ISSN:0365-6217    

DOI:10.1039/AR95552FP001

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

ERRATAVOL. 51, 1954.Page111 Referencet!9 should read E. A. Guggenheim, Trans. Furaday SOC., 1940, 36,398 ; Thermodynamics,” North-Holland Publ. Co., 1949, p. 36.258 Formula (25) should rea

ISSN:0365-6217    

DOI:10.1039/AR9555200006

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.GENERAL AND PHYSICAL CHEMISTRY.1. KINETICS OF CHEMICAL CHANGE.Kinetic Studies in Gaseous Reactions.-Much work on the kinetics ofgaseous reactions has been published in the past year. Most of it concernsfresh experimental studies of thermal decompositions, slow oxidations, com-bustions, and the reactions of radicals produced by pyrolysis or photolysis.There have not been any major changes in the theories of gaseous reactions,but an interesting and useful book on gas kinetics has been publishedwhich summarises recent investigations and the present status of theoriesof gaseous decompositions and transfer and addition reactions. Thetranslation of Frank-Kamenetskii’s book on diffusion and heat exchangein chemical kinetics makes valuable material available at a reasonable pricewhich compensates for the poor quality of reproduction.The full paperspresented at the Fifth Symposium (International) on Combustion have beenprinted; * many of these papers were discussed in last year’s Report. Thesecond half of a book% on physical measurements in gas dynamics andcombustion deals inter aha with the measurements of burning velocities,spectroscopic measurements of temperature, and flame photography. TheLiversidge lecture was upon the reactions of radicals in gaseous systems.*A timely review discusses reactions of the nitrogen dioxide-dinitrogentetroxide system.Vogelaere and Boudart 6 have examined the changes in the transmissioncoefficient of the reaction AB + A + A + BA by methods found usefulin the mathematically similar problem of the allowed cone of cosmic radiation.Y asumori has indicated a modified bond-eigenfunction method of calculat-ing potential energy surfaces, and its application to the reactionA.F. Trotman-Dickenson, “ Gas Kinetics,” Butterworths Scientific Publications,London, 1955.a D. A. Frank-Kamenetskii, “ Diffusion and Heat Exchange in Chemical Kinetics,”translated by N. Thon, Princeton Univ. Press, 1955.Fifth Symposium (International) on Combustion, “ Combustion in Engines andCombustion Kinetics,” Reinhold Publ. Corporation, New York, and Chapman andHall, Ltd., London, 1955.8b “ Physical Measurements in Gas Dynamics and Combustion,” ed. R. W. Laden-burg, B. Lewis, R. N.Pease, and H. S. Taylor, Oxford University Press, London, 1955.Liversidge Lecture, “ Reactions of Radicals in Gaseous Systems,” by E. W. R.Steacie, J., 1956, in the press..P. Gray and A. D. Yoffe, Qua+$. Rev., 1955, 9, 362.R. de Vogelaere and M. Boudart, J . Chem. Phys., 1965, 23, 1236.I. Yasumori, ibid., p. 15668 GENERAL AND PHYSICAL CHEMISTRY.H* + H, __t H, + He. Hammond gives a qualitative discussion ofappropriate models for the transition complex. The transition-state theoryhas come under fresh 10311Papers upon the theory of chain reactions have discussed the principleand conditions of applicability of the Semenov-Bodenstein method of quasi-stationary states l2 and an estimate of the accuracy of the method,l3 con-secutive reactions and chain reactions,14 catalysis and inhibition of chainreactions,15 and the action of inhibitors upon branched-chain reactions.16In the analysis of experimental results, Wideqvist l7 has emphasised theusefulness of substitutions of the form 8 = f(c)dt, f(c) being a suitablearbitrary function of the concentration and 8 being obtained graphically.Tobin l8 has indicated methods of treating second-order reactions which areautocatalytic or reversible.The applications of least-square deviations tothe evaluation of rate constants have been discussed.lg, 2o Janz and Wait 21have justified the use of space-time yield as measures of velocities of reaction,provided certain experimental conditions are fulfilled. Other short paperson intramolecular energy transfer,22 methods of calculating collision dia-meters,% revised values of diffusion coefficients of certain hydrocarbons,24rates near eq~ilibrium,,~ kinetics in non-isothermal systems,26 kinetics andthermodynamics of irreversible and the concept of rate ofreaction 28 have appeared.Some fresh complexities have been suggested in the kinetics of somereactions previously thought simple.Benson and Srinivasan 29 have arguedthat the high temperature coefficients of the forward and backward velocityconstants in the gaseous reaction H, + I, + 2HI indicate that the reactionproceeds by concurrent bimolecular and chain processes, but their sugges-tions cannot properly be tested because of the scatter of the available dataon the two velocity constants at different temperatures.In this connectionP6neloux 30 suggests a differential method of analysing Bodenstein's data onthe decomposition reaction which gives more consistent results for thevelocity constant. The oxidation of nitric oxide by oxygen has been studiedG. S. Hammond, J . Amer. Chem. Soc., 1955, 77, 334.N. I. Kobozev, Zhur. fiz. Khim., 1954, 28, 2067.lo V. A. Pal'm, ibid., 1955, 29, 1116.l1 V. A. Roiter, Ukrain. khim. Zhur., 1955, 21, 296.12 Yu. S. Sayasov and A. B. Vasil'yeva, Zhur. $2. Khim., 1955, 29, 802.l3 I. F. Bakhareva, Doklady Akad. Nauk S.S.S.R., 1955, 102, 1151.l4 E. Abel, Osterr. Chem.-Ztg., 1955, 56, 305.16 2. G. Szabo, P. Huhn, and A. Bergh, Magyar Kbm. Folyydirat, 1955, 61, 137,*? S. Wideqvist, Arkiv Kemi, 1955, 8, 325.lo S.Huyberechts, A. Halleux, and P. Kruys, Bull. SOC. chim. belges, 1955, 64, 203.2o D. F. DeTar, J . Amer. Chem. Soc., 1955, 77, 2013.21 G. J. Janz and S. C. Wait, jun., J . Ckem. Phys., 1955, 28, 1550.22 H. 0. Pritchard, Rec. Trav. chim., 1955, 14, 779.23 E. Bauer, J . Chem. Phys., 1955, 23, 1087.24 G. A. McD. Cummings and A. R. Ubbelohde, J., 1955, 2524.25 A. Pbneloux, Corn@ rend., 1955, 240, 758.26 H. Gaensslen and H. A. E. Mackenzie, J . Appl. Chem., 1955, 5, 552.A. PBneloux, Compt. rend., 1954, 239, 1379.2 8 J . E. Verschaffelt, Bull. Classe Sci., Acad. roy. Be&.. 1955, 41, 316.20 S. W. Benson and R. Srinivasan, J. Chem. Phys., 1955, 23, 200.30 A. P6neloux, Compt. vend., 1955, 240, 2142.English summary, 145.D. G. Knorre, Zhur.$2. Khim., 1955, 29, 1285.M. C. Tobin, J . Phys. Chem., 1955, 59, 799KINETICS OF CHEMICAL CHANGE. 9by Treacy and Daniels31 between 1 and 20 mm. by a photometricmethod : they report progressive deviations from the simple expressionrate cc [NOI2[Od as the pressure is lowered. A complex scheme withreactions involving nitrogen trioxide and dinitrogen pentoxide is suggestedto account for the deviations, but the role of those involving the pentoxide isnot clearly explained.Johnston and White 32 have extended certaintests 33 of the mutual consistency of the experimental values of the velocityconstants of unimolecular decomposition, and applied them to the decom-positions of cyclobutane, cyclopropane, dinitrogen pentoxide, and nitrousoxide.They agree with Kassel that there appears to be asystematic errorin the value of k , for the decomposition of dinitrogen pentoxide. They alsoemphasised the unreliable nature of the data then available on the decom-position of nitrous oxide. However, two important papers on this decom-position at 720" have since appeared. shows that the well-known breaks in the plot of the first-order velocity constant against pressureare inherent in the step N,O N, + 0- and are not caused by the subse-quent reactions of the oxygen atom, concurrent homogeneous and hetero-geneous reactions, or the catalytic effect of nitric oxide. In the secondpaper 35 the addition of inert gases (argon, nitrogen, carbon dioxide, carbontetrafluoride, and sulphur hexafluoride) is shown to produce similar breaks atpressures characteristic of each gas.The important conclusion is drawnthat these results can only be explained if collisions with reactant or inert-gasmolecules can affect the step from energised to activated species in thesequence :Most previous treatments considered that the step could only proceed intra-molecularly. The activated states may be triplet states ; 35 Hinshelwoodand Jach3, have studied carefully the effect of inert gases on the decom-position of a-butane and of n-pentane, in the absence and presence of nitricoxide. Each gas increases the rate of decomposition by an amount which isindependent of the pressure of nitric oxide present. This is strong evidencethat the " fully-inhibited " decomposition is a molecular reaction, for if itwere the chain-starting process the inert gases should produce a greatereffect on the uninhibited reaction, and it is difficult to see how inert gasescould affect any chains started and stopped by nitric oxide.In a furtherpaper:' a detailed interpretation of the effects of the inert gases again showsthat they must act on the second stage of the sequence (1).The occurrence of exchange reactions38s39 between C,D, and C,H,or CH, in the presence of nitric oxide is discussed by Danby, Spall, Stubbs,and Hinshelwood,4O together with their own discovery that the formation ofGaseous decompositions.The firstNormal energised activated -+ products . (1)31 J. C. Treacy and F. Daniels, J. Amer. Chem. SOC., 1955, 77, 2033.33 H.S. Johnston and J. R. White, J . Chem. Phys., 1954, 22, 1969,a* L. Kassel, i b d , 1953, 21, 1093.34 F. J. Lindars and (Sir) C. Hinshelwood, Proc. Roy. SOC., 1955, A , 231, 162.36 Idem, ibid., p. 178.s8 J. Jach and (Sir) C. Hinshelwood, ibid., 1955, 229, 143.37 Idem, ibid., 1955, 231, 145.38 L. A. Wall and W. J. Moore, J , Awer. Chem. Soc., 1951, 73, 2840.3s F. 0. Rice and R. E. Vaxnerin, ibid., 1954, 16. 324.*O C. J. Danby, B. C. Spall, F. J. Stubbs, and (Sir) C. Hinshelwood, Proc. Roy. SOC.,1955, A , 228, 44810 GENERAL AND PHYSICAL CHEMISTRY.CH3D from mixtures of wbutane and deuterium is not affected by the pre-sence of nitric oxide. They conclude that the formation of CH,D mayoccur after the formation of but-l-ene, and that the occurrence of exchangedoes not necessarily imply the intervention of alkyl radicals in the decom-position of a-butane.This conclusion is reasonable, and other evidence 36for the molecular nature of the residual reaction is convincing ; nevertheless,it is slightly unsatisfactory that so many diverse reasons have to be given *Ofor the occurrence of isotopic exchanges in the presence of nitric oxide.Maccoll, Thomas, and their co-workers have published a very interestingseries of papers on the pyrolyses of organic bromides using a static system andfollowing the reactions by pressure change after establishing that thereactions had a common stoicheiometry)CH*CBr( __t )CC( + HBr.The mechanisms of the reactions are very different, and the investigatorsset out to establish the mechanisms and to relate the rates of reaction to thestructure of the compounds.Some of their findings are summarised inTable 1.TABLE 1.Temp.Ref. Bromide Range41 ally1 320-380"42 n-propyl 300-38043 isopropyl 310-35044 sec.-butyl 300-35045 cyclohexyl 300-35046 tert.-butyl 230-280E (kcal.Order A (sec.-l) mole-l) MechanismComplex radical non-1.5 (7.24 x 10'0) * 33.8 ChainUnimolecular elimina-1 4.17 x 1013 tion of HBr, but the1 4.27 x 10l2 reverse reactionbecomes important1 3.24 x 1013 Unimolecular elimina-1 1.0 x 1014 tion of HBr1 2.11 x lo1' 45.4 { chain* A for n-propyl is in mole-112 cm.3/2 .sec.-l.By comparing the kinetics of decomposition of these and other organicbromides and chlorides, and their activation energies, Maccoll and Thomas 47conclude that there is a common mechanism for the molecular elimination ofhydrogen bromide or of hydrogen chloride in the gas phase.The activationenergies of the elimination reactions correlate better with the bond dissoci-atiqn energy into ions, D(R+-X-), than with the bond dissociation energyinto radicals, D(R*-X.). The authors suggest that the hydrogen on the pcarbon atom can exert an influence like that of a polar solvent and help tostabilise the transition state, R1R2CHa+*CR3R4HS-. They point out theneed for re-examining the view that all gas reactions are in principle homo-lytic with mechanisms differing greatly from those applying to heterolyticreactions in solution.From experiments on the changes in the ratio 12C/13C in the ethyleneformed during the decomposition of ethyl bromide, Friedman, Bernstein,41 A.Maccoll, J., 1955, 965.42 P. J. Agius and A. Maccoll, ibid., p. 973.O3 A. Maccoll and P. J. Thomas, ibid., p. 979.44 Idem, ibid., p. 2445.45 J. H. S. Green and A. Maccoll, ibid., p. 2449.46 G. D. Harden and A. Maccoll, ibid., p. 2454.4 7 A. Maccoll and P. J. Thomas, Nature, 1955, 176, 392KINETICS OF CHEMICAL CHANGE. 11and Gunning 48 considered that the reaction proceeded by a unimolecularelimination of hydrogen bromide. However, the observed rates were high,attributed by the authors to failure to remove oxygen. Maccoll and Thomascomment 49 on this, suggesting that oxygen could not increase the rate of anintramolecular elimination, but could increase the rate of a concurrentchain process ; the measurements 48 do not exclude this p0ssibility.4~Laurie and Long 50 pyrolysed dimethylmercury in a static system between294" and 333", finding a homogeneous first-order decomposition withA = 1.9 x 1014 sec.-1.The rate-determining step appears to be 51 thebreaking of an Hg-C bond and the value of the activation energy, 51-3 & 0.5kcal. mole-1, is in excellent agreement with determinations 52 by flow methods.The energy of dissociation for the second Hg-C bond is very low, 6-5 & 3kcal. mole-1.Walters and his co-workers have examined the thermal decomposition ofcyclobutanone and cyclopentanone.5q That of cyclobutanone is homo-geneous and simple, with a first-order velocity constant given by 3-6 x 1014exp (-52,WO/RT) sec.-l between 333" and 373". The products are ethyleneand keten.By contrast, the decomposition of cyclopentanone shows aninduction period (by pressure measurements and by chemical analysis), andproducts appear from breaking and dehydrogenation of the ring. Waltersand Bittker 55 find that the decomposition of trimethylene oxide between420" and 460" is homogeneous and of order 1.0, with complex products;with inhibitors, the products are ethylene and formaldehyde, and the sameresidual rate is reached with nitric oxide, propene, or toluene. The activ-ation energy, 60 3 1 kcal. mole-1, is close to that for the decomposition ofcyclobutane. W e ~ t o n , ~ ~ from work on the decomposition of tritium-labelledcyclopropane, concluded that the critical co-ordinate (on the Slatermechanism) is C-H, not C-C.The toluene carrier technique has been used 57 to study the decom-position of ethane labelled with 14C, because at the temperature used (1000-1100" K) the toluene gives methane rapidly (in this connection, the warninggiven by Blades and Steacie 58 must cast doubt on some applications of thesimple toluene carrier technique).The activation energy found 59 forC,H,+2CH3* is between 85 and 89. The corresponding values ofA (7 x 1014 or 5 x 1015 sec.-l) are low (ref. 1, page 125).The same technique has been used to determine the bond energy of the0-0 bond in diacetyl peroxide 59 (29-5), propionyl peroxide 6o (30.0), andbutyryl peroxide 6o (29.6 kcal.mole-1). These values may be compared with4 8 H. L. Friedman, R. B. Bernstein, and H. E. Gunning, J . Cltem. Phys., 1955, 23,4n A. Maccoll and P. J. Thomas, ibid., p. 1722.50 C . M. Laurie and L. H. Long, TtFans. Faraday Soc., 1955, 51, 665.31 L. H. Long, ibid., p. 673.s2 B. G. Gowenlock, J . C. Polanyi, and E. Warhurst, Proc. Roy. Soc., 1953, A , 218,260.5s M. N. Das, F. Kern, T. D. Coyle, and W. D. Walters, J . Arnev. Chem. Soc., 1954,54 E. R. Johnson and W. I). M'alters, ibid., p. 6266.6c, D. A. Bittker and W. D. Walters, ibid., 1955, 77, 1429.G6 K. E. Weston, jun., J . Chew. Phys., 1955, 23, 988.u7 C. H. Leigh, M. Szwarc, and J . Bigeleisen, J . Amer. Chem. SOC., 1966, 77, 2193.OU A. T. Blades and E.W. K. Steacie, Canad. J . Chem., 1954, 32, 1142.59 A. Rembaum and M. SzwarcIdem, J . Chenz. Phys., 1955,109.76, 6271.. Arne?,. Chem. SOC., 1954, 76, 5975.90912 GENERAL AND PHYSICAL CHEMISTRY.29.0 for four alkyl hydroperoxides and 31.7 for diethy! peroxide, and con-trasted with 36.0 kcal. mole-l for di-tert.-butyl peroxide, all obtained by thesame method. Another paper 62 on the kinetics of thermal decomposition oforganic peroxides has appeared.Acetaldehyde decomposes five 63 times as fast as does formaldehyde at476", but in the mixed gases the rates of decomposition are very nearly thesame, Both decompositions can be sensitised 63 by radicals from decom-posing ethylene oxide, and so clearly can proceed by chain mechanisms.Other studies on thermal decompositions include the detection of acetonein the pyrolysis of d i a ~ e t y l , ~ ~ the pyrolysis of organic esters,G5 the initiationof cracking of paraffins by addition of azomethane,G6 the effect of hydrogenpressure on the velocity of destructive hydrogenation of alkylben~enes,~~ andthe kinetics of thermal decompositions of paraffins in the presence ofacetylene 68 or divinyl.69Johnstonand his collaborators 70 have extended their studies of the decomposition ofnitric acid vapour to lower pressures, from 0.5 to 25 mm., and have investig-ated the effects of adding inert gases, nitric oxide, and nitrogen dioxide.The broad features of the decomposition are as found in earlier work.The thermal decom-position of nitric oxide between 1170" and 1530" K in quartz vessels has beenstudied by Kaufman and Kelso 71 by spectrographic analysis.Above1400" K the reaction is of the second order and independent of the surface :volume ratio or of added inert gases, and has an activation energy of63.8 & 0.6 kcal. inole-l. Added nitrous oxide produces a slight increase inthe rate of decomposition, so any chains are evidently very short. Kaufmanand Kelso 72 have similarly examined the reaction between nitric and nitrousoxide at 924-1028" K. The rate is directly proportional to the partialpressure of each gas, and the activation energy is 50 Ircal. mole-l.The oxidation of sulphur dioxide by nitrous oxide, between 680" and736", is a complex homogeneous reaction i3 with rate = k'[N,0]p45 +k'~[N,0]058[S0,].The mechanism may be a splitting of nitrous oxide,N,O _t N, + 00, together with a direct bimolecular reaction.A photometric study of the thermal reaction between nitrogen dioxideand hydrogen has been made by Ashmore and L e ~ i t t . ' ~ The reaction, whichyields nitric oxide and water, is rapid at about 400" C , and is inhibited byhydrocarbons and by nitric oxide. The rate law is given as : initial rate =Slow reactions involving oxides of nitrogen and their compounds.The oxidation of nitric oxide has been mentioneda3l61 J. R. Thomas, J . Amer. Chem. SOC., 1955, 17, 246.62 Ye. K. Varfohomeyeva, Ukrain. khim. Zhur., 1955, 21, 218.63 J. E. LongfieId and W. D. Walters, J . Amer. Chem. SOC., 1955, 77, 810.64 W.B. Guenther, C. A. Whiteman, and W. D. Walters, ibid., p. 2191.65 R. J. Lee, Diss. Abs., 1955, 15, 1173.66 A. D. Stepukhovich and V. V. Tatarintsev, Doklady Akad. Nauk S.S.S.R., 1954,67 M. G. Gonikberg and V. Y e . Kikitenkov, ibid., 1955, 102, 949.68 A. D. Stepukhovich, L. S. Stal'rnakhova, and V. V. Yeremin, Zhuv.fiz. Khinz.,A. D. Stepukhovich and L. V. Derevenskikh, ibid., p. 1720.70 H. S. Johnston, L. Foering, and J. R. White, J . Amer. Chern. SOC., 1955, 77, 4208,71 F. Kaufman and J. R. Kelso, J . Chem. Phys., 1955, 23, 1702.73 Idem, ibid., p. 602.73 T. N. Bell, P, L, Robinson, and A. B. Trenwith, J., 1955, 1440.74 P. G. Ashmore and B. P. Levitt, Nature, 1955, 176, 1013.99, 1049.1954, 28, 1878KINETICS OF CHEMICAL CHANGE. 13a/([NO] + b).a and b are of the first order with respect to NO,; a increasesas [H,]" where 1 < x < 1.5. However, as b decreases over much the samerange as [NO] increases during a run, the rate is nearly of the first order withrespect to [NOJ. It is rather extraordinary that this reaction betweensimple molecules has been so little studied previously.Gray has given a detailed review 75 of the reactions of free hydrocarbonradicals with nitrogen dioxide, relating the relative extents of formation ofR*NO,, ROONO, and ROO + NO* to the bond strengths C-N, C-0, and 0-Nin the alkyl nitrites and nitro-compounds. Adler, Pratt, and Gray 76 havediscussed the formation and fission of alkoxy-radicals during the pyrolyses ofalkyf nitrites, and present a useful table summarising the available inform-ation.Gray and Yoffe 5 have discussed other reactions of nitrogen dioxide.SZo3 oxidations involving 0xyge.n. The oxidation of ammonia has beefistudied by van Tiggelen ; '7 it has an activation energy of 50 kcal. mole-1 withor without hydrogen present, but is much faster with it present. The nitricoxide formed appears to inhibit the oxidation. The non-catalysed thermaloxidation of ammonia has also been studied by Blatz 78 and by Stephens.79The thermal oxidation of formaldehyde is thought by Homer, Style, andSummers 80, 81 to proceed by the same general scheme as the photochemicaloxidation except that chains are started as well as terminated on the walls.Their scheme, however, will not account 82 for all of the results of M. D.Scheer who prefers a scheme with H*CO and HCO, as chain carriers.Thekinetics of the slow oxidation of gaseous acetaldehyde and propionaldehydehave been described by Combe, Niclause, and Letort.=Satterfield and Reid 8p have examined earlier experimental work on thereactions of propyl radicals with oxygen to deduce the plots of In kJk,against 1/T where k, and k, are the respective velocity constants for(1) Prn* + 0, __t Prn*O*O* and (2) Prn* + O2 -+ C,H, + HO,., anddeduce E, - E , = 19 kcal. mole-l and PJP, - 4 x lo6. Cullis has out-lined 85 the r81e of free radicals in gaseous oxidations. There have beentwo short papers on the theory of oxidation of 87 Neimanand his co-workers have continued their investigations of the oxidation ofbutane at 306-330" c, by using 14CH,*CH0 to follow 88 the rate of form-ation of acetaldehyde, and also by studying 89 the formation of carbonmonoxide and dioxide.They have also studiedQ0 the accumulation ofperoxides and aldehydes during the Oxidation of hexa-2 : PHYSICAL PROPERTIES OF GASES, LIQUIDS, AND SOLUTIONS. 61its derivation by de Boer and Michel~,~o by P i t ~ e r , ~ l and by Guggenheim ' 9 92from the phase integral of classical statistical mechanics. The principle isobeyed by spherical molecules whose potentials contain only two variableparameters and for which the functional form of the potential is the Samefor all substances. ter Haarg3 has considered the applicability of thisrestriction to molecules with exponential repulsions.It has recently beenrealked that deviations from this principle are not random discrepanciesbut systematic differences which can give useful information about the shapesof intermolecular potentials. Riedel 94 and Pitzer 95 have made vevextensive empirical collations of the departures from the principle of thevapour pressure, orthobaric densities, surface tension, critical ratio, andcompressibility factor. These empirical collations compare very well withthose calculated theoretically by Cook and Rowlinson and by Hamann andLambert (see above).The solvent power of compressed gases was briefly reviewed two yearsago.1 Much new experimental work has since been published, particularlyon the technically important problem of the solubility of salts and quartzin steam at high pressure^.^^-^^ The expression for this solubility in termsof the virial equation of state is applicable only at comparatively low den-sities.It has been used by Ewaldw to measure directly the coefficient B,,for the interaction of xenon with helium, hydrogen, and nitrogen, and theinteraction of carbon dioxide with helium and hydrogen. It is probable thatthe solubility lo0 of carbon monoxide and nitrogen in compressed hydrogencould also be usefully expressed in terms of this equation of state. Thethird virial coefficient, C,,,, needed for such calculations has recently beencomputed l01 for a 12 : 6 inverse power potential.that the solvent effect of compressed gases on liquid mercury might affectseriously the accuracy of experimental work on the compressibility of gasesat high temperatures and pressures.Tsiklis lo3 has reported that binarygas mixtures can separate into two phases at high temperatures and pressures(above the critical temperatures of both components) if the molecules ofthe two components are of very different size or polarity, as in helium-ammonia, helium-propane, and argon-ammonia.There are equilibrium properties of a gas, other than the second virialcoefficient, which are functions only of the interactions of molecules inIt has been suggestedJ. de Boer and A. Michcls, Plzysica, 1938, 5, 945.91 K. S. Pitzer, J . Chent. Phys., 1939, 7, 853.92 E. A. Guggenheim, ibid., 1945, 13, 253.93 D. ter Haar, Physica, 1953, 19, 375.94 L.Riedel, Chcm.-l?zg.-Tech., 1954, 26, 83, 259, 679; 1955, 27, 209.*ti K. S. Pitzer, J . Amev. Ckcm. SOL, 1955, 77, 3427; K. S. Pitzer, D. 2. Lippman,K. F. Curl, C. M. Huggins, and D. E. Peterson, ibid., p. 3433.98 C. S. Copeland, J. Silverman, and S. W. Benson, J . Chem. Phys., 1953, 21, 12;S. W. Benson, C. S. Copeland, and D. Pearson, ibid., p. 2208.9 7 M. A. Styrilcovich, I. Kh. Khaibullin, and D. G. Tskhvirashvili, DokZady Ahad.Nabck. S.S.S.R., 1955, 100, 1123.98 J. Wyart and G. Sabatier, Compt. rend., 1955, 240, 2157.OD A. H. Ewald, Tvms. Favaduy SOC., 1955, 51, 347.100 2. Dokoupil, G. van Soest, and M. D. P. Swenker, AfipZ. Sci. Res., A , 1955,5, 183.101 J. S. Rowlinson, F. H. Sumner, and J. R. Sutton, Trans. Faruday SOC., 1954,102 W.€3. Jepson and J. S. Rowlinson, J . Ckenz. Phys., 1955, 23, 1599.10s D. S. Tsiklis, Doklady Akad. Nauk, S.S.S.R., 1952, 88, 993, 2159; 1955. 101,50, 1.129; D. S. Tsiklis and Y. N. Vasilev, Zkur. $2. Khim., 1955, 29, 153062 GENERAL AND PHYSICAL CHEMISTRY.independent pairs. One of the most interesting of these is the coefficientwhich measures the initial departure of the polarisation of a gas from(a + p2/3kT) with increasing gas density (where c( is the electron and atomicpolarisability and p the dipole moment). This coefficient is the polarisationanalogue of the second virial coefficient and, although it is generally onlyof the order of 10 ml./mole, successful measurements 103-107 of it have beenmade, and their interpretation is worth considering.Three effects contri-bute to this coefficient for non-polar molecules : (1) the electron polarisationof a molecule is directly affected by the presence of a neighbour, (2) whentwo molecules are close together the moment induced in the first by theapplied field induces an extra moment in the second, and (3) two moleculeswhich are initially both non-dipolar may develop induced dipoles in eachother's presence owing to the fields of their quadrupoles. The first effectis the least understood although there have been several discussions 108-110of it, mostly on the basis of the quantum mechanics of a polarisable systemconfined to a box. The second effect was first treated by Kirkwood 111for rigid spheres. More refined models have since been considered byde Boer and others 112 and by Buckingham and Pople.l13 The last authorshave also considered the third effect and shown that it is appreciable incarbon dioxide, owing to its large quadrupole moment.I n dipolar moleculesthe treatment is more complicated 114* 115 but it is clear that, given suffi-ciently accurate measurements, the coefficient can be a useful source ofinformation about the properties of molecules and the orientational com-ponents of intermolecular forces.The Theory of Liquids.-Two types of theory of the liquid state are stillbeing studied-the cell theory,4Q originally proposed by Lennard- Jonesand Devonshire, and the method 4u, based 011 a direct calculation of theradial distribution function proposed by Kirkwood and by Born and Green.The cell theory starts from the configuration-integral of classical statisticalmechanics, which is an integral over all the co-ordinates of all the molecules,and attempts to evaluate it by dividing the total volume into N cells, eachof which normally contains one molecule.This approximation enables anN-fold factorisation of the integral to be made and so greatly simplifies theproblem. Recent attempts to improve the crude theory have been madeby Dahler and Hirschfelder,llG by de Boer and others,l17 and by Barker.l18Dahler and Hirschfelder attempt to obtain the maximum accuracy froin a104 F. G. Keyes and J. L. Oncley, Chem. Rev., 1936, 19, 195.105 J. G. Miller, Trans. Amer. SOC. Mech. Eng., 1948, 70, 645.lo6 A. Michels and A.Botzen, Physica, 1949, 15, 769.107 H. G. David, S. D. Hamann, and J. F. Pearse, J . Chem. Phys., 1951,19, 1491.108 A. Michels, J. de Boer, and A. Bijl, Physica, 1937, 4. 981.100 S. R. de Groot and C. A. ten Seldam, ibid., 1947, 18, 47.110 L. Jansen and P. Mazur, ibid., 1955, 21, 193, 208.111 J. G. Kirkwood, J . Chenz. Phys., 1936, 4, 592.112 J. de Boer, F. van der Maesen, and C . A. ten Seldam, Physica, 1953, 19, 265.113 A. D. Buckingham and J. A. Pople, Trans. Faraday SOL, 1955, 51, 1029.114 F. E. Harris and B. J. Alder, J . Chetn. Phys., 1953, 21, 1351.1 1 5 A. D. Buckingham and J. A. Pople, Trans. Favaday Soc., 1955, 51, 1179.116 J. S. Daliler and J. 0. Hirschfelder, Univ. of Wisconsin Tech. Report ONR-12lli J. de Boer, Physica, 1954, 20, 655; E.G. I). Cohen, J. de Boer, and 2. 117.118 J . A . Barker, Aztstral. J . CheJn.. 1954, 7, 28; Proc. Boy. SOC., 1955, A , 230, 390.(1954); ONR-15, 17 (1955).Sslsburg, zbid., 1956, 21, 137PHYSICAL PROPERTIES OF GASES, LIQUIDS, AND SOLUTIONS. 63variation treatment proposed by Kirkwood l19-a treatment which is U-doubtedly an improvement on the crude theory but whose basis is, accordingto Barker,ll* not entirely satisfactory. de Boer and Barker consider, indifferent ways, the modifications which can be made to the crude theoryto remove the restrictions that only one molecule occupies each cell, thatthe cells are spherical, and that there is no correlation between the motionsof molecules in neighbouring cells. It is the last restriction which seemsto introduce most error.The direct determination of the pair (or radial) distribution function interms of temperature and volume would give all the thermodynamic pro-perties, but it cannot be found without previous knowledge of the tripletdistribution function.This, in turn, can only be found in terms of thequadruplet function, and so on. This infinite regression is avoided bymaking an assumption about the form of the triplet function, and muchrecent work has been an examination of this, the so-called " superposition "approximation. Thus, Nijboer and Frieschi 120 consider the effect of thisapproximation in an assembly of rigid spheres, where numerical results canbe obtained relatively easily, and so are able to test further the modificationsto the theory proposed by Rushbrooke and S ~ 0 i n s .l ~ ~ Alder, Frankel, andLewinson 122 have used the Monte Carlo method of computing to test theapproximation for the same assembly, but their test is not as searching asthat of Nijboer and Frieschi. This method of computing is a very directone in which the high speed of an electronic computer is used to enable thenumber of permissible arrangements of an assembly to be counted directly.The method is thus close to the fundamental method of statistical mechanics,but cannot, even with the largest machines, handle an assembly of N mole-cules. Instead, a small assembly of about 100 molecules is artificiallyassumed to extend indefinitely in space. M. N. Rosenbluth, A. W. Rosen-bluth, and others,lB who made the original applications of this method tothe calculation of the equation of state of fluids, were able to show that atwo-dimensional fluid composed of molecules with 12 : 6 potentials shows agas-liquid critical point at kTJe N- 1.(The experimental value for a three-dimensional assembly is about 1-25.) They were also able to obtain anaccurate equation of state for rigid spheres and to evaluate the fifth virialcoefficient with an accuracy of about 10%. However no adequate numericalsolution has yet been obtained for the radial-distribution function for athree-dimensional assembly of 12 : 6 molecules. This may be due to thesuperposition approximation, to the numerical methods of calculation, oreven, although this is less likely, to the inadequacy of the 12 : 6-p0tential.l~~Zwanzig lab has developed an ingenious method of calculating the equationof state at high temperatures for a potential similar to the 12 : 6 by treatingthe attractive forces as a perturbation of an assembly of rigid spheres.110 J .G. Kirkwood, J. Chem. Phys., 1950, 18, 380.l a l G. S. Rushbrooke and H. I. Scoins, Proc. Roy. Soc., 1953, A , 216, 203.122 B. J . Alder, S. P. Frankel, and V. A. Lewinson, J. Chem. Phys., 1055, 23, 417.lZ3 N. Metropolis, A. W. Rosenbluth, M. N. Rosenbluth, A. 13. Teller, and E. Teller,124 (a) H . W. Zwanzig, J . G. Kirkwood, K. 1;. Stripp, and I. Oppenfieim, ibid., 1953,B. R. A. Nijboer and R. Frieschi, Physzca, 1953, 19, 645.i6id., 1953, 21, 1087; M.N. Rosenbluth and A. W. Rosenbluth, ibad., 1954, 22, 881.21, 1268; 1954, 22, 1625; ( 6 ) R. W. Zwanzig, ibid., pp. 1420, 2099.lZ5 D~SCUSS. F ~ ~ a d a y SOC., 1953, 15, 108--11164 GENERAL A" MYSXCAL CHEMISTRY.L@id Solutions.-The theories of liquid solutions may similarly bedivided into two classes-those which are based on a cell (or lattice) modelof the liquid, and those which are not. The excess thennodynamic pro-perties of a binary mixture of substances I and 2 depend primarily on thesign and size of the differences (h12 - - %)/c12and (2a1, - all - cn)/cI2.However, the excess functions depend also on differences such as( E ~ ~ - E ~ ~ ) / E ~ ~ and {all - 022)/012 and on cross-terms involving both E and a.Although the terms in the expressions for the excess tlierrnodynamic func-tions proportional to these last differences are formally of a lower order ofmagnitude than those proportional to - E~~ - .z22)/c12, it does notalways fdlow that they are physically less important.I t is the principaladvantage of the lattice theories that, by assuming random mixing, theypermit explicit calculation (even if only approximately) of these second-order terms. One of the most striking successes of these theories, in thehands of Prigogine and his colleagues,126 has been the prediction that theexcess heat will be positive and the excess volume will be negative in solutionsfor which (cll - 022)/012 is zero or small and for which ( E ~ ~ - E ~ ~ ) / E ~ ~ islarge. If only first-order terms are retained then such a solution wouldhave ail its excess thermodynamic functions, A*G, A*H, A*S, and A*V,of the same sign.Experimental confirmation of the occurrence of oppositesigns for A*H and A*V for such solutions has recently been obtained bothfor non-polar and for pdar m i ~ t u r e s . ~ ~ ~ - ~ ~ l However, the theoretical basisand the quantitative predictions of lattice theories still leave much to bedesired.The extension to mixtures of the Kirkwood-Born-Green theory of fluidshas been made formally 132-134 but no quantitative results have yet beenobtained which could be compared with experiment, although Alder 135 hasobtained some interesting results for mixtures of rigid spheres.The theory of solutions put forward by Longuet-Higgins 136 was inde-pendent of any model of the liquid but permitted calculation of only the first-order terms discussed above in terms of known thermodynamic functions.It has since been shown that certain of the second-order terms which appearif the molecules are dipolar,13' or otherwisc non-~pherical,~~~ can be incor-porated in this treatment.This greatly increases the scope of the theoryand leads to a satisfactory interpretation of the behaviour of those solutionswhich form an azeotrope only over a limited range of temperature.13& A126 I. Prigogine, ref. 2, p. 301; I. Prigogine and A. Bellemans, Discuss. FavadaySot., 1953,15, 80 ; I. Prigogine and S. Lafleur, Bull. Classe Sci. Acad. roy. BeZg.. 1954, 40,484, 497; A. Englert-Chwoles, J . Chem.Phys., 1955, 23, 1168; cf. also P. Meares,ibid., 1954, 22, 955.127 P. Meares, Trans. Favaday SOC., 1949, 45, 966; 1953, 49, 1133.128 V. Mathot and A. Desmytcr, J . Chein. Phys., 1953, 21, 782; V. Mathot, L. A. K,129 R. Thacker and J. S. Rowlinson, ibid., 1954, 50, 1036.330 F. Kohler and E. Rott, hfonatslt., 1954, 85, 703.131 H. G. Markgraf and A. Nikuradse, 2. Naturforsch., 1954, 99, 27.132 G. S. Rushbrooke and H. I. Scoins, Phil. Mug., 1951, 42, 582; 1952, 43, 1276.133 J. G. Kirkwood and 2. W. Salsburg, Discuss. Faraday SOC., 1953, 15, 28.134 F. P. Buff and R. Brout, J . Chem. Phys., 1955, 23, 468.135 B. J. Alder, ibid., p. 263.136 H. C. Longuet-Higgins, PYOC. Roy. Soc., 1951, A , 205, 247.137 J . A. Barker, J . Chem. Phys., 1951, IS, 1430.138 J .S . Tcowlinson and J. R. Sutton, fa) Pvoc..Roy. SOC., 1955, A, %29, 271 ; (6) p. 396.Staveley, J. A. Young, and N. G. Parsonage, ibid., 1955, 23, 1551ELTON : COLLOID CHEMISTRY. 66mixture of spherical molecules of similar sizes either forms an azeotrope atall temperatures or never forms one, but a mixture of non-spherical moleculescan form an azeotrope over only a limited temperature range.Recent experimental work on solutions has been concerned more withheats and volumes of mixing than with vapour-pressure measurements.Many new calorimeters 129s 139-143 have been described, most of which aim atminimising errors due to evaporation by reducing the vapour space, andsome of which are designed for use over considerable ranges of temper-a t ~ r e .~ ~ ~ ~ ~ 1 4 1 3 142 It is becoming increasingly clear from this work, and fromwork on the temperature variation of other thermodynamic functions,lM, 145that none of the solutions commonly studied is the simple mixture of sphericalmolecules envisaged by most of the theories which have been developed inthe last twenty years. Even in solutions such as carbon tetrachloride-cyclohexane and benzene-dichloroethane the temperature variations of theexcess thermodynamic functions are probably too large to be treated by anyconsistent statistical theory which ignores non-central forces. Accuratework 145 has also shown to be unfounded the view that the excess func-tions for mixtures formed at constant volume would be simpler to interpretthan those of mixtures formed at constant pressure.In particular A*S, isprobably not appreciably smaller in most solutions than A*Sp. Indeed,there appear to be theoretical reasons 13& for regarding measurementsmade at constant pressure as being more directly related to the inter-molecular force-field than those made at constant volume.J. S. R.3. COLLOID CHEMISTRY.This topic was last the subject of a Report in 1952. Attention will beconfined mostly to the properties of lyophobic colloids.Adsorption of Ions from Solution.-Various papers 1-4 have appearedon the adsorption of ions by mercury, measurements being made by electro-capillary methods. Fluoride ions are not specifically adsorbed by mercury,2even when the mercury is anodic to the electrocapillary maximum.Manyother anions are, however, specifically adsorbed,l, even when the mercuryisnegatively charged.Parsons 5 has studied the form of the adsorption isotherm of iodide ionson mercury at constant surface charge, and concludes that the results arelS0 ( a ) G. H. Cheesmanand A. M. B. Whittaker, Proc. Roy. Soc., 1952, A , 217,406;(b) G. H. Cheesman and W. R. Ladner, ibid., 1956, 229, 387; (c) J. Canning and G . H.Cheesman, J.. 1955, 1230.I4O G. Kortum, G. Dreesen, and H. J. Freier, 2. Naturforsch., 1953, 8a, 546.141 A. E. Korvezee, L. H. Ruiter, and A. L. Stuyts, Rec. Trav. cltim., 1953, 72,462; L. H. Ruiter, ibid., 1955, 74, 1131.143 I. Brown and W. Fock, Aust~al. J . Chem., 1955, 8, 361.144 M. L. McGlashan, J. E. Prue, and I.E. J. Sainsbury, Trans. Faraday Soc., 1954,145 L. A. K. Staveley, W. I. Tupman, and K. R. Hart, ibid., 1955, 51, 323.146 E.g., J. H. Hildebrand and R. L. Scott, J . Chem. Phys., 1954, 20, 1520.M. A. V. Devanathan and P. Peries, Trans. Faraday SOC., 1954, 50, 1236.D. C. Grahame and B. A. Soderberg, J . Phys. Chem., 1964, 58, 449.R. Parsons and M. A. V. Devanathan, Trans. Faraday SOC., 1953, 49, 673.R. S. Maizlish, I. P. Tverdovskii, and A. N. Frumkin, Zhur.fiz. Khim.., 1954,28, 87.R. Parsons, Trans. Faraday Soc., 1955, 51, 1518.D. S. Adcock and M. L. McGlashan, Proc. Roy. SOC., 1954, A , 226, 266.50, 1284.REP-VOL. LIT 66 GESERAL AND PHYSICAL CHEMISTRY.best represented by an Amagat isotherm, or by an empirical square-rootisotherm, and not by a Langmuir isotherm, as assumed by Stern.6* Mirnikand Tezak * have shown that the adsorption of constituent ions by freshlyprepared silver iodide sols varies linearly with the logarithm of their activity.A similar relation has been found to hold for adsorption by fused ~ i l i c a , ~ andby carborundum lo from solutions of mineral acids.The adsorption of sulphate ions by iron surfaces has been studied, radio-active sulphur being used as a tracer.ll A limiting adsorption capacityequivalent to 0.35 of a monolayer was found.The extent of surface coveragewas also found to be always less than a monolayer for the adsorption ofiodide ions by iron,12 and for the adsorption of copper sulphate by copperand ~i1ver.l~ In the latter case, variation of temperature had little effect onthe extent of adsorption. Adsorption of silver sulphate by silver, and theaccompanying silver-exchange process have been studied l4 with radioactiveisotopes of sulphur and silver.Exchange occurs rapidly in the initial stages,and is later greatly retarded as the adsorbed ions interfere with the exchangeprocess.Bolt l5 has discussed in detail the validity of the Gouy-Chapman theoryof the structure of the diffuse part of the electrical double layer, with specialreference to the approximations and assumptions introduced. He concludesthat the effects of the various approximations tend to cancel one another out,so that the theory represents the structure of the diffuse layer better thanmight at first be expected.A solution of the Poisson-Boltzmann equationfor the electrical double layer of a single spherical colloid particle has beengiven,16 and the interaction of Gouy layers between two plane, parallel, non-conducting particles ca1c~lated.l~ The distribution of counter-ions in dilutesolutions of rigid, spherical, macromolecular ions, in the absence of addedsalt, has been considered theoretically.18Electrokinetic Phenomena.-Agreement between various methods ofdetermining electrokinetic potentials (c) has improved considerably in thepast few years, and, provided that proper attention is paid to corrections forsurface conductance, relaxation effects, etc., reliable results can be obtainedfrom measurements of electrophoresis, or of streaming potentials or electro-osmosis in single capillaries.If surface conductance is negligible, measure-ments of streaming potentials or electro-osmosis in diaphragms also givereliable results. The determination of c from measurements with diaphragmsin which the surface conductance is not negligible, or from measurements ofsedimentation velocities or potentials, is not yet so well established.Butterworths, London, 1954, pp. 153-157.6 R. Parsons in “Modern Aspects of Electrochemistry,” ed. J. O’M. Bockris,0. Stern, 2. Elektrochem., 1924, 30, 508,M. Mirnik and B. Tezak, ibid., 1954, 50, 65.D. P. Benton and G . A. H. Elton, Trans. Faraday SOC., 1953, 49, 1213.lo G. A. H. Elton and J . W. Mitchell, J., 1954, 741.l1 N. Hackerman and S. J . Stephens, J. Phys. Chew?., 1954, 58, 904.l2 2.A. Iofa and G. B. Rozedestvenskapa, Doklady Akad. Nauk S.S.S.R., 1953,l3 L. R. Scharfstein and C. V. King, J. Phys. Chem., 1954, 68, 180.l4 C. V. King and B. Levy, ibid., 1955. 59, 910.l6 G. H. Bolt, J. Colloid Sci., 1955, 10, 206.l6 N. E. Hoskin, Trans. Furuday SOC., 1953, 49, 1471.l7 E. C. Childs. ibid., 1954, 50, 1356.18 H. Fujita, J. Chew. Phys., 1955, 23, 837.91, 1159ELTON COLLOID CHEMISTRY. 67Overbeek and van Est l9 have deduced from theoretical considerationsthat < cannot be obtained by use of the Helmholtz-Smoluchowski equationfrom measurements of streaming potentials or electro-osmosis in diaphragms,unless surface conductance is negligible, or unless all capillaries in thediaphragm are of equal cross-section. Ghosh and his co-workers 20-24 have,however, used with some success a semiempirical method of correlatingresults obtained by either experimental technique with diaphragms ofdiffering permeabilities.Values of < calculated for Pyrex glass by thismethod 23 agreed well with those obtained from single capillarie~.~~ Ballou 26reports that the relation between electro-osmotic flow and hydrostaticpermeability in diaphragms of ltaolinite is compatible with the Helmholtz-Smoluchowski equation. There seems to be no doubt that the measurementof streaming potentials in diaphragms gives a method of determining theisoelectric points of solids2’ Overbeek and Wijga’s 28 theory for thestreaming potential set up in a system of capillaries of differing radii in serieshas been confirmed e~perimentally.~~A very large number of papers on electrophoresis has appeared.30 Tracerelectrophoresis has been used to determine the mobility of the Na+ con-stituent of sodium lauryl sulphate solutions.31 Electrophoresis measure-ments have been used in the study of the properties of minerals32 and ofbacterial spores.= Paine 34 has studied the electrophoretic mobility ofcupric oxide sols in solutions of potassium chloride and of copper sulphate,and has used Booth 35 and Overbeek’s 36 theory, which allows for relaxationeffects, to calculate the size of the particles. The effect of surface conduct-ance of the particles 373 38 was found to be negligible in this case.Electro-phoresis of various solid particles, and of water, in non-aqueous media hasbeen studied; 399 40 in this work, low field strengths must be used to avoidovershadowing of the electrophoresis (proportional to field strength E ) byelectrostatic phenomena (proportional to E2).Booth41 has given a detailed theory for the sedimentation potential set19 J. Th.G. Overbeek and W. T. van Est, Rec. Trav. chim., 1953, 72, 97.20 B. N. Ghosh, S. C. Rakshit, and D. K. Chattoraj, J . Indian Chem. SOC., 1953,21 B. N. Ghosh, Trans. Faraday SOC., 1953, 49, 1477.22 B. N. Ghosh, S . C. Rakshit, and D. K. Chattoraj, ibid., 1954, 50, 729.23 B. N. Ghosh, V. K. Choudhury, and P. K. De, ibid., 1954, 50, 955.24 B. N. Ghosh and S. Ghosh, J . Indian Chem. SOC., 1955, 31, 649.25 P. W. 0. Wijga, Thesis, Utrecht, 1946; quoted in ref.23.26 E. V. Ballou, J . Colloid Sci., 1955, 10, 450.2’ T. Abe, E. Sheppard, and I. S. Wright, J . Phys. Chem., 1955, 59, 266.Z 8 J . Th. G. Overbeek and P. W. 0. Wijga, Rec. Trav. chim., 1946, 65, 556.29 A. J. Rutgers and R. Janssen, T n s . Faraday SOC., 1955, 51, 830.30 A. Henley and C . L. Schuettler,31 K. J. Mysels and C. I. D u b , J . Colloid Sci., 1955, 10, 461.33 H. W. Douglas, ibid., 1955, 51, 146.34 H. H. Paine, ibid., 1955, 51, 995.35 F. Booth, Proc. Roy. Soc., 1950, A , 203, 514.36 J. Th. G. Overbeek, Kolloid-Beih., 1943, 54, 287.37 F. Booth, Trans. Faraday Soc., 1948, 44, 955.3* D. C. Henry, ibid., 1948, 44, 1021.9x1 J. L. van der Minne and P. H. J. Hermanie, J . Colloid Sci., 1952,7,600 ; 1953,8,38.40 H.Koelmanns and J. Th. G. Overbeek, Discuss. Faraday SOC., 1954, 18, 52.41 F. Booth, J . Chem. Phys., 1954, 22, 1956.30, 601.Electrophoresis Bibliography,” American Inst.Co., Silver Spring, Maryland, 1953.H. W. Douglas and D. Adair, Trans. Faraday SOC., 1954, 50, 125168 GENERAL AND PHYSICAL CHEMISTRY.up by spherical particles sedimenting in an ionic liquid. For particles whoseradius is much greater than the double-layer thickness, his equation reducest o the Smoluchowski equation. This equation has been tested by Eltonand who measured sedimentation potentials of glass and silicaparticles in aqueous solutions, using an apparatus similar to Quist andWa~hburn’s.4~ Hermans’s equation,& which attempts to allow for the effectsof surface conductance, does not give such satisfactory results.Centrifugation potentials have been measured for sols of arsenioussulphide 45 and silverfor the particles.Troelstra4’ has criticised this work on the grounds thatthe equation used in the calculation of c neglects relaxation effects, whichmay be important.Electrokinetic charges and potentials of glass,** silica,49* 50 and car-borundum 61 surfaces in various electrolyte solutions have been calculatedfrom the observed rates of sedimentation of very dilute suspensions of smallparticles of the solid in the solution. This is a relatively new and untriedmethod, but seems to give results in reasonable agreement with thoseobtained by established methods. The main labour involved is in obtaininga monodisperse suspension, and, when < is low, it is necessary to avoideffects due to coagulation.Elton 52 proposed a simple equation governingthe rate of sedimentation; a more refined mathematical treatment forspherical particles has been given by B0oth.~1Measurements are reported of the surface conductivity in water ofquartz, corundum, rutile, cassiterite, and haematite.% Results for quartzand corundum agree fairly well with those calculated on the assumption thatthe surface conductance is due entirely to the extra concentration of ions inthe diffuse layer, but the other oxides show much higher surface conductivi-ties than are predicted by this method. on the basis ofsemiconducting properties.There is at present no reliable information concerning the variation ofelectrokinetic properties with temperature.Stability of Lyophobic Colloids.-Most theoretical work on the stabilityof lyophobic colloids is based on Derjaguin’s theory,= as used by Venveyand O ~ e r b e e k .~ ~ Levine 56 has used an electronic computing method totest Derjaguin’s approximate equation for the energy of interaction of theelectrical double layers of two identical spherical particles. Levine’scalculation, which was based on a numerical solution of the appropriateand the results have been used to calculateThis is explained4 2 G. A. H. Elton and J. B. Peace, J., 1956, 22.43 J. D. Quist and E. R. Washburn, J . Amcr. Chem. SOC., 1940, 62, 3169.44 J J. Hermans, Phil. Mag., 1938, 26, 650.46 G.Jacobs, Trans. Faraday SOC., 1952, 48, 355.4 6 A. J. Rutgers and P. Nagels, Nature, 1953, 171, 568.4 7 S. A. Troelstra, Ann. Rev. Phys. Chem., 1954, 5, 291.48 G. A. H. Elton and F. G. Hirschler, J., 1952, 2953.4s C . I. Dulin and G. A. H. Elton, J., 1952, 286; 1953, 1168, 2099; 1954, 1324.50 D. P. Benton and G. A. H. Elton, J., 1953, 2096.51 G. A. H. Elton and J. W. Mitchell, J., 1953, 3690.52 G. A. H. Elton, J . Chem. Phys., 1951, 19, 1317.59 D. J. O’Connor, N. Street, and A. S . Buchanan, Austval. J . Cheni., 1954, 7, 245.54 B. V. Derjaguin, Trans. Faraday SOC., 1940,,‘ 36, 203, 360.56 E. J. W. Verwey and J. Th. G. Overbeek, Theory of the stability of lyophobiccolloids,” Elsevier, Amsterdam, 1948.$. Levine, Discuss. Faraday SOC., 1954, 18, 187ELTON : COLLOID CHEMISTRY.69Poisson-Boltzmann equation , demonstrated that Derj aguin’s equation givesa good approximation for the electrical energy of interaction in the range ofparticle separations which are relevant to stability properties. Calculationsof the electrostatic forces between non-identical colloid particles have been1nade,~7-~~ and the coagulation of non-identical colloid particles disc~ssed.~7Venvey and Overbeek’s theory has been developed for plate-like particles ; 6othe equations obtained provide an explanation of the Schulze-Hardy rule.While there is a good measure of agreement between various workersconcerning the repulsive forces produced by double-layer interaction, theposition concerning the magnitude of the van der Waals attractive forcesbetween colloid particles is much less satisfactory. The theoretical value ofthe Hamaker 61 force constant, A , for glass or quartz 62 is about 10-l2 erg.Reerink and Overbeek 63 obtained values of A of the order of erg bycalculations based on measurements of the kinetics of coagulation of silveriodide and other sols, but these calculations have been criticised by M i r n d ~ .~Overbeek and Sparnaay 65 used a sensitive microbalance to measure theforce of attraction between flat glass plates in vacuo, and obtainedA h 4 x 10-11 erg, while Derjaguin et aZ.,66 using rather similar apparatus,obtained the result A < 5 x lO-l* erg. Howe, Benton, and Puddington 67obtained A == lO-l2 erg from measurements of the force of adhesion betweena glass sphere and a glass plate, using a sensitive pendulum-type apparatus.Until these wide discrepancies between values of A , determined by differentmethods and by different experimenters, can be resolved, it will be impossibleto predict the net energy of interaction between colloid particles, and itsvariation with distance of separation.This appears to be the outstandingproblem in the theory of colloid stability at present.Several studies of the kinetics of slow coagulation of colloids have been6&70 Experimental results are usually interpreted in terms ofthe Smoluchowski equation for slow coagulation, although the systems oftendo not satisfy all the assumptions made in the derivation of the equation,e.g., the particles are often not spherical either before or after coagulation.followed the coagulation of silver iodide solsby a turbidimetric method.Sols prepared in various ways were used, andvarious coagulating electrolytes studied. By assuming the efficiency ofcollision to be unity for particles undergoing rapid coagulation, the efficiencyof collision in any given system where slow coagulation was occurring wascalculated. In all cases, the logarithm of the collision efficiency variedReerink and Overbeek67 B. V. Derjaguin, Discuss. Faraday SOC., 1954, 18, 85.58 A. Bierman, J. Colloid Sci., 1955, 10, 231.be idem, Proc. Nut. Acad. Sci. U.S., 1955, 41, 245.6o E. J. W. Verwey, Kolloid Z., 1954, 136, 46.61 H. C. Hamaker, Physica, 1937, 4, 1058.H. Margeneau, Rev.Mod. Phys., 1939, 11, 1.H. Reerink and J . Th. G. Overbeek, Discuss. Faraday SOC., 1954, 18, 74.M. Mirnik, ibid., p. 204.6 5 J . Th. G. Overbeek and M. J . Sparnaay, J. Colloid Sci., 1952, 7, 343; Discuss.6 6 B. V. Derjaguin, A. S. Titijevskaia, I. I. Abricosova, and A. D. Malkina, ibid.,6 7 P. G. Howe, D. P. Benton, and I. E. Puddington, Canad. J. Chem., 1955, 33, 1375.6 8 Amal K. Bhattacharya and Abani K. Bhattacharya, Kolloid 2.. 1955, 141, 95.69 M. van den Tempel, Rec. Trav. chim., 1953, 72, 419, 433, 442.70 A. S. C. Lawrence and 0. S. Mills, Discuss. Favaday Soc., 1954, 18, 214.Faraday SOC., 1954, 18, 12.1954, 18, 2470 GENERAL AND PHYSICAL CHEMISTRY.linearly with the logarithm of the electrolyte concentration, in agreement witha theoretical prediction for sols of monodisperse, spherical particles.Sincethe particles in the silver iodide sols were neither spherical nor monodisperse,the obtaining of the predicted linear relation was assumed to be due to acancelling of errors. The coagulation of arsenious sulphide sols by lithium,sodium, and potassium chlorides has been studied by a viscometric method,6sthe time of coagulation t being taken as the time at which there was a pointof inflexion in the -q-t curves. Plots of l / t against the electrolyte concentra-tion, gave, as intercept on the l / t axis, the critical stability concentration ofelectrolyte.Van den Tempe1 69 showed that coagulation of an oil-in-water emulsionmay occur in two main stages : (1) flocculation to form aggregates ofspherical droplets, a second-order process, governed by double layer effects,and obeying the Schulze-Hardy rule, and (2) coalescence within the aggre-gates, a first-order process, governed by the structure of the interfacialfilm at the oil-water interface.The magnitudes of the energy barriers forthe two processes were calculated from experimental results. Lawrenceand Mills 70 studied coagulation of emulsion droplets under conditions wherethe effect of clustering of droplets in aggregates was negligible, and sphericaldroplets were almost invariably formed after fruitful collisions. The resultsagreed with the predictions of the Smoluchowski equation, and in this casealso the energy barrier to collision and coalescence was calculated forstabilised and unstabilised emulsions.Wiley 71 observed the occurrence oflimited coalescence in coarse oil-in-water emulsions, the droplets growingto a definite limiting size, after which further growth ceased. A necessarycondition was the presence of a water-dispersible colloid, or of a finely-dividedsolid of high molecular weight.Tezak and his co-workers have continued their studies of the stabilityof colloids in statu nascendi, and experiments are reported on sols of silverhalides 72-74 and of ferric hydr0xide.7~ Similar studies have been made bySloan 76 with barium sulphate. Tezak 72 explains the Schulze-Hardy rulein terms of Bjerrum’s ion-pair theory, assuming that at electrolyte concen-trations sufficient to bring about coagulation the double layer is effectivelysuppressed by ion-pair formation between its constituent ions.As evidencefor this, a linear relation between the logarithm of the coagulation valuesand the Bjerrum critical distance is found for many colloidal systems, bothin water and in aqueous organic mixtures.Booth 77 has derived equations governing the kinetics of coagulation ofnon-spherical particles undergoing Brownian motion. For spheroidalparticles, fairly exact expressions for the mutual coagulation rate can begiven for systems which contain only particles of two types, these differingappreciably in size.Jonker and Kruyt 78 describe a new type of coarsening in freshly-71 R. M. Wiley, J . Colloid Sci., 1954, 9, 427.7 2 B. Tezak, Discuss.Faraday SOC., 1954, 18, 63.73 J . Herak and B. Tezak, Arhiv Kern., 1954, 26, 1.7 4 B. Tezak, E. Matijevic, and I<. F. Schulz, .I. Phys. Chem., 1955, 59, 769.76 B. Tezak and R. Wolf, Arhiv Kern., 1953, 25, 39.76 C. K. Sloan, J. Phys. Chem., 1955, 59, 834.7 7 F. Booth, Discuss. Furaday Soc., 1954, 18, 104.7 8 G. H. Jonker and H. R. Kruyt, ibid., 1954, 18, 170ELTON : COLLOID CHEMISTRY. 71prepared, very dilute silver bromide sols. This occurred in the region ofnormally stable negative sols, and was attributed to a recrystallization toform ideal crystals, followed by an oriented flocculation, which can give a muchgreater decrease of free energy than flocculation to form random aggregates.Semiquantitative studies of the stabilities of sols in non-aqueous disper-sion media have been reported.7s82 Koelmanns and Overbeek 82 concludefrom a theoretical discussion that double-layer effects are unlikely to be largeenough to produce stabilisation except in the case of coarse particles (radiusgreater than 1 p).Stability is usually low unless other stabilising influencesare present (e.g., the entropic effect of hydrocarbon chains has been suggestedas an explanation of the effect of non-ionic stabilisers).79, 82Aerosols.-Methods of determination of particle-size distributions inaerosols (and other disperse systems) have been reviewed.= Most attentionis at present devoted to determination of size distribution from measurementsof light scattering; 83-85 the comparatively new “ diffusion battery ”method 86 is capable of giving accurate results for particles of radius lessthan 0.3 p.Larger particles may be collected in a suitable manner 83 (e.g.,by use of a cascade impactor 87-s9) and examined by optical or electronmicroscopy,=, or by X-ray diffraction.91 Methods for the identificationof aerosol particles collected from the atmosphere, by means of chemicaltests under the microscope, have been de~cribed.9~ Permanent records ofthe size distribution of aerosols of water droplets can be obtained by impact-ing them on to slides coated with gelatin containing Naphthol-green dye.93Each droplet forms a stain of radius proportional to the droplet radius;the method has to be calibrated by using drops of known radius.The filtration of aerosols is of increasing importance, owing partly to theincrease of atmospheric p o l l ~ t i o n , ~ ~ ~ 94 and a detailed review on the filtrationof aerosols by fibrous media has a~peared.~5 Fundamental studies of theadhesion of aerosol droplets and particles to solid surfaces (of importance infiltration) have been reported,96> 97 and the effect of electrification of aerosol79 E.L. Mackor and J. H. van der Waals, J. Colloid Sci., 1952, 7, 535.8o J. L. van der Mime and P. H. J. Hermanie, ibid., 1953, 8, 38.81 Y. M. Glazman, Colloid J. (U.S.S.R.), 1953, 15, 231.82 H. Koelmanns and J. Th. G. Overbeek, Discuss. Faruduy Soc., 1954, 18, 52.83 R. D. Cadle, ‘‘ Particle size determination,” Interscience Publishers, Inc., New84 W. Heller, J. Chenz. Phys., 1955, 23, 342; F.T. Gucker and A. H. Peterson,“ Handbook of Aerosols,’’ U.S. Atomic Energy Commission, Washington, D.C.,York, 1955.J . Colloid Sci., 1955, 10, 12.1950.86 J. W. Thomas, J . Colloid Sci., 1955, 10, 246.87 K. R. May, J. Sci. Instr., 1945, 22, 187.L. S. Sonlun, J . Ind, Hyg. and Toxicol., 1946, 28, 269.G. R. Gillespie and H. F. Johnstone, C h e w Eng. Pmgr., 1955, 51, 74F.J . P. Lodge and B. J . Tufts, J. Colloid Sci., 1955, 10. 256.91 J. E. Manson, J. Appl. Phys., 1955, 26, 423.9z “The Smog Problem in Los Angeles County,’’ Stanford Research Institute,Stanford, California, 1954.93 N. F. Wootton, Porton Technical P u p s , 1955, No. 506.94 S. J . Davenport and G. G. Morgis, Air Pollution-” Bibliography.” BulletinNo.537, U.S. Bureau of Mines, Washington, D.C., 1954; J. B. Murk, Ind. Eng. Chenz.,1955, 47, 976.9B C. Y. Chen, Chem. Rev., 1955, 55, 595.s6 T. Gillespie and E. K. Rideal, J. Colloid Sci., 1955, 10, 281.97 T. Gillespie, ibid., p. 26672 GENERAL AND PHYSICAL CHEMISTRY.particles 989 99 on the efficiency of filtration discussed.looJ lo1 Electrificationof aerosol particles decreases their tendency to penetrate filters, the effectincreasing as the particle size decreases.The coagulation of many smokes, the particles of which are in Brownianmotion, follows the Smoluchowski equation for rapid c0agulation,8~ indicat-ing that the energy barriers to collision and adhesion of the particles arenegligible. However, for water droplets of radius greater than about 1 P(where Brownian motion is negligible compared with motion under gravity)there is theoretical and experimental evidence 102-105 that collision andcoalescence efficiencies are not usually unity, indicating that energy barriersto collision and coalescence exist.The magnitudes of these barriers dependon the sizes of the colliding particles,lO2$ lo5 the relative humidity,lo3 and theproperties of the electrical double layer at the water-air interface.lo4G. A. H. E.4. SPECTROSCOPY AND MOLECULAR STRUCTURE.The present Report reviews the literature on ultraviolet, infrared, Raman,microwave, and radio-frequency spectroscopy that appeared during the pastyear. High-resolution nuclear magnetic resonance spectra of liquids andsolutions have been included, but analogous work on solids will be dealtwith in the section on crystallography. As electronic spectra are treated for thefirst time in two years it has proved impossible to report on non-spectroscopictopics, e.g., dipole moments, electron diffraction, paramagnetism, and massspectrometry.Electronic Spectra.Introduction.-The last five years have seen a marked increase in thestudy of molecular electronic spectra.This has been prompted largely bya rapid expansion of the field of valency theory, for which experimentallydetermined energies, symmetry-types of excited electronic states, andtransition oscillator strengths provide the most direct and exacting tests.Such determinations are difficult and form the greater part of recent efforts,for the number of excited states which have been unambiguously identifiedin polyatomic molecules is still quite small.Two other subjects receivingmuch attention recently are the detection of short-lived species, e.g., freeradicals ; and the spectra of transition-element complexes. The presentstatus of the theory of electronic structures of molecules has been treated inan excellent review by Parr and Ellison,l and an extensive review by Sponerdeals with electronic spectroscopy up to the end of 1954. A book by Gillamand Stern 3 gives a general account of the spectra of organic compounds andtheir relations to molecular structures; attention is drawn to a report *98 B. L. Hinkle, C. Orr, and J. M. DallaValle, ibid., 1954, 9, 70.99 R. Gum, ibid., 1955, 10, 107.100 T. Gillespie, ibid., p.299.101 G. G. Goyer, R. Gruen, and V. K. LaMer, J . Phys. Chem., 1954, 58, 137.lo2 I. Langmuir, J . Meteorology, 1948, 5, 175.lo$ P S. Prokhorov, Discuss. Faraday SOL, 1954, 18, 41.lo4 G. A. H. Elton, ibid., 1954, 18, 216.106 D. Sartor, J . Meteorology, 1954, 11, 91.1 R. G. Parr and F. 0. Ellison, Ann. Rev. Phys. Chern., 1955, 6, 171.2 H. Sponer, ibid., p. 193.A. E. Gillam and E. S. Stern, “ An Introduction to Electronic Spectroscopy inJoint Commission for Spectroscopy, J . Chern. Phys., 1955, 23, 1997.Organic Chemistry,” Edward Arnold, London, 1954SPECTROSCOPY AND MOLECULAR STRUCTURE. 73dedicated to unifying the notation for spectra of polyatomic molecules.The present Report is confined to selected topics from the literature of 1955.Experimental Techniques.-Considerable advances have greatly helpedthe expansion mentioned above, mainly in two directions.First, thevacuum-ultraviolet region below ZOOOA, in which lie most of the spectraof the simpler and hence more interesting molecules, has become much moreaccessible. An extensive review is given by Inn.5 Discharges maintainedin the rare gases at pressures of the order of 100 mm. by means of micro-wave radiation or condensed potentials are very good sources of continuousradiation over limited ranges of the shorter wavelengths, depending on thegases used. Xenon, krypton, and argon cover the range down to 1000 A.A modified Lyman-type source requiring no filler-gas and a convenientform of hydrogen discharge tube for longer wavelengths have also beendescribed.Hitherto, resolving power has always been limited becausevacuum-grating instruments could only be used in the first order; thisdifficulty has been partly overcome by the use of lithium fluoride cylindricallenses which act both as condenser and, used off-axis, as f~re-prism.~ Thusblazed * concave gratings can be used down to 1300 A with high efficiencyin up to the fourth order, giving resolving powers lo up to 200,000, or less than0.5 cm.-l. Wilkinson l1 gives measurements of 245 atomic lines as pro-visional wavelengths standards in the vacuum region.Secondly, through Bausch and Lomb’s acquisition of the Chicago ruling-engine, many new concave and plane replica gratings of a very high quality,both of blaze and resolving power-up to 200,000 in the first order 12-haverecently come into use.New mounts, e.g., that of Ebert,13 or cameras, e.g.,that of Schmidt with refracting corrector-plate and high speed,14 have beentried. To be used to the full, such large instruments require extremelyaccurate wavelength calibration and a new type of hollow-cathode irondischarge tube has therefore been devised.15 This gives an iron arc spectrumwith very sharp lines of constant and easily controlled intensity. Part ofthe spectrum from this source has been measured interferometrically.16 Therefractive index of air has also required revision.17 Other methods of obtain-ing high resolution use echelles,l8 or Fabry-Perot interferometers ; relativemerits are discussed by Ja~quin0t.l~ A method of measuring resolvingpower experimentally is given by Rank.20E. C.Y . Inn, Spectrochim. Acta, 1955, 7, 65.P. G. Wilkinson and Y. Tanaka, J . Opt. Soc. Amev., 1955,45, 344,710, 1044,1075.J. Romand, G. Balloffet, and B. Vodar, Compt. rend., 1955, 240, 412.G. Milazzo, Mikrochim. Acta, 1955, 542.P. Brix and G. Herzberg, Canad. J . Phys., 1954, 32, 110.lo E. Miescher, ibid., 1955, 33, 355.l1 P. G. Wilkinson, J . Opt. SOC. Amer., 1955, 45, 862.l2 A. E. Douglas and C. K . Maller, Canad. J. Phys., 1955, 33, 125.lS R. F. Jarrel, J. Opt. SOC. Amer., 1955, 45, 259.l4 C . Moser, ibid., 1954, 44, 660; ref. 29.l5 H. M. Crosswhite, G. H. Dieke, and C. S. Legagneur, ibid., 1955, 45, 270.l6 R.W. Stanley and G. H. Dieke, ibid., p. 280.l7 B. EdlCn, ibid., 1953, 43, 339.G. R. Harrison, S. P. Davis, and H. J. Robertson, ibid., p. 856.lS P. Jacquinot, ibid., 1954, 44, 761.2o D. H. Rank, J. N. Shearer, and J,.,M. Bennet, ibid., 1955, 45, 762. * A grating is said to be “blazed if the profiles of its rulings are cut so thatdiffracted light of any particular wavelength is concentrated mostly into one orderonly74 GENERAL AND PHYSICAL CHEMISTRY.Diatomic Molecules.