 37.Konig, E., 214.Konig, W., 456.Konigsberg, W., 468, 475.Konno, K., 313.Konovalova, L. N., 125.Konovalova, M. I., 491.Konrad, D., 42.Konrad, P., 453.Konstantinov, B. P., 533.Kooyman, E. C., 276, 293,Kopanica, M., 540.Kopecky, K. P., 88.Kopecky, K. R., 106.Hopple, K. D., 466.Korchemnaya, T. B., 57.Kornblum, N., 260, 261,Kornegay, R. L., 248, 364.Kornelli, W., 204.Korner, A., 511, 513.Kornilov, I. I., 208.Korobkov, V. I., 37.Koronko, I. I., 545.Korotkov, A. A., 113.Korshun, M. O., 560.Korte, F. 320, 323.Kortum, G., 8, 20, 29.Korvtkov, A. A., 113.KoSciolak, J., 493.398.294.296.342INDEX O F AUTHORS’ NAMES 641Kosel, C., 316.Koshkin, N.V., 534.Koski, W. C., 154.Koski, W. S., 132, 182.Koskikallio, J., 291.Kosolapova, T. Ya., 204.Kosower, E. M., 330, 390.Kosower, E. N., 391.Kost, A. N., 386, 387.Kostkowski, H. J., 145.Kothyarevskii, I. L., 378.Kotov, Yu. I., 136.Koubek, E., 345.Koutecky, J., 54.Kovacic, P., 339.Kovredov, A. I., 184.Kovtun, V. Y., 333.Koyama, H., 605.Koyama, K., 342.Kozak, P., 554.Kozminskaya, T. Z., 186.Kraak, A., 326.Kraihanzel, C. S., 139, 232.Krajewski, J., 563.Kramm, D. E., 547.Kramolowsky, R., 236.Krapcho, A. P., 390.Krasinski, A. H. A., 333.Krasnaya, Z. A., 332.Krasulina, V. N., 113.Kratzer, P., 182.Kratzl, K., 325.Krauch, C.H., 334, 343.Kraus, C. A., 21.Krause, L., 121.Krause, R. A., 227.Krause, R. M., 497.Krauss, M., 153.Kraut, J., 468, 608.Krebs, B., 199.Krebs, F., 192.Kreevoy, M. M., 15, 50, 57,Kreil, G., 468, 476.Kreilich, R., 347.Kreimer, S. E., 538.Kreiter, V. P., 51.Krejci, I., 484.Krentsel, B. A., 378.Krepinskgi, J., 366.Kresge, A. J., 58, 59, 276.Kreshkov, A. P., 542, 564.Krespan, C. G., 397.Kresze, G., 272.Kretchmer, R. A., 68, 265.Kretov, A. E., 554.Kreuder, M., 350.Kreutzberger, A., 378.Kreuzbichler, L., 190.Krewson, C. F., 333.Kreye, W. C., 79.Krieger, A. L., 289.Kriegsmann, H., 134.Krikorian, 0. H., 571.Kriloff, H., 365.Krimen, L. I., 378.58, 265.XKrisher, L. C., 169, 174.Krishnan, K., 132.Krishnan, M.G., 77.Krishna Pillai, M. G., 169.Krishna Ras, P. V., 543.Kristal’nyi, E. V., 98.Kristiansen, L. A., 142, 143.Kritchevsky, T. H., 421.Krivis, A. F., 553.Krivtsov, N. V., 36.Kroc, It. L., 502.Krohnke, F., 378.Krogh-Moe, J., 581.Krogmann, K., 590.Kromholtz, K. L., 571.Kromhout, R. A., 51.Krone, W., 515.Krongauz, V. A., 99.Kropf, A., 153.Kropp, P. J., 285, 417, 428.Krot, N. N., 205.Krueger, P. J., 146.Krug, R., 524.Kruh, R. F., 220, 593.Krumholz, P., 139.Krupski, E., 556.Kruse, F. H., 205.Krysin, E. P., 463.Kryukov, P. G., 125.Kuang, Y.-T., 461.Kuba, P., 539.Kubaniova, O., 549.Kubertschek, E., 210.Kubo, M., 220.Kubose, D., 157.Kubota, H., 541.Kubota, S., 412.Kuby, S. A., 504.Kucera, J., 548.Kuchen, W., 198.Kucherov, V.F., 332.Kuchitsu, K., 142,164, 165.Kuckertz, H., 191.Kuczkowski, R. L., 171,Kuhlthau, H. P., 304.Kuster, H., 576.Kuff, E. L., 514.Kuhls, J., 343.Kuhn, J. L., 154.Kuhn, L. P., 186.Kuhn, M., 135.Kuhn, R., 434, 490, 491.Kuhn, S. J., 118, 252.Kuivila, H. G., 58, 193,Kula, M.-R., 195.Kul’ba, F. Ya., 541.Kulkarni, K. S., 365.Kull, U., 135.Kullbom, S. D., 556.Kumaoka, S., 502.Kumler, W. D., 391.Kummer, D., 191.Kump, W. G., 159, 410.Kunde, J., 460.172, 201.316.Kundu, N., 422.Kuntz, I., 113, 115.Kuntz, N. L., 115.Kuntz, R. R., 88.Kunz, H. W., 480.Kunz, M., 30.Kunze, R. W., 19.Kupchan, S. M., 290, 375,403, 412, 433.Kuril’chikova, G. E., 132.Kurland, C.G., 513, 517.Kurland, R. J., 297, 362.Kuroda, R., 536.Kuroda, Y., 220.Kuromo, &I., 372.Kurowski, S., 14, 144.Kurtz, A. N., 290.Kushida, H., 437.Kustin, K., 24, 40, 50.Kutney, J. P., 407.Kutschke, K. O., 75.Kutsenko, Yu. I., 209.Kuwata, K., 100.Kuzel, P., 240.Kuz’mina, N. N., 554.Kuznetsova, A. I., 272.Kuznetsova, V. M., 564.Kwart, H., 258, 259.Kwei, G. H., 170.Kwok, J., 128.Kwon, J. T., 193.Kynaston, W., 299.Kyriakis, A., 339.Labes, M. M., 51.Labouesse, B., 290.Lachowicz, D. R., 289.Lack, R. E., 432.LaCourt, R. B., 359.Ladner, W. R., 137.Lady, J. H., 138.Lafferty, W. J., 122, 299,La Flamme, P. M., 329.Laframboise, E., 563.Lagally, P., 105.Lagowski, J. J., 185, 242.Laidler, K. J., 12, 35,-294.Laiho, S., 292.Laine, F.K. H., 433.Laitenberger, K., 135, 195.Laity, R. W., 59.Laki, K., 489.Lakin, H. W., 634.Lakomy, J., 560.Lakshminarayanan, G. N.,LaLancette, E. A., 274, 360,La Lau, C., 308.Lalor, G. C., 231.Lambert, J. B., 284, 358,Lambert, J. L., 274, 364.Lambert, R., 437.Lambertsen, G., 333.300.19.363.362642 INDEX O F AUTHORS' NAMESLamfrom, H., 516.L a m , B., 277.Lamola, A. A., 89.Lampe, F. W., 75, 99, 155.Lampert, F., 377.Lampman, G. M., 358.Lancaster, J. E., 237.Land, E. J., 77, 78.Landau, A., 127.Lande, S., 460, 484.Landesman, H., 323.Landheer, C. A., 390.Landor, S. R., 329.Lane, A. P., 228.Lane, C. A., 58.Lang, R. P., 295.Langdon, R. G., 506.Lange, L. J., 71.Lange, R.J., 289.Lange, R. M., 339.Langford, C. H., 231.Langridge, R., 518, 608.Langworthy, W. C., 275.Lannogl, R. A., 541.Lanoux, S., 197.Lansbury, P. T., 188, 313,Lanz, P., 460.La Paglia, S. R., 72.Lapidot, A., 265.Lapina, T. A., 532.Laplaca, S. J., 243.Lappert, M. F., 185.Lapporte, S. J., 313.La Prade, J. E., 260.Larcombe, B. E., 186.Lardy, H. A., 504,505, 506,Larina, N. I., 664.Larkin, D. M., 161, 302.Larkin, F. S., 9.Larkins, T. H., jun., 199.Larkworthy, L. F., 210,Larner, J., 441.Laroche, L., 226.Larsen, B., 445.Larsen, L. P. O., 448.Larson, A. C., 571, 576,Larson, M. L., 211.Larson, R. C., 17.Larsson, C. E., 539.Larsson, K., 596, 599.Larsson, R., 17, 216.Larsson, S., 333.Laskin, A. I., 524.Laskov, R., 440.Lasoski, S.W., 108.Last, W. A., 197.Laszlo, P., 309, 365.Latimer, G. W., jun., 540.Laubengayer, A. W., 185.Lauer, W. M., 283.Laughton, P. M., 259.Laureut, T. C., 490.358.507.216.580, 607.Laurie, S. H., 34.Laurie, V. W., 142, 163,164, 167, 169, 171, 174,175, 300, 302, 303.Lautenshaeger, F., 307.Lauterbur, P. C., 309.Lauwers, A., 144.Lauwers, H. A., 14.Lavagnino, E. R., 388.Lavaux, J. P., 419, 420.Lavelle, D. E., 204.Law, D. A., 413.Law, H. D., 466, 484.Law, R. W., 154.Lawler, E. A., 552.Lawler, R. G., 277.Lawlor, J. M., 293,Lawrie, R. A., 440.Lazarev, Yu. A., 143.Leach, S. J., 297.Leahy, J., 512.Leane, J. B., 294.Leath, M. J., 509.Leatherwood, J. M., 446.Leaver, D., 388.Lebedeva, A.I., 558, 560.Le Bel, N. A,, 249,263, 268,Le Bel, R. G., 443.Le Blanc, 0. H., jun., 169.Lebowitz, J. L., 84.Lecar, H., 169.Leciejeewicz, J., 576.Lecomte, J., 138.le Count, D. J., 169, 410.Ledaal, T., 546.Leden, I., 34.Lederberg, S., 614, 516.Lederberg, V., 516.Lederer, E., 372, 446, 450,Lederer, F., 366.Lederer, M., 331.Ledger, R., 265.Ledig, K. W., 426.Ledvina, M., 487.Ledwith, A., 108, 118, 337.Lee, C. C., 259.Lee, C. L., 111, 113, 296.Lee, C. M., 408.Lee, G. H., jun., 186.Lee, G. R., 551.Lee, H. S., 290.Lee, I., 277.Lee, M., 296.Lee, P. A. H., 190.Lee, Y.-P., 506.Leebrick, J. R., 111.Leeming, H. E., 156.Leermakers, P. A., 88, 89.Lees, E. M., 434.Leete, E., 399.Le FGvre, C. G., 312.Le Fi.vre, R.J. W., 301,Leffler, J. E., 297.364.494, 495.306, 310, 312, 360.Legare, R. J., 45.Legay, F., 129.Legendre, P., 71.Le Goff, E., 359.Legrand, M., 433.Lehar, L., 560.Lehman, P. A., 601.Lehman, W. J., 154.Lehmann, H., 184.Lehmann, H.-A., 185, 578.Lehmann, J., 435.Lehmann, R., 138.Lehmann, W. J., 142.Lehn, J. M., 374, 376, 377,Lehninger, A. L., 508.Lehrle, R. S., 156.Lehtinen, T., 332.Leibowitz, J., 436.Leicht, C. L., 327.Leiderer, G., 200.Leidy, G., 498.Leifer, L., 29.Leighton, P. A., 62, 69, 81.Leisegang, E. C., 123.Leist, M., 18.Leja, L., 554.Le Mahieu, R., 419.Lemal, D. M., 358.Le Men, J., 169, 409, 412,Lemieux, R. U., 301, 333,Lemmon, R. M., 394.Lemons, J. F., 224.Le Neindre, B., 188.Lengyel, B.A., 146.Lengyel, P., 523, 527.Lengyel, S., 23.Lenhard, R. H., 418.le Noble, W. J., 260, 261,Lento, H. G., 547, 553.Leonard, J. A., 346, 347.Leonard, M. A., 563.Leonard, N. J., 379, 398.Lepard, D. W., 122, 300.Le Postollec, M., 139.Leppanen, K., 33.Lergier, W., 460.Le Roy, D. J., 38.Lesage, M., 254.Lesiak, T., 386.Lessard, G., 422.Lessor, H. E., 604.Lester, G. R., 21.Leto, M. F., 94.Letsinger, R. L., 267.Lettr6, H., 417.Leung, C. Y., 481.Leuthardt, F., 516.Levart, E., 60.Levchuk, L. E., 203.Lever, A. B. P., 217, 227.Lever, B. G., 26.Levich, V. G., 41, 61.416.414.436.331, 342INDEX OF AUTHORS’ NAMES 643Levin, E. S., 546.Levin, I. W., 145.Levina, R. Ya., 378.Levine, I. N., 170, 305.Levine, S.G., 367, 418.Levintow, L., 520.Levisalles, J., 263.Levison, S. A., 47.Levitan, J., 46.Levitt, B. W., 281.Levitt, L. S., 281.Levy, A. J., 268.Levy, D. H., 75.Levy, E., 534.Levy, H. A., 179, 573.Levy, J., 159, 409.Levy, J. F., 254.Levy, M. N., 241, 353.Levy, R. M., 17.Lewak, S., 438.Lewbart, M. L., 318.Lewin, A. H., 247, 364.Lewin, R., 183.Lewis, A., 275, 363.Lewis, A. F., 394.Lewis, B. A., 434, 549.Lewis, B. B., 429.Lewis, D., 191.Lewis, D. T., 564.Lewis, E. J. C., 510.Lewis, E. S., 280.Lewis, G. P., 483.Lewis, G. S., 323.Lewis, J., 85, 206, 217, 220,Lewis, J. W., 321.Lewis, K. G., 374.Lewis, T. B., 316.Lewis, T. D., 96.Lewis, T. J., 226.Leydon, R. J., 354.Li, C. H., 455, 459, 481,Liao, S., 511, 526.Libby, E.M., 277.Libby, W. F., 41.Liberek, B., 456.Lichstein, B. M., 132, 187.Lichtenstein, J., 515.Lichtin, N. N., 21, 297.Lide, D. R., 302.Lide, D. R., jun., 135, 165,168, 170, 171, 172, 173,174.225, 227, 235, 594.482.Liebau, F., 582.Lieber, E., 195.Liebl, H., 64.Liechti, P., 450.Lieder, W., 73.Liedtke, U., 493.Lieflander, M., 491.Liehr, A. D., 222, 226.Liemry, R., 45.Lienhard, K., 191.Liesemer, R. N., 268.Lieser, K. R., 25, 44.Lieske, C. N., 259.Lietzke, M. H., 16, 28, 33,Lifson, S., 297.Light, A., 469.Likhoshertsov, L. M., 491.Liler, M., 294.Lillycrop, J. E., 292.Lin, C. C., 162, 163, 166,169, 173, 174, 300.Lin, J. H., 153.Lin, Y.-Y., 376.Lind, J. E., 19, 21.Lindahl, U., 490.Lindberg, B., 441.Lindberg, O., 501, 506.Linde, H., 432.Lindell, E., 31.Lindholm, E., 156, 157.Lindquist, I., 592.Lindquist, L. C., 68.Lindsay, W.T., 19.Lindsey, A. S., 341.Lindstrom, R. E., 37.Lineback, D. R., 436, 438.Linek, A., 580.Linek, K., 542.Linevsky, M. J., 126.Lingafelter, E. C., 218, 590,591, 593.Link, H., 259.Linke, K.-H., 202, 572.Linn, W. J., 380.Linnell, R. H., 295.Linnett, J. W., 191, 339.Linschitz, H., 79, 383.Lions, F., 227, 228.Lipmann, F., 506, 507, 512,Lippert, E., 73.Lippincott, E. R., 16, 129,Lippman, I., 64.Lipschitz, L., 171.Lipscomb, W. N., 179, 182,183, 184, 223, 468, 573,587, 598, 608, 611.37.523, 525.130, 301.Liptay, W., 295.Lischeta, L. I., 55.Lisitsa, M.P., 146.Lissitzky, S., 503, 525.Lister, J. H., 378.Littauer, U. Z., 517.Little, J., 543.Little, L. H., 124.Little, R., 138.Little, W. F., 355.Littlefield, J. W., 513.Littlewood, P. S., 429.Litvin, K. I., 537.Liu, T.-Y., 446, 459.Liveris, M., 279, 390.Livigni, R., 108.Liwschitz, Y., 451.Llewellyn, D. R., 257.Llewellyn, F. J., 590, ,599.Lloyd, D. R., 17.Lo, T., 481.Locchi, S., 584, 585.Lockhart, J., 253.Lodge, J. E., 343.Lods, L., 372.Loeser, E., 418.Low, H., 501, 508.Loewenstein, A., 5 1.Lofgren, P., 580.Logan, M. A., 449.Logothetis, A. L., 201.Logullo, F. M., 346.Lohmann, D. H., 219.Lohr, L. L., 223.Lohr, L. L., jun., 179, 573,Lokshin, G. B., 462.Lombardo, G., 556.Lomekhov, A. S., 538.Lomer, T. R., 596, 604.Long, D.A., 132, 133, 140,Long, F. A., 12, 277, 287,Long, L. H., 183, 199.Long, M. W., 161.Long, R. E., 585.Long, R. F., 594.Longeville, P., 412, 415.Longhi, R., 195, 228.Longo, J., 578.Longuet-Higgins, H. C.,Loofburrow, R., 470.Looker, J. H., 396.Looney, C. E., 305.Lopez-Castro, A., 218.Loraas, J. A., 204.Lord, R. C., 121, 123, 299,Lorenz, D. H., 316.Lorenz, R. L., 322.Lorenzelli, V., 299.Lorquet, A. J., 157.Lossing, F. P., 281, 306.Lotspeich, J. F., 166.Lottes, K., 236.Loubser, J., 168, 169.Louden, M. C. L., 399.Loudon, J. D., 281, 345,Loudon, R., 148.Louw, R., 276, 296.Love, J., 439.Love, W. E., 597.Lovejoy, R. W., 137.Lovell, R. J., 123.Lovelock, J. E., 504.Lovrien, R., 296.Low, B.W., 468.Low, M., 459.Lowe, G., 328.Lown, J. W., 309.LO, T.-B., 459.598.141, 143, 292.296.142.LOO^, M., 407.310.387644 INDEX OF AUTHORS’ NAMESLowry, B. R., 363.Lowry, G. C., 100.Loy, H. L., 22.Lucas, S., 384.Lucchesi, P. J., 294.Lucken, E. A. C., 312, 347,Luddy, F. E., 333.Ludi, A., 215.Ludwig, M. L., 468, 478.Lubke, K., 463.Lueck, C. H., 292.Luderitz, O., 495.Lussi, H., 272.Luttke, W., 138.Luttringhaus, A., 388.Luff, B. B., 36.Luft, R., 507.Lugg, G. A., 550.Lui, R. S. H., 88.Luijten, T. G. A., 104.Lukas, G., 389.Lukaszewicz, K., 593.Lukaszewski, G. M., 211.Luke, H. H., 543.Lukin, A. M., 533, 536.Lumbroso, H., 296.Lumme, P., 221.Lumry, R., 290.Lund, E., 452.Lund, H., 391.Lundborg, C., 110.Lundeen, A.J., 265, 319.Lunt, T. G., 561.Luskina, B. M., 554.Lustig, M., 196.Lutz, R. E., 259, 265, 268.Lutz, R. P., 365.Luz, z., 51.Luzzati, A., 506.Luzzati, V., 518.Lwowski, W., 76, 335, 341,Lyalikov, Yu. S., 547.Lyamina, G. C., 558.Lygin, V. I., 124, 125.Lykos, P. G., 394.Lyle, R. E., jun., 316.Lynch, B. M., 386.Lynch, P. F., 109.Lynch, P. P., 321.Lyng, S., 684.Lynn, K. N., 355.Lynn, K. R., 276.Lynton, H., 579.Lyon, R. K., 75.Lysenko, Yu. A., 208.Lysloff, I., 114.Lythgoe, B., 372, 429.Lyttleton, J. W., 514.Lyubimova, A. K., 99.Ma, J. C. N., 263.Ma, T. S., 542.Lu, Y.-H., 461.397.LWO, S.-Y., 402.379, 384.Mabbs, F., 206.Mabis, A. J., 599.Mabry, T. J., 385.McAuley, A., 31, 35.McBride, D.W., 242.McBryde, W. A. E., 228.McCaffery, A. J., 223.Maccagnani, G., 272.McCaldin, D. J., 399.McCall, E. B., 386.McCalla, K., 479.McCapra, F., 346, 414.McCarley, R. E., 209.McCarroll, B., 15.McCartliy, D. A., 457, 460.McCarthy, J. L., 12.McCarty, M., 497.McCasland, G. E., 308.Maccioni, A., 320.McClanahan, J. L., 336.McClenon, J. R., 306.McCleverty, J. A., 233, 241,McCloskey, A. L., 186, 187.McCloskey, J. A., 451.McCluer, R. H., 493.McClung, F. J., 147, 148.McClure, D. S., 68.Maccoll, A., 77.McColluin, J. D., 158.McComie, J. W. F., 325.McConnell, J. F., 591.McCormick, B. J., 216.McCormick, H. W., 111.McCory, L. D., 132.McCoy, E. F., 299.McCrae, W., 326.McCrindle, R., 375.McCullough, J., 296.McCullough, J.D., 560.McCullough, J. P. M., 297.MacDermott, T. E., 224.MacDiarmid, A. G., 190,Macdonald, A. M. G., 558.McDonald, B. J., 579.McDonald, C. E., 371, 413.McDonald, J. E., 36.MacDonald, S. G. G., 604.McDonald, T. R. R., 675.McDonald, W. S., 576.MeDougall, A. C., 12.McDowell, C. A., 62, 71,McDowell, R. S., 123, 139.Maceira Vidan, A., 537.McFadden, W. H., 150,301.McFarland, J. W., 416,417.McFarlane, W., 237, 241.McGavin, A. S., 468.McGeachin, H. RlcD., 574,McGhie, J. F., 332, 373,MacGillavry, C. H., 580,587.191, 193, 201.151.583.374, 376, 419.611, 612.McGlynn, S. P., 209.McGonagle, M. P., 355.McGovern, T. P., 319.McGrath, W. D., 83.MeGregor, D. N., 465.Machherndl, L., 562.Machida, K., 142.Machin, D.J., 206, 209,Machinskaya, I. V., 324.Maciejewska, E., 656.McIntyre, P., 389.McIver, E. J., 682.McKay, J., 441.McKean, D. C., 128, 145.McKean, J. E., 465.McKee, S. C., 443.McKenna, J., 266.McKenney, D. .B., 538.Mackenzie, D. R., 179.McKenzie, E. D., 216, 220.Mackenzie, S., 439.Mackey, J. L., 36.McKie, A. S., 585.Mackie, R. K., 280.Mackie, R. P., 296.Mackie, W., 439.McKinnell, J. P., 439.McKinnon, D. M., 388.Mackley, C. J., 196.McKnight, J. T., 51.McLafferty, F. W., 158.McLaren, R., 260.McLauchlan, K. A., 436,McLay, D. B., 172.Maclean, D. B., 257.MacLean, I. R., 370.McLean, P., 506.Macleay, 8. E., 313.McLoughlin, B. J., 426.McMenamin, J. R., 426.MeMichael, K.D., 254.McMillan, G. R., 76.MacMillan, J. D., 445.MeMorris, T. C., 356.MacMullan, E. A., 446.McMullan, R. K., 676.McMurray, W. J., 409.McMurry, T. B. H., 332.McNamee, R. W., jun., 126.McNelic, E., 346.McNesby, J. R., 66, 67, 80.McNicholl, H., 283.McPhail, A. T., 396, 609.McQuillan, G. P., 134, 194.McQuillen, K., 513.McQuillin, F. J., 324.McTigue, P. T., 287, 297.McWain, P., 396.McWeeney, R., 64.McWhan, D. B., 205, 571.MacWilliam, I. C., 439.Madan, S. K., 226.Madden, M. J., 524.Maddock, A. G., 205.225.449INDEX OF AUTHORS’ NAMES 645Madeja, K., 214.Madhavan, P., 611.Madison, J. T., 513.Maeda, K., 462.Maeda, S., 145.Maemori, M., 67.Markl, G., 397.Maes, S., 164.Magat, M., 98, 103.Magdoff, B.S., 468.Mage, R. G., 498.Magee, E. M., 66.Magee, R. J., 534.Mager, J., 515.Magi, M., 314, 422.Magin, R. W., 340.Maginn, R. E., 240.Magnani, A., 429.Magno, S., 385.Magnuson, J. A., 545.Magnusson, L. B., 26.Maguire, K. D., 195.Maguire, K. E., 277.Mah, R. W. H., 259.Mahan, B. H., G4, 81.Maher, J. P., 189, 303.Maheshwari, M. L., 367.Mahgoub, A. E. S., 21.Mahieux, F., 180.Mahler, H. R., 391.Mahler, W., 190, 198.Maier, L., 196.Maier, W., 160.Maiman, T. H., 146.Maina, G., 420.Mains, G. J., 71, 88.Mainwaring, W. I. P., 468.Mair, A. D., 35.Mairanovski, S. G., 54, 55,Maitlis, P. M., 239.Major, J. R., 73.Major, W. B., 156, 157.Majeste, R., 604.Majumdar, M. K., 185.Mak, T. C. W., 601.Makarenko, G. N., 204.Makarov, L.L., 32.Maki, A., 133, 139.Maki, A. G., 122, 123,Maki, A. H., 215, 309.Makin, S. M., 322, 332.Makino, K., 100.Makino, M., 486, 487, 455.Makita, M., 434.Makkova, V., 536.Maksimova, I. N., 37.Malaguti, A., 47.Malan, 0. G., 145.Malani, C., 332.Malatesta, L., 217, 236.Malcolm, G. N., 35, 39.Malcovati, M., 490.Maley, G. F., 507.Malhotra, S. K., 416.57.181.Malik, W. U., 540.Malinina, R. D., 540.Malinowski, E. R., 408.Malissa, H., 562.Malkiewich, E. J., 208.Malkin, S., 68.Mallory, F. B., 68, 373.Malm, J. G., 130, 138, 179,Malmberg, C. G., 9.Malter, L., 558.Mal’tsev, A. A., 132.Mal’tseva, N. N., 130.Malzahn, R. A., 321.Mamedov, Kh. S., 582.Mamedova, V. M., 557.Mammi, M., 605.Manabe, T., 99, 104.Manasevit, H.M., 185, 187.Manastyrskyj, S., 240.Mandal, R., 64.Mandel, M., 165.Mandelkern, L., 130.Ma.ndel1, L., 382, 401.Mandels, M., 439.Mandelstam, M. H., 496.Manella, G. G., 195.Mangini, A., 120, 305.Mangoni, L., 373.Manhas, M. S., 360.Mani, N. V., 609.Mania, D., 462.Mankowski, J., 131.Mann, G. R., 38.Mann, C. K., 551.Mann, C. R., 172.Mann, D. E., 126, 135, 168,Mann, F. G., 397.Mann, L. T., 561.Mann, R. H., 146.Mann, W., 560.Manners, D. J., 435, 438,439, 440, 441, 442.Manniello, J. M., 497.Manning, D. L., 538.Manning, H. R., 209.Manning, P. G., 35.Manno, R. P., 195.Mannsfeld, S.