-Those formed from the elements up to neon areof special importance, as they form one of the foundation-stones of molecularvalency theory. Measurements on hydrogen and deuterium molecules havebeen extended into the infrared region ; new attempts to analyse Schuler'sOH and OD system 22 are still not satisfactory, for the lower state is eitherperturbed or observed only near the dissociation limit.Several new statesof CN and CN+ have been found,23 but the dissociation energy has not yetbeen settled. New sources of the Vegard-Kaplan 24 (A3C--X1X) and Gay-don Green 25 systems of nitrogen have been described, the latter free fromthe usually overlapping First Positive bands, and the absorption spectrummeasured26 down to 1075a. There are new measurements on nitricoxide : rotational analysis lo has shown the B state to be ,Ai (formerly 211i),and new vibrational analyses of measurements 27 between 1300 and 6000bring the number of known excited doublet states to 12. An emissionsystem in the infrared region is ascribed to quartet 29 The spectrumof NO+ has also been analysed.1°Because of their importance in many t hermochemical cycles, ground-state dissociation energies Do continue to receive much attention.That ofthe oxygen molecule has been finally decided purely spectroscopically(117.96 3 0.04 kcals./mole) ; but, as is well known, in most cases thespectroscopic method gives a number of possible values, each quiteaccurately, with no way of deciding between them unless the products ofobserved dissociations can be identified, which is rarely possible. A choicebetween the two possible values for the nitrogen molecule has now beenmade by two essentially thermal methods; in 0ne,~0 the concentration ofnitrogen atoms in nitrogen gas at 3400" K is measured with an atomic-beamapparatus, and the lower value of Do excluded; in the 0ther,~1 which usesshock waves through nitrogen gas, this concentration is effectively measuredup to 12,000" K and the higher value (225.1 kcal.) confirmed.The valuesfor nitrogen and oxygen fix that of nitric oxide at 149 kcal./m~le.~, 29s 32That for carbon monoxide, with its bearing on the heat of sublimation ofgraphite, is still in doubt, although the possibilities have been reduced.12Other molecules whose spectra have been described or newly found are :PO, ?O+, PS, PS+, P,, NS+,33 Si,;34 AlF,35 InF,36 BrF,37 MnF, MnCl,21 S. P. S. Porto and G. H. Dielte, J . Opt. SOC. Amer., 1955, 45, 447.22 S. Benoist, Ann. Phys., 1955, 10, 363.23 A. E. Douglas and P. M. Routley, Astrophys.J., 1954, 119, 303; ibid. (Suppl.24 N. D. Sayers, G. R. Taylor, and K. G. Emelkus, Nature, 1955, 175, 254.Z 5 A. E. Griin, 2. Naturforsch., 1954, 9a, 1017.26 Y . Tanaka, J . Opt. SOC. Amer., 1955, 45, 663.27 M. Ogawa, Sci. Light, 1955, 3, 90; M. Ueda, ibid., p. 143.28 M. Ogawa, ibid., 1954, 3, 39.2Q M. Brook and J. Kaplan, Phys. Rev., 1954, 96, 1540.30 J. M. Hendrie, J . Chem. Phys., 1954, 22, 1503.31 R. H. Christian, R. E. Duff, and I;. L. Yarger, ibid., 1955, 23, 2045.s2 Y . Tanaka, ibid., 1954, 22, 2045.33 K. Dressler, Helv. Phys. Acta, 1955, 28, 563.34 ( a ) A. E. Douglas, Symposium on Molecular Structure and Spectrascopy, Colum-bus, Ohio, June, 1955; ( b ) Canad. J . Phys., 1955, 33, 801.35 P. G. Dodsworth and R. F. Barrow, Proc.Phys. SOC., 1955, 68, A , 824; S. M.Naud6 and T. J. Hugo, Canad. J . Phys., 1955, 33, 573.36 R. F. Barrow, D. V. Glaser, and P. B. Zeeman, Proc. Phys. Soc., 1955, 68, A , 962.37 P. H. Brodersen and J. E. Sicre, 2. Physik, 1955, 141, 515.Ser.), 1955, 1, 295; P. K. Carrol, Canad. J . Phys., 1956, 34, 83SPECTROSCOPY AND MOLECULAR STRUCTURE. 75MnBr ; 38 Cu,, Ag,, Au, ; 39 CrH ; 40 Ba0,41 Zr0,42 V0,43 and Ta0.44 Herz-berg has reviewed 45 the role of diatomic molecules in comets and interstellarmatter.Simple Polyatomic Molecules.-An increasing number of free radicals,whose electronic spectra have been identified, come under this heading, forelectronic spectroscopy offers many advantages for their detection. First,the method of flash photolysis 46 allows the electronic absorption spectraof short-lived molecules (> 20 psec.) to be recorded photographically, andthe effects of relatively high concentrations of short duration integrated.Secondly, only small partial pressures of radicals are needed, for the absorb-ing path may be lengthened with multi-reflection mirror systems; 47 and inbands with rotational fine-structure, unlike in the microwave region, somepressure-broadening increases the sensitivity, which is greatest when theline-width equals the resolving power of the recording spectrometer.Thirdly, the electronic spectra of radicals, unlike their vibrational infraredspectra, usually lie in different wavelength regions from those of the parentmolecule ; and fourthly, because of a frequency-factor in the expressions forabsorption coefficients, electronic spectra are relatively intense. Most ofthese points apply also to other sources, such as discharges and furnaces.To the free radicals whose spectra were known previously, i.e., C3?,,4sC, (13C3),49 HCO (DCO),47 NH, (ND,; 15NH2),m have been added PH,(PD,),51 CaOH (CaOD),52 and The spectrum of the first of thesethree was detected by flash photolysis, and is analogous to the a-bands ofNH,; the second was found in an arc.The third spectrum was found in acarbon furnace containing silicon, and its assignment to Sic, (analogousto C,) is based on vibrational analysis. Its bands are identical with theso-called Sandford bands known previously in the spectra of certain carbon-type stars.In the same experiments which produced the Ramsay bands ofHCO and DC0,47 two bands of a second discrete system of DCO were observednear 7500 A. The corresponding system of HCO could not be found; butits expected appearance could be calculated from the rotational constantsderived from the DCO bands. Apart from a gross shift due to zero-pointenergies, which cannot be calculated because of insufficient vibrational databut which is reasonable, the calculated spectrum for HCO agrees remarkablywith one discovered by Kuiper in the planet Uranus.45 Thus it seems prob-able that HCO joins NH,, C,, and Sic, among unstable polyatomic moleculesknown from outside the earth.38 W. Hayes and E. E. Nevin, Proc. Phys. SOC., 1955, 68, A , 665, 1097.40 B.Kleman and B. Liljeqvist, ibid., p. 346.41 L. Huldt and A. Lagerqvist, ibid., p. 227.42 U. Uhler and L. Akerlind, Naturwiss., 1955, 42, 438.d3 A. Lagerqvist and L.-E. Selin, ibid., p. 66.44 D. Premaswarup, Nature, 1955, 175, 1003.45 G. Herzberg, Mem. SOC. Roy. Sci. Liige, 1955, 15, 291.46 R. G. W. Norrish, G. Porter, and B. A. Thrush, Proc. Roy. Soc., 1953, .4, 216, 165.4 7 G. Herzberg and D. A. Ramsay, ibid., 1955, A, 233, 34.48 R. K. Laird, E. B. Andrews, and R. F. Barrow, Trans. Faraday SOC., 1060,46, 803.4g K. Clusius and A. E. Douglas, Canad. J. Phys., 1954, 32, 319.50 G. Herzberg and D. A. Ramsay, Discuss. Fuvaday SOC., 1953, 14, 11.51 D. A. Ramsay, paper presented at a meeting of the Canadian Royal Society, 1955.52 A. G.Gaydon, Proc. Roy. SOC., 1955, A , 231, 437.53 B. Kleman, ref. 34a; Astrophys. J., 1956, 123, 162.B. Kleman and S. Lindqvist, Arkiv Fys., 1954, 9, 38576 GENERAL AND PHYSICAL CHEMISTRY.Discharge tubes of the type developed by Schiiler have been anotherpromising source of free-radical spectra. Here, however, the major difficultylies in identifying the molecules whose spectra are observed,% for they maybear little relation to the starting materials. Thus, the carrier of Schuler's" V " spectrum is still in doubt, but is thought to be either C,H,*C 55 orC6H5*CH,.56 His " T " found with substances as diverse asacetylene and naphthalene, has been shown 58 to be due to the (linear)diacetylene ion C,H,+. Two new spectra, " C " and " D ", extending from5200 to 8500 A have been found in a high-frequency discharge maintainedin ammonia at pressures up to an atmosphere.The " C '' spectrum, nowfree from the usually overlapping a-bands, includes the long-known " Schusterband of ammonia," 6o and partially resolved rotational structure and isotopicshifts suggest that the carrier contains hydrogen and more than one atom ofnitrogen.Attempts to identify the electronic states of a spectrum unambiguouslyinvolve two problems : the determination of the nuclear equilibrium con-figurations of the states, i.e. molecular symmetries ; and the directionsrelative to these symmetries of the total electronic angular momenta (not tobe confused with permanent dipole moments), i e . electronic symmetries.The first is specifically mentioned here because it is being found in an in-creasing number of cases that on exciting an electron in a simple polyatomicmolecule a gross change of equilibrium geometry occurs.Such a possibilitywas first suggested 61 by Mulliken (1935) to explain the absorption spectrumof carbon disulphide. It has now been spectroscopically confirmed for thefollowing molecules (the upper states being named first) : HCO (Ramsaysystem only) linear-bent ; 47 HCN (first absorption), bent-linear ; 62 C,H,(acetylene, first absorption), trans-bent-linear ; 63 NH, (a-bands), linear-bent 64 (the PH, spectrum is analogous) ; C,H, (ethylene, first absorption),90" twisted-planar ; 65 and H,CO (formaldehyde, first absorption), non-planar-planar.66 According to the Frank-Condon principle, long pro-gressions result in those vibrational modes which tend to convert the oneshape into the other, but this is no help in identification unless vibrationalnumberings and assignments can be made.Vibrational analysis is of evenless help in cases, such as NH, and HCO, in which nothing is known a @rioriof either state; and rotational analysis is required to give additionalinformation.For molecules in the gas phase, solutions of the second problem, that ofelectronic symmetries, can only be obtained from rotational analysis,although in simple cases the presence or absence of Q-branch heads mays4 H. Schiiler and L. Reinebeck, Spectrocliim. Acta, 1954, 6, 288.5 5 S. Walker and R. F. Barrow, Trans. Faraday Soc., 1964, 50, 541.5 6 H.Schiiler and A. Michel, 2. Naturforsch., 1955, 10a, 459.5 7 H. Schiiler and L. Reinebeck, ibid., 1954, 9a, 350.5 8 J. H. Callomon, 1955, ref. 34a.6 9 H. Schiiler, A. Michel, and A. E. Griin, 2. Naturforsch., 1955, lOa, 1.6O W. B. Rimmer, Proc. Roy. SOC., 1923, A , 103, 696.R. S. Miilliken. Phys. Rev., 1941, 60, 506.62 G. Herzberg and K. K. Innes, unpublished, mentioned in ref. 47.C. K. Ingold and G. W. King, J., 1953, 2702 et seq.64 D. A. Ramsay, 1955, in lit.6 5 W. J. Potts, J . Ckem. Phys., 1955, 23, 65; P. G. Wilkinson and R. S. Mulliken,66 J. C . D. Brand, Chem. and Ind., 1955, 167; J . , 1956, in press.ibid., p. 1895SPECTROSCOPY AND MOLECULAR STRUCTURE. 77suffice. Thus, as a rule, excited electronic states can only be identifieddefinitely if the spectra of isotopically substituted molecules can be obtained(for the vibrational numbering) and at least a partial rotational analysismade.It is here that the new large gratings should prove most valuable.The analysis of the HCO bands is a good example of the difficulties involvedand of the information reauired to overcome them.On the theoretical side, the relations between electron-configuration andmolecular geometry 67 and force-constants 68 have been discussed. Calcul-ations of the type which predict more or less correctly 69 the separation andgeometries of the states of NH, observed in the a-bands have been appliedto the methyl radical and predict 70 that the only low-lying level to beexpected (6.8 ev) cannot combine with the ground state.Electronic com-putors are coming into use.71Brief mention must be made of ionisation potentials. Although deter-minations from Rydberg series ~ontinue,'~ Watanabe 73 has devised a photo-ionisation method analogous to that used in electron-impact determinations.A vacuum-ultraviolet monochromator produces a beam of photons which is,however, almost monochromatic (61, - 1 A), and the curves of photo-ionisation current plotted against photon energy show much sharper inflec-tions, so that excited states of ions can also be detected. Values obtainedare nearly as good as those from Rydberg series, but the method is moreuniversal. It is interesting that through recent refinements by narrowingthe energy band-width of the electron beam to 0.1 ev (equivalent to 8 A atl O O O A ) the electron-impact method can give results which are nearly asgood.74Aromatic Molecules.-The polyacenes. Because of mathematicaldifficulties, attempts to treat the electronic structures of larger moleculestheoretically have been confined to those in which many of the propertiescan be ascribed largely to a small proportion of x-electrons, and the x-electronapproximation is most directly applied to predicting the spectra of benzeneand its homologue~.~~ In its recently greatly improved forms, parametersthat have been adjusted empirically to fit the spectrum of benzene are usedin predicting the spectra of the higher homologues (naphthalene, etc.) ; 1*and here again, although the spectra are easily measured, the number ofexcited states whose symmetries have been definitely identified is still small.In these larger molecules the bonding-power of one electron is relativelysmall, and hence in identifying states changes of geometry on excitation arenot important.In favourable cases a vibrational analysis can, combinedwith known selection rules, reduce the choice of electronic symmetry to67 A. D. Walsh, J., 1953, 2260 et seq.6 8 J . Duchesne, Menz. Classe Sci., Acad. roy. Belg.. 1955, 28, viL6B J . Higuchi, Bull. Chem. SOC. Japan, 1955, 28, 238.70 Idem, J . Chern. Phys., 1956, 23, 2197.71 R. K. Nesbet, Pvoc. Roy. Soc., 1955, A , 230, 322.72 C. R. Zobel and A. B. F. Duncan, J. Amer. Chem. SOC., 1955, '77, 2811.73 K.Watanabe, J. Chem. Phys., 1954, 22, 1564.74 D. C. Frost and C. A. McDowell, PYOC. Roy. Soc., 1955, A , 232, 227.7 5 J . R. Platt, J. Chem. Phys., 1949, 17, 484; D. P. Craig, Rev. Pure APpl. Uzem.(Australia), 1953, 3, 207; W. hloffitt, J. Chew. Phys., 1954, 22, 320, 1820; H.-H.Perkampus, 2. phys. Chem. (Frankfuyt), 1954, 2, 160; J. A. Pople, Proc. PAYS. SO^.,1955, 68, A , 81.7 6 D. S . McClure, J. Chem. Phys., 1954, 22, 166878 GENERAL AND PHYSICAL CHEMISTRY.only one or two possibilities, as in the classic case of benzene. Here the firsttransition was shown to be electronically forbidden and the excited state(2600 A) to be either B1, (polarised long-axis through para-atoms) or B2,(short-axis in-plane perpendicular to B1,), with some additional evidence forthe latter.The second state (2000 hi) has now been shown 77 to be possiblyEzg, but in any case not Blt, as hitherto thought. A vibrational analysis ofthe second spectrum of naphthalene vapour (2800 A) shows 78 that thetransition is allowed and compatible with an upper state Bzu (short axis).Rotational analysis is out of the question, but the symmetries of excitedstates relative to the (non-polarised) ground states can be found directlywith polarised radiation if the molecules can be held suitably oriented, as insome crystals ; for the absorption and emission (fluorescence) spectra arepolarised in the same directions as the excited molecules. Thus, the firsttwo systems in hexamethylbenzene 79 are polarised in-plane (although longand short axes could not be distinguished).With symmetry reduced fromDch of benzene to DZh by $ara-disubstitution, the axes are more readilydistinguished ; and the first spectra of 9-dimethoxybenzene 8o and NNN’N‘-tetramethylphenylenediamine 81 were shown to be short-axis (or possiblyout-of-plane) polarised, equivalent to B2, in benzene if the effects of sub-stituents are small.In general, however, spectra of crystals differ markedly from those of the“ oriented gas.” The site-symmetry of a molecule is usually less than thatof the molecules itself, so that the principal axes of the latter each haveprojections along all three crystal axes. This can have three effects, cal-culable if the crystal structures are accurately known, on the spectra.First, bands involving polarised states are displaced relative to their positionsin the gas-phase.Secondly, they are split (“ Davydov splitting ”) intocomponents of different wavelengths which are polarised in different direc-tions; the splitting is proportional amongst other things to the strength ofthe transition and the distances between similar molecules. Thirdly, thepolarisation ratios differ from those expected purely from the relativeorientations of crystal and molecular axes. The effect has been shown mostelegantly by McClure, who measured the first spectrum of naphthalene(3200 A) in dilute solid solutions in durene crystals 76 (approximating closelyto the oriented gas) and the pure crystal.82 The first state is Bsu (long-axis),the (0.0) band split by 166 cm.-l; the second state (2800 A in the gas) isBzU (short axis).Crystal spectra can also distinguish between 231, and B2uin benzene, and the latter is confirmed 83 for the first state. Outstandingis Craig and Hobbins’s treatment of anthracene crystal spectra. The firstsystem 84 (weak) is found to be short-axis polarised (Bzzc), Davydov splitting-30 cm.-l; the second 85 (strong) long-axis polarised (&), Davydov split-ting 16,000 cm.-f. Agreement between observed and calculated values forT 7 T. M. Dunn and C. K. Ingold, Nature, 1955, 176, 65.78 H. Sponer and C. D. Cooper, J . Chem. Phys., 1955, 23, 646.79 D. P. Craig and L. E. Lyons, Nature, 1952, 169, 1102; R. C. Nelson and W.A. C. Albrecht and W. T. Simpson, ibid., 1953, 21, 940.8L Idem, J .Amer. Chem. SOC., 1955, 77, 4454.D. S. McClure and 0. Schnepp, J. Chem. Phys., 1955, 23, 1575.83 D. Fox and 0. Schnepp, ibid., p. 767.84 D. P. Craig and P. C. Hobbins, J . , 1955, 2302, 2309.s 5 Idem, ibid., p. 530; I1. E. Lyons, J . Chem. Phys., 1955, 23, 1973.Simpson, .I. Chem. Phys., 1955, 23, 1146.TSPECTROSCOPY AND MOLECULAR STRUCTURE. 79all three effects enumerated above is remarkable. The order of the twostates relative to those of naphthalene is seen to be reversed.A start has been made on tetracene,8G coro~iene,~~ and the N-heterocyclic(pyridine) series.88Triplet states. Although phosphorescence spectra have long been con-nected with excited molecules in triplet states (two unpaired electrons), andmeasurements of magnetic susceptibility have shown such molecules to beformed in the process which leads to phosphorescence, the two have now beendirectly connected by Evans,8s who showed that the rates of decay of bothphosphorescence and photomagnetism were identical and of a form whichexcludes other mechanisms.With the flash-absorption technique, themechanisms of excitation and phosphorescence can be studiedand (higher) excited triplet states ~bserved.~l Moleciiles in triplet statesare in fact free radicals ; hence their photochemical interest.92The term is applied to transitions in moleculesin which an electron is transferred from a bonding to the corresponding" anti-bonding " orbital, usually accompanied by a considerable redistri-bution of charge within the molecule.The same concepts have been appliedto certain intermolecular complexes between molecules with labile electronssuch as those of benzene-trinitrobenzene type,= for their spectra, which arefrequently the only prominent signs of their existence, show the two char-acteristics of charge-transfer spectra : high intensities, and (new) frequenciesnot related to those of the spectra of the separate components, but rather totheir ionisation potential^.^^ The spectra of iodine in different solvents arewell-known examples.95 The subject has been reviewed by Orge1.96Transition-element Co-ordination Complexes.-Most absorption bandsof the complexes of the first group of transition elements can be classifiedinto two groups according to their molar-extinction coefficients ( E ) : those of(i) e > 1000; and (ii) E < 100.The former usually occur in the ultravioletregion, and for a given element, M, depend greatly in strength and frequencyon the nature of the ligands, X. They are identified as charge-transferspectra.96* 97 Their frequencies are functions of ionisation potentials andelectron affinitie~,~~ and on the basis of a simple theory the direction ofelectron transfer was shown 99 to be M _+ X (X is H,O or NH,) for thecomplexes R'IX, and MX, of the elements M =Ti to Mn, except for thereverse cases of MX,, where bl = Fe3+ or Ce4+.Charge-transfer spectra.8 6 D. P. Craig, P. C. Hobbins, and J. R. Walsh, J . Chenz. Phys., 1954, 22, 1616;E. J . Bowen and B.Brocklehurst, J . , 1954, 3875; J. W. Sidman, J . Chem. Phys.,A. Bree and L. E. Lyons, ibid., 1630.1055, 23, 1365.8 8 V. Zanker, 2. phys. Chena. (Frankfurt), 1954, 2, 53.*O D. F. Evans, Nature, 1955, 176, 777.O 1 D. S. McClure and P. L. Haust, J . Chem. Phys., 1955, 23, 1772.O2 M. Szwarc, ibid., p. 204.O3 G. Briegleb and J. Czekalla, Nalzcrwiss., 1954, 4l. 448.95 D. F. Evans, ibid., p . 1424.96 L. E. Orgel, Qzrari. Rev., 1954, 8, 422.97 Y . Kondo, Bull. Chem. SOC. Japan. 1955, 28. 497.98 Idem, ibid., p . 263.G. Porter and F. J . Wright, Trans. Faraday SOC., 1955, 51, 1205; R. S. Beckerand M. Kasha, J . Amer. Chem. SOC., 1955, 77, 3669.L. E. Orgel, J . Chem. Phys., 1955, 23, 1352; S. Nagakura, ibid., p. 1441.H. L. Schlafer, 2. p h j ~ s .Chem. (Frankfzrrt), 1955, 3, 23280 GENERAL AND PHYSICAL CHEMISTRY.Bands of the second (weaker) type range through the visible into theinfrared region and depend relatively little on the type of ligand. It hasbeen possible to explain them very successfully, as if they were due only tonon-bonding 3d-electrons on the central ion M, by means of the so-calledcrystal-field theory, due to Bethe (1929) and applied to the magnetic pro-perties of the transitim-element salts notably by Van Vleck. In essence,an ion M in isolation has 5 indistinguishable 3d orbitals in which are nelectrons (maximum 10) of equal energies if the electron-configurationincludes the term 3d". If the ion is now surrounded by a cage of (usuallypolar) ligands, the central ion is subjected to a corresponding pattern ofelectric fields centred at the ligands as in a crystal lattice, which produces aninternal Stark effect on the 3d-electrons whose degeneracy is removed. Theenergy-levels of the free ion (other than S and P terms) are split, the numberof components and their separations depending on the strengths and sym-metries of the ligand fields.lW Transitions between these split levels areelectronically forbidden, but become allowed through vibrational perturb-ations and give rise to the weak spectra observed.101The relative splittings may be calculated and the energy-levels E , whichreduce to those of the free ion for zero field, plotted as functions of aneffective ligand-field parameter, Dq,102 or (El - E,).103 The parameter Dqmay be determined empirically from such diagrams by using the experi-mental value for the lowest observed frequency, or it may be calculated byassuming values of effective ligand dipoles and M-X distances (e.g.[CrX,I3+).lM The observed spectra of many of the 3d3 - 3d7 MX, complexesare fully in accord with cubic symmetry,l05 i.e. a regular octahedral con-figuration of the ligands; however, those of cupric complexes (3ds) couldonly be explained by assuming tetragonal symmetry lo6 (elongated octa-hedron); and in nickel (3ds) tetragonal (square planar) symmetry isfavoured,l07 making both paramagnetic and diamagnetic complexespossible. The effects of ligand substitution in a unicomplex compoundMX, depend not so much on the destruction of symmetry as on the relativevalues of the parameter Dq of the ligands, which, as obtained from thespectra, closely follow Fajans's electronegative series ; but they can in somecases allow cis- and trans-isomers to be distinguished.lo8 The spectra of[MnX,I2+ and [FeX,13+ complexes are especially weak (E -0.1) as all transi-tions from the 6S ground state go to levels of lower multiplicity(quartets).l05, lo9 Band-widths, which may vary between 20 and 2000 cm.-l,are also accounted for.ll0 The crystal-field theory can also be appliedto the spectra of the rare-earth salts (4f-electrons).1l1 Different methods areloo F.E. Ilse and H. Hartmann, 2. phys. Cheni. (Leipzig), 1951, 197, 239.lol C. J. Ballhausen, Actu Chem. Scand., 1955, 9, 821.lo2 L.E. Orgel, J., 1952, 4756; J . Chem. Phys., 1955, 23, 1004; A. E. Martell, Ann.lo3 C. K. Jsrgensen and J. Bjerrum, Actu Chem. Scand., 1955, 9, 116.lo4 H. Hartmann and H.-H. Kruse, 2. phys. Chem. (Frankfurt), 1955, 5, 9.lo5 C. K. Jsrgensen, Acta Chem. Scand., 1954, 8, 1502.loQ J. Rjerrum, C. J. Ballhausen, and C . K. Jsrgensen, ibid., p. 1275.lo' H. Hartmann and H. Fischer-Wasels, 2. phys. Chem. (Franhfurt), 1955, 4, 397.lo8 C. J. Ballhausen, Acta Chem. Scand., 1955, 9, 810.lo9 H. L. Schlafer, 2. phys. Chem. (Frankfurt), 1955, 4, 116.110 C. K. Jsrgensen, Act& Chem. Scand., 1954, 8, 1495; L. E. Orgel, J . Chem. Phys ,111 E. V. Sayre, K. M. Saucier, and S. Freed, ibid., p. 2060.Rev. Phys. Chem., 1955, 8, 239.1955, 23, 1824SPECTROSCOPY AND MOLECULAR STRUCTURE.81compared by Hartmann; 112 and Orgel 113 discusses the meaning of theparameter Dq.Infrared, Raman, Microwave, and Radio-frequency Spectroscopy.This report summarises the main lines of study and new developmentsthat have been made during 1955 in infrared, Raman, microwave, and radio-frequency spectroscopy. The literature coverage is approximately fromDecember, 1954, to November, 1955.Introductions to molecular spectroscopy as a whole,l and to infraredspectroscopy,2 have been published. Townes and Schawlow have writtenan authoritative book on the microwave spectra of gases, and Wilson,Decius, and Cross * a treatise on molecular vibrations. A very useful surveyof radio-frequency spectroscopy has appeared, and a punched-card indexof spectroscopic data has been announced.6During the year international conferences were held on molecularspectroscopy (Oxford), and on microwave and radio-frequency spectroscopy(Cambridge).8 The full proceedings of the latter have appeared (althoughthey were published too late for detailed coverage in this Report).Papers pre-sented at meetings held during 1954 at Gmunden (Austria) on general spectro-scopy, and at Parma (Italy) on infrared spectroscopy are collected together inspecial numbers of Mikrochimica A cia lo and Nuovo Cimento,ll respectively.Pure Rotation Spectra.-Pure rotation spectra of gases may be studiedby the methods of microwave, infrared, and Raman spectroscopy. For thefirst two methods it is a requirement that the molecule has a dipole moment,for the last that it has a non-spherical polarisability ellipsoid.Microwavespectroscopy, when applicable, has in general the highest precision, but eachof the other methods has its own field of application. The main resultsobtained from such studies are molecular moments of inertia.A general review of the microwave spectroscopy of gases has appeared,l2and experimental methods have been described which enable resolution tobe obtained in excess of the Iimjt usually set by Doppler broadening.lsWork in the millimetre region has revived interest in the spectra of molecules112 H. Hartmann, 2. phyr. Chem. (Fvankfurt), 1955, 4, 376.113 L. E. Orgel, J . Chenz. Phys., 1965, 23, 1819.B. Bak, “ Elementary Introduction to Molecular Spectra,” North-Holland Publ.Co., Amsterdam, 1954.W.Briigel, “ Einfiihrung in die Ultrarotspektroskopie,” Verlag Steinkopff,Darmstadt, 1954.C. H. Townes and A. L. Schawlow, “ Microwave Spectroscopy,” McGraw-Hill,London, 1955.E. B. Wilson, jun., J. C. Decius, and P. C . Cross, “ Molecular Vibrations,” McGraw-Hill, London, 1955.ri D. J. E. Ingram, “ Spectroscopy a t Radio and Microwave Frequencies,” Butter-worth:,, London, 1955.Documentation of Molecular SpectroscDpy,” Butterworths, London, and VerlagChemie, Weinheim, 1955; an account of the code used has been given in 2. angew.Chon.. 1955, 67. 685; cf. also J., 1955, 45014509 (index issue).Report by H. W. Thompson, Nature, 1955, 176. 680.Report by D. H. Whiffen, ibid., p.18.Discuss. Farada.y SOC., 1955, 19.lo Mikrochanz. Ada, 1955, parts 2-3, 217-760.l2 J. Sheridan, Research. 1955, 8, 88.l3 R. H. Romer and R. H. Dicke, Phys. Rev., 1955, 99, 532; J. P. Gordon, H. J.Zeiger, and C . H. Townes, ibid., p. 1264.NUOVO ~ i m . , 1955, 2, NO. 3 (Suppl. Vol.), 491-85082 GENERAL AND PHYSICAL CHEMISTRY.with low moments of inertia such as the tritium halides,14 and high-temper-ature techniques have enabled much precise information to be obtainedabout the alkali halides.15 Typical symmetrical-top molecules studied aredeu t erium-con t aining analogues of methyl cyanide and met h ylacet ylene,16and of arsine and stibine.17 However, an increasing effort is being madeto analyse the complex microwave spectra of asyrnmetrical-top molecules,among them nitryl chloride (N0,C1),18 trans-a~raldehyde,~~ trimethyleneoxidez0 (the skeleton of which has been shown to be planar), the ethylhalides (ethyl chloride has been proved to have the staggered con-figuration), and formic acid.22 For some of these molecules the dipolemoments and barriers to internal rotation have been obtained from themicrowave measurements.The determination of barriers has been theprincipal aim of studies of methanol,23 methanethiol,= and meth~larnine.~~The theory of the interaction of overall and internal rotation has beendiscussed in two important papers.26Among other studies of pure rotation the spectra of deuterium bromide,hydrogen iodide, deuterium iodide, and hydrogen selenide have been studiedby use of infrared methods,27 and of ethylene by Raman spectroscopy.28Herzberg and Stoicheff 29 have discussed accurate values of C-C and C-Hdistances in various molecules, some of which have been obtained recentlyby Raman spectroscopy.Vibration-rotation Spectra.-The main bands in infrared and Ramanspectra which correspond to molecular vibration frequencies split under highresolution into series of lines corresponding to transitions between rotationalenergy levels.Under this heading only such high-resolution studies will bediscussed as have yielded data on molecular moments of inertia.A new development in experimental infrared methods has been the use ofinterferometry (so far only in the near infrared region) to achieve resolutionshigher than can be obtained with diffraction-grating spectrometer^.^^Jaff6, Rank, and Wiggins report a resolution of 0.043 cm.-l by this means.It has also been shown that compactly designed commercial spectrometersl4 B.Rosenblum and A. H. Nethercot, Phys. Rev., 1955, 97, 84; C. A. Burrus, W.l5 A. Honig, M. Mandel, M. L. Stitch, and C. H. Townes, ibid., 1954, 96, 629.l6 L. F. Thomas, E. I. Sherrard, and J. Sheridan, Trans. Faraday Soc., 1955, 51, 619.l7 G. S. Blevins, A. W. Jache, and W. Gordy, Phys. Rev., 1955, 97, 680, 684.la D. J. Millen and K. M. Sinnott, Chem. and Ind., 1955, 538.lo J. Fine, J. H. Goldstein, and J. W. Simmons, J . Chem. Phys., 1955, 23, 601.2o J. Fernandez, R. J. Myers, and W. D. Gwinn, ibid., p. 758.21 K. Kraitchman and B.P. Dailey, ibid., p. 184; R. S. Wagner, N. Solimene, and33. P. Dailey, ibid., p. 599; R. S. Wagner and B. P. Dailey, ibid., p. 1355.22 R. G. Lerner, J. P. Friend, and B. P. Dailey, J . Chem. Phys., 1955, 23, 210.23 P. Venkateswarlu, H. D. Edwards, and W. Gordy. ibid., pp. 1195, 1200; J. D.Swalen, ibid., p. 1739.24 N. Solimene and B. P. Dailey, ibid., p. 124; R. W. Kilb, ibid., p. 1736; T .Kojima and T. Nishikawa, J . Phys. SOC. Japan, 1955, 10, 240.25 T. Nishikawa, T. Itoh, and K. Shimoda, J . Chem. Phys., 1955, 23, 1735.26 E. B. Wilson, C. C. Lin, and D. R. Lide, ibid., p. 136; D. G. Burkhard and J . C.Irvin, ibid., p. 1405.27 E. D. Palik, ibid., pp. 217, 980.28 J. Romanko, T. Feldman, E. J. Stansbury, and A. McKellar, Canad. J . Phys.,1954, 32, 735.20 G.Herzberg and B. P. Stoicheff, Nature, 1955,175, 79.R. Chabbal and I?. Jacquinot, Nuovo cim., 1955, 2 (Supp.), 661 : J. H. Jaff6, D. H.Rank, and T, A. Wiggins, .J. Opt. SOC. Amer., 1955,45, 636; R. G . Greenler, ibid., p. 788.Gordy, B. Benjamin, and R. Livingston, ibid., p. 1661SPECTROSCOPY AND MOLECULAR STRUCTURE. 83can give useful high-resolution spectra when the prism is replaced by agrating.31carbon dioxide 33 (Fermi resonance effects), dideuteroacetylene,% tri-de~terosilane,3~ silyl iodide,,6 and mon~deuteroethane.~~Welsh and his collaborators38 have given a very good account of themethods and possibilities of high-resolution Raman spectroscopy, and havereported results with methane.39Vibration Spectra.-The determination of the vibration frequencies ofmolecules from infrared and Raman spectra continues to be a major activity.Indeed, as will be apparent from the following sections, there is now hardlyany branch of chemistry for which useful structural conclusions cannot beobtained by these methods. The infrared method in particular has provedof tremendous versatility.Experimental developments of infrared spectroscopy have included theuse of prisms40 and gratings41 to explore the usually inaccessible low-frequency region. Experimental techniques in the near infrared regionhave been re~iewed,4~ with the emphasis on analytical applications.Apowerful photoelectric Raman spectrometer has been described.&Fairly complete analyses have been made of vibrationspectra of the oxides of nitrogen,44 and of a considerable number of inorganichalides including NF,,45 S02F214s SOF2,469 47 SeOF2,48 N02Cl,49 SC12,60S2F2,51 BrF, and BrF,,52 and PCl, 53 (solid; PCl,+*PCl,-).Among organicderivatives, substituted methanes,54 ethanes (CH,*CD,, 55a and C2H5*CN 55a),High-resolution results have been reported for nitricSmall molecules.31 R. C. Lord and T. K. McCubbin, J . Opt. SOC. Amer., 1955, 45, 441.32 N. L. Nichols, C. D. Hause, and R. H. Noble, J . Chem.. Phys., 1955, 23, 57.34 R. M. Talky and A. H. Nielsen, ibid., 1954, 22, 2030.35 D. R. J. Boyd, J . Chem. Phys.. 1955, 23, 922.36 R. N. Dixon and N. Sheppard, ibid., p. 215.37 R. van Riet, C. Courtoy, and M. de Hemptinne, Ann. SOC. Sci. Bruxelles, 1954,3E H.L. Welsh, E. J. Stansbury, J. Romanko, and T. Feldman, J . Opt. Soc. Anzer.,3B T. Feldman, J. Romanko, and H. L. Welsh, Canad. J . Phys., 1955, 33, 138.E. K. Plyler and N. Acquista, Nuovo ciin., 1955, 2, (Supp.) 629; I. M. Mills,J. R. Scherer, B. Crawford, and M. Youngquist, J . Opt. SOC. Amer., 1955, 45, 785.41 E. K. Plyler and N. Acquista, J . Chem. Phys., 1955, 23, 752.42 W. Kaye, Spectrochim. Acta, 1955, 7, 181.43 J. U. White, N. L. Alpert, and A. G. Debell, J . Opt. Soc. Amer.. 1955, 45, 154.I4 R. E. Nightingale, A. R. Downie, D. L. Rotenberg, and B. Crawford, J . Phys.45 E. L. Pace and L. Pierce, J . Chem. Phys., 1955, 23, 1248.46 P. Bender and J. M. Wood, ibid., p. 1316.4 7 J. K. O’Loane and M. K. Wilson, ibid., p. 1313.48 J. A. Rolfe and L.A. Woodward. Trans. Faraday Sot., 1955, 51, 778.O9 R. Ryason and M. K. Wilson, J . Chem. Phys., 1954, 22, 2000.50 G. M. Barrow, J . Phys. Chem., 1955, 59, 987; H. Stammreich, R. Forneris, andK. Sone, J . Chem. Phys., 1955, 23, 972.61 J. R. Barcel6 and C. Otero, Anales Fis. Quim., 1955, B, 51, 223.E.* H. M. Haendler, S. W. Bukata, B. Millard, E. I. Goodman, and J. Littman,J . Chenz. Phys., 1954, 22, 1939.63 H. Gerding and H. Houtgraaf, Rec. Trav. chinz., 1955, 74, 5.64 H. 33. Weissmann, R. B. Bernstein, S. E. Rosser, A. G. Meister, and F. I;. Cleve-land, J . Chem. Phys., 1955, 23, 544 (see also other papers in the series on substitutedmethanes by Cleveland and his colleagues in J . Chem. Phys.) ; A. Hadni, Compt. rend.,1955, 240, 1702, 1983.6 5 ( a ) R.van Riet, Bull. Classe Sci., Acad. my. Belg., 1055, 41, 188; (b) N. E.Duncan and G. J. Janz, J . Chem. Phys., 1955, 23, 434.C. P. Courtoy and G. Herzberg, ibid., p. 975.Ser. I , 68, 193.1955, 45, 338.Chem., 1954, 58, 104784 GENERAL AND PHYSICAL CHEMISTRY.and ethylenes (CF,:CHD and CF2:CD2,56 br~moethylenes,~~ and CHIXHI 58)have been studied. Interest continues in the interpretation of the spectraof such amides as f ~ r m a m i d e , ~ ~ N-methylacetamide,60 and diformylhydr-azine.61 Other molecules that have been investigated include CH,*CO,Hand CH3*C0,D,62 CD,*C0,*CD3,63 HN364a (and some metastable decom-position products 64b), SiH,Br and SiH2Br,,65 (SiH,),X 66 (X = 0, S, Se),cyclupropane and hexadeuter~cyclopropane,~~ benzene, 68 and na~hthalene,~Sthe tropylium ion 70 (C7H,+; planar with a seven-fold symmetry axis),s-triazineJ71 and trimethylene oxide.72 It is claimed that the infraredspectrum has been obtained of the HO, radical in the solid state 7%; thespectra of H,O,, HDO,, and D,O, have been studied.73bLarge molecules. The infrared spectra of the %-paraffins continue toengage attention,'* and a study has also been made of hexa-o-deutero-octane.75 The interaction between separate methylene chains in crystallineparaffins and in polythene has been in~estigated.~~ Assignments of hydro-carbon frequencies have been made by comparison with those of analogouspolar molecules. 77 The frequencies of angle-deformation vibrations of CHgroups in saturated m01ecules,~8 and in aromatic rings,79 have been consideredin relation to the chemical surroundings. Characteristic frequencies in theinfrared spectra of substituted naphthalenes,m diphenylpolyenes 81 (cis-trans-configurations), and OH and OD deformation frequencies in phenols *,have been discussed.Infrared spectra of polyesters,= poly(ethy1ene66 W. F. Edge11 and C. J. Ultee, J . Chcm. Phys., 1954, 22, 1983.5 7 J. C. Evans and H. J. Bernstein, Canad. J . Chem.. 1955, 33, 1171.6 8 S. I. Miller, A. Weber, and F. F. Cleveland, J . Chem. Phys., 1955, 23, 44.6D T. Miyazawa, J . Chem. SOC. Japan, 1955, 76, 821; Y. Mikawa, ibid., p. 804.6o M. Davies, J. C. Evans, and R. L. Jones, Trans. Furaday SOC., 1955, 51, 761.61 T. Miyazawa, J . Chem. SOC. Japan, 1955, 76, 341.62 W. Weltner, J .Amer. Chem. SOC., 1955, 77, 3941.63 M. Corval and J. Lecomte, Mihochim. Acta, 1955, 25.6( ( a ) D. A. Dows and G. C . Pimentel, J . Chem. Phys.. 1955, 23, 1258; ( b ) Same66 D. W. Mayo, H. E. Opitz, and J. S. Peake, ibid., p. 1344.6 6 H. J. Emeldus, A. G. MacDiarmid, and A. G. Maddock, J . Inorg. Nuclear Chem.,e7 A. W. Baker and R. C. Lord, J . Chem. Phys., 1955, 23, 1636.68 D. H. Whiffen. Phil. Trans., 1955, A , 248, 131.69 G. C. Pimentel, A. L. McClellan, W. B. Person, and 0. Schnapp, J . Chem. Phys.,70 W. G. Fateley and E. R. Lippincott, J . Anzer. Chem. Soc., 1955, 77, 249.71 J. Goubeau, E. L. Jahn, A. Kreutzberger, and C. Grundmann, J . Phys. Chem.,72 R. F. Ziircher and H. H. Gunthard, Helv. Chim. Acta, 1955, 38, 849.7s (a) P.A. Gigubre, J . Chem. Phys., 1954, 22, 2085; (b) 0. Bain and P. A. Gigubre,74 H. Tschamler, J . Chem. Phys., 1954, 22, 1845; M. Brini, BuEZ. SOC. chim. France,7 5 G. C. Pimentel and W. A. Klemperer, J . Chem. Phys., 1955, 23, 376.7 G R. S. Stein and G. B. B. M. Sutherland, ibid., 1954, 22, 1993; M. C. Tobin, ibid.,7 7 N. Sheppard and D. M. Simpson, ibid., 1955, 23, 582.78 I. Nakagawa, J . Chem. SOC. Japan, 1955, 76, 540.79 M. Margoshes and V. A. Fassel, Spectrochim. Ada, 1955, 7, 14; L. J. Bellamy,81 K. Lunde and L. Zeclimeister, Acta Chem. Scand., 1954, 8, 1421 ; J . Amer. Chem.82 R. Mecke and G. Rossmy, 2. EZektrochem., 1955, 59, 866.as TV. H. T. Davison and P. J. Corish, J.. 1955, 2428, 2431.authors with E. Whittle, ibid., p.1606.1955, 1, 194.1955, 23, 234, 230, 245; E. R. Lippincott and E. J. O'Reilly, ibid., p. 238.1954, 58, 1078.Canad. J . Chem., 1955, 33, 527.1955, 996.1955, 23, 891; R. S. Stein, ibid., p. 734.J . , 1955, 2818.SOL, 1955, 77, 1647.R. L. Werner, W. Kennard, and D. Rayson, Austral. J . Chem., 1955, 8, 346SPECTROSCOPY AND MOLECULAR STRUCTURE. 86glycol),s* and polyfonnaldehyde 85 have been studied in relation to theconfigurations of the polymer chains.Lecomte 86 has published a comprehensive review of the literature onC=O stretching frequencies ; a previously reported significant discrepancy be-tween the infrared and Raman carbonyl frequencies of liquid ketones has notbeen confinned.87 The direct effect of the electronegativity of neighbouringsubstituents on the carbonyl frequency has been demonstrated.88 Character-istic infrared group frequencies have been found for C=S,sa unsaturatedethers (Raman data also), borate e s t e r ~ , ~ l sulphonamides,92 fluorinatedcompounds containing the S-0 link,93 sulphinic acid~,~4 acid salts of carboxylicacids,95 salts and esters of phosphorus oxy-acids g6 (infrared 96a andRaman Os6), esters and nitriles,97 heavily chlorinated hydrocarbons 98(Raman data), nitroso-c~mpounds,~~ hydroperoxides,lM carbohydrates,loland chelate compounds.1O2 In a number of cases structural conclusions havebeen drawn from these st~dies.~l, 93, 94, 95, 99The structures of proteins and nucleic acids and their simpler derivativescontinue to be investigated by infrared spectroscopy.The significance ofdifferent carbonyl frequencies of polypeptides and proteins has been dis-cussed.lo3 The interaction of amide with other polar groups has beeninvestigated by spectroscopic work on solutions.lm The spectra of acrystalline diamide,lo5 polypeptides,1°6 collagen,l07 and globular proteins inwater solution lo8 have been studied. The infrared spectra of purines,log,a4 W. H. T. Davison, J., 1955, 3270.8 5 A. R. Philpotts, D. 0. Evans, and N. Sheppard, Trans. Faraduy SOC., 1955, 51,8 6 J. Lecomte, Bull. SOC. ckim. France, 1955, 716, 1026.87 M.-L. Josien, J. Lascombe, J. Lecomte, and J.-P. Mathieu, Compt. rend., 1955,89 R. Mecke and A. Luttringhaus, 2. Natuvforsch., 1955, lob, 367.91 R. L. Werner and K.G. O’Brien, Austral. J . Chem., 1955, 8, 355.O2 J. N. Baxter, J. Cymerman-Craig, and J. B. Willis, J., 1955, 669.Ba R. N. Haszeldme and J. M. Kidd, J., 1955, 2901.94 S. Detoni and D. Hadii, J., 1955, 3163.95 D. Hadii and A. Novak, Nuovo cim., 1955, 2 (Suppl.), 716.96 ( a ) D. E. C. Corbridge and E. J. Lowe, J., 1964, 4555; (b) M . Baudler, 2. Elektro-97 D. G. I. Felton and S. F. D. Orr, J., 1955, 2170.98 H. Gerding and H. G. Haring, Rec. Trav. chim., 1955, 74, 841, 957, 981.99 P. Tarte, Bull. SOC. chim. belges, 1954, 83, 525; J . Chem. Pltys., 1955, 23, 979;loo H. R. Williams and H. S. Mosher, Analyt. Chem., 1955, 27, 517.Iol S. A. Barker, E. J. Bourne, R. Stephens, and D. H. Whiffen, J., 1954,421 1,4550.Io2 L. J . Bellamy and L. Beecher, J., 1954, 4487; L.J. Bellamy and R. F. Branch,lo3 S. Krimm, J . Chem. Phys., 1955, 23, 1371.lo4 C. G. Cannon, Mikrochim. Acta, 1955, 555; S. Mizushima, M. Tsuboi, T. Shima-nouchi, and Y . Tsuda, Spectrochim. Ada, 1955, 7, 100.lo6 I. Sandeman, Proc. Roy. Soc., 1955, A , 232, 105.lo6 A. Elliott, ibid., 1954, A , 226, 408; M. Asai, M. Tsuboi, T. Shimanouchi, andS. Mizushima, J . Phys. Chem., 1955, 59, 322.G. N. Ramachandran, J . Chem. Phys., 1955, 23, 600.lo8 G. Ehrlich and G. B. B. M. Sutherland, J . Amer. Chem. Soc., 1954, 76. 5268.J. R. Lacher, J. L. Bitner, D. J. Emery, M. E. Seffl, and J. D. Park, J . Phys.110 C. H. Willits, J. C. Decius, K. L. Dille, and B. D. Christensen, J . Amer. Chem.1051.240, 1982.R. E. Kagarise, J . Amer. Chem.SOC., 1955, 77, 1377.A. Kirrmann and P. Chancel, Bull. SOC. chim. France, 1954, 1338.chem., 1955, 59, 173.R. N. Haszeldine and J. Jander, ibid., p. 979.ibid., p. 4491.Chem., 1955, 59, 615.Soc., 1955, 77, 256986 GENERAL AND PHYSICAL CHEMISTRY.pyrimidines,lo9 nucleic acids,111 and keto-steroids 112 (below 1350 cm.-l) havebeen investigated.A number of investigations of solids have been madein which the vibrational spectra (mostly infrared) are interpreted in relationto the detailed crystal structure. Studies of the hydrogen halides,l13ammonia and nitrogen trideuteride 114 (Raman data), ammonium fluoride 115and azide,l16 sodium hydroxide and deuteroxide,1l7 the out-of-plane vibra-tions of nitrates and carbonates,llg diamond,l19 and some micas and poly-mers 120 fall into this category.Studies of the intensities of infrared and Ramanvibrational bands yield interesting information about the dipole momentand polarisability changes, respectively, that occur during the vibrations.The experimental data can be related to bond properties, although only withpartial success.Detailed infrared studies have been made of the smallmolecules bromine chloride and iodine chloride,121 acetylene and dideutero-acetylene,122 formaldehyde,123 hexafluoroethane,lH dimethyla~etylene,~~~and benzene.68 Raman measurements have been interpreted for benzene 68and the deuterobenzenes.126 A theoretical study of the effects of vibration-rotation interaction on the intensities of individual lines in vibration-rotation bands of diatomic molecules has been p~b1ished.l~~Interest is growing in the investigation of intensities of bands associatedwith small groups within large molecules as a method of following thevariation of the properties of such groups with chemical surroundings.Infrared studies of this type have been made on characteristic bands of alkylesters,128 the NH group,128 and the CEN A review has been givenof Russian work of this type on aromatic compound~,1~0 with special refer-ence to conjugation effects.A theoretical treatment of intensities of groupvibrations in large molecules has been developed. 131Rotational isomerism. The spectra of flexible molecules that can takeup a number of different configurations by restricted rotation about singlebonds present special problems in interpretation, and the spectral data giveinformation about the preferred configurations of the rotational isomers.ll1 E.R. Blout and H. Lenormant, Biochinz. Biophys. Acta, 1954, 15, 503; 1955,17, 325; Compt. rend., 1954, 239, 1281.112 R. N. Jones, F. Herling, and E. Katzenellenbogen, J . Amer. Chem. SOC., 1955,77,651.113 D. F. Hornig and W. E. Osberg, J . Chem. Phys., 1955, 23, 662.lf* F. P. Reding and D. F. Hornig, ibid., 1954, 22, 1926; 1955, 23, 1053.115 R. C. Plumb and D. F. Hornig, ibid., 1955, 23, 947.116 D. A. Dows, E. Whittle, and G. C . Pimentel, ibid., p. 1475.11' W. R. Busing, ibid., p. 933.118 J. C . Decius, ibid., p. 1290.119 G. B. B. M. Sutherland, D. E. Blackwell, and W. G.Simeral, Nature, 1954,174,901.120 G. B. B. M. Sutherland, Nuouo cim., 1955, 2 (Suppl.), 635.121 W. V. F. Brooks and B. Crawford, J . Chem. Yhys., 1955, 23, 363.lZ2 E. C. Wingfield and J. W. Straley, ibid., p. 731.123 I. C. Hisatsune and D. F. Eggers, ibid., p. 487.124 D. G. Williams, W. B. Person, and B. Crawford, ibid., p. 179.125 I. M. Mills and H. W. Thompson, Proc. Roy. SOC., 1955, A , 228, 287.126 G. Allen and H. J. Bernstein, Canad. J . Chem., 1955, 33, 1137.12' R. Herman and R. F. Wallis, J . Chem. Phys., 1955, 23, 637.128 R. A. Russell and H. W. Thompson, J . , 1955, 479, 483.129 M. W. Skinner and H. W. Thompson, J . , 1955, 487; P. Sensi and G. G. Gallo,u0 P. Schorygin, L. Kuzina, and L. Ositjanskaja, Mikrochinz. Ada, 1955, 630.131 H.Prirnas and H. H. Gunthard, Helv. Chim. Acta, 1955, 38, 1254.Studies on crystals.Spectral intensities.Gazzetta, 1955, 85, 224, 235SPECTROSCOPY AND MOLECULAK STRUCTURE. 87Molecules of this type that have been examined include CHBr2CHBr2J132CHC12*CHC12,133 CFC12*CFC12,13Q CF2Br*CF2Br, 135 CH,(CN) -CH2*CN,136CH3*CH2*CH2X (X = C1, Br),137 and X*[CH,],,*X’ (X, X’ = C1, Rr, I ;n = 3, 4, 5, In most cases configurations have been assigned to theforms present in the crystalline state; succinonitrile 136 and several of thepolymethylene halides 138 have unusual non-planar staggered configurations.Thespectrum of methyl nitrate has been interpreted in terms of free rotationabout the N-0 bond l40 (a somewhat surprising result in view of the highbarrier reported previously for nitric acid lal), and methyl borate has beenshown to have very probably a single symmetrical planar configuration ofthe heavy atoms with a three-fold symmetry axis.142s91 A number of cor-relations and discussions of potential barriers restricting rotation have beenpublished.l&This is a potentially very importantaspect of physical chemistry that is being opened up by infrared spectro-scopy.A summary by Terenin lU of recent Russian work on the physicaladsorption of molecules on porous glass gives references to studies (withsurface coverages apparently near unity) of a number of aromatic hydro-carbons and molecules with 0x0-groups. Yates, Sheppard, and Angell 145have shown that in certain cases higher sensitivity can be achieved, and haverecorded changes in the spectrum caused by the adsorption of down to & ofa monolayer of ammonia on porous glass.The spectra of 1 : 2-dichloro-ethane and acetylacetone have been observed on silica gel,146 and an interest-ing study has been made by Mapes and Eischens of the chemisorption ofammonia on cracking catalysts.The interaction of molecules with themetal atoms in co-ordination complexes can readily be studied by infraredspectroscopy. Spectra have been recorded of the molecules or ionsCH2(SCN)*CH2*SCN,14s NO 2 -,149 NH 3, 1499 150 CN-,151 CO,1S2 and NO+ 152b132 R. E. Kagsrise, J . Chem. Phys., 1955, 23, 207.133 K.Naito, I. Nakagawa, K. Kuratani. I. Ichishima, and S. Mizushima, ibid., p. 1907.ls4 R.E. Kagarise and L. W. Daasch, ibid., p. 113.135 Idem, ibid., p. 130.136 G. J . Janz and W. E. Fitzgerald, ibid., p. 1973.13’ C. Komaki, I. Ichishima, K. Kuratani, T. Miyazawa, T. Shimanouchi, and S.13* J . K. Brown and N. Sheppard, Proc. Roy. Soc., 1955, A , 231, 555.139 G. Allen and H. J . Bernstein, Canad. J. Chem., 1955, 33, 1055.140 J. C. D. Brand and T. M. Cawthon, J. Amer. Chem. Soc., 1955, 77, 319.l4l H. Cohn, C. I(. Ingold, and H. G. Poole, J., 1952, 4272.142 H. J . Becher, 2. fihys. Chem. (Frankfurt), 1954, 2, 276.143 N. W. Luft, J. Phys. Chem., 1965, 59, 92, 572.144 A. N. Terenin, N. G. Jaroslavsky, A. W. Karjakin, and A. N. Sidorov, Mikrochim.145 D. J . C. Yates, N. Sheppard, and C. L. Angell, J. Chem. Phys., 1955, 23, 1980.146 T.Yoshino, ibid., p. 1564.147 J. E. Mapesand R. P. Eischens, J. Phys. Chem., 1954, 58, 1059.148 S. Mizushima, I. Ichishima, I. Nakagswa, and J . V. Quagliano, ibid., 1955,59,293.14g P. E. Merritt and S. E. Wiberley, ibid., p. 55.150 M. Kobayashi and J . Fujita, J. Chenz. Phys., 1955, 23, 1354; S. Mizushima,I. Nakagawa, and J . V. Quagliano, ibid., p. 1367.lS1 E. F. G. Herington and W. Kynaston, J., 1955, 3555.152 ( a ) F. A. Cotton, A. D. Liehr, and G. Willtinson, J . Inorg. Nuclear Chem., 1955,1, 175; (b) T. S. Piper, F. A. Cotton, and G. Wilkinson, ibid., p. 165; (c) R. A. Friedel,I. Wender, S. L. Shufler, and H. W. Sternberg, J. Amer. Chenz. SOC., 1965, 77, 3951Rotational isomerism has also been reported in furfuraldehyde.The spectra of adsorbed molecules.Inorganic co-ordination complexes.Mizushima, Bull.Chenz. SOC. Japan, 1955, 28, 330.Acta, 195.5, 46788 GENERAL AND PHYSICAL CHEMISTRY.in complexes of this type. These include a discussion of the interestingcompound, C O ( C O ) ~ H . ~ ~ ~Other molecdar and ionic complexes ; association phenomena. Thecharge-transfer type of molecular complex such as those of chlorine withbenzene 153 and iodine and iodine cyanide with other organic molecules 154have given interesting results in the infrared region. HF,ClF, 155 has beenstudied by the same method, and Raman techniques have been used in theinvestigation of A1C13,NH3 156 and ether-borine complexes.157 The crystal-line complexes between water and the hydrogen halides have been shown tobe of the type H30+, X-.158 Raman studies of water solutions and meltshave enabled the ionic species GaBr4-,159 InBr4-,160 and MX,2- (M = Cd, Zn,Hg; X = C1, Br, I)161 to be identified.Vibrational spectra, and particu-larly Raman spectra, are very useful in detecting symmetrical ionic species.The interaction of hydrogen chloride 162 and deuterochloroform 163 withvarious solvents has been followed by infrared spectroscopy. The lattersystem is particularly interesting in that the absorption band of the CD groupvaries widely in intensity from solvent to solvent, although the frequencyvaries little. The association of furfuraldehyde and aromatic nitroso-compounds,164 and hydrogen-bonding effects in alcohols 165 and chelatedhydroxy- and amino-anthraquinones 166 have also been studied by infraredspectroscopy.The effects of solvents on the frequencies and intensities ofG O 1673 168, C-H,167 and C-C lG7 vibrations have been reported.Intermolecular interaction in gases at high pressure, and in liquids or solidsmay cause frequencies to be observed in the spectrum which are otherwisesymmetry forbidden. The pure rotation spectrum of hydrogen has thusbeen observed in the infrared region,169 and some beautiful vibration-rotation spectra of hydrogen have also been observed in the liquid and solidstates; 1'0 these show that the hydrogen molecule is rotating in the crystallattice. The effects of high pressure (with or without added gases) have beenstudied for hydrogen chloride, hydrogen fluoride, and carbon m0noxide.1~1lS3 J.Collin and L. D'Or, J . Chem. Phys., 1955, 23, 397.lo* D. L. Glusker and H. W. Thompson, J., 1955, 471 ; R. N. Haszeldine, J., 1954,155 J. P. Pemsler and D. F. Smith, J . Chem. Phys., 1954, 22, 1834.lS6 H. Gerding and H. Houtgraaf, Rec. Trav. chim., 1955, 74, 15.lS7 B. Rice and H. S. Uchida, J . Phys. Chem., 1955, 59, 660.16* C. C. Ferris0 and D. F. Hornig, J . Chem. Phys., 1955, 23, 1464.lSD L. A. Woodward and A. A. Nord, J., 1955, 2655.160 L. A. Woodward and P. T. Bill, J.. 1955, 1699.4145.J. A. Rolfe, D. E. Sheppard, and L. A. Woodward, Trans. Faraday SOC., 1954,50, 1275; M. L. Delwaulle, Bull. SOC. chim. France, 1955, 1294; W. Bues, 2. anorg.Chem., 1955, 279, 104.lci2 M.-L. Josien and G. Sourisseau, Bull. SOC.chim. France, 1955, 178.R. C. Lord, B. Nolin, and H. D. Stidham, J . Amer. Chem. SOC., 1955, 77, 1365;C. M. Huggins and G. C . Pimentel, J . Chem. Phys., 1955, 23. 896.164 D. L. Glusker and H. W. Thompson, Speclrochim. Acla, 1954, 6, 434; see alsoref. 139.166 B. Y . Levin, Zhur.$z. Khim., 1954, 28, 1399.lU6 D. N. Shigorin and N. S. Dokunikhin, DokZady Akad. Nuuk, S.S.S.R., 1955,100, 323, 745.16' N. S. Bayliss, A. R. H. Cole, and L. H. Little, Austral. J . Chem., 1955, 8, 26.168 M.-L. Josien and J. Lascombe, J . Chim. phys., 1955, 52, 162.170 E. J. Allin. W. F. J. Hare, and R. E. Macdonald, Phys. Rev., 1955, 98, 554.171 R. Coulon and B. Vodar, Nuovo cim., 1955, 2 (Suppl.), 670.J. A. A. Ketelaar, J. P. Colpa, and F. N. Hooge, J .Chem. Phys., 1955, 23, 413SPECTROSCOPY AND MOLECULAR STRUCTURE. 89In two-component systems simultaneous transitions of frequency VA + VBcan be observed,l72 where vA and vB represent frequencies of molecules Aand B separately. This fact has been developed in an interesting fashion byKetelaar and Hooge172 as a method of determining the low-frequencyspectrum of molecule B by searching for simultaneous transitions in theneighbourhood of a strong (and preferably isolated) fundamental of moleculeA. Considerable path-lengths of solution are needed for this work and thistends to limit its applicability, but nevertheless some very interesting resultshave been reported.Ultraviolet and visible spectra havebeen used for some time to study flames and electrical discharges; infraredemission and absorption spectra are now being used for the same purpose.Results have been reported during 1955 for the methane-~xygen,~~~acetylene-oxygen,l73 and ammonia-oxygen 174 flames from which inform-ation has been obtained about the molecules and diatomic radicals present.The cool flame of ethyl ether 175 and the high-frequency discharge spectrumof carbon monoxide and carbon dioxide 1713 have been studied.The purerotation spectrum of the hydroxyl radical has been 0b~erved.l~~Theoretical topics. I t has not been possible to refer to specific applicationsof calculations of vibration frequencies, but some papers devoted to generalmethods are noted below.Perturbation methods have been applied to normal co-ordinate calcul-ations,l78 and a new form of harmonic potential function has been proposedwhich takes into account repulsions between non-bonded atoms.179 A newanalytical function relates the potential energy of a bond to the inter-nuclear distance; 1~ it is claimed to be an improvement on the well-knownMorse function.This new function has been applied to the calculation ofthe properties of hydrogen bonds.181Nuclear Magnetic Resonance. ?-A nucleus with a non-zero magneticmoment has, when placed in a magnetic field, a resonance frequency in theradio-frequency range at which it absorbs electromagnetic radiation. For agiven type of nucleus, such as a proton, the value of the resonance frequencyobserved depends on the effective surrounding magnetic field; this in turndepends principally upon the field applied by an external magnet, butpartially on the screening effects of the surrounding electrons.The screeningvaries with the chemical environment of the nucleus and differs from onechemical compound, or group within a compound, to another. If, forexample, the resonance frequency of the protons in water is taken as standard,all other chemically bound protons will have resonances which differ fromthis by the so-called ‘‘ chemical shifts ”. Conversely, the analysis ofSpectra of flames and discharges.172 J. A. A. Ketelaar and F. N. Hooge, J . Chem. Phys., 1955, 23, 749, 1549; R.173 E. K. Plyler, Mikrochim. Acta, 1955, 421.174 D. A. DOWS, E. Whittle, and G. C. Pimentel, J . Chew.Phys., 1955, 23, 499.176 R. E. Donovan and W. G. Agnew, ibid., p. 1592.176 N. Y. Dodonova, Doklady Akad. Nauk, S.S.S.R., 1954, 98, 763.177 R. P. Madden and W. S. Benedict, J . Chenz. Phys., 1955. 23, 408.178 S. Bratoi, ibid., p. 159; P. W. Higgs, ibid., pp. 1448, 1450.17@ E. J. Slowinski, ibid., p. 1933.180 E. R. Lippincott and R. Schroeder, ibid., p. 1131.181 Idem, ibid., p. 1099. t Seep. 72.Coulon, J. Robin, and B. Vodar, Compt. vend., 1955, 240, 95690 GENERAL AND PHYSICAL CHEMISTRY.observed chemical shifts provides valuable information about the presenceor otherwise of protons in particular types of chemical groupings. Some ofthe individual resonances may be split into multiplets by spin-spin inter-action between neighbouring nuclei, and the patterns then observed alsogive information about chemical surroundings.,411 these effects can beexperimentally resolved under conditions in which molecules are free torotate in all directions, viz., in the gaseous and liquid states and in solution.Most work is currently carried out with proton (hydrogen) resonances.These have, for example, been used to confirm the now generally acceptedstructures of BH4- and B,H6,1s2 to study the chemical shifts in the methyl-pyridines,l= to distinguish between alternative structures for a cyclic ~ l e f i n , ~ ~ and to show that the rotation about the C-N link in an amide is highlyre~tricted.1~~ Proton resonances have also been used to study the associ-ation phenomena between chloroform and various solvents,ls6 of propionicacid,ls7 and of concentrated aqueous electrolytes.ls8 Chemical shifts havebeen tabulated for the nitrogen 189 and 1'0 nuclei 190 in different chemicalsurroundings, and for the phosphorus nuclei in polyphosphates.lgl Spin-spin fine structure has been considered theoretically,lg2 and an experimentalmethod of eliminating it in certain cases has been dem0n~trated.l~~ Observedspin-spin patterns have been discussed for proton resonances in aromaticrings lg4 and boron compounds.ls2Nuclear magnetic resonance is likely to find wide application in the studyof large as well as small molecules because the resonances are usually char-acteristic of small parts of the larger molecules, i.e., they have many applic-ations to the detection of chemical groups.Although the abundant nucleiof carbon and oxygen do not give rise to magnetic resonance spectra, manyothers which are of common occurrence in organic chemistry, such ashydrogen, fluorine, nitrogen, chlorine, and phosphorus, do so.(Electron) Paramagnetic Resonance.-The magnetic moment of anunpaired electron moving in its orbital interacts with an applied magneticfield in a similar way to a nucleus, as described in the previous section. Theresonance frequencies usually occur in the microwave region, and the methodis applicable to the study of the odd-electron free radicals and ions of organicchemistry, and to derivatives of the transition elements and the rare earthswhich have incomplete electronic shells associated with the metal atoms.During the year a sensitive spectrometer for this work has been182 R.A. Ogg, J . Chem. Phys., 1954, 22, 1933.183 E. B. Baker, ibid., 1955, 23, 1981.1134 E. J. Corey, H. J. Burke, and W. A. Remers, J . Amer. Chem. Soc., 1955, 77,186 C. M. Huggins, G. C. Pimentel, and J. N. Shoolery, ibid., p. 1244.18' B. N. Bhar and G. Lindstrom, ibid., p. 1958.188 J. N. Shoolery and B. J. Alder, ibid., p. 805.189 B. E. Holder and M. P. Klein, ibid., p. 1956.19O H. E. Weaver, B. M. Tolbert, and R. C. La Force, ibid., p. 1956.lgl J. R. Van Wazer, C. F. Callis, and J. N. Shoolery, J . Amer. Chem. Soc., 1955,192 H. M. McConnell, A. D. McLean, and C. A. Reilly, J . Chem. Phys., 1955, 23,lg3 A. L. Bloom and J. N. Shoolery, Phys. Rev., 1955, 97, 1261.lS4 13.S. Gutowsky, L. H. Meyer, and D. ?V. McCall, .J. Chem. Phys., 1955, 23, 982;4941.W. D. Phillips, J . Chem. Phys., 1955, 23, 1363.77, 4945.1152 : M. K. Banerjee, T. P. Das, and A. K. Saha, Proc. Roy. SOL, 1954, A , 226, 490.E. B. Baker, ibid., p. 984SPECTROSCOPY AND MOLECULAR STRUCTURE. 91described.lg5 Application of the method has been made to odd-electronsystems such as the superoxide " broken " carbon-carbon bonds,lo7the free radicals present in polymers, lg8 semiquinones,lg9 and several poly-aromatic free radicals and ions.200 Copper phthalocyanine,201 and ferri-haemoglobin and myoglobin derivatives 202 have been investigated through theresonances of the electrons associated with the copper and iron atoms.Inorganic salts of iron,m3 manganese,m c~pper,~O~ titanium,m6chromium,m7 praseodymium,208 and rare earths have been studied.In anumber of cases, the analysis of the fine-structure pattern associated with themain resonances gave information about the symmetry properties of thecrystal fields surrounding the ion in the crystalline lattice.205Nuclear Quadrupole Resonance.-Pure quadrupole resonance spectraare observable in the radio-frequency region and are caused by the inter-action of nuclei which have quadrupole moments with the surrounding elec-trical fields in crystals. Once again the relative positions of the resonancesobserved for a given nucleus in different chemical compounds provideinformation about the electronic environment. More detailed directionalproperties can be deduced by studying single crystals and investigating theZeeman splitting of the main resonances when external magnetic fields areapplied. Nuclear quadrupole interactions are also responsible for finestructure effects in pure rotation microwave spectra. Although so far theresonances in halogen derivatives have been studied predominantly, work isnow being extended to the considerable number of other nuclei with quadru-pole moments.Useful reviews of the general experimental 210 and theoretical aspects 211of this branch of spectroscopy have been published recently. Other papershave been concerned with theoretical aspects of the subject,212 including theIg5 J. M. Hirshon and G. K. Fraenkel, Rev. Sci. Inst., 1955, 26, 34.J. E. Bennett, D. J. E. Ingram, M. C. R. Symons, P. George, and J. S. Griffith,Phil. Mug., 1955, 46, 443.197 J. E. Bennett, D. J. E. Ingram, and J. G. Tapley, J . Chem. Phys., 1955, !B, 215.195 C. H. Bamford, A. D. Jenkins, D. J. E. Ingra-m, and M. C. R. Symons, Nature,1955, 175, 894.19@ B. Venkataraman and G. K. Fraenkel, J . Clzem. Phys., 1955, 23, 588; J . Arner.Chem. SOC., 1955, 77, 2707; R. Hoskins, J . Chem. Phys., 1955, 23, 1975.2oo L. S. Singer and C. Kikuchi, ibid., p. 1738; G. Berthet, Compt. rend., 1955, 240,57; Y . Yokozawa and I. Tatsuzaki, J . Chem. Phys., 1954, 22, 2087; 0. R. Gilliam,R. I. Walter, and V. W. Cohen, ibid., 1955, 23, 1540.201 J. E. Bennett and D. J. E. lngram,.Nuture, 1955, 175, 130.202 J. E. Bennett, D. J. E. Ingram, P. George, and J. S. Griffith, ibid., 176,394.203 M. Tinkham, Proc. Phys. Soc., 1955, A , 68, 258.2oc N. S. Garifyanov and B. M. Kozyrev, Doklady Akad. Nauk, S.S.S.R., 1954, 98,929.205 B. Bleaney, K. D. Bowers, and D. J. E. Ingram, Proc. Roy. SOC., 1955, A , 228,147; B. Bleaney, K. D. Bowers, and R. S. Trenam, ibid., p. 157; B. Bleaney, K. D.Bowers, and M. H. L. Pryce, ibid., p. 166.206 B. Bleaney, G. S. Bogle, A. H. Cooke, R. J. Duffus, M. C. M. O'Brien,andK. W, H. Stevens, Proc. Phys. Soc., 1955, A , 68, 57.207 Y . Ting, L. D. Farringer, and D. Williams, Phys. Rev., 1955, 97, 1037; L. S.Singer, J . Chew. Phys., 1955, 23, 379.208 J. H. Anderson and C. A. Hutchison, Phys. Rev., 1955, 97, 76.209 A. H. Cooke and H. J. Duffus, Proc. Roy. SOC., 1955, A , 229, 407.210 M. Buyle-Bodin, Ann. Physique, 1956, 10, 533.211 Y . Ayant, ibid., p. 487.212 Y . K6i, A. Tsujimura, and T. Fuke, J . Chem. Phys., 1955, 23, 1346; M. H.Cohen, Phys. Rev., 1954, 96, 127892 GENERAL AND PHYSICAL CHEMISTRY.Zeeman effect.213 Measurements on chlorine resonances have been made onsodium chlorate (Zeeman effect) ?l4 organic acid chlorides,215 and chloro-acetic acid,216 chloroben~enes,~~~ and substituted chlorobenzenes,218 and asurvey has been made of a range of chloro-c~mpounds.~~~ Bromine deriv-atives investigated include bromates,220 bromobenzenes 221 (also withZeeman splitting 222), and cyanogen Resonances have also beenstudied in iodine,22P arsenic,225 and antimony derivatives.226Finally Duchesne and Monfils 227 claim to have observed radio-frequencyspectra with analogous apparatus, under conditions where quadrupoletransitions are not possible. The temperature dependence and the effect ofother experimental variables on the observed spectra led these authors tointerpret the very low frequencies observed in terms of transitions betweenclose-lying high-quantum-number vibrational levels of low frequencyfundamentals. J. H. C.D. M. S.N. S.P. G. ASHMORE.G. C. BOND.J. H. CALLOMON.F. S. DAINTON.G. A. H. ELTON.N. MILLER.R. M. NOYES.J. S. ROWLINSON.N. SHEPPARD.D. M. SIMPSON.L. VALENTINE.213 C. Dean, Phys. Rev., p. 1053.214 Y. Ting, E. R. Manring, and D. Williams, ibid., p. 408.215 P. J. Bray, J . Chem. Phys., 1955, 23, 703.316 H. Negita, ibid., p. 214.217 P. J. Bray, ibid., p. 220; J. Duchesne, A. Monfils, and J. Garsou, ibid., p. 1969;H. Negita, H. Yamamura, and H. Shima, BuU. Chem. Soe. Japan, 1955, 28, 271.218 K. Torizuka, J . Phys. Soe. Japan, 1954, 9, 645.*20 K. Shimomura, T. Kushida, N. Inoue, and Y. Imaeda, J . Chem. Phys., 1954, 22,221 P. J. Bray and R. G. Barnes, J . Chem. Phys., 1964, 22, 2023.s22 S. Kojima, K. Tsukada, and Y . Hinaga, J . Phys. SOC. Japan, 1955, 10, 498.223 S. Geller and A. L. Schawlow, J . Chem. Phys., 1955, 23, 779.224 S. Kojima, K. Tsukada, S. Ogawa, and A. Shimauchi, ibid., p. 1963.*25 R. G. Barnes and P. J. Bray, ibid., p. 407; S. Kojima, K. Tsukada, S. Ogawa,R. G. Barnes and P. J. Bray, J . Chem. Phys., 1955, 23, 1177; T-C. Wang, Phys.A. Monfils, Compt. rend., 1955, 241, 561.1944; T. Kushida, Y . K6i, and Y . Imaeda, J . Phys. SOC. Japan, 1954, 9, 809.A. Shimauchi, and Y. Abe, J . Phys. SOC. Japan, 1954.0, 805.Rev., 1955, 99, 566.227 J. Duchesne and A. Monfils, Bull. Classe Sci., Acad. voy. Belg., 1955, 41, 165

ISSN:0365-6217    

DOI:10.1039/AR9555200007

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.PREPARATIVE inorganic chemistry has seen some advances of the greatestimportance and interest during the year, but there have also been valuableadvances in valency theory particularly in relation to octahedral complexesand cycZopentadienyls.2Some of the most striking progress has concerned hyrides and relatedcompounds. The discovery that magnesium hydride can readily be pre-pared from the elements under moderate pressure may result in importantdevelopments, since it is possible that this hydride might undergo someuseful reactions analogous to those of lithium hydride. There have beeninteresting developments in the chemistry of aluminium hydride and itsderivatives; compounds prepared in the course of this work include, forexample, (AlH,*NMe,),.However, the greatest interest has centred aboutthe alkyl hydrides of aluminium which are involved in some of the recentprocesses, due to I<. Ziegler, for the polymerisation of olefins. The directsynthesis of trialkylaluminiums, e.g., A1 + 3C2H4 + 14H2 = AlEt,, is aparticularly important development, and triethylaluminium has foundfurther application as its double salt NaF,ZAlEt,, in processes for thelow-temperature purification of aluminium, for the electrodeposition ofaluminium, and for the preparation of tetraethyl-lead. Much interest hasbeen shown in the silicon hydrides in a variety of new compounds con-taining the silyl (SiH,) group ; these include the mixed hydride SiH,*PH,,and a number of compounds such as (SiH,),S, (SiH,),Se, which are devoid ofdonor properties on account of internal co-ordination, and the halidesSiH,*PI, and SiH,*AsI,.There has again been much progress in the study of allotropy and thepreparation of unstable forms of elements and compounds.The method offreezing unstable species on a " cold finger,'' which had earlier been used toprepare imine and some unusual forms of sulphur, has now been applied tooxygen. By the use of a trap cooled to 4.2" K, a colourless deposit can beseparated from oxygen which has been subjected to an electric discharge.Since this deposit, when allowed to warm slightly, gives a violet solid con-taining ozone, it was considered to contain an appreciable amount of atomicoxygen. Freezing out the product of an electric discharge on hydrazinehas given a bright yellow unstable compound, thought to be tetrazan,NH,*NH*NH*NH,. Another method of stabilising an unstable species isby solid solution in a stable solvent ; thus red solid solutions of europium(1x)oxide in barium oxide have been prepared.The preparation of black phosphorus has been achieved without the useof high pressures, since mercury has been found to catalyse the trans-formation P4 + Pblack.The value of much previous work on the allotropyof sulphur would appear to have been reduced by the discovery of the photo-sensitivity of freshly shock-chilled liquid sulphur ; this complicated systemis the subject of much current work.L. E. Orgel, J . Chem. Phys., 1955, 23, 1819.J. D. Dunitz and L. E. Orgel, ibid., p.95484 INORGANIC CHEMISTRY.There have been more developments in the inorganic chemistry ofsulphur, particularly of sulphur-nitrogen compounds, including, as examples,the violet monomeric and benzene-soluble tetra(thionitrosyl)nickel, Ni(NS),,LiAl(NS), (from LiAlH, + N,S4H4), and the fluorides N,S,F, and N,SF,(b. p. - 11"). Further interesting sulphur-fluorine compounds includethe tetrafluoride, SF, (b. p. -40.4"), whose existence had occasionally beenquestioned, the very strong acid CF,*SO,H (b. p, 162"), and the oxyfluoridesS,O,F,, S206F2, and S,O,F,.The preparation of milligram quantities of several di- and tetra-halidesand double halides of polonium has been a considerable experimentalachievement in view of the very high activity (138 day) of polonium.The highest oxide of bromine, previously described as Rr,O,, is actuallyBrO,.More metal alkoxides have been prepared, e.g., the liquid tantalum(v)ethoxide, Ta,(OEt),,.The structures and hydrolytic (and other) reactionsof this class of compound are dominated by the tendency of the metals toassume a covalency of six by co-ordination.Progress in the chemistry of the carbonyls, cyclopentadienyls, and relatedcompounds has been well maintained. The curious bonding of the hydrogenin the carbonyl hydrides is in course of being settled, and it seems that thehydrogen is situated symmetrically with respect to three carbonyl groupsand the bonding involves polycentric orbitals derived from three carbon andthree oxygen atoms as well as the hydrogen atom. The most notableadvances in cyclopentadienyls have been concerned with compounds con-taining both cyclopentadienyl and other groups in the molecule.Examplesare the carbonyls C,H,Mo(CO), (stable to air), (C,H,),Fe(CO),, and(C,H,Fe) , (CO) 4, the carbonyl hydride C,H,Cr (CO) ,H, the ni trosylsC,H,Ni(NO) and C,H,Cr(CO),(NO), and the hydride (C,H,),ReH.The nature of the benzene-chromium compounds, which have long beensomething of a mystery, is in course of elucidation. Most of the earlierfindings (Hein) have been confirmed, and it appears that these compoundsare closely related to the ~yclopentadienyls.~ Interesting developments inthe chemistry of this group of compounds are to be expected shortly.Review articles have been published on boron hydrides? boron hydro-gen sulphide (BHS), and its derivatives,, silicon chemistry,6 condensedphosphate^,^ cycZopentadienyls,8 and the alkyl and aryl derivatives of thetransition metals3 Reports have been published of symposia on isomerismin inorganic chemi~try,~ and organo-metallic compounds.1° Attention shouldalso be drawn to a new journal, the Joztrnal ofIizorganic and Nuclear Chemistry.Complexes.-The ' I Proceedings of the Symposium on Co-ordinationChemistry" have been published by the Danish Chemical Society.Thissymposium was held in August 1953, and was followed by another11 in3 F. A. Cotton, Chem. Rev., 1955, 55, 551; P. L. Pauson, Quart. Rev., 1955, 9, 391.4 I?. G. -4. Stone, ibid., p . 174.5 E. Wiberg and W.Sturm, Angew. Chem., 1955, 67, 483. * R. Schwarz, ibid., p . 117.E . Thilo, ibid., p . 141. * E. 0. Fischer, ibid., p. 475; P. L. Pauson, Quart. Rev., 1955, 9, 391.J. Phys. Chem., 1955, 59, 289.lo J. Chatt, Nature, 1955, 176, 159.Angew. Chem., 1955, 67, 401COATES ,4ND CLOCKLING. 95Amsterdam in 1955. Attention has been drawn to the desirability ofcomputing the formation constants of complexes by independent experi-mental methods, and an absorption spectrum procedure has been developedwhich has proved useful in determining the formation constants of 1 : 10-phenanthroline complexes with cobalt, nickel, copper, and zinc. Somediscrepancies in these constants had been noted.12There has been further use of magnetic measurement to investigate theequilibria between complexes differing in magnetic susceptibility.Forexample, heat and entropy changes have been obtained for the equilibriabetween the planar and tetrahedral forms of bis-N-methylsalicylaldimine-nickel in various non-donor solvents. Isotopically labelled ligands derivedfrom [~arbonyZ-~*C]salicylaldehyde were used to show that rapid ligandexchange occurred in pyridine solutions of bis-salicylaldoximenickel, bis-N-methylsalicylaldiminenickel, and bis-salicylaldiminenickel, in contrast tothe zero exchange with bis-salicylaldehyde-ethylenedi-iminenickel and bis-salicyaldehyde-o-phenylenedi-iminenickel. In general, complexes involvingthe use of outer (4d) orbitals undergo relatively rapid exchange.13Spectroscopic examination of a series of nitro-, nitrito-, thiocyanato-, andazido-pentammino-chromium(m) and -cobalt (111) salts indicates that whena choice is available chromium tends to become bonded to oxygen or sulphurand cobalt to nitrogen.Thus the azidopentamminochromium(I1I) salts aremuch less stable than the cobalt analogues. Similarly, Cr-NO, and Cr-NCScomplexes are pot known, and CO-O-NO passes spontaneously into CO-NO,.~*The possibility of using infrared measurements to distinguish cis- and trans-isomers has been examined for a series of cobalt(m) complexes. In ethylene-diamine complexes absorption in the 6*2--6*5-p region, due to N-H bending,is stronger in the trans-isomers and at wavelengths 0-04-0*08 p shorterthan those of the cis-isomers.15 Bisglycinecopper(r1) monohydrate andbisglycinenickel dihydrate have also been examined by infrared spectro-scopy.The absorption in the 6.25-p region indicates equivalence of thecarbon-oxygen bonds in the carboxyl groups. The metal-oxygen bonds inthese chelate complexes are regarded as essentially ionic.16A further example of the influence of steric hindrance on the formationof metal complexes is provided by 1-2’-pyridylisoquinoline (I) which givesa colour with traces of ferrous ion in contrast to the sterically hindered1 : 1’-diisoquinolyl (II).17Quantitative studies are reported on the co-ordination of thirteeniminodiacet ic acids, RON (C H,*CO,H),, to twelve met a1 cat ions. Particularlyl2 H. Irving and D. H. Mellor, J., 1955, 3457.l3 H. C. Clark and A.L. Odell, J., 1955, 3431, 3435.l4 M. Linhard, H. Siebert, and M. Weigel, 2. anorg: Chem., 1955. 278, 287.l6 D. N. Sen, S. Mizushima, C. Curran, and J. V. Quagliano, J. Anzer. Chem. SOC.,l7 11. Irving and A. Hampton, J., 1956, 430.P. E. Rlerritt and S. E. Wiberley, J. Phys. Chem., 1955, 59, 55.1955, 77, 21196 INORGANIC CHEMISTRY.interesting results were obtained by including a donor atom in the group R;for example, when R = *CH,*CH,*SH very stable complexes were formedwith heavy metals and there was a linear relation between the logarithm ofthe formation constant of the complex and that of the solubility product ofthe corresponding metal sulphide.18 The stability order Pb2+ >Cd2+ >Zn2+was found for co-ordination to the sulphur-containing amino-acids, cysteine,glutathione, and cysteine methyl ester.19In an investigation of the effect of electronically active substituents onco-ordination by phosphorus and arsenic, a number of complexes of copper(z),silver(r), zinc, cadmium, mercury, cobalt, and nickel with ligandsPh.P(or As)R2 (R = Me or Et) were prepared, and the effect of para-substituted NMe, and CF, groups noted.Steric effects were avoided sincethe active substituent is remote from the site of co-ordination. In general,metals which co-ordinate by both a ts and a strong x bond (e.g., mercury) arenot appreciably affected by electronic effects which greatly influence com-plexes (e.g., zinc) involving only Q or weak x bonds20 The formation of3-co-ordinate silver complexes, noted in this investigation, has been inter-preted in terms of the trigonal 5s5p2 arrangement of Q bonds allowing theremaining silver 59 orbital and two 4d orbitals to combineand form three x-type orbitals with the ligands.,lThiazone complexes of copper(r1) and nickel@) withconsiderable solubility in organic solvents have been prepared,and the effects of systematic variation of the groups R, R’,N-c*R1 and R” in (111) studied.22 The absorption spectra of thecomplexes are scarcely affected by variations in R and R’.Nickel complexes with some ligands containing formazyl groups have beendescribed,23 and magnetic moments are reported for complexes of bothnickel(I1) and palladium(I1) with vic.-dio~imes.~~Formation constants have been reported for complexes of substitutedcarboxy-pyridines and -quinolines in aqueous d i ~ x a n , ~ ~ quinoline-2- and-8-carboxylic acids,26 N-2-hydroxyethylethylenediaminetriacetic acid,27iron complexes of NN-bishydroxyethylglycine (OH*C,H,)2N*CH,*C02H,28 anumber of amin~-acids,~g and substituted phenols,30 histamine Complexes ofcobalt(rI), nickel(II), and copper(11) ,3l dimethylglyoxime complexes ofcobalt (11) and copper(11),32 hydroxyaldiminohydroxamic acid, oxyaldimineN-?RA sR*C// 1 / R<i r’,9( 718 G.Schwarzenbach, G. Anderegg, W. Schneider, and H. Senn, Helv. Chim. Acta,1Q N. C. Li and R. A. Manning, J . Amer. Chem. SOC., 1955, 77, 5226.20 R. C. Cass, G. E. Coates, and R. G. Hayter, J., 1955, 4007.21 S. Ahrland and J. Chatt, Chem.and Ind., 1955, 96.22 G. Bahr and E. Schleitzer, 2. anorg. Chem., 1955, 278, 136; 280, 161.23 M. Seyhan, Monatsh., 1955, 86. 545.24 C. V. Banks, R. W. V. Haar, and R. P. V. Wal, J . Amer. Chem. Sot., 1955, 77, 324.26 F. Holmes and W. R. C. Crimmin, J., 1955, 3467.2u Idem, ibid., p. 1175.17 S . Chaberek and A. E. Martell, J . Amer. Chem. SOC., 1955, 77, 1477.28 P. E. Toren and I. M. Kolthoff, ibid., p. 2061: R. M. Milburn, ibid., p. 2064.2e H. T. Bielig and E. Bayer, Chem. Ber., 1955, 88, 1158.30 A. Agren, Acta Chem. Scand., 1955,9, 39, 49; R. M. Milburn, J . Amer. Chem. SOL,31 B. L. Mickel and A. C. Andrews, ibid., p. 323.32 A. K. Babko and M. V. Korotun, Zhur. obshchei Khim., 1953, 23, 1302; 1954,1955, 38, 1147.1955, 77, 2064.24, 597COATES AND GLOCKLING.97and salicylaldimino-acid complexes of copper(I1) , nickel(@, cobalt(Ir), anduranium(v1) ,% nickel(I1) and copper(I1) complexes of p-ethoxyphenyldi-guanide and related compounds,~ and silver and copper 2 : 2'-dipyridylsa5Formation constants for the acetylacetone complexes of thorium(1v) and avariety of M3+ ions (e.g., A13+, Ga3+, In3+) have been determined,% togetherwith both enthalpy and entropy changes for the formation of the acetyl-acetone complexes of cerium(II1) and a range of M2+ ions.37Group I.-The previously described compound Li3Si has been shownnot to exist, but lithium does form a blue-violet crystalline silicide Li,Si,and a silver-grey one, Li4Si.38 Further phase-rule studies are reported onlithium borate 39 and on the ternary system Li20-B,03-H,0.40The absorption of hydrogen by fused alkali-metal hydroxides is greatlyinfluenced by their state of purity; hydrogen is extremely insoluble inthe pure fused hydroxide^.^^ The reasonably stable complexes formed bylithium and sodium with ethylenediaminetetra-acetic acid enable thesemetals to be separated by ion-exchange techniques.P2The vapour pressure of sodium in the pressure range 0.047-6.489 atm.is given by log Patm.= 4.521 - 5220/T. Thermodynamic data have beenobtained for the system 44 Na-NaH-H, at 500-600". Phase investigationson the systems Na,S0,-Li,S04-H,0 45 and N~SO4-Na,MoO4-H2O 46have been reported.A spectroscopic examination of the liquid compound Na(NH3),I revealsthe existence of the remarkably stable [Na(NH,!,]+ ion.It is suggestedthat ion-dipole forces are more important in this ion than in the transition-metal ammines.47Further investigations on the reaction between sodium amalgam andcarbon dioxide, whereby sodium oxalate is formed, show that the reaction isremarkably insensitive to carbon dioxide pressure over the range 1 - 4 0 atm.,and also to temperature. The reaction rate appears to be determinedmainly by the rate of exposure of fresh surface on shaking.48The copper fluorides have been examined by X-ray and electron micro-scopy. All attempts to obtain cupric fluoride were unsuccessf~l.~9 Thereaction between cupric chloride and acetone, 2CuC1, + COMe,---t2CuC1 + HC1 + CH,Cl*COMe, has been studied kineti~ally.~OA.K. Mukherjee and P. R%y, J . Indian Chem. Sot., 1955, 32, 605, 667, 681, 604.34 S. P. Ghosh and A. K. Banerjee, ibid., pp. 32, 141, 222.E. Scrocco and 0. Salvetti, Boll. sci. Fac. Chim. ind. Bologna, 1954, 12, 98.3e R. M. Izatt, W. C. Fernelius, C . G. Haas, and B. P. Block, J . Phys. Chem., 1955,37 Idem, ibid., p. 235.38 W. Klemm and M. Struck, 2. anorg. Chem., 1955, 278, 117.3D A. P. Rollet and R. Bouaziz, Compt. vend., 1955, 240, 1104, 2417.40 W. T. Reburn and W. A. Gale, J . Phys. Chem., 1955, 59, 19.*l E. A. Sullivan, S. Johnson, and M. D. Banus, J . A m r . Chem. Sot., 1955,77, 2023.42 F. Nelson, ibid., p. 813.43 M. M. Makansi, C. H. Muendel, and W. A. Selke, J . Phys. Chem., 1955, 59, 40.l4 M. D. Banus, J. J. McSharry, and E. A.Sullivan, J . Amer. Chm. Sot., 1955,77,2007.46 J. A. Skarulis and H. A. Horan, ibid., p. 3489.46 W. E. Cadbury, J . Phys. Chem., 1955, 59, 257.4 7 W. Leonard, E. R. Lippincott, R. D. Nelson, and D. E. Sellers, J . Amer. Chem.48 K. Schwabe and G. Gebbardt, 2. anorg. Chem., 1954, 277, 339.49 J. M. Crabtree, C. S. Lees, and K. Little, J . INorg. and Nmleav Chem., 1966,1, 213.6o J. K. Kochi, J . Amer. Chem. SOC., 1955, 77, 6274.59, 170.Soc.. 1955, 77, 2029.REP.-VOL. 1,II 98 INORGANIC CHEMISTRY.Some evidence has been found for the existence of an unstable copper(1)carbonyl cyanide. Copper(1) cyanide monoammine, CuCN,NH,, is onlysparingly soluble in liquid ammonia at -79", but dissolves to a concentrationof 0.05 molar when carbon monoxide is passed through the suspension.The electrical conductivity of the solution rises at the same time.If thecarbon monoxide stream is replaced by nitrogen, the cyanide ammine isprecipitated again, and the conductivity falls. No carbonyl cyanide couldbe isolated.51Copper(1) complexes with 2 : 2'-dipyridyl and other amines have beeninvestigated spectrophot~metrically.~~ Bisethylenediaminecopper(I1) evi-dently forms the [Cu(en),OH]+ ion in the presence of hydroxide.53 In thepresence of cis-3 : 4-dihydroxytetrahydrofuran and excess of hydroxide ionexchange of one chelating group occurs.54isoBut-l-enylsilver has been obtained by the reaction : Et,Pb*CH:CMe,+AgNO, + AgCHXMe, + Et,PbNO,. It is an unstable orange solidwhich decomposes above -20" into silver and isobut-l-enyl radicals.55 Anargentic oxide has been obtained by oxidation of Ag,O with alkaline hypo-chl0rite.~6Solutions of silver a i d e in sodium azide containing sodium perchloratehave been studied potentiometrically, and by the use of ll0Ag. The com-plexes formed are probably AgN,, [Ag(N,),]-, and [Ag(N3)4]3-, of which thesecond is the most stable.57 The species A&-, [A@,],-, and [AgIJ3- areprobably present in the system AgI-KI, but in the system Hg1,-KI onlythe complex ion [HgI,I2- was found.58The solubilities of silver acetate and silver nitrate in acetic acid, and theeffect on the solubilities of other added salts have been studied.59 Unstablesilver salts of cobalti-, mangani-, and ferri-cyanides have been prepared.60Ozone has been used in the quantitative oxidation of Ag(1) to Ag(r1) in thedipyridyl complex :2[Ag(C,oHJJ,)21f + 2Hf + 0, ~ [ A ~ .( C I O H P ~ ) ~ I ~ + H2O + 0 2Stability data are reported for the 3-co-ordinated thiourea-silver com-plex 62 and for Ag(1) complexes with some 3- and 4-substituted pyridines,e.g., 3-metho~ypyridine.~~Group 11.-Beryllium boride, Be,B, formed from the elements at 1400°,has been further studied, together with its dissolution in acids with form-ation of boron hydrides.@ In continued investigations on systems analogous51 H. Weiss, 2. anorg. Chem., 1955, 280, 284.62 R. T. Pflaum and W. W. Brandt, J . Amer. Chem. SOC., 1955, '77, 2019.53 H. B. Jonassen, R. E. Reeves, and L. Segal, ibid., p. 2748.64 Idem, ibid., p.2667.55 F. Glockling, J., 1955, 716.56 .R. L. Dutta, J . Indian Chem. SOC., 1955, 32, 95.5' I. Leden and N. H. Schoon, Trans. Chalmers Univ. Technol., Gothenburg, 1954,5 8 A. M. Golub, Ukrain. khim. Zhur., 1953, 19. 467.60 A. Malaguti and T. Labianca, Gazzetta, 1954, 84, 979.61 Idem, ibid., p. 976.62 W. S. Fyfe, J., 1955, 1032.63 R. K. Murmann and F. Basolo, J . Amer. Chem. SOC., 1955, 77, 3484.64 L. Y. Markovskii, Y . D. Kondrashev, and I. A. Goryacheva, DorZZady Akad.144,3.R. I<. Birdwhistell and E. Griswold, J . Amer. Chem. SOC., 1955, 77, 873.Nauk, S.S.S.R., 1955, 101, 97COATES AND GLOCKLING. 99to silicates, another tetrafluoroberyllate, Na3Li(BeF4),, has been obtainedby crystallisation from solutions weakly acidic with respect to hydrofluoricacid.65 Three complexes have been found in the beryllium-citrate systemin the pH range 3 4 , viz., BeH,Cit+, BeHCit, and BeCit-; above pH 4polynuclear complexes are formed.66Magnesium hydride, MgH,, which had earlier been obtained by thepyrolysis of the dialkyls of magnesium, has now been prepared in quantityfrom magnesium and hydrogen.It is necessary to use moderate pressuresof hydrogen in the direct synthesis since the reaction rate is appreciable onlyat temperatures at which the dissociation pressure is also appreciable. Thehydride was obtained as a light grey powder stable to air and only slowlyhydrolysed by water, in contrast to the hydride obtained by the pyrolysis of,for example, diethylrnagne~ium.~~The carbides of magnesium are of considerable interest since one ofthem, Mg,C,, is hydrolysed to propyne.The conditions under whichthese carbides are formed from calcium carbide and magnesium chloride havebeen studied in detail; in the presence of sodium chloride, which gives alow-melting (425") ternary eutectic (MgCl,,CaCl,,NaCl), reaction occurs at500", giving the acetylide MgC,. Above 550" the acetylide is transformedinto Mg2C,, which is decomposed into its elements above 740-750". Thereaction ZMgC, + Mg,C, + C could not be reversed.68Vaporisation from giant molecules has recently attracted some attention,and, for example, the species C, has been identified in the products of theevaporation of graphite. Similarly the diatomic species Mg, has been foundin the immediate products of the evaporation of magnesium nitride, Mg,N,.The final products are Mg (gas) and nitrogen.69Solubility and phase-rule data are reported for the systems Mg(BrO,),-H20,70 MgO-MgC1,-H,O, 71 and CaSi0,-CaF,.72 Alkaline-earth (M) molyb-dates, tungstates, and uranates of the type M,BO, (B = Mo, W, or U) areformed by heating MBO, at 800-1000" in oxygen. The compounds M,BO,(B = Mo or W) are formed similarly.73 Preparative methods have beendescribed for the calcium phosphates CaHP0,,2H20, and Ca,P,O, 74 andfor hydr~xyapatite,~~ all in good purity. Barium bromide and iodide forma series of complexes with urea, identified in aqueous solution, from(BaX,),,urea to BaX,, (urea),. 76 The double nitrate Ba(N0,),,2KN03 hasbeen identified in a study of the Ba2+-K+-N03--H,0 system.7765 W.Jahn, Z . anorg. Chem., 1954, 277, 274.66 I. Feldman, T. Y . Toribara, J. R. Havill, and W. F. Neuman, J . Amer. Chew.67 F. H. Ellinger, C. E. Holley, B. B. McInteer, D. Pavone, R. M. Potter, E. Staritzky,68 A. Schneider and J. F. Cordes, 2. anorg. Chem., 1955, 279, 94.69 J. R. Soulen, P. Sthapitanonda, and J. L. Margrave, J . Phys. Chem., 1955, 59,70 W. F. Linke, J . Amer. Chem. Soc., 1955, 77, 866.71 T. Demediuk, W,.F. Cole, and H. V. Hueber, Austral. J . Chem., 1955, 8, 215.72 T. BQBk and A. Olander, Acta Chem. Scand., 1955, 9, 1350.78 R. Scholder and L. Brixner, 2. Naturforsch., 1955, lob, 178.74 P. D. S. St. Pierre, J . Atner. Chem. Sot., 1955, 77, 2197.75 E. Hayek and W. Stadlmann, Awgew.Chem., 1955, 87, 327.7 6 C. S. Pande and M. P. Bhatnagar, 2. anorg. Chem., 1955, 280, 147, 153.7 7 M. M. Markowitz, J. E, Ricci, and I?. F. Winternitz, J . Amer. Chem. Sot., 1955,Sot., 1955, 77, 878.and W. H. Zachariasen, ibid., p. 2647.132.77, 3482100 INORGANIC CHEMISTRY.The species [Zn(NH,-OH)(H,0),]2+ and [Zn(NH2*OH),(H,0),]2+ havebeen identified in aqueous solution by polarographic methods.78 A rangeof cadmium o-phenylenediamine complexes of the type (Cd[C6Hp(NH2)2]2)X,(X = halogen, CNS, NO,) are reported in which the phenylenediamine groupmay be partly or wholly replaced by ammonia, ethylenediamine, orthiourea. 79A new rhombohedra1 form of mercuric oxide, orange in colour, has beenobtained in well-crystallised form by slow precipitation from aqueoussolution. It is transformed irreversibly into the orthorhombic form above200".8*Mercury forms complexes of the type [Hg(diamine),12+ with ethylene-diamine, propane-1 : 2-diamine, and diethylenetriamine.Formation con-stants were obtained polarographically.81 Investigations of the ionicspecies present in mercuric chloride solutions have been extended, andevidence found for the existence of the HgOH+ ion; the complexHg(0H) [Cr(SCN),(NH,),] was isolated. Several other basic mercury saltswere also prepared. 82Group III.-Rapid exchange occurs between diborane and lOB-enricheddiborane at 25" which is consistent with the accepted hydrogen-bridgedstructure for diborane. In contrast, pentaborane, with a pyramidal struc-ture, does not exchange even at high temperatures.a The solid-liquidequilibrium for diborane and tetrahydrofuran shows the existence of theexpected co-ordination compound, 84 C,H,O,BH,.Diborane and perfluoro-ethylene undergo a slow reaction at room temperature. Some of theolefin is polymerised and volatile products include BF,, EtBF,, andEt2BF.85The formation and reactions of alkali-metal borohydrides continue toattract attention. Pure water at 0" dissolves lithium borohydride withouthydrogen evolution. At higher temperatures partial hydrolysis occurs : 86LiBH, + LiBH,(OH) + LiBH,(OH),. In a preliminary account of thereactions occurring between sodium borohydride and carbon dioxide it isfound that in a sealed tube at 125" two mols.of carbon dioxide react toform a white solid which yields methanol and formic acid on hydrolysis.The reaction suggested is : NaBH, + 2C0, NaBO(H*CO,)(OMe). Atlower temperatures in dimethyl ether solution 3 mols. of carbondioxide combine, forming a formatoborohydride : NaBH, + 3c02 +NaBH(H*CO,),. 87 Lithium borohydride and polymeric aminoborine,BH,*NH2, are formed from diborane and lithium amide in ether solution.88Lithium borohydride and monoalkylammonium halides in ether solution78 C. J. Nyman, J. Anzer. Chem. Soc., 1955, 77, 1371.79 I. A. Fedorov. Imest. Sekt. Platiny drug. blogorod. Metal., Inst. obshchei neorg.80 P. Laruelle, Compt. rend., 1955, 241, 802.81 C. J. Nyman, D. K. Roe, and D. B. Masson. J. Amer. Chem. SOC., 1955, 77, 4191.S2 K.Damm and A. Webs, 2. Naturforsch., 1955, lob, 534.83 I. Shapiro and B. Keilin, J. Amer. Ckeem. Soc., 1955, 77, 2663.84 B. Rice, J. A. Livasy, and G. W. Schaeffer, ibid., p. 2750.8 5 F. G. A. Stone and W. A. G. Graham, Chem. and Ifid., 1955, 1181.8E V. I. Mikheeva and E. M. Fedneva, Doklady Akad. Nauk, S.S.S.R., 1955, 101,T. Wartik and R. K. Peanon, J . Amer. Chem. Soc., 1955,77, 1075.88 G. W. Schaeffer and L. J. Bade, ibid., p. 331.zoo loooKkim. Akad. Nauk S.S.S.R., 1954, 28, 166 (Cheem. Abs., 1955, 49, 3714).99COATES AND GLOCKLING. 101form the borines, H,B*NH,R, which are converted into the N-trialkyl-borazoles on pyrolysis :LiBH, + RNH,CI LiCl + H, + H,B*NH,R3H,B*NH,R __+ B,H,N,R, + 6H,Under milder conditions methylamineborine forms the hydrogenatedtrimer, N-methylaminoborane :3Me*NH,*BH, 3H, + (Me-NH-BH,),Pyridine-borine, C,H,N*BH,, is very conveniently prepared by thereaction : py,HCl + NaBH, -% py,BH, + NaCl + H,.91The well-known analogy between borazole and benzene has stimulatedvarious spectroscopic and other investigations , which have shown thatborazole has considerably less aromatic character than benzene on accountof the tendency of the 7c electrons to remain close to the nitrogen atoms.Anew series of heterocyclic compounds containing carbon, boron, and nitrogenhas recently been described. The complex (IV) formed by ethylenediamineand trimethylboron loses methane at -250°, with the formation of thediborazen (V). As might be expected, this polymerises very easily, to anMe,B-$H,*CH,*CH,*~H,-BMe, Me,B=~H*CH,.CH,.~H=BMe,(IV) (V)unfamiliar type of co-ordination polymer.Elimination of methane froma 1 : 1 mixture of trimethylboron and ethylenediamine affords, in additionto polymeric matter, a compound (VI), whose Raman spectrum and reactions/ \Me Me me Me(=> m 4 m b )with hydrogen chloride point to a cyclic structure. At about 440470'another mol. of methane is lost, with the formation of (VIIa, b), m. p.43*5*, b. p. 106". The Raman spectrum of (VIIa, b) is consistent with B-Nbonds of order 1-5. It is remarkable that (VIIa, b) has a smell very similarto that of the isosteric (or homomorphic) N-methylpyrroline. A similarseries of six-membered ring compounds has been obtained from trimethyl-boron and trimethylenediamine.gzSome physical properties are reported for bora~ole.~~ B-Trichloro-borazole, (CIBNH),, can be conveniently obtained from boron trichloride andammonium chloride at temperatures above 1 Thermal decompositionof tri-n-butylboron yields dibutyldiborane and either tram-but-2-ene orbut-l-ene depending on the decomposition temperat~re.~~W.V. Hough, G. W. Schaeffer, M. Dzurus, and A. C. Stewart, J . Arner. Chem.SOC., 77, 1955, 864.O0 T. C. Bissot and R. W. Parry, ibid., p. 3481.91 M. D. Taylor, L. R. Grant, and C. A. Sands, ibid., p. 1506.92 J. Coubeau and A. Zappel, 2. anorg. Chem., 1955, 279, 38.98 L. B. Eddy, S . H. Smith, and R. R. Miller, J. Aswzev. Chem. Sor., 1955, 77, 2105.O4 C. A. Brown and A. W. Laubengayer, ibid., p. 3699.96 L.Rosenblum, ibid., p. 5016102 INORGANIC CHEMISTRY.Further work is reported on cyclic boron-sulphur compounds derivedfrom (BHS),. Thus, bromoboron sulphide, (BBrS),, and trimethyl borateform the methoxyboron sulphide (MeOoBS), , which disproportionates whenheated into B2S3 and (MeO),B. The related dimethylamino-compound[B(NMe,)S], was similarly obtained from B(NMe,), or Al(NMe,), and thebromoboron sulphide or metathioboric acid [B(SH)S], ; from most of thesereactions fairly stable addition compounds can first be isolated. Withhydrogen iodide metathioboric acid forms iodoboron sulphide, (BSI), ascolourless needles, m. p. 122" (decomp.). Similarly, trimethylboron andmetathioboric acid give the compounds (BMe-S), which can be oxidisedreadily to the methoxyborosulphide, [B(OMe)S],.The corresponding phenylcompound was obtained by the reaction : SBPhBr, + 3H,S + (BPh-S), +6HBr. Vacuum distillation of the ethyl ester of metathioboric acid at150-160" gave an interesting dimeric form of the ester : 96[B(SH)SI, + B(SEt)3 __+ [B(SEt)SI, [B(SEt)SIzSeveral methods have been devised for obtaining tetra-alkoxy-boratesof the alkaline-earth metals, e.g.,M + 2ROH + 2B(OR), - M[B(0R),I2 + H2Thermal decomposition of these alkoxyborates follows the courseM[B(OR)4]2 -+ M(OR), + 2B(OR),, whilst treatment with diborane givesthe metal borohydride : 97M(BH4)Z + 8ROH __t M[B(OR)4]z + 8H23M[B(OR)4?2 -k 4BzH13 3M(BH4)z + 8B(OR)3Triphenyl borate forms addition compounds with a variety of amines.The phenoxyboron chlorides disproportionate reversibly and also co-ordinatewith ~yridine.~* n-Butyl difluoroboronite, BuO*BF,, obtained from boronfluoride and tributyl borate, is dimeric like the corresponding methyl com-pound.99 The primary alkyl dichloroboronites are stable to 20" but thosewith secondary alkyl groups are much less stable.loO Quaternary ammoniumhalides and boron trifluoride-dimethyl ether or fluoroboric acid form quatern-ary ammonium fluoboratesJlo1 Me4N*BF4.When a mixture of boron tribromide (b.p. 92") and boron trichloride(b. p. 12") is fractionally distilled, the boiling point rises continuously as allfour possible substances, BCl,, BCl,Br, BClBr,, and BBr,, are present inmobile equilibrium. The equilibrium constant has been obtained fromRaman spectrum intensities : 10,[BCl,Br] [BClBr,] /[BCl,][BBr,] z 7.8Similarly, the equilibrium constant for boron trifluoride-boron trichloridemixtures has been evaluated from infrared absorption measurements : lo3[BFC12][BF~Cl]/[BF3][BCl,] = 0-53 f 0.04 at -28Os6 E.Wiberg and W. Sturm, 2. Nuturforsch., 1955, lob, 108.9' E. Wiberg and R. Hartwimmer, ibid., p. 290.98 T. Colclough, W. Grrard, and M. F. Lappert, J., 1955, 907.ss M. F. Lappert, J., 1955, 784.100 W. Gerrard and M. F. Lappert, J., 1955, 3084.lol C. M. Wheeler and R. A. Sandstedt, J , Amer. Chem. Soc., 1955, 77, 2024.Io2 J. Goubeau, D. E. Richter, and H. J. Becher, 2. umorg. Chem., 1955, 278, 12.Io3 T. H. S. Higgins, E. C. Liesegang, C.J. G. Raw, and A. J. Rossouw, J . Chenz.Phys., 1955, 23, 1544COATES AND GLOCKLING. 103The earlier finding lo4 that boron nitride is fluorinated to boron tri-fluoride and nitrogen rather than to nitrogen trifluoride, has been confirmedby more elaborate experiments. Boron nitride forms ammonium boro-fluoride with hydrogen fluoride.lo5The complex reactions occurring between aluminium hydride andammonia have received detailed study. The initially formed adduct,A1H3*NH,, decomposes with loss of hydrogen at -30", forming the polymerichydride (AlH,*NH,),. At room temperature a further mol. of hydrogen isevolved, again giving a polymeric product, (AlH:NH),. Further decom-position to the nitride, AlN, was incomplete at temperatures up to 150".With excess of ammonia a stepwise amidation takes place ; the final product,aluminium amide, Al(NH,),, is unstable and decomposes stepwise intoaluminium nitride :- soo - 60" - 30° 20°AlH, AlHa'NHa __t AlH(NH2)Z Al(NH2)S +4 days430'Al(NH)*NH, __I) AlNMethylamine forms an analogous series of compounds ; those characterisedinclude AlH,(NHMe), AlHINMe, AlH(NHMe),, and Al(NHMe),.Di-methylamine and aluminium hydride behave rather differently, and at-40" equimolar quantities form the adduct A1H3,NHMe, which at roomtemperature decomposes into the dimer [AlH,*NMeJ,. The conipoundsAlH(NMe,), and Al(NMe,), are formed when excess of amine is present.The latter is evidently monomeric in boiling ether. Tertiary amines andtriethylphosphine co-ordinate readily with aluminium hydride, forming1 : 1 adducts, e.g., AlH,,NR,.The behaviour of pyridine is more complex.At low temperatures (-30") two addition compounds are formed : AlH,,pyand A1H3,2py, both of which are unstable and at room temperature undergoan exothermic reaction with formation of highly-coloured pyridyl com-plexes.1O6The importance of organic aluminium compounds in connection withprocesses for the polymerisation of olefins is well known, and has stimulatedmuch work on the organic chemistry of aluminium. Developments of someinorganic interest include measurements of the heats of co-ordination totriethylaluminium of a number of ethers and amines. These heats areEt+I - ,CHrC* N C 4 E t 2 .:'t"-l%NEtrCH, %Et-CH,(nm) (=-Imostly in the range 10-20 kcal./mole.Conductometric titration of tri-ethylaluminium in benzene solution with an ether or tertiary amine (e.g.,isoquinoline) indicates some degree of self-dissociation : 107 2R3Al &R2A1+ + R,Al-. Other developments include the preparation of some innercomplexes such as (VIII), (IX), and the thio-analogue of (VIII).lO*lo* G. E. Coates, J. Harris, and T. Sutcliffe, J., 1951, 2762.lo5 0. Glemser and H. Haeseler, 2. alzorg. Chem., 1955, 279, 141.E. Wiberg and A. Map, 2. Naturforsch., 1955, lob, 229.lo' E. Bonitz, Chem. Ber., 1955, 88, 742.l o 8 G. B a r and G. E. Muller, ibid., pp. 251, 1765104 INORGAN'IC CHEMISTRY.A preliminary account has been given of the formation of aluminiumalkyls from the metal, hydrogen, and an olefin (ethylene, mono- and 1 : l-di-substituted ethylenes), e.g., A1 + 3C2H4 + liH2 Et,Al.Under theappropriate conditions the dialkyl hydride can be obtained : 2R3Al + A1 +14H2 + 3R2AlH. Thermal decomposition of triisobutylaluminium can becarried out in two stages :150' 250'(Me,CHCH,),Al+ (Me,CH*CH,),AlH + A1 + H, + Me,C:CH,Electrolysis of the liquid compound Na[Et,AIF],Et,AI has been used toobtain high-purity aluminium. With a lead anode and an aluminiumcathode on which aluminium is deposited a quantitative yield of tetraethyl-lead can be obtained; this is equivalent to an overall synthesis : 109Pb + 4C2H4 + 2H2 = Et,Pb.In an investigation on the physical properties of aluminium oxide-chromium(II1) oxide mixed crystals, the characteristic ruby colour was foundto appear up to 8% Cr203 content ; at higher chromium contents the colourchanges through grey to green at >30y0 of Cr203 when chromic ions arefrequently adjacent to each other.l1°Cryoscopic investigations ll1 on NaF-A1F3-A1,0, melts, of importancein connection with the extraction of aluminium, show that the anions[A102FJ3- and [A1F5~AI0,F4*AlF,]g- are present as well as [A1Fs]3-.The conductivity of aluminium bromide in dry ethyl bromide has beenre-investigated.The initial molar conductivity ( 10-2-10-1 mho) is duemainly to solvated [AIBr2]+ and [AlBrJ ions. The increase in conductivitywith time is due to decomposition of the EtBr-A1,Rr6 complex into olefinand hydrogen bromide.l12 A relatively stable soluble complex having thecomposition Al(NH2)l.51p5 has been obtained 113 from the reaction betweenA11,,6NH3 and solutions of alkali and alkaline-earth metals in liquid ammoniaat -70".The extraction of scandium from the minerals thortveitite and wolframitehas been investigated by ion-exchange techniques.The precipitation ofscandium hydroxide by caustic alkali or ammonium hydroxide is evidentlyincomplete owing to formation of scandate and hexamminoscandate ionsrespectively. Scandium oxalate, which is incompletely precipitated, formshydrates with 3, 6, and 18 molecules of water. The hydrated oxalate formsthe complex [Sc(NH,),],(C,?,), with ammonia.l14The rare-earth metal oxides and ethylenediaminetetra-acetic acid formcomplexes of the type Ln[Ln(enta)],,xH,O and H[Ln(enta)],yH,O (Ln =lanthanon), the latter being moderately strong acids.115 Methylaminecombines readily with the rare-earth chlorides, forming the complexesMCl,,nMe*NH, where n lies between 1 and 5.116 Hexanitrito-complexes of109 K.Ziegler, H. G. Gellert, K. Zosel, W. Lehmkuhl, and W. Pfohl, Angew. Chem.,1955, 67, 424.110 E. Thilo, J. Jander, and H. Seeman, 2. anorg. Chem.. 1955, 279, 2.1 x 1 T. Forland, H. Storegraven. and S. Umes, ibid., p. 205.112 F. Fairbrother and N. Scott, J., 1955, 452.11s W. L. Taylor, E. Griswold, and J. Kleinberg, J . Amer. Chenz. Soc., 1955, 77, 294.114 R. C. Vickery, J., 1955, 245, 251.115 T. Moeller, F. A. J. Moss, and R. H. Marshall, J . A m y . Chem. SOC., 1955, 77,3182 ; G. Brunisholz, Helv.Chim. Acta, 1955, 38, 455, 1654 ; G. Brunisholz, E. Vescovi,and M. Lorktan, ibid., p. 1186; see also J. Loriers, Compt. rend., 1955, 240, 1537.A. I. Popov and W. W. Wendlandt, J . Amer. Chem. SOC., 1955, 77, 857COATES AND GLOCKLING. 105several rare-earth metals have been reported, e.g., Cs,Na[M(NO,),] (M = La,Pr, Y). Each complex contains four molecules per unit cell.l17Ion-exchange experiments indicate t h a t the trisulphitolanthanon ion[Ln(S0,),l3- is the main component of lanthanon bisulphite " solutions.Such solutions are readily oxidised to the sulphate Ln,(SO,),. The normallanthanon sulphites are obtained by partial removal of sulphur dioxide fromthe trisulphito-complexes.l18High-temperature studies, using radioactive cerium, on the systemBaCl2-CeC1,-BaZrO, have shown the formation of the phase Ce20,,2Zr0,which is readily oxidised to Ce02,Zr02.119 The high-temperature reductionof cerium(rv) oxide by hydrogen is accelerated by the admixture of smallamounts of other rare-earth oxides or uranium oxide.These experimentsare of particular interest in connection with solid-state reaction theory.120The composition of cerous citrate complexes over a wide pH range isreported. l 2 1Europium can be efficiently separated from samarium by electrolysis ofthe citrate at a lithium amalgam cathode.f22 Europium dichloride is slowlyoxidised in hydrochloric acid solution : Eu2+ + H+ + Eu3* + 4H2. Inthe presence of oxygen the reaction is more rapid : Eu2+ + H+ + Q02+Eu3+ + +H,0.123Compounds in which a metal has an unstable oxidation level can some-times be stabilised by solid solution in a stable medium of similar crystalstructure.Thus, europium(rr) oxide, which has not previously been pre-pared, has been obtained in the form of red solid solutions of EuO in stron-tium oxide. These solid solutions have been formed by thermal decom-position of the mixed carbonates, by reducing the mixed oxides (SrO +Eu203) with hydrogen, or by pumping oxygen, at low pressure, from themixed oxides at 1000°.124The use of basic nitrates for the enrichment of erbium and holmium hasbeen described.125Actinium has been prepared on the milligram scale by reduction of thefluoride with lithium vapour. It has m. p. 1050" &- 50" and resembleslanthanum both chemically and physically.126The first structure analysis of a gallium(I1) compound, Gas, reveals alayer lattice which must contain Gat+ ions.127Gallium iodide, GaI, (m. p.211"), disproportionates into GaI, and GaIin contrast to the behaviour of the chloride, GaCl,, which gives the metaland GaC1,.12* Gallium(1) and indium(1) chlorides can be prepared by heatingthe metals in a gaseous mixture of 99% argon and 1% chl0rine.1~~117 A. Ferrari, L. Cavalca, and M. Nardelli, Gazzetta, 1953, 83, 1082.11* R. C. Vickery, J., 1955, 2360.11s J. J. Casey, L. Katz, and W. C. Orr, J . Amer. Chem. SOC., 1955, 77, 2187.lZo G. Brauer and U. Holtschmidt, 2. anorg. Chem., 1955, 279, 129.121 M. Bobtelsky and B. Graus, J . Amer. Chem. SOC., 1955, 77, 1990.122 E.I. Onstott, ibid., p. 2129.C. T. Stubblefield and L. Eyring, ibid., p. 3004.G. Brauer, R. Miiller, and K. H. Zapp, 2. anovg. Chem., 1955, 280, 41.125 J. K. Marsh, I., 1955, 336.126 J . G. Stites, M. L. Salutsky, and B. D. Stone, J . Amer. Chem. SOC., 1955, 77,H. Hahn and G. Frank, 2. anorg. Chem., 1955, 278, 340.12* J. D. Corbett and R. K. McMullan, J . Amer. Chem. SOC., 1955, 77. 4217.lzD E. Gastinger, Angew. Chem., 1955, 67, 103.237106 INORGANIC CHEMISTRY.The luminescence of solutions containing alkali halides and t hallouschloride has been attributed to the presence of thallium halide complexes.Solubility data have now revealed the presence of the [TICIA- ion in thesesolutions.130Group 1V.-The partial pressure of carbon vapour has been measured inequilibrium with graphite, tantalum carbide, and tungsten carbide.Thepartial pressures were very similar for the three substances and the gas wasconsidered to consist largely of C,; these results gave 170 kcal. as the heatof sublimation of carbon at 0" K. Supplementary mass-spectrometermeasurements confirm this value and indicate that the heats of sublimationto C, and C, molecules are 190 and 200 kcal./mole, respectively.132Aluminium chloride may be added to the list of substances which can bemade to enter the graphite lattice. The compounds, in which aluminiumchloride is present as Al,Cl, molecules, are formed by heating the componentsat temperatures between 200" and 440", and contain a chloride layer toevery one, two, or four carbon layers according to preparative conditions.lSThe decomposition of carbon monoxide, mainly the reaction 2CO =Cgr.+ CO,, is of interest in various metallurgical processes, and has beenstudied in some detail in the presence of iron and its nitrides andphosphides.lXThe electrolytic formation of paracyanogen (Hittorf, 1892) has beeninvestigated ; the black deposit is rather intractable but differs markedlyfrom paracyanogen produced by other methods, being similar to the ill-defined product, azulmic acid, formed in the polymerisation of hydrogencyanide.135 The formation of guanidine from carbon tetrahalides andammonia at temperatures between 25" and 300" has received fairly detailedstudy. 136A number of rather novel compounds containing the silyl (SiH,) grouphas been prepared, starting from silane or silyl iodide.Silyl iodide itselfforms 1 : 1 addition compounds with trimethylamine, trimethylphosphine,and trimethylarsine, the first two adducts being electrolytes in vinyl cyanide.The compounds SiH,-PI, and SiH,*AsI, have been isolated from the reactionof silyl iodide with phosphorus and arsenic; they decompose belowSilyl sulphide and selenide have been prepared by the reactionsSiHJ + HgS __tc (SiH,),SandSiHJ + Ag,Se __+ (SiH,),SeBoth these compounds and the oxide (SiH,),O lack donor properties, owingno doubt to back co-ordination [cf. (SiH,),N] .138Although silylphosphine SiH,*PH, was briefly reported in 1953 ,139 details130 K. H. Hu and A. €3. Scott, J .Amer. Chem. SOC., 1955, 77, 1380.131 M. Hoch, P. E. Blackburn, D. P. Dingledy, and H. L. Johnston, J . Phys. Chem.,132 W. A. Chupka and M. G. Inghram, ibid., p. 100.13s W. Riidorff and R. Zeller, 2. anorg. Chem., 1955, 279, 182.194 P. Royen and W. Blumrich, 2. anorg. Chem., 1955, 280, 294.135 J. S. Fitzgerald, Chem. and Ind., 1955, 17.196 G. W. Watt and H. T. Hahn, J . Amer. Chem. SOL, 1955, 77, 312.137 B. J. Aylett, H. J. Emeleus, and A. G. Maddock, J . Inorganic and Nuclear Chem.,138 H. J. EmelCus, A. G. MacDiarmid, and A. G. Maddock, ibid., p. 194.180 G. Fritz, 2. Naturforsch., 1953, 8b, 776.1955, 59, 97.1955, 1, 187COATES AND GLOCKLING. 107have only just been published. Silane is less stable to thermal decom-position than phosphine, and heating a mixture of the two hydrides resultsin attack on the phosphine by hydrogen atoms from the silane.At 450"silylphosphine, b. p. 12*7", is formed. This mixed hydride is very sensitiveto air and is spontaneously inflammable. Although unreactive to water itis hydrolysed by alkali with formation of silica, silane, and phosphine. Theinitial reaction is likely to beSiH,-PH, + H,O = H,Si*OH + PH,followed by disproportionation of the H,Si*OH. Similarly, reaction withhydrogen bromide affords silyl bromide and phosphine (or phosphoniumbromide) .l40 The rapid and quantitative reaction,SiH, + 8HgC1, + 4H,O = Si(OH), + 8HgCl + 8HC1has been applied to the determination of Si-H bonds in various ~i1anes.l~~Earlier X-ray evidence that silicon monoxide can be produced frommixtures of silicon and silica has been criticised. The X-ray pattern is nowascribed to a mixture of p-cristobalite and p-silicon carbide, the latter formedas an impurity.142 On the other hand, silicon monosulphide is formed fromthe elements via the d i s ~ l p h i d e , ~ ~ ~ SiS, -t Si = 2SiS.The high-temperature (700-1 100') reactions between silicon tetra-chloride and hydrogen sulphide have been studied in further detail and haveled to the isolation of the following compounds : SiCl,*SH, (SiCl,),S, Si,S,Cl,,and (SiSC1,),.144 The first of these is reported to be tetrameric and decom-poses thermally with formation of some thiochloride Si,SCl,, which is alsoformed from silver sulphide and C1,SiI at 250°.145Fluorosulphonic acid has found further laboratory application in a con-venient preparation of silicon tetrafluoride ; this can be carried out inconventional glass apparatus : 146Thermodynamic data have been obtained for the diammine, SiF,,2NH3.147SiO, + 2H,O + 4H*SO,F = SiF, + 4H,SO,A variety of polysilicate esters has been prepared bythe use of 2 : 2'-dihydroxydiphenyl, which affords (X)with excess of silicon tetrachloride.A number of metalo\s I oxides, particularly silver oxide, react with (X) by exchangeo/ \ci of chlorine for oxygen. The products consist of spiro-siloxanes which can be polymerised to molecular weightsup to 5000.148Two new calcium hydrogen silicates have beendescribed, Ca(H,SiO,), and Ca(H,S!,O,). An interestingaspect of the preparation of the first is the use of liquid ammonia as a low-temperature dehydrating agent.149 By variation of silver and silicate8 (=)140 G. Fritz, 2. anorg. Chem., 1955, 280, 332.141 Idem, ibid., p. 134.142 S. Geller and C. D. Thurmond, J. Amer. Chem. Soc., 1955, 77, 5285.143 W. C. Schumb and W. J. Bernard, ibid., p. 904.144 D. J. Panckhurst, C. J. Wilkins, and P. W. Craighead, J., 1955, 3395.145 W. C. Schumb and W. J. Bernard, J. Amer. Chem. Soc., 1955, 77, 862.146 L. J. Belf, Chem. and Ind., 1955, 1296.147 D. B. Miller and H. H. Sisler, J . Amer. Ckem. Soc., 1955, 77, 4998.148 R. Schwarz and W. Kuchen, 2. anorg. Chem., 1955, 279, 84.149 H. Funk and E. Thilo, 2. anorg. Chern., 1955, 278, 237108 INORGANIC CHEMISTRY.concentrations a series of reddish-brown to yellow silver silicates have beenprepared of general composition Ag, + ~ ( H ~ S i n 0 3 ~ + 1).These are formulatedas acid salts of linearly condensed silicate anions. Salts have been obtainedwith as many as eight silicon atoms in the anion.150 Phase relations havebeen established for the somewhat complex system Na&-CaO-SiO,-C0,.151All the metals of Group IVA are now becoming commercially available,and there has been some interest in their corrosion-resisting properties.Thorium is the most acid-resistant, but is fairly easily dissolved by aquaregia, in which titanium dissolves slowly. All the metals are rapidlyattacked by hydrofluoric acid, titanium dissolving as Ti3+ and the othersas M4+ ions.Titanium, zirconium, and hafnium dissolve even in weakacids in the presence of fluoride i0ns.1~2Useful thermodynamic data have been published relating to heats offormation of titanium t e t r a ~ h l o r i d e , ~ ~ ~ vaporisation of the oxides,f% anddisproportionation of the trioxide,l=and the t r i ~ h l o r i d e , ~ ~ ~Ti,03(s.) __t TiO(g.) $- TiO,(g.) ; Moo = 296 kcal./moleTiCl,(s.) TiCl,(g.) + TiCl,(s.)The methods by which titanium dichloride have previously been preparedhave generally given products contaminated with metallic titanium or thetrichloride. A pure dichloride has been obtained by reduction of thetetrachloride by atomic hydrogen, i.e. , the action of a low-pressure electrode-less discharge on a mixture of the tetrachloride and hydrogen.Titaniumdichloride is a dark reddish-brown powder which immediately takes fire inthe air.156Addition compounds between titanium chlorides and amines have beenfurther investigated, and include Ti@) complexes such as TiC13(NMe3),.157Oxidation of titanium trifluoride with chlorine affords TiF3C1 as a yellowpowder; both this and the tetrafluoride yield the air-stable oxyfluorideTiOF, on hydr01ysis.l~~The hydrolysis of titanium tetraethoxide in ethanol has been studiedwith the use of an improved ebulliometric method. It is suggested that inthe tetraethoxide and in the oxide-ethoxides fonned in hydrolysis, thetitanium maintains a co-ordination number of six. On this basis the structureof trimeric Ti(OEt), is as given in Fig.1 and hydrolysis is then considered toinvolve cross-linking of trimer units with formation of Ti-O-Ti bridges : 1592 -Ti*OEt + H,O = b i 0 T i - + 2EtOHA silicon analogue of titanium tetra-tert.-butoxide (b. p. 106"/7 mm.) hasbeen prepared by the reaction TiCl, + Me,Si*OH + NH,+ Tj(OSiMe3),.16*\ // / \160 E. Thilo, F. Wodtcke. and H. 'Funk, 2. anorg. Chem., 1955, 278, 225.161 C. Kroger and J . Blomer, ibid., 1955, 280, 51.152 M. E. Straumanis and J. I. Ballass, ibid., 1955, 278, 33.153 G. B. Skinner and R. A. Ruehrwein, J. Phys. Chem., 1955, 59, 112.154 W. 0. Groves, M. Hoch, and H. L. Johnston, ibid., p. 127.155 M. Farber and A. J. Darnell, ibid., p. 156.1513 V. Gutmann, H. Nowotny, and G. Ofner, 2. anorg. Chem., 1955, 278, 78.157 M.Antler and A. W. Laubengayer, J. Amer. Chem. SOC., 1955, 77, 5250.168 K. S. Vorres and F. B. Dutton, ibid., p. 2019.159 D. C. Bradley, R. Gaze, and W. Wardlaw, J., 1955, 722, 3977.160 W. D. English and L. H. Sommer, J. Amer. Chem. SOC., 1956, 77, 170COATES AND GLOCKLING. 109Distribution ratios and equilibrium constants have been reported for theextraction of zirconium and hafnium from 4~-perchloric acid with fluorinatedB-diketones in organic so1vents.l6lFIG 1A series of solid non-crystalline and evidently polymeric amides andimides of thorium has been prepared from potassium thorium nitrate andpotassamide in liquid ammonia ; typical members are (NH),ThNH,Kand (NH),Th,(NH,),K,. The tetra-amide, Th(NH,),, is converted into anammine, Th(NH,),I,, by ammonium iodide.The thermal decomposition ofthe amide-imides is complex, but a nitride salt K3Th3N5 has been isolated.ls2Thorium oxalate dihydrate loses its water at 270". The oxalate decom-poses at 330" either entirely into carbonate or into a mixture of carbonateand dioxide, according to experimental conditions.lm The dehydration ofTh(N0,),,4H20 to the anhydrous nitrate has been studied in some detail.With N,O,-HNO, mixtures the compound Th(N0,),,2N,05 is formed, fromwhich the anhydrous nitrate may be obtained by thermal decomposition.ls4The existence of the previously described " pentagermanoic acid,"H,Ge,O,!, has been disproved by an X-ray and vapour-pressure study of thedehydration of hydrated germanium dioxide. No definite hydrate could bedetected.Ion-exchange experiments on germanate solutions containingsulphate and phosphate ions have shown that extensive depolymerisation ofthe germanate ion occurs as the pH is reduced from 9 to 4. The [GeO2S0,l2-and [HGeO,PO4I2- ions appear to be formed in the pH range 7-9-5.166In contrast to the behaviour of silicon, the partial hydrolysis of ger-manium tetrachloride does not yield any volatile oxychloride ; only poly-meric products of approximate composition Ge203C!, are obtained.16' Anearlier report that germanium oxychloride, GeOCl,, is formed when HGeCl,is passed over silver oxide has been corrected; the product of this reactionis a liquid modification of germanium dichloride.16*E. F. Huffman, G. M. Iddings, R. N. Osborne, and G.V. Shalimoff, J. Amer.Chern. SOC., 1955, 77, 881.le2 0. Schmitz-Dumont and F. Raabe, 2. anorg. Chem., 1954, 277, 297.163 R. W. M. D'Eye and P. G. Sellman, J . Inorg. and Nuclear Chem., 1955, 1, 143.164 J. R. Ferraro, L. I. Katzin, and G. Gibson, J . Amer. Chem. Sot., 1956, 77, 327.165 G. Brauer and H. Renner, 2. anorg. Chem., 1965, 278, 108.166 D. A. Everest and J. E. Salmon, J., 1955, 1444.168 Idem, ibid., p. 3003.W. C. Schumb and D. M. Smyth, J . A w r . Chem. Soc., 1955, 77, 2133110 INORGANIC CHEMISTRY.A study of the hydrolysis of stannic salts in dilute sulphuric acid has givenevidence for the existence of the SnS0,2f The bromohypophosphitesof tin, SnBr,,SSn(H,PO,), and SnBr,,Sn(H,PO,),, and the iodo-salt,SnI2,3Sn(H,PO,),, have been isolated. They are all colourless crystallinesolids with sharp melting points.170Group V.-Experiments in which gaseous-ion diffusion was controlledby a suitable electrode arrangement have shown that the activity of " activenitrogen " is not due to positive ions, but rather to excited neutral mole-cules.171A detailed study of the ammines of the ammonium halides has beencompleted, with the use of a quartz helix balance.Several new ammineswere found, e.g., NH,F,NH,, and the dissociation pressures were related tothe pK values of the acids HX.17, Tetra-alkylammonium halides reactrapidly with amide ions in liquid ammonia, e:g.,Et4Nf + NH2- = NH3 + Et3N + C2H4Some saturated hydrocarbon was found, attributed to reduction of theolefin. The salt tetraethylammonium diphenylamide, Et,N*Ph,N- , wasisolated as a yellow air-sensitive solid, stable at room temperature.173Low-pressure decomposition of hydrazine at 850", with use of the coldfinger technique, has yielded a bright yellow diamagnetic substance, stableat -195", which decomposed suddenly at -178" to nitrogen and ammonia.This yellow compound is considered 17* to be tetrazan, NH,*NH*NH*NH,,rather than the hydrazino-radical NH,*NH*.Free hydrazine and hydroxyl-amine (and related bases) have been obtained in high yield and in a goodstate of purity by the ammonolysis of their salts in liquid ammonia.176A study of the reactions of solutions of chloramine in liquid ammonia,prepared by the reaction C1, + 2NH3.= NH,C1 + NH,C1, confirms E.C.Franklin's suggestion 176 that chloramine behaves as an acid in ammoniaanalogously to hypochlorous acid in water :NH2CI + N H , e N H 4 + + NHC1- HOCl + H,O -. H30+ + C1-The nature of the decomposition of chloramine solutions is consistent withthe initial step,177 NHCl- = NH + Cl-. The influence of OH- and NH,+ions on the reaction between chloramine and aqueous ammonia has alsobeen examined.178Calcium hydrazinesulphinate, Ca(O,S*NH*NH,),, has been prepared inthe form of yellow crystals by the action of thionyl chloride on hydrazine inchloroform containing calcium oxide in suspension. No definite product160 C. H. Brubaker, J. Amer. Chem. SOC., 1955, 77, 5265.170 D. A. Everest, J., 1954, 4698.1 7 1 R. N. Varney, J . Chem. Phys., 1955, 23, 866.172 G.W. Watt and W. R. McBride, J. Amev. Chem. SOC., 1955, 77, 1317.1 7 3 W. L. Jolly, ibid., p. 4958.174 F. 0. Rice and F. Scherber, ibid., p. 291.175 G. W. Watt and W. R. McBride, ibid., p. 2088.176 E. C. Franklin, &id., 1924, 46. 2137.177 J. Jander, 2. aworg. Chem., 1955, 280, 264, 276.1 7 8 R. S. Drago and H. H. Sisler, J. Amer. Chem. Sot., 1955, 77, 3191; see alsoM. M. Jones, L. F. Audrieth, and E. Cotton, ibid., p. 2701COATES A N D GLOCKLING. 