-P., 343.Manohar, H., 609.Manoharan, P. T., 236.Manohin, B. M., 558.Manolov, K. R., 533.Mansell, A. L., 84.Mansfeldova, D., 560.Manson, D.L., 341.Manson, J. A,, 108.Manuel, T. A., 242.Manzoor-Khuda, M., 333.Maranville, L. F., 16.Marcel, J., 150.March, R. E., 64.Marchant, N. K., 220.Marchessault, R. H., 442.Marcus, L., 523.180, 213.172.Marcus, R. A., 34, 41, 71,Marcus, Y., 34.Marcuse, D., 162.Marczewski, A., 556.Marecek, J., 537.Marezio, M., 581.Margenau, H., 127.Margerison, D., 108, 109,Margerum, D. W., 231.Margerum, J. D., 64.Margoliash, E., 440, 468,Margolis, E. I., 558.Margolis, J., 483.Margosian, F. F., 38.Margrave, J. L., 132, 359.Maricich, T. J., 249, 335,Mariner, R., 394.Marini, M. A., 500.Marino, G., 279.Marinsky, J. A., 204.Mark, H., 101.Mark, H. F., 91, 103.Mark, V., 379.Markby, R., 339.Markgraf, J.H., 285.Mark6, L., 234.Markov, P., 316.Markova, V., 535.Markowitz, M. M., 198.Marks, G. S., 486, 487.Marks, P. A., 521.Marlow, W., 396.Marmet, P., 151, 152.Marsy, K., 202.Maroz, L., 550, 552.Marquart, J. R., 154.Marques, M., 130.Marquet, A., 374.Marsel, J., 180.Marsh, F. D., 190.Marsh, J., 418.Marsh, K. N., 22.Marsh, M. M., 482.Marsh, R. E., 585,586, 597.Marshall, J. A., 419, 429,Marshall, M., 510.Marshall, R. D., 289, 486,Marshall, R. L., 230, 344.Marshall, W. L., 37.Marsi, K. L., 277.Marsili, A., 375.Martell, A. E., 391.Martell, M. J., 402.Martelli, M., 215.Martens, G., 337.Martin, A. J. P., 491.Martin, B., 287.Martin, D. F., 230.Martin, D. H., 351.Martin, H., 144.79.181.476.341.315.487646 INDEX OF AUTHORS’ NAMESMartin, J., 309.Martin, J.B., 344.Martin, J. C., 293, 355, 381.Martin, K., 138.Martin, R. G., 515, 523.Martin, R. J., 526, 527.Martin, R. L., 208, 225.Martin, R. St., 365.Martin-Smith, H., 421.Martin-Smith, M., 367.Martins, C., 506, 507.Marumo, S., 462, 581.Marx, A. F., 412.Marx-Figini, M., 440.Maryott, A. A., 9.Marzadro, M., 553.Maschke, A., 75.Maslen, E. N., 373, 599,Mason, H. S., 470.Mason, J., 77.Mason, R., 239, 242, 352,Mason, R. W., 196, 202.Mason, S. F., 223, 276, 294,Masschelein, W., 297, 307.Massey, A. G., 79, 93, 177,184, 185, 187, 197, 233,234.Massie, W. H. S., 560.Masson, C. R., 63.Masthoff, R., 181.Masuda, S., 310.Mateos, J. L., 146, 423.Mathai, K.G., 32.Mathes, W., 378.Matheson, D. S., 184, 259.Matheson, M. S., 11, 48, 64,Matheson, N. A,, 471, 552.Matheson, R. A., 19.Mathews, F. S., 606.Mathewson, J. H., 382.Mathieson, A. McL., 312,360, 411, 608, 609.Mathieson, A. R., 118.Mathieu, J. P., 139, 140,Matijevic, E., 23, 32.Matkovic, B., 589.Matossi, F., 121.Matousek, P., 554.Matsubara, H., 476.Matsuda, H., 53.Matsufuji, K., 370.Matsui, Y., 433.Matsumara, C., 168, 172,Matsumara, S., 359.Matsuoka, K., 342.Matsusato, N., 313.Matsushita, S., 124, 517.Matsuura, S., 394.Mattauch, H., 179.Mattes, R., 194, 379, 590.610.587, 588, 594.299, 311, 392.84, 179.423.303.Matthaei, J. H., 523, 524,Matthews, R. S., 313.Matthews, W. S., 328.Matthias, A.P., 472.Mattingly, T. W., 341.Mattingly, T. W., jun., 335.Mattox, V. R., 318.MaturovA, von M., 402.Matveeva, N. M., 208.Matzuk, A. R., 384.Maulbecker, D., 22 1.Maung, M. T., 242.Mausser, H., 89.May, A. D., 128.Mayer, A., 189.Mayer, H., 396.Mayer, J.: 558.Mayer, R., 336, 380, 389,Mayer, R. M., 601.Mayer, U., 360.Maynard, J., 325.Mayo, F. R., 101.Mays, M. J., 133, 167, 190,Mazhar-U1-Haque, 368,609.Mazor, L., 563.Mazur, R. H., 292,455,465.Mazur, Y., 325, 343, 420.Mead, C. A., 15, 50.Mead, J. F., 503.Mead, T. E., 294.Meadows, L. F., 65.Meakins, G. D., 421.Means, R. E., 333.Mearns, A. M., 74.Mecke, R., 135, 145.Medcalfe, T., 429.Medgyesi, G., 489.Medvedev, S., 103.Medvedev, S. S., 113.Medzihradsky, K., 459.Meek, D.W., 226, 228.Meek, J. S., 394.Meek, M., 39.Meeks, F. R., 34.Meen, R. H., 381.Meenvein, H., 118.Megaw, H. D., 578, 581.Mehltretter, C. L., 552.Mehmedbasich, E., 268.Mehrotra, R. C., 204, 536.Mehta, A. S., 264.Meiboom, S., 22, 51, 52.Meienhofer, J., 452, 457,Meier, J. F., 110.Meier, W. M., 581.Meinwald, J., 249, 266, 275,363, 364, 423.Meinwald, Y. C., 266, 364.Meisel, M., 198.Meisels, A., 376.Meisingseth, E., 143.Meites, L., 47.526, 527.396.202.459, 461.Mekhtiev, S. D., 324.Melera, A., 374.Melia, T. P., 92.Melikhova, L. P., 145.Mellon, E. K., jun., 185.Mellor, D. H., 228.Mellor, J. M., 372.Mel’nikov, A. Kh., 181.Melson, G. A., 230.Melton, C. E., 155, 156.Meltzer, R.I., 502.Melville, H. W., 105.Menahem, J. S., 202.Menapace, L. M., 316.Menashi, J., 11, 12.Mendelsohn, M. A., 225.Mendelson, W. L., 319,419.Menger, F., 358.Menning, K., 202.Merbach, A., 258.Mercer, G. A., 435, 438.Mercer, R. A., 181.Meredith, R. E., 123.Merhyi, R., 239.MerilBinen, P., 33.Meriwether, B. P., 503, 507.Meriwether, L. S., 94.Merrifeld, R. E., 131.Merrifield, R. B., 456.Merrill, C. I., 201.Merritt, F. M., 106.Merritt, L. L., 604.Merten, D., 191.Merz, G., 199.Meschi, D. J., 154, 169.Meschia, G., 475.Meschino, J. A., 314.Meshitsuka, G., 100.Messerly, J. F., 297.Messwarb, G., 97.Mesker, L., 489.Meterson, S., 158.Meth-Cohn, O., 387.Metten, J., 198.Metz, D. J., 100.Metzenberg, R.L., 510.Metzger, J., 387.Meuche, D., 384.Meunier, P. F., 332.Meuwsen, A., 200.Mexperoro, A. J., 541.Meyer, B., 126.Meyer, D., 488.Meyer, E. F., 267.Meyer, K., 432, 490, 499.Meyer, N. J., 28, 206.Meyer, R. T., 166.Meyer, W. L., 391.Meyers, C. Y., 283.Meyers, E. A., 198.Meyers, E. E., 563.Meyers, M. B., 346.Meyers, W. W., 259.Meyerson, S., 158, 251.Meyerstein, D., 10, 11.Meystre, Ch., 424, 425Mez, H. C., 588.Meza, S., 146.Mezey, E. J., 183.Mezhirova, L. P., 98.Michael, J., 70.Michael, J. V., 77.Michaelis, H., 289.Michaels, R. J., 260.Michail, K. F., 219.Micheel, F., 486.Michel, G., 144, 494, 547.Michel, O., 508.Michel, R., 508, 510.Michels, J. G., 314.Michels, R., 509.Micka, K., 60.Midgley, J.M., 517.Miescher, K., 428.Mietens, G., 206.Migchelsel, T., 574.Miginiac, P., 321.Mihailovic, M. Lj., 424.Mijs, W. J., 433.Mikawa, Y., 133.Mikeg, O., 463, 469.Mikhailov, B. M., 182, 184,Mikheeva, N. N., 378.Mikhlina, E. E., 378.Miki, T., 426.Mikolaiezack. K. L.. 332.186.INDEX OF AUTHORS’ N AMikschi, G. k., 325:Mikulaschek, G., 187.Mildner, G., 136.Mile, B., 97.Miles, M. L., 320.Miles, P., 345.Millen, D. J., 165, 169,Miller, A., 604.Miller, F. A., 133, 136,Miller, H. C., 131, 182.Miller, H. J., 436.173, 299, 312.299.70,73,Miller, J., 279, 280, 390.Miller, J. B., 563.Miller, J. C., 302.Miller, J. M., 186.Miller, M., 551.Miller, M. A., 309.Miller, M. C., 198.Miller, M. L., 114.Miller, M.W., 16.Miller, P., 128.Miller, R., 521.Miller, R. C., 9.Miller, R. E., 17.Miller, R. F., 169.Miller, R. G., 281, 346.Miller, R. L., 394.Miller, R. P., 181.Miller, R. S., 523, 526, 527.Miller, S. I., 326.Miller, S. S., 385.Miller, W. B. T., 22.Miller, W. L., 108.Milligan, D. E., 81, 126,Millington, J. P., 491.Mills, A. R., 444.Mills, H. H., 597, 613.Mills, I. M., 123, 140, 141.Mills, J. F. D., 607.Mills, 0. S., 587, 588.Millward, G. L., 181.Milne, D. G., 65, 89.Milner, C. E., 9.Milner, D. C., 143.Milner, R. S., 186.Mina, G., 360.Minato, H., 433.Minc, S., 14, 20, 144.Minck, R. W., 148.Minczewski, J., 536.Minczlwskii, J., 542.Minisci, F., 387.Minnemeyer, I€. J., 283.Mirlina, S. Y., 115.Mirone, P., 15.Mironor, V.E., 541.Miroschnichenko, L. D.,Mirri, A. M., 166, 169, 170.Mirsch, M., 342.Mirsky, I. A., 469.Misaki, A., 441.Mishra, H. C., 225.Mislow, K., 415.Misono, A., 330.Misra, S. N., 204.Misra,, T. N., 204.Misumi, S., 320.Mitchard, D. A., 365.Mitchell, D. L., 435.Mitchell, J. C., 72.Mitchell, J. P., 442.Mitchell, M. J., 341.Mitchell, P. C. H., 212.Mitchison, J. M., 514.Mitra, R. B., 369.Mitra, R. P., 85.Mitsuhashi, H., 432.Mitsui, S., 313.Mitsui, T., 545, 565.Mitsuoka, H., 108.Mittal, R. K., 536.Mitzengendler, S. P., 113.Mitzui, T., 561.Miwa, G. C., 333.Miwa, K., 333.Miyahara, A., 169.Miyama, H., 92.Miyawaki, M., 402.Mizuhara, S., 449.Mizuike, A., 537.Mizuno, D., 522.Mizushima, M., 163, 166.Mlejnek, O., 548.Mlinko, S., 560.Mocquot, G., 490.Moczar, E., 489.Moeller, K.D., 142.129, 179.335.ES 647Moeller, T., 197, 200, 230.Moller, W. J., 524.Moelwyn-Hughes, E. A.,Moerikofer, A. W., 267,315.Moffatt, J. G., 319.Moffat, M. E., 252.Moffett, R. B., 283.Mogilyanski, A. I., 541.Mohacsi, E., 275.Mohan, M. S., 46.Mohilner, P. R., 532.Mohr, M., 388.Mohr, R., 220.Mohr, S. C., 285.Moiseyev, Y. V., 292.Mokrf, J., 410.Mold, J. D., 333.Moll, H., 342.Molnar-Perl, I., 550, 552.Molodkina, A. N., 181.Monahan, J. E., 153.Money, W. L., 502.Monier, R., 516.Monk, C. B., 8, 11, 21, 28,Monod, J., 501, 509.Monroy, A., 526.Montanari, F., 272.Monteiro, H. J., 374.Montel, G., 542.Montgomery, H., 593.Montgomery, J.A., 434.Montgomery, R., 487, 500.Montijn, P. P., 326.Montonnier, C., 419.Montreuil, J., 487.Moodie, R. B., 277, 292,Mooney, E. F., 186, 309.Mooney-Slater, R. C. L.,Moore, C. B., 133, 170.Moore, D. W., 187, 238.Moore, F. H., 214.Moore, F. W., 211.Moore, G. E., 123.Moore, J. E., 114.Moore, P. W., 142.Moore, R. H., 438.Moore, S., 468, 470, 472,Moore, W. M., 65, 68, 88,Moore, W. R., 91, 260, 296,Moormeier, L. F., 111.Moran, W., 68.Morand, P., 356.Morand, P. F., 424.Morath, R. J., 278.Morawetz, H., 290, 292.Morduchowitz, A., 69, 358.Moreau, R. C., 387.Morello, E. F., 186.231.Mole, T., 188.34, 35.391.583.478.340.320, 329648 INDEX OF AUTHORS’ NAMESMoreillo, J., 145.More O’Ferrall, R.A,, 257Morgan, D. D., 68, 340.Morgan, G. L., 193.Morgan, R. S., 32, 514, 516Morgan, S., 560.Morgan, W. T. J., 438.Morgans, D. E. B., 11.Moriarty, R. M., 420.Morimoto, H., 455.Morin, R. B., 388.Morino, Y., 164, 168, 172Morisawa, Y., 417.Morita, K., 449.Moritani, I., 293.Moriyama, M., 26.Mork, H. M., 386.Morkved, E., 78.Moron, J., 495.Moros, S., 540.Moros, S. A., 47.Moroz, E., 423.Morrett, S. D., 31.Morrey, J. R., 205.Morris, C. J. 0. R., 481.Morris, D. F. C., 16, 34, 130.Morris, J. H., 182, 235.Morris, M. L., 223.Morris, M. P., 335.Morrison, J. D., 151, 152,Morrow, J. C., 593.Mom, W. B., 374.Morschel, H., 118.Morse, S. I., 497.Morten, J. R., 170.Mortimer, C. T., 389.Morton, M., 108, 110, 113,Moscowitz, A., 299.Moser, F.H., 378.Moser, H., 121.Moser, H. C., 198.Moser, W., 195.Moser, W. R., 260.Mosher, R. A., 186.Moshier, R. W., 223.Mosse, J., 548.Mossel, A., 360.Mothes, K., 391.Mottern, J. G., 133.Mould, R., 133.Moule, H. A., 556.MoulB, Y., 513.Mousseron, M., 7 1.Mousseron-Caset, M., 71.Moyer, C. E., 285.Moyle, M., 320, 326, 327,Moza, B. K., 402.Mrose, M. E., 582.Muchowski, J. M., 383.Mudd, J. A., 512.Mudd, S. H., 507.518.303, 308.257, 400.115.329.Muelder, W. W., 142.Muhle, H., 419.Miihlethaler, K., 440.Muller, E., 80, 315, 341Mueller, G. C., 511.Muller, H., 277.Muller, H. C., 316.Muller, J., 237.Muller, P., 356.Mueller, R. A., 388.Mueller, W. H., 335.Muller-Schiedmayer, G.,Muenter, J.S., 167.Muetterties, E. L., 131,182, 183, 190, 198, 201,210.Mugno, M., 335.Muhammad, S., 375.Muhammed, S. S., 83.Mui, J. Y. P., 80.Mujamoto, M., 535.Mukai, T., 319.Mukawa, F., 418.Mukerjee, P., 36.Mukherjee, A. K., 235.Mukherjee, R. N., 181, 188.Mukhtarov, I. A., 303Mulac, W. A., 64, 84.Mulay, L. N., 239.Mulders, J., 264.Mullac, W. A., 11.Mullen, R. T., 80.Muller, E., 83.Muller, G., 423.Muller, N., 167, 189.Muller, R. J., 275.Mumma, R. O., 376.Mundell, P. M., 396.Muney, W. S., 22.Munke, H., 213.Munnik, J., 604.Munro, M. H. G., 560.Mumon, M. S. B., 155.Mumon, R. A., 22.Murad, E., 72, 73, 78.Murahashi, S. I., 293.Murakami, H., 476.Murakami, M., 313.Murdoch, H. D., 237.Murgulescu, I.G., 140.Murphy, W. M., 489.Murr, B. L., 18, 256.Murray, A. W., 402.Murray, H. C., 433.Murray, R. K., 434.Murray, R. W., 293.Murrell, J. N., 344.Murthy, A. R. V., 200.Murti, V. V. S., 484.Murty, K. S., 543.Murty, K. S. R., 167.Murty, N. L., 544.Murty, S. V. S. S., 541, 542.Musgrave, 0. C., 341.361, 379, 385, 419.196.Musgrave, W. K. R., 342.Musha, S., 542.Musil, A., 532.MUSSO, H., 342.Mustafa, A., 66.Muto, Y., 220.Muzzucato, U., 71, 76.Myers, H. W., 183.Myers, R. J., 135, 164, 166,Mysels, K. J., 18.Naas, H., 28, 33.Nabney, J., 414.Nachbaur, E., 135.Nadzhafova, K. N., 541.Naegele, W., 269, 321, 329.Nasanen, R., 12, 13.Nag, S., 500.Nagai, E., 108.Nagai, M., 374.Nagai, T., 293.Nagai, Y., 295, 310.Nagamatsu, A., 475.Nagarajan, K., 407.Nagasampagi, B.A., 369.Nagata, W., 371, 412, 414,Nagel, C. W., 445.Nagorsen, G., 584.Nagy, P. L. I., 238, 241.Nagy, S. K., 478.Nahabedian, K. V., 58.Naik, V. G., 369.Naile, B., 504.Nair, C. G. R., 200.Nab, P. M., 395, 396.Nair, V. S. K., 11, 31, 35.Nakagawa, C., 536.Nakagawa, K., 318.Nakagawa, M., 320.Nakamoto, K., 121.Nakamura, S., 42, 462.Nakamura, T., 600.Nakanishi, K., 121, 372,Nakano, T., 418.Nakashima, T., 476.Nakata, T., 124.Nakatsu, K., 590.Nakazaki, M., 366.Namba, Y., 607.Nancollas, G. H., 19, 31, 35.Nanda, R. K., 11.Nann, B., 423.Nannelli, P., 197.Nano, G. M., 547.Napier, E. A., jun., 545.Narasimhem, K. V., 123.Narath, A., 161, 172.Narayanan, C.R., 415.Nardelli, M., 579, 591, 593,Narisada, M., 371, 414.Narita, K., 476.Narr, B., 315.169, 172, 175, 301.429.376.594INDEX OF AUTHORS’ NAMES 640Nash, €3. W., 272.Nasielski, J., 264, 275, 279.Naslain, R., 182.Naslund, L., 275.Nast, P., 238.Nast, R., 220.Nasutavicus, W. A., 391.Natalis, P., 306, 307.Nathans, M. W., 204.Nath Nunshi, K., 532.Natori, S., 376, 522.Natsume, S., 312.Natta, G., 115.Naughton, M. A., 483.Navares, V., 138..Nawojska, J., 47.Nayar, V. S. V., 207.Naylor, P. G., 266.Naylor, R. E., 108.Nazarenko, V. A., 534.Nazarov, I. N., 272.Neale, A. J., 386.Neaumann, C. L., 355.Nebel, E., 11.Nechaeva, L. N., 17.Nedic, M., 556.Needleman, S. B., 476.Neelakanten, P., 307.Neelin, E.M., 518.Neelin, J. M., 518.Neemuchwala, N., 197.Neff, L. D., 124.Neff, V., 275.Nefkens, G. H. L., 455.Neher, R., 356.Neikarn, W. C., 307.Neilands, J. B., 462.Nekrasov, L. N., 61.Nelson, C. A., 473.Nelson, H. M., 136.Nelson, 0. E., 442.Nelson, P. F., 387.Nelson, R., 175.Nelson, S. M., 229.Nelson, T. E., 439, 441.Nelson, W. H., 210.Nemer, M., 526.Nemes, J., 541.NQmethy, G., 297.Nenitzescu, C. D., 277.Nerdel, F., 289.Nerrigan, P. J., 342.Nes, W. R., 418, 433.Nesmeyanov, A. N., 353.Nestler, F. H. M., 544.Nesvadba, H., 459.Nethercot, A. H., jun., 166.Neuberger, A., 486, 487.Neufeld, E. F., 438.Neukom, H., 445.Neumann, C. L., 306.Neumann, H. M., 216.Neumann, N. P., 472.Neumann, W. P., 193.Neunhoffer, O., 347.Neurath, H., 469.Neurieter, N.P., 250.Neus, N., 409.Neuvar, E. W., 167.Neuwirth, W., 177Nevett, B. A., 31.Neville, 0. K., 259.Nevitt, T. D., 331.Newbould, J., 370.Newman, D., 259.Newman, E. J., 536.Newman, H., 436.Newport, J. P., 108, 181.Newsom, H. C., 185.Newton, T. W., 44, 45.Ng, W. K., 147.Nguyh, D., 158.Nichimura, S., 480.Nicholas, J. E., 80.Nicholls, D., 209.Nicholson, A. E., 106.Nicholson, A. J. C., 151,Nicholson, D., 225.Nicholson, R. T., 433.Nickell, E. C., 334.Nickon, A., 274, 319, 364,Nicol, M. J., 45.Nicoladies, E. D., 457, 460.Nicolaus, B. J. R., 381.Nicolaus, R. A., 378.Nicolini, M., 139, 215.Niedenzu, K., 184, 155.Niederprum, H., 191.Nielsen, A. H., 123.Nielsen, H.H., 164.Nielsen, J. R., 301.Nielsen, J. T., 173.Nielsen, K. H., 544.Nielsen, L., 187.Nielsen, P. H., 218.Nielsen, R. P., 197.Niemann, C., 290, 503.Niemeyer, M., 506.Nier, A. O., 157.Nikitenko, J. F., 541.Nikitin, V. S., 132.Nikolaev, N. S., 213.Nikolaeva, N. A., 558, 560.Nilsson, S. K., 540.Nirenberg, M. W., 523, 524,525, 526, 527.Nishida, H., 534.Nishida, S., 293.Nishimura, S., 313.Nishioka, A., 108.Nishioka, S., 359.Nist, B. J., 308.Nitecki, D. E., 464.Nitschmann, H., 490.Nitta, I., 591, 596.Nitzschke, M., 336.Nitzschmann, R. E., 146.Nivard, R. J. F., 455.Nixon, E. R., 196.Nixon, J., 16.400.419.Nixon, W. L., 500.Noda, L., 504.Noddack, W., 204.Nolting, C., 221.Noth, H., 184, 186, 187,197, 199, 225.Noguchi, T., 590.Nolan, F., 163.Noll, H., 519, 521, 522.Noltes, A.W., 314.Noltes, J. G., 193.Nomind, G., 427.Nomura, K., 402, 410.Nomura, T., 432.Nonhebel, D. C., 221.Nordin, I. C., 253.Nordin, J. H., 440.Nordin, P., 434, 435.Nordman, C. E., 187, 575.Nordstrom, J. D., 77.Norell, J. R., 380.Norin, T., 366, 374.Norman, R. 0. C., 275,292,Normant, H., 320, 321.Norris, W. G., 130.Norrish, R. G. W., 64, 69,80, 81, 82, 83, 84, 85, 105,106.North, A. M., 104, 105, 106.Northrop, R. C., 451.Norton, D. A., 610.Norton, F. J., 155.Norton, W. T., 494.Novak, V. L., 554.Novelli, G. D., 524.Novikov, S. S. 67.Novikova, E. N., 547.Novikova, E. V., 546.Novikova, K. F., 563.Novoselova, A. V., 130.Novotny, J., 340.Novozhenyuk, Z.M., 139.Nowicka, A., 456.Nowotny, H., 205.Nowotry, A., 545.Noyce, D. S., 58.Noyce, 0. S., 58.Noyes, A. A., 34.Noyes, R. M., 3G, 65, 97,177, 179, 259.Noyes, W. A., 63, 64, 69,70, 72, 77.Nozabi, Y., 433.Nozoe, S., 369, 417, 421.Nozoe, T., 319, 366.Nucci, L., 61.Niirnberg, H. W., 54.Nuesch, J., 356.Nugent, L. J., 174.Nuhn, P., 259.Nui, H. Y., 227.Nukada, K., 301.Nunez, L. J., 30.NUSS, G. W., 384.Nussim, M., 294, 420.293, 344650 INDEX OF AUTHORS’ NAMESNuttall, P. M., 581, 682.Nuttall, R. H., 217.Nutter, J. D., 36.Nyburg, S. C., 36, 607.Nye, M. J., 258.Nygaard, B., 218.Nyholm, R. S., 85,139,190206, 216, 217, 222, 225227, 235, 594.Nyman, C. J., 11.Oae, S., 336.Oalby, J.S., 382.Oberender, H., 210.O’Brien, J. P., 386.O’Brien, R. J., 134, 194,O’Brien, S., 395.Occolowitz, J. L., 396.Ochiai, E., 318, 392.Ochoa, S., 526, 527.Ocone, L. R., 224.O’Connell, M., 484.Oda, E., 100.Oda, T., 607.O’Driscoll, K. F., 108, 110.Ohmen, J., 440, 441.Oeshmuth, G. S., 541.Osthagen, K., 208.Ostman, B., 386.O’Farrell, S., 249, 364.Ofner, A., 331.Ofri, S., 555.Ogata, M., 312.Ogata, N., 535.Ogawa, K., 591, 598.Ogilvie, J. F., 126.Ogle, H. D., 449.Ogle, P. R., 212.Ogrins, I., 31.Oh, J. S., 224.O’Hara, W. F., 35.Ohashi, M., 404, 415.Ohki, E., 417.Ohl, R. S., 161. ’Ohloff, G., 319.Ohno, M., 360.Ohno, T., 330.Ohrt, J. M., 610.Ohshima, N., 313.Ohta, A., 318, 392.Ohta, M., 320.Ohta, N., 317.Ohtaka, Y., 514, 52G.Oishi, Y., 99.Okay T., 164, 168, 169, 174,302, 303.Okabe, H., 66, 67, 73, 80.Okabe, K., 406.Okada, H., 537.Oksmoto, T., 522, 523.Okamura, S., 98, 99, 100,104, 117, 119.Okanishi, T., 433.Okawara, R., 134, 194.Okhlobystin, 0.Iu., 324.588.Oksengom, B., 127,Okuda, S., 406.Okuda, T., 461.Okumura, T., 433.Okura, Y., 536.Olah, G. A., 118, 252.Olcay, A., 286.O’Leary, M., 291.Olin, A., 31, 36.Oliphant, M., 542.Olivi?, S., 104.Oliver, J. P., 189.Olivera, E., 146.Oliveto, E. P., 433.Olivier, L., 159, 409.Ollis, W. D., 396.Olnos, A. W., 335.Olovsson, I., 580.Olson, D. C., 231.Olson, D. H., 575.Olson, W. B., 122, 137.Onak, T. P., 183, 184.Ondetti, M. A., 460, 484.O’Neal, E., 71.O’Neal, J.M., 150.O’Neill, C. E., 124.O’Neill, G. J., 390.Ono, H., 75.Onsager, L., 18, 26.Onsager, 0. T., 110.Onuma, N., 536.Onyszchuk, M., 134, 186,Ooi, T., 473.Oomori, S., 449.Openshaw, H. T., 403.Opitz, G., 358.Drban, I., 69, 358.Drchin, M., 259, 334.O’Reilly, J. M., 174, 175.Drentas, D. G., 446.3restova, V. A., 558.3rge1, L. E., 93, 139.X i , S., 600.Xoli, P. I., 591.3rioli, P. L., 218.Irlova, N. D., 128.3rr, R. J., 92.h e l l , S. A., 440.Irzech, C. E., 326.Isaka, K., 319.3sawa, S., 522.Isbond, J. M., 333.Isborne, A. G., 85, 235,lsborne, D. W., 133.lshurkova, 0. V., 533.lsipov, 0. A., 208.lstmann, E. A., 486.htroumov, E. A, 531.lsugi, J., 11.lswald, A. A., 269, 321,lswald, H.R., 584.)taka, E., 522.hake, Y., 375.192.297.329.Otaki, P. S., 292.Otermat, A. L., 189.Otsuka, S., 330.Ott, H., 463.Otten, H. G., 454.Otter, R. J., 38.Otto, K., 133.Ottolenghi, A., 114.Ottolenghi, M., 79, 84.Ouellette, R. J., 250.Oughton, J. F., 421.Ou Kuin-Houo, 321.Oura, H., 522.Ourisson, G., 366, 372, 374,375, 415.Ovchinnikov, Yu. A., 451,463.Ovechkina, T. I., 561.Overberger, C. G., 114,312.Overend, J., 141, 142.Overend, W. G., 434, 436,Overton, K. H., 370, 375.Owellen, R. J., 159, 410.Owen, B. B., 9.Owen, E. D., 297.Owen, N. L., 301.Owen, W. S., 551.Owens, F. H., 114.Owings, F. F., 429.Owston, P. G., 215, 590.Ozaki, T., 108.Ozawa, H., 480.Ozipov, 0. A., 134.Paabo, M., 12, 27, 30.Paakkola, K., 12.Paal, S., 210.Pabon, H.J. J., 333.Pacak, J., 437.Pachler, K., 368.Packer, J., 287.Packer, K. J., 210.Packter, A., 19.Paddock, N. L., 136, 197.Padgett, C. D., 201.Padilla, J., 368.Padlo, I., 576.Padma, N., 312.Padova, J., 37.Padwa, A., 331.Paetzdd, R., 202.Page, I. H., 482.Page, J. M. J., 268.Pahil, S. S., 539.Pai, B. R., 402.Paik, W. K., 510.Painter, T. J., 438, 439.Paiva, A. C. M., 469, 482.Paiva, T. B., 482.Pajakoff, S., 537.Pajakoff, S. W., 205.Pajaro, G., 238.Paknikar, S. K., 365.Pakrashi, S. C., 376.Palade, G. E., 513.437INDEX OF AUTHORS’ NAMES 65 1Palamarchuk, N. A., 564.Palenik, G. J., 575, 604.Palko, A. A., 131.Palm, J. H., 612.Palmade, M., 366.Palmer, D.J., 500.Palmer, G. C., 296.Palmer, M. H., 267, 323.Palmer, P. J., 323, 419.Palmer, R. A., 468.Palmer, T. F., 306.Palumbo, R., 238.Panar, M., 293.Panattoni, C., 219, 587,591, 594, 599.Panchak, J. R., 112.Panckhurst, M. H., 10.Panda, B. P., 21.Pandarese, F., 148.Pande, C. S., 235.Pande, K. C., 247, 250, 364.Panfilov, A. A., 321.Panfilova, E. S., 544.Pankratov, A. V., 196.Pannell, J., 169.Panouse, J. J., 315, 419.Pant, L. M., 597.Paoletti, P., 36, 218.Paoloni, L., 131.Papay, K. M., 563.Papee, H. M., 35.Papetti, S., 183.Papisov, I. M., 92.Papkoff, H., 490.Papp, C. A., 64.Pappas, B., 339.Pappas, P., 263, 312.Pappas, S. P., 339, 360.Pappo, R., 428.Paquette, L. A., 261, 342,Parasaran, T., 397.Parbock, H.D., 152.Parcell, R. F., 379.Pardoe, G. I.. 439, 488.Parfitt, G. D., 19, 21.Pariseau, M., 142.Parish, D. J., 100.Park, A. J., 184, 233.Park, C. P., 507.Park, C. R., 469, 503.Park, J. H., 503, 507.Park, J. T., 497.Parkanyi, C., 277.Parke, K., 542.Parker, A. J., 25, 258, 279.Parker, C. A., 64.Parker, C. O., 261.Parker, H., 290.Parker, P. M., 163.Parker, R. E., 258, 259,278, 293, 418.Parker, W., 370.Parkes, A. S., 572.Parkin, C., 139, 219.Parks, P. C., 181, 290.398.Parmenter, C. S., 72.Parrish, F. W., 439.Parry, R. W., 187, 189, 575.Parshall, G. W., 182, 323.Parson, W., 509.Parsons, R., 53.Partch, R. E., 318.Parthasarathy, P. C., 371,Parton, H. N., 35.Partos, R. D., 274, 338, 349,Pascard-Billy, C., 600.Pascual, C., 360.Pashaev, T.A., 324.Pass, G., 201.Passchier, A. A., 36.Pastuska, G., 542.Pasty, B., 161.Patchett, A., 440.Patchett, A. A., 426.Patel, A. N., 329.Patel, D. J., 358.Patel, H. P., 383, 387.Patel, K. S., 210.Patel, V. C., 221.Pathak, S. R., 420.Patnaik, D., 21.Patrick, C. R., 73.Patrick, S. R., 104.Pattengill, M., 543.Patterson, A. L., 597.Patterson, C. S., 39.Patterson, D. B., 306.Patterson, S. J., 548.Patterson, W. G., 52.Pattison, F. L. M., 326.Pattison, T. W., 426.Pattison. V., 358.413.359.Patty, R. R:, 129.Paukstelis, J. V., 3Paul, E. G., 301.Paul, I. C., 468, 61Paul, R., 452, 455.Paul, R. C., 539.Paule, R. C., 132.Paulett, G. S., 305.Paulik, F., 273.Paulik, F.E., 275.9.Pauling, P. J:, 594.Paulsen, H., 434.Paulson, H., 317.Pavanarum, S. K., 432.Pavlova, 0. V., 186.Pavlovec, A,, 514.Pavri, E. D., 382.Pawley, G. S., 468.Payne, D. S., 228.Payne, D. W., 434.Payne, G. B., 334, 380.Pchelkina, M. A., 132.Pchelkina, M. V., 46.Peace, L., 396.Peach, M. E., 22, 131, 203.Peacock, R. D., 179, 180,194, 207, 211, 213, 214.Pearlrnan, R., 527.Pearse, G. A., 549.Pearson, D., 37.Pearson, D. E., 277, 344.Pearson, M. J., 297, 304.Pearson, R. G., 22, 57, 203,229, 231, 257, 292.Pearson, R. K., 196.Peat, F. D., 47, 219, 223.Pechance, V., 564.Peciar, C., 542.Pecile, C., 138, 139, 215.Peddle, G. J. D., 193.Pedersen, B., 436.Pedersen, B. F., 579, 590.Pedersen, C. T., 218.Pedersen, K., 49.Pedersen, L.G., 20.Pedersen, S., 506, 523.Pedone, C., 595.Pedrali, C., 418.Peiffer, G., 330.Peiperl, A., 12.Pelah, Z., 415.Pell, E., 562.Pella, E., 561.Pellerin, F., 554.Pelletier, S. W., 371, 413.Pence, D. T., 169, 171, 302,Penfold, €3. R., 213, 594.Penman, S., 517, 520.Penneman, R. A., 17, 139,Pentin, Yu. A., 145.Penzo, L., 554.Peover, M. E., 504.Pepper, D. C., 116, 117.Peradejordi, F., 294, 298.Perai-Koshits, M. A., 591.Peraldo, M., 139.Percheron, F., 550.Percival, E., 434, 439, 445,Percival, E. G. V., 434.Perera, D., 451.Perisutti, G., 460.Perkin, W. H., 402.Perkins, H. R., 446, 405,Perkins, M. J., 345.Perkins, N. A., 351.Perlin, A. S., 436, 438, 441,Perrin, C., 275.Perrin, D.D., 31, 220,Perron, Y. G., 388.Perros, T. P., 181.Perry, D. D., 132, 187.Perry, E., 102.Perry, M. B., 446, 491.Perry, S. G., 291.Pershina, E. V., 125, 132.Person, W. B., 145, 295.Persson, G., 34.303.205, 206.446.496, 497.442.285652 INDEX OF AUTHORS’ NAMESPerumareddi, J. R., 226.Perutz, M. F., 468.Pesez, M., 547, 551.Pesnelle, P., 366.Pesterfield, C. E., 382.Pete, J. P., 263.Peter, H., 451.Peter, R., 163.Peterlik, M., 353.Petermann, M. L., 513, 514,Peters, C. W., 123.Peters, D., 63, 303.Peters, F. M., 187.Petersen, D. H., 168, 433.Petersen, E. W., 470.Petersen, N. C., 46.Peterson, J. O., 188.Peterson, L., 158.Peterson, L. H., 380.Peterson, P. E., 267.Peterson, R. G., 285.Peterson, R. L., 200.Petit, G. R., 432.Petit, M., 493.Petragagni, N., 202.Petrarca, A.E., 314.Petrov, A. D., 190.Petrov, Y. N., 167.Petrova, L. N., 547.Petrow, V., 416, 418.Petrowitz, H. J., 542.Petrucci, S., 19, 20.Petterson, L. L., 185.Pettit, L. D., 227.Pettit, R., 351, 386.Petzoldt, K., 565.Pews, R. G., 260.Peyronel, G., 591.Pfab, F., 184.Pfaff, J., 546.Pfannemuller, B., 440.Pfister, V., 487.Pfitzner, K. E., 319.Pfleiderer, W., 378.Pfluger, C. E., 210.Phadke, P. S., 396.Phaff, H. J., 445.Philbin, E. M., 394.Phillip, A. T., 227.Phillips, A. H., 506.Phillips, J. B., 352.Phillips, P. C., 426.Phillips, W. D., 218, 305.Philpott, P. G., 333.Photaki, I., 454.Piasek, Z., 296.Piatkowiak, E., 582.Piattelli, M., 385.Piccolini, R.J., 251.Pickering, 13. T., 482.Pickering, G. B., 328.Pickett, L. W., 295.Picou, D., 539.Pidcock, A., 43, 230.Pielmeier, G., 486.518.Pierce, L., 164, 168, 172,Pierce, S. B., 203.Pietra, F., 278.Piette, L., 312, 397.Pignedoli, A., 59 1.Pike, J. E., 428.Pilla, A. A., 60.Pilz, W., 545.Pimentel, G. C., 79, 81, 82,126, 170, 179.Pimentel, M. J., 126.Pine, S. H., 274.Pink, P., 261.Pinkerton, R. C., 187.Pinner, 8. H., 98.Piotrowska, H., 305.Piozzi, F., 371.Piper, J. U., 382.Piper, T. S., 210, 215,Piras, R., 434.Piret, P., 599.Pischel, H., 289.Pischtschan, A., 137.Pischtschan, S., 134.Pitcher, E., 139.Pitt, C. G., 316.Pittman, C. S., 502.Pittman, C. U., 251.Pitt-Rivers, R., 501.Pitts, E., 18.Pitts, J.N., 62, 64, 69, 71,Pitzer, K. S., 35, 135.Pitzler, L. G., 562.Pizzolotto, G., 138.Placzek, D. W., 65, 86.Placzek, G., 121.Plane, R. A., 10, 15, 16,Platonov, Yu. N., 559.Plattner, P. A., 450, 463.Pleasonton, F., 156.Plein, W., 168.Pleskov, Yu. V., 61.Pless, J., 455, 460.Plettinger, H. A., 581.Plieth, K., 199.Pliska, V., 459.Pliva, J., 142.Ploss, G., 350, 351.Plowman, R. A,, 220, 238.Pluchet, H., 315, 419.Plummer, T. H., jun., 491.Plyler, E. K., 122, 123, 127,Poche, R., 508.Pocker, Y., 118.Podall, H., 193.Poddar, S. N., 531.Poddubnaya, N. A., 463.Po& A. J., 221, 224, 234.Poesche, W. H., 393.Pohlke, R., 341.Poholsky, F. D., 185.173, 174, 175, 302.224.82.144, 189.133, 300.Poirier, J.C., 26.Poirier d’Ange d’Orsay, E .,Poisoner, A. M., 484.Polacco, E., 162.Polachek, J. W., 318.Polak, H. L., 530.Polanyi, J. C., 64, 85, 120.Polgar, N., 332.Poljak, R. J., 592.Polk, M., 397.Pollak, M. M., 532.Polonovski, J., 493.Polonski, J., 373.Polonsky, J., 356.Polyak, E. A., 537.Pombo, M. M., 254.Pomianowski, A., 554.Ponder, B. W., 223.Ponnamperuma, C., 394.Poole, C. P., 67.Pop, G., 541.Popescu, A., 533.Popjak, G., 333, 377.Popov, E. M., 296.Popova, E. A., 137.Poppenburg, G., 192.Popper, E., 532.Porter, G., 64, 77, 78, 84,Porter, G. B., 69, 74, 85.Porter, K., 63, 72.Porter, L. A., 400.Porter, M., 555.Porter, R. F., 132, 154, 185,Porter, R. R., 491.Porto, S. P. S., 146, 147,Portyanskii, A.E., 557.Posener, D. W., 163, 168.Post, B., 202.Potapov, V. M., 296.Potier, P., 414.Potrafke, E. M., 213.Potsepkina, R. N., 545.Pottie, R. F., 157.Potts, J. T., 471, 472.Pouchly, J., 92.Poulet, H., 139.Poutsma, M. L., 259.Powell, D., 295.Powell, H. B., 242.Powell, H. M., 217, 222,568, 584, 591.Powell, J. E., 36.Powell, R. E., 184.Powell, W. A., 546.Powers, J. C., 68, 263.Poynter, R. L., 162.Pozdnev, V. F., 184.Poziomek, E. J., 390.Praefcke, K., 331.Priikel, H., 188.Praisnar, B., 275.Prajsnar, D., 534.60.89.186.163INDEX OF AUTHORS’ NAMES 653Pratt, A. L., 146.Pratt, D. E., 186.Pratt, E. F., 287, 319.Pratt, L., 230, 237, 241.Pratt, M. R. A., 601.Prelog, V., 356, 372, 463.Premuzic, E., 296.Preobrazhenski, N.A., 335.Pressman, D., 481.Prevedorou-Demas, C., 207.Pribil, R., 540.Price, C. C., 101, 103, 397.Price, H. A., 557.Price, S. J., 73.Price, W. C., 64.Prichard, F. E., 309.Priestley, P. T., 538.Prince, R. H., 17.Prinzbach, H., 68, 361.Privett, 0. S., 334.Prochhzka, V., 367, 368.Prokhorov, A. M., 167.Proll, P. J., 11, 47, 219,Proskow, S., 267.Prostakov, N. S., 378.Protas, J., 578.Prout, C. K., 584, 587, 590.Prox, A., 451, 456.Prudchenko, A. T., 324.Prue, J. E., 18, 19, 20, 23,Pruitt, M. E., 21.Prusik, Z., 469.Przybylowicz, Z., 556.Przybylska, M., 204, 609.Puar, M. S., 21, 297.Puck, R. T., 31.Puff, H., 676.Pugnct, T., 548.Pullman, B., 330.Pullman, B. J., 199, 202.Pump, J., 188, 191.Pumphrey, N.W. J., 360.Purdue, N., 45.Purlee, E. L., 31, 51.Putnam, R. E., 183.Pyatenko, Yu. A., 682.Pyatintsky, I. V., 541.Pyszora, H., 185.Pytlewski, L. L., 196.Quacchia, R. H., 279.Quade, C. R., 174, 300.Quagliane, J. V., 228.Quail, J. W., 203.Quan, P. M., 330.Quane, D., 193.Quattrone, J. J., jun., 543.Quereshi, M., 543.Quilico, A., 371, 387, 462.Quinkert, G., 423.Quinn, H. W., 118.Quiram, E. R., 269, 321,Quisenberry, K. S., 157.223.28, 38.329, 556.Quist, A. S., 11, 37.Quitt, P., 451, 463.Rnab, G., 181.Rabani, J., 11, 84.Rabanis, J., 48.Rabin, B. R., 472.Rabindran, K., 368.Rabinovitch, B. S., 65, 86,Rabinsohn, Y., 461.Radda, G. I<., 275, 293.Radecki, A., 564.Rader, C. P., 416.Radhakrishnan, M., 144.Radin, N.S., 332.Radlick, P., 350, 362.Rado, W. G., 148.Radomski, M. W., 439.Radoslovich, E. W., 581.Rae, A. I. M., 599.Rafferty, G. A., 436.Rafos, R. R., 252.Raghavacheri, K. V., 85.Raghavan, Y. K. V., 611.Ragsdale, R. O., 195, 207.Rahim, A. M., 412.Rajan, J. B., 280, 345.Rall, J. E., 508.Ralph, B. J., 344.Ralph, P. D., 292.Ralph, R. K., 512.Ramachandran, G. N., 611.Ramachandran, J., 455,Ramachandran Nair, C. G.,Ramakrishna, T. V., 536.Raman, S., 608.Ramanchandran, L. K.,Ramaseshan, S., 609.Ramaseul, R., 71.Ramaswamy, R., 319.Ramdas Nayak, U., 369.Ramette, R. W., 33.Ramirez, F., 293.Rampey, W. C., 32.Ramuz, H., 399.Randall, E. W., 299.Randall, M. H., 435.Randic, &I., 123.Ranga Rao, V.P., 632.Rank, D. H., 122, 127.Ranney, H. M., 475.Rao, A. L. J., 543.Rao, B. R., 583, 584.Rao, B. S., 122, 127.Rao, C. N. R., 120,195, 292.Rao, C. R., 555.Rao, K. N., 123.Rao, K. V., 392.Rao, N. V., 532, 639.Rao, S. L. N., 448.Rao, T. N., 83.Rao, V. M., 174.153, 293.459.200.448.Rao, V. S. R., 436.Raper, O., 83.Raphael, R. A., 370.Rapoport, H., 314, 407.Rapp, J. R., 290.Rappoport, Z., 268.Rashid, M. H., 401.Raskin, Sh. Sh., 125, 130,Rasmussen, H., 469.Rasmussen, M., 401.Rasmussen, P. G., 33.Rasmussen, S. E., 698.Raspi, G., 61.Rastrup-Anderson, J., 17 1,173, 174.Rathjens, G. W., jun., 172.Ratka, J. S., 304.Ratkowsky, D. A., 12.Ratts, K. W., 289.Rausch, M. D., 239, 353.Rawalay, S.S., 318.Rawat, J. P., 643.Rawlings, T. J., 386.Rawlinson, D. J., 259Rawson, R. W., 502.Ray, 13. L., 608.Ray, S. K., 198.Ray, W. J., jun., 525.Raymond, M. A., 320.Read, G., 328, 356.Readio, P. D., 293.Reavill, R. E., 391.Rebbert, R. E:, 69, 74, 75,Reber, H., 20.Rebers, P. A., 497, 498,499.Records, R., 416.Reddington, R. L., 300.Reddoch, A. H., 204.Reddy, G. K. N., 139.Reddy, G. S., 301, 389.Reddy, J., 608.Reddy, J. M., 468.Reddy, T. B., 13, 294.Redemann, C. E., 503.Redfern, J. P., 211, 537.Redford, D. G., 311.Redington, R. L., 126, 137.Redinha, J. S., 297.Redman, M. E., 188.Redmore, D., 310.Reed, G. A., 104, 105,Reed, J. M., 607.Reed, J. W., 572.Reed, R. I., 149, 155, 169,Reed, W. C., 68.Reed, W.L., 58.Rees, A. H., 398,Rees, C. W., 346, 347.Rees, D. A., 435, 445.Rees, N. H., 112.Rees, R., 411.Rees, T., 259.Rees, T. C., 358.132.76, 77.299654 INDEX OF AUTHORS’ NAMESReese, E. T., 438, 439.Reeves, L. W., 296.Reeves, R. E., 498.Reeves, R. L., 286.Reeves, R. M., 28.Rege, V. P., 438.Reichstein, T., 432, 433,Reid, D. H., 351, 384.Reid, J., 437.Reid, J. A., 265.Reid, J. G., 233.Reid, P. E., 438, 443.Reid, S. T., 66, 79, 362.Reif, E., 318.Reilley, C. N., 538.Reilly, E. L., 305.Reilly, P. J., 116.Reim, R. H., 75.Reimlinger, H., 335.Reinecke, M. G., 381, 383.Reiner, J. R., 183.Reinert, K. E., 60, 171.Reinhart, R. E., 95.Reinheimer, J. D., 25, 259.Reinisch, R. M., 198.Reisch, J., 327.Reiss, J., 307.Reist, E.J., 435.Reitzner, B., 196.Rembaum, A., 112.Rembold, H., 394.Rendi, R., 513.Rendina, J. F., 64.Renk, E., 259.Ronnie, R. A. C., 437.Rentzeperis, P. J., 583.RBrat, C., 578.Rerick, M. N., 314.Retcofsky, H. L., 301.Reusch, R. N., 94.Reusch, W., 73, 419.Reutov, 0. A., 275.Reynaud, P., 387.Reynaud, R., 398.Reynolds, B. E., 384.Reynolds, C. A., 216, 543.Reynolds, G. A., 392.Reynolds, G. F., 557.Reynolds, W. L., 44.Reynolds- Wamhoff, P. ,Rezabek, K., 459.Reznik, B. E., 46.Reznikova, E. B., 146.Rhee, K. H., 134, 135.Rhoads, S. J., 285.Rhodes, A., 355.Ricca, A., 462.Rice, S. A., 179.Rich, A., 519,520, 521, 60G,Richards, D. H., 226.Richards, E. W. T., 64.Richards, F. M., 472, 474,434.319.608.485.Richards, R.E., 18.Richards, S. M., 572.Richardson, A. C., 436.Richardson, C. B., 309.Richardson, E. H., 121.Richers, C., 238.Richey, H. G., 251, 252,Richey, H. G., jun., 308,Richtmyer, N. K., 436.Rickards, R. W., 370, 382.Rickborn, B., 307.Ridd, J., 293.Ridd, J. H., 257, 263, 277,Riddle, V. M., 642.Rideal, E. K., 79.Ridgewell, B. J., 277.Riedel, H. W., 351.Rieger, P. H., 209.Riemerschneider, R. W.,Riemschneider, R., 565.Riezebos, G., 334.Rifkind, R. A., 521.Rift, M. R., 274, 361.Riganti, V., 585.Rigassi, N., 356.Rigg, B., 11.Riggs, A., 474.Riley, R. F., 236, 389.Riley Schaeffer, 185.Rimmer, B. M., 610.Rinaldi, C., 283.Rinaldi, F., 581.Rinaudo, M. T., 506.Rinehart, E. A., 162.Rinehart, K.L., 353.Rines, H. W., 442.Ringold, H. J., 416, 418.Riniker, B., 452, 457, 482.Rink, H., 460.Riordan, J. C., 259.Ripamanti, A., 137.Ripan, R., 541.Ripley, R. L., 210.Ripoll, J.-L., 306, 358, 359.Rippie, W. L., 398.Rippon, J. A., 95.Risebrough, R. W., 519.Risinger, G. E., 316.Risley, E. A., 384.Risse, S., 316.Risset, G. W., 484.Ritchey, W. M., 234.Ritchie, C. D., 145.Ritchie, E., 401.Ritchie, G. L. D., 39.Ritchie, M., 62.Ritson, D. M., 31.Rittel, W., 452, 457, 459.Ritter, A., 394.Ritter, G. J., 204.Rittner, R. C., 6G4.Rivest, R., 131, 207.358.364.391.333.Riviore, G., 148.Robb, E. W., 344, 542.Robb, J. C., 73, 156.Robba, M., 387.Robert, M., 450.Roberts, D. L., 372.Roberts, H.L., 137, 201.Roberts, J. D., 251, 271,303, 327, 358, 365.Roberts, J. L., 294.Roberts, R., 98.Roberts, R. B., 613.Roberts, R. M., 285.Roberts, W. K., 447, 499.Robertson, A. V., 401, 432,Robertson, G. B., 594.Robertson, J. M., 396, 572,Robertson, R. E., 259.Robertson, W. A. H., 388.Robin, M. B., 214.Robins, R. K., 394.Robinson, B., 323, 382.Robinson, C. C., 145.Robinson, C. G., 119.Robinson, C. H., 433.Robinson, C. L., 524.Robinson, D. W., 137.Robinson, E. A., 15, 132,136, 137, 138, 201.Robinson, G., 587, 592.Robinson, G. C., 275.Robinson, G. W., 128.Robinson, M. J. T., 288,Robinson, M. S., 64.Robinson, R. A., 12, 19, 27,28, 29, 30, 31, 32, 294.Robinson, R. R., 56.Robinson, S. D., 239.Robinson, V.J., 93.Robinson, W. R., 215.Robinson, W. T., 213, 594.Robson, E., 335.Robson, R., 79, 362.Rocek, J., 291.Roche, J., 508, 510.Rochow, E. G., 188, 191.Roden, L., 490.Rodin, J., 508.Rodnyanskii, I. M., 37.Roe, D. W., 172, 303.Roebber, J. L., 79.Rodder, K. M., 179.Rohrborn, H.-J., 578.Romming, C., 600.Roeske, R., 323, 452.Roesky, H., 211.Roev, L. M., 125.Rogers, A,, 231.Rogers, A. B., 64.Eogers, C. E., 115.Rogers, D., 368, 609.Rogers, S. J., 462.Rogers, T. E., 10, 24.449.609, 611.360INDEX OF AUTHORS’ NAMES 655Rogier, M. V. S., 307.Rogowski, F., 169.Rogozinski, M., 548.Rohde, W. A., 368.Roig, E., 24.Roland, G., 541.Roland, J. R., 397.Rollins, E. L., 446.Roman, L., 532.Romantsev, M. F., 546.Romeo, A., 450.Romers, C., 360, 605.Romeyn, H., 95.Romo, J., 368.Romo de Vivar, A., 368.Ron, A., 294.Ronchi, S., 490.Rondestyedt, C.S., 289.Ronkainen, Z., 544.Itonsch, H., 413.Roodyn, D. B., 508.Rooksby, H. P., 579.Rooymans, C. J. M., 578.Roquitte, B. C., 72, 75, 78,Rorabacher, D. B., 231.Rosaz, J. J., 139.Rose, S. H., 183.Rosegay, A., 384.Rosen, I., 108.Rosenberg, B., 297.Rosenberg, C. F., 515.Rosenberg, E., 498.Rosenberg, R. M., 201.Rosenberger, M., 354.Rosenblum, B., 166.Rosenblum, M., 277, 353,Rosencrantz, D. R., 259.Rosenfeld, E., 441.Rosengren, K., 78.Rosenstein, R., 592.Rosenstern, R . D., 580.Rosenstock, H. M., 153.Rosenthal, D., 30.Rosenthaler, J., 482.Rosevear, J. W., 491.Rosich, R.S., 372.Rosmus, J., 542.Rosolovskii, V. Ya., 36.Ross, B., 206.Ross, B. L., 234.Ross, G., 538.Ross, I. G., 163, 299.Ross, K. M., 442.Ross, S. D., 129, 277.ROSS, W. A., 332.Rosseinsky, D., 26.Rosseinsky, D. R., 45, 46,Rossd, T., 533.Rosset, R., 516.Rossi, I., 99.Rossi-Fanelli, A., 470, 476.Rossini, L., 506.Rossotti, F. J. C., 8.339.354, 355.47.Rossotti, H., 8.Rost, J., 331.Rostetter, Ch., 450.Roszinski, H., 132.Roth, E. S., 224.Roth, W., 67.Roth, W. R., 283, 362.Rothberg, I., 293.Rothenberg, M., 33.Rothfus, J. A., 491.Rothrock, H. S., 336.Rothschild, W. G., 172.Rothstein, M., 356.Rottenberg, M., 290.Roudier, A. J., 444.Rouiller, C., 513.Rousseau, Y., 85, 86.ROUX, L., 450.Rouxel, J., 188.Rovery, M., 469.Rovinskii, M.S., 554.Rowe, C. A., 275.Rowe, J. M., 215, 590.Rowe, P. E., 21, 297.Rowland, R. L., 372.Rowlette, J. J., 83.Roy, S. K., 395.Royer, R. A., 564.Ruben, H., 584.Ruben, H. W., 580.Rubin, M. B., 428.Rubstov, M. V., 378.Rudinger, J., 448, 452, 459,Rudisch, I., 193.Rudloff, V., 468.Rudolph, H. D., 175.Rudolph, P. S., 156.Rucker, G., 327.Rudorff, W., 190.Ruegg, R., 396.Ruf, H., 192, 202.Ruff, J. K., 187, 198.Ruidisch, I., 192.Rukhadze, E. G., 537.Rule, L., 134, 194.Rulfs, C. L., 213.Rumanova, I. M., 582.Rummens, F. H. A., 9.Rumpel, W. F., 64.Rumpf, P., 398.Rundel, W., 379.Rundle, R. E., 179, 220,239, 675, 586, 587, 593.Rupley, A., 473.Rusche, J., 342.Ruschig, H., 421.Rush, R.H., 11.Rusk, J. R., 165.Russatt, A., 71.Russell, D. R., 225.Russell, D. W., 434, 463.Russell. G. A., 293, 345,Rutgers, A. J., 23.Ruth, J. M., 333.484.348.12utherford, D., 447.Rutherford, K. W., 591.Rutner, H., 314.Ruzicka, L., 370.Ryabokobylko, Yu. S., 276.Ryason, P. R., 144.R yderstedt -Nahringbauer,Rydon, H. N., 454.Ryf, H., 422.Ryhage, R., 158, 451.Rylander, P. N., 158.Ryle, A. P., 468.Ryley, J. F., 441.Ryschkewitsch, G., 195.Ryschkewitsch, G. E., 183.Ryss, I. G., 31.Ryzhkof, E. M., 20, 30.Rzeszotarska, B., 456.Rzucidlo, E., 360.I., 597.Sacconi, L., 36, 218, 691.Sachs, M. L., 502.Sachs, T., 50.Sackman, J. F., 199.Sadanaga, R., 581.Sadeh, T., 73.Sadek, H., 30.Saettone, M. F., 290.Safarik, L., 553.Safranko, J., 560.Safronov, A.P., 556.Sage, G., 173, 299.Sage, M. L., 175.Sager, W. F., 181, 290.Sagi, S. R., 