111could be obtained in the absence of a base to neutralise hydrogen chloride.The salt is decomposed by water, but .is more stable in alkali in whichcomplete decomposition occurs within three hours. It is a strong reducingagent : 179SO,H*NH*NH, + 31, + 2H20 = H$O, + N, + 6HIHydrazinesulphonic acid, SO,H*NH*NH,, is somewhat less stable to hydro-lysis than sulphamic acid, and is a weaker acid (pK = 3.85) ; a zwitter-ionstructure for the solid is indicated by the infrared spectrum.lsOThe thermal decomposition of nitrites and nitrates is often complicated.At about 550" strontium nitrite decomposes mainly according to the equationSr(NO,), + SrO + NO + NO,, but part of the nitrogen dioxide combineswith the strontium oxide, giving nitrate.Nitrogen also is produced bythe reaction, Sr(NO,), + 2NO = %(NO,), + N,.181 Strontium hyponitrite,SrN20,,5H,O, decomposes at temperatures up to 350", forming nitrous oxideand nitrogen ; nitrogen dioxide and nitrate are absent.18,-0 0- The salt K,N,SO,, obtained from nitric oxide andpotassium sulphite, has a structure la3 (XI) such that it may'so; be regarded as a sulphur trioxide adduct of the cis-hyponitriteion. The sulphur trioxide fragment can be detached bymeans of pyridine; the pyridine complex py,SO, is notisolated as such, but as its decomposition product glutacon-aldehyde, anilinium chloride resulting from treatment withaniline and hydrochloric acid.The failure to obtain hyponitrites is attributedto the cis-form of the hyponitrite fragment in the salt K,N,SO,, since thestable fonn of the hyponitrite ion is trans.ls4The conductances of solutions of dinitrogen tetroxide in sulphuric,selenic, and orthophosphoric acids have been measured.It has long seemed remarkable that the most stable allotrope of phos-phorus, black phosphorus, should be the least accessible. Hitherto blackphosphorus has been obtained only by the application of rather highpressures.186 Recently, however, the transformation of white into blackphosphorus has been shown to proceed without the use of pressure under thecatalytic influence of mercury and in the presence of a seed of black phos-phorus. White phosphorus, with a little of the powdered black form, issealed with an equal weight of mercury in a tube packed with copperedwelding rod. The tube is shaken when the phosphorus is melted, whereuponthe mercury distributes itself on the welding rods, and is heated from 220"to 370" during eight days.The transformation is complete.ls7In the course of an investigation on " Hittorf's phosphorus," obtained bycrystallising red phosphorus from lead, the addition of zinc, cadmium, or' N-N +'m179 M.Goehring and H. Kaspar, 2. anorg. Chem., 1955, 278, 255.180 L. F. Audrieth and S. F. West, J. Amer. Chem. Sot., 1955, 77, 5000.181 T. M. Oza and S. A. Patel, J. Indian Chew. Sot., 1054, 31, 518.182 Idem, ibid., p. 523.183 I . G. A. Jeffrey and H. P. Stadler, J., 1951, 1467.184 M. Goehring and R. Otto, 2. anorg. Chem., 1955, 280, 143.lS6 G. Hetherington, M. J. Nichols, and P. L. Robinson, J., 1956, 3141.187 H. Krebs, H. Weitz, and K. H. Worms, 2. anorg. Chenz., 1955, 280, 119.P. W. Bridgman, J . Amer. Chem. Sot., 1914, 36, 1344; 1916, 38, 609; P. L.Gunther, P. Geselle, and W. Rebentisch, 2. anorg. Chem., 1943, 250, 373112 INORGANIC CHEMISTRY.mercury was found to produce some remarkable phosphides MPbP,, (Ad = Zn,Cd, or Hg).These grey, crystalline polyphosphides are not electricallyconducting; their chemical reactivity is low, but they are slowly oxidisedto polyphosphoric acid by moist air.lss Some higher barium phosphideshave also been obtained; a dark grey product, BaP,, results from bariumand phosphorus vapour at 400450"; this is transformed into BaP, when itis heated in uacuo at 740°.189The pyrolysis lgo of NaPH2,2NH, results first in loss of ammonia, thenof phosphine : NaPH2,2NH, NaPH, Na,PH __t Na,P,.Phosphorus oxychloride and antimony pentachloride form a 1 : 1addition compound which, from its Raman spectrum, is formulated as[POClJ + [SbClJ -. lglThe kinetics of the polymerisation of phosphorus nitrile chlorides havebeen studied,lg2 and an interesting new azido-derivative of phosphorus,P,N,!, is reported from the reaction between the trimeric phosphonitrilechlonde and sodium azide :This hexa-azide is a colourless oil soluble in common organic solvents.When slowly heated it evaporates without apparent decomposition at about250".It is fairly stable to alkali, but is readily hydrolysed by acids. It isvery sensitive to shock.lS3Increasing use is being made of infrared methods for the identification ofstructural groupings in inorganic molecules. Over 60 salts of phosphorusoxyacids have been examined in the rock-salt region, enabling characteristicfrequencies to be assigned to a variety of P-X bonds.lW In an extensivespectroscopic investigation of the metaphosphoric acids, attempts have beenmade to obtain anhydrous trimetaphosphoric acid but highly polymericmaterial always resulted.Anhydrous polymeric metaphosphoric acid showsno 0-H absorption bands.lS5Sodium tetrametaphosphate has been obtained in a state of purity by ananion-exchange resin method,lS6 and preparative procedures have beengiven for pure CaHP0,,2H20 and Ca,P207.1S7 The salt 3NaPO,,KPO, hasbeen shown to be a trimetapho~phate.1~8Polyphosphates of zinc, cadmium, and lead have been examined by pHand conductometric methods and by the photometric study of suspensions.188 H. Krebs, I. Pakulla, and G. Ziirn, 2. anorg. Chem., 1955, 278, 274.189 S. A. Shchukarev, M. P. Morozova, and E.A. Prokof'eva, Zhur. obshchei Khim.,180 W. Zschaage and A. Wutschel, Angew. Chem., 1955, 67, 75.191 A. Maschka, V. Gutmann, and R. Sponer, Monatsh., 1955, 86, 52.192 F. Patat and K. Frombling, ibid., p. 718.193 C. Grundmann and R. RBtz, 2. Naturforsch., 1955, lob, 116.104 D. E. C. Corbridge and E. J. Lowe, J., 1954, 493, 4555.195 A. Simon and E. Steger, 2. anorg. Chem., 1954, 277, 209.198 D. L. Barney and J. W. Gryder, J . Amer. Chem. Soc., 1965, 77, 3195.197 P. D. S. Pierre, zbid., p. 2197.198 E. J. Griffith and J. R. Van Wazer, ibid., p. 4222.1954, 24, 1277COATES AND GLOCKLING. 113The pyrophosphate anions [M(P,O,)A 8- and [MP20,I2- and the triphosphateanion [MP,010]3- were identified.lD9Phase equilibria have been reported for the systems NH,+-H+-NO,--P043--H20 and HN03-H,P04-NH3-H20,zoo and part of the Na,O-K,O-P,O, system.201 The presence of a P-P bond in hypophosphoric acid(H,P,O,) has been confirmed spectroscopically.202Further work on phosphorus acids containing trifluoromethyl groups hasresulted in the isolation of bistrifluoromethylphosphinic acid, (CF,),PO,H,by hydrolysis of the chlorides (CF3),PC1, or (CE',),PCl,.This acid is excep-tionally strong. Trifluoromethylphosphonous acid, CF,*P(OH),, has notyet been obtained free from water. In concentrated aqueous solution itdisproport ionat es to t rifluorome t hylphosphine and t rifluoromet hylphos-phonic acid. A comparison of the strengths of various acids leads to theorder :HC104(360) > (CF3),P0,H(250) > HBr(l80) > H,S0,(32)> CF,CO,H, HNO, (l),approximate relative strengths being given in parentheses.2o3 The hithertounknown tristrifluoromethylphosphine oxide, (CF,),PO, is readily obtainedfrom the dichloride and anhydrous oxalic acid :> CF,*PO(OH),, HCl(9) > (CF3),AsO8H(3-5) > CF3.As0(OH),(2.5)(CF3),PC12 + H2C,04 = (CF,),PO + CO + CO, + 2HC1Paper chromatography of the products of hydrolysis of mixed poly-arsenophosphates, with other evidence, has shown that the phosphate andarsenate groups are randomly arranged in the long-chain p0lymers.~05Some complexes of arsenic trifluoride have been described, e.g.,~ A S F , , ~ S O , .~ ~ ~ When chlorine is led into ice-cold arsenic trifluoride acolourless crystalline substance, AsCl,F,, is deposited. This is extremelyhygroscopic, and decomposes with melting about 130".The conductivityin arsenic trifluoride increases linearly with concentration and indicates asalt constitution [AsClA+ [AsF,] -. Other compounds containing AsCl,+cations and AsF,- anions are known.207A number of amino- and imino-derivatives of arsenic trisulphide havebeen prepared from the sulphide and liquid ammonia :The primary ammonolytic product is an ammonium thioamidoarsenitewhich is very unstable and at about 0" decomposes with loss of ammonia andformation of the orange-red iminosulphide As,S,NH. This compound reactswith ammonium sulphide in liquid ammonia, forming the colourless crystal-199 M. Bobtelsky and s. Kertes, J . AppZ. Chem., 1955, 5, 125.100 R.Flatt, G. Brunisholz, 0. Blumer, and P. Rod, HeZv. Chim. Acta, 1965, 38,*01 G. W. Morey, F. R. Boyd, J. L. England, and W. T. Chen, J . Amer. Chew. Soc.,202 M. Baudler, 2. anorg. Chem., 1955, 279, 115.203 H. J. EmelCus, R. N. Haszeldine, and R. C. Paul, J., 1955, 563.204 R. C. Paul, ibid., p. 574.205 E. Thilo and L. Kolditz, 2. anorg. Chem., 1955, 278, 122.206 A. Engelbrecht, A. Aignesberger, and E. Hayek, Munatsh., 1955, 86, 471.207 L. Kolditz, 2. anorg. Chem., 1955, $280, 313.AS4S6 + 7NH3 __t (NH4),[-S-A~(NH,)-S-A~(NH,)-S-] + NH,HS763, 769.1955, 77, 5003114 INORGANIC CHEMISTRY.line thioarsenite, (NH,),AsS,.lysed by alkali :and decomposes when heated to 360°,208It is stable to water and acids but is hydro-As,S,NH + 120H- = 3[As02SJ3- + [AsOS2I3- + NHa + 5H,O350°6As4S,NH __t 2NH, + 5As4S6 f 4AsNA number of alkali-metal bismuth sulphides has been studied, e.g.,LiBiS2,RbBi,SS.Those of formula MBiS, have simple cubic structures witha random distnbution of alkali-metal and bismuth atoms among the cationicposit ions .,09Some intermetallic compounds of vanadium, niobium, and tantalumhaving the p-tungsten structure have been described. These includeV,Sn, Nb,Sn, Ta,Sn, Nb,Os, Nb,Ir, and Nb3Pt.,10A variety of rather obscure lower oxides and hydroxides of vanadiumhas been described from time to time. The position has recently beenclarified by the preparation of the rose-coloured VO(OH), and the blackV,0,(OH)4 ; both are crystalline and have been characterised by X-raydiffraction.The former is slowly precipitated when the blue solutionobtained by reducing an aqueous suspension of vanadic acid by sulphurdioxide is concentrated in a nitrogen atmosphere, and the latter resultswhen vanadic acid is reduced by zinc in the presence of concentratedammonium chloride.211 Some vanadites have been prepared from thetrioxide, V20,, and metal oxides,212 e.g., Li20 + V203 _+ LiVO,. Somecomplex chlorides of vanadium(1v) containing ions from VCI,- to VClS4-have been isolated as salts such as [Me4N+]4[VCls4-] ; it is necessary to usenon-aqueous solvents (POCl,, S02C12) .,13Two niobium carbides have been prepared by heating the metal orNb,O, or Nb,O, with carbon to 1600-1700". The higher carbide has a widecomposition range, NbC0.72-1.00, and the lower carbide may vary fromNbC,.,, to NbC0.50.214The preparation of metaniobates and metatantalates of the alkali metals,e.g., RbNbO,, has been described, starting from the mixed oxides Nb20, +T%O, from which tantalum was separated as K4Ta,0,F,,.215 Alkali-earthanalogues have been prepared by the reaction illustrated by : 216CaF1300"Nb,O, + CaCO, __t Ca(NbO,),Five potassium niobates have been identified by differential thermal analysisof the product of the reaction between potassium carbonate and niobiumpent oxide.21208 H. Behrens and L. Glasser, Z . anorg. Chem., 1956. 278, 174.209 0. Glemser and &I. Filcek, ibid., 1955, 279, 321 ; 0. Glemset and J . Zemann, ibid.,210 S. Geller, B. T. Matthias, and R.Goldstein, J. Amer. Chew. SOC., 1955, 77, 1502.211 0. Glemser and E. Schwarzmann, 2. anorg. Chem., 1955, 278, 249.212 W, Riidorff and H. Becker, 2. Naturforsch., 1954, 9b. 613.213 V. Gutmann, Monatsh., 1954, 85, 286.214 G. Brauer, H. Renner, and J . Wernet, 2. anorg. Chem., 1954, 277, 249.215 M. A. Pchelkina and A. V. Lapitskii, Zhur. obshchei Khim., 1954, 24, 1101, 1105.216 M. A. Pchelkin, A. F. Efimov, and A. V. Lapitskii, ibid., p. 1284.217 A. Reisman and F. Holtzberg, J. Amer. Chem. SOC., 1955, 77, 2115.p. 324COATES AND CLOCKLING. 115Knowledge concerning the lower valency states of niobium is still ratherconfused, and somewhat ill-defined niobium(II1) and niobium(1v) compoundshave occasionally been described. The reduction of acidic niobium(v)solutions has been studied by spectrophotometric examination of thesolutions obtained in the vicinity of a dropping-mercury cathode.In13lv-hydrochloric acid, in which niobium(v) is probably present as [NbOClJ-or [NbOClSl2-, orange-red solutions are formed on reduction and theseprobably contain [NbOC1,J2- ions. In 10-12~-hydrochloric acid thepolarographic character of the reduction is the same, but the resultingsolutions of niobium(1v) are blue-violet ; the significance of the colourdifference is not yet clear. Solutions of niobium(1v) salts are immediatelyoxidised by air, and slowly disproportionate to niobium(v) and niobium(II1)salts. The niobium in the yellow-brown niobium(II1) solutions is presentpartly as cation and partly as anion, depending on the halide concentration :Nb3+ + 6CI- NbC1,3-Yellow niobium(I1) solutions could only be obtained in the presence ofethyleneWhen a mixture of niobium(v) and tantalum(v) oxides is reduced byhydrogen at 1000" two separate phases are formed, viz., a tantalum-rich(Nb,Ta),O, and a niobium-rich (Nb,Ta)O, phase.Only the latter dissolvesin 80% sulphuric acid, and a useful niobium-tantalum separation can beachieved in this way.219Tantalum alkoxides, Ta(OR), (R = Me, Et, etc.), are dimeric in boilingbenzene. In these compounds dimerisation allows the tantalum to achieve aco-ordination number of six.22oGroup V1.-The technique of cooling gases containing reactive or transientspecies whereby interesting and unstable compounds become deposited on acold finger (often at -196O), has been extended to oxygen. The use of asurface cooled to 4.2" K exposed to the products of the action of an electrode-less discharge on oxygen a t 0.1-3 mm.results in the deposition of a violetsolid. This melts to a deep blue-violet liquid and contains much ozone. Ifthe walls of the cold trap are coated with ice, a different deposit is obtained,mostly colourless, which decomposes between 4" and 50" K with the form-ation of a new, this time purple, solid. The colourless deposit is consideredto contain a substantial proportion of atomic oxygen since it changes, whenwarmed, into a material containing ozone.221The pale yellow commercial sodium peroxide is shown 222 to containabout 10% of the superoxide NaO,.Phase studies are reported for varioussystems involving aqueous hydrogen peroxide and sulphates, selenates, andtellurates. Solid compounds, e.g., Na,S0,,0.5H20,,H20 have been isolated,as well as compounds such as K2H,Te0, which may be peroxytellurates.2~3The infrared spectra of the monohydrates of the hydrogen halides haveshown that these are all ionic crystals of oxonium halides,224 e.g., H,O+F-,H30+Cl-.218 D. Cozzi and S. Vivarelli, 2. anorg. Chem., 1955, 279, 165.219 H. Schafer and M. Jori, ;bid., 1954, 217, 341.220 D. C. Bradley, W. Wardlaw, and A. Whitley, J., 1955, 726.221 H. P, Broida and J. R. Pellam, J. Chem. PAYS., 1955, 23, 408.212 P. Geurge, J., 1955, 2367.22% S . Pani and H. Terrey, &id., p. 3066.224 C.C . Ferris0 and D. F. Hornig, J. CAem. Phys., 1956, 83, 1464116 INORGANIC CHEMISTRY.Attention has been drawn, in an extensive study of the allotropy ofsulphur, to the wide discrepancies between the various results of previousworkers. On the basis of detailed experimental evidence this is partlyattributed to the 9hotosensitivity of freshly shock-chilled liquid sulphur, andpartly to the relative ineffectiveness of attempting to freeze the complexliquid sulphur equilibrium in water. The effect of impurities on the S,-S,equilibrium has been known for quite a long time, but has now been closelyinvestigated. The results of this study have been interpreted on the basisof an equilibrium between s8 (ring) molecules and a small proportion of S,open chains.225Investigations continue on compounds containing chains of sulphuratoms, and recent developments include the preparation of the trichloro-methyl polysulphides : 2262CC13*SCI + H,S = 2HCI + C13C.S*S*SCC132CC13.SC1 + H,S, = 2HC1 + C13C*S.S.S.S*CC13Several lower metal sulphides have been obtained from reactions betweenthe metal and hydrogen sulphide at high temperatures; “g., 21n + H2S =In2S + H,.Germanium and gallium sulphides, GeS and Ga2S, wereobtained in the same way, and aluminium sulphide, A12S, was preparedfrom Al,S, and hydrogen sulphide. These lower sulphides can be sublimedat high temperatures i?z vacuo as black solids.227The striking developments in the chemistry of tetrasulphur nitride,S,N,, and its derivatives have been reviewed.228 Tetrasulphur nitrideand cobalt chloride, carbonyl, or carbonyl hydride form tetra(thionitr0-syl)cobalt, Co(NS),.It is, like the nickel analogue, Ni(NS),, deep violetand monomeric in nitrobenzene, but is paramagnetic (pee. = 1.90 B.M.).2%Several salts of the thionitrosyl anion, NS-, have also been prepared mainlyby reaction in liquid ammonia between sulphur nitride and a metal salt.An example is the lead(x1) compound, Pb(NS),, which is dark red-brown, andsensitive to heat and shock. The salt is hydrolysed by aqueous acids tolead(I1) and ammonium ions and sulphur dioxide. Hydrolysis by water oralkali gives lead sulphate, sulphite, and ammonia. Silver, copper, andthallium salts have also been obtained. The silver(1) salt, AgNS, givestetra(ethy1nitrogen sulphide) (EtNS), with ethyl iodide, and it is possiblethat the various salts still contain the N4S4 eight-membered ring.230 Tetra-sulphur tetra-imide, S,(NH),, and lithium aluminium hydride form thecomplex salt Li[Al(S,N+)] and hydrogen.231The use of radioactive sulphur in the preparation of the oxynitride ofsulphur, S,N202, from sulphur nitride, thionyl chloride, and sulphur dioxidesuggests that N2S2 molecules are essential intermediates in the reaction.If the oxynitride is prepared from inactive sulphur nitride and active thionylchloride the resulting compound has one third of the activity of the thionyl225 P.W. Schenk, 2. anorg. Chern., 1955, 280, 1.226 F. Feher and H. J . Berthold, Chem. Ber., 1955, 88, 1634.227 E.Gastinger, 2. Naturforsch., 1955, lob, 116.228 M. Goehring and J. Ebert. ibid., p. 241.229 K. W. Daum, M. Goehring, and J . Weiss, 2. anorg. Chern., 1955, 278, 260.230 M. Goehring, J. Weiss, and G. Zirker, ibid., p. 1.231 M. Goehring and G. Zirker, 2. Naturforsch., 1955, lob, 58COATES AND GLOCKLING. 117chloride, but on hydrolysis the whole of the activity appears in the sulphurdioxide f o ~ ~ ~ e d . ~ ~ ~Several fluoronitrides of sulphur have been prepared by the action ofsilver(I1) fluoride on sulphur nitride in carbon tetrachloride. When thefluorination is carried out at room temperature colourless needles can beisolated consisting of S,N,F,, which is quantitatively hydrolysed by warmdilute alkali : S,N,F, + 12H,O = 4NH,F + 4H,SO3.\ Thus the sulphur must be in the +4 oxidation levelBS-N\s,F and the proposed structure (XII) is supported by theN observed zero dipole moment.Fluorination in boilingI carbon tetrachloride affords a colourless gas, m. p. I- S//N -108", b. p. -11", F*N:S:N*F, which is also hydrolysed\F to NH,+, F-, and Another gas, probably SNF, isformed together with SN,F, under some conditionsthough it has not been isolated in a state of purity.This gas mixture slowly deposits greenish-yellow crystals of yet anotherfluoronitride of sulphur which is under investigation.=Trifluoromethanethiol and anhydrous ammonia form a range of productsincluding trifluoromethyl fluorodithioformate, CF,*S*CSF, a yellow liquid,b. p. 43" ; bistrifluoromethyl trithiocarbonate, (CF,S),CS, a red liquid,b.p. 1 lo", and probably the dithiocarbamate CF,*S*CS*NH,. Both liquidproducts form carbonyl sulphide on aqueous hydrolysis. The trithio-carbonate has also been obtained by two other methods jnvolving di(tri-fluoromethy1thio)mercury : 234F(xn)2Hg(S*CF3), + CSCI, + (CF3*S),CS + 2CF,*S*HgClHg(S*CF3), f CF3*S°CSF __t (CF,*S)&S + CF,*S*HgFOxidation of di(trifluoromethylt1iio)mercury with hydrogen peroxide givestrifluoromethanesulphonic acid, CF3*S0,H. This acid (b. p. 162") is con-siderably more volatile than methanesulphonic acid ; its silver salt issoluble in benzene and it is a sufficiently strong acid to liberate hydrogenchloride from sodiumAn improved preparative method for the lower halides of sulphur S,X,(X = C1 or Br) has been devised involving the hot-cold tube which allowsa vapour mixture to be cooled rapidly after contact with a hot surface.The reduction of sulphur monochloride by hydrogen begins at a hot surfacetemperature of about 400°, but the resulting orange-coloured viscous lowerchlorides always contain a considerable amount of elemental sulphur.Even after allowance for this, chain lengths up to S, have been obtained.Thereduction of sulphur monobromide, for which an improved preparation hasbeen devised in which sulphur and bromine are heated for 2 hours at 110"in beer bottles, takes place at lower temperatures (230-250"), though thereduction products again contain much sulphur. No products of the typeX*S,*SH could be detected.236 Details of the formation of sulphur tetra-232 hl.Goehring and J. Heinke, 2. anorg. Chem. 1955, 278, 53.233 0. Glemser, H. Schroder, and H. Haeseler, ibid., 1955, 279, 28.234 R. N. Haszeldine and J. M. Kidd, J., 1955, 3871.235 Idem, J., 1954, 4228.236 F. Fehbr, J. Kraemer, and G. Rempe, 2. anorg. Chem., 1955, 279, 18118 INORGANIC CHEMISTRY.fluoride from its elements have been reported, together with some of itsphysical proper tie^.^^An extensive study has been reported on the behaviour of thionylchloride as an ionising solvent. Most typical salt-like substances are in-soluble, but organic coinpounds and covalent halides are often soluble. Thesmall conductance of the pure solvent is ascribed to the ionisationSOCI, SOC1+ + C1-. Ionised or ion-pair chlorides, e.g., tetraethyl-ammonium chloride, behave as ' I solvo-bases " in thionyl chloride, andsubstances which can accept chloride ions behave as ' I solvo-acids." Various' I acid-base " titrations can be followed both conductometrically and alsopotentiometrically by using a molybdenum electrode, which responds to thechloride-ion concentration.Thus the reaction,Et4NCl + SOCl+SbCl,- = Et4N+SbC16- + SOCl2solvo-base solvo-acid salt solventproduces a potential change of about 1-4 volts when the equivalence pointis passed. Conductance measurements show that the strongest '' solvo-bases," e.g., Et,NCl, are present mainly as ion-pairs in solution, the disso-ciation constant being 10" at 78" in this instance. Tertiary amines behaveas bases in the following manner : 238R3N + SOC1,andR3N.SOC1, =+E [R3N*SOC1]+ + C1-2R3N + SOCI, @ (R,N),:SOCl, =+k (R3N),SOC1+ + C1-The action of a silent electric discharge on a mixture of thionyl fluorideand oxygen at -50" results in the condensation of a complex liquid mixtureof at least five components. This mixture is extremely reactive, attackingtap grease, Silicone grease, and mercury, but by low-temperature fraction-ation two new oxyfluorides of sulphur have been isolated, S,O,F, andS,O,F,.The first could not be obtained in a pureF state, but S20SF, was isolated as a volatile liquid (m. p.-95", extrapolated b. p. 35") which slowly decomposedF ' \/ 'F above -20" to sulphuryl fluoride and oxygen. Its(xIII) structure was considered to be (XIII) which involvesnot only a peroxy-group, but also a co-ordination numberof five for The anhydride of fluorosulphonic acid, pyrosulphurylfluoride, S,O,F,, has been obtained by dehydration of fluorosulphonicacid with arsenic pentoxide : 240O=S F\ /o-o\s/oAs,O, + 10F-S03H + 2AsF2(S03F), + 4H2SO4 + H,O~ A s F ~ ( S O ~ F ) ~ __t ~S,OF,F, + AsSOJ?,The preliminary investigations on nitrososulphuryl fluoride 241 reportedlast year have been much extended. The triple point is 8" and 3100 mm.,the vapour at room temperature being largely dissociated into SO, and NOF237 F.Brown and P. L. Robinson, J., 1955, 3147.238 H. Spandau and E. Brunneck, 2. anovg. Chem., 1955, 278, 197; see also idem,239 U. Wannagat and G. Mennicken, ibid., 1955, 278, 310.240 E.Hayek, A. Aignesberger, and A. Engelbrecht, Monatsh., 1955, 86, 735.241 G. Balz and E. Mailander, 2. anovg. Chem., 1934, 217, 161 ; F. See1 and H. Meier,ibid., 1952, 270, 201.ibid., 1953, 274, 202COATES AND GLOCKLING. 119a t about atmospheric pressure. The substance can be kept in glass onlybelow -lo", and can most conveniently be handled in liquid sulphur dioxide.Nitrososulphuryl fluoride reacts with various halides with the formation ofnitrosyl complex fluorides, e.g.,N0.S02F + BF, = SO, + NO-BF,6NO*SO,F + P(As,Sb)CI3 = NO[P(As,Sb)F,] + 2N0 + 3NOC1 + 6S0,Of particular interest is the formation of nitrosyl hexafluoroiodateICl + 6NOS02F = NO[IF,j + 2N0 + 3NOC1 + 6S0,which easily dissociates into nitrosyl fluoride and iodine pentafluoride : 242NO[IF6] NOF + IF,.Reduction of selenium hexafluoride with various elements has beenstudied, though few clear-cut reactions were observed.With arsine bothSeF, and AsF, were isolated from the reaction mixture.2q3 Selenium tetra-fluoride forms a complex, SeF,(py)Et,O, with pyridine and ether.244Some alkoxides of tellurium(rv) have been obtained from the tetra-chloride or ammonium hexachlorotellurate and sodium alkoxides. Themethoxide is a solid, the others being liquids, and all are very readilyhydr01ysed.W~Tellurium dibromide is formed in the reaction : 2CF3Br + Te --wC,F, + TeBr,. Its vapour is purple or pink depending on the temperature,and solutions in solvents such as ether are unstable. Bromine converts itinto the tetrabromide, and iodine into the mixed halide, TeBr,I,.246 Tel-lurium dichloride can be conveniently prepared from the element anddichlorodifluoromethane at 500".247The spontaneous deposition of tracer amounts of 210Po on other metals(Ag, Ni, Pt) has been used to obtain milligram quantities of polonium.Oxidation of the metal is rapid at 250-3(30", giving the dioxide, PoO,.Polonium dissolves in dilute hydrochloric acid, giving on evaporation thetetrachloride as a yellow solid,2q8 m.p. -300". At 400" the tetrachloridevolatilises to a purple brown vapour which becomes blue-green at 500".The dichloride, PoCl,, was obtained by reduction (SO,) of the tetrachlorideas a ruby-red solid which sublimed with decomposition at aboutPolonium tetrabromide was obtained as a bright red solid (m.p. -330")from the metal and bromine or by dissolving the metal or its dioxide inaqueous hydrogen bromide. It is converted into the dibromide on thermaldegradation or by reduction with hydrogen sulphide. Other compoundsprepared include PoCl,Br,, Cs,PoBr,, and (NH,),POBI-,.~~~A complex acetylide of chromium has been isolated from the reactionbetween potassium acetylide and hexamminochromium(IrI) nitrate in liquidammonia : [CT(NH~)J(NO~)~ + KCiCH --+ K,[Cr(CiCH),]. It forms an242 F. See1 and H. Massat, 2. anorg. Chem., 1955, 280, 186.z43 C. Dagron, Compt. rend., 1955, 241, 418.244 E. E. Aynsley and G. Hetherington, J., 1954, 4695.246 P. Dupuy, Compt. rend., 1955, 240, 2238.24, E. E. Aynsley and R.H. Watson, J., 1955, 2603.247 Idem, ibid., p. 576.248 K. W. Bagnall and R. W. D'Eye, J., 1954, 4295.249 K. W. Bagnall, R. \V. D'Eye, and J . H. Freeman, J.. 1955, 2320.260 Idem, ibid., p. 3959120 INORGANIC CHEMISTRY.orange paramagnetic powder which is sensitive to air, water, and shock.is decomposed by cyanides :K,Cr(CiCH), + 6CN- + 6H20 __t K,Cr(CN)& + 6C2H2 + 60H-A similar derivative from propyne can be obtained, but is difficult toisolate .251The reaction between iron or cobalt carbonyls and aqueous alkali hasbeen known for some time; the carbonyl hydrides result from acidificationof the reaction mixtures. Hitherto, no similar derivatives of chromiumcarbonyl have been obtained, since the reaction with aqueous alkali appearsto be difficult, perhaps for steric reasons.Recently, however, reaction withalcoholic potassium hydroxide in a sealed tube at 100" with careful exclusionof oxygen has been shown to give a hydroxyaquocarbonyl salt :ItCr(CO)B + MeOH + 4KOH + 2H20 = K[Cr(CO),(H,O),OH] + CH,.CO,K+2H*CO,K + H,There is some evidence that the reaction involves the intermediate formationof a carbonyl hydride :Cr(CO)6 + 3KOH = K[Cr(CO),H] + K,CO, + H,OK[Cr(CO),H] + H,O = [Cr(CO),] + KOH + H,[Cr(CO),] + 3KOH + 2H20 = K[Cr(CO),(H,O),OH] + 2H*CO,KThe final product is soluble in water with a red colour, the solution beinglargely hydrolysed :K[Cr(CO)3(HaO)zOHl + H2O Cr(CO),(H,O), + KOHAmmonia irreversibly replaces water in the triaquo-complex, theresulting yellow crystalline diamagnetic triamminotricarbonylchromiumCr(CO),(NH,), being quite stable in the absence of air and water.Exposuret o air causes slow disproportionation to hydrated chromium(Ix1) oxide andthe hexacarbonyl. A slightly different disproportionation takes place inacid solution with exclusion of oxygen :but there is also some complete decomposition :Cr(CO),(NH,), + 5H30+ = Cr2+ + H2 + 3CO + 3NH,+ + 5H,OPyridine displaces ammonia with the formation of the previously describedcomplex Cr(CO),(py),, and isocyanides afford stable colourless (aliphatic) oryellow (aromatic) derivatives Cr(CO),(R*NC),. In contrast the cyanidecompound K3[Cr(CO),(CN),] ,2NH3 is very unstable, decomposed rapidly bywater, and insoluble in organic solvents.252Oxidations by chromium(v1) oxide must involve intermediates contain-ing chromium in some oxidation state between (VI) and (111).A largelykinetic study of the oxidation of butanols and sec.-hexanol by chromium(v1)oxide has indicated that complexes of Cr@) take part in the reaction, whichis subject to pronounced retardation by manganese ions.253 Decompositionof chromium trioxide at 420" under an oxygen pressure of 200-300 atm.251 R. Nast and E. Sirtl, Chem. Bey., 1955, 88. 1723.262 W. H. Hieber, W. Abeck, and H. K. Platzer, 2. anorg. Chem., 1955, 280, 241, 252.259 V. Antony and A. C. Chatterji, ibid., p. 110.2Cr(CO),(NH3), + 8H,0C = Cr(CO), + Cr2+ + H, + 6NHlf + 8H,COATES AND GLOCKLING. 121leads to the formation of chromium dioxide, CrO,, which is ferromagneticand reported as having a Curie temperature of 115°.254A phase-diagram study of the system Cr20~-P205-H20 has shown thepresence of four stable solid phases at 0" containing all three components aspurple solids.At 40" three green solids were identified, again containing allthree components. Ion-exchange studies on the latter indicated the pre-sence of the complexes 255 [Cr(P04),,aq.-J3- and [Cr(HPO,),aq.] +. Acidsolutions of chromium-( 111) and -(vI) ions are believed, from light-absorptionexperiments, to contain the chromato-chromium(II1) complexes 256 [CrCrOJ +and [CrCrO,HI2+.A series of orange-red fluoropentamminochromium(Ir1) salts similar tothe recently examined cobalt(II1) series 257 has been prepared by the reaction :Hydrolysis in acid solution 258 causes substitution of water for ammonia, notfluorine, giving [Cr(NH3),F(H20)]2+.Azidopentamminochromium( 111) saJ ts have been investigated and arecarmine-red to violet, light-sensitive, and less stable than the correspondingcobalt (HI) salts.Triazidotriamminochromium(m), CrN,,H,, is insoluble inwater and less sensitive to shock than might be expected.259Several series of alkaline-earth molybdates, tungstates, and uranateshave been reported, of the types M2B05 and M,BO, (M = Ba, Sr ; B = Rfo,W, U). Compounds of the type MBO, which are highly coloured (CaUO,and MgMoO, are black) were in general obtained by three methods : 260H,( a ) MBO, __t MBO,; ( b ) MO + BO, ___+ MB03 ;(c) ZBaMoO, + Mo + BaO __+ 3BaMo0,The complex 6-molybdoheteropoly-anions have been further investigatedby conductivity and potentiometric titration methods, which indicate theformula [(X06*Mo60&]3"-, where x =.A13', cr3+, Fe3+, Co3+, and in which nis small but greater than unity. This investigation indicates that the6-heteropoly-anions as a class cannot be represented by a general formulaor by a single structuralUraniwn and the Transuranic Elements.-Mixed yttrium-uranium oxideshaving a variety of colours have been prepared by ignition of the nitratesand studied by X-ray analysis. Some of the mixed oxides must containhranium ions in several states of oxidation.262 The two uranates Na2U,,O4,and Na2U,0, have been isolated by addition of sodium hydroxide to uranylchloride solutions. The former gives Na,U,O,, when washed with water.263254 S.M. Ariya, S. A. Shchukarev, and V. B. Glushkova, Zhur. obshchei Khinz., 1953,255 R. F. Jameson and J. E. Salmon, J., 1955, 360.256 E. L. King and J. A. Neptune, J . Amer. Chem. SOC., 1955, 77, 3186.2 5 7 M. Linhard and M. Weigel, 2. anorg. Chem., 1951, 266, 73.2s8 Idem, ibid., 1955, 278, 24.Z5* M. Linhard and W. Berthold, ibid., 1955, 2'79, 173.2~ R. Scholder and L. Brixner, 2. Naturforsch., 1955, lob, 178.e61 L. C. W. Baker, G. Foster, W. Tan, F. Scholnick, and T. P. McCutcheon, J .262 F. Hund, U. Peetz, and G. Kottenhahn, 2. anorg. Chem., 1955, 278, 184.263 J. Sutton, J . Inorg. and Nuclear Chem., 1955, 1, 68.23, 1241.Amer. Chem. Soc., 1955, 77, 2136122 INORGANIC CHEMISTRY.Phase studies are reported for the systems Na,0-U0,-H,0264 at 50"and 75" and U0,-P,O,-H,O. In the latter system the existence of theequilibrium solid phases U(HP0,),,6H20 and U(HPO,),,H,PO,,H,O hasbeen dem~nstrated.,~~Potassium uranyl nitrate, which dissolves in liquid ammonia withformation of a non-fluorescent diammine, gives a precipitate of uranyl amideon addition of potassium amide. Uranyl amide, UO,(NH,),, is a brownpowder which exhibits amphoteric behaviour since it forms the ammineiodide, UO,(NH,),I,, with ammonium iodide and potassium uranyl di-imide,K,UO,(NH),, with potassium amide.The di-imide decomposes to a nitrideK6(U02),N, when heated, but uranyl amide gives the dioxide, probablythrough an imide : UO,(NH,), + U0,NH + NH, + UO, + N, + NH,.The potassium salt decomposes in several steps 266 between 170" and 370" :K,(U02),N4 __t 6K + 3U0, + ZN,.An examination of the uranium-sulphur system has shown that the lower sulphide U,S, previously describedis a solid solution of uranium in the monosulphide US. The new sulphidesU2S3 and U,S, were obtained.267The catalytic effect of chloride ions on the isotopic exchange reactionsbetween negtunium-(v) and -(vI) have been interpreted in terms of theformation of the complexes, [NpO,Cl]+ and Np0,C1,.26*Two further procedures are reported for the isolation of plutonium fromuranium. One method involves a modification of the zirconium phosphatecycle devised for neptunium , and the other extraction with thenoyltrifluoro-acetone in benzene.269 A plutonium hydride, PuH,.,, has been obtained bydirect combination of the elements at 150-250". It forms a hard, black,metallic-like solid which is slowly hydrolysed by hot water.The hydride,PuH,, and deuteride, PuD,, have also been described, and their dissociationpressures measured. 270Cationic-exchange resins which have recently been used to effect separ-ations of the rare-earth metals have now been applied to some of the ter-valent actinides. Tartrate and lactate elutions result in good separation ofamericium and curium, which have proved very difficult to separate byother methods.271Group VI1.-Anodic fluonnation , a very useful preparative methoddiscovered by 0. Ruff and developed largely by J. H. Simons, is now thesubject of quantitative physicochemical investigation, and some preliminaryresults are available on the fluorination of fluorosulphonic acid : 272F.S02*OH + 3HF - 4e- = S02F2 + OF, + 4H+Conductivity and electrolysis experiments on fluorosulphonic acid indicatethat it ionises according to 2F*SO,H e- F*SO,H,+ .+ F*SO,-.The con-ductances of a range of fluorides in fluorosulphonic acid are reported; some264 J. E. Ricci and F. J. Loprest, J . Amer. Chem. SOC., 1955, 77, 2119.265 J. M. Schreyer. ibid., p. 2972.266 0. Schmitz-Dumont, F. Fuchtenbusch, and H. Schneiders, 2. anorg. Chem.,267 M. Picon and J. Flahant, Compt. rend., 1955, 240, 535, 784; 241, 655.$68 D. Cohen, J. C. Sullivan, and J. C. Hindman, J . Amer. Chem. SOL, 1955, 77, 4964.269 J.Rydberg, Acta Chem. Scand., 1955, 9, 1252.270 F. Brown, H. M. Ockenden, and G. A. Welch, J., 1955, 3932; R. N. R. Miilford2 7 1 R. A. Glass, ibid., p. 807.272 H. Schmidt and H. D. Schmidt, 2. anorg. Chem., 1955, 279, 289.1954, 277, 315.and G. E. Sturdy, J. Amer. Chem. SOC., 1955, '97, 3449COATES AND GLOCKLING. 123behave as "acids," e.g., AuF, and TaF,, and others, such as AsF,, SbF,,BrF,, and IF,, as " bases." 273Tetramethylammonium fluoride and excess of sulphur dioxide form acolourless addition product Me,N,SO,F, from which metal fluorosulphinateshave been prepared by reaction with alkali metal halides (e.g., RbS02F).274The reaction between silver salts of fluorocarbon carboxylic acids and halo-gens is well known as a method for obtaining fluorocarbon halides, and it hasbeen demonstrated that the reaction proceeds via silver complexes of thetype (RCO,) 2AgX.275A very unstable hydrate of hydrochloric acid, HC1,6H20, m.p. -70°,has been found; 276 other phase-rule studies include the system NaC10,-NaC1-H20.277A new preparation of chloryl fluoride has been described :12KC10, + 20BrF, = 12KBrF, + 4Br, + 60, + 12C10,FWith boron trifluoride and antimony pentafluoride, chloryl fluoride forms solid1 : 1 compounds which are regarded 27* as the chloronium salts ClO,+BF,-and ClO,+SbF,-. A preliminary communication has appeared concerningthe highly reactive bromyl fluoride, BrO,F, which has been obtained by thedirect low-temperature fluorination of bromine dioxide. Iodyl fluoride andperiodyl fluoride are formed in the reactions : 2791 2 0 , + F, - 2IOz.F + $ 0 2HFHFHIO, + F, --w I03F + HF + $0,The formula Br308 of one of the oxides of bromine has always appearedrather surprising, and a recent study of the compound has shown it to beBrO,.The oxide, obtained like " Br,08 " by the action of a glow dischargeon a mixture of bromine and oxygen between -10" and + Z O O , is a whitesolid of crystalline appearance, stable below -70". The oxides of bromine,Br20, BrO,, and BrO,, are now more nearly analogous to those of chlorine,and the absence of Br20., corresponds to the absence of perbromic acid.280The behaviour of mixtures of iodine bromide with potassium bromideand with aluminium bromide on electrolysis has provided evidence for thecomplexes KIBr, and I(A1Br,),21Br.281Some preparative methods have been described for anhydrous metalhalides; these may be illustrated by the use of acetyl chloride : 282and the use of metal hydrides : 283Cu(OAc),,H,O + 3AcCl = CUCI, + 2Ac20 + AcOH + HClEt,O PY2LiH + I, 2LiI + H,; BaH, + 2NHJ + BaI, + 2NH, + H,Z73 A.A. Woolf, J., 1955, 433.274 F. See1 and H. Jonas, Angew. Chem., 1955, 67, 32.2 7 5 G. H. Crawford and J. H. Simons, J. Amer. Chem. SOL, 1955, 77, 2605.276 G. Vuillard, Comfit. rend., 1955, 241, 1308.277 G. L. Cunningham and T. S. Oey, J. Amer. Chem. Soc., 1955, 77, 799.278 A. A. Woolf, J., 1954, 4113.279 M. Schmeisser, E. Pammer, and K. Lang, Angew. Chem., 1955, 67, 156.280 A. Pflugmacher, H. J. Rabben. and H.Dahmen, 2. anorg. Chern., 1955, 279, 313.281 Y. A. Fialkov and 0. L. Shor, Zhur. obshchei Khim., 1953, 23, 357, 363.282 G. W.Watt, P. S. Gentile, and E. P. Helvenston, J. Amer. Chem. SOC., 1955,77, 2752.283 M. D. Taylor and L. R. Grant, ibid., p. 1507124 INORGANIC CHEMISTRY.Manganese nitride, Mn,N,, can be prepared by electrolysis of manganesechloride, a mercury cathode being used; evaporation of the m e r c y leavesa pyrophoric form of manganese which is converted into the nitride undera 10 atm. pressure of nitrogen at 860".Attention has recently been directed to compounds of manganese withoxidation levels between 3 and 6, since these must be involved in oxidationprocesses in which permanganates are used. In this connection studies onalkali-metal salts of the manganate(v) anion are of considerable interest.Earlier methods for preparing sodium manganate always gave productscontaining sulphate, but the pure compound Na,MnO,,+NaOH, 12H,O canbe obtained by reduction of sodium manganate(v1) in alkaline solution bysodium formate.The hydrate Na3Mn04,7H20 separates from the brightblue solution of the double salt in cooled sodium hydroxide. Lithium,sodium, and potassium salts, M3Mn0,, result from the permanganates andthe hydroxide at higher temperatures; they are all blue to blue-green.These manganese(v) salts disproportionate readily in solution, as might beexpected, to manganese dioxide and to manganates(v1) .285Potassium hexafluororhenate, K,ReF,, has been obtained in good yieldfrom ammonium hexaiodorhenate and potassium hydrogen fluoride,286and hypophosphorous acid has been found a very convenient reducing agentfor the preparation of hexahalogenorhenate~.~~~ Some oxyfluorides ofrhenium(vI1) have been prepared from per-rhenates and bromine trifluoride,e.g., KRe0,F4.28sGroup VIE-Iron pentacarbonyl forms conducting solutions in a varietyof amines and, on the basis of infrared evidence, it is suggested that theionisation involved is :2Fe(CO), [Fe(CO)6]2+[Fe(C0)~2-the ions being highly s ~ l v a t e d ., ~ ~ The interesting phenylacetylenederivative, Fe(CO),(CiCPh),, is stable but photosensitive.289uIron and palladium thionitrosyls have now been obtained in additionto the previously described nickel and cobalt complexes.Methods offormation involve the action of tetrasulphur nitride, S,N,, on the metalcarbonyl or halide, and reaction between disulphur nitride, S2N2, and thefinely divided metal in tetrahydrofuran. Only the iron compound issensitive to hydrolysis.290Aromatic amines react with the salt Na,[Fe(CN),NH,] to form highlycoloured compounds which afe believed 291 to be radical-ions having thegeneral formula [FeI1(CN),R'*N*Rl3-.A spectrophotometric study of the hydrolysis of ferric ions has shownthat, when the ferric-ion concentration is greater than 1 0 " ~ ~ polynucleariron(II1) species are present.292 The complexes [Fe(OH) (RS)]- and284 0. G. Koch, Monatsh., 1955, 86, 868.285 R. Scholder, D. Fischer, and H. Waterstradt, 2. anorg.Chem., 1954, 277, 234.286 R. D. Peacock, Chem. and Ind., 1955, 1453.287 C. L. Rulfs and R. J . Meyer, J. Amer. Chem. Soc., 1955, 77, 4505.288 R. D. Peacock, J., 1955, 602.289 H. W. Sternberg, R. A. Friedel, S. L. Shufler, and I. Wender, J. Amer. Ckem.2890 E. R. H. Jones, P. C. Wailes, and M. C. Whiting, J., 1955, 4021.290 M. Goehring, K. W. Daum, and J . Weiss, 2. Naturforsch., 1955, lob, 298.291 E. F. G. Herington, Nature, 1956, 176, 80.292 R. M. Milburn and W. C. Vosburgh, J . Amer. Chem. SOL, 1955, 77, 1352.SOC., 1955, 77, 2675COATES AND GLOCKLING. 125[Fe(RS)J2- are found between pH 10 and 12 in the ferrous-cysteinesystem .293The course of the reaction between carbon monoxide and cobalt ornickel sulphide in aqueous alkali, whereby carbonyls are formed, is sensitiveto traces of oxygen.Experiments with carefully purified carbon monoxidehave demonstrated that the reactions with nickel sulphide are essentially :andNiS + 4G0 Ni(CO), + SS + CO + 40H- + Se- + CO,2- + 2H,OSome sulphur also appears as thiosulphate, together with a trace as sulphite.Quantitative conversion into carbonyl can be achieved if soluble sulphurcompounds are continuously removed from the reaction system. Sincevolatile cobalt carbonyls are not formed in alkaline solution, conversions intothe cobalt carbonyl anion are smaller, but appear to follow the equation : 2942CoS + l l C 0 + 120H- 4-0 2[Co(CO),]- + 3COS2- + 6H,O + 2S2-Further structural investigations have been reported on cobalt carbonylsOne feature of great interest is the and the carbonyl hydride, Co(CO),H.FIG.2.--Structure of dicobaltoctacarbonyl.(The three carbon atomsC‘ are in one plane, and thethree C“ in another parallelto that of C’.)position of the hydrogen atom in the latter and the nature of the bondinginvolved. Proton magnetic resonance measurements on the hydride, andinfrared studies on the hydride and deuteride, CO(CO),~H, have been used inthe elucidation of this problem, which cannot yet be regarded as finallysettled. However, it now appears that the structure can be best explainedby a tetrahedral distribution of carbonyl groups about the cobalt atom,with the hydrogen atom embedded in one face of the tetrahedron, thusforming a bridge between three carbonyl groups.The hydrogen atom isvery weakly bound, and this formulation appears to be compatible withmolecular orbital theory, which suggests that the Co-H distance is justunder 2.A and leads to the general picture that the hydrogen atom is‘‘ immersed in a sheath of negative charge.” 2953 297In last year’s Report 296 the structure given for dicobalt octacarbonylwas wrongly reproduced. However, more recent infrared studies have ledto the proposal of a new tram-structure (Fig. 2). The infrared spectrumof tetracobalt dodecacarbonyl, Co,(CO) shows bands corresponding toterminal and bridge carbonyl groups in the ratio of 2 : l.297293 N. Tanaka, I. M. Kolthoff, and W. Stricks, J. Anzer. Chem. Soc., 996.294 H. Behrens and E. Eisenmann, 2. anorg. Chew., 1955,278, 155, 166,296 W.F. Edge11 and G. Gallup, J. Amer. Ckem. SOC., 1965, 77, 5762.296 Ann. ReBorts. 1954. 51. 147.297 R. A. Fciedei, I. Wender, S. L. Shufler, and €3. W. Sternberg, J. Amer. Chem.SOC., 1955, 77, 3951126 INORGANIC CHEMISTRY.isocyanides and dicobalt octacarbonyl form ionic complexes of the type,[(RNC),Co] [CO(CO),].~~*Continuation of earlier work on cobalt amides has resulted in the pre-paration of a crystalline potassium cobalt (111) nitride. Prolonged shakingof cobalt(rr1) amide (formed from [CoNH,),] (NO,), and potassium amide)with potassium amide in liquid ammonia causes the deposition of violetcrystals to which the structure (XIV) has been assigned. The black pyro-(XIV)phoric and crystalline nitride K,Co2N, results from thermal decompositionof this complex amide at 20-76" in a stream of nitrogen : 299[COZ(NHZ)~(NHK)~]~~- (K3Co,N3)n f 3nNH3Several cobalt complexes containing co-ordinated chlorite groups havebeen prepared,300 e g .,[Co(OH) (NH3)51 (NO3)2,HzO > [cO(c1oz) (NH3)5] (NO,),Iodopentamminocobalt(I11) salts are obtained by oxidation of cobalt (11)salts with iodine in the presence of high concentrations of the requiredammonium salt .,O1Some rather peculiar hydrides of iron, cobalt, and nickel were describedin 1926; these were obtained by the action of hydrogen on solutions ordispersions of the appropriate halide in ethereal phenylmagnesiumbromide.302 These reactions have been studied again with particularreference to the use of nickel chloride.The earlier results were to someextent confirmed and considerably extended. A black hydride was formedon the surface of the nickel chloride crystals, but X-ray diffraction revealedonly the chloride. The use of very finely divided nickel chloride resulted inthe formation of a dark oil and no crystalline material. When an excess ofphenylmagnesium bromide was used a proportionately large amount ofhydrogen was taken up, since the nickel hydride acts as a hydrogenationcatalyst. Attempts to obtain a pure substance from the dark oil, for exampleby washing with ether, did not succeed as the product always containedmagnesium, halogens, and organic matter. However, analyses by variousmethods showed 303 that the Ni : H ratio was about 1 : 2.Further details have been published concerning the nickel acetylenecomplexes mentioned in the Report for 1953.3w These diamagnetic, air-sensitive compounds are analogous to the carbonyls in that the metal-carbon bond order is between one and two : Ni*CiC*R - Ni:C:C*R.3052D8 A.Sacco, Gazzetta, 1953, 83, 632.300 G. R. Levi, R. Curti, and G. Brignani, Gazzetta, 1954, 84, 753.301 R. G. Yalman, J , Amer. Chem. SOC., 1955, 77, 3219.304 T. Weichselfelder, Annalen, 1926, 447, 64.304 Ann. Reports, 1953, 50, 118.305 R. Nast and K. Vester, 2. anorg. Chew., 1955, 279, 146.0. Schmitz-Dumont and N. Kron, 2. anorg. Chern., 1955, 280, 180.B. Sarry, 2. anorg. Chem., 1955, 280, 65, 78COATES AND GLOCKLING. 127Reduction with hydrazine of equimolar ratios of potassium nickel(@cyanide and nickel(r1) cyanide in alkaline solution is known to give thebinuclear complex, K,[Ni,(CN),].However, if excess of nickel cyanide isused the light red paramagnetic complex, potassium tetracyanonickel(1) ,K,Ni(CN),, can be isolated. This is the first case of a mononuclear complexof nickel(1) ; it is highly sensitive to oxidation by air.306Anhydrous complex oxides of a number of platinum metals have beenobtained by heating the metal and an alkali carbonate in a stream of oxygen.Two types of oxides are formed depending on the temperature and ratio ofmetal to alkali carbonate. Typical examples are cubic compounds of thetype Na,Pt,O,, and a series of oxides isomorphous with sodium stannate,e g . , Na,PtO, and Li2Rh0,.307Mono- and bis-2 : 2‘-dipyridylruthenium(111) complexes have beenidentified as intermediates in the formation of the stable tris-c~mplex.~~~The fluoro-complexes of the platinum metals have been the subject offurther study.Ruthenium, iridium, and osmium show the unusual valencyof five in a series of complex fluorides of the type M,M,F,(M, = Ru, Ir,or Os), though the simple pentafluorides are as yet unknown. Magneticmeasurements on the ruthenium 309 and osmium complexes correspond tothree unpaired electrons (d2sSp3 bonding). For the iridium(v) complex theobserved moments (-1.2 B.M.) are considerably lower than corresponds totwo unpaired electrons. This discrepancy is attributed to a breakdown ofHund’s rule of maximum m~ltiplicity.~10 Other complex fluorides reportedinclude K,RhF, and K,IrF, which are formed by fusion of the complexnitrites with potassium hydrogen d i f l ~ o r i d e .~ ~ ~Further details about the diisocyanopalladium(0) compounds reportedlast year have been published.312X-Ray analyses of the palladium chloride-ethylene and -styrene com-plexes 313 are in agreement with the ‘ I symmetrical ” structure recentlyproposed by Chatt. Co-ordination complexes of palladium with o-dimethyl-aminophenyldimethylarsine (XV) have been investigated,314 e.g.,Me, Me, , N gAs*C,H,*NMe,C H‘\AsflPd\C1306 R. Nast and T. von Krakkay, 2. Naturforsch., 1954, Qb, 798.307 J. J. Scheer, A. E. van Arkel, and R. D. Heyding, Canad. J . Chem., 1955,33, 683,308 R. R. Miller, W. W. Brandt, and S.M. Puke, J . Amer. Chem. SOC., 1955, 77, 3178.300 E. Weise and W. Klemm, 2. anorg. Chem., 1955, 279, 74.310 Ri. -4. Hepworth, P. L. Robinson, and C. J. Westland, J., 1954, 4269.311 R. D. Peacock, J., 1955, 3291.312 L. Malatesta, ibid., p. 3924.813 J. N. Dempsey and N. C. Baenziger. J . Amer. Chem. SOC., 1955, 77, 4984, 4987.314 F. G. Mann and F. H. C. Stewart, J., 1955, 1269128 INORGANIC CHEMISTRY.Chloro-complexes of palladium, obtained from solutions of palladium(11)perchlorate containing varying amounts of chloride ion, have been examinedspectrophotometrically. Evidence was obtained of the existence of all sixcomplexes : 315 PdCl+ , PdZl,, PdC1,- , PdC142-, PdC153-, PdC164-.Further advances have been made in the chemistry of platinum(r1)complexes.tram-Directing effects in substitution reactions of platinouscomplexes are attributed to the mesomeric effect of the directing ligand,rather than inductive release of the Q bonding electrons.316 Methods avail-able for the preparation of binuclear platinum complexes of the type (XVI)have been further investigated and extended (L = olefins, amines, alkylatedderivatives of P, As, Sb, S, Se, Te).317 The reversible reactions of this typeof complex with amines have been studied for a range of amines and ligands :Except when L is itself an amine, the mixed trans-complex is formed rapidly.When X is chlorine or bromine the equilibrium lies well to the right.318Ethylene in its platinous complexes labilises the group in the trans-positionto itself.This is true of the [C,H,PtCl,]- complex which has beenused to determine the relative tendency of halide and thiocyanate ions(F < C1 < Br < I < SCN) to form complexes with platinum(11).~1~Platinum(I1) and tin(I1) chlorides in hydrochloric acid solution form red ,soluble products. Spectrophotometric investigation reveals seven complexeshaving different Pt : Sn ratios. The coloured product In aqueous solutionprobably contains the ion [PtSn4C1J4+ in which platinum is in its zerooxidation state.320cycloPentadienyls and Related Compounds.-The major experimentaladvances during the year concern cyclopentadienylcarbonyls and similarsubstances .Some of the magnetic measurements on biscyclopentadienylmanganesereported last year have been corrected, and extended to include solid solutionsof the manganese and the magnesium compounds.The paramagnetism ofbiscyclopentadienylmanganese varies with temperature in an irregular way,peff. rising from -1 at 20" K to -4.8 at 158" c, suggesting a transition froma covalent to an ionic structure. The white variety (above 158" c, peff. =5-8) is presumably an essentially ionic compound. The temperature-dependence of the magnetic susceptibility of the manganese-magnesiumsolid solution is, in contrast, quite regular, the ionic and strongly para-magnetic form of the manganese compound being stabilised by solid solutionin the ionic magnesium compound.=IL,Pt,X, + 2Amine 2[L, Amine, PtX,]515 A. K. Sundaram and E. B. Sandell, J .Amer. Ckem. SOC., 1955, 77, 855.816 J. Chatt, A. Puncanson, and L. M. Venanzi, Chem. and Ind., 1955, 749.517 Idem, J., 1955, 2787.318 Idem, ibid., p. 3858.81s I. Leden and J. Chatt, ibid., p. 2936.320 A. S. Meyer and G. H. Ayres, J . Amer. Chem. SOC., 1955, 77, 2671.821 E. 0. Fischer and H. Leipfinger, 2. Nattqforsch., 1956, lob, 353 ; E. 0. Fischerand E. Weiss, ibid., p. 68COATES AND GLOCKLING. 129Biscyclopentadienyltitanium &chloride undergoes interesting reactionswith aryl-lithium compounds , e.g.,(C,H,),TiCI, + 2PhLi = (C,H,),TiPh, + 2LiC1The orange-coloured crystalline product is monomeric in benzene and appearsto react reversibly with more phenyl-lithium : 322(C,H,),TiPh, + PhLi e. Lit[ (C,H,),TiPh,]-Some cyclopentadienyl carbonyls were reported last year, e.g., C,H,V(C0)4and cyclopentadienylrnanganese tricarbonyl, C,H,Mn(CO),, m. p. 77", whichis quite stable to air. The cobalt compound, C,H,Co(CO),, from (C,H5),Coand carbon monoxide at 90-150" and 200 atm., is an unstable reddish-brownliquid, b. p. 75"/22 mm.323Since vanadium , manganese, and cobalt afford monomeric cyclopenta-dienylcarbonyls C,H,M(CO), (where ?z = 4, 3, or 2, respectively), analogyFIG. 3.0ii 0with established carbonyl chemistry would suggest not only dimeric cyclo-pentadienylcarbonyls of the intervening metals, chromium and iron , but alsocyclopentadienylcarbonyl hydrides of vanadium, manganese , and cobalt.The action of carbon monoxide (under pressure) on biscyclopentadienyl-chromium produces, with increasing temperature, 100" _t 250", first a darkbrown paramagnetic salt [(C,H,),Cr]+ [C,H,Cr(CO),i-, then the blue green[C5H5Cr(CO)J2, and finally Cr(CO),. A carbon monoxide-hydrogen mixturesiniilarly affords the golden-yellow, volatile, diamagnetic cyclopentadienyl-chromium tricarbonyl hydride, C,H,Cr(CO),H, m. p. 57-58'. The carbonyl-hydrogen is fairly acidic and can be replaced by aqueous alkali. In thecourse of this investigation an unusual tricyclopentadienyldichromium tri-carbonyl was obtained, (C,H,),CI-~(CO)~, m. p. 190-193", pea. = 3-97.Molybdenum and tungsten analogues result from the reaction sequence : s24Me,NCHO H,O+Mo(or W)(CO), + C,H,Li - Li[C,H,Mo(CO),] __.+ C,H,Mo(CO),HSimilarly iron has afforded the dimeric [C,H,Fe(CO)J,, whose remarkableThis322 L. Summers, R. H. Uloth, and A. Holmes. J . Amer. Chem. Soc., 1955, '77, 3604.323 E. 0. Fischer and R. Jira, 2. Naturforsch., 1955, lob, 355.324 E. 0. Fischer and W. Hafner, ibid., p. 140.325 0. S. Mills and P. L. Pauson, personal communication; P. L. Pauson, Quart.structure has very recently been elucidated 32, and is given in Fig. 3.Rev., 1955, 9, 395.REP.-VOL. LII 130 INORGANIC CHEMISTRY.compound is obtained in good yield from cyclopentadiene and iron penta-carbonyl under pressure, or by the use of dicyclopentadiene without pressure.A bromide, C,H,Fe(CO),Br, results from atmospheric oxidation of the di-meric carbonyl in the presence of hydrogen bromide.326 Thecompound, (C,H,),Fe(CO), (XVII), from the bromide andcyclopentadienylsodium, appears to contain one cyclopentadienering bound by a normal (0) bond and the other bound as inferrocene. The dimeric carbonyl [C,H,Fe(CO)J, is reducedto Na[C,H,Fe(CO)J by sodium amalgam, and this saltgives an insoluble mercury derivative, Hg [C,H,Fe(CO),],,with mercuric cyanide.327Various other groups which can form partial double bondspentadienyls. Nitric oxide displaces one mole of cyclo-with transition metals have been introduced into cyclo-pentadiene from biscyclopentadienylnickel, forming the volatile brown liquidcyclopentadienylnitrosylnickel, C,H,NiNO, b. p. 49" /27 mm. Other examplesof recently described nitrosyl derivatives are [C,H,Mn(CO),NO]+X-,C,H,Cr(CO),NO, and molybdenum and tungsten analogues.32* The com-pound C,H,Cr(NO)2C1 has afforded a methyl derivative, C,H,Cr(NO),CH,,on reaction with methylmagnesium iodide, and C,H,Cr(NO),CH,Cl withdiazomet hane .329A remarkable compound, biscyclopentadienylrhenium hydride,(C,H,),ReH , has been prepared from rhenium pentachloride and cyclo-pentadienylsodium. A yellow crystalline diamagnetic solid, m. p. 161-162", it is stable to water but not to air. The nuclear magnetic resonancespectrum provides evidence for the hydride nature of the compound, whichin contrast to the carbonyl hydrides, behaves as a base, e.g., in dilute hydro-chloric acid the cation [(C,H,),ReH2]+ is formed, from which alkali liberatesthe original hydride. The salt [(C,H,),ReHJ [Cr(NH,),(SCN)J was pre-pared.=OcycloPentadienyls, particularly those of iron, have also been the subjectof much work of a sufficiently organic nature to be outside the scope of thissection.o=C-Fe-CEO 9R (xvII)G. E. COATES.F. GLOCKLING.928 B. F. Hallam and P. L. Pauson, Chem. and Ind., 1955, 653; B. F. Hallam,0. S. Mills, and P. L. Pauson, J. Inorg. and Nuclear Chem., 1955, 1, 313.m7 E. 0. Fischer and R. Bottcher, 2. Naturforsch., 1955, lob, 600.328 T. S. Piper, F. A. Cotton, and G. Wilkinson, J. Inorg. and Nuclear Citem., 1955,1, 165; E. 0. Fischer, 0. Beckert, W. Hafner, and H. 0. Stahl, 2. Naturforsch., 1955,lob, 598.320 T. S. Piper and G. Wilkinson, Chem. and Ind., 1955, 1296.930 G. Wilkinson and J . M. Birmingham, J. Amer. Chew SOC., 1955, 77, 3421