639.Saglietto, G., 13.Saha, J. G., 390.Sahini, V. E., 140.Sahyun, M. R.V., 262,266.Sainsbury, M. F., 396.Saito, M., 496.Saito, T., 330.Saito, Y., 590.Sakai, K., 433.Sakai, Y., 565.Sakakibara, S., 479.Sakamoto, M., 166.Sakata, M. K., 365.Sakata, Y., 596.Sakiyama, F., 449.Sakurai, T., 599, 614.Sala, O., 139.Salaria, G. B. S., 213.Salemink, C. A., 355.Salesin, E. D., 537.Salinger, R. M., 275.Sallach, R. A., 204.Sallantin, M., 548.Salmon, G. A., 65.Salmony, D., 507.Salomaa, P., 292.Salter, D. A., 226.Saltiel, J., 88, 293.Salton, M. R. J., 495.Salvadori, G., 289656 INDEX OF AUTHORS’ NAMESSalvetti, O., 124.Samour, D., 494.Sampson, J.A. R., 64.Samsonov, G. V., 204.Samuel, D., 49, 265.Samuelson, O., 543.Sanborn, R. H., 126.Sanchex-Pedreno, C., 538.Sanchez Parereda, J., 332.Sancin, P., 547.Sandbu, S. S., 85.Sandel, V. R., 275,293, 343.Sandhu, S. S., 235.Sandler, S., 602.Sandor, E., 579.Sandoval, A. A., 198, 480.Sandrin, E., 455, 460, 484.Sandros, K., 74.Sands, D. E., 571.Sandulescu, D., 277.Sanger, F., 468, 483.Sang Up Choi., 277.Sankawa, U., 401.Santavy, F., 50, 402.Santer, J. O., 277, 364.Santer, M., 519.Sarachman, T. N., 176,302.Warammn, K., 259.Sarel, S., 292.Sarett, L. H., 384.Sargent, F. P., 348.Sargent, L. J., 407.Sargent, M. V., 340.Sargeson, A. M., 224, 231.Sarkisyan, R.S., 562.Sarrach, D., 189.Sartain, D., 603.Sartori, G., 125.Sasadi, Y., 600.Sasaki, Y., 406.Sass, J., 556.Sass, R. L., 580, 595, 596.Sasse, W. H. F., 387.Sastry, K. V. L. N., 165,170, 174, 306.Sastry, P. S., 494.Sastry, T. P., 550.Satake, K., 476.Satchell, D. P. N., 268, 292.Satchell, R. S., 275.Sato, K., 313.Sato, S., 89.Sato, Y., 359, 433.Satoda, I., 367.Satoh, D., 433.Satoh, S., 108.Sattar, A. B. M. A., 72, 78.Satyanarayana, D., 532.Sauer, M. C., 66, 86.Sauers, R. R., 253, 306.Saul, A. M., 154.Saunders, M., 284, 308, 362.Saunders, R. A., 155, 311.Sausen, G. N., 201.Rauter, R., 559.Saveant, J. M., 60.Saville, B., 555.Savitsky, G. B., 129.Savitz, M. L., 68.Savoie, R., 137, 138, 139.Savory, J., 324.Sawicki, E., 546, 547.Sawyer, A.K., 193.Sawyer, D. T., 17, 226,Sax, M., 595, 596.Saxby, J., 305.Saxby, J. D., 310.Sayre, R. N., 440.Scaletti, J. V., 439, 441.Scanlon, W. B., 388.Scarpati, R., 378.Scatchard, G., 23, 26.Schaaf, R. L., 214.Schaa,l, R., 30.Schachtschneider, J. H.,Schaechter, M., 513.Schafer, H., 187, 275, 575.Schaefer, J. P., 325.Schaefer, T., 306, 309.Schaeffer, A. D., 292.Schaeffer, R., 182.Schatzle, E., 290.Schafer, H. N. S., 533.Schaffer, R., 436.Schaffner, K., 69, 358, 422,Schallus, E., 177.Scharff, M. D., 520.Scharpen, L. H., 175.Schatz, P. N., 145.Schaumann, C. W., 224.Schawlow, A. L., 146, 165.Scheben, J. A., 111.Scheel, J., 254.Scheffler, G., 192.Scheiner, P., 251.Scheldrick, P., 407.Schellenbaum, M., 356.Schenck, G.O., 359, 385.Schenk, G. O., 66, 331, 334,Schenk, P. W., 200.Schepers, R., 320, 398.Scheraga, H. A., 296, 297,471, 473, 482.Scherer, H., 188.Scherer, J. R., 142.Scherer, O., 191, 200.Schemer, K., 517.Scheuerman, R. F., 580,Schiemenz, G. P., 403.Schiorlein, 356.Schiess, P. W., 259, 370,Schiff, H. I., 21, 151.Xchildknecht, C. E., 98.Schiller, A. M., 114.Schindler, K., 295.Schindler, P., 33.304.142.423.343.595.413, 431.Schirdewahn, H.-G., 164.Schissel, P. O., 154.Schlafer, K. L., 8.Schlatter, J. M., 292, 465.Schlatter, V., 353.Schlenk, H., 332.Schlesinger, H. I., 187.Schlessinger, D., 513, 516,517, 518, 521, 522.Schlessinger, R.H., 383.Schleyer, P., 295.Schleyer, P von R., 17, 252,308, 309, 364, 365.Schlingloff, G., 405.Schlitt, R. C., 551.Schlotter, H. A., 394.Schmid, F. D., 146.Schmid, G., 225.Schmid, H., 159, 283, 407,Schmid, K., 487, 488.Schmidbaur, H., 189, 191,Schmidhammer, L., 466.Schmidlin, J., 428.Schmidt, A. P. O., 447.Schmidt, E. W., 83.Schmidt, G. M. J., 73,602.Schmidt, M., 191, 192, 193,194, 200, 202.Schmidt, R., 468.Schmidt, U., 389.Schmidt, W., 215.Schmidt-Thome, J., 421.Schmir, G. L., 293.Schmitt, J., 315, 419.Schmitz, R., 315.Schmitz-Dumont, O., 191,Schmuckler, G., 531.Schmulbach, C. D., 230.Schmutzler, R., 198.Schnabel, E., 456, 457, 459,Schneebeli, J., 513.Schneider, C. H., 459.Schneider, H., 24.Schneider, M., 508.Schneider, R., 587.Schneider, R.A., 308.Schneider, W., 25, 220, 479,Schneider, W. G., 309.Schneider, W. P., 425.Schneko, H. W., 107.Schnering, H. G., 578, 693.Schnoes, H. K., 159, 408,Schogl, K., 353.Schollkopf, U., 275, 337.Schoen, L. J., 126, 135.Schoeneck, W., 316.Schoniger, W., 557.Schonowsky, H., 328.Schofield, J. A., 346.410.192.206.461.584.436INDEX OF AUTHORS’ NAMES 657Schofield, K., 277, 281, 391,Schofield, P. J., 344.Scholder, R., 199.Schole, J., 546.Scholz, C., 422.Schomaker, V., 587.Schonbaum, G. R., 289.Schonberg, S. S., 64.Schonhorn, H., 29.Schoo, W., 345.Schoone, J. C., 592.Schorta, R., 423.Schott, E., 367.Schott, G., 192.Schrauzer, G. N., 94.Schreck, J.O., 292.Schreiber, J., 451, 454.Schreiber, K., 413,430,431.Schriesheim, A., 265, 275,Schroder, E., 463, 483.Schroder, G., 284, 334, 362.Schroeder, H., 183.Schrijder, H., 342.Schroeder, R. A., 129.Schroeder, W. A., 468, 475,Schropp, W. K., 240.Schruefer, J. J. P., 474.Schubert, M., 403.Schubert, W. M., 279, 289.Schudel, P., 396.Schuly, H., 378.Schuett, W. R., 313.Schiitte, H. R., 391.Schuetz, R. D., 386.Schug, J. C., 309.Schug, K., 192.Schugar, H. J., 271.Schulek, E., 550, 552.Schuler, R. H., 307.Schuller, F., 127.Schulte, K. E., 327.Schulte-Elte, K. H., 334.Schultz, G., 350.Schultz, G. V., 440.Schultz, H. P., 322.Schultz, J., 483.Schultz, J. W., 13, 144.Schultze, C., 220.Schultze-Frohlinde, D., 68.Schulz, G.V., 103.Schulz, M., 508.Schulze-Steinen, H.-J., 200.Schumacher, H., 181.Schumacher, H. J., 83, 84,135, 201, 203.Schumann, H., 194.Schunn, R. A., 228.Schurin, B., 145.Schuster, D. I., 343, 359.Schuster-Wolden, H., 240.Schutte, D., 150.Schwabe, K., 11, 30.Schwager, I., 277.392.317, 320.476, 479.YSchwartz, M., 365.Schwartz, W. F., 135.Schwarz, E. C. A., 444.Schwarz, H., 205.Schwarz, M. J., 259.Schwarz, S. E., 148.Schwarzenbach, G., 31.Schwebke, G. L., 324.Schweet, R., 521, 525.Schweet, R. S., 512.Schweiger, R. G., 445.Schweiss, H., 61.Schweizer, E. E., 320, 390,Schwendeman, R. H., 163,Schwenk, E., 418.Schwerin, S., 342.Schwochau, K., 213, 579.Schwyzer, R., 448,452,453,455, 457, 459, 466, 468,482.Scoggins, M.W., 557.Scolman, T. T., 157.Scott, A. I., 346, 414.Scott, €3. D., 311.Scott, D. W., 297.Scott, F. L., 259.Scott, M. D., 315.Scott, W. E., 333.Scott, W. L., 268.Searle, G. H., 231.Searles, S., jun., 295.Sears, C. T., 349.Sears, D. R., 170.Sears, P. G., 21.Sebastian, J. F., 381, 383.Sebbon, J., 103.Sebborn, W. S., 538.Sebek, 0. K., 433.Sebera, D. K., 41.Secci, M., 320.Sechan, R. D., 533.Sederstrom, R. J., 31.Seebach, D., 382, 385.Seefelder, M., 325.Seel, F., 195, 201.Seese, W. S., 423.SefEoviE, P., 410.Seibl, J., 451.Seibles, T. S., 478.Seichter, F. S., 196.Seidel, W., 452.Seidl, G., 250, 344.Seidl, L., 342.Seifer, G. B., 192.Seiler, H., 353.Sela, M., 465, 471, 473, 474,Selbin, J., 209, 219.Selby, B.D., 553.Selig, H., 138, 213.Selman, R. F. S., 538.Seltzer, R., 260, 342.Seltzer, S., 270.Selvaratnam, M., 22.398.173, 174.480.Semeluk, G. P., 89.Semenenko, K. N., 130.Semmes, R. T., 16.Sen, A. B., 538.Sen, A. K., 462.Sen, S. K., 442.Senda, Y., 313.Seng, F., 320.Sen Gupta, A. K., 371.Sengupta, N. R., 531.Sengupta, P., 373.Senko, M. E., 568.Senoh, S., 313.Senyavina, L. B., 333, 464.Sephton, H. H., 436.Serafini-Cessi, F., 435.Serebryakova, G. V., 533.Serencha, N. M., 550.Seres, J., 356, 450.Sergeant, G. A., 535.Serota, S., 422.Seshadri, K. S., 145.Seto, S., 359.Setser, D. W., 65, 86.Setterfield, G., 518.Sevchenko, A. N., 138.Severin, T., 315.Severinets, L.Ya., 565.Seydel, G., 188.Seyferth, D., 181, 185, 192,Seymour, D., 101.Shackelford, J. M., 193.Shaeffer, R., 183.Shafer, J. A., 290.Shah, R. A., 561, 563.Shain, I., 60.Shaker, M., 553.Shakhova, N. V., 535.Shaligram, A. M., 367.Shalitin, Y., 465.Shamma, M., 404.Shanina, T. M., 565.Shao-Chuntung., 547.Shapiro, B. L., 304, 358.Shapiro, B. S., 75.Shapiro, C. L., 381.Shapiro, I., 154, 184.Shapiro, P., 316.Shapiro, P. J., 194.Shapiro, R. H., 415.Sharif, L. E., 215.Sharma, B. D., 574, 601.Sharma, M., 376.Sharma, M. M., 57.Sharnburger, B., 219.Sharon, X., 495.Sharon, P. R., 292.Sharp, D. W. A., 135, 186,Sharp, J. H., 82.Sharpe, L. H., 125.Sharpless, N. E., 76.Shatkin, A. J., 520.Shavel, J., 408.Shaw, B.L., 217, 239, 242.193.217, 225658 INDEX OF AUTHORS’ NAMESShaw, D. C., 373, 483.Shaw, G. B., 47.Shaw, R. A., 197, 198.Shchegoleva, T. S., 186.Shchelokov, V. I., 464.Shcherbachev, G. P., 564.Shchukarev, S. A., 17.Shchukovskaya, L. L., 186,Shdo, J. G., 184.Shea, J. L., 386.Sheard, D. R., 91.Shearer, H. M. M., 588.Shechter, H., 350.Shedlovsky, T., 19.Sheehan, J. C., 449, 451,Sheehan, J. J., 484.Sheehan, J. T., 460.Sheft, I., 180.Sheinblatt, M., 51, 52.Sheinker, A. P., 98.Sheinker, Yu. N., 464.Sheline, R. K., 139, 234.Shelton, B., 438.Shelton, J. B., 468.Shelton, J. R., 468.Sheludyakov, V. D., 186.Shemin, D., 389.Shemyakin, M. M., 320,333,Shemyatenkova, V. T.,Shen, T. Y., 384.Sheppard, J. C., 43, 44.Sheppard, N., 123, 128, 138,200, 301, 303.Sheppard, R.C., 382, 448,449, 452, 464, 466.Sheppard, W. S., 344.Sheridan, J., 160, 166, 167,170, 172, 173, 174, 300.Sheridan, R. C., 30.Sherif, F. G., 219.Sherman, G. M., 383.Sherrington, P. J., 20.Sherry, H. S., 204.Shibaeva, R. P., 582.Shibata, S., 374, 401, 537.Shida, H., 502.Shida, S., 67, 86.Shigorin, D. N., 130.Shilman, A., 71.Shiloh, M., 34, 214.Shimaoka, A., 433.Shimidzu, H., 517.Shimizu, K., 535.Shimizu, M., 481.Shimizu, T., 162, 536.Shimizu, Y., 432.Shimo, K., 324.Shimoda, K., 162, 169.Shimulis, V. I., 124.Shin, K. H., 479.Shine, H. J., 283, 312,Shin-en Nu, 360.452, 453, 462, 465.463, 464.564.397.Shiner, V. J., 18, 256, 263Shiner, V.J., jun., 58, 188Shinoznka, F., 542.Shively, J. H., 557.Shkrob, A. M., 464.Shmatko, R. I., 536.Shmueli, U., 608.Shnulin, A. N., 557.Shockman, G. D., 496.Shoemaker, C. B., 571.Shoemaker, D. P., 571.Shoffner, J., 391.Sholette, W. P., 154, 186.Shoolery, J. N., 308.Shoop, E. C., 410.Shooter, E. M., 476.Shoppee, C. W., 418, 432.Shore, S. G., 183, 185.Shorr, L. M., 548.Short, E. L., 16, 34, 130.Shorter, J., 292.Shoup, C. S., 133.Shozda, R. J., 201.Shreiner, N. M., 534.Shriver, D. F., 132, 189,Shryne, J. M., 95.Shub, N. S., 539.Shuger, D., 393.Shuikin, N. I., 313.Shulgin, A. T., 283.Shul’ts, M. M., 32.Shumyatskaya, N. G., 582.Shustri, N. K., 48.Shuvalov, I. K., 147.Shvachkin, Yu. P., 393.Shvyrkova, L.A., 564.Siau, J., 23.Sicher, J., 263, 266, 360.Sicre, J. E., 84.Siddall, J. B., 419, 426.Sidman, J. W., 69.Sidran, M., 163.Seber, P., 455, 457, 459,Siecke, F. W., 190.Siedel, W., 459, 460.Siegal, F. P., 286.3iege1, B., 201, 206.Segel, S., 179, 573.Sieker, L. C., 468.Siekevitz, P., 513.Sierra, F., 538.Sievers, R. E., 223.Sifniades, S., 71.Siggia, S., 550, 557, 560.3ih, C. J., 412, 433.Silberg, I., 394.Silbert, L. S., 302, 335.SillBn, L. G., 27.Silver, B., 49.silver, B. L., 265.silver, H. G., 128, 300.Silver, H. P., 185.silver, M. S., 254, 289.287, 291.226, 240.468.Silverman, D. A., 526.Silverman, J., 601.Silverman, S., 123.Silvers, S., 609.Silverstein, R. M., 551.Silverton, J. V., 222, 223,Silverwood, H.A., 325.Silvestri, A. J., 341.Sim, G. A., 396, 609, 610,Sim, K. Y., 396.Simamura, O., 295, 310.Simes, H. V., 374.Simes, J. J. H., 374.Simha, M., 113.Simmons, H. E., 267, 397.Simmons, R. A., 260.Simon, A., 137, 138.Simon, H., 287.Simon, I., 38.Simon, P., 419.Simon, W., 360, 559.Simonov, A. P., 130.Simonov, V. I., 582.Simons, J. P., 62, 73, 77.Simons, J. W., 293.Simpson, P., 518.Simpson, P. G., 182, 183,Simpson, P. L., 324.Simpson, W. B., 195.Sims, J. J., 389, 408.Singer, E., 537.Singer, L. A., 251, 274,345.Singer, M. F., 525.Singer, S. J., 481.Singh, B., 554.Singh, D., 541.Singh, K. P., 401.Singh, P., 72.Singleton, D. A., 78.Sinha, s. N., 534.Sinn, H., 109, 110.Sinnott, K. M., 170, 174.Sinsheimer, J.E., 551.Siore, J. H., 201.Siqueira, J. B., 147.Sisler, H. H.: 183, 195, 197.SitaE, J., 402.Sixma, F. L. J., 275, 277,Sizer, I. W., 470.Sjoberg, B., 452.Sjostrand, F. S., 508.Skell, P. S., 261, 262, 293,Skellon, J. H., 330.Skelly, N. E., 550.Skoczylas, B., 564.3korbo-Trybula, Z., 536.Skorchev, B., 128.3korcz, J. A., 383.Skrivastava, R. K., 37.Skulski, L., 296.Skvortsova, A. B., 547.396, 589.611.228.345.337, 382INDEX OF AUTHORS’ NAMES 659Slack, R., 387.Slade, L., 230.Slade, L. T., 259.Slagg, N., 71, 76.Slawson, V., 546.Slayer, H. S., 515.Slayter, H. S., 520.Sleezer, P. D., 250.Sleight, A. W., 205, 578.Slick, P. I., 295.Slisarenko, F. A., 547.Slivnik, J., 179, 180.Slobin, L.I., 470.Slodki, M. E., 435.Sloneker, J. H., 446.Sloth, E. N., 150, 180.Slusarchyk, W. A., 404.Slusker, J. P., 597.Smak, A., 179.Smalc, A., 180.Small, R. W. H., 595.Smaller, R. B., 65.Smallwood, S. E. F., 132.Smeby, R. R., 482.Smejkal, J., 358.Smid, J., 111,112, 113,296.Smidsrod, O., 445.Smirnov, V. N., 145.Smirnova, G. P., 324.Smirnova, K. A., 535.Smirnova, R. V., 539.Smith, A. L. 19, 21.Smith, B., 548.Smith, B. C., 198, 205.Smith, B. E., 294.Smith, C. R., jun., 332.Smith, C. W., 322.Smith, D. C. C., 395.Smith, D. E., 60.Smith, D. F., 179, 180, 573.Smith, D. L., 588.Smith, D. M., 281, 345.Smith, D. R., 97.Smith, E. A., 212.Smith, E. D., 551.Smith, E. E., 438.Smith, E. L., 468, 469, 476,Smith, E.N., 190.Smith, F., 434, 439, 440,Smith, F. T., 84.Smith, G. F., 34, 409.Smith, G. G., 275, 292.Smith, G. M., 475.Smith, G. S., 568.Smith, G. V., 307, 365.Smith, H., 426.Smith, H. F., 556, 564.Smith, H. G., 414.Smith, H. M., 16.Smith, H. P., 95.Smith, J. E., 38.Smith, J. J., 195.Smith, J. P., 215, 223.Smith, J. V., 581.491.441, 549.Smith, L. F., 468.Smith, L. W., 400.Smith, M., 419.Smith, M. A., 527.Smith, M. D., 439.Smith, M. L., 263.Smith, P. B.; 265.Smith, P. F., 64.Smith, P. J., 323.Smith, R. A. D., 559.Smith, R. E., 501, 506.Smith, R. F., 322.Smith, R. H., 504.Smith, R. N., 190.Smith, R. R., 105.Smith, S. G., 291, 36.Smith, S. L., 361.Smith, S. R., 71.Smith, W., 332.Smith, W. F., 286.Smith, W.L., 123.Smithers, M. J., 461, 472.Smolinsky, G., 293.Smova, P. D., 128.Smyth, J., 455, 468, 471,475, 478, 479, 480, 483,484.Snaith, R. W., 383.Snatzke, G., 373, 377, 419.Sneen, R. A., 255.Snell, A. H., 156.Snellman, O., 489.Snider, N. S., 294.Snyder, C. H., 265.Snyder, H. R., jun., 314.Snyder, L. C., 248, 364.Snyder, R. G., 142, 588.Soane-Stanley, G. H., 561.Sobkowski, J., 46.Sobue, H., 99, 100.Sochava, I. V., 92.Sochevanov, V. G., 531.Soderberg, R. H., 222.Sorlin, G., 385.Soine, T. O., 402.Sojolov, V. I., 275.Sokoloff, L., 509, 510.Sokolov, V. I., 275.Sokolova, M. A., 100.Sokolova, N. P., 124.Sokolowska, T., 452, 456.Soldano, B. A., 39.Solodovnik, V. D., 320.Solovkin, A. S., 208.Solymosi, F., 539.Somasekhara, S., 293, 343.Somerfield, G.A., 355.Sommer, A., 126, 154.Sommer, L., 534.Sommer, P. F., 360.Sondheimer, F., 340, 352,Sonnenberg, F., 325.Sonnenberg, J., 253.Sonnenbichler, J., 512.Sonnet, P. E., 306.420.Sooy, W. R., 148.Sorensen, T. S., 330, 391.sorm, F., 366,367,368,415,416, 422, 459, 463, 469,484.SouEek, M., 368.Souten, J. R., 135.Sowa, W., 441, 446.Spackman, D. H., 468.Spahr, P. F., 516, 517, 522.Spanier, E. J., 193.Speakman, J. C., 597, 613.Spedding, F. H., 36.Spedding, H., 52.Spell, A., 114.Spell, J. F., 107.Spencer, J. B., 33.Spencer, J. F. T., 446.Spencer, M., 525, 606.Spencer, R. E., 389.Spencer, R. R., 435.Spenser, I. D., 399.Spero, G. B., 425.Speyer, J.F., 523,526, 527.Speziale, A. J., 258, 264,Spicer, C. K., 315.Spiegelman, S., 501, 517.Spiegler, K. S., 214.Spielfgelman, S., 526.Spikner, J. E., 549.Spilners, I. H., 155.Spink, C. H., 34.Spinner, E., 311, 390.Spirin, Y. S., 113.Spiro, M., 23.Spiro, T. G., 11.Spiteller, G., 159, 299, 401,Spiteller-Friedmann, M.,Spitnick-Elson, 5 18.Spittler, E. G., 86.Spivak, L. L., 294.Spoerri, P. E., 314.Spokes, G. N., 280.Sporn, M. B., 517, 524.Spotswood, T. M., 387.Spotswood, T. McL., 295.Spratley, R. D., 179.Spriessler, W., 190.Sprio, V., 371.Spyrides, G. J., 523.Srinivasan, R., 67, 68, 69,71, 72, 87, 362.Srivastava, J. P., 540.Srivastava, K. K., 21.Srivastava, R. D., 23.Srivastava, S. N., 601.Srivastava, T.N., 134.Srivastava, T. S., 538.Sroka, W., 461.Stacey, F. W., 269.Stacey, M., 435, 437, 439,441, 446, 487, 488, 498,500.289, 338.409, 410.159660 INDEX OF AUTHORS’ NAMESStadler, P. A., 463.Stadler, R., 437.Staehelin, T., 519, 521,522.Stallberg-S tenhagen, S.,Stafford, S. L., 186, 242.Stafiej, S. F., 182.Stahl, C. R., 557.Stahl, R. F., 196.Stahlberg, R., 136.Stahmann, M. A., 527.Stain, C. H., 611.Stakhanova, M. S., 32.Stamhuis, E. J., 267.Stamm, R. F., 269.Stammer, C. H., 384.Stammreich, H., 138, 139.Stamper, W. E., 344.Stanek, J., 435, 437.Stanford, R. H., 605.Stang, A. F., 183.Stanko, V. I., 183.Stanley, T. W., 546, 547.Stanley, W. M., 468.Stannett, V., 98.Stanton, G. M., 349.Stanton, H. E., 152, 153.Staples, C.E., 339.Staples, P. J., 231.Stapleton, I. W., 454.Starck, B., 164, 165.Staricco, E. H., 84, 201.Stark, G. R., 472, 478, 479.Stark, J. R., 439, 441.Stark, K., 237.Starr, J. E., 365.Starr, L. D., 390.Stasilli, N. R., 502.Staude, E., 190.Staudinger, H., 335.Staunton, J., 399.Steacie, E. W. R., 73.Stead, J. B., 46.Steadman, R., 581, 582.Steams, R. S., 109.Stecher, O., 190.Stedman, D. I., 259.Steel, C., 75.Steele, D., 299.Stefani, A. P., 75, 269, 330.Steffa, L. J., 263.Steffensen, G. R., 162.Stegemeyer, H., 68.Steger, A., 137.Steger, E., 136, 138.Steglich, W., 400, 455.Stehr, C. E., 448.Steigelmann, E. F., 73.Stein, G., 79, 84.Stein, L., 179.Stein, O., 510.Stein, R. A., 546.Stein, W.H., 468, 470, 472,Steinberg, I., 297.Steinberg, 0. Z., 296.158, 451.478.Steiner, B., 67, 152.Steiner, E., 142.Steiner, K., 437.Steinfield, J. I., 230.Steinfink, H., 581.Steinhardt, C. K., 379.Steinkopff, D., 121.Steinmetz, R., 66, 331, 385.Steinrauf, L. K., 468.Stekhanov, A. I., 137.Stelos, P., 481.Stenger, V. A., 560.Stenhagen, E., 158, 451.Stenlake, J. B., 367.Stepanov, R. G., 387.Stepanova, V. A., 544.Stephen, A. M., 444.Stephens, F. S., 220.Stephens, R., 314.Stephens, R. D., 282.Stephenson, J. S., 328.Stephenson, L., 421.Stephenson, M. L., 512.Stephenson, N. C., 218,Sterin, Kh. E., 144.Sterinmetz, R., 359.Stermitz, F. R., 68, 340,Stern, A., 316.Stern, J. H., 36.Stern, K. H., 17.Sternberg, H.W., 339.Sternhell, S., 416, 432.Steronov, F. N., 384.Sterr, G., 194.Steudel, R., 200.Stevens, C. L., 437.Stevens, I. D. R., 75.Stevens, L. G., 189.Stevens, R. K., 333.Stevens, T. E., 289.Stevenson, H. B., 336.Steward, F. C., 449.Steward, 0. W., 276.Stewart, B. B., 207.Stewart, H., jun., 198.Stewart, J. A., 290.Stewart, J. L., 37.Stewart, J. W., 476.Stewart, L., 435.Stewart, R. F., 33.Stiddard, M. H. B., 85, 234,Stiefvater, 0. L., 174, 300.Stier, A., 563.Stiles, E., 114.Stiles, M., 280, 281, 289,Still, I. W. J., 395.Stimson, V. R., 292.Stirling, C. J. M., 454.Stock, A. J., 462.Stock, D. I., 11.Stock, L. M., 275, 344.Stockel, R. F., 323.219.402.235.346.Stoessl, A., 78.Stoffel, W., 333.Stoffyn, P.J., 500.Stoicheff, B. P., 121, 147,Stokes, J. M., 19, 29, 