ISSN:0365-6217    

DOI:10.1039/AR9555200093

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

ORGANIC CHEMISTRY.1. INTRODUCTION.BY using a " plastic " model for initial and transition states, the contributionof steric strain to the energy of activation and the entropy of activation ofnucleophilic bimolecular halogen exchange in alkyl halides has been cal-culated from first principles.Phenanthrophenanthrene has been resolved and becomes the firstknown optically active hydrocarbon which owes its asymmetry to molecularovercrowding.Impressive progress has been made in the identification of naturallyoccurring amino-acids and in the study of benzotropylium and allied cations,azulene synthesis, and the structure of the extraordinary growth factormycobactin.The common stereochemical pattern of many naturally occurring sesqui-and di-terpenes is being exposed from year to year by a combinatior, ofdirect correlation with substances of known configuration and use of opticalrotations.A valuable theory to explain the stereochemistry of steroids andtriterpenes has been published ; this theory is probably applicable to thesmaller terpenes.The structure of a-amyrin has been the subject of much discussion andexperiment. Evidence has been described suggestive of the presence in thea-amyrins of a five-membered ring (E), with an attached isopropyl group.However, more evidence in favour of the older structure has also appeared.The position is still fluid, but the Reviewer is of the opinion that on balancethe evidence favours the older structure.In the steroid field one of the principle achievements has been the totalsynthesis of aldosterone.Important progress has also been made in thestereochemistry of the trimethyl-steroids.Two outstanding events of the year were the deduction of the detailedstructure of vitamin B,,, an excellent example of the use of chemical andX-ray techniques, and a brilliant two-stage synthesis of usnic acid from asimple derivative of acetophenone. The latter has cast light from a newangle on the oxidation of phenols.G. B. w. c.2. THEORETICAL,Sterically Hindered Unip1anarity.-In numerous unsaturated compounds,changes in configuration , usually out-of-plane displacements , which decreasethe intramolecular compression (destabilising) energy between non-bondedatoms also decrease the resonance (stabilising) energy.The preferred con-figurations, i.e. , those of lowest energy content, are those in which the ratesof change of compression and resonance energy, with change of configuration ,are equal. In these preferred configurations the molecules have energy inexcess of what they would have had in the absence of steric interaction132 ORGANIC CHEMISTRY.the excess comprises loss of resonance energy and gain of compression energyand is referred to as the steric strain.It is generally found that non-bonded carbon atoms do not approachcloser to each other than about 3.0 A, and that the shortest distance betweenhydrogen atoms in aliphatic hydrocarbon crystals is about 2 4 A . Indianthronylidene (1) the centre-to-centre distance between the over-crowded carbon atoms 4 and 4, and 8 and 8', is 2.90 A; it is achieved bya 40" rotation of the benzene rings out of the plane of the central ethylenicsystem.The observed bond lengths and angles indicate that resonanceinteraction is considerably reduced, the molecule consisting of an isolatedethylenic group attached by single bonds to normal benzene rings1The overcrowding in 3 : 4-5 : 6-dibenzophenanthrene (2) is partiallyrelieved by out-of-plane buckling of the molecule, which decreases the com-pression energy at the expense of the resonance energy. This bucklingdisplaces the various carbon and hydrogen atoms in a direction normal tothe original undisturbed molecular plane and is distributed over the fivefused rings in such a manner as to cause the minimum distortion in anyindividual ring.It provides2 a clearance of about 3-0A between thenon-bonded carbon atoms 4' and 1". The loss of resonance energy causedby the deformation is about 18 kcal. mole-l, while the total steric strainenergy may be about 28 kcal. moled1.These deformations affect chemical properties. It appears that foraromatic compounds, increase in departure from a uniplanar structureincreases the localisation of the electrons which are usually delocalised inaromatic rings and hence leads, for example, to increased availability ofelectrons for reaction with free radicals. Methyl radicals add to aromaticcompounds (A + CH, __t ACH,), and the relative rate constants arereferred to as methyl affinities. Those of benzene, naphthalene, anthracene,and naphthacene are 1, 22, 820, and 9250 respectively; * their logarithmsvary linearly with the singlet-triplet excitation energies.Now, whereasthe methyl affinities of 2-, 3-, 4-, 5-, and 6-methylbenzo[c]phenanthrene areroughly the same and about equal to that of the parent hydrocarbon (3),overcrowding causes the methyl affinity to rise somewhat in the l-methyland considerably in the 1 : 12-dimethyl derivative. Again, the logarithmsE. Harnik and G. M. J. Schmidt, J., 1954, 3295.A. 0. McIntosh, J. M. Robertson, and V. Vand, J., 954, 1661.C. A. Coulson and S. Senent, J., 1955, 1813, 1819.M. Levy and M. Szwarc, J . Chem. Phys., 1954, 22, 1621; J . Amer. Chem. SOC.,M. Szwarc, J . Chem. Phys., 1955, 23, 204.M. Levy, M. S.Newman, and M. Szwarc, J . Amer. Chem. SOL, 1955,77, 4225.1955, 77, 1949BADDELEY : THEORETICAL. 133of the reaction constants for interaction of l-chloro-2 : 4-dinitrobenzene andamino-naphthalenes, -anthracenes, and -phenanthrenes in ethanol are in-versely proportional to the localisation energy as calculated for the hydro-carbon analogues of the amines. 4-Aminophenanthrene is an exception ;this misfit is caused by the steric strain in this amine.'Strain similar to that in (2) would arise if 1 : 1'-diisoquinoline (4) par-ticipated in the ferroin reaction; the essential condition for this reaction isthe specific grouping *N:C*C:N-, forming part of an aromatic system andcapable of forming a five-membered chelate ring with ferrous ion. In fact,the base (4) does not give the reaction 8 whereas 1-2'-pyridylisoquinoline doessSpectroscopic evidence for the steric inhibition of uniplanarity withconsequent reduction of conjugation has recently received further attentionwith a view to a quantitative interpretation.There are two different typesof spectral manifestation : (i) decrease in absorption intensity (transitionprobability) without appreciable increase in the frequency (transitionenergy) ; and (ii) change in both. o-Substituted acetophenones, benzo-phenones,l* and styrenes exhibit steric effects of type (i), o-substituteddiphenyls those of type (ii), and 5-o-substituted 2 : 4-diaminophenyl-pyrimidines those of both types.11 It is reasonable to assume that those oftype (ii) are associated with transitions between the non-planar ground stateand the non-planar excited state, whereas the former are associated withtransitions between the non-planar ground state and the planar or near-planar excited state.12 This assumption leads to the conclusiorr that inmanifestations of type (i) the absorption process is mainly concerned withthose molecules in which, during vibration, the interplanar angle 0 2i 0" ;for in accordance with the Franck-Condon principle the relative positions ofthe atomic nuclei, including the value of 0, do not change during the processof absorption. The absorption intensity (E) depends on the populationdistribution and the transition probability as functions of 0, and if we assumethat the transition probability for 0 = 0" is not affected appreciably by stericstrain, the decrease in the absorption (as measured by &/so = r ) may betaken as a measure of the fraction of the molecules which, at any instant,have 6 N 0". Thus Y may be a measure of the energy required to imposeuniplanarity.Calculation has, however, taken another course : on theassumption that r is related to O,, the interplanar angle for the molecule inits lowest energy state, by Y = cos2 0, (a relation which may be difficult tojustify), r has been used in calculations of interplanar angles.13, 14One condition for the display of steric effects of type (i) is that sterichindrance to planarity should not exceed about 3 kcal. mole-l. It is pleasingto find that when the hindrance is expected to be about the same in differentcompounds, i.e., when changes of resonance and compression energy severallywith change of 0 are similar in different compounds, the absorption intensitiesof these compounds afford similar values of Y. For example, the absorptionF. L. J Sixma, Rec. Trav. chinz., 1956, 74, 168.F. H. Case, J . Org. Chem., 1952, 17, 471.H. Irving and A. Hampton, J., 1955, 430.E. A. Braude, F. Sondheimer, and W. Forbes, Nature, 1954,175, 117.lo R. F. Rekker and W. T. Nanta, Rec. Trav. chim., 1954, 73, 969.l1 P. B. Russell, J., 1954, 2951.lS E. A. Braude and F. Sondheimer, J., 1955, 3754.l4 L. H. Klemm, H. Ziffer, J. W. Sprague, and W. Hades, J . Org. Chem., 1955,20,190134 ORGANIC CHEMISTRY.intensity of styrene is decreased by an o-methyl substituent l5 (r = 0.78) tothe same extent as by an a-methyl substituent (r = 0.78) [cf.(5) and (S)].The absorption intensity of a-alkylstyrenes decreases progressively withincrease in bulk of the alkyl substituent ; this indicates that steric inhibi-tion of uniplanarity exists here. There is a small but significant hypso-chromic effect. The absorption intensities of the compounds Ph*OR,17Ph*NHR, and Ph*COR decrease with increase in the bulk of the alkylgroup (R) and are similarly interpreted.Unlike benzamide and its N-methyl derivative, the NN-dimethylderivative (7) cannot have a completely planar structure because of inter-ference between one of the methyl groups and the benzene ring. This inter-ference, which is apparent in the ultraviolet absorption of the compound, isprobably relieved mainly by rotation about the Ph-CO bond since resonanceinteraction, and hence the need for uniplanarity, is greater about the Me,N-CO bond.la The electric moments of N-monosubstituted benzamidesindicate that the amide group is planar and that the less strained conform-ation has the substituent in the cis-position with respect to the carbonylgroup.As a conseq~ence,~~ these compounds seem to associate to formlinear complexes (8) whereas the unsubstituted amides form ringcomplexes (9).Ar.An interesting problem arises when attempting to relate steric hindranceof uniplanarity in cyclahexenyl derivatives with that in the correspondingphenyl derivatives. It has been argued 2o that l-acetyl-2-methylcyclo-hexene is more stable in the s-traas-conformation (10) than in the s-cis-conformation (11).There is, however, no reason for the benzenoid analogueto have a conformation other than one approximating to (12). Analysis 21of the electronic moments of a number of @-unsaturated aldehydes andl5 P. Ramart-Lucas and J. Hoch, Bull. SOC. chim. France, 1935, 327; 1938, 848;l6 P. Ramart-Lucas, Proc. XIth Inst. Congr. Pure Appl. Chem., London, 1947,l7 G. Baddeley, N. H. P. Smith, and M. A. Vickers, in the press.l8 J. T. Edwards and S. C. R. Meacock, Chem. and Ind., 1955, 536.l9 J. E. Worsham, jun., and M. E. Hobbs. J . Amer. Chem. Soc., 1954, 76, 206.*O E. A. Braude and C. J. Timmons, J . , 1955, 3766.81 G. K. Estok and J. S. Dehn, J .Amer. Chem. SOL, 1955, 77, 4769.E. A. Braude and F. Sondheimer, J., 1955, 3773.Vol. 11, p. 267; C. G. Overberger and D. Tanner, J . Amer. Chem. Sac., 1955, 77, 360BADDELEY : THEORETICAL. 135ketones indicates that the p-disubstituted unsaturated ketones have pre-dominantly the s-&-conformation, eg., see ( l l ) , that the aldehydes havethe s-trans-, and that the p-monosubstituted unsaturated ketones haveapproximately equal contributions from both the s-trans- and the s-cis-conformation. The quasi-theoretical and experimentally establishedstability sequence of five stereoisomeric perhydro-1 : 4-dioxophenanthrenes(13) indicates 22 that the energy increment due to the non-bonded inter-action of the oxygen atom of a carbonyl group and a p-situated C-H bondin an eclipsed (equatorial) position is 0.8-1-2 kcal.mole-l. The energy ofnon-bonded interaction of carbonyl and o-methyl group in (11) and (12) willnot be greater than this amount and may be appreciably less.a:.Me a!:o O@"M I Me Me(10) ( 1 ' ) (1 2) (13)A qualitative correlation has been made 23 of Amax. values for up-un-saturated carbonyl compounds in which there is bond deformation in onepart of the chromophore. The excitation energy is found to be lower forcompounds in which the electron displacement of excitation is away froma site of strain. This relationship is in accordance with the idea2* thatgreater electronegativity is associated with greater s-character of the carbonbonds and hence with less directional and more deformable bonds.The absorption intensity for the o-halogenonitrobenzenes is in theorder F > Cl > Br > I, which is the reverse of that for the absorptonintensity of the p-halogenonitrobenzenes and the 2-halogenopyridines.Thedifference is interpreted as being caused by steric inhibition of uniplanarityof nitro- and phenyl-groups by the o-halogen substituent; a similar effectis not possible in the 2-hal0genopyridines.~~Polymethylene chains have conformational preferences which mayoppose the uniplanarity required for maximum conjugation. Compoundsof type (14) and (15), in which X = )CO, )C:N-NHAr, )C:N*OH,)C:N*NH*CO*NH,,15* 26a 2 7 3 2* )NH, )NMe, )N*COR, )O ; l7 XY =-CH:CH-,26, 27 -NH*CO- ; 29 and n = 5-9 ; and those of type (16), in whichY =)CO and )C:N*OH, and w = 13-18,30 have been studied and theirproperties discussed.The data do not, however, provide a quantitativelyconsistent pattern. The spectroscopic results for compounds of type (16),where Y is a carbonyl group, show the interplanar angle of the carbonyl and22 P. A. Robins and J. Walker, J., 1955, 1789; Chem. and Ind., 1955, 727.23 W. M. Schubert and W. A. Sweeney, J. Amer. Chem. SOC., 1955, 77, 2297.24 A. D. Walsh, Discuss. Faraday SOC., 1947, 2, 18.2 5 H. C. Brown and D. H. McDaniel, J. Amer. Chem. SOC., 1955, 77, 3752; H. E.26 G. Baddeley and J. Chadwick, J., 1951, 368.27 R. Huisgen, W. Rapp, I. Ugi, H. Walz, and E. Mergenthaler, Annalen, 1954,28 F. Ramirez and A. F. Kirby, J. Amer. Chew SOC., 1954, 76, 1037.2o R.Huisgen, I. Ugi, H. Brade, and E. Rauenbusch, Annalen, 1954, 586, 30.30 R. Huisgen, W. Rapp, I. Ugi, H. Walz, and I. Glogger, ibid., p. 52.Ungnade, ibid., 1954, 76, 1601.586, 1136 ORGANIC CHEMISTRY.the phenyl group to be wide (Y = 0.45) when n = 13, to decrease with in-crease in n, and to be negligibly small (P = 0.99) when n = 18. In com-pounds (14) and (15) the steric strain is least when n = 5 and increases withincrease in the value of n up to 8. Values of 9 or higher for n probablycause less strain by providing a rotation which is greater thanIt should be noted that the carbonyl frequencies of the benzocycl-anones (14, X = )CO) vary with increase in n, as do those of the correspond-ing cyclanones, and therefore do not afford evidence for steric hindrance ofuniplanarit y .The alicyclic moiety of these compounds has been shown by both physicaland chemical methods to cause no significant bond fixation of the typeproposed by Mills and Nixon.The frequency shifts, Av(CO), in theinfrared carbonyl vibration frequency arising from conjugated chelation ofadjacent hydroxyl and carbonyl groups are the same when these groups arein the 4 : 5- or the 5 : 6-position in indane as in the corresponding positionsin o-~ylene.~~ Again, comparison of the spectra of 3 : 4- and 4 : 5-dimethyl-,3 : 4- and 4 : 5-cycZopenteno-, and 3 : 4- and 4 : 5-cycZohexeno-pyridazine,~and of the rates of unimolecular solvolysis of the chlorides (17; n = 5,6, or 7) 34 demonstrates that the Mills-Nixon effect is not significantlyoperative.Ph 'SO, , ,CH;CO,HPh 'CHCI LCH2 I,, dMe (17) -$is c H2 Z (1 8 )The effect of ring-size on the steric inhibition of uniplanarity is indicatedby the study of the optical stability and ultraviolet absorption spectra ofbridged diphenyls : 35 the passage through the planar conformation of amolecule of the ortho-substituted diphenyl type is facilitated by the joiningof the two blocking groups into a ring; further, the planar conformationis more easily achieved the shorter the bridging chain of atoms.In accord-ance with expectation, the extent to which conformational preference of apolymethylene chain prevails over that of conjugation in the compounds (14)decreases with increase in the capacity of X to conjugate with the benzenering.Thus change of f i from 5 to 7 has less effect on the absorption intensity31 G. Baddeley, G. Holt, N. H. P. Smith, and F. A. Whittaker, Nature, 1951,168,386.32 I. M. Hunsberger, D. Lednicer, H. S. Gutowsky, D. L. Bunker, and P. Taussig,33 R. H. Horning and E. D. Amstutz, J . Org. Chem., 1955, 20, 1069.34 G. Baddeley and M. Gordon, J., 1952, 2190.35 D. M. Hall and E. E. Turner, J., 1955, 1242; G. H. Beaven, G. R. Bird, D. M.J . Amer. Chew. SOC., 1955, 77, 2466.Hall, E. A. Johnson, J. E. Ladbury, M. S. Leslie, and E. E. Turner, J., 1955, 2708BADDELEY : THEORETICAL. 137when X is )CO (r = 0.82) than when X is )O (Y = 0.23). This relation isalso apparent in the optical stabilities of diphenyls and related compounds,e.g., electron-withdrawing substituents 2 in the amine (18) increase theconjugation of the nitrogen atom and the benzene ring and thereby increasethe rate of racemisation. Electron-supplying substituents have the oppositeeffect .36These considerations cast doubt on the significance of interplanar anglesderived from scale models, and of calculations in which the conformationalpreference of polymethylene chains is assumed to prevail over that ofcon jugation. l3 Conventional steric considerations can be misleading, e.g. ,systems containing tram-fused cyclopentane rings are more readily formedthan steric cmsiderations would suggest 37 and optically active 1 : 1'-di-naphthyl derivatives racemise even when a mechanical interpretation by useof models indicates this to be inipos~ible.~~ Further, there is need for cautionin ascribing to steric hindrance of uniplanarity small differences of intensityof absorption between even closely related compounds : 39 e.g., whereas thecis- and the trans-forms of penta-1 : 3-diene and pent-3-en-1-yne absorbwith practically equal intensity, extension of the chromophore by additionof a methoxycarbonyl group in each case results in an appreciable differencebetween geometrical isomers, the ratio being remarkably constant.Stericinhibition of uniplanarity can be discounted here ; apparently other factorsare involved.39 It should be noted that stereoisomeric hexa-2 : 4-dienoicesters differ appreciably in both h,,, and absorption intensity, the trans-trans-isomer absorbing maximally at the shortest wavelength, exactly theopposite behaviour to that predicted on the basis of one of Zechmeister'sgeneral is at ion^.^^ This rule must be inverted for simple, laterally unsubsti-tuted polyenes.39s 41Steric hindrance of uniplanarity in 1 : 1 : 2 : 5 : 6 : 6-hexachlorohexa-1 : cis-3 : 5-triene (19) and 3 : 4-dibromohexachlorohexa-1 : trans-3 : 5-triene(20) is clearly indicated by their absorption spectra.42Intermolecular Strain.-Most chemical reactions involve one or more ofa number of possible steric effects and, for any one reaction, it is seldomapparent which will be the most important one and whether it will outweighelectronic influences. A complete theory of the effect of substituents on thecourse and rate of reaction and on equilibrium will incorporate a quantitativetreatment of spatial and electronic influences ; in the meantime, evidence fors6 R.Adams and K. V. Y. Sundstrom, J . Amer. Chem. SOC., 1954, 76, 5474.37 L. N. Owen and A. G. Peto, Chem. and Ind., 1955, 65.38 F. Bell and W. H. D. Morgan, J., 1954, 1716.40 L. Zechrneister, Experimentia, 1954, 10, 1.41 P. Nayler and M. C. Whiting, J., 1954, 4006.4z A. Roedig and K. Kiepert, Chem. Bey., 1955, 88, 733.J. L. H. Allan, E. R. H. Jones, and M. C. Whiting, J., 1955, 1862138 ORGANIC CHEMISTRY.the relative importance of the various influences and their dependence onreaction mechanism is rapidly accumulating.This sub-section is concerned with recent examples of reactions in whichnon-bonding interaction of one reactant with another (intermolecular strain)increases the energy content of the transition state or product and therebyinfluences reaction rate or equilibrium.Other types of strain are discussedin later sub-sections.This intermolecular strain has a pronounced influence on the interactionof iodine monochloride with 1 : 3 : 5-tri-tert.-butyl- and pentaethyl-benzene 43and on the methyl affinity of chloranil 44 and di-tert.-butyl-1 : 4-benzo-q~inone.*~ The structure of the product of the primary addition of themethyl radical is still undetermined and it is not clear whether the reactingradical attacks initially at an oxygen atom or at an ethylenic bond of thequinone. The latter is indicated by the steric effect : it seems that wheneverthe ethylenic bond is shielded by bulky atoms or groups the reactivity ofthe quinone decreases.The methyl affinities of styrene (792), trans-stilbene(105), triphenylethylene (46), and tetraphenylethylene (< 10) show thatsteric strain is more important than resonance stabilisation of the resultingradicals in determining these relative rates.46 o-Methyl substituents havetwo mutually opposing steric effects on the dissociation of hexaphenyl-ethane : by imposing a greater degree of non-planarity on the triphenyl-methyl radical they lower its stability and thereby hinder dissociation, whilefacilitating this process by providing additional overcrowding in the ethane.The latter effect outweighs the former.47Whereasthe alkaline rearrangement of 3- and 4-chlorobenzil48 and 2- and 3-chloro-phenanthraquinone 49 results in the preferential migration of the substitutedring, that of 2-chlorobenzil and l-chlorophenanthraquinone results in the pre-ferential migration of the unsubstituted ring.50 Apparently, steric hindranceby an adjacent chlorine atom overshadows electronic effects transmittedwithin the molecule, and the hydroxide ion attacks more readily at thecarbonyl group adjacent to the unsubstituted ring. However, o-substituentsare expected to provide only little hindrance to the approach of a nucleophileto a carbonyl group which is held in the plane of the benzene ring, for the lineof approach is perpendicular to this plane. Thus alkaline hydrolysis ofphthalide is only little affected sterically by substituents in the 7-positioi~~lThe product of the condensation of aryl aldehydes with phenylaceticanhydride in the presence of sodium phenylacetate is mainly the tram-cinnamic acid (22); in this the bulkiest groups are cis with respect to oneanother.REP.-VOL.LII 226 ORGANIC CHEMISTRY.analogous euphadiene by oxidation and partial Meystre-Miescher degradationinto products carrying the 17-side chain -CMe:CHCH:CPh,, in which theasymmetry of Ctzo) has been eliminated. The identity of the two productsshows that the starting materials differed in stereochemistry only at C(,l.yMe =C-RThe name " tirucallane " has been proposed 163 for the fundamentalhydrocarbon (88) 13a : 14p : 17a : 20-efilanostane (configuration a t Ct8) andC(9) uncertain), instead of " elemane " which might cause confusion with thesesquiterpenes.The important members of the tirucallane series are :Tirucallol Tirucalla-8 : 24-dien-38-01Elemadienolic acid 3a-Hydroxytirucalla-8 : 24-dien-21-oic acidEuphorbol 24-Methylenetirucal1-8-en-3/3-01Euphol 20-epiTirucalla-8 : 24-dien-315-01Butyrospermol (89) is one of the A7:24-isomers of euphol. Dihydro-butyrospermol, on treatment with acid, yields dihydroeuphol ( A7+As),and with perbenzoic acid gives 7-oxo-20-e~itirucal1-8-en-3~-ol. 165 " Bas-seol " is a mixture of butyrospermol and fi-amyrin.9 : 1 O-secosteroids (Calciferol and its Isomers).-Many papers have beenpublished in the last two years on the numerous isomers of calciferol whichhave been obtained by irradiation, heat, and partial synthesis.Theseisomers, which differ in configuration about double bonds, (perhaps) con-formation about single bonds, and, in some cases, the position of the doublebonds, offer a confusing picture at present and it seems profitable to deferdiscussion until workers in the field are agreed. A review 166 of the positionat the end of 1953 summarises the older literature. Among the factors usedas evidence for configurations are ultraviolet absorption (combined withsynthesis of simple reference compounds and/or theoretical arguments) andreactions with maleic anhydride.The views of various schools are given in the references165 D. S. Irvine, W. Lawrie, A. S. &Nab, and F. S. Spring, Chem.and Ind., 1955,626; M. C. Dawson, T. G. Halsall, E. R. H. Jones, G. D. Meakins, and P. C. Phillips,ibid., p. 918.lBB H. H. Inhoffen and K. Bruckner, Fortschr. Chem. org. Naturstoffe, 1954, 11, 83.187 I. T. Harrison, B. Lythgoe, and S. Trippett, J., 1955, 4016.lB8 F. Sondheimer and 0. H. Wheeler, Chem. and Ind., 1955, 714.169 E. A. Braude and 0. H. Wheeler, J , , 1955, 320, 329.l7O L. Velluz, G. Amiard, and B. Goffinet, Bull. SOC. chirn. Frunce, 1955, 1341.171 H. H. Inhoffen, K. Bruckner, G. F. Domagk, and H. M. Erdmann, Chem. Ber.,1955, 88, 1415; H. H. Inhoffen, K. Briickner, K. Irmscher, and G. Quinkert, ibid.,p. 1424; H. H. Inhoffen, K. Briickner, R. Griindel, and G. Quinkert, ibid., 1954, 87,1407; H. H. Inhoffen and G. Quinkert, ibid., p.1418; H. H. Inhoffen and J. Kath,ibid., p. 1589.17a E. Havinga, A. L. Koevoet, and A. Verloop, Rec. Truv. chirn., 1955, 74, 1230.173 L. Velluz and G. Amiard, Bull. SOC. chim. France, 1955,205 ; L. Velluz, G. Amiard,and B. Goffinet, Compt. rend., 1955, 240, 2076, 2326KLYNE STEROIDS. 227The configuration (90) of calciferol suggested by Lythgoe and his colleagues167agrees with that proposed on X-ray evidence seven yearsAmong the new compounds discussed may be noted (i) the pre-calciferolof Velluz and his colleagues 1703 173 which is apparently the immediateprecursor of calciferol and is transformed into the latter by a non-photo-chemical reaction, (ii) the " trans "-vitamins D, of Havinga 175 andInhoffen,176 (iii) the dihydrovitamin D,-I1 of Schubert,l77 (iv, v) the iso-tachysterol 178 and a(" umgelagertes ")-tachysterol 171 of Iiihoffen.The Leiden school have employed isotopically labelled 'I-dehydro-cholesterol to follow the pattern of the photochemical conversion of thevarious provitamins D.172Total Synthesis.-New work includes many improvements in synthesesdiscussed in the two previous revie~s.l7~~ 180 A general review by Cornforthhas recently appeared.ls1The Monsanto group have given details of their total synthesis ofcortisone based on the Harvard method (cf.ref. 180), and have described theresolution of the bicyclic intermediate (91) and its correlation with naturalsteroids.ls3have described a numberof lines of work directed towards a more elegant synthesis within the frame-work of their original method.A stereospecific synthesis of a trans-anti-trans-perhydrophenanthrene derivative takes the course (92-95).The Wisconsin school 185 have extended their ingenious total synthesis ofepiandrosterone to prepare an 1 l-hydroxy-compound from the intermediateCornforth, Robinson, and their colleagues(96).174 D. Crowfoot and J. D. Dunitz, Nature, 1948, 162, 608.175 A. Verloop, A. L. Koevoet, and E. Havinga, Rec. Trav. chim., 1955, 74, 1125.176 H. H. Inhoffen, J. l?. Kath, and K. Briickner, Angew. Chem., 1955,67, 276.17' K. Schubert, Naturwiss., 1954, 41, 231; Biochem. Z . , 1954, 326, 132.178 H. H. Inhoffen, K. Briickner, and R. Griindel, Chem. Ber., 1954, 87, 1.17O Ann. Reports, 1952, 49, 190.180 Ibid., 1953, 50, 21:;181 J.W. Cornforth, Progress in Organic Chemistry," ed. J. W. Cook, Butter-worths, London, 1955, Vol. 111, p. 1.182 L. B. Barkley, M. W. Farrer, W. S. Knowles, and H. Raffelson, J . Amer. ChewSOC., 1954, 76, 5017.183 A. J. Speziale, J. A. Stephens, and Q. E. Thompson, ibid., p. 5011 ; L. B. Barkley,M. W. Farrer, W. S. Knowles, H. Raffelson, and Q. E. Thompson, ibid., p. 5014.lE4 A. R. Pinder and (Sir) R. Robinson, J., 1955, 3341 ; J. W. Cornforth, 0. Kauder,J. E. Pike, and (Sir) R. Robinson, J., 1955, 3348.185 W. S. Johnson, R. Pappo, and A. D. Kemp, J . Amer. Chem. SOC., 1954,76, 3353228 ORGANIC CHEMISTRY.Reagents: 1, KOEt. 2, Li-NII,. 3, H,-Ni(94)Hon the ketal.AcOI(961(101") @a)* And AIB-isomer.Reagents : 1, Li-EtOH-NH,. 2, Pb(OAc),.3, AcOH. 4, H*CO,H.5, ( a ) Li-EtOH-NH,; (b) Hf. 6, Ha-Pd.Then as in ll-deoxy series.The introduction of the ll-hydroxy-group via 12-acetoxy-, All-, 11 : 12-diol groupings is noteworthy. Other papers from the same school deal with18 : 19-bisnor-D-homotestosterone lS6 and testosterone.187A number of papers from the Merck laboratories have described in detaillater stages in the total synthesis of cortisone (cf. ref. 179) and its subse-quent refinements,lsg~ lgo Two new methods of closing ring D are note-worthy. In the first,la9 oxidation of the primary alcohol (103) to an alde-188 W. S . Johnson, H. C. Dehm, and L. J. Chinn, J . Org. Chem., 1954, 19, 670.187 W. S. Johnson, B. Bannister,-R. Pappo, and J. E. Pike, J .Amer. Chem. SOC.,1955, 77, 817.188 G. E. Arth. G. I. Poos, R. M. Lukes, F. M. Robinson, W. F. Johns, M. Feurer,and L. H. Sarett, J . Amer. Chezn. Soc., 1964, 16, 1715; W. F. Johns, R. M. Lukes, andL. H. Sarett, ibid., 5026; G. I. Poos, R. M. Lukes, G. E. Arth, and L. H. Sarett, ibid.,p. 5031.189 G. I. Poos, W. F. Johns, and L. H. Sarett, ibid., 1965, 77, 1026.180 G. E. Arth, G. I. Poos, and L. H. Sarett, ibid., p. 3834WILSON : HETEROCYCLIC COMPOUNDS. 229hyde is followed by removal of the 20-methylene group by known pro-cedures ; cyclisation of the &-keto-aldehyde (105) with aqueous potassiumhydroxide (free from oxygen) then yields a A16-20-ketone (106). The secondCOMc Y Y Yo13 J '* CH,OH J A j'# 7""u. bHo & ~ ti H r5 l i(103) (1041 (*s) (*6)C OMcb o 2 k Y 'fa Yo T0,Me fi.0 4- 5,i ri k( 0 7 ) (lo@ ( 109)Reagents : 1, Cr03-pyridine.2, (a) OsO,, (b) HIO,. 3, KOH. 4, as 1 and 2.5, NaOMe.method 190 starts from the methoxycarbonyl compound (107) correspondingto (103). Cyclisation of the E-keto-ester (108) with sodium methoxide inbenzene gives the 16 : 20-diketone (log), which can then be transformed intothe A16-20-ketone and the saturated 20-ketone.The Ciba group,lgl continuing their total synthesis which has led to a~-homo-17a-ketone (1 lo), have described a method of contracting a six-membered to a five-membered ring which involves ring-opening of a hydr-oxyimino-ketone (1 11).Reagents : 1, C,H,,*O*NO-ButOK. 2, p-C,H,Me*SO,Cl-NaOH. 3, (a) KOH ;( b ) CH,N,.4, NaOMe.An extensive series of papers by Nazarov and his colleagueslg2 dealsOther work on poly- chiefly with bicyclic and tricyclic intermediates.hydrophenanthrenes has been reported.lg3W. K.8. HETEROCYCLIC COMPOUNDS.Small Rings.-The oxetanones (1; R = Me and Ph) have been made,the latter in 47% yield by autoxjdation of sym.-tetraphenylacetone inacetic acid.1 Azetidine-2-carboxylic acid ( 2 ) has been isolated from Con-vallaria majalis Lin., and its structure established by ring scissions2 Certainlgl P. Wieland, G. Anner, and K. Miescher, Helv. Chim. Ada, 1953, 56, 1803.lg2 I. N. Nazarov, L. D. Bergelson, I. V. Torgov, and S. N. Ananchenko, Izvest.193 C . A. Grob and 0. Schindler, Experientia, 1954, 10, 367; N. Chaudhuri and P. C.1 B.L. Murr, G. B. Hoey, and C. T. Lester, J . A m y . Chew SOC., 1955, 77, 4430;Akad. Nauk, S.S.S.R., Otdel. Khim. Nauk, 1953, 889, and subsequent papers.Mukharji, Sci. and Cult., 1954, 19, 463.G. B. Hoey, D. 0. Dean, and C. T. Lester, ibid., p. 391.L. Fowden, Nature, 1955, 176, 347230 ORGANIC CHEMISTRY.P-lactones are formed surprisingly easily from @-hydroxy-acids in diluteacids3Simple Lactones, Fwans, and Pyrans.-Glutaconic anhydrides formdihydro-oxopyridazines (4) with diazonium salts, hydrazones (3) probablybeing intermediate^.^ An analogous mechanism operates in the formationof pyrazolines from a-acetobutyrolactone and diazonium compounds.5%Lactones have given hydroxymethylene derivatives (e.g., 5), which areconverted, with rearrangement, into the esters (6) in methanolic hydrogenchloride ; 6 y-lactones behave similarly.7 a-Carboxy-y-phenylbutyrolactoneforms a Mannich base with simultaneous decarboxylation ; exhaustivemethylation of the product affords the methylene-lactone (7). Anothermethylene-lactone, protoanemonin (€9, has been obtained in 99% yield bytreating a-angelicalactone dibromide with q~inoline.~Passage of mixtures of 2-alkyltetrahydropyrans and primary amines overalumina at 300" affords piperidines, pyrrolidines, and acyclic unsaturatedbases. l o The dimers of several @-unsaturated carbonyl compounds are2-acyl-2 : 3-dihydr0pyrans.1~A large number of 2-substituted 3-hydroxypyridines has been made l2from 2-fury1 ketones and alcoholic ammonia at 165". Electrolytic methoxyl-ation of furan gives potential bdicarbonyl compounds, which have beenused in a number of interesting syntheses.13* 14* l5 For example,l3 electro-lysis of 2-acetamidomethylfuran in methanol gives the dihydrodimethoxy-furan (9), which is converted into 3-hydroxypyridine (93%) in N-hydro-9 J.H. Wotiz and J. S. Matthews, J. Org. Chem., 1955, 20, 155.4 R. H. Wiley and C. H. Jarboe, J. Amer. Chern. SOC., 1955, 77, 403; R. H. Wileyand H. G. Ellert, ibid., p. 5187.6 G. F. Duffinand J. D. Kendall, J., 1955, 3470.6 F. Korte and H. Machleidt, Chem. Bey., 1955, 88, 136, 1676.7 Idem, ibid., p. 1685.8 E. E. van Tamelen and S. R. Bach, J. Amey. Chem. Soc., 1955, 77, 4683.9 C. Grundmann and E. Kober, ibid., p. 2332.10 H. P. Richards and A.N. Bourns, Canad. J. Chem., 1955, 33, 1433.11 J. Matti and M. Perrier, Bull. SOC. chim. France, 1955, 525; J. Dreux, ibid.,p. 521 ; M. Delepine, G. Amiard, M. Badoche, P. Compagnon, A. Horeau, J. Jacques,and A. Willemart, Ann. Chim., 1955, 10, 5 ; R. H. Hall, J., 1954, 4303.12 W. Gruber, Chem. Ber., 1955, 88, 178.13 N. Clauson-Kaas, N. Elming, and 2. Tyle, A c f a Chem. Scand., 1955, 9, 1.14 J. T. Nielsen, N. Elming, and N. Clauson-Kaas, ibid., p. 9; N. Clauson-Kaas andP. Nedenskov, ibid., p. 14; P. Nedenskov, N. Elming, J. T. Nielsen, and N. Clauson-Kaas, ibid., p. 17; N. Clauson-Kaas and P. Nedenskov, ibid., p. 27; J. T. Nielsen,N. Elming, and N. Clauson-Kaas, ibid., p. 30; J. T. Nielsen, N. Clauson-Kaas, andP. Dietrich, ibid., p. 182.15 N.Elming and N. Clauson-Kaas, ibid., p. 23WILSON : HETEROCYCLIC COMPOUNDS. 231chloric acid.from a suitably substituted furan.15Pyridoxine has been made by a similar method in 76% yieldp p 2 3 , . C O P fi lG%7 ,'CO2H(13)s-s(I 2)SuZ+hur Com$oztnds.-Recent developments in thiophen chemistry havebeen reviewed.16 Several long-chain acids have been made from substitutedthiophen acids (e.g., 10 + 11) by Raney nickel des~lphurisation.~~ Di-and tri-carboxylic acids of thiophen, furan, and pyrrole have been de-scribed.l* There has been continued interest 1 9 9 2 0 in the synthesis ofa-lipoic (6-thioctic) acid (12) ; one ingenious synthesis 2o employs theintermediate (13), made by Prins condensation of formaldehyde withhept-6-enoic acid. 1 : 2-Dithiole-3-thiones (14) appear to be fairly stable;they have been made from p-oxo-esters and phosphorus pentasulphide,21and by heating a-methylstilbenes 22 or cumenes 23 with sulphur.The dioxide(15) is a much weaker base than 4-aminotetrahydrothiopyran, probablybecause of the intramolecular interaction shown.%0 9 -"'NH, R'!,-i +.. O + ~ H H ~ N ~ ; ; no/ V0 C H2ClC y04) (1 5) (16) (17)Five-membered Rings containing Nitrogen.-Good yields of N-alkyl-pyrrolidones are obtained from y-alkylbenzylamino-acid hydrochlorides inboiling acetic anhydride, debenzylation occurring sim~ltaneously.~~ Re-ductive condensation of hydroxyiminomalonic ester with p-dicarbonylcompounds, effected with zinc dust in acetic acid, provides a valuable newsynthesis of substituted pyrrole-2-carboxylic esters.26 Several relativelysimple pyrroles form stable crystalline salts with hydrogen bromide in dryether.27l6 F. F. Nord, A. Vaitiekunas, and L. J. Owen, Forlschr. chem. FOYSC~., 1955, 3,l7 M. Sy, Bull. SOC. chim. France, 1955, 1175; G. M. Badger, H. J. Rodda, and1* R. G . Jones, J . Amer. Chem. Soc., 1955, 77, 4069, 4163.1s L. J. Reed and C . Niu, ibid., p. 416; E. Walton, A. F. Wagner, F. W. Batchelor,20 E. A. Braude, R. P. Linstead, and K. H. R. Wooldridge, Chem. and Ifid., 1955,21 L. Legrand and N. Lozac'h, Bull. SOC. chim. France, 1955, 79; J. Teste and22 J. Schmitt and M. Suquet, ibid., p. 84.28 E. K. Fields, J . Amer. Chem. SOC., 1955, 77, 4255.24 C. Barkenbus and J. A. Wuellner, ibid., p.3866.26 M. W. Gittos and W. Wilson, J., 1955, 2371.26 G. G. Kleinspehn, J . Amer. Chem. SOC., 1955, 77, 1546.27 R. J. Stedman and S. F. MacDonald, Canad. J . Chem., 1955, 33, 468.309-333.W. H. F. Sasse, J., 1954, 4162.L. H. Peterson, F. W. Holly, and K. Folkers, ibid., p. 5144.608.N. Lozac'h, ibid., p. 437232 ORGANIC CHEMISTRY.2-Aryloxazolines are obtained from p-azido-alcohols and aromaticaldehydes in concentrated sulphuric acid.28 The chemistry of oxazol-5-onehas been reviewed,29 and linear polyamides made by the reaction of 2 : 2'-bis (oxazolones) with diamines30 Oxazolid-2-ones are conveniently made byheating substituted et hanolamines with ethyl trichloroacet at e, chlorof o mbeing formed simultaneously ; whilst y-aminopropanols similarly give thesix-membered cyclic analogues, 8-aminobutanols behave differently andafford pyrr~lidines.~~ The isooxazolid-%one structure (16) for the anti-biotic oxamycin, which is identical with cycbserine, has been established bydegradative studies and by total synthesis.32 2-Aminothiazole hydro-chloride can be made in 91% yield from thiourea and 2-chloromethyl-1 : 3-dioxolan (17), which is readily ac~essible.~~ The infrared absorption pro-perties of thiazolines have been recorded,34 and it has been found thatthiazol-5-ones, obtained by heating a-thioacylamino-acids with aceticanhydride, resemble oxazolones in reactions with carbonyl compounds andwith a m i n e ~ .~ ~A series of novel glyoxaline derivatives (20) has been made, in additionto previously recognised products, by treating 4-alkylidene-2-thiothiazolid-5-ones (18) with ammonia, thioamides (19) being probable intermediate~~6The nitration of pyrazoles has been studied ; N-nitro-compounds areformed first, and rearrange in acid media to 4-nitropyra~oles.~' Pyrazolesare easily iodinated 38 and br~rninated.~~ Bromine affords crystallineadducts (e.g., 21) ; in the presence of iron powder, 4-bromo-, 3 : 4-dibromo-,and 3 : 4 : 5-tribromo-pyrazoles are obtained.Several condensation pro-ducts are formed from pyrazoles and aqueous sodium hypobromite; forexample, the complex compound (22), m. p. 278", is one of the productsfrom 3 : 4-dimethylpyra~ole.~~ The formation of furoxans (23) from arylmethyl ketones and nitric acid probably involves 40 dimerisation of inter-mediate nitrile oxides (24).28 J.H. Boyer and J. Hamer, J . Amer. Chem. SOL, 1955, 77, 951.2@ E. Baltazzi, Quart. Rev., 1955, 9, 150.80 C. S. Cleaver and B. C. Pratt, J . Amer. Chem. SOL, 1955, 77, 1544, 1541.31 G. Y. Lesher and A. R. Surrey, ibid., p. 636.32 F. A. KueN, F. J. Wolf, N. R. Trenner, R. L. Peck, E. Howe, B. D. Hunnewell,G. Downing, E. Newstead, R. P. Buhs, I. Potter, R. Ormond, J. E. Lyons, L. Chaiet,and K. Folkers, ibid., p. 2344; P. H. Hidy, E. B. Hodge, V. V. Young, R. L. Harned,G. A. Brewer, W. F. Phillips, W. F. Runge, H. E. Staveley, A. Pohland, €3. Boaz, andH. R. Sullivan, ibid., p. 2345; C. H. Stammer, A. N. Wilson, F. W. Holly, and K.Folkers, ibid., p. 2346.33 M. J.Astle and J. B. Pierce, J . Org. Ckem., 1955, 20, 178.94 W. Otting and F. Drawert, Chem. Ber., 1955, 88, 1469.95 J. B. Jepson, A. Lawson, and V. D. Lawton, J., 1955, 1791.9s F. P. Doyle, D. 0. Holland, and J. H. C. Nayler, J., 1955, 2265.87 R. Huttel, F. Buchele, and P. Jochum, Chem. Ber., 1955, 88, 1577; R. Huttel38 R. Huttel, 0. Schafer, and P. Jochum, Annalen, 1955, 593, 200.89 R. Huttel, H. Wagner, and P. Jochum, ibid., p. 179.40 H. R. Snyder and N. E. Boyer, J. Amer. Chem. SOC., 1955, 77, 4233.and F. Buchele, ibid., p. 1586WILSON : HETEROCYCLIC COMPOUNDS. 233Several 1 : 2 : 4-oxadiazoles have been made by heating amidoximes withacetic anhydride or benzoyl chloride,41 and 1 : 3 : 4-oxadiazoles (25) fromacylhydrazines and orthoesters, via alkoxymethylenehydrazides.42 1 : 3 : 4-Oxadiazol-2-ones (26) are best made from hydrazides and carbonyl chloride,MemMe(24) A r -CO*CIN-tObut they can be obtained by treating N-acyl-N'-chloroureas with sodiumcarbonate ; the products undergo ring scission with amines, yielding semi-carbazides and finally hydrazide~.~~ Substituted 1 : 2 : 4-thiadiazoles (27;X = O R and N q ) are obtained from O-alkylureas 44 or NN-dialkyl-guanidines 45 by N-chlorination and reaction with sodium thiocyanate ;and 5-alkylamino-3-amino-compounds (27 ; X = NH,) from N-alkyl-N'-amidinothioureas and hydrogen peroxide in aqueous ethan01.4~ Thereaction of thionyl chloride with certain acylhydrazones gives photosensitive1 : 2 : 3-thiadiazoles (e.g., 28 + 29), which thus become readilyacce~sible.~' The acids (30; R = H) are cyclised in alkali to 1 : 3 : 4-oxadiazoles (25; R' = SH), whereas the corresponding benzyl esters (30;R' = CH,Ph) yield 1 : 3 : 4-thiadiazoles (31) in concentrated sulphuricacid .48Current usage of theIt has been stressed 50+(31) (32 (33)term '' mesoionic " has been strongly critici~ed.~~that mesoionic compounds have true benzenoidaromatic structures, as seen in the betaine forkulations (32) or (preferably)(33) for N-phenylsydnone.If the description " mesoionic " is retained, itshould be applicable to all mesomeric aromatic betaines, including suchcompounds as (34) and tropone. Acid hydrolysis of alkylsydnones has beendl K. Clarke, J., 1954, 4251.42 C. Ainsworth, J . Amer.Chem. Sot., 1955. 77. 1148.O3 A. Stempel, J. Zelauskas, and J. A. Aeschlimann, J . Org. Chem., 1955, 20, 412.44 J. Goerdeler and F. Bechlars, Chem. Ber., 1955, 88, 843.O6 J. Goerdeler and M. Willig, ibid., p. 1071.O6 F. Kurzer, J., 1955, 1, 2288.O7 C. D. Hurd and R. I. Mori, J . Amer. Chem. Sot., 1955, 77, 5359.48 R. W. Young and K. H. Wood, ibid., p. 400.6o W. Baker and W. D. Ollis, ibid., p. 910; T. I. Bieber, ibid., p. 1055; W. J. 0.A. R. Katritzky, Chem. and Ind.. 1955, 521, 1391.Thomas, ibid., p. 533234 ORGANIC CHEMISTRY.used for the preparation of substituted hydrazines ; 51, 52 3-3'-pyridyl-sydnone is reversibly phototropic, the normal colourless form becomingdeep blue in sunlight.52 A new series of mesoionic compounds (36) has beenmade from alkylsemicarbazides and nitrous acid.53The extensive chemistry of tetrazolium salts has been reviewed.=Six-membered Nitrogenous Rings.-The properties of six-memberedaromatic rings containing nitrogen have been discussed,55 also the mechanismC\aAcRON - N Q- A!$)*- 0 & Re41 (35 1 (36 1 (37)of nucleophilic substitution in these and related compounds. 56 Passingmixtures of alkyl or aryl cyanides or cyanogen with 1 : 3-dienes over aluminaat 400" affords useful quantities of substituted pyridines ; 57 and 2-2'-pyridylethylamines are conveniently made by the addition of secondaryamines to 2-~inylpyridine.~* Results are now available on the basicstrengths and ultraviolet-light absorptions of a large number of alkyl-,59halogeno-,60 and 3-hydroxy-pyridines 61 and pyridine N-oxides.62 Largea-substituents in pyridine markedly hinder quaternary salt formation.Oxidation of gaseous alkylpyridines with air at 380" over mixed vanadium-molybdenum oxides gives mainly pyridine-aldehydes. IX Moderate yieldsof pyridinecarboxylic acids are obtained from alkylpyridines and seleniumdioxide, but 3-methyl groups are not attacked.65 Dilute nitric acid is apromising reagent for the oxidation of alkylpyridines ; 66 thus, with a mixtureof 10% nitric acid and 89% phosphoric acid at 230" in a stainless-steelautoclave, y-picoline gives isonicotinic acid in yields up to 95%. Ringexpansion of pyrrole to 3-chloropyridine (33%) occurs 67 when a mixture withchloroform is passed through a glass tube at 550".It has been known forsome time that pyridine is mercurated at position 3 ; pyridine-2-sulphinicacid has now been converted into 2-pyridylmercuric chloride.68 PyridineN-oxide is sulphonated with great difficulty, to the 3-sulphonic a ~ i d . 6 ~Boiling acetic anhydride converts 70 4-methylpyridine N-oxide into a mixtureof the acetates (36) and (37).6 1 J. Fugger, J. M. Tien, and I. M. Hunsberger, J . Amer. Chem. SOC., 1955, 77, 1843.62 J. M. Tien and I. M. Hunsberger, Chem. and Ind.. 1955, 119.53 J. H. Boyer and F. C. Canter, J. Amer. Chem. SOC., 1955, 77, 1280.64 A. W. Nineham, Chem. Rev., 1955, 55, 355-483.55 A. Albert, Chem. SOC. Special Publ. No. 3, 1955, p. 124.66 N. B. Chapman, ibid., p. 155.67 G. J. Jang and W. J. H.McCulloch, J. Amer. Chem. SOC., 1955, 77, 3014, 1343.6 8 H. E. Reich and R. Levine, ibid., p. 4913.69 H. C. Brown and X. R. Mihm, ibid., p. 1723.60 H. C. Brown and D. H. McDaniel, ibid., p. 3752.61 D. E. Metzler and E. E. Snell, ibid., p. 2431.62 H. H. Jaff6 and G. 0. Doak, ibid., p. 4441; H. JaffC, ibid., p. 4451.63 H. C. Brown and A. Cahn, ibid., p. 1715.64 W. Mathes and W. Sauermilch. Chem. Ber., 1955, 88, 1276.65 D. Jerchel, E. Bauer, and H. Hippchen, ibid., p. 156.S8 E. B. Bengtsson, Actu Chem. Scand., 1955, 9, 832.67 H. L. Rice and T. E. Londergan, J. Amer. Chem. SOC., 1955, 77, 4678.68 C. D. Hurd and C. J. Morrissey, ibid., p. 4658.6@ H. S. Mosher and F. J. Welch, ibid., p. 2902.70 J. A. Berson and T. Cohen, ibid., p. 1281WILSON : HETEROCYCLIC COMPOUNDS. 235The rearrangement 71 of l-methylpynmidinium compounds, eg., (38) +(39), recalls several other rearrangements in the heterocyclic field.72 Ultra-violet-light absorption studies show that 2- and 4-hydroxypyrimidines existlargely in the lactam form in solution; these compounds afford chieflyN-methyl derivatives with diaz~methane.~~ A series of 1 : 2 : 4-triazines(41) has been made by treating or-diketone acylhydrazones (40) withammonia.74 1 : 3 : 5-Triazine can be made in fair yields by heating form-amidine hydrochloride with bases ; it is a powerful noble-metal catalystp0ison.7~Condensed Ring Systems.Naturally occurring Oxygen Ring Compounds.-Some of these compounds are discussed in a recent rn~nograph.~~ TheAuwers synthesis of 2-acylcoumaran-3-ones (43) from o-acyloxy-w-chloro-acetophenones probably involves intermediates (42) formed by a Baker-Venkataraman transformation.77 Fair yields of flavonols (45) are obtainedfrom a-chloro-o-hydroxyacetophenones in cold ethanolic potassium hydrox-ide, and 2-arylidenecoumaran-3-ones (aurones) (48) are formed at highertemperatures ; epoxides (44) are likely intermediates in this condensation. 78Aurones (48) undergo ring expansion to flavones (49) in ethanolic potassiumcyanide 79 and give either aurone epoxides or flavonols (45) with alkalinehydrogen peroxide. 80 Rearrangement of 2-acylcoumarone oxime toluene-P-sulphonates is a convenient route to chromonols (especially) and flavonols ;71 H. C. Carrington, F.H. S. Curd, and D. N. Richardson, J., 1955, 1858.7 2 Ann. Reports, 1953, 50, 238.74 R. Metze, Chem. Ber., 1955, 88, 772.7s C. Grundmann, H. Schroder, and W. Ruske, ibid., 1954, 87, 1865 (cf. C. Grund-76 Y. Asahina and S. Shibata, Chemistry of Lichen Substances,” Japanese7? E. M. Philbin, W. I. A. O’Sullivan, and T. S. Wheeler, J., 1954, 4174.J. E. Gowan, P. M. Hayden, and T. S. Wheeler, J., 1955, 862.70 D. M. Fitzgerald, J. F. O’Sullivan, E. M. Philbin, and T. S. Wheeler, J., 1955,W. E. Fitzmaurice, W. I. O’Sullivan, E. M. Philbin, and T. S. Wheeler, Chem.D. J. Brown, E. Hoerger, and S. F. Mason, J., 1965, 211.mann and A. Kreutzberger, J . Amer. $ ? m . SOL, 1955, 77, 44).Society for the Promotion of Science, Tokyo, 1954.860.and Ind., 1955, 652236 ORGANIC CHEMISTRY.the mechanism of this reaction has now been studied.*l Flavonoidsfrequently rearrange in acid media [q., (46) + (47)], probably by ether-scission of the pyrone ring followed by cyclisation in the alternative way.82OHOH MeHO ij( 5 0 ) (50HO 0WM* 7 q R HO ~ ~ ~ ~ c , , i c o , ” Ma od 52) (53) O R’ (54)Infrared absorption properties of flavones and flavanones have beenreported,m and reactivity sequences in the methylation of A avone-hydroxylgroups and in the demethylation of methyl ethers established.a A newtype of flavonoid pigment, represented by distemonanthin (50) has beendi~covered.~~ Details of the synthesis of Zeztcoanthocyanidins have beenpublished,86 and the conformational structure (51) has been proposed forcatechin ; epicatechin is the 3-epimer.87The structure of mellein (ochracin) (52) has been confirmed 88 by synthesis0 0MeOHof the (&)-methyl ether, and that of isogalloflavin 8~ (53; R = CO,H,R = H; or vice versa) by degradation to the acid (54).Two groups ofworkers 90 have synthesised trimethylbrevifolin (55).81 T. A. Geissman and A. Armen, J . Amer. Chem. SOC., 1955, 77, 1623.82 S. K. Mukerjee and T. R. Seshadri, Chem. and Ind., 1955, 271.as B. L. Shaw and T. H. Simpson, J., 1955, 655.84 T. H. Simpson and J. L. Beton, J., 1954, 4065.86 F. E. King, T. J. King, and P. J. Stokes, J.. 1955, 4594.88 F.. E. King and J. W. Clark-Lewis, J., 1955, 3384.8’ F. E. King, J. W. Clark-Lewis, and W. F. Forbes, J.. 1955, 2948; J.W. Clark-Lewis, Chem. and Ind., 1955, 1218; cf. E. A. H. Roberts, zbid., pp. 631, 1551.8 8 J. Blair and G. T. Newbold, J., 1955, 2871.J. Grimshaw, R. D. Haworth, and H. K. Pindred, J., 1955, 833.*O R. D. Haworth and J. Grimshaw, Ckem. and Ind., 1955, 199; K. Bernauer and0. T. Schmidt, Annalen, 1955, 591, 153WILSON : HETEROCYCLIC COMPOUNDS. 237Structure (56) is proposed for fuscin, and the total synthesis of dihydro-Purpurogenone (probably 57) has been fuscin methyl ether reported.g1isolated Q2 from a strain of Penicillium purpurogenum Stoll.The total synthesis of usnic acid (60) has been accomplished elegantly;ferricyanide oxidation of methylphloracetophenone (58) affords the hydroxy-diketone (59), which is dehydrated by concentrated sulphuric acid to(-j-)-usnic acid;93a this had been resolved p r e v i o ~ s l y .~ ~ The mode ofdimerisation of p-cresol derivatives involved in this synthesis appears to befairly general, and is possibly significant in the biogenesis of dibenzofuranlichen s u b ~ t a n c e s . ~ ~ ~ The formation of dibenzofurans and diquinones fromquinones has been d i s c u ~ s e d . ~ ~ An important advance is the synthesis ofthe product (61) of ozonolysis of usnic acid.94Chromic acid oxidation of bergapten (62) gives ajwxanthoxyletin (63) ;methylation, and treatment with acid hydrogen peroxide, then gives fraxinol(64). Similar reactions are employed in the conversion of visnagin intobaicalein .95(65) (66)(R = 3 : 4-methylenedioxyphenyl)The structure of sesamolin (65), which with sesamin (66) is mainlyresponsible for the pyrethrum-synergistic activity of sesame oil, has beenconfirmed by degradati~n.~~ Fagarol is identical with (-!-)-~esamin.~~Condensed Ring Systems containing Nitrogen.-Ultraviolet-light absorp-tion by mono- and di-cyclic N-heteroaromatic systems has been di~cussed.~sO1 D.H. R. Barton and J. B. Hendrickson, Chem. and I n d . , 1966, 682; A. J. Birch,;bid., p. 682.O 2 J. C. Roberts and C. W. H. Warren, J.. 1955, 2092.08 (a) D. H. R. Barton, A. M. Deflorin, and 0. E. Edwards, Chem. and Ind., 1955,1039; (b) F. M. Dean, P. Halewood, S. Mongkolsuk, A. Robertson, and W. B. Whalley,J., 1953, 1250; (c) F. M. Dean, A. M. Osman, and A. Robertson, J . , 1966, 11.94 F. M. Dean and A.Robertson, J., 1955, 2166.O 6 A. Schonberg, N. Badran, and N. A. Starkowsky, J . Amer. Chem. SOL, 1955,77, 5390.O 6 M. Beroza. ibid., p. 332; E. Haslam and R. D. Haworth, J., 1956, 827; H. Erdt-man and 2. Pelchowicz, Chem. and I n d . , 1965, 567; B. Carnmalm, H. Erdtman, and2. Pelchowicz, Acia Chem. Sand., 1965, 9, 1111.O 7 B. Carnmalm and H. Erdtman, Chem. and I n d . , 1966, 670.0 8 S. F. Mason, Chem. Soc. Special Publ. No. 3, 1966, p. 139238 ORGANIC CHEMISTRY.Monographs have been published dealing with indoles and carbazoles ~9 andwith condensed thiophen ring systems.1001-Acylated products are obtained from indolylmagnesium bromide andcertain lactones. lol Indoles and oxalyl chloride readily give highly crystal-line 3-glyoxyloyl chlorides, and lithium aluminium hydride reduction of theamides therefrom is a convenient route to tryptamines.lo2 Ring scission ofindoles to o-acylamino-acids or -ketones is effected by ozone lo3 or by aut-oxidation ; l o 3 9 lo4 in the latter case, hydroperoxides (67) are intermediates.Indoles react with nitro-olefins, yielding 3-2'-nitroalkyl derivatives,105 andwith a-acetamidoacrylic acid in acetic acid-anhydride, indole gives acetyl-tryptophan.lo6 Piperidine-ring expansion occurs during the ferricyanideoxidation of the substituted derivatives (68), and the cycloheptenoindole(69) is formed.lo7Ultraviolet-light absorptions and base strengths for quinolines havebeen reported.108 The chemistry of Reissert compounds has received furtherattention,lm and this subject has been reviewed.ll0 Nitration of quinolineaffords only a small yield of nitro-compound, mainly the 3-isomer.111 1 : 2-Dihydroisoquinoline has been isolated for the first time ; 112 reactive dihydro-isoquinolines are intermediates in several interesting syntheses.113~ 114Thus, reduction 114 of the N-substituted isoquinolinium salt (71) (from09 W.C. Sumper and F. M. Miller, "Chemistry of Heterocyclic Compounds.Vol. VIII. Heterocyclic Compounds with Indole and Carbazole Systems," IntersciencePubl. Inc., New York, 1954.loo H. D. Hartough and S. L. Meisel, "Compounds with Condensed ThiopheneRings," Interscience Publ. Inc., New York, 1954.101 A. R. Katritzky and Sir R. Robinson, J., 1955, 2481.102 M. E. Speeter and W. C. Anthony, J .Amer. Chem. Soc., 1954, 76, 6209.10s G. Clerc-Bory, M. Clerc-Bory, H. Pacheco, and C. Mentzer, BUZZ. SOC. chim.104 R. J. S. Beer, T. Donavanik, and A. Robertson, J., 1954, 4139.106 W. E. Noland, G. M. Christensen, G. L. Sauer, and G. G. S. Dutton, J . Atner.106 H. R. Snyder and J. A. MacDonald, ibid., p. 1257.107 J. Harley-Mason and A. H. Jackson, J., 1955, 374.108 S. B. Knight, R. H. Wallick, and C. Balch, J . Amer. Chem. Sot., 1955, 77, 2577.109 R. F. Collins, ibid., p. 4921; R. L. Cobb and W. E. McEweo, ibid., p. 5042.110 W. E. McEwen and R. L. Cobb, Chem. Rev., 1955, 55, 511.111 M. J. S. Dewar and P. M. Maitlis, Chem. and Ind., 1955, 685.112 L. M. Jackman and D. I. Packham, ibid., p. 360.118 A. R. Battersby, R. Binks. and P. S.Uzzell, ibid., p. 1039.114 K. T. Potts and Sir R. Robinson, J., 1955, 2675.France, 1955, 1229.Chem. Sot., 1955. 77, 456WILSON HETEROCYCLIC COMPOUNDS. 239homophthalaldehyde and tryptamine) by lithium aluminium hydride, givesthe yohimbine skeleton (72). Bromine forms N-bromoacridinium bromideswith acridine in carbon tetrachloride, and 3-bromo- and 3 : 7-dibromo-compounds in acetic acid.115 Thiolutin and aureothricin are yellow crystal-line antibiotics isolated from various Streptomyces ; they have beenassigned 116 the unique pyrrolo-1 : 2-dithiole structures (70; R = Me andEt respectively).A large number of derivatives of indazole (73), including chlorination,nitration, and sulphonation products, has been de~cribed.1~' Phosphorusoxychloride cyclises 2-acylaminomethylpyridines to 2 : 3a-diazaindenes(74), which very rapidly undergo Friedel-Crafts reactions at C(l>, or at C(3)if the former position is substituted. 118 The related pyrrocoline system (75)readily undergoes Friedel-Crafts and C-alkylation reactions ; 119 in this case,07 &N2 3 mi 3 @6 (76) NO2(73) (74) (7s)substitution occurs most easily at Co).Several derivatives of the system(76) have been made from 2-aminopyridines and 2-chloro-1 : 3-dinitro-benzene.120 The chemistry of quinolizine (pyridocoline) (77) has beenreviewed.121 Dehydrobenzoquinolizinium salts (78) have been made 122by treating a-halogenated ketone-2-phenylpyridineconcentrated hydrobromic acid ; and acridiziniumquaternary salts withsalts (79) have beenprepared 123 analogously, from 2-formylpyridine and benzyl bromides.2-Aminopyridine gives the bicyclic system (80) with P-propiolactone, and2-aminothiazoles behave similarly.l% Glyoxalinothiazolium salts (81) havebeen made by several routes,125 and dihydroglyoxalinothiazolium salts have116 R.M. Acheson, T. G. Hoult, and I<. A. Barnard, J., 1954, 4142.116 W. D. Celmer and I. A. Solomons, J. Amer. Chenz. SOL, 1955, 77, 2861.117 R. R. Davies, J., 1955, 2412.11* J. D. Bower and G. R. Ramage, J., 1055, 2834.11* D. 0. Holland and J. H. C. Nayler, J., 1955, 1504.120 K. H. Saunders. J., 1055, 3275.121 B. S. Thyagarajan, Chem. Rev., 1954, 54, 1019.122 C. K. Bradsher and L. E. Beavers, J . Amer. Chem. SOC., 1955, 77, 453.128 Idem, ibid., p.4812.126 A. Lawson and H. V. Morley, J., 1955, 1695; B. Kickhofen and F. Krohnke,C. D. Hurd and S. Hayao, ibid., p. 117.Chem. Ber., 1955, 88, 1109240 ORGANIC CHEMISTRY.been made from &-halogenated ketones and tetrahydro-2-thioglyoxaline.126Derivatives of the little known 1 : 7-naphthyridine system (82) have beenmade; 12’ polyaza-naphthalene and -indene derivatives are of interest asisosteres of biologically important purines and pyrimidines.128 A numberof glyoxalino-pyridines and -quinolines have been de~cribed.1~~Kinetin (83) has been synthesised from furfurylamine and 0-methyl-thiopurine; 130 it is a cell-division factor, with the properties of a plant“wound hormone,” and has been isolated in crystalline form from auto-claved deoxyribonucleic acid.131Pteridims.-The proceedings of a symposium on pteridines have beenpublished,132 and infrared and ultraviolet absorptions for a large number ofmonosubstituted pteridines r e ~ 0 r d e d . l ~ ~ Ring scission of hydroxypteridinesby acids and alkalis has been studied carefully.134 Reaction of the chloro-pyrazines (84; R = C02Me or CN) with amidines (or guanidine) provides anew route to 4-hydroxy- and 4-amino-pteridines. 135 Many quin~xalines,~~~(84 (8 5) (86)pteridines,13’ and other polycyclic compounds 138 have been made by thecondensation of appropriate o-aminonitroso-compounds with cyanoaceticesters. Among new pterins isolated from Drosophilia species are [85;R = CH(OH)*CH(OH)*CHJ 139 and [85; R = CH(OH)*C02H].140 Theformer is probably identical with a growth factor for Crithidia fasciculata,biopterin, isolated from urine.141 The structure of urothione (86) has beenelucidated,142 and some progress made in the synthesis of related thiophano-and dihydrof~rano-pteridines.~~~Porphyrins.-The condensation product from pyrrole and acetone1z6 W.Wilson and R. Woodger, J., 1955, 2943.127 H. E. Baumgarten and A. L. Krieger, J . Amer. Chem. SOC., 1955, 77, 2438.1z8 F. L. Rose, J., 1954, 4116; C. L. Leese and H. N. Rydon, J., 1956, 303.1 Z g K. Schilling, F. Krohnke, and B. Kickhofen, Chem. Ber., 1955, 88, 1093;F. Krohnke and B. Kickhofen, ibid., p. 1103; B. Kickhofen, ibid., p. 1114.130 C. 0. Miller, F. Skoog, F. S. Okumura, M. H. von Saltza, and F. M. Strong, J .Amer.Chem. Soc., 1955, 77, 2662.131 C. 0. Miller, F. Skoog, M. H. von Saltza, and F. M. Strong, ibid., p. 1392.132 G. E. W. Wolstenholme and M. P. Cameron (Editors), Ciba Foundation Sym-posium on Chemistry and Biology of Pteridines, J. and A. Churchill, London, 1954.133 S. F. Mason, J., 1955, 2336.134 A. Albert, J., 1955, 2690.135 G. P. G. Dick and H. C. S. Wood, J., 1955, 1379; E. C. Taylor, jun., and137 Idem, ibid., p. 2036.138 F. C. Copp and G. M. Timmis, J., 1955, 2021; T. S. Osdene and G. M. Timmis,139 H. S. Forrest and H. K. Mitchell, J . Amer. Chem. Soc., 1966, 77, 4865.l 4 0 M. Viscontini, E. Loeser, P. Karrer, and E. Hadorn, Helv. Chim. Acta, 1955, 38.141 E. L. Patterson, H. P. Broquist, A. M. Albrecht, M. H. von Saltza, and E.L. R.142 R. Tschesche, F. Korte, and G. Heuschkel, Chem. Bev., 1966, 88, 1251.143 R. Tschesche, H. Barkemeyer, and G. Heuschkel, ibid., p. 1258; R. TschescheW. W. Paudler, Chem. and Ind., 1955, 1061.T. S. Osdene and G. M. Timmis, J., 1955, 2027.J., 1955, 2032, 2214.397, 1222.Stokstad, J . Amer. Chern. SOC., 1955, 77, 3167.and H. Barkemeyer, ibid., p. 976WILSON : HETEROCYCLIC COMPOUNDS. 241probably l* has the structure (87), and analogous structures are suggestedfor the anhydrotetramers obtained from furan and methyl ket0nes.1~~Factors involved in the stability of metal-porphyrins have been studiedCH;CO,H1HO,CH 0,CCH,€O N H,IMecarefully ; copper complexes are markedly stabilised, relatively to mag-nesium complexes, by the introduction of ethoxycarbonyl groups into thepyrrole residues.146 The structure of chlorophyll 14' and the hydrogenationof porphyrins 148 have been discussed; and a series of papers deals withsynthetic tetra-azaporphyrins and intermediate imidines.149P.Rothemund and C. L. Gage, J . Amer. Chem. Soc., 1955, 77, 3340.145 R. G. Ackman, W. H. Brown, and G. F. Wright, J. Org. Chew., 1955, 20, 1147.14% W. S. Caughey and A. H. Corwin, J . Amer. Chem. SOC., 1955, 77, 1609; A. H.Corwin and M. H. Melville, ibid., p. 2755.147 R. P. Linstead, U. Eisner, G. E. Ficken, and R. B. Johns, Chem. SOC. SpecialPubl. No. 3, 1955, p. 83.14* M. Whalley. ibid.? p. 98.1955, 3521;G. E. Ficken and R. P. Linstead, J . , 1965, 3525; R. P. Linstead and k Whalley, J.,1965, 8630; J.A. Elvidge and R. P. Linstead, J.. 1955, 3536.M. E. Baguley, H. France, R. P. Linstead, and M. Whalley242 ORGANIC CHEMISTRY.The proposa11501151 of a detailed structure (89) for vitamin B,, is aremarkable achievement, and a full account of this work is eagerly awaited.It was shown in a brilliant X-ray crystallographic study 151 that the hexa-carboxylic acid, previously obtained by alkaline degradation of thevitamin, has the probable structure (88), and that the vitamin itself is aporphyrin of the same type. The fine structure (89) for the vitamin issupported by chemical evidence,150 which, inter aZia, enables the conjugatedsystem to be located satisfactorily. It is noteworthy that in the conversionof the vitamin into the hexacarboxylic acid the conjugated system migratesand a lactam ring is formed.The oxidation products of the vitamin wereshown recently to include 3 : 3-dimethyl-2 : 5-dioxopyrrolidine-4-propion-amide.153 It has been recognised that “ Factor I11 ’’ isolated from fermentedsewage, is a vitamin B,, analogue, containing a 5-hydroxybenziminazolenucleotide fragment. w. w.9. ALKALOIDS.VOLUME V of ((The Alkaloids” (Manske) has appeared during the yearreviewed. It covers the pharmacology of alkaloids, including narcotics andanalgesics, cardio-active alkaloids, respiratory stimulants, antimalarials,uterine stimulants, alkaloids as local anmthetics, pressor alkaloids, mydriaticalkaloids, curare-like effects, lycopodium alkaloids, and minor alkaloids ofunknown structure., The yohimbine, corynantheine, alstonine, cinchon-amine, and Erythrina alkaloids of the indole group have been reviewed, andpossible schemes for their biogenesis discussed.lU Structural relations inthe alkaloid field have been reviewed.lb Reviews of curare alkaloids haveappeared.2 A new synthesis of bufotenine has been rep~rted.