32.Stokes, R. H., 12, 18, 19,28,Stokker, G., 265.Stolyarov, B. V., 556.Stolz, I. W., 139, 234.Stomberg, R., 590.Stone, A. L., 446.Stone, B. A., 442.Stone, E. W., 309.Stone, F. G. A., 139, 184,233, 235, 238, 241, 242.Stone, N. W. B., 127, 128.Stopperka, K., 137.Storck, R., 514.Stork, G., 323, 376, 410,Storni, A., 365.Storr, A., 132, 189.Story, P. R., 248, 308, 364.Stotz, E. H., 434.Stoughton, R. W., 28, 33,Strafelda, F., 61.Straley, J. W., 145.Strametz, H., 199.Strandberg, B., 139, 592.Stranks, D. R., 42.Stranski, I. N., 199.Stratton, C., 198.Straub, D. K., 195, 226.Strauch, R., 165.Straughan, B. P., 187.Straughan, D. P., 132.Strauss, H.L., 308.Strausz, 0. P., 85.Stravropoulus, W. C., 308.Straw, H., 120.Street, G. B., 234.Strehlow, H., 24, 229.Streib, E., 184.Streith, J., 366.Streitwieser, A., 250, 255,Streng, A. G., 179, 203.Streng, L. V., 179.Stretch, C., 11 1.Strickler, S. J., 65.Strieter, F. J., 595.Strobach, D. R., 438.Stroh, H. H., 549.Strohmeier, W., 21,84,235.Strolenberg, K., 198.Strominger, J. L., 495, 496.Strouf, O., 408.Stroupe, J. D., 107, 114.Struchkov, Yu. T., 601.Struck, C. W., 581.Strumia, E., 506.Strunin, B. N., 324.Stryland, J. C., 128.148, 171, 174, 300.29, 32.429.37.275, 277INDEX OF AUTHORS’ NAMES 661Stuart, K. L., 405, 406.Stuben, K. C., 455.Stuber, J. E., 254.Stuckwisch, C. G., 380.Studer, P., 432.Studer, R.O., 463, 484.Studier, M. H., 150, 180.Stuehr, J., 50.Stiirmer, E., 455.Stuhl, F., 80.Stull, D. R., 297.Stump, E. C., 201.Stumpp, E., 190.Stupin, D. Yu., 32.Sturgeon, R., 434.Sturm, E., 350.Sturm, K., 452, 459, 460.Sturmer, E., 460.Sturtz, G., 320.Subba Rao, B. C., 315.Suchanek, P., 322.Suchomelova, L., 555.Suchf, M., 367, 368.Sudhalatha, K., 533.Suec, H., 552.Susse, P., 593.Sugasawa, T., 371, 414.Sugawara, H., 434.Sugden, T. M., 167, 169,Sugisawa, Y., 505.Sugista, R., 536.Suglobov, D. N., 138.Suhadolnik, R. A., 399.Suhr, H., 315, 385, 419.Suida, J., 426.Sukhotin, A. M., 20, 30.Sukornick, B., 196.Sullenger, D. B., 571.Sullivan, D., 351, 386.Sullivan, J. C., 205.Sulramanian, P.M., 263.Sulzberg, T., 252.Sumarokova, T. N., 134.Sumimoto, M., 367, 370.Summers, G. H. R., 416.Summitt, R., 139.Sumratis, J. D., 331.Sundaralingam, M., 252,Sundaram, A., 305.Sundaram, K. M. S., 301,Sung Moon, 249.Sunr, H., 309.Supp, G. R., 553.Suprunovich, V. I., 541.Surak, J. G., 541.Surawski, H., 21.Surendranath, M., 541.Surtees, J. R., 188.Surtees, J. W., 188.Suschitzky, H., 345, 387,Sushchinskii, M. M., 147.Suskind, S. P., 319.171, 190.599.305.390.SUEZ, B. P., 134.Sutcliffe, L. H., 11, 47, 219,Sutherland, G. (Sir), 299.Sutherland, H. H., 598.Suthers, B. R., 344.Suitin, N., 40, 44, 45, 46,Sutor, D. J., 608, 613.Sutton, G. J., 220.Sutton, M. M., 84.Sutton, P. W., 222.Su Yu-Jhg, 32.Suzuki, J.417.Suzuki, K., 228, 457, 460.Suzuki, M., 92, 505.Svec, H., 159, 451.Svehla, G., 531, 552.Svennerholm, E., 493.Svennerholm, L., 492, 493.Sverdlov, L. M., 142.Svidzinskii, K. K., 163.Svoboda, M., 266.Svoboda, V., 555.Swaddle, T. W., 230.Swain, C. G., 25, 51, 259.Swalen, J. D., 163, 164,Swallow, A. G., 594.Swallow, A. J., 78.Swaminathan, K., 218.Swan, J. M., 454.Swanson, J. A., 35.Swart, E. R., 256.Sweeley, C. C., 434, 492.Sweeney, D. M. C., 122,300.Sweeting, 0. L., 394.Swensen, R. F., 557.Swenson, G. W., 79.Swern, D., 302, 335.Swiderski, J., 556.Swinehart, D. F., 31, 150.Swinehart, J. H., 17.Swirski, J., 394.Swithenbank, C., 275, 363.Syavtsillo, S. V., 545, 564.Sykes, A. G., 43, 46, 231.Sykes, K.W., 10.Symons,M. C. R., 9, 11, 36,83, 204, 225.Synecek, V., 580.Syrkin, Ya. K., 178.Szabo, F., 450.Szab6, L., 438.Szaboles, J., 331.SzBntay, C., 403.Szmek, W. A., 437.Szasz, G., 556.Szasz, K., 408.Szathmary, I., 533.Szekeres, L., 539.Szkrybalo, W., 307.Szmuszkovica, J., 323.Szpilfogel, S. A., 433.Szwarc, M., 74, 75, 111, 112,113, 269, 296, 330.223.47.174, 175.Tabata, Y., 99, 100.Taber, W. A., 441.Tabner, B. J., 297.Tabrizi, F. M., 155.Tachi, I., 55.Tackett, J. E., 17, 226, 304.Tackie, A. N., 408.Taddei, F., 272.Tadokoro, H., 142.Tadros, T. F., 30.Taft, D. D., 386.Taft, R. W., 25.Taguchi, H., 313.Taha, F., 213.Tahara, A., 371.Taimsalu, P., 134.Takacs, E. A., 182.Takagi: K., 169, 302.Takahashi, H., 320.Takahashi, R., 55.Takahashi, S., 487.Takahashi, T., 505.Takahashi Inukai, 275.Takai, M., 522.Takaki, Y., 600.Takamizawa, M., 185.Takanami, M., 516, 522,Takano, T., 575.Takashi, M., 156.Take, T., 476.Takeda, K., 433.Takehara, M., 317.Takemori, A., 506.Takemori, I., 432.Takeshita, H., 72.Taketoni, T., 330.Takeuchi, T., 562.Takbuchi, Y., 581.Takiyama, K., 537.Takuma, H., 162, 169.Tal, M., 516.Talalaeva, T.V., 130.Talapatra, S. K., 410.Taliaferro, J. D., 269.Taller, R. A., 304.Tal’roze, V. L., 99.Tamas, J., 23.Tamberg, M., 295.Tamm, Ch., 368, 419, 433.Tamm, K., 24.Tamres, M., 295.Tanabe, K., 417.Tanabe, M., 327, 337.Tanaka, A., 494.Tanaka, I., 80.Tanaka, M., 89, 317.Tanaka, N., 497.Tanaka, O., 374.Tanaka, Y., 370.Tanford, C., 91, 296.Tang, Y .- S . , 461.Tani, H., 327.Tank, F., 172, 306, 359.Tanner, D. D., 271.Tanner, K., 121, 306.523, 524662 INDEX OF AUTHORS’ NAMESTannewald, P. E., 148.Tao Ping Li, 259.Tapley, D. F., 501, 508.Tardella, P. A., 381.Tare, S. A., 144, 145.Tarket’taub, N. M., 564.Tarrant, P., 324.Tarutani, O., 488.Taschner, E., 452, 454, 456.Tashiro, Y., 517.Tasman, H. A., 154, 155.Tata, J. R., 501, 506, 508,Tatawadi, S. V., 541.Tate, J. F., 27.Tate, M. E., 435.Tatevskii, V. M., 121, 135,Tatlow, J. C., 194, 314.Taube, H., 8, 17, 41, 46,215, 224, 231.Taube, R., 213.Tavale, S. S., 597.Tavs, P., 200.Taye, D. P., 238.Taylor, A., 383.Taylor, A. F., 13.Taylor, B.L., 10.Taylor, E. C., 393.Taylor, G. A., 392, 437.Taylor, J. C., 374, 608.Taylor, J. F., 475.Taylor, K. A., 143.Taylor, L. J., 259.Taylor, M. J., 134, 136.Taylor, M. W., 542.Taylor, R., 133, 275, 390.Taylor, R. C., 132, 138,Taylor, R. P., 64.Taylor, W. C., 401.Taylor, W. H., 100.Taylor, W. I., 384,407,408.Taylor, W. J., 159.Taylor Smith, R., 329.Tazuke, S., 97.Teare, J. W., 30.Tebbe, F., 183.Tebby, J. C., 389.Tedder, J. M., 335, 383,Tejima, S., 260.Temkin, 0. N., 541.Temme, H.-L., 315.Tempest, W., 152.Templeton, D. H., 179, 180,568, 573, 579, 580, 584,595.510.146.236.387.Templeton, W., 416, 417.Tennant, G., 387, 393.Tepperman, H. M., 501.Tepperman, J., 501.Teranishi, R., 150.ter Borg, A.P., 361.Terenin, A. N., 125.Terent’ev, A. P., 296, 554.Terentiev, P., 537.Teresawa, J., 412.Teresawa, T., 429.Terheide, R., 547.Terhune, R. W., 129, 148.Terrell, R., 323.Tertoolen, J. F. M., 535.Tertzakian, G., 280, 345.Teske, W., 192.Tesser, G. I., 455.Tessier, J., 433.Testa, A. C., 89.Testa, E., 381.Teufer, G., 578.Tevanen, K.,31.Tewari, P. H., 21.T6z6, A., 30.Tezuka, T., 319.Thaddeus, P., 168, 169.Thaker, G. P., 315.Thanh, N. V., 123.Thayer, G. L., 270.Theander, O., 434.Theard, L. P., 154.Theilacker, W., 261, 342.Theimer, O., 145.Theimer, R., 145.Theobald, D. W., 372.Theobald, J. M., 454.Thibault, R. J., 127, 133.Thieberg, K. J. L., 373.Thiele, K.-H., 242.Thill, B. P., 296, 307.Thilo, E., 196.Thirsk, H.R., 26.Thom, K. F., 194.Thoma, J. A., 434.Thomas, A. L., 378.Thomas, D. M., 332.Thomas, D. W., 156.Thomas, E. L., 143.Thomas, G. H., 416.Thomas, G. M., 400.Thomas, H. J., 434.Thomas, J. K., 48.Thomas, L. F., 167, 170,Thomas, R. M., 119.Thomason, W. E., 548.Thompson, A., 396, 438.Thompson, C. E., 534.Thompson, D. T., 238.Thompson, E. 0. P., 468.Thompson, H. W., 128,144, 145, 258, 338, 340.Thompson, J. A., 315.Thompson, J. L., 425.Thompson, L. C., 204.Thompson, N. R., 185.Thompson, R. C., 220.Thompson, R. D., 379.Thompson, W. A., 209.Thomson, R. H., 346, 382.Thorley, J., 135.Thornhill, D. P., 259.Thornton, E. R., 263, 293.173, 436.Thrush, B. A., 67.Thumm, H., 28, 33.Thurkauf, M., 290.Thweat, J.G., 336.Tice, B. B. P., 277.Tichy, M., 360.Tidd, B. K., 333.Tidwell, E. D., 122.Tieckelmann, H., 283.Tiers, G. V. D., 107, 108.Tillett, J. G., 275, 312.Tilney-Bassett, J. F., 240.Timasheff, S. N., 518.Timberlake, C. E., 438.Timell, T. E., 289, 442,443,Timmons, C. J., 319, 340.Tims, J. C. W., 335.Tincher, W. C., 108.Tin Xin-Gen, 321.Tipton, I. H., 509.Tipton, S. R., 509.Tishler, P. V., 505.Tissieres, A., 509, 513, 516,Titani, K., 476.Titeica, S., 277.Ti Tien, H., 32.Titov, Yu, A., 272.Tittle, B., 201.Tiu-Ou Huo, 124.Tobe, M. L., 231, 232.Tobias, R. S., 31, 33, 210.Tobiason, I., 216.Tobolsky, A. V., 108, 110,112, 113, 115.Toby, S., 74.Toda, F., 327.Todd, Lord (A. R.), 355,356, 396.Todd, S.S., 297.Todt, E., 189.Toei, K., 538.Toeniskoetter, R. H., 185.Torring, T., 166.Toft, R. J., 538.Tbke, L., 403.Tokita, K., 487.Tokolies, J., 426.Tokonami, M., 581.Tolberg, R., 71.Tolentino de Carvalho Bra-zBo da Silva, G. B. C.,374.444.517.Tolg, G., 564.Tolgyesi, W. S., 252.Tolles, W. M., 169, 172.Tomask, V., 469.Tometsko, A., 457, 461,Tomilov, A. P., 317.Tomita, K., 592.Tomita, M., 319, 403, 405.Tomlinson, G., 355.Tomlinson, R. C. B., 21.Tomomatsu, H., 499.468INDEX OF AUTHORS’ NAMES 663Tong, L. K. J., 91.Tonge, B. L., 190.Toohey, A. C., 106.Toole, J., 96.Toothill, R. B., 314.Topp, N. E., 22.Topping, G., 123.Topping, R. M., 286.Torelli, V., 427.Torgov, I. V., 426, 427.Tori, K., 433.Torigoe, M., 321.Torp, B.A., 209.Torrible, E. G., 207.Toubiana, R., 324, 372.Tome, J. C., 549.Tomes, C. H., 148, 163,Tomley, E. R., 76.Towns, D. L., 249.Towns, M. B., 28.Toya, T., 125.Toyama, M., 308.Toyama, O., 75.Trapeznikova, 0. D., 92.Traub, W., 608.Traylor, T. G., 266, 275,Traynham, J. G., 293.Treacy, E. B., 160.Trecker, D. J., 68, 269, 330.Treficante, D. D., 338.Trefonas, L. M., 598, 604.Treibs, A., 382.Treichel, P. M., 235.Treinen, A., 10, 11.Trelst, A., 287.Trenczek, G., 188.Trevalion, P. A., 83.Triaille, E. A., 123.Trifan, K., 252.Triffett, A. C. K., 612.Triggle, D. J., 258.Tripp, L. A., 295.Trippett, S., 320.Trischmann, H., 434.TrojBnBk, J., 408.Trokowicz, D., 551.Tromans, F.R., 574.Tromsdorff, E., 106.Troncoso, E., 540.Troszkiewicz, C., 391.Trotman-Dickenson, A. F.,Trotter, J., 194, 573, 587,Trotter, P. J., 307.Trottier, C. H., 314.Trowbridge, J. C., 138.Trozzolo, A. M., 293.Truce, W. E., 268,292, 336,Trueblood, K. N., 603, 611.Trulson, 0. C., 154.Trumbull, E. R., 264.Truscott, T. G., 292.165, 166.379.73.588, 599, 601, 602.380.Truter, M. R., 218, 579,Trutnovsky, M., 564.Tschesche, R., 373, 377.Tsenter, M. Ya., 145.Tsitovich, I. K., 532.Tsitsishvili, G. V., 125.Ts’o, P. 0. P., 514, 517,Tsuchihashi, G.-I., 25.Tsuda, K., 406, 417, 421,Tsuda, Y., 99, 100.Tsugita, A., 468.Ts’ui Hsien-Hang, 537.Tsuji, T., 318.Tsurutrt, T., 103.Tsutsui, M., 241, 353, 354.Tsutsuni, S., 342.Tsvetkova, S.V., 208.Tsyashchenko, Yu. P., 146.Tu, C.-T., 461.Tuck, D. G., 221.Tuck, D. J., 203.Tucker, B. G., 73.Tucker, W. P., 454.Tul’chinskii, V. B., 31.Tuleen, D. L., 293.Tulinsky, A., 609.Tullock, A. P., 544.Tully, W. F., 549.Tulus, M. R., 548.Tulyupa, F. M., 541.Tunder, R., 201.Tung, C. C., 258, 264.Tun-Kyi, A., 466.Tunnicliff, D. D., 144.Tuppy, H., 468, 476.Turck, H. E., 30.Turco, A., 138, 139, 215,Turgeon, J. C., 26.Turkova, J., 463.Turnbull, J. P., 372, 375.Turner, A. C., 167.Turner, D. W., 309, 375.Turner, H. S., 186.Turner, J. J., 79.Turner, J. W., 33.Turner, W. B., 328.Turova, N. Ya., 130.Turrell, G. C., 128.Turro, N. J., 88, 89.Tursch, E., 374.Turse, R., 64.Turvey, J.R., 435.Tur’yan, Ya. I., 55, 56,540.Tushaus, L. A., 306, 358.Tutwiler, F. B., 329.Tuzhilina, N. V., 538.Tyler, A., 526.Tyler, J. K., 166, 167, 173,304.Tyree, S. Y., 32, 208, 209,211, 212.Tyrrell, V., 33.591, 594, 603.578, 579.433.219.Tyson, G. J., 579.Tyulin, V. I., 121, 146.Uberwasser, H., 428.Uchida, K., 514.Uchida, Y., 330.Uda, H., 369.Udupa, H. V. K., 319.Ueda, K., 368, 372.Uehara, R., 95.Ugo, R., 217.Uhlig, H., 468.Ui, N., 488.Ujijira, Y., 537.Ukaji, T., 303.Ulbricht, T. L. V., 526.Ulery, H. E., 306.Uliasz, A., 556.Ulitko, V. W., 545.Ullman, E. F., 73, 350, 394.Ulm, K., 240.Ulmer, H., 136.Ul’yanova, 0. D., 145.Uma, M., 305.Umbach, W., 347.Umehara, M., 394.Umoh, A. T., 328.Umreiko, D.S., 138.Underhill, A. E., 242.Underwood, A. L., 16.Undheim, K., 452.Unger, H. J., 135.Unger, I., 89.Unni, A. K. R., 21.Uno, T., 142.Unrau, A.M., 435,444,447.Untch, K. G., 297,350,362.Urbanski, J., 539.Urbinski, T., 195, 296, 305.Urbas, B., 443.Urch, D. S., 203.Urech, J., 356.Urenovitch, J. V., 191.Urheim, H., 290.Urry, G., 187.Usanovich, M. I., 134.Usatenko, Yu. I., 541.Usher, D. A., 293.Usov, A. I., 437.Utley, J. H. P., 292.Utsumi, T., 104.Utzinger, E. C., 422.Uyeo, S., 372.Vaciago, A., 3 88.Vaidya, A. S., 365.Vaidya, M. S., 42.Vajda, M., 552.Vakrushev, Yu. A., 55.Valenta, Z., 401.Valenti, V., 214.Valkanas, G., 259.Vallee, B. L., 504.Vanacek, J., 476.van Allan, J. A., 392.Van Dalen, J.J., 326664 INDEX OF AUTHORS’ NAMESVan de Grampel, J. C., 200.Vanden Heuvel, W. J. A.,Van der Auwera, D., 86.Van der Does, L., 390.Van der Kelen, G. P., 14,van der Kerk, G. J. M., 194.van der Ploeg, H. J., 329.van der Sijde, D., 412.van der Steen, D., 333.van der Waard, W., 412.van der Waard, W. F., 433.Vanderzee, C. E., 11, 35, 36.Vandi, A., 200.van Dorp, D. A., 332, 333,van Dyke, C. H., 190, 181.Vane, F. M., 251, 304.van Effen, C. H., 337.Vangedal, S., 433.van Ghemen, M., 196.Van Hall, C. E., 560.Van Hoang, D., 469.Van Hoozer, R., 265, 319.van Iperen, B. B,., 161van Kranendank J., 128.Van Ligten, J. W. L., 533.van Meerssche, M.: 599.van Meurs, N., 361.Vannerberg, N.-G., 199,van Riesenbeck, G., 54.van Tamelen, E., 360, 365.van Tamelen, E.E., 339,Van Tassel, J. H., 64.van Thanh, N., 123.Van Thiel, M., 126.van Veljen, J. C., 345.van Voorst, J. D. W., 384.van Woerden, H. F., 336.Varma, K. R., 367.Varna, I. D., 193.Varrone, S., 508.Vars, R., 295.Varsel, C. J., 546.Vasil’ev, A. F., 146.Vasilev, V. A., 32.Vasilieva, N. L., 535.Vasina, L. G., 386.Vaska, L., 243.Vaslow, F., 26, 36.Vassileva-Alexandrova, P.,Vasudeva Murthy, A. R.,Vatakencherry, P. A., 252,Vatsuro, K. V., 296.Vaughan, J., 38, 259, 287.Vaughn, J. W., 21.Vaver, V. A,, 333.Vdovenko, V. M., 138.Vdovin, V. M., 190.Vcber, D. F., 384.343.144.334.590.403.533.200.364.Vecera, M., 560.Veenland, J. V., 345.Vehli, Z., 179.Velarde, E., 420.Velichko, F.K., 378.Velluz, L., 427.Venanzi, L. M., 217, 237,Venezky, D. L., 209.Venkatachalapathy, M. S.,Venkataraghavan, R., 292.Venkataraman, K., 395,Venkataraman, R., 611.Venkatasetty, H. V., 21.Venkateswarlu, K., 144.Venkateswarlu, P., 168.Verbeke, G., 337.Vercellotti, J. R., 438,Verderame, F. D., 302.Verdier, P. H., 161, 162.Vereshchagin, L. I., 378.Verisor, V. Y., 541.Verkade, J. G., 215.Verma, B. C., 554.Verma, M. R., 534.Verma, S. P., 540.Vernon, J. M., 382.Vesely, K., 118.Vest, R. D., 397.Vestal, M., 153.Vestin, R., 267.Vetter, G., 562.Vetter, H.-J., 197, 199.Vetter, W., 412, 415, 450.Vianello, E., 60.Vickers, W. H. J., 80.Vickery, B., 79.Vickery, M. L., 393.Vidulich, G. A., 9.Viehe, H.G., 326, 330.Vieland, L., 189.Viet, A., 57.Vignau, M., 433.Vigurea, J. M., 332.Vilkas, E., 446.Vinard, D. R., 57.Vincent, J. F., 197.Vincent, L. St., 383.Vincent, W. A., 548.Vinciguerra, A., 228.Vining, L. C., 356.Vinnik, M. I., 15, 292.Vinograd, J., 514, 519.Vinogradova, E. I., 463.Vinogradova, Z. F., 132.Vintila, I., 533.Vischer, E., 356.Viswamitra, M. A., 592.Viswanathan, N., 368.Vitalina, M. D., 564.Vithayathil, P. J., 485.Vizgert, R. V., 293.Vlasov, A. V., 115.591.319.396.499.VlEek, A. A., 42, 222.Vodor, B., 127.Vopel, K., H., 350, 351.Vofsi, D., 94, 269.Vogel, A. I., 311.Vogel, E., 341, 361, 365.Vogel, M., 282.Vogel, W., 8.Vogelfanger, E., 250.Vogeller, K., 455.Vogg, H., 24.Vogl, J., 233.Vogler, A., 249.Vogler, K., 451, 460.Vogt, G., 24.Volavgek, B., 179, 180.Volger, K., 463.Vol’kenau, N.A., 353.Volkmann, D., 249.Volkov, J. I., 531.Volkova, A. S., 386.Vollbracht, L., 275, 556.Vollema, G., 326.Vollmar, P. M., 14, 144.Volman, D. H., 63, 72,Volod’ko, L. V., 138.von Daehne, W., 374.von der Decken, A., 525.von der Helm, D., 604.von Ehrenstein, G., 512,von Hobe, D., 84.von Koch, H., 156.von Saltza, M., 437.von Stackleberg, M., 54.Vorbriiggen, H., 308, 376,Voronkov, A. A., 582.Voronkov, M. G., 186.Voronkova, V. V., 545.Vos, A., 200, 574, 604.Vossos, P. H., 220.Vouler, K., 455.Vrancken, A., 111,Vranckin, A., 296.Vreeland, J. H., 38.Vreeland, R. V., 150.Vrieze, K., 216.Vrko?, J., 366.VrkEaj, V., 150, 180.Vullo, W..J., 257.Vulterin, J., 552.Vyas, V. A., 263.Vydra, F., 536.Vyelra, F., 535.Wache, H., 394.Wada, H., 536.Wada, K., 172, 367.Wada, Y., 135.Waddington, T. C., 22, 131,Waddington-Feather, S. M.,Wade, H. E., 516.82.524, 525.454.203.429INDEX O F AUTHORS’ NAMES 665Wade, N. G., 312.Wade, R. D., 513.Wadsley, A. D., 583.Wadsworth, M. E., 129.Waegell, B., 360.Wagner, C. D., 100.Wagner, C. R., 261.Wagner, G., 289.Wagner, H., 138.Wagner, R., 396.Wahba, A. J., 523,526,527.Wahid, A., 96.Wahl, A. C., 44, 46.Wahl, P., 103.Wahrhaftig, A. L., 153.Waiblinger, H., 264.Waight, E. S., 259.Waind, G. M., 10, 24.Wait, S. C., 120.Wait, S. C., jun., 163.Wakabayashi, T., 371, 414.Wakamatsu, H., 234.Wakamatsu, S., 324.Wake, R.G., 478.Wakefield, B. J., 316.Walasek, 0. F., 476.Walborg, E. F., 491.Walborsky, H. M., 274.Wald, G., 89, 332.Waldron, J. D., 299.Wale, P. D., 292.Walisch, W. W., 559.Walker, A., 181.Walker, D. C., 66, 100.Walker, J., 482, 612.Walker, L. E., 322.Walker, S., 120.Walkinson, J. G., 292.Wall, A. A., 265.Wall, H. M., 436.Wall, M. E., 422.Wallace, J. M., 517.Wallace, R. A., 290.Wallace, R. J., 320.Wallace, T. J., 265, 317.Wallbridge, M. G. H., 132,Wallenfels, K., 342, 434.Wallenstein, M. B., 153.Waller, J.-P. 518.Walling, C., 101, 269, 271,Wallis, S. R., 284.Wallmann, J. C., 205, 571.Walmsley, D. A. G., 91, 92.Walrafen, G. E., 13, 15, 16,137, 144, 189.Walsh, R,.A., 337, 469.Walsh, T. D., 255.Walters, D. R., 437.Walton, R. A., 206.Walz, H., 210.Wampler, D. L., 233, 586.Wanders, A. C. M., 285.Wang, C.-C., 461.Wang, C.-H., 345.183, 189.331.Wang, I. C., 294.Wang, S. S., 257.Wang, T.-Y., 514, 518.Wang, Y., 461.Wanger, C. R., 251.Wan Kai-Yan, 279.Wankat, C., 540.Wannagat, U., 188, 191,Warburton, D., 31 1.Ward, C. H., 134, 142.Ward, D. N., 491.Ward, H. R., 296, 320,Ward, R., 205, 578.Wardlaw, A. C., 461, 469.Ware, J. C., 275.Ware, M. J., 139.Wariger, N. S., 77.Waring, A. J., 296.Wark, K., jun., 146.Warner, J. R., 519, 520,Warnhof, E. W., 418.Warnhoff, E. W., 319.Warren, C. D., 438.Warren, C. K., 331.Warren, K. D., 280.Warren, K.S., 259.Warren, L. F., 400.Warren, R. A. J., 462.Warren Smith, H., 598.Warshawsky, A., 548.Wartik, T., 188.Waser, J., 607.Wasielewski, C., 456.Wasiellewski, C., 452.Wasserman, E., 293.Wasserman, H. H., 272,Wassermann, L., 549.Watanabe, A., 599.Watanabe, H., 312.Watanabe, T., 607.Waterlow, J. C., 539.Waters, D. N., 16, 130.Waters, J. A., 275.Waters, J. H., 179, 261.Waters, J. M., 590.Waters, T. N., 591.Waters, W. A. 348.Watkins, K. O., 224.Watkins, W. M., 438.Watson, A. A., 555.Watson, D., 312, 435.Watson, D. H. R., 426.Watson, I. D., 35.Watson, J. D., 512, 513,Watson, P., 30.Watson, W., 292.Watson, W. H., 607.Watt, G. W., 213, 215.Watterson, K., 185.Watthey, J. W. H., 361.Watts, B. M., 547.207.329.524.465.519.Watts, M.L., 325.Watts-Tobin, R. J., 521.Wawzonek, S., 77.Wayne, J. P., 69.Wayne, R. P., 106.Weakley, F. B., 552.Weakley, T. J. R., 113.Weakliem, H. A., 571.Weale, K. E., 106.Wear, J. D., 48.Weatherly, T. L., 170,Weaver, S. D., 381.Webb, M. W., 584.Webb, R. L., 99.Webber, J. M., 434, 435,Weber, A., 121, 306.Weber, C. W., 550.Weber, G. G., 168.Weber, H. P., 368.Webster, D. E., 131, 134,Webster, D. W., 194.Webster, G. C., 516.Webster, M., 134, 136, 192,Webster, M. S., 611.Webster, 0. W., 380.Wechter, W. J., 314, 433.Weeden, D. G., 223.Weedon, B. C. L., 331.Weeks, J. L., 179.Weeks, W. T., 142.Wegner, E., 261, 342.Wehrli, H., 422, 423.Wehrli, W., 433.Wei, C.-H., 234, 239.Weidlein, J., 136, 199.Weigel, F., 204, 434, 438.Weil, L., 478.Weill, C.E., 434.Weilmuenster, E. A., 183.Weinberg, K., 422.Weinberg, N. L., 342.Weiner, D., 148.Weiner, H., 255.Weinstock, B., 214.Weinstock, M., 259.Weir, C. E., 129.Weir, D. S., 70, 74.Weisberger, A. S., 524.Weisblum, B., 525, 527.Weisbuch, F., 316.Wei-Shin Chou, 291.Weiss, A., 187, 575, 584.Weiss, B. H., 74.Weiss, C., 277.Weiss, C. D., 336, 389.Weiss, E., 181, 237, 434.Weiss, E. K., 432.Weiss, H. G., 190.Weiss, R., 584.Weiss, U., 355.Weiss-Berg, E., 433.Weissermel, K., 331.172.437, 500.194.194, 198, 610666 INDEX OF AUTHORS’ NAMESWeissman, S. I., 48, 297.Weissmann, C., 407.Weitkamp, L. R., 481.Welch, C. A., 326.Welch, D. E., 181.Welch, F.J., 108, 110.Welcman, N., 202.Welge, K. H., 80.Weller, A., 53, 63.Wellman, K., 415.Wellman, K. M., 265, 288.Wells, C. H. J., 89.Wells, E. J., 163, 296.Wells, M., 474, 578.Wells, M. J., 121.Wells, P. R., 293, 297.Wells, R. D., 482.Wells, R. J., 392.Wells, W. W., 343.Welsh, H. L., 121,122, 128,Welsh, P. N., 154.Wender, I., 339.Wendlandt, H. G., 199.Wendlandt, W. W., 204,215, 220, 223.Wendt, G. R., 426.Wendt, H., 24, 229.Wenger, F., 114.Wenkert, E., 327, 399.Wenschuh, E., 213.Wentorf, R. H., jun., 571.Wentworth, G., 275.Wentworth, R. A. D., 209.Wenz, D. A., 295.Werblan, L., 20.Werner, D., 195.Werner, H., 236.Werner, R., 440.Wertheim, G. K., 214,Wescott, L. D., 337.Weser, U., 202.Wessely, F., 318.West, B.G., 163.West, B. O., 199, 202.West, P. W., 531.West, R., 130, 227, 295.West, R. W., 181.West, T. S., 534, 536.Westbrook, J. J., tert., 542.Westerdahl, A., 596.Westheimer, F. H., 57, 275,Westmark, G. W., 502.Westoo, G., 565.Weston, B. A., 30.Weston, R. E., 14.Weston, R. E., jun., 144.Westphal, O., 437, 495.Westwood, J. H., 435, 437.Westwood, J. V., 529.Wetter, G., 198.Wettstein, A., 424, 425.Wettstein, F. O., 519, 521,300.233.287, 293.522.Wettstein, W., 428.Wetzel, W. H., 275.Wexler, S., 156.Weyell, D. J., 323.Weygand, F., 451,453,454,Whaite, T. J., 292.Whalley, E., 257, 288.Whalley, W. B., 396.Wharmby, D. H. W., 203.Wharry, D. M., 330.Wharton, L., 165.Wharton, P. S., 429.Whatley, L., 295.Wheat, R.W., 446.Wheatley, P. J., 191, 574,Wheeler, T. S., 394.Whelan, W. J., 438, 441,Wherrett, J. R., 493.Whipple, E. B., 310, 381.Whistler, R. L., 436, 437,White, A. M., 523.White, D., 126, 154.White, D. C., 560.White, D. E., 372, 373.White, D. G., 181.White, E. A. D., 579.White, E. H., 254.White, F. H., 469, 480.White, J. A., 203.White, J. G., 575, 581.White, R. F. M., 165, 197.White, R. M., 156.White, T. G., 496.Whitehead, G., 37.Whitehead, P. H., 488.Whitehead, T. H., 533.Whitehurst, J. S., 426, 428.Whiter, P. T., 329.Whitesides, G. M., 303.Whitham, G. H., 420.Whiting, M. C., 328.Whitney, E. D., 217.Whitney, F. D., 183.Whitney, G. C., 254.Whitney, J. C., 449.Whittaker, D., 188, 257.Whittaker, N., 403.Whittemore, I.M., 74.Whittle, E., 73.Wiberg, E., 190, 196.Wiberg, K. B., 172, 249,259, 306, 358, 363.Wiberg, N., 191.Wiberley, S. E., 186.Wicken, A. J., 447.Wickens, J. C., 333.Wickham, P. P., 316.Widmer, H., 150.Widnell, C. C., 510.Wieber, M., 191.Wiechers, A., 400.Wiedemann, W., 361.455, 456.575.442.440, 443.Wieder, G. M., 145.Wiegandt, H., 491.Wiegers, G. A., 574.Wieland, P., 424, 428.Wieland, T., 289, 407, 452,Wielopolski, A., 563.Wiemanxi, J., 316.Wierzchowski, K. L., 393.Wiesboeck, R. A., 183.Wiessbach, J. A., 410.Wiggins, T. A., 122, 127.Wightman, R. H., 401.Wigley, P. R. F., 177.Wigley, P. W. R., 214.Wijnen, M. J. H., 71, 77,Wilborn, W., 192.Wild, A,, 556.Wild, J., 557.Wilde, R.E., 123.Wildman, W. C., 365, 400.Wilen, S. H., 277.Wiles, D. M., 113, 114.Wiles, L. A., 201.Wiley, R. H., 100: 378.Wilhelm, I., 202.Wilhelmi, K.-A., 580.Wilkins, C. J., 198.Wilkins, M. F., 525.Wilkins, R. G., 229, 230.Wilkinson, D. I., 375, 432.Wilkinson, F., 62, 74, 89.Wilkinson, G., 213, 216,220, 233, 237, 238, 241,243.455, 462.78.Wilkinson, G. R., 133.Wilkinson, S. M., 179.Will, G., 604.Willett, J. D., 384.Willett, J. E., 454.Willett, R. D., 220, 593.Willi, A. V., 12, 276.Williams, A., 84.Williams, A. E., 155, 311.Williams, A. H., 500.Williams, D., 128, 129, 133,Williams, D. G., 603.Williams, D. H., 159, 321,Williams, D. L., 302.Williams, D. L. H., 266.Williams, F., 351.Williams, G.A., 509.Williams, G. H., 78, 345.Williams, L. L., 46.Williams, M. W., 454, 456.Williams, N. J., 448.Williams, N. R., 436.Williams, Q., 170, 172.Williams, R., 355.Williams, R. E., 184, 369.Williams, R. G., 212.Williams, R. J. P., 113.Williams, R. O., 266, 364.145.415, 429INDEX O F AUTHORS’ NAMES 667Williams, R. W. J., 421.Williams, T., 11.Williams, T. F., 100.Williams, T. H., 360.Williams, T. P., 435.Williams, W. D., 66, 367.Williams-Ashman, H. G.,Williamson, A. R., 446,498.Williamson, D. G., 299.Williamson, M. J., 277.Williamson, S. M., 180,573.Willis, B. T. M., 576.Willis, J. E., 226.Willix, R. L. S., 44.Wilmenius, P., 157.Wilmshirst, J. K., 128.Wilski, H., 29.Wilson, A. D., 535, 564.Wilson, A. N., 384.Wilson, C. O., 154.Wilson, C. S., 414.Wilson, C. W., 108.Wilson, D. A., 272.Wilson, D. J., 65, 82.Wilson, D. W., 529.Wilson, E. B., 171, 299.Wilson, E. B., jun., 160,162,164, 167, 169, 170, 172,174, 175.Wilson, E. G., 179.Wilson, H. R., 606.Wilson, I. R., 292.Wilson, J. G., 471.Wilson, J. M., 159, 401,404, 408, 409, 410, 415.Wilson, J. W., jun., 329.Wilson, M. K., 134.Wilson, R., 280, 345, 348.Wilson, R. K., 394.Wilson, S., 461, 469.Wilson, W. E., 139.Wilt, J. R., 139.Wimette, H. J., 295.Windholz, T. B., 384, 389,Windrath, 0. M., 396.Winefordner, J. D., 541.Wingrove, A. S., 274.Winkaus, G., 237.Winkler, A., 199.Winnewisser, M., 165, 168,170, 306.Winstein, S., 119, 247, 250,251, 252, 253, 262, 285,318, 345, 350, 361, 363,364.504, 511, 526.426.Winter, C. A., 384.Winter, G., 208.Winter, M., 563.Winter, R., 252, 364.Winter, R. A. E., 320.Wintersteiner, O., 437.Wirth, H. E., 19, 37, 295.Wirth, W.-D., 362.Wise, E. N., 541.Wiskott, E., 337.Wiswall, R. H., jun., 179.Wiswell, J. G., 505.Witanowski, M., 305.Witekowa, S., 47.Withey, R. J., 257, 288.Witkop, B., 311, 346, 449,Witt, H. S., 95.Witt, N. F., 550.Witte, K., 315.Wittig, G., 320, 322, 360.Wittmann, J. W., 318.Wittstruck, T. A., 416.Witz, J., 518.Witz, P., 375, 415.Witzel, B. E., 384.Witzel, H., 473.Woidt, J., 204.Wojciechowski, W., 222.Wojicki, A., 233.Wojtczak, L., 508.Wold, J. K., 445, 446.Wolf, A. P., 80, 285.Wolf, H., 415.Wolf, K. H., 394.Wolfe, S., 388, 524.Wolff, E. C., 501, 504,Wolff, I. A., 332, 333, 337.Wolff, J., 501, 504, 509.Wolff, M. E., 429.Wolford, R. K., 289.Wolfrom, M. L., 396, 436,437, 438, 499, 549.Wolfstirn, K. B., 101.Wolman, Y., 461, 472.Wolosowicz, N., 552.Wolpers, J., 341.Wolsey, W. C., 216.Wong, W.-K., 208.Wood, C. S., 68.Wood, D. L., 146, 225.Wood, J. L., 121, 128, 134,Wood, J. S., 241, 586.Wood, R. H., 35.Wood, T. M., 443.Woodbury, E. J., 148.Woodbury, W. J., 147.Woodhead, J. L., 214.Woodhouse, E. J., 203.Woods, M. J. M., 10.Woods, W. G., 185.Woodward, L. A., 15, 16,131, 133, 134, 136, 137,139, 143.Woodward, R. B., 271, 366,367, 392.Woody, C. D., 364.Wooldridge, K. R. H.,Woolley, J. M., 487.Woolven, M. J., 392.Worden, L. H., 316.Worrall, J., 114.471.505.299, 300.387.Worrall, R., 98.Worrell, L. F., 551.Worsfold, D. J., 108, 109,Wright, A., 440.Wright, G. F., 307.Wright, H. E., 137.Wronski, M., 543, 555.Wu, E., 142.Wunsch, E., 448, 452.Wursch, J., 396.Wunderlich, J. A., 400.Wylde, J., 71.Wyler, H., 385.Wylie, A., 370.Wylie, A. G., 346.Wyman, J., 470, 474, 475.Wynberg, H., 285.Wynne-Jones, W. F. K., 17,Wysocki, A. J., 257.Yager, B. J., 292.Yager, W. A., 293, 359.Yagil, G., 49.Yagil, S., 13.Yagodovskii, V. D., 124.Yagu, W. A., 348.Yajima, H., 459, 482.Yajima, T., 162.Yakel, H. L., 578.Yakhontov, L. N., 378.Yakovlev, P. Ya., 540.Yakovleva, M. K., 98.Yamada, M., 349.Yamada, S., 411.Yamaguchi, I., 309.Yamaguchi, K., 67.Yamaguchi, L., 309.Yamaguchi, S., 406.Yamaguchi, T., 317.Yamakawa, T., 493.Yamanota, R. T., 358.Yamamoto, O., 132.Yamamoto, Y., 372.Yamamura, S., 369.Yamasaki, K., 228.Yamashina, I., 486, 487,Yamashita, S., 68, 75.Yamasita, K., 540.Yamazaki, H., 81.Yamazaki, M., 166.Yampol’skaya, M. A., 184.Yanaihara, N., 459, 461,Yang, D. H., 69.Yang, H., 319.Yang, N. C., 69, 71, 321,357, 358.Yang, T., 319.Yang, T. H., 405.Yang, W. Y., 215.Yankofsky, C., 517.110, 115.WU, C.-H., 36.WU, Y.-C., 487.28, 29.488.472668 INDEX OF AUTHORS’ NAMESYankwich, P. E., 73.Yannoni, N. F., 601.Yaoi, Y., 476.Yaphe, W., 434.Yarovenko, A. N., 542.Yarwood, A. J., 73, 77.Yasonobu, K. T., 470, 476.Yates, B. L., 292.Yates, D. J. C., 124.Yates, P., 366, 367, 395.Yatsimirsky, K. B., 539.Yatsimirsky, V. R., 539.Yatsun, G. I., 209.Yeager, E., 50.Yeh, C. S., 558.Yellin, W., 16.Yemer, G., 177.Yeou, T., 161.Yevdokimov, V. F., 100.Yiannios, C. N., 336.Yip, R. W., 79, 362.Yoe, Y. H., 535.Yokley, 0. E., 262.Yokoi, M., 22.Yokoyama, N., 403.Yokoyama, S., 493.Yoncoskie, B., 114.Yonemitsu, O., 359.Yonezawa, K., 375.Yoshiaki Furuya, 292.Yoshida, H., 535.Yoshii, E., 367.Yoshikawa, K., 565.Yoshio Iwakura, 292.Yoshiro Ogala, 292.Yoshizaki, T., 564.Young, A. R., 132.Young, A. R., jun., 187.Young, D. A., 190.Young, D. W., 414, 598.Young, G. T., 448, 454,Young, J., 468.Young, J. D., 481.Young, M., 296, 472.Young, R., 444.Young, R. J., 512.Young, T. F., 15, 16, 33.Young, W. G., 250.Youngman, E. A., 95.Youssefyeh, R. D., 325.Yu-Cang, D., 469.Yuki, H., 434.Yuk-Yung Hung, 386.Yulikova, E. K., 296.Yun-Teh Shen, 290.Yu-Shang, Z., 469.Yushkevish, V. F., 37.456.Young, w. L., 349.Zabel, R., 460, 461.Zabrodina, K. S., 546.Zachariasen, W. H., 568,Zachau, H. G., 512.Zachrisson, M., 136.Zado, F., 211.Zagal’skaya, Yu. G., 582.Zagorets, P. A., 10.Zagoreviskii, V. A., 395.Zahler, P., 490.Zahler, W. D., 277.Zahn, E., 234.Zahn, H., 449, 454, 460,Zahradnik, R., 277.Zaidi, S. S. H., 435, 545.Zaitev, P. M., 56.Zaitzeva, Z. V., 56.Zakharkin, L. I., 183, 184,188, 317, 324.Zalkin, A., 179, 180, 568,571, 573, 579, 584.Zalkow, L. H., 367.Zalkow, V. B., 367.Zamecnick, P. C., 512, 513,Zamenhof, S., 446, 498.Zamojski, A., 386.Zand, R., 290.Zandstra, P. V., 297.Zanetti, G., 437.Zankowska- Jasinka, W.,Zaoral, M., 455, 459.Zarakhani, N. G., 15.Zarinsky, V. A., 564.Zaslowsky, J. A., 290.Zaugg, H. E., 260, 292.ZBvada, J., 263, 266.Zavarikhina, G. B., 535.Zbiral, E., 318.Zderic, J. A., 429.Zeeh, B., 419.Zeidler, M. D., 18.Zeigel, R. F., 514.Zeiger, H. J., 148.Zeil, W., 132, 133, 134, 139,Zelewsky, A. V., 220.Zel’manova, I. Ya., 542.Zemann, A., 580.Zemann, J., 580.ZemljiE, R., 179.ZemlkiE, Z., 180.Zencker, N., 501.Zengin, N., 138.Zerbi, G., 141.Zerbo, G., 556.Zerner, B., 289, 290.Zervas, L., 453, 454.Zhantalai, B. P., 540.Zharkov, V. V., 557.Zharovskii, F. G., 532.580, 581.461.523.450.168.Ziegler, G. R., 326.Zielen, A. J., 28.Zierler, K. L., 505.Ziffer, H., 76.Zijderveld, G. R. D., 162.Zilka, A., 114.Zillig, W., 515.Zilliken, F., 437.Zimm, B. H., 297.Zimmer-Galler, R., 382.Zimmerman, E. F., 520.Zimmerman, H., 595.Zimmerman, H. E., 66,293,Zimmerman, J. E., 452,Zimmermann, F., 358.Zirnmermann, H., 384.Zimmermann, I., 295.Zimmermann, I. C., 569.Zingaro, R. A., 198.Zi-Nian, L., 469.Zinke, H., 334.Zinkel, D. F., 544.Zinn, J., 173.Zinn, M. F., 268.Zinnes, H., 408.Zinov’ev, A. A., 36.Ziolkowski, J., 236.Zioudrou, C., 293.Zirin, M. H., 179.Zirner, J., 285, 361.Zito, R., 470.Zittel, H. E., 538.Zlamal, Z., 119.Zlobowska, Z., 540.Zlotchenko, S. I., 554.Zobel, H., 337.Zollinger, H., 48.Zolotov, Iu. A., 535.Zoretic, P. A., 259.Zotchik, N. V., 335.Zozulya, A. P., 546.Zubay, G., 515.Zuber, H., 452.Zubov, V. A., 145, 147.Zubov, V. P., 92.Ziircher, R. F., 416.Zulaica, J., 556.Zulalian, J., 399.Zuliani, G., 169.Zumach, G., 454.Zuman, P., 50, 55.Zussman, J., 580.Zutty, N. L., 103.Zwanenberg, B., 267.Zweifel, G., 267, 315.Zwick, A., 452.Zwicker. E. F., 79.Zwolenik, J. J., 67, 79,Zyka, J., 541, 555.343.455.187

ISSN:0365-6217    

DOI:10.1039/AR9636000617

出版商:RSC    

年代:1963

数据来源: RSC

摘要:

INDEX O F SUBJECTScis-Acenaphthene- 1, 2-diol, planarity of,Acenaphthylene, addition of deuteriumAcetaldehyde, photolysis, 72.Acetone, photolysis, 71.Acetonitrile, microwave spectrum of, 303.Acetylcholine bromide, two molecularAcetylenes, preparation of, 326.Acidity function, 48.Acids, amino-, 448.601.bromide to, 265.forms of, 598.metal complex, 238, 588.amino-, analysis of, 551.amino-, asymmetric synthesis of, 450.amino-, polynucleotide code for, 526.u-amino-jl-hydroxy-, stereospecific syn-N-methylamino-, optically pure, syn-aromatic carboxylic, halogenation of,carboxylic, analysis of, 542.carboxylic, structure of, 595.fatty, and related compounds, 332.long-chain, bent-form structure of, 596.thesis of, 451.thesis, 451.344.synthesis of, 333.Acrylic acid, structure of, 596.Actinides, 205.Acyclic compounds, structure of, 597.Adamantane, structure of, 570.Adenosine-5' phosphate, structure of, 608.Akuammidine methiodide, structure of,y-Akuammigine, structure of, 409.Alcohols, determination of, 548.Aldehydes, analysis of, 546.609.long-chain, polymorphism of, 599.reaction of, Buchner-Curtius-Schlotter-reactions of, 286.beck, 325.Aldosterone, total synthesis of, 428.Alginic acid, hydrolysis of, 445.Alicyclic compounds, 357.Aliphatic compounds, 300, 326.Alkali borohydrides, uses of, 31 4.Alkaloids, aporphine, spectra of, 404.biogenesis of, 399.indole, 407.lupin, 401.lycopodium, 413.morphine, 406.pyridine group, 400.pyrrole group, 400.quinoline and isoquinoline group, 401.Senecio, structure of, 400.Solanum, 430.steroid, 41 2.structure of, 608.6terpene, 413.Alkanes, photolysis, 66.Alkenes, analysis of, 556.Alkoxyiminium salts, preparation of, 336.Alkoxyl compounds, determination of,Alkyl halides, dipole-moment measure-545.ments of, 302.photolysis of, 77.nitrites, dipole moments of, 304.Alkylation, 323.Alkylidenecarbenes, preparation of, 337.Alkynes, analysis of, 557.Allenecarboxylates, preparation of, 329.Allenes, synthesis of, 329.Ally1 alcohol, reactions of, 322.iodide, addition of hypochlorous acid to,Allylamine, complexes with platinum, 236.Allyldiazomethane, photolysis of, 358.Aluminium alkoxides, structure of, 188.hydride, reactions of, 187.hydride-trimethylamine adducts,niobium oxide, structure of, 579.266.spectra of, 132.Ambident nucleophiles, 260.Americium, crystallographic structure of,571.sexivalent, preparation of, 206.Amides, aliphatic, spectra of, 304.co-ordination with transition metals,226.Amidomycin, structure of, 463.Amine N-oxides, 227.Amines, analysis of, 550.photolysis of, 77.2-Amino-3-methylbenzoic acid, structure5-Amino-l,2,4-selenadiazoles, preparationAmmonium carbonylferrates, prepara-hydrogen dicinnamate, short hydrogentetrasulphimide, formation of, 200.of, 597.of, 388.tion of, 234.bonds in, 597.Amorphin, hydrolysis of, 395.Amosamine, synthesis of, 437.Amylose, configuration of, 440.Analysis, inorganic qualitative, 531.inorganic quantitative, 534.organic elemental, 557.through functional groups, 542.Androsta- 1,4-diene-3,17-dione, rearrangement to the phenol, 417.5a-Androstan- 1 1 -one, circular dichroismof, 415.Angiotensin, analogues of, 482.Anionic polymerisation, 108.1conformation of, 482670 INDEX OF SUBJECTSAnions, analysis of, 539.Annulenes, syntheses of, 352.Anthraquinones, structure of, 602.Antibodies, anti-hapten, chemical modi-fications of, 481.preparation of, 480.antigens, peptide, 480.Antimony, compounds of, 199.trifluoride dichloride, structure of, 199.Trisilylstibine, preparation of, 199,Arabinogalactans of the larch, 443.Arene n-complexes, preparation of, 353.Argemonine , ident Scat ion with N -me t h yl-Aristolactone, structure of, 367.Aromatic compounds, 339.pavine, 402.LCAO-MO calculations in, 343.hydroxylation, mechanism of, 344.isomerisations, 285.molecules, planarity of, 599.substitution, electrophilic, 275.nucleophilic, 277.phenoniurn-ion participation in, 345.Arsenic, compounds of, 198.acid, reactions of, 199.oxides, 199.Aspidospermine, total synthesis of, 410.(-J-)-Atisine, total synthesis of, 371, 413.Aureomycin, stereochemistry of, 61 1.Azines, 393.Aziridine, derivatives of, 378.Azo -alkanes, pho t ol y sis , 7 4.Azobenzene, czs-tram interconversion, 75.Azo-functional group, in analysis, 553.Azoles, synthesis of, 386.Azulene- 1-acetic acid, synthesis of, andAzulenes, synthesis of, 350.Azulenium fluoroborate, preparation of,Bacteria, cell-wall and capsular poly-Barium manganate, perovskite structureBenzene, electrochemical reduction of,related compounds, 351.351.saccharides of, 495.of, 578.339.rr-electron distribution in, 339.kinetics of mercuration, 275.reaction with diazomethane, 341.Benzenediazonium chloride, packing ofions in, 600.ions, 280.tions of, 346.Benzenediazonium-2-carboxylate, reac-Benzhydryl thiocyanates, substituted,Benzidine rearrangement, 282.Benzimidazoles, synthesis of, 387.Benzo[c]cinnoline, preparation of, 393.1,2-Benzocyclen-4-y1 toluene-p-sulphon-ates, aryl participation in solvolysisof, 250.p-Benzoquinone, Diels-Alder reaction ofderivatives, 272.infrared study of, 309.reactions of, 256.Benzylacetone, p.m.r.spectrum, 302.3-O-Benzyl- 1,2-O-isopropylidene-5-0~0-a-D-xylofuranose, conversion of, 333.Benzyne intermediates, generation of, 346.p-Bergamotene, preparation of, 365.Beryllium, reaction of, 181.Betanidin, correct structure of, 385.Biacetyl, photolysis, 74.Biaryls, improved preparation of, 345.Bicyclo[ 1,l ,O]butane, preparation of, 358.Bic yclo[ 2,2,0] hexa- 2,5 -diene, preparationof, 339.Bicyclo[3,1 ,O]hexylamine, deamination of,253.trans- Bic yclo[ 4,2,0]oc tane system, pre-paration of, 362.Bicycle[ 2,2,2]octatriene, derivatives of,237.endo- and ex0 -Bic yclo[ 2,2,2]oc t - 5-en-2 - yltoluene-p-sulphonates, acetolysis of,249.transient spectrum of, 280.spectra of compounds of, 130.Biflorin, elucidation of structure, 356.Biphenyl, Raman spectra of, 144.Biphenyl-2-carboxylic acids, formation of,2,2’ -Bip yrid yl, 228.planarity of, 311.reaction with methylene iodide, 387.Bisbenzenechromium, structnre of, 241.Bisbiuretzinc chloride, structure of, 593.178-Bisdehydro[ 14Jannulene, structure of,352.2,2 -Bis- ( 3,5-di- t -but yl-4- hydrox yphenyl) -propane, biradical interaction of, 347.Bis( methylthio jdiazomethane, thermal de-composition of, 337.Bismuth monochloride, structure of, 199.9,9’-Bixanthenylidene, structure of, 607.Bonding, in sulphur-containing anions,Boranes, reactions of, 183.Borates, complex, structure of, 581.Boron, preparation of, 181.347.579./3-rhombohedra1 form of, 571.hydrides, 182.mass spectrometric study of com-perchlorates, preparation of, 186.sub-halides, 186.trifluoride complexes, spectra of, 131.Boron-nitrogen ring compounds, 185.Bradykinin, mechanism of action of,pounds of, 154.483.synthesis of, 460.synthetic analogues of, 484.Brassicasterol, configuration of 24-methylBromination, mechanisms of, 276.Bromine hydrate, 203.m-Bromonitrobenzene, planarity of, 599.Bromo-mstrone, structure of, 610.N-p-Bromophenylsydnone, planarity of,N-Bromosuccinimide, reactions of, 330.group, 433.604INDEX O F SUBJECTS 67 1t-Butylazetidine, open-chain structure of,j3-t-Butyl benzyloxycarbonylaspartate,t-Butyl hypobromite, reaction witht-Butyloxycarbonylazide, preparation of,Butyric acid, structure of, 595.Cadmium, ionic, hydrolysis of, 221.Calciferol, stereochemistry of, 61 0.