~ Theabsolute stereochemistry of the morphine, benzylisoquinoline, aporphine,and tetrahydroberberine alkaloids has been discussed ; the change of opticalrotation with polarity of solvents is of the same type in the benzyliso-quinoline and tetrahydroberberine series, but there is an inversion in theaporphine series.The benzylisoquinoline, aporphine, and tetrahydro-berberine alkaloids accompanying the morphine and sinomenine alkaloids inNature are enantiomorphous with the latter.4Tropane Group.-A review of the chemistry and biochemistry of tropane150 D.C . Hodgkin, Sir A. R. Todd, and A. W. Johnson, Chem. Soc. Special Publ. No.3, 1955, p. 109; R. Bonnet, J. R. Cannon, A. W. Johnson, I. Sutherland, Sir A. R. Todd,and E. L. Smith, Naturs, 1955, 176, 325.161 D. C. Hodgkin, J. Pickworth, J. H. Robertson, K. N. Trueblood, R. J. Prosen,and J. G. White, ibid., p . 325.162 J. R. Cannon, A. W. Johnson, and Sir A. R. Todd, ibid., 1954, 174, 1168.153 F. A. Kuehl, C. H. Shunk, M. Moore, and K. Folkers, J . Amer. Chem. Soc.,1955, 77, 4418.164 F. M. Robinson, I. M. Miller, J. F. McPherson, and K . Folkers, ibid., p . 5192.1 “ The Alkaloids,” ed. R.H. F. Man:?, Academic Press, New York, 1955, Vol. V.Progress in Organic Chemistry,” ed. J. W.Cook, Butterworths Sciettific Publications, London, 1955, Vol. 3, Chapter 5, p. 218.1b Sir R. Robinson, The Structural Relations of Natural Products,” Oxford Univ.Press, 1955.2 D. Vovet, Boll. sci. Fac. Chiin. ind. Bologna, 1954, 12, 172; P. Karrer, Nature,1955,176, 277; P. Karrer and H. Schmid, Angew. Chem., 1955, 87, 361.5 A. Stoll, F. Troxler, J. Peyer, and A. Hofmann, Helu. Chim. Acta, 1955, 88, 1452.4 K. W. Bentley and H. M. E. Cardwell, J . , 1955, 3252 ; see also refs. 84 and 85.V. Boekelheide and V. Prelog, iPINDER ALKALOIDS. 243alkaloids has appeared,5 and further investigations on their stereochemistryhave been reported.6Lupinane Grou@.-The stereochemistry of the lupin alkaloids has beendiscussed further,’ and the synthesis of ( -j-)-cytisine announced. 2-Y-Pyr-idylallylmalonic acid (1) condensed with benzylamine and formaldehyde, togive l-benzyl-5-2‘-pyridylpiperidine-3-carboxylic acid (2 ; R = C0,H).u1-.(31The derived ethyl ester with lithium aluminium hydride afforded the alcohol(2; R = CH,*OH), which with hydrogen bromide gave the derivative(2; R = CH,Br).This quaternised to the salt (3), which on mild oxidationyielded (&)-N-benzylcytisine (4 ; R = CH,Ph). Debenzylation gave(-J-)-cytisine (4; R = H), identical with the racemic natural base. This isalso a synthesis of caulophylline (4; R = Me) and rhombifoline (4; R =CH,:CH*CH,*CH,).8The alkaloid (-)-spartalupine, found in Lupinus sericeus Pursh, is oneof the enantiomorphs of the third and remaining racemic pair stereoisomericwith (&)-sparteine and ($)-a-isosparteine.The base has been epimerisedto (+)-sparteine and to (+)-a-isosparteine, an$ has been compared with(-j-)-spartalupine, synthesised by the method of Sorm and KeiLg* 10(+)-e#iLupinine N-oxide has been found in seeds of Lupinus uarius L. ;this is the first reported natural occurrence of an N-oxide in the lupinanePyridine Group.-The controversy regarding the occurrence of pelle-tierine in Punica granatum L. cannot yet be regarded as settled.12 Wibautand his co-workers l3 have established that “ base C,” isolated from theplant, is not identical with isopelletierine. It is possible that the originalgroup.11ti A.Stoll and E. Jucker, Chimia (Switz.), 1955, 9, 25.a A. Heusner, 2. Naturforsch.. 1954, 9b, 683; G. Fodor, J. Tbth, J. Lestyan, andI. W. Vincze, Szevves Kkm. Konf. Debvccen, 1953, 293 ; G. Fodor, Acta Chim. Acad. Sci.Hung., 1955, 5, 379; Experientia. 1955, 11, 129; G. Fodor, J. Tbth, and I. Vincze, J.,1955, 3504; cf. Ann. Reports, 1954, 51, 253.7 F. Galinovsky and H. Nesvadba, Monatsh., 1954, 85, 1300; F. Galinovsky,P. Knoth, and W. Fischer, ibid., 1955, 86, 1014; J. Ratusky, R. Reiser, and F. Sorm,Chem. Listy, 1954, 48, 1794; Coll. Czech. Chem. Conam., 1955, 20, 798; cf. Ann. Reports,1954, 51, 254.E. E. van Tamelen and J. S. Baran, J . Amer. Chem. Soc., 1955, 77, 4944.M. Carmack, B. Douglas, E. W. Martin, and H.Suss, ibid., p. 4435.lo F. Sorm and B. Keil, Coll. Czech. Chem. Comm., 1948, 13, 544.11 W. D. Crow and N. V. Riggs, Austral. J . Chem., 1955, 8, 136.l2 Ann. Reports, 1954, 51, 254.1s J. P. Wibaut, H. C. Beyerman, U. Hollstein, Y . M. F. Muller, and E. Greuell,Proc. k. ned. Akad. Wetenschap., 1955, 58, €3, 56244 ORGANIC CHEMISTRY.'' pelletierine " of Hess and Eichel l4 is identical with an unidentified basefound in the bark.The tobacco alkaloid myosmine is best represented as 2-3'-pyridyl-A1-pyrroline (5). It shows a strong infrared band characteristic of a )GN-group conjugated with an aromatic ring, but no band in the }NH region.15Quinoline Group.-The pyranoquinoline alkaloid flindersine has beenproved to have the angular structure (6) by a lengthy series of degradations.On distillation with zinc dust quinoline is obtained; on treatment withpotassium hydroxide the product is 4-hydroxy-2-quinolone (7 ; R= R' = H).The alkaloid has one ethylenic bond, conjugated with the quinoline nucleus.Oxidation gives flindersinjc acid (7 ; R = CMe,*CO,H ; R' = C0,H) , whichis further degraded by hydrolysis to carbon dioxide , a-hydroxyisobutyricacid, and the quinolone (7 ; R = R' = H).Flindersinic acid, when boiledwith 95% ethanol, yields the acid (7; R = H, R = C0,H) and the corre-sponding ethyl ester, and the constitution of the latter has been proved bysynthesis. Similar degradations have been carried out on chlorodeoxy-flindersine and N-methylfindersine. The analogous aldehydic degradationproducts, a-hydroxyisobutyraldehyde and the compound (7; R = H,R' = CHO) are obtained by oxidation of flindersine with osmium tetroxideto the glycol (8; R = R = OH), followed by periodate oxidation andhydrolysis.16 Final confirmation of the structure (6) is provided by syn-thesis1' Reaction of 4-hydroxy-2-quinolone (7; R = R' = H) withp-methylcrotonyl chloride gives the ester (7; R = Me,C:CH*CO, R' = H),which undergoes a Fries rearrangement and cyclisation to the pyrano-quinolone (8; R = H, R = to).Reduction of the ketonic carbonyl groupyields the alcohol (8; R = H, R' = OH), which on dehydration affordsfiindersine (6).Dictamnic acid has been proved to have structure (7; R = Me, R' =CO,H), by unambiguous synthesis; dictamnine therefore has a linearstructure.lG2 : 3 : 4-Trimethoxy-lO-methylacridone has been found in the bark ofEvodia alata F. Muell.; it was identified by synthesis.l* Evolatine, fromthe same source, is a furanoquinoline alkaloid isomeric with ev0xine.1~ Ithas been degraded by methods similar to those used for evoxine; on potashfusion it gives the phenolic base (9 ; R = H) , which on methylation affordskokusaginine (9; R = Me), and on treatment with acid it is converted14 K. Hess and A. Eichel, Bey., 1917, 50, 1192.l6 B. Witkop, J . Amer. Chem. SOC., 1954, 76, 6597.l6 R. F. C . Brown, J. J. Hobbs, G. K. Hughes, and E. Ritchie, Austra2. J . Chem.,17 R. F. C. Brown. G. K. Hughes, and E. Ritchie, Chenz. and Ind., 1955, 1385.R. J. Gell, G. K. Hughes, and E. Ritchie, Austral. J .Chem., 1966, 8, 114.lB Ann. Reports, 1954, 51, 255.1954, 7, 3.48PINDER : ALKALOIDS. 245into the ketone (9; R = Me,CH*COCH,), isomeric with evoxoidine. Evol-atine is therefore [9 ; R = Me2C(OH)-CH(OH)*CH.J.18Methyl skimmianinate has been proved by synthesis to have structure(10) ; this provides confirmatory evidence for the linear structure of skim-mianine. Similarly, methyl O-methylkokusagininate (1 1) has been syn-thesised, proving that kokusaginine has a linear, tricyclic structure.20The alkaloid maculine, from FZindersia maculosa Lindl., is 6 : 7-methylene-dioxydictamnine (12). On hydrogenolysis it yields 3-ethyl-2 : 4-dihydroxy-6 : 7-methylenedioxyquinoline, identified by synthesis.,1Indole Grou$.-A review of ergot alkaloids has appeared.22 The stereo-chemistry of lysergic and dihydrolysergic acid % and their amides 24 has beendiscussed.A series of lumi-compounds has been obtained from ergotalkaloids and other lysergic acid derivatives by ultraviolet irradiation inaqueous acid solution; the 9 : 10-double bond in the lysergic acid residue ishydrated by this procedure.25The stereochemistry of the aZZoyohimbanes,26 yohimbane, corynanthei-dane, and related compounds 27 has been discussed. The alkaloid voacan-OHIgine, C,,H,,O,N,, from Voacanga thoumsia', gives on hydrolysis methanoland an acid which is easily decarboxylated to ibogaine; it is therefore amethoxycarbonylibogaine, of probable structure (13 ; X = C0,Me) .2820 R. I;. C . Brown, Austral. J .Chem., 1955, 8, 121.21 R. J. Gell, G. K. Hughes, and E. Ritchie, ibid., p. 422.22 M. Semonsky, Cesk. Farm., 1955, 4, 198.23 A. Stoll, T. Petrzilka, J. Rutschmann, A, Hofmann, and H. H. Gunthard, Helv.2a A. Stoll and A. Hofmann, ibid., 1055, 38, 421.25 A. Stoll and W. Schlientz, ibid., p. 585.26 E. Wenkert and L. H. Liu, Experientia, 1955, 11, 302.27 W-M. Janot, R. Goutarel, A. Le Hir, G. Tsatsas, and V. Prelog, Helv. Chim. Ada,28 M.-M. Janot and R. Goutarel, Cornpi. rend., 1955, 241, 986.,Chim. Acta, 1954, 37, 2039.1955, 38, 1073246 ORGANIC CHEMISTRY.Karrer and his associates have described extensive investigations onindole alkaloids of curare.2?, 30 Of these, fluorocurine and mavacurine havebeen assigned partial structures (14) and (15), on degradative and spectro-scopic evidence.80The structure (16) is now preferred for aricine.On alkaline hydrolysisaricinic acid is obtained, which differs in molecular formula from aricine byCH,; the acid is reconverted into aricine by diazomethane. Ring E inaricine is therefore not lact~nic.~lInterest in alkaloids of Rauwolfia spp. continues to increase.32 A welcomeattempt to clarify ambiguities in nomenclature amongst alkaloids of R.serpentina Benth. has been made, the intense activity in this field havingresulted in the assignment of several names to single compounds.33New structures have been proposed for ajmaline.32 The formation of3-acetonyl-3-hydroxy-l-methyloxindole (17) on oxidation confirms thepresence of a dihydro-N-methylindole system in the alkaloid.When heatedwith nickel, both ajmaline and isoajmaline yield decarbonoajmaline,C1,H2,PN,, a secondary base giving n-butyric, propionic, and acetic acid onoxidation. The formation of this base is explained by the elimination ofcarbon monoxide from the latent aldehyde group : )N*CH(OH)*CHEt +)NH + CO + *CH2Et, further reasons being given for believing such a groupto be present. Ajmaline is reduced by potassium borohydride in aqueoussolution to dihydroajmaline [)N*CH(OH) + )NH *CH,*OH], but is notreduced by lithium aluminium hydride; a possible explanation of thisdifference is that in aqueous solution an equilibrium exists between thecarbinolamine and a small proportion of the aldehyde-imine forms. Di-hydroajmaline yields a neutral dibenzoyl derivative, which has a freehydroxyl group.34 A number of carboline bases have been obtained bydehydrogenation of deoxydihydroajmaline and deoxyajmaline ; one of theseis alstyrine, and another, probably, id-N-methylalstyrine.The structure(18) for the alkaloid best explains these and other observations.34335 Otherinvestigators prefer a cyclic semiacetal structure (19), there being some doubtabout the position of the methyl group and the form of ring E . ~ ~29 H. Asmis, E. Bachli, E. Giesbricht, J. Kebrle, H. Schmid, and P. Karrer, Helv.Chirn. Acta, 1954, 37, 1968; E. Giesbricht, H. Meyer, E. Bachli, H. Schmid, and P.Karrer, ibid., p. 1974; H. Asmis, H. Schmid, and P. Karrer, ibid., p. 1983; H. Asmis,E. Bachli, H.Schmid, and P. Karrer, ibid., p. 1993.80 H. Bickel, H. Schmid. and P. Karrer, ibid., 1955, 38, 649.31 A. Stoll, A. Hofmann, and R. Brunner, ibid., p. 270; cf. Ann. Reports, 1954,51, 258.32 Ibid., p. 256.33 D. D. Phillips and M. S. Chadha, Chem. and Ind., 1955, 414.=4 Sir R. Robinson and co-workers, ibid., p. 285.35 F. C. Finch, J. D. Hobson, Sir R. Robinson, and E. Schlittler, ibid., p. 653.36 A. Chatterjee and S. Bose, Sci. and Cult., 1955, 20, 606PINDER ALKALOIDS. 247Confirmation of the location of the three vicinal substituents in ring Eof reserpic acid (20 ; R = C02H, R' = OH) has been provided by degrad-ation. The toluene-P-sulphonic ester (20; R = CO,Me, R' = p-Me*C,H,*SO,) on removal of the sulphonyl residue yields methyl anhydro-reserpate (21), which is the enol ether of a (3-keto-ester, since it is readilyhydrolysed and decarboxylated to the ketone reserpone (22).The sametoluenesulphonate , on reduction with lithium aluminium hydride, affordsreserpinol (20; R = CH,*OH, R' = H), which on dehydrogenation yields7-hydroxy-yobyrine (23) ; the structure of the last is proved by synthesis ofits methyl ether.37A new alkaloid, deserpidine, C3&&&,N2, has been found in R. canescens.On hydrolysis it yields 3 : 4 : 5-trimethoxybenzoic acid and methyl deser-pidate. It is probably a demethoxyreserpine (24; R = H), since its ultra- .?,-. (24) McOaC OMeOMe OMeMe(25)nviolet absorption curve is almost coincident with that of yohimbine 3 : 4 : 5-trimethoxybenzoate.38 Methyl deserpidate has been converted into a-yohimbine by a simple series of reactions, an inversion occurring at C(,).37 C .F. Huebner, H. B. MacPhillamy, A. F. St. Andrd, and E. Schlittler, J. Amer.Chem. SOC., 1955, 77, 472.38 E. Schlittler, P. R. Ulshafer, M. L. Pandow, R. M. Hunt, and L. Dorfman,ExFerieniia, 1955, 11, 64248 ORGANIC CHEMISTRY.Hence deserpidine, and also reserpine, are derivatives of 3-e#i-a-y0himbine,~~which has itself been found in R. se~pentirta.~~ Structures (24; R = H)and (24; R = OMe) are proposed for deserpidine and reserpine respectively.39Amongst other alkaloids found in R. canescens are canescine 41s 42 and re-~anescine,~~ the latter identical with deserpidine and, probably, withcanescine.Several groups of workers have investigated the stereochemistry ofreserpine and related alkaloids.The D/E ring junction of reserpine is provedto be cis by the stereochemically unambiguous synthesis 45 of ll-methoxy-alloyohimbane (reserpane) (22 ; replace CO by CH,), identical, apart fromthe racemic character of the synthetic material, with the Wolff-Kishnerreduction product of reserpone (22). Considerable divergence of view isfound regarding the absolute stereochemistry of reserpine, and the mattercannot yet be regarded as 46Tetraphyllin and tetraphyllicine are two alkaloids isolated from R. tetra-ptbylla L. The former has been assigned structure (25) on spectral evidence;it is a stereoisomer of reserpinine. The latter, C,,H,,N,, is the first oxygen-free RauwolJia alkaloid.47Strychnos Group.-Strychnospermine, C,,H,,O,N,, and spermostrychnine,C,1H260,N,, are two alkaloids of Strychnos psilosperma, the former being amethoxy-derivative of the latter.Strychnospermine (two C-Me) showsultraviolet absorption characteristic of a l-acetyl-2 : 3-dihydroindole, anddeacetylstrychnospermine of a 1 : 2-dihydroindole, both with a methoxylgroup in the benzene ring; the infrared absorption confirms this. Of thetwo nitrogen atoms, one “ ( a ) ] is weakly and the other strongly basic; themethoxyl group is meta to N(a). The oxidation of demethylstrychno-spermine or spermostrychnine with chromic acid yields apospermostrychnine(26), and zinc dust distillation of both deacetyl-alkaloids gives 3-ethyl-pyridine. Deacetylspermostrychnine gives with hydrogen bromide a3g H.B. MacPhillamy, L. Dorfman, C. F. Huebner, E. Schlittler, and A. F. St. Andre,J . Anzer. Chem. SOC., 1955, 77, 1071.40 F. E. Bader, D. F. Dickel, C. F. Huebner, R. A. Lucas, and E. Schlittler, ibid.,4 1 A. Stoll and A. Hofmann, ibid., p. 820.42 M. W. Klohs, F. Keller, 13. E. Williams, and G. W. Kusserow, ibid., p. 4084.43 N. Neuss, H. E. Boaz, and J. W. Forbes, ibid., p. 4087.44 E. E. van Tamelen, P. D. Mance, K. V. Siebrasse, and P. E. Aldrich, ibid., p. 3930.45 C. F. Huebner, Chern. and Ind., 1955. 1186.4 6 P. A. Diassi, F. L. Weisenborn, C . M. Dylion, and 0. Wintersteiner, J . Amer.Chem. Soc., 1955, 77, 2028, 4687; C. F. Huebner and E. Wenkert, ibid., p. 4180; E. E.van Tamelen and P.D. Hance, ibid., p. 4692; M.-M. Janot, R. Goutarel, A. Le Hir,G. Tsatsas, and V. Prelog, Helv. Chim. Acta, 1955, 38, 1073; H. B. MacPhillamy, C.F.Huebner, E. Schlittler, A. F. St. Andr6, and P. R. Ulshafer, J. Amer. Chem. SOC., 1955,77, 4335; C. F. Huebner, H. B. MacPhillamy, E. Schlittler, and A. F. St Andre, Ex-perientia, 1965, 11, 303.p. 3547.4 7 C . Djerassi and J. Fishman, Chem. and Ind., 1955, 627PINDER : ALKALOIDS. 249bromo-derivative, which is reduced by zinc dust to deoxydihydrospermo-strychnine (27). This base has been synthesised from the Wieland-Gumlichaldehyde (28), reduction of which in two stages gives the glycol (29), whencesuccessive treatment with hydrogen bromide and zinc dust-acetic acid,followed by acetylation, yields the base (27).Spermostrychnine andstrychnospermine have therefore structures (30; R = H and OMe respec-tively) .48The methoxyl group of aspidospermine is at the 7-position, as in vomi-cine ; on demethylation N-acetylaspidosine is obtained, which shows no OHband in the infrared spectrum because of hydrogen bonding involving thephenolic group. Two structures (31) and (32) have been suggested foraspidospermine ; the latter provides the better explanation of the formationof 3 : 5-diethylpyridine and 3-ethylindole on zinc dust distillation, but ismore difficult to reconcile with Woodward’s biogenetic scheme.49Erythrina Groz@.-The structure (33) has been proposed for a-erythro-idine,50 which has been degraded by methods similar to those employed forthe isomeric @-erythr~idine.~l Dihydro-a-erythroidinol on Hofmann de-gradation gives the aromatic base (34).Oxidation of this base yieldsphthalic acid; it is an isomer of the des-base of dihydro-@-erythroidine.Further Hofmann degradation gives the vinyl derivative (36 ; R = CHXH,),which can be reduced to the ethyl derivative (35; R = Et) ; oxidation ofthe latter yields o-ethylbenzoic acid. A final stage of Hofmann decom-position affords the tetrahydrofuran (36), which on mild oxidation is con-verted into the ketone (37), and on more vigorous oxidation into o-ethyl-benzoic acid. These and other observations show that a-erythroidine has48 F. A. L. Anet and Sir R. Robinson, J., 1955, 2253.B. Witkop and J. B. Patrick, J . Amer. Chem. SOC., 1954, 76, 5603.6o J.C. Godfrey, D. S. Tarbell, and V. Boekelheide, ibid., 1956, 77, 3342.Ann. Reports, 1952, 49, 225250 ORGANIC CHEMISTRY.the same carbon skeleton as 8-erythroidine, but the two differ in the arrange-ment of the lactone ring.50The structure (38) proposed for a9oerysopine 52 has been confirmed bysynthesis of its dimethyl ether.%AporPkine Grou$.-Spath and Hromatka’s synthesis 54 of apomorphinedimethyl ether, hitherto held in considerable doubt, has been vindicated.The critical stage, the cyclisation of the amide (39), has been found 55 oncareful re-investigation to give yields of the corresponding 3 : 4-dihydro-isoquinoline of the order of 20%.Quinazolone Grou$.-The synthesis of the Hydrangea alkaloid (40) hasbeen de~cribed,~6 the route being as shown in outline.IC02.CH2.CH:CHHHCO2*CH2*CH:CH>Reagents: (1) a, Aq.NH,; b, methyln. (2) MeCHO. (3) a, 3H,; b, CrO,;(4) a, Br2-HBr ; b, Cl-CO,.CH,CH:CH,. (5) Quinazol-4-one. (6) Aq. HCl.Phenanthridine Groz@.-Further evidence in support of the structureOn periodate oxidation, dihydro- (41) for lycorine has been advanced.62 M. Carmack. B. C. McKusick. and V. Prelog, Helv. C h h . Acla, 1951, 34, 1601.K. Wiesner,-Z. Valenta, A. J . Manson, and-F. W. Stonner, J . Amer.-Chenz. Soc.,1955, 77, 675.64 E. Spath and 0. Hromatka, Bar., 1929. 62, 325.65 D. H. Hey and A. L. Palluel, Chem. and Ind., 1955, 40.6 6 B. R. Baker and F. J. McEvoy, J . Org. Chem., 1955, 20, 136PINDER : ALKALOIDS. 251lycorinone yields a 4-acylisocarbostyril derivative, the formation of whichcan be explained satisfactorily if lycorine is a disecondary glyco1.57The structure of tazettine methine has been proved to be (42) by syn-thesis.58 Reduction of tazettine with lithium aluminium hydride yieldssecot azet t ine, which on dehydration gives anhydrosecot azet t ine.Hofmanndegradation (two stages) of the latter affords a nitrogen-free product whichdoes not show an infrared carbonyl band but forms a 2 : 4-dinitrophenyl-hydrazone. On oxidation, first the lactone (43) and then the diphenic acid(44) are obtained, both structures being proved by synthesis. The pseudo-carbonyl Hofmann product therefore has structure (45), anhydroseco-0CHa- 0 IMe0l I p O "CH,*OH0CH2-0 IMe00 CHa-0 I F i& ...- a4" .....CH2-0(49)0 0 @OM*W eHO H4ii$:tazettine (46), secotazettine (47), and tazettine (48).59 The same structurehas been proposed for tazettine on different grounds 6o and is preferred to theearlier structure (49) proposed on the basis of extensive degradations.61Infrared measurements suggest that homolycorine, C,8H,10,N, an5 7 S.Takagi, W. I. Taylor, S. Uyeo, and H. Yajima, J., 1955, 4003 ; cf. Ann. Reports,58 W. I. Taylor, S. Uyeo, and H. Yajima, J., 1955, 2962.58 T. Ikeda, W. I. Taylor, and S. Uyeo, Chem. and Ind., 1955, 1088.6o R. J. Highet and W. C. Wildman, ibid.. p. 1159.61 E. Wenkert, Experientia, 1954, 10, 476.1954, 51, 261252 ORGANIC CHEMISTRY.alkaloid of Lycaris radiata Herb., is a 8-lactone 62 and not a y-la~tone.~~Lycorenine, C,,HaO,N, from the same source, gives homolycorine on mildoxidation; it is a cyclic semiacetal. Structures (50) and (51) have beenproposed for homolycorine and lycorenine respectively,62 and have beenconfirmed by Wolff-Kishner reduction of lycorenine to the dihydrodeoxy-compound (52).This on dehydrogenation affords the arylindole (53), whichhas been synthesised from the Emde base of lycorine.64OMc(52)The product formed by reaction of lycorine anhydromethine with methyliodide & the phenanthridinium salt -(54); previous workers may haveobtained anhydrolycorine methiodide, which has the same m. p. as this salt,since anhydrolycorine is known to accompany lycorine anhydromethine inthe Hofmann degradation of l y ~ o r i n e .~ ~Pyrrolizidine Group.-A review of these alkaloids has appeared. 66 Thestructure (55; R = OH) for rosmarinecine 67 has been confirmed by con-version of this alkaloid into compounds of known constitution. On de-hydration it gives anhydrorosmarinecine (56; R = OH), which with thionylchloride yields anhydrochloroplatynecine (56 ; R = Cl), reduced to anhydro-platynecine (56; R = H), identical with the product obtained by dehydrat-ing platynecine (55; R = H). Further confirmation is provided by thesynthesis of rosmarinecine from retronecine (57), which with perbenzoic acidHYL I Jo 5H2*OH HqL H iJ 5H2*0H CHMcli HO,C C CH, CM :,CMc. COfi (60) 0OHI CHMc0 (58) (59) H0,C.C- II CH,*CHMc-CMe*COfi (61)yields epoxyisatinecine (58).Reduction then affords epoxyretronecine(59) , further reduced to rosmarinecine (55 ; R = OH). The various trans-formations indicate the similarity in stereoconfiguration of the hydroxyl62 T. Kitagawa, W. I. Taylor, S. Uyeo, and H. Yajima, J., 1955, 1066.63 H.-G. Boit, L. Paul, and W. Stender, Chem. Ber., 1955, 88, 133.64 S. Uyeo and H. Yajima, J., 1955, 3392; Ann. Reports, 1954, 51, 261.6 5 T. Shingu, S. Uyeo, and H. Yajima, J., 1955, 3557.66 F. L. Warren, Fortschr. Chem. org. Naturstoffe, 1955, 12, 198.67 M. F. Richardson and F. L. Warren, J., 1943, 452PINDER : ALKALOIDS. 253groups in rosmarinecine and platynecine, where the 7-hydroxyl group is cisto the 1-hydroxymethyl group, and both are trans to the 7a-hydrogenatom .68The alkaloid rosmarinine on dehydration gives anhydrorosmarinine,hydrolysed to rosmarinecine (55 ; R = OH) and, probably, anhydrosenecicacid (60).The toluene-fi-sulphonic ester of the same alkaloid yields onhydrolysis senecic acid (61) and eihirosmarinecine (55; R = OH, and inver-sion at C,,)) ; the same ester with pyridine affords senecionine, with elimin-ation of toluene-p-sulphonic acid. Senecionine is therefore (62), andMe*CH OH Me*CH OH$.@:Ha*CHMe?Me I 70 C It * C H 2 * C H M e e II@JCH~-~ I L+J.-;H2-0 toR(62 ) (63)rosmarinine and platyphylline have structures (63; R = OH and H respec-tively) .69 Integerrimine, known to be the tram-form of ~enecionine,~~ there-fore has structure (62; Me.5I-I replaced by H$;Me).69Hieracifoline 71and pterophine 72 have been shown by paper chromatography each to bemixtures of senecionine and seneciphylline.73Diterpeize Grou$.-Interest in alkaloids related to the tricyclic diterpenesis increasing.74 On the basis of oxidation and dehydrogenation, structures(64) and (65) have been proposed for veatchine and ganyine re~pectively.~~Selenium dehydrogenation of both alkaloids gives the benzoisoquinoline (66),identified by ~ y n t h e s i s . ~ ~ ~ 76 Cuauchichicine, a new member of the group,The Senecio alkaloids also occur as their N-0xides.6~(64) ( 6 5 ) (66)found in Garrya Zaurifolia Hartw., is isomeric with veatchine, but containsno CXH, group and is ketonic. On degradation it yields products identicalwith, or similar to, those obtained from veatchine under the same conditions,and its pK value is comparable with that of veatchine, rather than of68 L.J. Dry, M. J. Koekemoer, and F. L. Warren, J., 1955, 59.M. J. Koekemoer and F. L. Warren, ibid., p. 63.7O M. Kropman and F. L. Warren, J., 1950, 700.7l R. H. F. Manske, Canad. J . Res., 1939, 17, B, 8.72 H. L. de M’aal, Nature, 1940, 146, 777.73 C. C. J. Culvenor and L. W. Smith, Chem. and Ind., 1954, 1386; R. Adams andM. Gianturco, J . Amer. Chenz. SOL, 1956, 78, 398.74 For a review, see E. S. Stem, in “ The Alkaloids,” Manske and Holmes, AcademicPress, New York, 1954, Vol. 4, p. 275.75 K. Wiesner, R. Armstrong, M. F. Bartlett, and J. A. Edwards, J . Amer. Chem.SOC., 1954, 76, 6068.7 6 M. F. Bartlett and K. Wiesner, Chem.and Ind., 1954, 542254 ORGANIC CHEMISTRY.garryine, which suggests that the oxazolidine ring is fused to CU7) rather thanto C(ls,. Structure (67) explains these and other observations most satis-factorily.77, ' 8 Laurifoline,* an isomeric alkaloid from the same source, isreadily isomerised by acids to cuauchichicine and by hot ethanol to iso-laurifoline ; it is 19-epiveatchine (64 ; with inversion at C(lg)).7* Theinfrared absorption spectra of atisine and isoatisine hydrochlorides show aband characteristic of the >C:N( group, and in the ultraviolet region thesalts show more intense absorption above 220 mp than the bases. This can+c I'be explained if the salts are quaternary chlorides of structures (68) and (69)respectively. 79 Some observations have been made on the stereochemistryof diterpenoid alkaloids, in relation to basic strength.80Morphine Groz@.-Stnictures (70) and (71) for a- and p-codeimethineshave been confirmed by considerations of their mode of formation, reactions,and spectra. 81 The four isomeric thebainone methines have been prepared,and structures assigned to them on spectral and other evidence.82 77HOMcOHONMc(70) (71) ( 7 2 )X-Ray crystallographic determinations support the view that ( -)-morphine has the stereochemistry (72) or its mirror image,83 and a con-77 C.Djerassi, C. R. Smith, S. K. Figdor, J. Herran, and J. Romo, J. Amer. Chem.SOC., 1954, 76, 5889.'8 C. Djerassi, C. R. Smith, A. E. Lippman, S. K. Figdor, and J. Herran, ibid., 1955,77, 4801.78s Idem, ibid., p.6633.7@ S. W. Pelletier and W. A. Jacobs, Chem. and Ind., 1955, 1385.80 K. Wiesner and J. A. Edwards, Experiential 1955, 11, 255.81 I<. W. Bentley and A. F. Thomas, J., 1955, 3237.82 K. W. Bentley and H. M. E. Cardwell, ibid., p. 3245.83 M. Mackay and D. C. Hodgkin, ibid., p. 3261. * Laurifoline has been re-named garryf~line.~~ASPINALL AND SCHWARZ : CARBOHYDRATES. 255sideration of molecular-rotation differences establishes that the latter formularepresents the absolute stereochemical structure of the natural alkal~id.~Similar conclusions have been reached from a study of the degradation ofthebaine 84 and of N-nora$o~odeine.~~A. R. P.10. CARBOHYDRATES.Three years have elapsed since the last Report on po1ysaccharides.lThe greater part of the Section is therefore devoted to this subject, anddiscussion of other aspects of carbohydrate chemistry has been confined toa few selected topics.A recent book 2 provides authoritative surveys of methods for the isola-tion, identification, and estimation of plant carbohydrates.Attention isalso drawn to the new edition of E. Ott’s “ Cellulose and CelluloseDerivatives.’’Monosaccharides and oligosaccharides.General Methods.-The high efficiency of a mixture of methyl iodideand silver oxide in dimethylformamide as a methylating agent has beendemonstrated with ~ucrose,~ ~-galactal,~ and a-solanine,6 where a singletreatment gave products which no longer showed the characteristic infraredabsorption of the hydroxyl group.draws attention to the value of thealkali-labile 2 : 4-dinitrophenyl residue for protecting the amino-group inglucosamine reactions.Formation of an acid-labile orthoformate has beenused to protect the reducing group of a digalacturonic acid before reductionwith lithium aluminium hydride.8 Disaccharides can be smoothly reducedwith sodium borohydride; an earlier observation that this reduction isaccompanied by fission of the glycosidic link has not been confirmed.Degradation of 3-O-methyl-aldoses with periodate provides a useful routeto 2-methyl ethers of lower sugars.Io Periodate oxidation also forms thebasis of a useful micromethod for the determination of the ring structuresof sugar residues.ll Reactions of monosubstituted aldoses (e.g., mono-methyl ethers and disaccharides) with lead tetra-acetate in the presence ofpotassium acetate follow definite oxidation patterns depending on theposition of substitution ; this enables structural determinations to beA preliminary communication84 J.Kalvoda, P. Buchschacher, and 0. Jeger, Helv. Chim. Ada, 1955, 38, 1847.85 H. Corrodi and E. Hardegger, ibid., p. 2038.E. J. Bourne, Ann. Reports, 1952, 49, 235.‘ I Modern Methods of Plant Analysis,” Ed. K. Paech and M. V. Tracey, Springer3 “ Cellulose and Cellulose Derivatives,” Ed. E. Ott and H. M. Spurlin, Interscience4 R. Kuhn, H. Trischmann, and I. Low, Angew. Chem., 1955, 67, 32.6 R. Kuhn, I. Low, and H. Trischmann, zbzd., p. 1492.* J. K. N. Jones and W. W. Reid, J., 1955, 1890.Verlag, Berlin, 1955, Vol.11.Publ., New York, 1954 and 1955.R. Kuhn and H. H. Baer, Ckem. Ber., 1955, 88, 1537.P. F. Lloyd and M. Stacey, Chem. and Ind., 1955, 917.W. J. Whelan and K. Morgan, Chew and Ind., 1955, 1449.lo G. W. Huffman, B. A. Lewis, F. Smith, and D. R. Spriestersbach, J . Amer. Chem.11 M. Viscontini, D. Hoch, and P. Karrer, Helv. Chim. A d a , 1955, 38, 642 ; see alsoSOC., 1955, 77, 4346.F. Smith and J. W. van Cleve, J . Anaer. Chem. SOC., 1955, 77, 3091256 ORGANIC CHEMISTRY.carried out on a few milligrams of material.12 As in periodate oxidation,the aldoses appear to be oxidised as cyclic hemiacetals yielding formates.The preparative value of oxidation with lead tetra-acetate is illustrated bythe production of formates of D-erythrose and L-glyceraldehyde fromD-glucose and L-arabinose , respectively.13Paper chromatography of carbohydrates has been re~iewed.1~ Chromato-graphy on paper impregnated with boric acid facilitated the separation ofcertain methyl ethers and polyols,15 and the value of borate complexes inthe preparative separation of glycosides and sugars has been emphasized.16The ionophoretic behaviour of many glucose derivatives in alkaline boratebuffer has been related to their structure.1'The classical method of separating 4-substituted monosaccharides frommixtures, by conversion of the other components into methyl furanosideswith methanolic hydrogen chloride at room temperature, has been appliedsuccessfully to oligosaccharides.18 It is noteworthy that 2 : 3 : 6-tri-O-methyl-D-mannose does not form a furanoside under the usual mild con-ditions; this can be used to separate it from 2 : 3 : 6-tri-O-methyl-~-glucose.The molecular weights of osazones of mono- and oligo-saccharides canconveniently be determined by a spectrophotometric method.20s 21Sugars from Antibiotics.-The amino-sugars , mycaminose (1 ;R = R = OH ; from magnamycin) 22 and rhodosamine (probably 1 ;R = H, R' = OH ; from rhodomycin) ,23 are closely related to desosamine(1 ; R = OH, R = H ; from erythromycin), which was discussed in lastyear's Report.% The stereochemistry of these compounds remains to be rxpH p:lHCH.OH el:' f CH I672Lf H d GC H.N Me,CHJH, 4%(2 1 (3) 0 1elucidated.Determination of the structure of cladinose (2) ,25 anotherhydrolysis product of erythromycin, shows that it is related to mycarose(3) ,26 the branched-chain sugar from magnamycin.The resemblance be-12 A. S. Perlin, Anulyt. Chem., 1955, 27, 396.13 A. S. Perlin and C. Brice, Canad. J . Chem., 1955, 38, 1216.14 G. N. Kowkabany, Adv. Carbohydrate Chem., 1954, 9, 303; F. A. Isherwood,1 5 G. R. Barker and D. C. C. Smith, Chem. and Ind., 1954, 19.16 M. V. Lock and G. N. Richards, J., 1955, 3024.1 7 A. B. Foster and M. Stacey, J., 1955, 1778.18 S. A. Barker, E. J. Bourne, and D. M. O'Mant, Chem. and Ind., 1955, 425.1s P. A. Rebers and F. Smith, J . Amer. Chem. SOC., 1954, 76, 6097.20 V. C. Barry, J. E. McCormick, and P. W. D. Mitchell, J., 1955, 222.21 R. Kuhn, A. Gauhe, and H.H. Baer, Chem. Be?., 1954, 8'7, 289.z2 F. A. Hochstein and P. P. Regna, J . Amer. Chem SOC., 1955, 77, 3353.23 H. Brockmann and E. Spohler, Nuturm*ss., 1955, 42, 154.24 J. C. P. Schwarz, Ann. Reports, 1954, 51, 262.z5 P. F. Wiley and 0. Weaver, J . Amer. Chem. SOL, 1955, 77, 3422.26 P. P. Regna, F. A. Hochstein, R. L. Wagner, jun., and R. B. Woodward, ibid.,Brit. Med. Bull., 1954, 10, No. 3, 202; D. J. Bell, ref. 2, p. 1.1953, 75, 4625ASPINALL AND SCHWARZ : CARBOHYDRATES. 267tween the amino-sugars and branched-chain sugars derived from magnamycinand erythromycin is of interest in view of their similar ‘ I microbiologicalspectra.”Phenylhydrazine Derivatives.-The formation of a formazan whensolutions of phenylhydrazine derivatives are coupled in pyridine withdiazotised aniline has been used as a diagnostic test for the groupCH:N*NHAr.27 This reaction indicates that two of the three knownmodifications of glucose phenylhydrazone have cyclic structures, while thethird is acyclic.27 The behaviour of glucose phenylosazone , which couplesin alkaline ethanol (but not in pyridine) to give a violet fonnazan, has beeninterpreted in terms of an open-chain structure in which the two phenyl-hydrazine residues are linked by a hydrogen bond.28 However, it seemsnecessary to reconcile this structure with the observation 29 that glucosephenylosazones mutarotate in dry pyridine.The close resemblance betweenthe ultraviolet absorption spectra of the sugar osazones and of glycerosazoneprovides further evidence for the open-chain structure, although it is rathersurprising that these spectra differ markedly from that of methylglyoxalbisphenylhydrazone.2* N-Alkylphenylosazones may differ in structure fromthe unalkylated compounds; in the former the hydrazine residue at C,,)is more reactive,30 while in the latter the hydrazine residue at Co) generallyshows the greater reactivity.29 The mechanism of osazone formation hasbeen discussed.31 Hydrazine exchange can be involved when two differenthydrazines are present.Inositols.-Seven of the nine possible stereoisomers of inositol werealready known ; the remaining two, rteoinositol (123/456) and cis-inositol(123456/), have now been synthesised. fieoInosito1 was prepared from(-)-inositol by inversion of the configuration of two adjacent carbon atomsvia an epoxide intermediate.32 cis-Inositol, which has been separated fromthe mixture obtained on hydrogenation of hexahydroxybenzene,= is ofconsiderable interest, as the chair conformation must involve three axialhydroxyl groups situated on the same side of the ring.A new C-methyl-inositol has been encountered in algae,% and three new 0-methylmyoinositolshave been isolated from natural sources; 35 the detailed structures of thesecompounds remain to be elucidated. The synthesis of DL-bornesitol bymethylation of 1 : 3 : 4 : 5 : 6-penta-0-acetylmyoinositol involves migrationof an acetyl residue from an equatorial to an axial hydroxyl Anumber of quercitols (cyclohexanepentols) , conduritols (cyclohexenetetrols) ,and cyclohexanetetrols have been synthesised from myo- and epi-inositol ; 3727 L.Mester and A. Major, J . Amer. Chem. SOC., 1955, 77, 4297.20 F. Weygand, H. Grisebach, K.-D. Kirchner, and M. Haselhorst, Chem. Bey., 1985,80 G. Henseke and H.-J. Binte, ibid., p. 1167.81 G. Henseke and H. Dalibor, ibid., p. 521; G. Henseke and M. Bautze, ibid.,p. 62; V. C. Barry and P. W. D. Mitchell, Nature, 1956, 175, 220.82 S. J. Angyal and N. K. Matheson, J . Amer. Chem. SOC., 1955, 77, 4343.aa S. J. Angyal and D. J. McHugh, Chem. and Ind., 1955, 947.s4 B. Lindberg and J. McPherson, Acta Chem. Scund., 1954, 8, 1875; B. Lindberg,s6 V. Plouvier, Compt. rend., 1955, 241, 765, 983.* I L. Anderson and A. M. Landel, J . Amer. Chem.SOC., 1954, 76, 6130.a7 G. E. McCasland and E. C . Horswill, ibid., p. 2373; G. E. McCasland and J. M.L. Mester, ibid., p. 4301.88,487.;bid.. 1955, 9, 1097; H. Bouveng and B. Lindberg, ibid., p. 168.Reeves, ibid., 1955, 77, 1812.REP.-VOL. LII 258 ORGANIC CHEMISTRY.one of the tetrols was also obtained from cyclohexa-1 : 4-diene by the actionof Pr6vost's reagent (silver benzoate and iodine) .380ligosaccharides.-Investigation of the terpenoid glycoside, stevioside,which is about 300 times as sweet as sucrose, has shown that two of thethree glucose units are present as a 1 : 2-linked disa~charide.~~ The remain-ing glucose unit is independently attached to a hindered carboxyl group ofthe aglycone by esterification at Co), and this glucose residue is eliminatedas 1 : 6-anhydro-~-glucose by the action of potassium hydroxide.2 : 3 : 4 : 6-Tetra-0-acetyl-1-0-(2 : 4 : 6-trimethylbenzoyl)-~-~-glucose also gives 1 : 6-anhydro-D-glucose on treatment with alkali.40 These unusual reactionspresumably involve " alkyl "-oxygen fission.A branched trisaccharide, O-or-~-rhamnopyranosyl-( 1-+2)-0-[$~-glucopyranosyl-( 1+3)]-~-galactose, has been obtained from the alkaloida-solanine.6 The related alkaloid, a-chaconine, contains a branched tri-saccharide in which two L-rhamnopyranosyl units are linked to the 2- and4hydroxyl groups of ~-glucose.~l Human milk continues to yield interest-ing oligosaccharides , one of which is 2'-O-a-~-fucopyranosyl-lactose.~~The observation 43 that disaccharide osazones are hydrolysed to mono-saccharide osazones under conditions which leave disaccharides unchanged ,suggests a method for the stepwise degradation of oligosaccharides.Oligosaccharides encountered during work on polysaccharides are dis-cussed in the latter part of this Report.Miscellaneous.-The reaction of 2-0-sulphonyl derivatives of arabinose,xylose, and fucose with alkali proceeds with inversion at C(,) giving ribose,lyxose , and talomethylose, respectively.u* 45 This inversion provides ao-arabinal and2- de ox y- D- r iborepromising route to some otherwise inaccessible sugar derivatives.3-0-Methanesulphonyl-D-glucose (4) reacts with alkali to give 2-deoxy-~-riboseand D-arabinal, C(l) being eliminated as formate ; 45 this interesting reactionhas a formal analogy in the alkaline cleavage of 3-tosyl esters of steroids* G.E. McCasland and E. C. Horswill, J. Amer. Chem. SOL, 1954, 76, 1654.39 H. B. Wood, jun., R. Allerton, H. W. Diehl, and H. G. Fletcher, jun., J. Ovg.Chem., 1955, 20, 875.40 H. B. Wood, jun., and H. G. Fletcher, jun., J. Amer. Chew. SOC., 1956, 78, 708;Eee also F. Micheel and G. Baum, Chem. B e y . , 1955, 88, 2020.4 1 R. Kuhn, I. Low, and H. Trischmann, Chem. Bey., 1955, 88, 1690.42 R. Kuhn, H. H. Baer, and A. Gauhe, ibid., p. 1135.43 P. A. Finan and P. S. O'Colla, Chem. and Ind., 1955, 1387.44 J. K. N. Jones and W. H. Nicholson, J., 1955, 3050.4 5 D. C. C. Smith, Chem. and Ind., 1955, 92ASPINALL AND SCHWARZ : CARBOHYDRATES. 2593 : 5-diols. 2-Deoxy-DL-ribose has been synthesised from but-2-yne-l : 4-dio1,46 and the branched-chain sugars (-j-)-cordycepose (5 ; R = R' = H)and (-J-)-apiose (5; R = H, R' = OH) have been built up from bromoacetaland ethyl ~odiomalonate.~7 Self-condensation of dihydroxyacetone givesdendroketose (5; R = CH,*OH, R' = OH), which can be degraded to apionicacid (5; R = R = OH).48 4 : 4-Di-C-hydroxymethyl-~-threose, an aldoserelated to dendroketose, and 2-C-hydroxymethyl-D-xylose have been pre-pared from D-fructose by use of the cyanohydrin synthesis.49Recent additional evidence shows the importance of neighbouring-groupparticipation in the reactions of acetohalogeno-sugars and aldose acetates,although the relative reactivities of the a- and p-anomers cannot be entirelyascribed to this effect.This work and other studies on reaction mechanismsin carbohydrate chemistry are discussed in the section on TheoreticalChemistry.Reactions involving neighbouring-group participation have led to severalinteresting new orthobenzoic acid derivatives. Hydrolysis of tri-O-benzoyl-P-D-ribofuranosyl bromide gave 2 : 3 : 5-tri-O-benzoyl-p-~-ribose and thecrystalline orthoacid (6; R = H), which rapidly rearranged to 2 : 3 : 5-tri-0-benzoyl-p-mribose in the presence of a trace of base.50 The orthoacid ""q$ "10 Q\/Y H 0 HOHO 0- '-C).CH,Ph= ($9 I5, 8 2 <--ORLh(6) (7) Ph(6; R = H) can also be prepared by hydrogenolysis of the orthoester (6;R = benzyl), which is obtained when the above ribofuranosyl halide reactswith benzyl alcohol in the presence of quinoline.Reaction of tri-O-benzoyl-P-D-ribopyranosyl bromide with benzyl alcohol in the presence of quinoline,followed by debenzoylation, yields the labile orthoester (7) ,51 and underweakly acidic conditions this readily gives the crystalline 1 : 2 : 4-O-ortho-benzoyl-a-D-ribopyranose (8) ; 2 : 3 : 6-O-orthobenzoyl-~-fructofuranose hasbeen obtained in a similar way.52Poly saccharides.The period reviewed has seen the extended application of chromato-graphic methods in the determination of the detailed structure of poly-saccharides ; as a result many new polysaccharides have been investigated,and previously unknown structural features have been revealed in substanceswhose general structures were already known.Progress has been limitedin some investigations by difficulties in isolating individual molecular species46 M. M. Fraser and R. A. Raphael, J., 1955, 4280.47 R. A. Raphael and C. M. Roxburgh, ,/., 1955, 3405.4 8 L. M. Utkin, Doklady Akad. Nauk S.S.S.R., 1949, 67, 301.49 R. J. Woods and A. C. Neish, Canad. J. Chem., 1954, 32, 404.61 H. G. Fletcher, jun., and R. K. Ness, ibid., 1955, 77, 5337.62 B. Helferich and L. Bottenbruch, Chenz. Ber., 1953, 86, 651 ; B. Helferich andR. K. Ness and H. G. Fletcher, jun., J. Amer. Chem. Soc., 1954, 76, 1663.W. Schulte-Hurmann, ibid., 1954, 87, 977260 ORGANIC CHEMISTRY.from the complex mixtures present in natural sources. The greatest singleneed in this field, therefore, is for new and powerful methods for fractionationof polysaccharides, both for separation of structurally distinct molecularspecies and for resolution of closely-related substances of the same generaltype.A chromatographic method for the separation of acid mucopoly-saccharides has been described, which makes use of a " carrier " amine toincrease the solubility of such polysaccharides in the mobile organic phase ; 53not only was the separation of chondroitin-sulphuric acid and hyaluronicacid effected by this technique, but the resolution of hyaluronic acid fractionsof different molecular weight was achieved without apparent degradation.Fractional precipitation with ammonium sulphate has proved of value in theseparation of glucosans and araboxylans present in the water-soluble gumand hemicellulose fractions of cereal 55 An electrophoretic methodfor the analysis of neutral polysaccharides in borate buffer has been re-ported ; 56 separations were effected between amylose and amylopectin,and between yeast mannan and yeast glycogen. Electrophoretic separationof polysaccharides in alkali appears to be limited to the gross separation ofcharged from neutral molecules, e.g., sodium alginate and laminarin.57Paper-ionophoretic separations in the presence of borate buffer have beenachieved between amylose and amylopectin, although the ionophoresis ofamylose was complicated by absorption on the paper.58 Some mucopoly-saccharides can be resolved by paper electrophore~is,~~ whilst paper iono-phoresis in borate buffer has been employed in the separation of someneutral polysaccharides from cereals.60The value of serological cross-reactions, carried out on milligram quanti-ties, in the clarification of structural chemical relationships has been demon-strated in their application to the structure of lung galactan.61 The immuno-logical specificities of galactose-containing polysaccharides of known generalstructure have been determined.'j2 The nitrogen and sulphur contents ofthe polymers obtained by the condensation of periodate-oxidised poly-saccharides with isonicotinhydrazide and thiosemicarbazide give a measureof the proportion of sugar units attacked by p e r i ~ d a t e .~ ~ This methodprovides a useful check on direct measurements of periodate consumptionby polysaccharides, and in addition enables a polysaccharide containing both1 : 3- and 1 : 4-linkages to be distinguished from a mixture of polysaccharides,each containing only one type of linkage. The optical rotations of tri-carbanilates of polyglucosans in pyridine and morpholine have been shownto be dependent on the position and anomeric type of 1inkage.aCellulose and Hemicelluioses.-The use of paper-chromatographic6s G.S. Berenson, S. Roseman, and A. Dorfman, Biochim. Biophys. Acta, 1955,17,75.64 I. A. Preece and K. G. Mackenzie, J . Inst. Brewing, 1952, 58, 353, 457.55 I. A. Preece and R. Hobkirk, ibid., 1963, 59, 386; 1954, 60, 490.6 6 D. H. Northcote, Biochem. J., 1954, 58, 353.5 7 J. R. Colvin, W. H. Cook, and G. A. Adams, Canad. J .Chem., 1952, 30, 603.ti8 A. B. Foster, P. A. Newton-Hearn, and M. Stacey, J., 1956, 30.60 K. G. Rienits, Biochem. J., 1953, 53, 79.80 I. A. Preece and R. Hobkirk, Chem. and Ind., 1955, 257.62 M. Heidelberger, ibid., p. 4308.83 V. C. Barry, J. E. McCormick, and P. W. D. Mitchell, J.. 1954, 3692.64 I. A. WoIff, P. R. Watson, and C. E. Rist, J . Amer. Chem. SOL, 1953, 75, 4897.M. Heidelberger, 2. Dische, W. B. Neely, and M. L. Wolfrom, J . Amer. Chem.SOL, 1955, 77, 3511ASPINALL AND SCHWARZ : CARBOHYDRATES. 261techniques together with methylation end-group assay has enabled oneterminal group in a thousand to be detected in celluloses, which have beenmethylated with rigorous exclusion of oxygen to exclude degradati~n.~~The values obtained for the chain lengths of methylated celluloses by end-group assay were in reasonable agreement with those obtained from physicalmeasurements; it is necessary, therefore, to abandon the loop structureproposed for cellulose by W.N. Haworth.66 Kinetic studies of the acidhydrolysis of cellulose 67 have failed to provide evidence for the presenceof periodic abnormally-sensitive linkages of the type previously proposed. 68In the case of cotton cellulose, such acid-sensitive linkages may be presentin celluloses regenerated from cuprammonium and cupriethylenediaminesolutions.The close association of cellulose and other cell-wall polysaccharidescontinues to be emphasised, but there is still no conclusive evidence for thepresence or absence of formal linkages between these substances.Forexample, sugars other than glucose have been detected in the hydrolysatesfrom jute 69 and wheat-straw 70 a-celluloses. Careful fractionation of white-spruce a-cellulose nitrates 71 has yielded fractions of high and of low molecularweight which contain both glucose and mannose residues. The close associ-ation of glucose and mannose residues in coniferous woods has also beenindicated by the isolation of a disaccharide, composed of glucose andmannose units , from the acetolysis of slash-pine a-cellulose ; 72 hemicellulosescomposed of glucose and mannose residues occur in such woods, and theseresults may arise from the incomplete removal of these components.The cell-wall polysaccharides associated with cellulose are generallyreferred to as hemicelluloses , although this definition lacks precision inrespect of both chemical structure and biological function. In the followingaccount , these polysaccharides are classified according to their basic struc-tural features and are thus differentiated from those polysaccharides whosechemical structures and biological functions are more clearly defined, e.g.,the gums exuded from certain plants and reserve polysaccharides such asstarch and fructosans.The hemicellulose group of polysaccharides has beenreviewed in E. L. Hirst’s Pedler Lecture.73Xy1an.s.-A large number of polysaccharides of this group have receivedattention during the last three years. All the xylans from land plants, sofar examined, contain backbones of p-1 : 4-linked D-xylopyranose residues,but they differ in the number and nature of the other sugar residues present ;even within a single botanical species, it is clear that several different, butclosely related , xylans may be present.The L-arabofuranose residues presentin many of these hemicelluloses are integral parts of the xylan molecules,usually occurring as terminal groups and probably linked directly to themain chains as single-unit side-chains; there is no evidence at present for6 6 D. I. McGilvray, J., 1953, 2577.6 8 W. N. Haworth, Chem. and Ind., 1939, 917.67 A. Sharples, J . Polymer Sci., 1954, 13, 393; 14, 95.68 E. V. Schulz, J . Polymer Sci., 1948, 3, 365; E. Pacsu, ibid., 1947, 2, 565.70 G. A. Adams and C . T. Bishop, ibid., p.28.7 1 T. E. Timell, Pulp and Pafier Mag. Canada, 1955, 56, 104.72 J. G. Leech, T.A.P.P.I., 1952, 35, 249.79 E. L. Hirst, J., 1955, 2974.D. B. Das, M. K. Mitra, and J. F. Wareham, Nature, 1953, 171, 613262 ORGANIC CHEMISTRY.the occurrence, in the hemicellulose group, of arabans similar to those foundin the pectic substances. Methylation studies have shown that wheat-straw,74, 75 ~ o r n - c o b , ~ ~ and wheat-leaf 77 xylans contain L-arabo-furanose residues linked to the main chain through C(,) of the D-xyloseresidue, whilst in the more highly branched araboxylans from wheat endo-sperm ,78 arabinose residues are also linked through C(2) of doubly-branchedxylose residues. Additional evidence that the arabinose residues of wheat-straw xylans are integral parts of the molecule has been obtained by theisolation from enzymic hydrolysis of a series of oligosaccharides containingboth xylose and arabinose ~ n i t s .7 ~ Wheat-leaf 77 and some wheat-straw 749 81 xylans also contain D-glucuronic acid units as a part of theirmolecular structure. In wheat-straw xylans, some of the main chains ofxylose residues are linearJ81 whilst others contain branch points.82Xylans containing D-glucuronic acid (mainly as the 4-methyl ether) , butno arabinose, residues are found in elm,m beech,M and birch 85 woods.Structural investigation of beechwood hemicellulose A has shown thatevery tenth D-xylopyranose residue carries a single 4-O-methyl-~-glucuronicacid residue attached as a side-chain through C(2).The isolation of xylobioseand of 2-0-(4-0-methy~-D-g~ucuronosy~)-D-xy~ose from the partial acidhydrolysis of black spruce and Scots pine shows that xylans of the samegeneral type are also present in coniferous woods.86 Methylation of flax-straw hemicellulose 87 has indicated a structural similarity to the woodrather than to the cereal-straw hemicelluloses, in that the backbone ofxylose residues carries single 4-O-methy~-~-g~ucuronic acid units linked asside-chains, again through Ct2) of the xylose residues ; 2 : 4-di-O-methyl-~-rhamnose was also isolated from the hydrolysis of the methylated poly-saccharide, but its structural significance is not yet clear. Xylans of stillgreater complexity occur in the hemicelluloses of corn cobs (hemicelluloseB) and wheat bran,gl where some L-arabinose residues are present innon-terminal positions. Several oligosaccharides have been isolated fromcorn-cob hemicellulose B on partial acid hydrolysis, and it is clear from theisolation of four aldobiouronic acids 88 that both D-glucuronic acid and 4-0-methyl-D-ghcuronic acid residues are linked to separate D-xylose residuesthrough C(,> and C(*). The isolation of 2-O-a-D-xylopyranosyl-L-arabinose74 G.A. Adams, Canad. J . Chem., 1952, 30, 698; A. Roudier, Compt. rend., 1953,75 I. Ehrenthal, R. Montgomery, and F. Smith, J . Amer. Chem. SOC., 1954, 76, 3509.7g G. 0. Aspinall, E. L. Hirst, R. W. Moody, and E. G. V. Percival, J., 1953, 1631.7 7 G. A. Adams, Canad. J . Chem., 1954, 32, 186.R.Montgomery and F. Smith, J , Amer. Chem. SOC., 1955, 77, 2834, 3325.70 C. T. Bishop and D. R. Whitaker, Chem. and Ind., 1955, 119.C. T. Bishop, Canad. J . Chem., 1953, 31, 134.G. 0. Aspinall and R. S. Mahomed, J., 1954, 1731.82 C . T. Bishop, Canad. J . Chem., 1955, 33, 1073.83 I. Tachi and N. Yamamori, J . Agric. Chem. SOC. Japan, 1951-52,25, 12, 130,262.*4 G. 0. Aspinall, E. L. Hirst, and R. S. Mahomed, J., 1954, 1734.8 5 J. Saarnio, K. WathCn, and C. Gustafsson, Acta Chem. Scand., 1954, 8, 825.8 6 A. R. N. Gorrod and J. K. N. Jones, J., 1954, 2522.237, 840; Assoc. tech. ind. papetidre Bull., 1954, 53.F. Smith and J. D. Geerdes, J . Amer. Chem. SOC., 1955, 77, 3572.R. L. Whistler and L. Hough, ibid., 1953, 75, 4918 ; R. L. Whistler, H.E. Conrad,R. L. Whistler and D. I. McGilvray, ibid., 1955, 77, 1884.G. A. Adams, Canad. J . Chem., 1955, 33, 56.and L. Hough, zbzd., 1954, 76, 1668.O0 Idem, ibid., p. 2212ASPINALL AND SCHWARZ CARBOHYDRATES. 263shows that non-terminal arabinose residues are present in the polysaccharide,but does not indicate whether they are present in the furanose or pyranoseform. It is clear from methylation studies that wheat-bran hemicelluloseis a highly branched polysaccharide containing D-xylose and L-arabinose,each in three or four states of combination, together with uronic acidresid~es.~lGalactans and Galact0arabans.-The galactan from Strychnos nux-vomicaseeds 92 has been shown by methylation and periodate oxidation studies to bean essentially linear p-1 : 4-galactan, similar to that previously isolated fromLupinus albus pectin.93 The arabogalactan from Jeffrey pine 94 contains amuch higher proportion of L-axabinose residues than the E-galactan fromlarch,g5* 96 and in the highly branched molecular structure the majority ofL-arabinose residues occur in the furanose form as terminal groups; there isno evidence that any of the arabinose residues are present in the pyranoseform, as in larch e-galactan.96 The backbone of the pine galactan is probablycomposed of 1 : 6-linked D-galactopyranose units, some of which are branchedthrough C(3).The galactoaraban from Japanese larchJg7 like those fromEuropean 95 and Western 98 larches, contains galactose and arabinose residuesin the ratio of 6 : 1 ; fractionation of the methylated polysaccharide failedto yield components having different physical and chemical properties. Asa result of the application of Barry’s degradation 99 t o the galactogen of thesnail Helix pomatia, a dichotomously branched structure has been advancedto replace the comb-like structure of a backbone of galactose residues withsingle unit branches previously put forward for this polysaccharide on thebasis of methylation results.100 It is now clear from the results of cross-precipitin reactions that the uronic acid-containing moieties associatedwith beef-lung galactan 101 arise from a contaminating polysaccharide.Mannans, Glucomannans, and Galactomannans.-Methylation has shownthat the mannose-containing polysaccharides of Iris ochroleuca and I .sibiricaare composed of equal proportions of 1 : 4-linked D-mannose and D-glucoseresidues together with a small number of D-galactopyranose residues linkedsolely as non-reducing end-groups.1o2 A re-investigation, by chromato-graphic methods, of the sugars obtained on hydrolysis of the methylatedivory-nut mannans A and B indicates that both polysaccharides containmixtures of molecular species, terminated by D-mannopyranose and D-galactopyranose residues, respectively ; lo3 both species are linear, but inaddition to the 1 : 4-linked D-mannose units, some mannose units are presentin one or both types of molecule linked through C(I) and Cts). It is clear fromO2 P. Andrews, L. Hough, and J. K. N. Jones, J., 1954, 806.B3 E.L. Hirst, J. K. N. Jones, and W. 0. Walder, J., 1947, 1225.94 W. H. Wadman, A. B. Anderson, and W. 2. Hassid, J. Amer. Chem. SOC., 1954,96 W. G. Campbell, E. L. Hirst, and J . K. N. Jones, J., 1948, 774.96 J. K. N. Jones, J.. 1953, 1692.O * E. V. White, J. Amer. Chem. SOC., 1941, 63, 2871; 1942, 64, 302, 1507, 2838.loo E. Baldwin and D. J . Bell, J., 1938,1461 ; D. J . Bell and E. Baldwin, J., 1941, 125.lol M. L. Wolfrom, G. Sutherland, and M. Schlamowitz, J. Amer. Chem. Soc., 1952,lo2 P. Andrews, L. Hough, and J . K. N. Jones, J . , 1953, 1186.loS G . 0. Aspinall, E. L. Hirst, E. G. V. Percival, and I. R. Williamson, J., 1953,78, 4097.I. Tachi and N. Yamamori, J. Agric. Chem. SOC., Japan, 1953, 27, 139.P. O’Colla, Proc. Roy. Irish Acad., 1953, 55, B, 165.74, 4883.3184264 ORGANIC CHEMISTRY.structural investigations that the polysaccharide associated with yeastinvertaselM is identical with the mannan, yeast gum, obtained by theautolysis of yeast.lo5 Iles mannan,19 the polysaccharide extracted fromthe tubers of some ArnorPhoPhaElus species, is a mixture of two linear poly-saccharides, an a-1 : &linked polyglucosan resembling amylose and a p-1 : 4-linked glucomannan containing two mannose to every glucose residue.Thegalactomannan from Kentucky coffee bean lo6 has the same general structureas p a r and carob-bean galactomannans, containing a backbone of 1 : 4-linked D-mannopyranose residues with every fourth residue carrying ata D-galactopyranose residue as side-chain.G1ucosans.-Barley gum , the mixture of water-soluble polysaccharidesisolated from barley grain, has been fractionated by precipitation withammonium sulphate to give a lzvorotatory glucosan free from pent0san.aMethylation has shown that this polysaccharide contains unbranched chainsof p-D-glucopyranose residues with approximately equal proportions of1 : 3- and 1 : 4-linkages; lo7 the polysaccharide appears to be structurallyrelated to lichenin.An evidently similar polysaccharide, the so-called oat‘‘ lichenin ” has been shown by periodate oxidation and partial acetolysisto possess 1 : 3- and 1 : 4-linked D-glUCOSe units in the approximate ratio of1 : 2.108 The general character of pustulan, the polysaccharide obtainedfrom the lichen Umbilicaria pustulata, has been indicated by the isolationfrom partial acid hydrolysis of a series of g-1 : 6-linked oligosaccharides; Io9the absence of oligosaccharides containing other linkages suggests that thepolysaccharide is linear.Fructosans.-Chemical evidence now indicates that many fructosans ofboth the inulin and the levan type contain terminal glucose residues linked asin sucrose, thus supporting the view that these polysaccharides are built upin the plant from sucrose by transfructosylation.110- 111 The hydrolysis ofmethylated leafy cocksfoot levan 112 yields 1 : 3 : 4 : 6-tetra-O-methyl-~-fructose (4%), 2 : 3 : 4 : 6-tetra-O-methyl-~-glucose (1.8%), and 1 : 3 : 4-tri-o-methyl-D-fructose (93.3%) , showing the fructosan to be of levan type ;D-glucose residues occur only as non-reducing end-groups, and it is probablethat the majority of fructosan chains are terminated by sucrose-type linkages.The isolation of sucrose 113 from the partial hydrolysis of perennial rye-grasslevan 114 provides definite proof of the existence of this terminal group inthe polysaccharide.Perennial rye-grass also contains short-chain fructosansof chain length 5-10 having the same general structure.l15 OtherworkersY1l6 however, find no glucose residues in perennial rye-grass levanlo4 J. A. Cifonelli and F. Smith, J. Amer. Chem. Soc., 1955, 77, 6682.lo6 W. N. Haworth, E. L. Hirst, and F. A. Isherwood, J., 1937, 784; W. N. Haworth,lo6 E. B. Larson and F. Smith, J. Amer. Chem. Soc., 1955, 77, 429.10’ G.0. Aspinall and R. G. J. Telfer, J., 1954, 3519.108 L. Acker, W. Diemair, and E. Samhammer, 2. Lebansm.-Untersuck., 1955, 100,100 B. Lindberg and J. McPherson, Acta Chem. Scund., 1954, 6, 985.l 1 0 S. A. Barker and E. J. Bourne, Quart. Rev., 1953, 7, 56.111 J. S. D. Bacon, Ann. Reports, 1953, 50, 281.112 G. 0. Aspinall, E. L. Hirst, E. G. V. Percival, and R. G. J . Telfer, J., 1953, 337.*I3 G. 0. Aspinall and R. G. J. Telfer, J., 1955, 1106.R. A. Laidlaw and S. G. Reid, J., 1951, 1830.*16 V. D. Harwood, R. A. Laidlaw, and R. G. J . Telfer, J., 1954, 2364.116 H. H. Schlubach and K. Holzer, Annalen, 1953, 578, 207.R. L. Heath, and S. Peat, J., 1941, 833.180; 102, 225ASPINALL AND SCHWARZ : CARBOHYDRATES. 266and postulate a difructose anhydride type of termination.l17 Studies of thedegradation of fructosans in hot aqueous solution 113 emphasise the need forthe utmost caution in the isolation of these extremely labile polysaccharideslest scission of the fructosan chain results in loss of the glucose-containingmoiety. Methylation studies have shown that the fructosans from Ken-tucky blue,ll* red fescue,llQ and common fox-tail 120 grasses are of the levantype.Studies on the fructosans from the stems and ripening ears of thecommon cereals have been reviewed.121Starch and Glycogen.