(+)-Camphenilone, racemisation in, 364.Canarigenin, structure of, 432.Carapanubine, structure of, 408.Carbanions, a-sulphonyl, internal rotationCarbenes, reactions of, 337.Carbohydrates, 434.amino -derivat ives of, 43 6.analysis of, 549.degradation of, 435.deoxy-derivatives of, 436.phosphate derivatives of, 437.sequence determination in, 488.staphylococcal, 496.thio-derivatives of, 437.proton transfers to, 56.398.preparation of, 452.olefins, 321.452.in, 598.Carbon, organic elemental analysis of, 557.Carbonium ions, from deamination andrearrangements in bridged bicyclicrelated reactions, 252.systems, 247.Carbonyl compounds, photolysis of, 69.preparation of, 321.cyanides, of molybdenum, 233.Carbonyls, infrared spectra of, 232.initiators in polymerisation, 92.titrations, 538.metal, structure of, 586.molecular orbital energy level schemereactions with donor molecules, 234.for, 232.Carborane series, 183.Carboxylic acids, preparation of, 323.reactions of derivatives, 289.j3-Carotene, oxidation of, 332.Carotenoids, 331.Carrageenan, structure of, 445.( - )-Carvomenthone, total synthesis of,( f )-Caryophyllene, synthesis of, 369.X-Casein, fragmentation of, 490.Catalysis, by peptides, 465.Cationic polymerisation, 11 6.Cations, detection of, 533.Cedrelone, structure of, 609.Cellulose, 440.Cerium, election transfer in, 47.Ceruloplasmin, carbohydrate compositionD-Chalcose, synthesis of, 437.Chemisorption, spectroscopic study of,Chimonanthine, synthesis of, 41 1.o-Chlorobenzene, spectra of, 309.369.of, 491.123.a-Chlorodibenzyl ketone, methanolysis of,1 -Chloro- 2,3 - dimethylc yclopropane, n.m.r .l-Chloro-2,4-dinitrobenzene, reduction byChloroperfluoromethylarsines, reactions4-Chloroquinoline, rate of reaction withCholestanones, bromination of, 418.Cholest - 4- en- 3 -one oxides, reactions of,Chondroitin sulphate, serine content of,Chorismic acid, isolation of, 355.Chromium, complexes of, 210.fluoride, preparation of, 21 1.oxidation states of, 211.Cycloheptatrienylchromium(I), prepara-Hexacarbonylbiphenyldichromium,Hexachlorochromates(In), alkali-metal,Pentamminenitrosylchrornium(I) chlor-Chymotrypsin, mechanism of its action,O-Cinnamoyltaxicin-I, constitution of, 372.Claisen rearrangement, 283.Clathrate hydrates, new type of, 576.Clemmensen reductions, 315.Cobalt ammine complexes, thermal de-composition of, 215.complexes, structure of, 590.electron transfer in, 41.Cobalt(I1) acetylacetonate, reaction withCobalt(I1) halides, spectra of, 215.Acylcobalt tetracarbonyl, dissociationof, 234.Bis( trimethylphosphine oxide)cobalt(II)nitrate, 222.trans-Dimesitylbist diethylphenylphos-phine)cobalt( II), crystal structure of,215.Hexa-amminecobalt( 111) ion, co-ordina-tion sphere of, 216.Halogenopenta-amminecobalt (111) , 230.Triethylenetetraminecobalt, instabilityof trana-isomer, 216.Colchicine, synthesis of the skeleton, 414.Colorimetric analysis of metals, 534.Complex formation, charge-transfer, 295.Complexes, acetylene, 238.258.spectrum, 306.sodium borohydride, 315.of, 198.piperidine, 279.419.490.tion of, 241.tram-form of, 586.isolation of, 210.ide, preparation of, 236.290.pyridine, 2 15.co-ordination, structure of, 589.crystallographic forms of, 575.hydrolysis of, 231.inner and outer sphere, 10.inorganic, mechanisms of reaction, 229.olefin, 236.peroxy-, of transition-metals, 226.wallylic, 238.n-bonding in, 223.review of, 222672 INDEX O F SUBJECTSComplexes, spectroscopic study of, 139.with aromatic systems, 239.square planar, M.O.treatment for, 223.study. of by temperature-jump tech-Complexometric analysis, 531.Conductivity, in electrolyte solutions, 18.Conductometric method, Murr and Shin-ers, for measuring first-order rateconstants, 256.nique, 229.Conessine, total synthesis of, 412, 429.Copaene, structure of, 369.Copper complexes, structure of, 576.co-ordination in, 591.halides, complexes of, 220.Arylcarboxylat ocopper( 11) , magneticCopper(1) iodide, addition of acetyl-properties of, 220.acetone to, 220.Corymine, structure of, 409.Coumarone, preparation of, 386.Croconate ion, structure of, 603.Crotonosine, structure of, 405.Crystallographic disorder, 568.Crystallography of small molecules, 571.Cularine, total synthesis of, 405.Cyanides, complex transition-metal, 226.Cyanogen, structure of, 572.Cycloartane, total synthesis of, 376.Cyclobutane, non-planarity of, 306.Cyclobutanes, new route to simple andCyclobuxine, structure of, 412.cis- and trans-Cyclodecene, addition ofCycloheptatriene, i.r.spectrum of, 308.Cycloheptatrienide anion, preparation of,dyclo(hexaglycyl), structure of, 608.Cyclohexane- 1,2-dione, enolisation of di-Cyclohexanes, conformations of, 359.Cyclohexanol, equatorial and axial con-Cyclonona- 1,2-diene, hydroboronation of,Cyclononatetraenide anion, spectrum of,Cyclonona-cis-1, cis-4, cis-7-triene, spec-Cyclo-octane ring, stretched crown con-Cyclopentadiene, bonding to metals of,Cyclopentadienide anion, 349, 359.d2yclopentadienyl- wcycloalkadienyl-metal complexes, 239.Cyclopentane, spectrum of, 306.Cyclopenta[c]pyran, preparation of, 395.Cyclopropane, synthesis of derivatives of,2-Cyclopropyl[ 1 -14C]ethylamine, deamin-Cystine, degradation of, 449.structure of, 572.fused, 358.bromine to, 266.350.trapping of, 361.keto-form, 287.formers of, 307.315.350, 363.trum of, 362.formation for, 308.587.357.ation of, 253.Cytochrome c, amino-acid sequence of,Cytochrome c-551, degradation of, 478.Dealkylation of alkylated aromatic hydro-Deamination reactions, carbonium ionsDecafluorocyclohexene, reduction of, 314.Decalin, cis- and trans-, mass spectra of,7-Dehydrocholesterol, reaction withDehydronorcamphor, photolytic retro-3,4-Dehydroproline, reactions of, 450.Demissidine, synthesis of, 412, 430.Depsipeptides, cyclic, synthesis of, 463.Desmotroposantonins, configurations of,Desosamine , D -zyZo-configuration of, 436.Deuteroammonia, neutron diffraction of,572.erythro- and threo-3-Deuterobut-2-yl tolu-ene-p-sulphonate, cis and trans elim-inations in, 262.7-Deuterocyclohepta-lY3,5-triene, intra-molecular 1 &hydrogen transfer in,361.476.carbons, 344.from, 252.306.diborane, 420.diene fission of, 359.366.\Dialkylaminoborines, preparation of, 184.Dialkylboron carboxylates, preparation of,184.Diarsine complexes, crystal structure of,218.1 6-Diazodehydroepiandrosterone, stereo-chemistry a t (2-16, 423.Diazofluorene, reactions of, 348.Diazomethane, mass spectum of, 305.1,2 : 5,6-Dibenzo-octatetraene, prepara-Dibenzopentalene, preparation of theDiboric acids, preparation of, 184.Dibromoalkanes, debromination of, 264.Dicarbonyl-n-cyclopentadienylcobalt, re-action with cyclo-octatrienes, 241.2,5-Dichloroaniline, planarity of, 599.p-Dichlorobenzene, structure of, 599.1,2-Dichlorornethylenedioxybenzene,structure of, 170.tion of, 341.dianion, 341.carboxylation of aromatic compoundsby, 342.cis- and trans- lY2-Dicyano- 1,2-bistriffploro-methylethylene, addition reactionsof, 267.1,1 -Dicy ano - 2,2 - disodiomercaptoet hylene ,cyclisation of, 387.Diels-Alder reaction, 269.of pyrroles with acetylenedicarboxylicacids, 382.Dienes, conjugated, reactions of, 330.Difluoroamine, structure of, 1 7 1.1,4-Dihalogenobuta- 173-dienes, van dertrans- 2,3 -Dihalogenonorbornanes, cis-Waals forces in, 330.elimination of hydrogen halide, 263INDEX OF 3UBJECTS 673Dihydrodipentalenylion, preparation of,4,5-Dihydro-oxepin, preparation of, 398.Dihydro-N-propylnicotinamide, planarity13-Diketones, transition-metal chelates of,Dilituric (5-nitrobarbituric) acid, 606.1,4-Dimethoxybenzene, electrolysis of,Dimethyl ether, spectra of, 301.NN- Dime t h ylaniline, spectra of, 309.2- (NN-Dimethylcarbamoyl) -9 -methyl-354.of, 605.349.342.fluorene, steric course of deuteriumexchange, 273.,$p-Dimethylcinnamaldehyde, cyclisationof, 391.3,4-Dimethylenetetrahydrofuran, prepara-tion of, 385.Dimethylketen, preparation of, 335.NN - Dimethylnitrosamine, rot at ional bar -2,6-Dimethyl-4-pyrone, reactions of, 395.aa’-Dimethylstilbenes, n.m.r.spectra of,4,4’-Dinitrobiphenyl, planarity of, GOO.Dinitrogen tetroxide, molecular dimen-rier in, 305.310sions of, 571.reaction with metals, 195.reaction with tetra-alkyl-lead, 195.Dinitrosyliron halides, reactions of, 236.1,4-Dioxan, structure of, 605.1,3-Dioxans, preparation of, 322.Diphenyl sulphide, structure of, 305.( + )- 1,3-Diphenylallene, synthesis of, 329.Diphenylketen, reaction with 1 -deuterio-1,8-Diphenylnaphthalene, spectral pro-cyclohexene, 270.Derties of. 340.1, I -Diphenylphosphabenzene, preparationof. 397.Diphenylquinocyclopropene, spectrum of,3,4-Diphenyltetrahydrofuran, dehydro-Diphosphine disulphides, reactions of, 198.Disorder, crystallographic, 5 68.Diterpenes, 370.1,4-Dithian 1,4-dioxide, structure of, 312.1,2-Dithiet, stability of, 381.Dithiin, reactions of, 397.1,2-Dithiolium salts, preparation of, 388.Echitamine iodide, structure of, 609.Electroanalytical techniques, 541.Electrochemical methods in proton trans-Electrolyte solutions, colligative pro-349.genation of, 385.fer, 53.perties of, 32.conductivity of, 18.kinetics of, 24.measurements a t high temperaturesnuclear magnetic resonance spectro-solubility measurements of, 33.and pressures of, 37.scopy of, 17.spectrophotometry of, 9.thermochemical studies of, 35.Electron transfer, in solution, 40.Eledoisin, sequence of, 484.( - )-Emetine, total synthesis of, 403.E.m.f.measurements, techniques, 2i.Energies, pseudo-lattice, calculation of,Energy, bond-dissociation, 151.levels, asymmetric-rotor, 163.Enniatin A, structure of, 463.Equilibria, acid-base, 294.Ergoflavin, structure of, 396.Ergotamine, total synthesis of, 463.Erysipelothrix rhusiopathiae, antigenicEscherichia coli, ribosomal protein of, 51 8.Ethoxycarbonylnitrene, addition to cyclo-o-Ethoxyphenylacetylene, preparation of,Ethylenediamine complexes of copper, 220.Ethylenediaminetetra-acetic acid, spec-trum of, 226, 304.Ethyltrimethylammonium iodide, elimi-nation reaction with sodium ethoxide,263.synthesis of, 460.223.polymer from, 496.ribosomes of, 512.hexene, 335.346.Fenchone, rearrangement to 3,4- dime t hyl-acetophenone, 365.Ferrichrome, structure of, 462.Ferrocene, reactions of, 354.Fibrinogen, carbohydrate in, 489.Fluorides, complex possessing perovskiteFluorine, cyanide, structure of, 166.Fluoroethylenes, structure of, 170.Force constants, calculation of, 140.Formaldehyde, structure of, 169.Formaldoxime, structure of, 305.Formic acid, dipole moment, 302.Franck-Condon principle, application toFriedel-Crafts acylations of metallocenes,Fucoidan, methanolysis of, 445.Furans and condensed furans, reactionsFurfuraldehyde, spectrum of, 310.Fusidic acid, structure of, 433.Gallane, adducts of, 189.Gallium, preparation of, 188.Gangliosides, brain, oligosaccharides of,human erythrocyte stroma, glycolipidsGermanium, phosphine adducts of, 193.Bis ( pentacarbonylmanganese) germaneGermanes, preparation of, 192.Germylsilane, preparation of, 193structure, 225.reactions of, 202.structure of, 595.electron transfer, 41.353.of, 385.491.of, 493.isolation of, 233674 INDEX O F SUBJECTSGermanium, Tris( triphenylgermy1)ger-mane, preparation of, 193.Gibberellic acid, stereochemistry of, 610.y-Globulin, papain digests of, 491.Glucans, 439.~I-D-G~ucos~, structure of, 607.Glycogens, analysis of, 440.Glycolipids, 491.Glycopeptide, from cartilage, 490.Glycopeptides, from colostrum, 490.Glycopeptidolipids, 491.Glycoprotein, of ovine submaxillary gland,Glycoproteins, 486.a-acid from mammalian plasma, 487.of bovine plasma, 487.Glycosaminoglycuronoglycans of con-nective tissue, 499.Gold complexes, infrared spectra of, 21 9.Graphite, reactions of, 190.Gravimetric analysis, 537.Grignard reagents, p.m,r. spectra of, 303.Gums, in plants, 444.a- and /3-Gurjunene, 366.Hernoglobin, antigenic sites in, 480.489.conformation of, 475.pentaribosomes in the synthesis of, 520.three-dimensional structures of, 474.total amino-acid sequence of a- andHemoglobin F, complete sequence of, 474.Hemoglobin S, oxygen affinity of, 474.Ha?rnophilus species, polysaccharides of,Halide ion, solvation of, 9.Halides, ethyl, torsion in, 173.metallic, structure of, 165.Halogenopenta-amminecobalt(III), 230.5-Halogeno-2-phthalimidobenzoic acid,Halogens, determination of, 539.Helminthosporal, total synthesis of, 369.Hemicelluloses, structure of, 442.Heparin, composition of, 499.Heptafulvene, preparation of, 351.Heterocyclic compounds, 378.( + )-Hetisine hydrobromide, structure of,&Hexachlorobenzene, spectrum of, 308.Hexacyanobenzene, reactions of, 342.Hexafluorobut- 2-yne,‘ 238.Hexahornobenzene, synthesis of, 350.Hexamethylenetetramine, structure of,Hexarnethylphosphoramide, adducts of,trans-Hex-3-ene, ozonisation of, 334.Hofmann elimination reactions, 264.Homocyclic compounds, spectra of, 306.“ Homotropone,” synthesis of, 351.Hormone, adrenocorticotrophic, synthesis/3-chain, 474.498.planarity of, 601.organic elemental analysis of, 563.spectra of, 138.structure of, 604.609.569.228.of, 459, 481.a- and jI-melanophore stimulating, syn-thesis of, 457.Hormones, thyroid, action of, 501.cellular oxidation, 505.interaction with enzymes, 505.metal chelation of, 504.redox properties, 503.Hyaluronic acid, structure of, 500.Hydrazino-functional groups, in analysis,Hydrazo-functional group, in analysis, 553.Hydroboronation reactions, 267, 314.Hydrocarbons, photochemistry of, 66.Hydrogen bonding, 295.in carboxylic acids, 595.in hydrated organic crystals, 61 1.in solvents, 260.transition-state, 278.Hydrogenation, catalytic, 31 3.Hydrolysis, mechanisms of, 279, 289, 292.Hydroperoxide anion, nucleophilic2’- and 4’-Hydroxy-4-acetamidobiphenyl,1 7a-Hydroxyaldosterones, photochemical3-Hydroxy-“ metathyroxine,” activity of,4-Hydroxymethyl-~-proline, synthesis of,( f )-3-Hydroxy-~-proline, stereospecific3-Hydroxy-3,4,4-trimethylpent- 1 -yne, pre-p-Hydroxytriphenylamines, production of552.spectra of, 300.strength, 257.preparation of, 342.synthesis of, 423.503.449.synthesis of, 449.paration of, 329.radicals from, 347.Imidazole, structure of, 604.Indium ion, Raman spectral evidence for,Indoles, n.m.r.spectra of, 31 1.Indolizine, n-electron delocalisation in,189.synthesis of, 382.310.reactions of, 384.Inorganic compounds, photochemistry of,79.qualitative analysis, 531.quantitative analysis, 534.Insulin, action of, 469.total synthesis of A chain, 461.Iodates, structure of, 580.Iodine, electropositive compound, 203.@-Iodine chloride, structure of, 572.Ion-molecule reactions, 155.Ion-pair return, 254.Ionisation potentials, application of massIridium, compounds of, 214.spectrometry to, 151.Iridium(II1) halides, complexes of, 21 6.Penta-ammineiridium(O), synthesis of,Potassium hexabromoiridate(m), re-214.action of, 236INDEX 0%Iron, electron transfer in, 44.seven co-ordinated, 222.spectra of complexes of, 213.carbonyl carbide, polynuclear complex,pentacarbonyl, reaction with toluene-Ammonium carbonylferrates, 234.Cyclo-octa- 1,3,5- trieneiron( 0)cyclo -232.3,4 -dithiol, 2 3 5 .octa-l,&diene, preparation of, 237.acetate, 318.equilibrium between diamagneticplanar and paramagnetic tetra-hedral, 218.Isoborneol.oxidation by lead tetra-Isomers, conformational, 296.Isoprene polymerisation, 109, 115.Isothialene, synthesis of, 396.Isothiazoles, preparation of, 387.Isothiocyanic acid, structure of, 306.Jacobine derivatives, structures of, 608.Kallidin, synthesis of, 460.Ketones, determination of, 546.Kinetics, of electrolyte solutions, 24.Klebsiella pneumoniae, capsular poly-Koenigs-Knorr synthesis of di- and oligo-Kojibiose, synthesis of, 438.Krypton di- and tetra-fluoride, prepara-reactions of, 286.saccharides of, 497.saccharides, 438.tion of, 179.Lanthanides, 204.Lasers, description of, 147.(f )-Latifoline, synthesis of, 412.Lead azide, preparation of, 195.tetra-acetate, oxidation of hydroxy-steroids by, 424.Lithium, aluminium hydride, 313.compounds, spectra of, 130.trimethylgermanyl sulphide, use of, 193.Lunarine, structure of, 414.Lycomarasmine, structure of, 450.Macdougallin, structure of, 432.Macusine-A iodide, structure of, 609.Magnesium compounds, spectra of, 130.Magnetic susceptibilities of titanium com-Maleic anhydride, photochemical addi-Malformin, cyclic pentapeptide sequenceManganese, carbonyls, 233.election transfer in, 47.halides, reactions of, 213.oxidation states of, 213.r-Cyclohexadienylmanganese tricar-pounds, 206.tions of, 343.of, 462.bonyl, preparation of, 237.theory of, 153Mass spectra, of amino-acids, 451.SUBJECTS 675Mass spectrometry, analysis by, 148.applications to inorganic and thermo-review of, 148.chemistry, 154.(&)-Matrine, total synthesis of, 400.Membranes, mitochondrial, permeability2-Mercaptoethylamine, reaction with tran-Mercapto-functional group, in analysis,Mercury compounds, spectra of, 131.of, 508.sition-metal ions, 229.554.Alkylmercuric perchlorates, carboniumMercury(I1) halides, spectra of, 221.Mercury- pho t osensi t ised reac tions, 85.Metaboric acid, /3- and y-, structure of,Metallocenes, preparation of, 353.6-Methanesulphinylhexyl isothiocyanate,isolation of, 336.Methionine, enzymic demethylation of,336.anti-4 -Methoxybenzonorbornen- 7 - yl 4-bromobenzenesulphonate, solvolysisof, 249.Methyl halides, force constants for, 140.Methyl methacrylate polymerisation, 11 3,Methyl vinyl ether, rotational isomers,301.trans- 1 -Methylbut-2-enyl p-nitrobenzoate,reactions of involving ion-pairs, 254.Methylenecyclopropene system, prepara-tion of, 356.1 -Methylheptyl arenesulphonates, racem-isation of, 255.B-Methylhexa-2,3,4-trienal, preparation of,330.Methylisatoid, Hantzsch’s structure for,383.cis-l-Methyl-2-phenylcyclopropanol isom-erisation, 258.4-Methylproline, synthesis of cb- andtrans-, 449.trans-4-Methyl-~-proline, synthesis of,382.4-Methyltestosterone acetate, ketalisationof, 418.l0a-Methyltestosterone, photochemicalpreparation of, 422.1 -Methylthymine, structure of, 606.Na-Methyltryptophan, preparation of,451.Micrococcus lysodeikticus, cell-wall com-position of, 495.Mitragynine, structure of, 407.