-The fractionation of starch under conditionswhich minimise the possibility of degradation, particularly of the amylose,continues to attract much attention. The linear component appears to beespecially susceptible to degradation, which may occur in at least two ways.It has been shown viscometrically that potato amylose is degraded inaqueous solution in the presence of oxygen; 122 this oxidative degradation,which is appreciable in neutral solution, occurs much more rapidly in alkali.Amylose is degraded by alkali in the absence of oxygen with the formationof a mixture of D-glucoisosaccharinic acids.123 The fall in viscosity wouldbe much less obvious if degradation proceeds solely by the “peeling”reaction 1% from the reducing end of the chain, than if random oxidationresults in the formation of alkali-sensitive bonds in the middle of the chain.A method for the anaerobic fractionation of starch, which depends on thepreferential solubility of amylose in water, has been r e ~ 0 r t e d .l ~ ~ As a resultof other investigations, it has been suggested that amylose and amylopectinoccur naturally in chemical combination, 126 possibly through a phosphatidecross-link, and that preferential precipitation of the amylose with a com-plexing agent can only occur when the acid-labile linkage has been severed.The claim 12’ that amylopectin can be purified by selective precipitation ofthe amylose with stearic acid has been refuted.128The oxidation of starches by potassium metaperiodate has been studiedin detail, and an accuracy of k0.5 glucose residue is claimed for unit-chainlength determinations.129 The repeating units of many starches have beendetermined by this method, and from parallel determinations of their amylosethe average unit-chain lengths of the amylopectin componentscalculated.A valve microvoltmeter, which increases the accuracy ofdifferential potentiometric titrations,131 has been described and its use instudying the interaction of starches and other branched a-1 : 4-glucosanswith iodine reported.130 This sensitive method not only enables the amylose11’ H. H. Schlubach and K. Holzer, Annulen, 1953, 578, 213.H. H. Schlubach and L. Gassmann, ibid., 1953, 583, 81.llQ H. H. Schlubach and K. Holzer, ibid., p. 88.120 H. H. Schlubach, K. Holzer, and L. Gassmann, ibid., 1954, 587, 107.121 H. H. Schlubach, Experientia, 1953, 9, 230.lZ2 R. T. Bottle, G. A. Gilbert, C. T. Greenwood, and K. N. Saad, Chem. and Ind.,123 J. Kenner and G.N. Richards, ibid., 1954, 1483.124 W. M. Corbett and J. Kenner, J., 1955, 1431.126 H. A. Baum and G. A. Gilbert, Chem. and I.nd., 1954, 490.126 A. W. Bauer and E. Pacsu, Textile Res. J., 1953, 23, 853, 860, 864, 870.12’ K. H. Meyer and G. C. Gibbons, Helv. Chim. Acta, 1950, 33, 210.128 G. A. Gilbert, C. T. Greenwood, and F. J. Hybart, J., 1954, 4454.12Q D. M. W. Anderson, C. T. Greenwood, and E. L. Hirst, J., 1955, 225.lSo D. M. W. Anderson and C. T. Greenwood, J., 1955, 3016.lal G. A. Gilbert and J. V. R. Marriott, Trans. Faraday SOC., 1948, 44, 84.1953, 541266 ORGANIC CHEMISTRY.contents of starches to be accurately determined but also detects significantdifferences in iodine binding power between amylopectins and glycogens.In a detailed chemical and physical ~ t u d y , l ~ ~ the starch from rubberseeds was found to contain 20% of amylose and an amylopectin of averageunit-chain length 23 If 1 glucose units, and in which the majority of branchpoints were through C(6).Starches of abnormally high amylose content andwith amylopectins of increased unit-chain length have been isolated fromwrinkled-seeded peas and from a variety of maize.l= Whilst the starchfrom smooth-seeded peas contained 35% of amylose (Le., more than normal)and an amylopectin of normal unit-chain length (25 units), that fromwrinkled-seeded peas contained 66% of amylose and an amylopectin of chainlength 36.133 The abnormal maize starch contained ca. 50% of amyloseand an amylopectin with a repeating unit of 36 glucose residues; thep-amylolysis limit of 58% for this amylopectin indicated an inner chain of13 units (cf.5-8 units for an average amyl~pectin),l~~ and showed that bothinner and outer chains were longer than usual. Structural studies of thestarch from malted barley have indicated that malting results in the partialdegradation of the outer chains of the amylopectin (26 + 18 units) withrelatively little degradation of the amylose. 136Evidence that the inter-chain linkages in glycogens are only of the1 : 6-type has been provided by the virtual absence of glucose in the hydro-lysates of several periodate-oxidised glycogens,l37 and in the case of baker’syeast glycogen by “ linkage analysis ” in which the oligosaccharides formedon partial acid hydrolysis were shown to contain only a-1 : 4- and a-1 : 6-linkages.Both chemical and enzymic methods have been used in theinvestigation of the structure of baker’s 1389 139 and brewer’s 140 yeast glyco-gens. Similar methods have been used in the examination of an abnormalglycogen, from a case of von Geirke’s disease, which had a unit-chain lengthof only 6 ~ n i t s . 1 ~ ~Algal Po1ysaccharides.-Recent work on the fine structure of laminarinhas necessitated a modification of the view that this polysaccharide is com-posed solely of P-1 : 3-linked D-glucopyranose residues. In addition to themajor product, laminaribiose, gentiobiose, l-0-p-~-glucosyl-~-mannitol,~~~and 1-0-laminaribiosyl-~mannitol143 have been isolated on partial acidhydrolysis of the polysaccharide.It is evident, however, that not alllaminarin molecules are terminated by mannitol residues as some of thepolysaccharide is degraded on treatment with lime water ; lz4 it is probablethat two closely-related molecular species are present. The mercaptolysisof algal polysaccharides has given evidence of 3 : 6-anhydrogalactose residues.13* C. T. Greenwood and J. S. M. Robertson, J., 1954, 3769.A. L. Potter, V. Silveira, R. M. McCready, and H. S. Owens, J . Amer. Ckem. Soc.,134 I. A. Wolff, B. T. Hofreiter, P. R. Watson, W. L. Deatherage, and M. M. Mac-lS6 D. J. Manners, Quart. Rev., 1955, 9, 73.lS6 G. 0. Aspinall, E. L. Hirst, and W. McArthur, J.. 1955, 3075.lS7 D. J. Bell and D. J. Manners, J., 1954, 1891.S. Peat, W.J. Whelan, and T. E. Edwards, J., 1955, 355.13@ D. H. Northcote, Biochem. J., 1953, 53, 348.ld0 D. J. Manners and Khin Maung, J., 1955, 867.u1 D. J. Manners, J., 1954, 3527.142 S. Peat, W. J. Whelan, and H. G . Lawley, Chem. and Ind., 1955, 35.Ira S. Peat, W. J. Whelan, H. G. Lawley, and J . M. Evans, Biochem. J . , 1965, 61, x.1953, 75, 1335.Masters, ibid., 1955, 77, 1654ASPINALL AND SCHWARZ CARBOHYDRATES. 267The mercaptolysis of agar thus yields the diethylmercaptals of D-galactose,DL-galactose, and 3 : 6-anhydro-~-galactose, and of 3 : 6-anhydro-4-0-fb~-galactopyranosyl-L-galactose (agarobiose) . 145 The isolation from agar in69.5% yield of agarobiose dimethylacetal and its methanolysis products 146indicates that the agarobiose residue is the dominant repeating unit of thispolysaccharide.On the other hand, the mercaptolysis of the polysaccharidefrom Chondrus crispus yields the diethylmercaptal of 3 : 6-anhydro-~-gala~tose.1~~ The heterogeneous character of this polysaccharide has beenindicated by a fractionation which gave K-carrageenin, precipitated bypotassium chloride, and A-carrageenin.148 K-Carrageenin contains D-galac-tose, 3 : 6-anhydro-~-galactose, and sulphate groups in approximatelyequimolecular proportions, and the low consumption of periodate by thepolysaccharide suggests that the D-galactose 4-sulphate residues are linkedthrough positions 1 and 3.1g9 1-Carrageenin is composed mainly of D-galactose sulphate residues, only small quantities of the anhydro-sugarbeing present.149 A re-investigation 150 of Floridean starch has failed toproduce evidence for the presence of 1 : 3-linkages; the periodate oxidationof the polysaccharide and an examination of the thiosemicarbazide andisonicotinhydrazide derivatives of the oxidised polysaccharide indicate thatall the glucose residues are attacked by p e r i ~ d a t e .~ ~ The conversion of themain product of partial acetolysis of fucoidin into 2-O-~-fucopyranosyl-~-fucitol confirms the presence of 1 : 2-linked L-fucose residues in this poly-~accharide.1~1 A sulphated polysaccharide from Ulva Zactuca 152 containsmglucose, D-xylose, L-rhamnose, and D-glucuronic acid residues, andpreliminary evidence as to its molecular structure has been obtained frommethylation and periodate oxidation.A complex acidic polysaccharide, containing D-glucose, D-xylose, D-galactose, L-rhamnose, L-arabinose, and glucuronic acid units, has beenextracted from the fresh-water alga, Anabena cylindrica.153 The cellulosefrom the alga Chara 154 has been examined; extraction of the alga withalkali yields a starch-like polysaccharide 155 contaminated by small amountsof a xylose-containing polysaccharide.Plant Gums and Mucilages.-The occurrence of L-arabopyranose inaddition to L-arabofuranose residues in plant gums has been demonstrated inthe cases of cherry,156 peach,156 golden apple,157 lernon,l5* and Acaciakarroo 159 gums. In each case 3-0-~-~-arabopyranosyl-~-arabinose, pre-viously isolated from larch g gal act an,^^ was present amongst the products144 C.Araki and S. Hirase, Bull. Chem. SOC. Japan, 1953, 26, 463.146 C. Araki and S. Hirase, ibid., p. 109.14* D. A. I. Goring and E. G. Young, Canad. J . Chern., 1955, 33, 480.140 D. B. Smith, A. N. O’Neill, and A. S. Perlin, ibid., p. 1352.lSo P. O’Colla, PYOC. Roy. Irish Acad., 1953, 56, B, 321.161 A. N. O’Neill, J . Amer. Chem. SOC., 1954, 76, 5074.152 J. W. E. Brading, M. M. T. Georg-Plant, and D. M. Hardy, J., 1954, 319.163 C. T. Bishop, G. A. Adams, and E. 0. Hughes, Canad. J . Chem., 1954, 32, 999.lS4 El S. Amin. J., 1955, 281.lSs Idem, ibid., p. 282.ls6 P. Andrews, D. H. Ball, and J. K. N. Jones, J., 1953, 4090.157 P. Andrews and J. K. N. Jones, J., 1954, 4134.Is* Idem, I., 1955, 583.16* A. J.Charlson, J. R. Nunn, and A. M. Stephen, J., 1955, 1428.S. Hirase and C. Araki, ibid., 1954, 27, 105.E. Percival, Chem. and Ind., 1954, 1487; A. N. O’Neill, J . Amer. Chew. SOC.,1955, 77, 2837268 ORGANIC CHEMISTRY.of partial acid hydrolysis; although this disaccharide can be formed as anacid reversion product from L-arabinose,lG0 it is probable that in these casesits isolation has structural significance. Under similar conditions, 5-0-p-~-xylopyranosyl-L-arabinose has been isolated from peach 156 and cholla 156gums, and 3-0-cc-~-xy~opyranosyl-~-arabinose from golden-apple gum.157Lemon gum also yields 4-0-(4-0-methyl-~-glucuronosyl)-~-arabinose ongraded hydrolysis.161Successive applications of Barry’s degradation 162 have shown that gumarabic contains a central core of 1 : 3-linked D-galactopyranose residues; asimilar conclusion has been reached from a study of the fragment of thedegraded gum remaining after periodate oxidation and controlled hydrolysisto remove the cleaved aldobiouronic acid side-chains.la Several gums ofthe Acacia genus, namely A .senegalensis (gum arabic),lM A. moZZissima,165A . j5ycnantha,166 A . ~yanophyZla,l~~ and A . k a ~ ~ o o , ~ ~ ~ contain the same con-stituent sugars, although in different proportions; all yield the same aldo-biouronic acid, 6-O-~-D-glucuronosyl-~-ga~actose, on partial hydrolysis.In the case of A . karroo gum, a second aldobiouronic acid, 4-O-a-~-glucurono-syl-D-galactose, was i~olated.16~ The similarity of A . fiycnantha 166 andA .cyanophyZZa. 167 gums to gum arabic is emphasised by the isolationof 3-O-~-galact opyranosyl-D-galact ose 168 and 3-0- a-D-galact opyranosyl-L-arabino~e,l~~ respectively, from the products of partial hydrolysis. Gumghatti 1’0 resembles damson 1 7 1 and cherry 172 gums in respect of its con-stituent sugars, L-arabinose, D-galactose, D-mannose, xylose and D-glucuronicacid, and in yielding the same aldobiouronic acid, 2-O-~-~-glucuronosyl-~-mannose on partial hydrolysis, but the isolation also of 6-0-p-~-glucuronosyl-D-galactose suggests some similarity with the gums of the Acacia group.40-(4-O-Methyl-a-D-glucuronosyl)- and 6-0- (4-O-methyl-p-~-glucuronosyl)-D-galactose have been isolated from gum m ~ r r h , l ~ ~ and 4-O-~-glucuronosyl-D-galaCtOSe and 3-0-~-glucuronosyl-~-galactose from Neem gum 17* andKetha gum,l75 respectively.The partial methanolysis of methylatedsapote gum yields the methyl glycosides of 3-O-methyl-~-xylose, 2 : 3 : 4-tn-O-methyl-D-xylose, 2 : 3 : 4-tri-O-met hyl-L-arabinose, and 3 : 4-di-0-methyl-D-glucuronic acid, together with the methyl glycosides of thepartially methylated aldobiouronic acids, 3-0-methyl-2-0-(2 : 3 : 4-tri-O-methyl-D-glucuronosyl)-D-xylose and 2-O- (3 : 4-di-O-methyl-~-glucuronosyl)-1.0 D. H. Ball, J. K. N. Jones, and W. H. Nicholson, Amer. Chem. SOC. Meeting,Minneapolis, Sept., 1955, Abs. Papers, 7 ~ .161 P. Andrews and J. K. N. Jones, J.. 1954, 1724.T. Dillon, D. F. O’Ceallachain, and P. O’Colla, PYOC. Roy. Irish Acad., 1953,55, B, 331 ; 1954, 57, B, 31.~8 F.Smith and D. Spriestersbach, Amer. Chem. SOC. Meeting, Minneapolis, Sept.,1955, Abs. Papers, 1 5 ~ .Id* S. W. Challinor, W. N. Haworth, and E. L. Hirst, J., 1931, 258.lBS A. M. Stephen, J., 1951, 646.166 E. L. Hirst and A. S. Perlin, J., 1954, 2622.167 A. J. Charlson, J. R. Nunn, and A. M. Stephen, J., 1955, 269.188 J. Jackson and F. Smith, J., 1940, 79.ld0 F. Smith, J., 1939, 744.170 G. 0. Aspinall, E. L. Hirst, and A. Wickstrom, J., 1955, 1160.171 E. L. Hirst and J. K. N. Jones, J., 1938, 1174.17% J. K. N. Jones, J., 1939. 658.17a J. K. N. Jones and J. R. Nunn, J., 1955, 3001.17’ S. Mukherjee and H. C. Srivasta, J. Amm. Chem. SOC., 1955, 77, 422.176 G. P. Mathur and S. Mukherjee, J . Sci. Ind. Res. (India), 1964, 13, B, 462ASPINALL AND SCHWARZ : CARBOHYDRATES.2893-O-methyl-~-xylose.~~~ In contrast to these glucuronic acid-containinggums, Cochlospermum gossypizcm gum 177 contains residues of D-galacturonicacid, in addition to L-rhamnose and D-galactose. The hydrolysis productsfrom the methylated gum, together with the mixture of aldobiouronic acids,2-O-~-gdacturonosyl-~-rhamnose and 4-O-~-galacturonosyl-~-galactose, ob-tained on partial hydrolysis, indicate a highly branched structure.A re-investigation of the mucilage from Plantago arenaria seeds 178 stillleaves doubt concerning the homogeneity of the polysaccharide. Although2-O-a-~-galacturonosyl-~-rhamnose was isolated from the partial hydrolysisof the mucilage, the hydrolysis of the methylated polysaccharide gave acomplex mixture of methyl ethers of D-xylose, L-arabinose, and D-galactose,but no methylated derivatives of D-galacturonic acid or L-rhamnose could beisolated.Partial hydrolysis of okra mucilage 179 yielded PO-or-~-galacto-pyranosyl-D-galactose and 2-O-a-~-ga~acturonosy~-~-rhamnose. An acidicpolysaccharide isolated from the juice of ripe grapes consisted of residues ofD-galactose, D-mannose, L-arabinose , L-rhamnose, and D-galaCtUrOniC acid,and yielded 2-O-a-~-galacturonosyl-~-rhamnose on partial hydrolysis.l**Polysaccharides synthesised by Micro-organisms.-Further structuralexaminations of dextrans have shown that these polysaccharides have back-bones of cc-1 : 6-linked D-glucopyranose residues, but that they differ con-siderably in their degrees of branching and also in the nature of the branchpoints.Thus, Betacoccus arabinosaceous normally synthesises a brancheddextran with a repeating unit of 6-7 glucose residues and with branchingthrough C(3).181 The same organism, when grown in a magnesium-deficientmedium, elaborates a much less highly branched polysaccharide of the samegeneral type with a unit-chain length of 40--50.182 A large number ofdextrans, synthesised by different strains of Leuconostoc mesenteroides, havebeen examined by periodate oxidation,183$ and the proportions of 1 : 6-,1 : 4-, and 1 : 3-linkages determined. The results obtained from the quan-titative analysis of the products (glucose, glycerol, and erythritol) of hydro-lysis of the polyol, isolated from the catalytic reduction of the periodate-oxidised polysaccharides,l were in reasonable agreement with those calculatedfrom the titrimetric determinations of periodate consumed and formic acidreleased during the oxidation.183 Methylation has shown that the levansformed by Pseudomonas +runicola, Wormald and Bacillus subtilis BG2 F1are branched molecules, with repeating units of 9-10 2 : 6-linked @-D-fructo-furanose residues and with 2 : l-linkages at the branch p0ints.18~ A similarlevan, but of shorter average chain length (8-9 units), has been isolatedfrom B.Polymyxa.ls6176 E. V. White, J . Amev. Chem. Soc., 1953, 75, 257, 4692; 1954, 76, 4906.177 E. L. Hirst and S. Dunstan, J.. 1953, 2332.178 R. L. Whistler and H. E.Conrad, J . Amer. Chem. SOL, 1954, 76, 1673, 3544.lSo W. Biichi and H. DeueI, Helv. Chirn. Acta, 1954, 3'7, 1392.181 S. A. Barker, E. J. Bourne, G. T. Bruce, W. B. Neely, and M. Stacey, J., 1954,lS2 S. A. Barker, E. J. Bourne, A. E. James, W. B. Neely, and M. Stacey, J., 1955,lE8 J. W. SIoan, B. H. Alexander, R. L. Lohmar, I. A. Wolff, and C. E. Rist, J . Amer.180 J. C. Rankin and A. Jeanes, ibid., p. 4435.lS6 D. J. Bell and R. Dedonder, J.. 1954, 2866.la6 D. Murphy, Canad. J . Chem., 1952, 80, 872.E. L. Hirst, E. G . V. Percival. and C. B. Wylam, J., 1954, 189.2395.2096.Chem. SOC., 1954, 16, 4429270 ORGANIC CHEMISTRY.Several polysaccharides of the amylopectin-glycogen type have beenisolated from micro-organisms. The polysaccharides synthesised by theholotrichously ciliated protozoa present in the sheep’s rumen and byCyclopostium found in the colon and ca3cum of a horse 188 contain unitchains of 22-23 a-1 : 4-linked D-glucose residues joined by 1 : 6-linkages.The polysaccharides from the protozoa Trichomonas fEtus and T.gaZZinea,l*gand from BaciZZus megatherium lgo contain shorter unit chains of 15, 9, and10-1 1 residues, respectively.Serological cross reactions have been used in the comparison of the acidiccapsular polysaccharide from A zotobacter c3aroococcum 191 and the Type I1Pneumococcus specific polysaccharide lg2 with polysaccharides whose mainstructural features are known. Methylation has shown that the A . chroococ-cum polysaccharide contains D-glucose and D-galactose residues in theratio of 3 : 1, together with a small proportion of D-glucuronic acid residues.From similar experiments, it is clear that the Type I1 Pneumococcus poly-saccharide is highly branched and contains L-rhamnose, D-glucose, andD-glucuronic acid residues in the approximate ratio of 7 : 1 : 3; whilst thedetailed structure is not yet known, the molecule must contain chains of1 : 3-linked L-rhamnopyranose residues. Two serologically active poly-saccharides have been isolated from Bacillus antkracis; 1g3 one of the poly-saccharides is a mannan in which the residues are 1 : .Q-linked, whilst theother contains D-galactose and N-acetyl-D-glucosamine units in the ratioof 2 : 1.L-Fucose is a constituent sugar of three widely different polysaccharides.The capsular polysaccharide from Pseudomonas jkorescens, strain I1 , yieldson hydrolysis D-glucose, D-glucosamine, L-fucose, a crystalline disaccharidecomposed of glucose and fucose, and a crystalline tetrasaccharide composedof a glucose, a glucosamine, and two fucose residues.lM The extracellularpolysaccharide from Mucor racemosus195 is composed of residues of D-galactose, D-mannose, L-fucose, and o-glucuronic acid ; it is probable thatall the fucose residues occur in the furanose form in terminal positions asthey are all attacked by periodate and are all released on autohydrolysis ofthe polysaccharide.An extracellular polysaccharide from A erobacteraerogenes is composed of D-glucose (50y0), L-fucose (lo%), and unidentifieduronic acid residues (29Y0).lg6Mucopo1ysaccharides.-Although much work has been carried out duringrecent years on this group of polysaccharides, knowledge of their detailedchemical structure is still limited.Some aspects of the chemistry of thesesubstances, including their relation to proteins in protein-carbohydratecomplexes, formed a part of the Faraday Society Discussion on ‘ I TheG. Forsyth and E. L. Hirst. J., 1953, 2132.G. Forsyth, E. L. Hirst, and A. E. Oxford, J., 1953, 2030.la@ D. J. Manners and J. F. Ryley, Biochem. J., 1955, 59, 369.lgo C. Barry, R. Cavard, G. Milhaud, and J. P. Aubert, Ann. Insf. Pusteuv, 1953, 84,lD1 G. J. Lawson and M. Stacey, J., 1954, 1925.12@ K. Butler and M. Stacey, J., 1955. 1537.lnS J. E. Cave-Brown-Cave, E.J. S. Fry, H. S . El Khadem, and H. N. Rydon, J.,lg4 R. G. Eadon and R. Dedonder, Compf. vend., 1955, 241, 579.lg5 L. Hough and M. B. Perry, Biochem. J., 1955, 61, viii.lg6 J. F. Wilkinson, W. F. Dudman, and G. 0. Aspinall, Biochem. J., 1955, 59,446.605.1954, 3866BARKER AMINO-ACIDS, YEPTIDES, AND PROTEINS. 27 1Physical Chemistry of Proteins." lg7 The structure of chondrosin, thedisaccharide obtained from cartilage chondroitinsulphuric acid,l9* has beenestablished as 2-amino-2-deoxy-3-0- ( p-D-glucopyranuronosyl)-D-galact oseby degradation and reduction to 2-0-( p-D-glucopyranosy1)-D-lyxitol, whosestructure was proved by periodate oxidation.199 A similar conclusion wasreached from a study of the periodate oxidation of N-acetylchondrosin ethylester.200 Chondroitin,201 a mucopolysaccharide isolated from bovine cornea,has a very low sulphate content and also yields chondrosin on hydrolysis.The disaccharide isolated from the partial acid hydrolysis of hog gastricmucin with blood group A activity has been identified as 2-acetamido-2-deoxy-kO-P-D-galactopyranosyl-D-glucose by periodate oxidation,202s 203and by oxidative degradation (with ninhydrin) and synthesis from,2043-O-p-~-galactopyranosy~-~-arabinose, and also by comparison with thesynthetic disac~haride.~Os Hydrolysis of the periodate-oxidised hog-muchpolysaccharide after bromine oxidation yielded tartronic acid, D-glyceric acid,and D-glucosamine hydrochloride, and so showed that the galactose residuesare linked through Ct2>.206 Periodate oxidations of the polysaccharide andits degradation products suggest that the small proportion of L-fucoseresidues (<lo%) present in the molecule replace some of the D-galactoseresidues in the basic disaccharide repeating unit, probably near the ends ofthe chain~.~O'G.0. A.J. C. P. S.11. AMINO-ACIDS, PEPTIDES, AND PROTEINS.Natural Amino-acids.-A new attempt has been made to discover theultimate origin of natural amino-acids. In a remarkable paper evidencehas been presented that a wide variety of amino-acids is formed when amixture of methane, ammonia, hydrogen, and water are subjected to thecombined action of a silent electrical discharge and a high-frequency spark.In contrast with the results of earlier attempts to reproduce the synthesisof the raw materials of life ab initio, the products in this case were appreciablein quantity and identified with certainty, while proof that microbiologicalprocesses were not involved was adequate.Glycine, a- and f3-alanine,sarcosine, and a-aminobutyric acid were among the thirty or more ninhydrin-active compounds separated.A considerable number of new natural amino-acids has been reported,many of which occur in the free state. Recent surveys have been made oflg7 Discuss. Faraday SOC., 1953, 13, pp. 245-287.200 H. Masamune, 2. Yoshizawa, and M. Maki, Tohuku J. Exp. Med., 1951, 55, 47.201 E. A. Davidson and K. Meyer, J. BioE. Chem., 1954, 211, 605.202 2. Yoshizawa, Tohuku J. Exp. Med., 1950, 52, 111.203 F. Zilliken, P.N. Smith, R. M. Tomarelli, and P. Gyorgy, Arch. Biochem. Biophys.,204 2. Yoshizawa, Tohuku J. Exp. Med., 1950, 62, 145.206 R. Kuhn and W. Kirschenlohr, Chem. Bey., 1954, 87, 1547,t o 4 2. Yoshizawa, Tohuku J. Exp. Med., 1951, 54, 129.207 H. Masamune and 2. Yoshizawa, ibid., 1954, 60, 135,1 S. L, Miller, J, Amey. Chem. Soc., 1955, 77, 2351.E. A. Davidson and K. Meyer, J. Amer. Chem. Soc., 1954. 76, 5686.Idem, ibid., 1955, 77, 4796.1955, 54, 398272 ORGANIC CHEMISTRY.free amino-acids both in plant and animal tissues2 The biochemical signi-ficance of much recent work is outside the scope of this Report which willbe concerned with only a selection of papers published in 1954 and 1955.The methylsulphonium analogue of methionine has been obtained intwo laboratories and appears to be of wide occurrence in green plants.Itis more active than methionine as an antagonist of the toxicity of sulphanil-amide for certain micro-organisms. A substantial proportion of the organicsulphur of cabbage is believed to be present as one of the diastereoisomericforms of L-S-methylcysteine sulphoxide (8-methylsulphinylalanine) .4 Be-sides the occurrence of y-methylproline in young apple fruit, a further newproline derivative has been observed in both the fruit and the twigs of appletrees5 It is believed to be a hydroxymethylproline, but it is not as yetpossible to distinguish between the two possibilities (1) and (2).H 2 N l ; J p N H 2 FOPHO t-J C02"HHo*cHz-LJ C0,HH(1) (2) (3)Roseothricin, besides containing 3 : 6-diaminohexanoic acid,' yields anamino-acid " roseonine " to which the structure (3) has been assigned.8Permanganate oxidation of the material gave guanidine and a small quantityof glycine; one mol.of periodate was consumed quickly, producing form-aldehyde and ammonia, and, after twenty hours, a further mol. of oxidantwas used. This behaviour is similar to that of serine and was regarded assupport for structure (3). It seems to the Reporter, however, that thestructure needs further consideration in view of the fact that the pK,' valueis lower than that of isoserine.A previously unidentified peak in ion-exchange chromatograms of humanurine has been shown to be due to ~-3-methylhistidine,~ which has beenobtained also, together with other met hylhis tidines, by met hylation ofhistidine and is distinguished from l-methylhistidine by chromatographyon Dowex-50 resin and by its infrared spectrum.and of a-aminoy-hydroxy-pimelic acid 11 in hydrolysates of nerve proteins has been claimed, buta-aminobutyric acid, previously obtained therefrom,12 has now been shownto arise by decomposition of threonine hydrochloride and serine hydro-2 N.Grobbelaar, J. K. Pollard, and F. C . Steward, Nature, 1955, 175, 703; A. I.Virtanen, Angew. Chem., 1955, 67, 381; W. H. Stein and S. Moore, J . Baol. Chem.,1954, 211, 915; H. H. Tallan and S. Moore, ibid., p. 927.R. A. McRorie, G. L. Sutherland, M. S. Lewis, A. D. Barton, M. R. Glazener, andW. Shine, J . Amer. Chem.Soc., 1954, 76, 115; F. Challenger and B. J. Hayward,Biochem. J., 1954, 58, iv.R. L. M. Synge and J. C. Wood, ibid., 1955, 60, xv.5 A. C. Hulmeand W. Arthington, Nature, 1954,173, 588; A. C. Hulme, ibid., 1954,174, 1055; G. Urbach, ibid., 1955, 175, 170.13 A. C. Hulme and F. C. Steward, ibid., p. 171.7 K. Nakanishi, T. Ito, M. Ohashi, I. Morimoto, and Y . Himta, BUZZ. Ckem. Soc.Japan, 1954, 27, 639.The presence of a-aminopimelic acidK. Nakanishi, T. Ito, and Y . Hirata, J . Amer. Chem. SOC., 1954, 76, 2845.H. H. Tallan, W. H. Stein, and S. Moore, J . Biol. Chem., 1954, 206, 825.lo A. I. Virtanen and A.-M. Berg, Acta Chem. Scand.. 1954, 8, 1086.l1 A. I. Virtanen, E. Uksila, and E. J. Matikkala, ibid., p. 1091.l2 K. Heyns and W. Walter, 2.physiol. Chem., 1952, 289, 85BARKER : AMINO-ACIDS, PEPTIDES, AND PROTEINS. 273chloride.13 An imino-acid from species of Liliacm has been identified l4as an azetidine derivative (4). The tentative identification of y-methyl-glutamic acid and y-hydroxy-y-methylglutamic acid in PhyZZitis scolo-pendrium l5 and of y-hydroxyglutamic acid in Phlox decussata l6 is to beCH -CH I‘ N”qH’Co2H (4)contrasted with the finding that Dakin’s so-called p-hydroxyglutamic acid l7consists mainly of a mixture of glutamic and aspartic acid.ls It is also ofinterest that y-methyleneglutamine, first reported as a constituent of thepeanut plant,lg and y-methyleneglutamic acid have been recognised in thetulip bulb 2o and in hops.21 The structures of the natural materials havebeen confirmed by synthesis.22Synthetic Amino-acids.-Acylaminomalonic esters, for which an im-proved preparation is a ~ a i l a b l e , ~ ~ have been used in a large number of theC o p e C02MeI ICH-NHsCHO - CH,:CH.CH,-C- NH-CHO --DIC0,Mc C o p e(3C0,McIICOaMeMoSgCHiCH;CH,-C‘NH.CHO - MeS*CH,-CH,*CH .CHgCO,H(6) NH2C0,Et .C 02EtI IC 1.CHiCH.C 0,Et 4- CH*N H Ac - E t 0,C.CH-C H,*C*NHAcI I I I(7) (0)0 A c c 0,E t OAc C0,Et - HO,C* C H*C H2* CH-C02HI IOH NH,(9)syntheses of amino-acids described in the period under review. DL-Homo-methionine has been obtained 24 by the route (5) _t (6) and DL-y-hydroxy-glutamic acid 25 by route (7) + (8) + (9). The latter product was alsolS K. Heyns and W. Walter, 2. physiol.Chem., 1953, 294, 111.l4 A. I. Virtanen and P. Linko, Actu Chem. Scand., 1955,9, 551 ; L. Fowden, Nature,16 A. I. Virtanen and P. K. Hietala, ibid., p . 175.l7 H. D. Dakin, Biochem. J., 1918,12, 290; 1919,13, 398.1s C. E. Dent and D. I. Fowler, ibid., 1954, 56, 54.1* J. Done and L. Fowden, ibid., 1951, 49, xx; 1951, 51, 541.R. M. Zacharius, J. K. Pollard, and F. C. Steward, J . Amer. Chem. Soc., 1954, 76,21 G. Harris, Chem. and Ind., 1954, 244.22 P. C. Wailes, M. C. Whiting, and L. Fowden, Nature, 1954,174, 130; P. C. WailesH. Hellmann and F. Lingens, 2. physiol. Chem., 1964, 297, 283.24 A. Kjaer and S . Wagner, A d a Chem. Scand.. 1955. 9. 721.zs L. Benoiton and L. P. Bouthillier, Canad. J . Chern., 1955, 83, 1473.1955,176, 347; A. I.Virtanen, ibid., p . 984; Angew. Chem., 1955, 67, 619.A. I. Virtanen and A.-M. Berg, Acfu Chem. Scand., 1955, 9, 553.1961.and M. C. Whiting, J., 1956, 3636274 ORGANIC CHEMISTRY.obtained by bromination of a-phthalimidoglutaric anhydride, and its struc-ture was confirmed by the fact that the material obtained by either routewas unaffected by periodate. DL-Lysine has been synthesised by makinguse of the fact that l-bromo-4-chlorobutane (10) reacts 26 with the sodio-derivative (11) to give the acetamidomalonic ester (12), and a furtherC 02E t CO Et I I 2I IAc+JH.CNa + Br*CH,.CH,*CH;CH,CI --C Ac*NH*C*CH;CH;CH2Ci01) C0,Et 00) C02Et Q2)interesting adaptation 2' of this type of synthesis is the formation of glutamicacid through the intermediate (13).Glutamic acid has also been obtainedfrom ethyl a-bromoglut arate .28C02R C02RI IIC 02RII4 CH*CH *C*NHAcC02RIFH, + CHzO + CH'NHAcC02R C 02R C0,R C02R03)L-isoGlutamine has been synthesised 29 by an unambiguous route involv-ing the formation of a lactam (14) from N-toluene-P-sulphonylglutamic acidL-isoGlutamine is also pro- means of phosphorus pentachloride.CONH2I CDNH,C02H I CH*NH2I O{ '7H2 - 7% - y 2-2 CH*HOS ICH. NHlor7"2 y 2TosN-CCH'COCIFH2 -y 2C02H C02H C02H6s) 04)chromatographically pure form by conversion of y-benzyl-N-benzyl-oxycarbonyl L-glutamate into the amide, followed by hydrogenolysis of theprotective gr0ups.~0 It may be noted that removal of water by azeotropicdistillation 31 or by polyphosphoric acid 32 results in improved yields ofbenzyl esters of amino-acids. A modification of the Strecker synthesis hasbeen used for the preparation of DL-a-methylghtamic acid, which acts as aninhibitor of the synthesis and utilisation of glutamine.=Other innovations include the synthesis of homologues of glutamic acid,methionine, and diaminopimelic acid via the hydantoins,34 and the produc-tion of a-amino-acids by interaction of a-keto-aldehydes with ammoniumsalts in the presence of thi01s.~~Stereochemical Relations-An extensive study of the optical rotations26 M.Servigne and E. Szarvasi, Compt. rend., 1954, 2.38, 1595.27 H. Hellmann and F. Lingens, Angew. Chem., 1954, 66, 201.28 G. Pans, R. Gaudry, and L. Berlinguet, Canad. J . Chem., 1955, 53, 1724.2s J.M. Swan and V. Du Vigneaud J . Amer. Chem. SOC., 1954, 76, 3110.30 M. Kraml and L. P. Bouthillier, Canad. J . Chem., 1955, 33, 1630.31 J. D. Cipera and R. V. V. Nicholls, Chem. and Ind., 1955, 16.st B. F. Erlanger and R. M. Hall, J . Amer. Chem. SOC., 1954, 76, 6781.33 A. E. Gal, S. Avakian, and G. J. Martin, ibid., p. 4181.s4 K. Pfister, W. J. Leanza, J. P. Conbere, H. J. Becker, A. R. Matzuk, and E. F.35 T. Wieland, J. Franz, and G. Pfleiderer, Chem. Ber., 1955, 88, 641.Rogers, ibid., 1955, 77, 697BARKER : AMINO-ACIDS, PEPTIDES, AND PROTEINS. 275of amino-acids has been made and it is claimed that reliable conclusions canbe drawn from optical data concerning the structures both of amino-acidscontaining one asymmetric centre, and of diastereoisomeric amino-acid~.~~Diastereoisomers of amino-acids such as hydroxylysine and isoleucine arenow conveniently separated by ion-exchange chr~matography.~~X-Ray studies have shown that (the usual convention being followed) theamino-group of D(-)-isoleucine is cis with respect to the methylIt follows from this that, since L-isoleucine and D-alloisoleucine on treatmentwith ninhydrin give (+)-a-methylbutyraldehyde, and misoleucine andL-alloisoleucine give the laevorotatory aldehyde, the configurations of allfour isomeric isoleucines are kn0wn.~9 It is interesting to note that O-methyl-threonine acts as a competitive inhibitor for the incorporation of radioactiveisoleucine into proteins, a fact which is in agreement with the existence ofrelated configurations at both the asymmetric centres of the amino-a~ids.~~A method which may well be applicable to the determination of theconfigurations of diastereoisomeric amino-acids is exemplified by the con-version of L-alanine into y-aminovaleric a ~ i d .~ 1 L-a-Phthalimidoprop-aldehyde (16), previously obtained from L-alanine, was converted by aDoebner condensation into the pent-2-enoic acid (17) which, after hydrogen-ation and hydrolysis, gave ( +)-y-aminovaleric acid. This aminovalericacid is therefore related structurally to L-alanine..p4t04y cp4 ea, tiJMe-C-CHO Me - C- Cn : C 14. CO~HI IH H0s) Q7)Preparation of Amino-acids from Peptides and Proteins.-Variousmodifications of the methods of acid hydrolysis of peptides and proteinshave been introduced.Dissolution of tissue in 85% formic acid followedby addition of 2~-hydrochloric acid results in liberation of all amino-acids,except tryptophan, within two hours.42 It is agreed that different peptidebonds are split at different rates,43 but there appear to be differences ofopinion as to the mechanism of the hydrolysis.44 The preferential liberationof threonine and serine recorded by Elliott 45 has been observed also in thehydrolysis of wheat gluten under the conditions used by and also38 M. Winitz, S. M. Birnbaum, and J. P. Greenstein, J . Amer. Chem. SOC., 1955, 77,37 K. A. Piez, J . Biol. Chem., 1954, 207, 77; P. B. Hamilton and R. A. Anderson,38 J. Trommel and J. M. Bijvoet, Actu Cryst., 1954, 7, 703.3B W.S. Fones, J . Amer. Chem. SOC., 1954, 76, 1377.40 M. Rabinovitz, M. E. Olsen, and D. M. Greenberg, ibid., 1955, 77, 3109.I1 K. Balenovic and D. Cerar, J., 1955, 1631.42 S. U. Gurnani, U. S. Kumta, and M . B. Sahasrabudhe, Biochim. Biophys. Acfu,43 R. Hirohata, Y . Kanda, M. Nakamura, N. Izumiya, A. Nagamatsu, T. Ono,44 R. J. L. Martin, Nature, 1955, 175, 771.4 5 D. F. Elliott, Biochem. J., 1952, 50, 542.46 L. Wiseblatt, L. Wilson, and W. B. McConnell, Canad. J . Chem., 1955, 33, 1295.716; M. C. Otey, J. P. Greenstein, M. Winitz, and S. M. Birnbaum, ibid., p. 3112.ibid., 1955, 213, 249.1955, 16, 553.S. Fujii, and M. Kimitsuki, Z . physiol. Chem., 1953, 295, 368276 ORGANIC CHEMISTRY.during the hydrolysis of insulin4' by 10-5w-hydrochloric acid at 0'.Hydro-lysis of peptide bonds with acidic resins is being used increasingly. Dowex-50 is preferred>* but it is found that prolonged treatment with water causesappreciable breakdown of this resin , with liberation of sulphuric acid andsome brown material, particularly with high degrees of cross-linking of thepolymer.49 Temperature is an important factor, and the method is un-suitable in certain cases such as the hydrolysis of insulin.50During the alkaline fission of peptide bonds, a secondary reaction mayoccur whereby an N-terminal glycine residue reacts reversibly with analdehyde to give a hydroxyamino-acid or, conversely, a terminal hydroxy-amino-acid may be degraded to an aldehyde and gly~ine.~l A new reactionhas been reported which may prove useful in the degradation of peptidesand proteins.52Most developments in the isolation of amino-acids from protein hydro-lysates concern partition, ion-exchange, or electrophoretic techniques.However, it is useful to note that methionine may be isolated from hydro-lysates of casein and zein in 65% and 85% yield respectively by conversioninto the methylsulphonium derivative which is precipitated as the phospho-tungstate.63 Sublimation is possible with a number of amino-acids and thistechnique should find considerable use in the purification of labelledmaterials.54Partition Chromatography, Ion-exchange Chromatography, and Iono-graphy of Amino-acids.-Various minor modifications in the analysis ofamino-acid mixtures by partition chromatography have been introduced.Amino-acids are located on paper by spraying it with naphthaquinone-sulphonic acid and heating it to 60".The amino-acids appear as spots whichfluoresce strongly in ultraviolet light,55 and it is claimed that the methodis more sensitive than the ninhydrin technique. Modifications in techniquenow largely eliminate errors in the quantitative determination of amino-acids on paper chromatograms by the ninhydrin method,66 and improve-ments in the c,opper method have also been sugge~ted.~'Ion-exchange chromatography is probably more widely applicable to theseparation and isolation of amino-acids; and, of the many studies of theamino-acid composition of proteins which have come to the notice of theReporter during the last two years, over half have employed ion-exchangechromatography. Zeokarb-225 can be used 58 instead of Dowex-60, as inthe original work of Moore and Stein.59 It is recommended that '' waterregain" as defined by Pepper 60 be used instead of the degree of cross-47 G. L.Mills, Biochem. J., 1954, 56, 230.48 J. R. F i t a k e r and F. E. Deatherage, J . Amer. Chem. Soc., 1955, 77, 3360.A. S. Dlxon, Biochem. J., 1955, 59, xii; 60, 165.6o J. C. Paulson and F. E. Deatherage, J . Amer. Chem. SOC., 1954,76, 6198.61 T. Wieland and K. Dose, AIzgew. Chem., 1954, 66, 781.62 K. Heyns and K. Stange, 2. Naturforsch., 1955, lob, 129.6s N. F. Floyd and T. F. Lavine, J . Biol. Chem., 1954, 207, 119.64 D. Gross and G. Grodsky, J .Amev. Chern. Soc., 1955, 77, 1678.66 E. Kofranyi, 2. physiol. Chem., 1955, 299, 129.66 W. Gerok, ibid., p. 112.67 H. Boser, ibid., 1954, 296, 10.6* P. N. Campbell, S. Jacobs, T. S. Work, and T. R. E. Kressman, Chem. axd Id.,60 S. Moore and W. H. Stein, J . Biol. Chem., 1951, 192, 663.6o K. W. Pepper, J . Appl. Chem., 1951, 1, 124.1955, 117BARKER : AMINO-ACIDS, PEPTIDES, AND PROTEINS. 271linking to designate a particular resin since this quantity can readily bemeasured. Minor modifications in technique are advisable for effectiveresolution of basic amino-acids 61 and it is also recommended that acidicamino-acids should be first isolated on a strongly basic resin with a volatileacid as eluant.62Ionographic separation of amino-acids on filter paper results in poorerresolution than with partition chromatography or ion-exchange chromato-graphy, but better results are obtained at high potential gradients.Atechnique has been described 63 using 6000 v, giving a gradient up to130 v per cm.Determination of End-groups and Sequence in Polypeptides and Proteins.-Comparatively little work has been reported during the period underreview concerning improved or new techniques for the determination ofN-terminal residues. It has been pointed out 64 that determination ofN-terminal residues by the fluorodinitrobenzene method and of C-terminalresidues by using carboxypeptidase may lead to contradictory results. Thelarge number of papers dealing with the determination of C-terminal residuesis indicative of the fact that a wholly satisfactory method has yet to befound.The 2-thiohydantoin method still receives considerable attention,66but serine and proline are now added to the list of C-terminal groups whichvitiate the method. Anodic oxidation of C terminal residues according toBoissonnas 66 is found to be unsatisfactory with peptides containing phenyl-alanine or tyrosine since these amino-acids are destroyed irrespective of theirposition in the chain.67 An interesting modification of the previouslyreported 68 reaction of peptides with hydrazine has been d e ~ e l o p e d . ~ ~ Thisallows of simultaneous determination of N-terminal and C-terminal residues.Treatment of the benzyloxycarbonyl-peptide or -protein with hydrazinehydrate converts amino-acid residues in the middle of a peptide chain intoamino-acid hydrazides (18), and the N-terminal residue is converted into thedihydrazide (19), whereas C-terminal amino-acid is liberated as such.Thedihydrazides are converted into what may be either a triazine (20) or anaminohydantoin (21), and the products are separated chromatographically.The method is not satisfactory for the detection of glycine, serine, or cysteineas N-terminal residues, since compounds ot type (20) or (21) are not formed;difficulties also arise with glutamyl-peptides. Insulin has been subjectedto ammonolysis in liquid ammonia at 120" which converts all residues intoamides except the C-terminal residue which is recovered as the free amino-acid.70 C-Terminal groups have also been converted by acetic anhydrideP.B. Hamilton and R. A. Anderson, J. Biol. Chem., 1954, 211, 95.D. Gross, Natuve, 1955, 176, 72.M. Rovery and P. Desnuelle, Bull SOC. Chim. biol., 1954, 36, 95.62 C. H. W. Hks, S. Moore, and W. H. Stein, J. Amer. Chem. SOC., 1954,76, 6063.66 A. L. Levy, Biochim. Biophys. Acta, 1954,15, 589; R. A. Turner and G. Schmerz-ler, ibid., 1954, 13, 553; M. Dautravaux and G. Biserte, Compt. rend., 1965, 240, 1153;S . W. Fox, T. L. Hurst, J. F. Griffith, and 0. Underwood, J . Amer. Chem. Soc., 1955,77,3119.g6 R. A. Boissonnas, Nature, 1953, 171, 304.6 7 A. R. Thompson, Biochim. Biophys. Acta, 1954, 15, 299.*.a S. Akabori, K. Ohno, and K. Narita, BuIl. Chem. SOC. Japan, 1952, 25, 214;6s K. Schlogl and E.Wawersich, Naturmiss., 1954, 41, 38; K. SchIocrl. F. Wesselly,70 R. W. Chambers and F. H. Carpenter, J. Amer. Chem. SOC., 1955, 77, 1527.K. Ohno, -1. Biochem. Japan, 1953, 40, 621.and E. Wawersich, Monatsh., 1954, 85, 957278 ORGANIC CHEMISTRY.and pyridine at 150" into ketones which are liberated on complete hydrolysisof the peptide bonds.71Ph'CH200'C0.NH*FH.CO-ENn. H.CO-),-NH.Cl+C02H IR3'iR, R2H2NNH.CO-NHCH*C0.NHNH, + n H,N*YHCO*NHNH, + W N=CHC02HI 2 1R1 00) R2 08) IRit'+-CO-Y" oT R;CH I -C,O ,N.NH2NH- CO- NH NH-CO0a QOOf the methods of stepwise degradation for the determination of sequence,the route via an amino-alcohol is probably the most promising. It is gener-ally agreed 72 that lithium borohydride is preferable to lithium aluminiumhydride for reduction of the free carboxyl group, and it has been shownthat isomerisation of the p-hydroxy-amide (22) by acid or acid chloride tothe 9-amino-ester (23) is effected in 85-90% yield.73 Reduction of thisester with lithium borohydride gives the amino-alcohol in 8S-90% yieldand a new p-hydroxy-amide (24) which can then be treated with phosphorusoxychloride, so that the series of processes can be repeated.RCO*NHCHR*CO*NH*CHR'*CH2*OH R*CO.NH*CHR'*CO.O~CHXCHR".NH,(22) (23)(24)Biologically Active Peptides.-New methods involving chromatographyon charcoal and zone electrophoresis have been described 74 for the puri-fication of bacitracin A, which is now believed to have the empirical formulaC66H103016N1,S and to contain three isoleucine residues.75, 76 The presenceof alloisoleucine is c~nfirrned,~~ but there is general agreement that theamino-acid sequence of Porath 77 is incorrect and that the sequence (25) morecorrectly represents the structure.78, 79,809 81982 The possibilities cannot beruled out that interaction occurs also between phenylalanine and the terminalisoleucine residue 79 and that the two aspartic acid residues are joined in anunbranched chain.81 It appears probable that, of these two residues, thatRCO*NH*CHR*CH,*OH + HO-CH2*CHR"*NHa71 R.A. Turner and G. Schmerzler, J . Amer. Chem. SOC., 1954, 76, 949.72 W. Grassmann. H. Hormann, and H. Endres, Chem. Bar., 1953, 86, 1477; 1955,88, 102; M. Justisz, D. M. Meyer, and L. Penasse, Bull. SOC.chim. Fvance, 1954, 1087;J. C. Crawhall and D. F. Elliott, Biochem. J., 1955, 61, 264.J. L. Bailey, ibid., 1955, 60, 173.74 J. Porath, Acta Chem. Scand., 1954, 8, 1813.75 L. C. Craig, W. Hausmann, and J. R. Weisiger, J . Amer. Chem. SOC., 1954, 76,7 6 W. Hausmann, J. R. Weisiger, and L. C. Craig, ibid., 1955, 77, 721.77 J. Porath, Nature, 1953, 172, 871.7 8 A. 1. M. Lockhart, G. G. F. Newton, and E. P. Abraham, ibid., 1954, 173, 536.79 A. I. M. Lockhart and E. P. Abraham, Biochem. J., 1954, 58, 633.82 J. R. Weisiger, W. Hausmann, and L. C. Craig, ibid., p. 731.2839.Idem, J . Amer. Chem. SOC., 1954, 76, 2839.W. Hausmann, J R. Weisiger, and L. C . Craig, ibid., 1955, 77, 723BARKER : AMINO-ACIDS, PEPTIDES, AND PROTEINS. 259attached to lysine is L-aspartic acid and is joined to the c-amino-group.83aZZoisoLeucine is believed to be next to the latent cysteine residue, which, assuggested by Newton and Abraham,84 is combined to form a thiazoline ring.This formulation is in agreement with the ultraviolet absorption of theIleu*Cy.Leu*Glu*Ileu.Lys /Phe/Orn*Leu\\+sp-His(25) ASPpeptide and the fact that the yield of the dinitrophenyl derivative of iso-leucine is increased by previous oxidation of the sulphur-containing residuewith performic acid.75Oxytocin and vasopressin continue to receive considerable attentionand, following the full description of the first synthesis of o x y t o ~ i n , ~ ~ a newsynthesis of the hormone has been described 86 which makes use of the samefinal stage as was used by Du Vigneaud's school.The unusual fission withbromine water of a peptide bond in performic acid-oxidised oxytocin, dis-cussed in a previous Report,s7 has been shown not to be connected necessarilywith the bromination of tyrosine, since this can be achieved without cleavageof the peptide bond by using glacial acetic acid or dilute hydrobromic acidas solvent. 88 Nevertheless, prevention of bromination by conversion of thephenolic group of tyrosine into the dinitrophenyl ether renders the peptidebond stable towards bromine water.Full details of the determination of the sequence of amino-acids inarginine-vasopressin have now been published, 89 and, by similar methods tothose used for lysine-vasopressin, a synthetic polypeptide has been obtainedhaving the same relative pressor, antidiuretic, and avian vasopressoractivities as arginine-vas~pressin.~OVarious improvements in the preparation of hypertensin (angiotonin)have been introdu~ed,~~ and it has been demonstrated that treatment ofplasma with renin at 0" is advisable since, under these conditions, hyper-tensinase is inactive, whereas the renin activity remains.The purifiedpeptide shows the presence of only one active pressor principle after onehundred transfers in a counter-current apparatus. It contains the followingamino-acids in the molecular proportions indicated : aspartic acid (2),serine (l), glutamic acid (l), proline (2), glycine (l), alanine (l), valine (l),isolepcine (1), tyrosine (1), phenylalanine (1) , leucine (2), histidine (2), lysine(l), and arginine (2).Fission of the peptide by hydrazine indicates thateither leucine or isoleucine is the C-terminal residue, and examination of theA. I. M. Lockhart and E. P. Abraham, Biochem. J., 1954, 58, xlvii.84 G. G. F. Newton and E. P. Abraham, ibid., 1963, S3, 604.V. Du Vigneaud, C. Ressler, J. M. Swan, C. W. Roberts, and P. G. Katsoyannis,86 R. A. Boissonnas, S. Guttmann, P. A. Jaquenoud, and J. P. Waller, HeZv. Chim.87 Ann. Reports, 1953, 50, 269.J . Amer. Chem. SOC., 1954, 76, 3115.Acta, 1955, 38, 1491.C. Ressler and V. Du Vigneaud, J . Biol. Chem., 1954, 211, 809.E. A. Popenoe and V. Du Vigneaud, ibid., 1954, 206, 353; R. Archer and J.Chauvet, Biochim. Biophys. Acta, 1954, 14, 421.V.DU Vigneaud, D. T. Gish, and P. G. Katsoyannis, J. Amev. Chem. SOC., 1954,76, 4751.s1 L. C. Clark, C. Winkler, F. Gollan, and R. P. Fox, J . Biol. Chem., 1954, 206,717; A. A. Green and F. M. Bumpus, ibid., 1954. 210. 281280 ORGANIC CHEMISTRY.dinitrophenyl derivative shows aspaxtic acid as the only N-terminal group.The last fact supports the claim for the homogeneity of the preparation.02The complete sequence of amino-acids in P-corticotropin has beenThe order of most of the residues is also known for cortico-tropin-AJM and the N-terminal sequence has been confirmed by synthesis ofthe pentapeptide produced by peptic digestion.95 It appears that the onlypossible difference between corticotropin-A and p-corticotropin is in thesequence of seven residues, the positions of which are uncertain in theformer peptide ; also corticotropin-A probably contains no amide groupsP6a-Corticotropin has the same terminal tripeptide sequence as corticotropin-Abut differs from it in arnino-acid content and partition b e h a v i ~ u r .~ ~Synthetic Peptides-An excellent survey of the methods of peptidesynthesis has appearedg8 and only more recent developments will be dis-cussed. A thorough examination of the use of N-substituted amides ofphosphorous and phosphoric acids has been made.99 An unusual rearrange-ment of compounds such as the perchlorate of O-glycylsalicylamide (26) tosalicylglycine amide (27) affords a route for the synthesis of peptides asindicated, 100%*C H;NH,,HClO, -+ ao;NH-CHjC0.NH2 LCO-NY co(2 6) (21)In addition to the use of the benzyl residue for protecting the amino-group during peptide synthesisJlOl the triphenylmethyl residue has beenrecommended102 since it is readily removed with aqueous acetic acid.AO 2 F. M. Bumpus, A. A. Green, and I. H. Page, J . Biol. Chew., 1964, 210, 287.O3 K. S. Howard, R. G. Shepherd, E. A. Eigner, D. S. Davies, and P. H. Bell, J .W. F. White and W. A. Landmann, ibid., p. 771.96 K. Hofmann and A. Johl, ibid., p. 2914.O6 W. F. White and W. A. Landmann, ibid., p. 1711.97 J. I. Harris and C. H. Li, J . Biol. Chem., 1955, 213, 499.98 T. Wieland, Angew. Chem., 1954, 66, 507.OD S . Goldschmidt and F. Obermeier, Annalen, 1954, 588, 24.loo M. Brenner, J. P. Zimmermann, J. Wehrmiiller, P.Quitt, and I. Photaki, Ex-lol L. Velluz, J. Anatol, and G. Amiard, Bull. SOC. chim. France, 1954, 1449; L.l o 2 G. Amiard, R. Heymbs, and L. Velluz, ibid., p. 191.Amer. Chem. SOL, 1955, 77, 3419.perientia, 1955, 11, 397.Velluz, G. Amiard, and R. HeymBs, ibid., 1955, 201BARKER : AMINO-ACIDS, PEPTIDES, AND PROTEINS. 281further method of somewhat limited application is the use of the benzoyl-L-phenylalanyl residue which is removed by the action of chymotrypsin.103It has been found that reduction of the benzyloxyimino-group, first sug-gested by Weaver and Hartung,l@ in ammoniacal solution favours the form-ation of peptides and avoids the production of diketopiperazines.lo5 TheN-trifluoroacetyl residue as a protecting group 106 has found further applic-ation,l07 and an important new route to the synthesis of trifluoroacetamido-acids has been introduced.lo8 This involves transacylation between theamino-acid and ethyl trifluorot hiolacetate :The trifluoroacetylglycine was converted by the phenyl thiol ester methodof Wieland and his co-workers log into a dipeptide, and the protective groupwas readily removed at a pH above 10.No racemisation was observedduring the above processes. It has been reported that P-nitrophenyl estersare more satisfactory for peptide synthesis.110 A new method of forming thepeptide bond has been developed simultaneously in two laboratories, usingdicycZohexylcarbodi-imide.lll The method is not sensitive to moisture, incontrast to those using mixed anhydrides, and the dicyclohexylurea which isformed as a by-product is readily removed.CF,CO*SEt + NR,*CH,*CO,H + EtSH + CF,*CO*NH*CH,CO,HRC0,H + H,N*R + C6H,,*N:C:NC6H11 + R-CO-NH-R' + C,H,,*NH*CO~NH*C,H,,Space does not permit discussion of all the syntheses of polyamino-acidswhich have been described in the past two years.The method using the'' Leuchs anhydride " as monomer has been applied to the synthesis ofpolymers containing various side chains such as poly-(S-allylcysteine) ,112polytryptophan,l13 and poly-P-aminophenyl-~~-danine.~~~ By initiationof the polymerisation with polylysine, cross-linked polymers have been0btained.11~ Termination of the polymerisation of " Leuchs anhydrides "may take place as shown, since it has been found that ureido end-groups arepresent : 116CO*CHRCO*NHX.[COCHR-NH],,,-H + o< I -X.[CO*CHR*NH],* CO*NH-CHR*CO,HA polyglutamic acid has also been obtained by this method using y-benzylL-glutamate as monomer, the benzyl groups being removed with phosphon-lo3 R. W. Holley, J . Amer. Chem. SOC., 1955, 77, 2552.Io4 W. E. Weaver and W. H. Hartung, J . Org. Chem., 1950, 15, 741.lo5 W. H. Hartung, D. N. Kramer, and G. P. Hager, J . Amer. Chenz. Sot., 1954,76,2261.lo6 F. Weygand and E. Csendes, Angew. Chem., 1952, 64, 136.lo' F. Weygand and E. Leising, Chem. Ber., 1954, 87, 248; F. Weygand andlo8 E. Schallenberg and M. Calvin, J . Amer. Chem. Sot., 1955, 77, 2779.loo T. Wieland, W, Schafer, and E. Bokelmann, Annalen, 1951, 573, 99.110 J. A. Farrington, G.W. Kenner, and J. M. Turner, Chem. and Ind., 1955, 601.111 J. C. Sheehan and G. P. Hess, J . Amer. Chem. Sot., 1955, 77, 1067; H. G.112 M. Frankel and A. Zilkha, Nature, 1955, 175, 1045.114 M. Sela and E. Katchalski, ibid., p. 129.115 Idem, Experientia, 1955, 111, 62.116 M. Sela and A. Berger, J . Amer. Chem. SOC., 1955, 77, 1893.M. Reiher, ibid., 1955, 88, 26.Khorana, Chem. and Ind., 1955, 1087.A. Patchornik, M. Sela, and E. Katchalski, J . Amer. Chem. Soc., 1954, 76, 299282 ORGANIC CHEMISTRY.ium iodide.11’ It has been shown that removal of ester groups from methylpoly-a-glutamate with O*S~-sodium hydroxide in the presence of freshlyprecipitated copper hydroxide produces no racemisation. 118 Synthesis ofa y-linked polyglutamic acid 7)ia a dipeptide ester gave a product whichresembled a natural bacterial polyglutamic acid and differed from poly-a-glutamic acid in solubility, in giving a strongly positive ninhydrin reaction,in titration constant, and in infrared spectrum.llg A mixed ay-polyglutamicacid has also been obtained by polymerisation of an ay-dipeptide ester,followed by hydrolysis of ester residues.120 Among other studies of peptideester polymerisation, it is important to notice that di- and tri-peptide esterspolymerise more readily than higher members of the series.121 It was alsoshown that azides polymerise in aqueous solution to give polyamino-acidsof high molecular weight.On the other hand, the azide of triglycine hasbeen converted into a cyclic peptide 122 which it is now agreed 123 is a cyclichexaglycine identical with a product obtained by the *I Leuchs anhydride ”method.l= Other monomers which have been used include N-phenylthio-carbonyl derivatives 125 and acyl chlorides,126 the latter being particularlyuseful for the polymerisation of p-amino-acids. Synthetic polypeptidescontaining more than one type of functional group have been prepared bythe I ‘ Leuchs anhydride ” method,12’ and also by ester condensation.lZ8Finally, an interesting approach to the production of polyamino-acids isexemplified by the formation of a polyphenylalanine by introducing func-tional groups into a styrene p01ymer.l~~Isolation and Purification of Proteins.-It has been found 130 that, bycareful attention to conditions such as pH, some of the older protein pre-cipitants such as metallic tungstates, sulphosalicylic acid, and metaphos-phates can be used with advantage for the fractionation of serum proteins.On the other hand, precipitation of serum proteins by acids is complete onlyon heating.131 A very simple method has been described for carrying outpreliminary experiments as a guide in devising suitable techniques for theresolution of mixtures of proteins : 132 the solution containing the mixtureof proteins is diluted to enable its optical density to be measured in theultraviolet spectrometer ; pH and ionic strength are varied and the increasein optical density due to the development of turbidity is observed ; then thedecrease in soluble protein is indicated by measurement of the optical density11’ E.R. Blout, R. H. Karlson, P. Doty, and B. Hargitay, J . Amer. Chem. SOC.,1954, 76, 4492.11* V. Bruckner, K. KovBcs, J. KovQcs, and A. Kotai, Experientia, 1954, 10, 166.119 S. G. Waley, J., 1955, 517.120 V. Bruckner, M. Szckerke, and J. KOVBCS, Naturmiss., 1955, 42, 179.121 H. N. Rydon and P. W. G. Smith, J., 1955, 2542.lZ2 J. C. Sheehan and W. L. Richardson, J . Anzer. Chem. Soc., 1954, 76, 6329.123 J. C. Sheehan, M. Goodman, and W. L. Richardson, ibid., 1955, 77, 6391.lZ4 D. G. H. Ballad, C. H. Bamford, and F. J . Weymouth, Proc. Roy. Soc., 1955,A , 227, 155; C. H. Bamford and F. J. Weymouth, J . Amer. Chein. SOC., 1955, 77, 6368.126 J. Noguchi and T. Hayakawa, ibid., 1954, 76, 2846.126 M. Frankel, Y. Liwschitz, and 2. Zilkha, ibid., p. 2814.12’ B. G. Overell and V. Petrow, J., 1955, 232; F. Micheel and C. Berding, Chem.12* K. Schlogl and H. Fabitschowitz, Monalsh., 1955, 86, 233.129 Idem, ibid., 1954, 85, 1223.13a E. L. Hess and D. S. Yasnoff, J. Amer. Chem. SOC., 1954, 76, 931.Ber., 1955, 88, 1062.T. Astrup, A. Birch-Andersen, and K. Schilling, Acta Chem. Scand., 1954, 8, 901.K. Simon, Experientia, 1954, 10, 506BARKER AMINO-ACIDS, PEPTIDES, AND PROTEINS. 283of the supernatant liquid after centrifugation. It has been pointed out thatunexpected results may be obtained in the solubility test for homogeneityowing to what appears to be an isomorphic transformation in the solidphase.l= Fractional separation from concentrated aqueous solution has beenused for the purification of clupein, and the purified material had only proline asend-group. In a development of previous work, blood-clotting factors andserum proteins have been purified by chromatography on diatomaceous earths,different commercial specimens of which vary in adsorptive capacity.135The two chains of performic acid-oxidised insulin have been separatedand isolated with a recovery of 95% by counter-current di~tributi0n.l~~Although the phenylalanyl chain was not separated from unoxidised insulin,the recovery is much better than that originally obtained by solvent pre-cipitation. The isolated peptides may also be purified by partition chromato-g r a p h ~ . ~ ~ ' Chromatographic separation of the A and the B chain of reducedinsulin has also been reported.13* By careful choice of a critical pair ofphases, a direct separation of y-globulin and albumin can be obtained.13g Anoutstanding success has been achieved by using partition chromatography,in that y-globulin from immune rabbits has been partially separated intoinert globulin and antibody.140The separation of neutral proteins by chromatography on IRC-50 resinis well established. Closely related carbon monoxide hzemoglobins havebeen separated by this means and it has been shown that the eluted proteinsare unaltered and can be readily crystallised.141 Ion-exchange chromato-graphy of acidic proteins presents some difficulties since IRC-50 adsorbsthese too strongly and basic polystyrene resins such as Dowex-50 are un-suitable because of the physical form of the polymer. However, kieselguhrcoated with a cross-linked polystyrene resin has been used with su~cess.1~~Electrophoresis continues to be used very largely for the separation ofproteins, and the subject has been reviewed by T i ~ e l i u s . l ~ ~Structure of Proteins.-As indicated in a previous Report,87 the twooutstanding problems concerning the structure of insulin involve the positionsof the amide and the disulphide residue. It appears possible, however,from a study of optical rotations, that the structure of insulin itself may bedifferent from those present in the derived A and B peptides.la Thepositions of the amide groups have been determined by estimating therelative ionophoretic mobilities and amide contents of peptides obtainedfrom enzymic digests of A and B fractions of oxidised in~u1in.l~~ The diffi-culty introduced by the occurrence of disulphide-interchange reactions 146133 0. Smithies, Biochem. J., 1954, 58, 31,134 E. Waldschmidt-Leitz and R. Voh, 2. physiol. Chem., 1954, 298, 257.136 J. H. Milstone, J . Gen. Physiol., 1955, 38, 743.138 J. G. Pierce, J . Amer. Chem. SOC., 1955, 77, 184.13' W. Andersen, Actu Chem. Scund., 1954, 8, 359.13* H. Lindley, J . Amer. Chem. SOC., 1955, 77, 4927.139 P. von Tavel, HeZv. Chim. Actu, 1955, 38, 520.140 R. R. Porter, Biochem. J., 1955, 59, 405.141 N. K. Boardman and S. M. Partridge, Biochem. J . , 1955, 59, 543.142 N. K. Boardman, Biochim. BioFhys. Actu, 1955, 18, 290.143 A. Tiselius, Angew. Chem., 1955, 67, 245.144 K. Linderstrnm-Lang and J. A. Schellman, Biochim. Bio9hys. Actu, 1954,15, 156.145 F. Sanger, E. 0. I?. Thompson, and R. Kitai, Biochem. J., 1955, 59, 509.146 F. Sanger, Nature, 1953, 171, 1025; A. P. Ryle and F. Sanger, Biochem. J., 1955,60, 535284 ORGANIC CHEMISTRY.has been overcome by digesting insulin with chymotrypsin and oxidising thepeptides formed, and by this means the disulphide linkages have beenlocated. 14' Disulphide cross-linkages have been studied also in connectionwith other proteins. For instance, it has been shown that the reductionof disulphide groups in wheat gluten is accompanied by loss of elasticity andcohesion.148 However, in wool, the susceptibility of cystine linkages toreduction is governed by their accessibility to the reagent.149 A disulphidedimer of human mercaptalbumen has been produced by oxidation withiodine of the mercury dimer.150 Other types of interchain links are presentin collagen, and a direct correlation has been found between intermolecularcohesion in the protein and its hydroxyproline ~ 0 n t e n t . l ~ ~ It is believedthat linkages occur between hydroxyl and keto-imide g r 0 ~ p s . l ~ ~ There hasbeen considerable disagreement as to the nature of the units in the collagenmolecule, but it is now claimed that they are rigid, rod-shaped particles offairly uniform size.153Several studies have been made concerning the nature of the linkages inconjugated proteins. For instance, pepsin and ovalbumen have beendegraded to peptides to which the original phosphate residue of the proteinis still attached by esterification.l= Similarly, fibrinogen has yielded apeptide containing tyrosine O-sulphate 155 and cytochrome c has beendegraded by peptic digestion to a hzmopeptide, the configuration of whichhas been discussed.158 The present state of knowledge of the configurationof a number of proteins has been reviewed.15'G. R. B.147 A. P. Ryle, F. Sanger, L. F. Smith, and R. Kitai, Biockem. J . 1955, 60, 541.148 R. H. de Deken and M . De Deken-Grenson, Biochim. Biophys. Acta, 1955, 16,149 A. J. Farnworth, Biochem. J., 1955, 60, 626.160 R. Straessle, J . Amer. Chem. SOC., 1954, 76, 3138.161 K. H. Gustavson, Acta Chem. Scand., 1954, 8, 1298.162 Idem, ibid., 1299.lti5 H. Boedtker and P. Doty, J . Amer. Chem. SOC., 1955, 77, 248.M. Flavin, J . Biol. Chem., 2954, 210, 771.ls6 F. R. Bettelheim, J . Amer. Chem. SOC., 1954, 76, 2838.166 A. Ehrenberg and H. Theorell, Nature, 1955, 175, 158.lS7 J. T. Edsall, J . Polymer Sci., 1954, 12, 253.566