( f )-Mitraphylline, 408.Molar volumes, 36.Molecular complexes, 61 1,Molecular geometry, computation of fromMolecular interactions, 61 1.Molecular parameters, 300.Molecular structure, microwave studies of,ion stabilisation in, 250.580.termination of, 104.rotational constants, 164.165676 INDEX O F SUBJECTSMolecular structure, techniques for corre-lation of mass spectra with, 157.Molecules, asymmetric-top, 173.diatomic, 165.double top, 175.linear, 166.non-linear triatomic, 168.non-planar asymmetric top, 17 1.planar, 169.small-ring, planarity of, 574.symmetric-top, 166.Molybdenum, complexes of, 21 1.oxidation states of, 211.spectra, 212.Monosaccharides, 436.Monoterpenes, 365.Muramine, constitution of, 402.Mycochrysone, elucidation of structure,Mycosamine, constitution of, 437.Mycosides, from Mycobacteria, structureMyoglobin, amino-acid sequence of, 476.Myoinositol, structure of, 603.Naphthazarin, three crystalline forms of,1 -Naphthylethane, mechanism of forma-Natural products, acetylenic, 327.Nickel, ammine complexee, thermal de-356.of, 494.600.tion of, 348.composition of, 215.complexes, paramagnetic, 590.dicarbonyl, preparation of chelated,Bis( benzyldiphenylphosphine)nickel(II),Bis(pyridine)nickel(II) chloride, thermalNickel(n), complexes of, 217.Nickel(I1) halide complexes, codgura-Nickel(I1) halides, reaction with di-Nickel(I1) halides, spectra of, 215.Kickel(II), Schiff base complexes of, 218.Niobium, halides, preparation of, 209.spectrum of complexes of, 136.Nitramide, microwave spectroscopy of,Nitrates, spectra of solutions, 14.Nitric oxide, anion formed by reactionwith diethylamine, 195.N-p-Nitrobenzenesulphonyloxyurethane,reaction with triethylamine, 341.o-Nitrobenzonitrile, catalytic hydrogena-tion of, 342.Xitro-compounds, photolysis of, 26.Nitrogen dioxide, reaction with hydrogen234.stereochemistry of, 222.decomposition of, 217.tion of, 217.phenylphosphine, 21 7.173.fluoride, 195.structures of two dimers, 195.550.560.Nitrogen functional groups, in analysis,Nitrogen, organic elemental analysis of,spectra of compounds of, 135.Nitroprusside ion, 236.o-Nitrosobenzamide, preparation of, 345.Nitrosofluoroamine, N-N bond energy in,196.1 -Nitrosohex- 1 -yne, reaction with nitricoxide, 335.Nitrosohydroborate anion, formation of,183.Nitrosyltricarbonylcobalt, reactions andspectrum of, 235.Nitryl chloride, structure of, 170.Nona-2,3-diene, metal-ammonia reduc-tion of, 316.Non-benzenoid aromatic compounds, 349.Norbornadien-7-yl fluoroborate, n.m.r.anti-Norbornen-7-y17 solvolysis of deriva-endo- (ezo)-Norbornylamine, deaminationB-Norcholesteryl acetate, catalytic reduc-Nor-c-curarine-111, synthesis of, 407.19-Nor-3-keto-steroids, reactions of, 418.B-Nor-steroids, 416.Nuclear magnetic resonance study ofNucleophilic substitut'on a t saturatedspectrum, 248.tives, 247.of, 252.tion of, 416.proton transfers, 51.carbon, 247.A1(0) -2-Octalone, catalytic hydrogenationD-gluco-L-galacto-Octulose, synthesis of,Estrogen, structure of, 602.Estrone, synthesis of, 426.Olefin-forming eliminations, 262.Olefinic compounds, 330.Olefins, additions to, electrophilic, 265.of, 313.436.additions to, nucleophilic, 268.radical, 269.complexes of transition metals, 237.formation of, 319.(+ )-a-Onocerin, total synthesis of, 376.Organic elemental analysis, 557.Organic structure, 299.Organometallic compounds, 324.structure of, 586.Osmium, ammines of, 213.measurements of, 214.Hexahalogeno-osmates(1v) magneticOvalbumin, enzymic digest of, 486.Ovomucoid, carbohydrate composition of,Oxalates, metal, thermogravimetric analy-1 -Oxaphenalene, synthesis of, 395.Oxazoles, preparation of, 387.Oxepin rearrangement, 398.Oxidation, mitochondrial, control b jthyroid hormones, 506.organic, 31 6.Oxidations, enzymic, 355.Oxides, crystallography of, 576.of carbon, photolysis of, 79.of nitrogen, photolysis of, 81.487.sis of, 225INDEX O F SUBJECTS 677Oxindole alkaloids, 408.Oxirans, derivatives of, reactions, 379.Oxolaudanosine, preparation of, 402.20-0xopregn-16-enes, reactions of, 422.Oxovanadium complexes, co-ordinationOxyacid salts of heavy metals, 583.Oxyacids, d c p n bonding in, 579.Oxygen, atoms, location of by neutrondifluoride, spectroscopic study of, 168.functional group, in analysis, 542.organic elemental analysis of, 560.in, 209.diffraction, 576.Oxytocin, synthesis of, 459.analogues of, 484.Ozone, photolysis of, 83.Palladium(II), halides, reaction withorganophosphines, 21 9.reaction with azide ions, 219.Panose, constitution of, 438.Papaverine, mass spectra of, 404.[2,2]Paracyclonaphthalene, formation of,[2,2]Paracyclophane, strain in, 603.Paracyclophanes, benzene ring distortionPatchouli alcohol, structure of, 368.Pavarallidine, structure of, 41 2.Pectic acids, degradation of, 445.2,2’,4,5,5’-Pentamethoxybiphenyl, 342.Pentan-2-one, photolysis, 69.Pentaphenylcyclopentadienyl cation, de-monstration of, 348.Peptide bond, formation of, 454.Peptide synthesis, protecting groups in,452.Peptides, 448.antigenicity of, 480.cyclic, 462.natural. synthesis of, 457.racemisation of, 456.selective cleavage of, 479.sepaxatory technique for, 479.271.in, 309.Peptidoglycan, synthesis of S.aureus cellwall, 496.Perchlorates, depolymerisation of con-densed alkali-metal phosphates by,198.spectra of, 15.Perfluoroketones, photolysis, 73.Peroxy-compounds, “ so-called ” of silver,Pertechnetates, scheelite structure of, 579.Pertechnetyl fluoride, preparation of, 21 3.Phenanthrene, structure of, 602.1,lO -Phenanthrolines, 2 2 8.Phenazine 5,lO-dioxide, structure of, 606.Phenols, determination of, 548.Phenothiazine, derivatives of, 393.Phenoxide ion, action as ambidentatePhenoxymethylpenicillin, structure of, 61 0.Phenyl salicylate, oxidation by persul-structure of, 585.preparation of, 340.nucleophile, 261.phate, 346.Phenylacetylene, irradiation of, 344.9-Phenyl-9-arsafluorene, structure of, 6031 -Phenyl- 4- t - but ylc yclohexane,brium between cis and trans, 306.2-Phenylcinnamic acid, catalytic reductionof, 314.Phenylindoles, reactions of, 383.2-Phenylpentane, mechanism of formation,cis- 1 -Phenylpropene, deuterium bromidePhosphate minerals, structure of, 582.Phosphates, condensed alkali-metal, de-polymerisation of, 198.Phosphazens, 197.Phosphonitrilic halides, 197.configurations of, 574.Phosphorus, compounds of, 196.equili-348.addition, 331.mixed halides of, 198.pentachloride, spectrum of, 136.preparation of a vitreous form, 196.Methylaminophosphines, reactions of,196.Phosphorus-bridged carbonyls, 234.Phosphorus-nitrogen-sulphur compounds,Phosphorylation, mitochondria1 oxidative,Photochemistry, experimental techniques198.506.in, 63.of inorganic compounds, 79.of organic compounds, 66.of vision, 89.theoretical apsects of, 64.Photosensitised reactions, 85.Picraline, structure of, 409.Pilocereine, preparation of, 403.( f )-Pimaradiene, total synthesis of, 370.Pivalic acid, use for coupling peptides,Platinum boride, preparation of, 217.Platinum( 11) , ammine-nitrile complexesPlatinum(v) complexes, preparation of,Pleuromucoid, glycopeptides from, 488.Plutonium, eight crystallographic mods-Pneumococcus, capsular polysaccharidesPneumosamine, characterisation of, 436.Polar factors in polymerisations, 100.Polarographic analysis, 540.measurement of proton transfer, 54.Polycyclic compounds, structure of, 601.Poly(cytidy1ic acid), helical form of, 608.Polymer tacticities, measurement of, 107.Polymerisation, free-radical, new initiators455.of, 219.219.cations of, 568.of, 498.in, 92.free-radical, tacticities in, 106.homogeneous liquid-phase, review of,of benzene, 330.termination of, 103.tracer technique for investigating initia-91.tors, 95678 INDEX OF SUBJECTSPolynucleotides, interaction with ribo-Polyoxyacids, structure of, 580.Polyribosomes, structure of, 51 9.Polyuridylic acid, irradiation of, 528.Polyuronides, in plants, 444.Porphyrins, planarity of, 31 1.Potassium peroxodicarbonate, preparation(f)-P-Prodine hydrogen halides, structureProgesterone, synthesis of, 429.Proline derivatives, synthesis of, 449.Propene and derivatives, torsion barrier/%Propiolactone, spectrum of, 310.Propionic acid, structure of, 595.Prostaglandin Fz-1, structure of, 610.Protein, methods of fragmentation of, 478.Protein, structure of, in ribosomes, 517.synthesis, control of polysome functionin, 526.synthesis, regulation by thyroid hor-mones, 509.synthesis, ribosomal structure active in,519.Protein-metal interaction, copper com-plexes in, 592.Proteins, review of, 468.Protolytic equilibria, spectrophotometricmeasurements in, 11.Proton transfer, 48.electrochemical measurements of, 53,in organic compounds, 56.Purine, spectra of, 394.Purines, structure of, 606.Pyrazine, resonance energy of, 393.Pyrazoles, reactions of, 386.Pyridines, dipole moments of, 31 1.2- and 4-Pyridones, structure of, 391.4-Pyridylmalondialdehyde7 preparation of,N - (2-Pyridy1methyl)iminodiacetic acid,Pyrimidines, structure of, 606.Pyrroles, reactions of, 381.Pyrrolo[2,1,5-cd]indolizine, spectra of, 384.Pyrrolylmagnesium bromide, reactionwith alkyl halides, 261.Pyrylium salts, reactions of, 394.somes, 522.structure of, 605.of, 181.of, 607.in, 174.59.spectra of, 390.322.227.Qualitative analysis, techniques for, 532.Quebrachidine, structure of, 409.8-Quinolineboronic acid, catalytic action,Quinolines, preparation of, 391.Quinolizines, reactions of, 392.Quinoxaline N-oxides, synthesis of, 393.257.Racemisation of peptides, 456.Radiation initiation of polymerisation, 97.Radical addition to olefins, 269.Radical anions,methods of preparation,348.Radicals and radical-ions, aromatic, 347.Rare-earth ions, complexes of, 204.metals, photolysis, 85.oxides, separation of, 204.Rearrangements, aromatic, 282.benzidine, 282.Claisen, 283.Cope, 283.photochemical Fries, 343.Reticulin, glycopeptide from, 489.Rhenium chlorides, complexes of, 213.trioxyfiuoride, structure of, 167.Octafluororhenates(vI), hydrolysis of,Rhodium chlorides, isolation of ionicRhodium(m), hydrido-complexes, 242.degradation of, 470.reaction with iodoacetate, 472.structure-activity relationships in, 471.Ribonucleic acid, ribosomal, physicalRibosomes, dissociation into subunits, 515.213.species, 2 16.Ribonuclease, activity of, 461.properties of, 517.size of messenger, 521.in protein biosynthesis, 512.internal structure of, 518.properties of, 513.Ruthenium halides, magnetic propertiesof, 214.Saccharides, di-, 438.heteromeric, 486.oligo-, 438.poly-, algal, 445.analysis of, 439.bacterial, 446.of bacterial capsules, 497.of bacterial cell-walls, 495.synthesis of, 447.thesis of, 370.formation products of, 366.( f )-Sandaracopimaradiene, total syn-Santonic acid, stereochemistry of trans-(-)-Sarcomycin, configuration of, 359.Sarcostin, structure of, 432.Saturated carbon, electrophilic substitu-nucleophilic substitution at, 247.Selenium, compounds of, 202.heptafluoropropyl derivatives of, 202.trioxide, reactions of, 202.5 - h i n o - 1,2,4-~elenadiazoles, prepara-tion at, 273.tion of, 388.Sesquiterpenes, 365.structure of, 609.Silicate minerals, structure of, 581.Silicon, acetylacetonate complex, quasi-aromatic character, 349.halides, reactions of, 192.preparation of, 190.spectra of compounds of, 133.Alkylchlorosilanes, reaction of, 192.Disilane, preparation of derivatives of,191INDEX OF SUBJECTS 679Silane, synthesis of derivatives of,Silyl isoselenocyanate, preparation of,190.202.Silver, electron transfer in, 47.nitrate, chlorite, phosphate, structureSilver(I1) complexes, spectra of, 219.Soladulcidine, synthesis of, 431.Solvation, of halide ion, 9.numbers, technique for deriving, 23.Solvents, aprotic, 260.strongly hydrogen-bonded, 260.Solvolysis, amyl participation in, 250.Sophorose, synthesis of, 438.Spectra, analysis of, 163.environmental effects on Raman andof deuteroalkanes, 121.of ethane, 121.of Group I compounds, 130.of Group I1 compounds, 130.of Group I11 compounds, 131.of Group IV compounds, 133.of Group V compounds, 134.of Group VI compounds, 137.of Group VII compounds, 138.of xenon tetrafluoride, 130.of, 585.infrared, 12 7.Spectrometers, double resonance andbeam maser, 162.for microwave spectroscopy, 161.Spectrophotometry, ultraviolet andSpectroscopic techniques for study ofSpectroscopy, application of lasers in, 146.visible, 9.adsorbed molecules, 125.of chemisorption, 123.high resolution studies in, 121.infrared, 16, 120.infrared-intensity measurements in, 145.infrared, of free radicals, 126.matrix technique in, 126.microwave, of gases, 160.nuclear magnetic resonance, 17.Raman, 13, 120.Raman-intensity measurements in, 143.studies in solid state, 128.Spirilloxanthin, synthesis of, 331.Spiro-dienones, preparation of, 345.Sporidesmin, structure of, 41 1.Sporidesmolide I and 11, structures of,Spot tests, for inorganic ions, 531.Staphylococcus aurezls, enzymic digest ofStarch, components of, 439.Steroid enamines, reduction of, 419.Steroids, 415.463.cell wall of, 495.metabolism of, 441.addition of Grignard reagents t o A*-3-hydroxy-, lead tetra-acetate oxidationll-keto-, stability of, 421.photochemistry of, 422.physical measurements, of 415.keto-, 419.of, 424.reactions of ring A, 417.reactions of ring B, 420.reactions of ring c, 421.reactions of ring D and the side chain,synthesis of, 426.421.Stilbene, photoisomerisation, 68.cis- S tilbenes, photochemical transforma-Streptococci, polysaccharides of, 497.Strychnine, absolute configuration of, 407.Styrene polymerisation, 99, 108, 113, 116.Succinoxidase, thyroid hormone stimula-Sugar phosphates, synthesis of, 438.Sugars, amino-, synthesis of, 436.tion of, 340.termination of, 104.tion of, 505.deoxy-, synthesis of, 437.thio-, synthesis of, 437.Sulphanilic acid monohydrate, structureSulphanuric chloride, structure for tri-Sulphate radical-ion, 8.s.r.spectrum of, 83.Sulphates, anhydrous heavy-metal, struc-hydrated heavy-metal, co-ordinationspectra of, 15.compounds, spectra of, 137.functional group in organic analysis,halides, preparation of, 201.nitrides, preparation of polymeric, 200.organic elemental analysis of, 561.of, 599.meric cyclic, 200.ture of, 583.polyhedra in, 584.Sulphur, compounds of, 199.554.Sulphuric acid, spectral study, 15.Systems, intermetallic, crystallography of,3-Tachysterol, synthesis of, 429.Tantalum halides, preparation of, 209.Tautomerism, 296.Technetium tetracarbonyl, polynuclear,Technetium(vII), polrtrographic reductionTeichoic acids, 447.Tellurates, structure of, 580.Tellurium, complexes of, 202.dioxide, structure of, 576.Telomycin, structure of, 462.Tenulin, structure of, 368.Te trae t h y lenepentamine , 2 30.Tetrafluoro-3,4-dihydro-l,2-diazete, struc-Tetrafluoro- 1,3-dithietan, spectrum of,Tetrahydro - 2 - phenyl- 1,2 -oxazines, ther -Tetrahydrothiophen dioxide, planarity of,Tetrakistrimethylsiloxyaluminate, ionicTetramethylammonium-mercury tribrom-571.232.of, 213.ture of, 380.310.ma1 decomposition of, 358.305.structure of, 191.L de, structure of, 575680 INDEX OFTetraphenylcyclobutadienepalladium( 11)halides, complexes from, 239.3,5,3’,5’-Tetraphenyldiphenoquinone, ex-istence as biradical, 347.Tetrathiazyl fluoride, symmetry of, 574.Tetrazole, acidic character of, 604.Thalicarpine, constitution of, 403.Thallium : Alkyl- and aryl-thallium(III)chlorides, preparation of, 189.Thebaine, adducts of, 406.Thelopogine methiodide, structure of, 608.Thermochemistry, mass spectrometricThermodynamic properties, of electrolyte3-Thiadodecanoic acid, structure of, 596.Thiazoles, reactions of, 387.Thienotropylium perchlorate, synthesis of,Thietans, reactions of, 380.Thiocarbonyl fluoride, preparation of, 199.Thiocyanate, linkage isomerism of, 224.Thiocyanic acids, infrared spectra of,Thioketones, preparation of, 336.Thiolation, of proteins, 480.Thiophens, reactions of, 386.Thorium(1v) iodide, reactions of, 204.Thyroxine, complexes with bivalentinteractions with purified enzymes, 509.study of, 154.solutions, 25.386.200.metals, 504.L-Thyroxine, structure of, 501.Tin, evidence for 5-co-ordination, 194.spectra of compounds of, 134.Alkyl (aryl) tin compounds, reactionsDimethoxytin(n), preparation of, 195.Dimethylstannane, preparation of linearpolymers of, 193.Stannanes, addition reactions of organicderivatives, 193.Tin(I1) chlorides, 195.Trialkyltin cation, co-ordination of, 194.Trihalogenostannic acid esters, struc-Triphenyltin chloride, reaction withwith sulphur, 194.ture of, 194.silver nitrate, 194.Titanates, distorted octahedra in, 583.Titanium, complexes of, 206.compounds, magnetic susceptibilities of,1,3-diphenyltriazen derivatives, pre-halides, reactions of, 206.Titanium(v1) ethoxide, tetrameric, 207.Trimethyltitanium iodide, preparation206.paration of, 207.of, 242.Titrimetric analysis, 537.m-Toluamide, structure of, 600.Tomatidine, synthesis of, 431.Transition elements, 204.molecular hydrides of, 242.organometallic compounds of, 242.with toluene-3,4-dithiol, 2 15.Transition-metal bivalent ions, reactionmonophosphides, synthesis of, 210.SUBJECTSTransition metals, complexes of, 226.Transport numbers, 22.Trialkylindiums, preparation of, 189.Tri(aminoethy1)amine trihydrochloride,structure of, 598.Tricyanamethanide ion, spectra of, 133.Triethylenetetramine, 231.Trifluoroacetic acid addition to olefins,266.Trifluoromethanesulphenyl pseudohalides,200.1,1,1 -Trifluoropentane-2,4-dione, terva-lent-metal complexes of, 224.3,3’, 5 -Tri-iodo-L-thyronine, structure of,501.2,4,6-Tri-isopropylphenylacetylene, spec-trum of 327.endo-Trimethylenenorbornene, additionreactions of, 266.2,4,6-Triphenylthiabenzene, spectrum of,397.Triterpenes, 3 7 3.a-Tropolone methyl ether, photoisonierisa-tion of, 361.Tropone, reactivity of carbonyl group in,351.Tropones, synthesis of, 351.Tropylium bromide, reactions of, 351.Tungsten, complex halides of, 21 1.photolysis of, 84.oxidation states of, 211.Hexachloro tungs tates (v) , preparationof, 211.Uranium alkoxides, preparation of, 205.Uranyl salts, bond lengths in, 206.chlorides, reactions of, 205.Valinomycin, structure of, 463.Vanadium chlorides, reactions of, 200.complexes of, 208.hexacarbonyl, use as oxidising agent,240.Vasopressin, synthesis of, 459.Veratramine, stereochemistry of, 413.synthetical approach to, 431.Vilsmeier-Haack reaction, 322.Vincamine alkaloids, structure of, 408.Vinyl benzoates, photochemical Fries re-Vitamin A, acid, triclinic form of, 611.arrangement, 343.aldehyde, preparation of, 322.synthesis of, 332.Water, infrared spectrum of, 16.Water, pure, conductivity, 22.Raman spectrum of, 13.Wettstein’s reagent for oxidation ofWillardine, synthesis of, 393.Wittig reaction, 320.Wolff-Kishner reductions, 316.steroids, 424.Xanthone, reduction by diborane, 314INDEX OF SUBJECTS 681Xenon compounds, structure of, 573.fluorides, preparation of, 179.Xylans, degradation of, 442.o-Xylylene, preparation of, 340.Zinc compounds, spectra of, 131.Zirconium dioxide, structure of, 578.1 halides, preparation of, 221.I halides, reacticms of, 208Printed in Great Britain byButler & Tanner LtdFrome and Londo

ISSN:0365-6217    

DOI:10.1039/AR9636000669

出版商:RSC    

年代:1963

数据来源: RSC