ISSN:0365-6217    

DOI:10.1039/AR9555200131

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

BIOLOGICAL CHEMISTRY.1. INTRODUCTION.IN the past two issues of Annual RePorts the Reporters concerned withbiological chemistry have tended to review their topics rather than to confinethemselves to the immediate past. This policy is continued as we believethat most of our readers are likely to be unfamiliar with the background ofsome interesting current researches. For example, L( +) -ergothionehe,discovered many years ago in ergot and later in mammalian blood, is nowshown to be a widely distributed intracellular component; as yet its bio-logical function can only be guessed at. Most text-books neglect this sub-stance. Antithyroid substances in plants used for food of men and animalshave been known to exist for some time; two powerful chemicals have beenisolated, their structures have been determined, they have been synthesised,and their origins in the neglected class of mustard-oil glycosides ” have beenfairly clearly indicated.But there must, from the evidence, be other anti-thyroid factors in plants which do not contain mustard-oil glycosides. Hereis a little explored field.The plethora of steroids produced by animal tissues has led to extensivestudies on the mechanisms by which hydroxylation takes place in vivo.These studies received a great impetus from demands for cortisone and it isnoteworthy that certain moulds may be used to facilitate the synthesis ofthis clinically important substance because they possess the power of intro-ducing a hydroxyl group at exactly the right place in the perhydrocyclo-pentanophenanthrene system.Natural fatty acids have long been regarded by many as dull, difficultto deal with, and few in number.This Report should dispel such ideas.Chromatography, and improvements in the measurements of physicalcharacteristics and in analytical reactions, to say nothing of the dramaticdiscoveries centering around coenzyme A, have resulted in a new and growinginterest in the fatty acids and their natural relations. This section comple-ments the Report of 1953 and may introduce some to the natural acetylenicbond.Finally, a range of interesting oligosaccharides has been discovered inhuman milk through the nutritional “ fussiness ” of a Lactobacillus. Thiswork was made possible by the intimate collaboration of German carbo-hydrate chemists with microbiologists in the United States of America.D. J.B.2. L(+)-ERGOTHIONEINE.Structure and Synthesis.+ +) -Ergothionehe was first obtained by ex-traction of ergot by Tanret 1 in 1909. Since then it has been the subject ofl C. Tanret, J . Pharm. Chim., 1909, 30, 145; Compt. rend., 1909, 149, 222. Forpreparation from, and levels in, ergot, cf. N. W. Pirie, Biochem. J., 1933, 27, 202;G. Hunter, G. D. Molnar, and N. J. Wight, Canad. J . Res., 1949,27, El 226; G. Hunter,S. G. Fushtey, and D. W. Gee, ibid., p. 240286 BIOLOGICAL CHEMISTRY.periodic interest on account of its discovery in the blood and in other bio-logical situations in various species of animals. At the present time atten-tion is again being paid to this biologically bafing chemical.Its structure(1) is suggestive in view of the catalytic importance recently attributed toSH(3) (4)thiol-bearing cell-components and because of the transferring reactionsundergone by “ labile ” methyl groups carried by quaternary nitrogen atomsof certain metabolites.Ergothioneine was established as a derivative of histidine by Barger andEwins2 in 1911, after the isolation, also from ergot, of histamine (2) byBarger and Dale.3 In view of certain later observations the first two stepsin Barger and Ewins’s work are noted here : The compound, on treatmentwith concentrated (50%) aqueous potassium hydroxide is quantitativelytransformed into the yellow 2-mercaptourocanic acid (3) and trimethylamine.Dilute nitric acid oxidatively removes the sulphur atom from the last acid (3),to give @-4-glyoxalin ylacrylic acid and sulphuric acid.Mild acidic oxidisingagents quantitatively eliminate the thiol group, as sulphuric acid, fromergothioneine itself and from 2-mercaptohistidine : from ergothioneine (1)(by ferric chloride), hercyanine (4) is thus obtained; this substance has beenfound in the fungi Agavatus campestris and Boletus edulis.Barger and Ewins 2 pointed out that the thiol group in ergothioneine isquite different in character from that in cysteine. Not only is it stable toalkali, but also it is readily and quantitatively oxidised to sulphuric acidunder conditions which yield a sulphonic acid from cysteine. That thea-carbon system has the L-configuration arises from the synthesis, albeitaccompanied by some racemisation, through methylation of 2-ethyl-carbonylthio-~-histidine.5 It is unfortunate that this partially racemisedsynthetic ergothioneine has been erroneously described by a reviewer as“ in every respect identical with the natural material.”Analytical Methods.-The first, and most widely used, specific methodwas described by Hunter 7 in 1928, since when it has undergone modificationsonly with respect to concentration of the ergothioneine and elimination ofinterfering substances.It consists essentially in treating ergothioneine withG. Barger and A. J. Ewins, J., 1911, 99, 2336.G. Barger and H. Dale, J., 1910, 97, 2592.H. Heath, A. Lawson, and C. Rimington, J., 1951, 2215.6 Cf.also J. N. Ashley and C. R. Harington, J . , 1930, 2586; C. Tesar and D.Rittenberg, J . BioZ.,Fhem., 1947, 170, 35.6 K. Hofman, Imidazole and its Derivatives, Part I,” Interscience Publ., NewYork and London, 1953.G. Hunter, Biochenz. J . , 1928, 22, 4BELL : L( +)-ERGOTHIONEINE. 287diazotised sulphanilic acid and subsequently adding strong alkali, an intensered-purple colour being produced. It seems that this colour originates fromthe 2-mercaptourocanic acid derivative (cf. 3) and is not given by a numberof other 2-mercaptoglyoxalines examined by Lawson and his collabor-at0rs.*,8,~ So far as is known, 2-mercaptourocanic acid does not occurnaturally; if it does, it will be liable to be confused with ergothioneine in theHunter reaction.Hunter originally used tungstic acid for blood deproteinisation withsuccess.In 1949 he found lo that this reagent was not satisfactory andsuggested that there was some unknown difference between the originaland 1949 samples of tungstate. He has described a simple deproteinisationby boiling acidified diluted blood. In attempts to eliminate “ interferingsubstances ” which Hunter had noted, Lawson, Morley, and Woolf addedthe refinement of concentration of ergothioneine from Hunter’s blood filtrates(and from urine, etc.) by precipitation with potassium tetraiodobismuthate(Kraut’s, or Dragendorff ’s, reagent) or iodobismuthous acid.Baldridge and Lewis loa have applied the Hunter reaction to the deter-mination of ergothioneine in presence of histidine (which is also chromogenicwith the diazo-reagent although the colour produced is different) and uricacid.Touster l1 proposed a determination based on the ease of oxidation, byaqueous bromine, of the 2-mercapto-group of ergothioneine, sulphuric acidbeing formed (cf. ref.2). This method has been used by Mann and Leone l2in parallel with that of Hunter, and also by Heath et aZ.26 in experimentsusing 35S-labelled compounds (see below). This oxidative method may wellalso produce sulphuric acid from mercaptoglyoxalines other than ergo-thioneine. Melville and Horner l3 have devised a modified extractionprocedure for blood and other animal tissues which is sensitive to 10 pg. ofergothioneine per ml. of blood ; in it glutathione and dithionite are added tolaked, diluted erythrocytes, and protein is precipitated by trichloroacetic acidexcess of which, along with other ions, is removed by chloroform extractionand treatment with resins.Using chromatographic concentration on analumina column, Melville, Horner, and Lubschez l4 have detected andmeasured ergothioneine in animal tissues other than blood. Lawson,Morley, and Woolf and Mann and Leone l2 have described detection ofergothioneine and related compounds by paper chromatography.Occurrence.-Sixteen years after the discovery of ergothioneine in ergot,Hunter et aZ.15 reported that satisfactory uric acid determinations could notbe made on Folin-Wu filtrates of whole blood with “ direct ” addition ofBenedict’s reagent.16 They isolated from pig erythrocytes a crystallinesubstance giving the uric acid reaction; because they were unable to detect* H.Heath, A. Lawson, and C. Rimington, J . , 1951, 2218.!a A. Lawson, H. V. Morley, and L. I. Woolf, Biochem. J., 1960, 47, 573.lo G. Hunter, Canad. J . Res., 1949, 27, E, 230; Biochem. J., 1951, 48, 265.loo R. C. Baldridge and H. B. Lewis, J . Biol. Chem., 1953, 202, 169.l1 0. Touster, ibid., 1951, 188, 371.l2 T. Mann and E. Leone, Biochem. J . , 1953, 53, 140.l3 D. B. Melville and W. H. Horner, J . Biol. Chem., 1953, 202, 187.l4 D. B. Melville, W. H. Horner, and R. Lubschez, ibid., 1964, 206, 231.l6 F. M. R. Bulmer, B. A. Eagles, and G . Hunter, ibid., 1925, 65, 17 ; G. Hunter andl6 S. R. Benedict, ibid., 1922, 51, 187.B. A.Eagles, ibid., p. 623288 BIOLOGICAL CHEMISTRY.labile sulphur after boiling it with concentrated alkali they arrived at theempirical formula C,HI1O,N,. Benedict, Newton, and Behre 1 7 likewiseisolated a similar substance but, using metallic-sodium fusion, found that it,in fact, did contain sulphur. Both groups of workers l8 in 1927 showed itto be L(+)-ergothioneine (sometimes, in U.S.A., called " thioneine "). In1930 Gulland and Peters l9 isolated the substance from pigeon blood.In blood, ergothioneine is confined to the erythrocytes. Variousmeasurements have been made on different animals; in some, e.g., the ox,unknown blood constituents interfere with the diazo-reaction and theapparent ergothioneine level is low.? As noted above, Lawson et d9 andMelville et aZ.139 l4 have evolved methods to eliminate this " anti-diazo "-effect.Table I gives some findings.TABLE 1. Ergothioneine in mg./lOO ml. of whole blood.Man ..................Pig ..................ox ..................Rabbit.. .............Guinea pig .........Rat ..................Cat ..................Fowl ...............Chick ...............Hunter, 71928,Toronto,Canada1.2-4-02-26<11 4 . 51-4-1-5-10 -Hunter,lo1951, 1951,Edmonton, London,Canada U.K.2.5-9.5 1.8-4.46.0-9.3 3.3-5.3 - - - - - -2.9-8.8 1.3-3.1 - - - -I -* Germ-free chick.Lawson Melvilleet aZ.,B andLondon, Horner l3U.K.2.0-3.1 -4.3-4.6 -2.2 -4.5-5.0 -<04-2.2 -- -- -- -- 4 & 6 *The recent application of column chromatography to tissue extracts byMelville, Horner, and Lubschez l4 has shown that, in the rat a t least, ergo-thioneine is not confined to the erythrocytes but can be detected by theHunter reaction, as an intracellular component, in various tissues as shownin Table 2.TABLE 2. Ergothioneine (Ung.llO0 g.of fresh tissue) in the 7at.14Skeletal Intes- SeminalLiver Kidney Heart Lung Spleen muscle tine Stomach vesicles13.3 4.3 1.5 1.5 1.1 0.7 0.6 0.4 0-2Brain, testes and plasma contained no detectable amounts.In all these animal tissues ergothioneine occurs only as an intracellularconstituent. Boar seminal-vesicular secretion has been shown by Mannand Leone 12 to be particularly rich in ergothioneine; it is present thereextracellularly in amounts between -30 and 250 mg./100 ml.(average-80 mg.). Boar blood contained (average of three animals) -4.5 mg./100ml., while pig corpora Zutea, adrenals, thyroid, eye vitreous fluid, and foetal1' S. R. Benedict, E. B. Newton, and J. A. Behre, J . Bid. Chem., 1926, 67, 267.l8 B. A. Eagles and T. B. Johnson, J . Amer. Chem. SOC., 1927, 49, 675; E. B.Newton, S. R. Benedict, and H. D. Dakin, J . BioZ. Chem., 1927, 72, 367; G. Hunterand B. A. Eagles, ibid., p. 123.19 J. M. Gulland and R. A. Peters, Biochsm. J., 1930, 24, 91. For extraction fromblood, cf. S. W. Williamson and N. U. Meldrum, ibid., 1932, 26, 815; G. Hunter, G. D.Molnar, and N. J. Wight, Canad. J. Res., 1947, 27, E, 226BELL : L( +)-ERGOTHIONEINE. 289fluids showed no detectable amounts.In ram and human semen onlytraces of ergothioneine, if any, are present.Origin of Ergothionehe in Animal Tissues.-The origin of ergothioneinein the animal is no less obscure than is the reason for its presence in thefungal product, ergot.20 Some recent experiments have yielded apparentlyconflicting results. It is not yet known whether the ergothioneine found inanimal tissues is an essential metabolite of truly endogenous origin or whetherit is elaborated from a precursor in the food. In 1928 Eagles and Vars 21suggested that, in pigs, diet had a significant effect on the blood level whichcould be appreciably raised from low values by addition to a basal diet ofcertain proteins and of, more specifically, maize (US., corn).In 1951Hunter,10 besides commenting on environmental differences in blood ergo-thioneine between groups both of pigs and of men (cf. Table 2), repeated themaize experiment without finding support for Eagles and Vars’s hypothesis.None the less, he found that methanolic extracts of maize contain at leastthree different bodies which give colour reactions, which were atypical ofthe mercaptoglyoxaline system. These, however, he did not consider to benecessarily ergothioneine precursors ; methanol-extracted maize, fed to rats,was equally efficient as the unextracted cereal in maintaining the ergo-thioneine levels within identical ranges.About the same time, Spicer, Wooley, and Kessler 22 showed that theerythrocytes of rabbits fed on a purified diet with casein as sole protein werealmost devoid of ergothioneine.Melville et aZ.14 found similar results withrats fed on casein as sole protein ; in these animals not only were the erythro-cytes affected, but the ergothioneines in other tissues fell to vanishing point,i.e., 0.05 mg.1100 g. of fresh tissue (cf. Table 2). Melville et aZ.24 found that,in the rat, zein, like casein, did not provide an ergothioneine precursor. Onthe other hand, maize could do so; an aqueous acetone extract of maize waslikewise effective. A dietary concentration of as low as 1 in 10,000 parts wassufficient to lead to an accumulation of ergothioneine in the rat erythrocyte.Other workers 23 have also noted the inefficiency of casein in maintainingblood ergothioneine in rabbits and rats, but when rabbits were fed on oats 25and cabbage a “-fold increase was observed after 8-10 weeks.Inwhite rats fed on ground oats, or maize or casein for several weeks, theerythrocytes contained less than 1 mg./100 ml. ofThese casein experiments apparently show that the methionine residues,which bear nearly all the sulphur contained in the protein, are not availablefor ergothioneine synthesis. On the other hand, we have the results ofHeath et aZ.26 who fed a number of 35S derivatives to two adult boars;labelled sulphate, 2-mercaptohistidine, methionine, and ergothioneine wereseparately fed. Measurements of bromine-oxidisable sulphur 11 (afterremoval of inorganic and ester sulphate) were made on alcohol-precipitatedfiltrates of seminal plasma and urine; only p5S]methionine appeared to actte A.St. Garay, Nature, 1956, 177, 91.22 S. S. Spicer, J. G. Wooley, and V. Kessler, PYOC. SOC. Exp. Biol. Med., 1951,77, 418.23 R. G. Bartlett and U. D. Register, ibid., 1953, 83, 708.24 D. B. Melville, C. C. Otken, and V. Kovalenko, J . Biol. Chem., 1955, 216, 325.26 Cf. V. R. Potter and K. W. Franke, J . Nutrition, 1935, 9, 1 .2b R. C. Baldridge, Fed. Proc., 1954, 13, 178; see also ref. 10a.0s IT. Heath, C . Rimington, T. Glover, T. Mann, and E. Leone, Biochem. J., 1953,B. A. Eagles and H. M. Vars, J . Biol. Chem., 1928, 80, 615.64, 606.REP.-VOL. LII 290 BIOLOGICAL CHEMISTRY.as source of ergothioneine sulphur ; the labelled 2-mercaptohistidine wastotally eliminated in the urine.Heath 27 also administered 2-[35S]mercapto-histidine and [35S]ergothioneine to rats for 21 days and found that isotopefrom the latter only was incorporated into the erythrocytes, bone marrow,liver, and kidney, but not into the seminal vesicles. The mercaptohistidine(90%) was recovered unchanged in the urine; it therefore did not act as anergothioneine precursor (Lawson et aL9 found no ergothioneine in human orrat urine).Melville et aL2* fed ~-[~~S]methionine to an %weeks’ old boar, too youngto secrete vesicular fluid. Ergothioneine was isolated from the seminalvesicular tissue (49.5 mg./100 g. wet weight) and from the blood, but in thiscase no evidence for radioisotope incorporation was found. This does notseem to the Reporter an unreasonable finding since it may well be that theturnover of ergothioneine in the young, immature boar may be considerablyslower than it is in the sexually active adult.That the intestinal flora are not responsible for ergothioneine formationin the chick was shown by Melville and HornerI3 when the erythrocytelevels of ordinary and germ-free chicks were compared.The ergothioneinein the former was somewhat below the level of that in the germ-free animals.Suggested Functions of Ergothionehe.-In 1947 Lawson and Rimington 28concluded that ergothioneine had an anti-thyroid action, in rats, similar tothat of thiouracil; their claim was refuted, however, in the instances of ratsand man by Astwood and Stanley29 and of man and monkeys by Wilsonand M ~ G i n t y .~ ~Spicer et found that treatment of washed rabbit erythrocytes withsodium nitrite resulted in oxidation of the haemoglobin to methzmoglobinat a rate inversely proportional to the ergothioneine content. Moreover,added ergothioneine reversed the oxidation. The substance can thereforefunction as a reducing agent.Mann and Leone l2 have shown that ergothioneine can antagonise thiol-inactivators including Cu2+ and o-iodosobenzoate, and suggest, as a possiblefunction, the preservation of thiol groupings against dehydrogenation.In a brief communication Heath and Toennies 31 report that ergothioneinedisulphide is formed slowly by the action of oxygen in 5~-hydrochloric acidor very rapidly by one equivalent of hydrogen peroxide.The reaction canbe followed either spectrophotometrically or by paper chromatography.The disulphide can be rapidly reduced by excess of cysteine or reducedglutathione. Ergothioneine disulphide reacts with cysteine, to form first amixed disulphide ; this with excess of cysteine gives ergothioneine andcyst ine.It is not known if the disulphides containing ergothioneine give theHunter colour test. They should certainly give some colour when coupledwith diazotised sulphanilic acid. The Reporter considers that the followingare possible : (a) that oxidised ergothioneine may occur naturally and bemissed if it fails to give the Hunter test; (b) that oxidised ergothioneine27 H. Heath, Biochem, J., 1953, 54, 689.28 A. Lawson and C. Rimington, Lancet, 1947, 252, 586.20 E.B. Astwood and M. N. Stanley, ibid., 1947, 253, 905.30 M. L. Wilson and D. A. McGinty, Amer. J . Physiol., 1949, 156, 377.31 H. Heath and G. Toennies, 3me Congrb internat. Biochimie, Resume des com-munications, 1955, p. 42-MERCAPTO-A2-1 3-OXAZOLINES (2-THIO-1 : 3-OXAZOLIDINES). 291niay occur in plants and act as the precursor of (reduced) ergothioneine inanimals.Added in Proof.-Melville and Eich 32 have isolated ergothioneine from‘‘ Quaker ” oats. D. J. B. The optical rotation was not recorded.3. 2-MERCAPTO-As-1: 3-OXAZOLINES (Z-THIO-1: 3-OXAZOLIDINES)* ASANTI-THYROID SUBSTANCES FROM VEGETABLE SOURCES.The Discovery of ‘‘ Plant Goitr0gens.”-Following the original observation(U.S.A.) by Chesney, Clawson, and Webster,l a number of investigators havefound that rabbits and rats fed on diets containing a large proportion ofcabbage (Brassica oleracea) developed enlarged thyroid gland^.^-^ Wintercabbage seemed to be more potent than plants grown in summer. Tadpoles(Rana pipiens), fed with cabbage, attained maturity more quickly and hadlarger thyroids than controls fed with spinach.5aOther Brassica t species and members of other orders can provide goitro-genic factors : Kohlrabi leaves (Brassica oZeracea var.gongyZoides),6 rape orcolza (B. rapa oleifera), wild radish (Raphanus raphanistrum) ,7 Brassica seeds(rape, swede, soft and hard turnip),8 turnip roots,s Legumhosz seeds(soya and other beans, peas, lentils), ground nuts (Arachis hy$ogea),lo andalpine chestnuts.11 On the other hand, New Zealand winter cabbage 99 l2was poor in goitrogen.Rape seed oil meal, widely used in animal feeding, hasbeen shown to cause thyroid enlargement in poultry 13 and thyroid, liver,and kidney enlargement in pigs.14 Soya bean also gives goitre in chicks.15A number of researches point to the pituitary gland as the site of attackof the goitrogen, and not the thyroid itself. Chesney, Clawson, and Webster52 D. B. Melville and S. Eich, J . Biol. Chew., 1956, 218, 647.A. M. Chesney, T. A. Clawson, and B. Webster, Bull. Johns Hopkins Hosp., 1928,R. McCarrison, G. Sankaran, and K. B. Madhava, Indian J . Med. Res., 1933, 20,F. Blum, Endokrinologie, 1937,19,19; Schweiz. med. Wochenschr., 1941,71,1612;G. C. Bianchi, Beitr.pathol. Anat. allgem. Pathol., 1933, 90, 539.43, 61: B. Webster, T. A. Clawson, and A. 35. Chesney, ibid., 1928, 43, 278.23; D. Marine, E. J. Baumann, and A. Cipra, Proc. SOC. Exp. Biol., 1929, 26, 822.1943, 73, 1046; B. Webster, Endocrinology, 1932, 16, 617.6 N. D. Judina, J . Med., Ukraine, 1939, 9, 801.J. R. Borland, J . Exp. Zool., 1943, 94, 115.6 0. Stiner, Mitt. ges. Lebensmitteluntersuh. Hyg., 1933, 24, 1.N. D. Judina, J . Med., Ukraine, 1940,10, 71. * ( a ) T. H. Kennedy and H. D. Purves, Brit. J . Exp. Path., 1941,22,241; ( b ) W. E.Griesbach, T. H. Kennedy, and H. D. Purves, ibid., p. 249; (c) E. Maschmann, Natur-wiss., 1942, 30, 261.lo F. Blum, Schweiz. med. Wochenschr., 1942, 72, 1301, 1329; R. McCarrison, IndianJ . Med. Res., 1934, 21, 179.l1 B.S. Barton, “ A Memoir Concerning the Disease of Goitre as it prevails inDifferent Parts of North America,” Way and Groff, Philadelphia, 1800.12 C. E. Hercus and H. A. A. Aitken, J . Hyg., 1933, 33, 6 5 ; cf. I. T. Zwecker, Amer.J . Path., 1932, 8, 235.l3 R. M. Blakely and R. W. Anderson, Sci. Agric., 1948,28,393 ; C. W. Turner, PoultvySci., 1946, 25, 186; 1948, 27, 118; C. E. Allen and D. S. Dow, Sci. Agric,. 1952,82,403.l4 S . Nordenfeldt, N. Gellerstadt, and S. Falkmer, Acta Pathol. Mzcrobiol. Scand.,1954, 35, 217.l5 G. R. Sharpless and E. M. Hopson, Endocrinology, 1940, 27, 129; H. S. Wilgus,F. X. Gassner, A. R. Patton, and R. G. Gustavson, J . Nutrition, 1941, 22, 34. * The nomenclature of these substances in the literature shows a number of vari-ations from the customary rules.Th,: nomenclature of these plants is confused ; cf. J.Percival, ” AgriculturalBotany, Duckworth, London, 1945.C. E. Hercus and H. D. Purves, J . Hyg., 1936, 36, 182292 BIOLOGICAL CHEMISTRY.showed that the enlarged thyroid glands of their rabbits were due to ahyperplasia of the epithelial elements of the gland and not to an increase in“ colloid ” ; the latter tissue contains the active secretion of the thyroid.At the same time the animals suffered an enlargement of the suprarenalglands which paralleled the “ goitre.” Similar enlargements were found inrats * along with delay in development of immature ovaries and histologicalchanges in the pituitary. The latter were also seen by Sharpless and Hop-son l5 in rats fed with soya beans, and by Griesbach l6 in rats fed with rapeseed.Griesbach, Kennedy, and Purves 8b found that, in rats, hyperplasiaof the thyroid, previously induced by Brassica seeds, rapidly regressed afterremoval of the pituitary gland and did not return despite continued feedingof the seeds. Colloid formation and hormone storage took place afterhypophysectomy ; this was not prevented by feeding with goitrogenicvegetables. Purves,17 Whitehead,18 and Griesbach and Purves l9 concludedthat the goitrogenic factor acted by interfering with the synthesis of thyroxineand that the thyroid hyperplasia was due to increased production of thyro-tropic hormone by the pituitary gland.It seems reasonable to assume with Salter 2o “ that all diets are at leastmildly goitrogenic ” and that a balance should exist between the amounts ofavailable iodine and of goitrogens in the food.Webster and Chesneyalfound that extra dietary iodine protected rabbits against ‘‘ cabbage goitre,”and this was confirmed by Bianchi? Blum (1941, 1943),3 and Purves.17Blum22 has shown that iodine fertilisation of cabbage, linseed, and soyaplants apparently nullifies their goitrogenic properties.The agronomic significance of goitrogens in rape seed 23 has been reviewedby J. M. Bell.=Antithyroid Chemicals from Plants.-Klein and Farkass 25 found evidencefor the presence of thiourea in Laburnum; no confimatory work is knownto the Reporter. Thiourea is an antithyroid substance.26Thiocyanates, as the I‘ mustard oil gIycosides,” have long been known asconstituents of the Crucifera, to which order the Brassica genus belongs.The thiocyanate ion has antithyroid activity ; 27 it is a normal constituent ofthe saliva of many animals and it is metabolised by thyroid tissue, the sulphurbecoming bound in organic combination.This binding is inhibited by pre-treatment of the animal with another antithyroid substance, 2-thiouracil.It has been suggested that the thiocyanate ion may act by inhibiting com-petitively the enzyme which oxidises iodide ion to elementary iodine.2816 W. Griesbach, Brit. J . Exp. Path., 1941, 22, 246.17 H. D. Purves, ibid., 1943, 24, 171.18 V. I . E. Whitehead, ibid., p. 192.19 W. E. Griesbach and H. D. Purves, ibid., p.174.20 W. T. Salter, “ The Hormones,” Academic Press, New York, 1953, VoI. 11, p. 325.21 B. Webster and A. M. Chesney, Amer. J . Path., 1930, 6, 275.Sa F. Blum, Sckweiz. wed. Wochenschr., 1950, 80, 142.23 J. Matet, R. Montagne, and A. Buchy, Oleangheux, 1949, 303, 145.24 J. M. Bell, Canad. J. Agric. Sci., 1955, 35, 242.25 G. Klein and E. Farkass, osterr. botan. Z . , 1930, 79, 107.26 E. B. Astwood and M. M. Stanley, Trans. Amer. Assoc. Study Goiter, 1947, 216;M. M. Stanley and E. B. Astwood, Endocrinology, 1947, 41, 66.87 Cf. M. H. Wald, H. A. Lindberg, and M. H. Barker, J . Amer. Med. Assoc., 1939,112, 1120; R. W. Rawson, S. Hertz, and J. H. Means, Ann. Internal Med., 1943, 19,829; R. W. Robinson and J. P. O’Hare, New Engl. J .Med., 1939, 221, 964.28 J. L. Wood and E. F. Williams, J . Biol. Chem., 1949, 137, 592-MERCAPTO-A2-1 : 3-OXAZOLINES (2-THIO-1 : 3-OXAZOLIDINES) . 293Mustard oils, tested on rats, could not be shown to have any activity towardsthe thyroid.In 1938, Hopkins 29 isolated, by chloroform extraction of a water extractof seeds of hare's ear mustard (Coringia orientalis), a crystalline substance,C,H,ONS, m. p. 108.5". This was identified as 2-mercapto-5 : 5-dimethyl-A2-1 : 3-oxazoline (2a), which had just previously been synthesised by Brusonand Easte~,~* by treating l-amino-2-methylpropan-2-ol (1) with carbondisulphide and alkali. It seems to the Reporter that the substance may wellalso exist in the thione form (2b) as 5 : 5-dimethyl-2-thio-1 : 3-oxazolidine.This substance (2) was subsequently 31 shown to have antithyroid activityabout one-fifth of that of 2-thiouracil (3a) (2-mercaptouracil, 3b).H,C-CMe, ~ C S L Hs7-FMe2 ~ H2CrM42 I I I IHN\ PI F H,N OH -"" "\'c/oIn 1948 Greer and Astwood32 fed 61 different foodstuffs to humanvolunteers and assessed any antithyroid action by measuring the diminutionof 131 I-uptake by their thyroids.Of the foods tested the Swedish turnip(Brassica napobrassica) (U.S.A., rutabaga) was the most active. Materialsfrom the following plant orders were also markedly potent : Chenopodiacea,Compositz, Cruciferae, Cupuli ferae, Juglandacez, Leguminosz, RosaceE,and Umbelliferze. In addition, cow's milk, beef liver, and oysters showedsome activity.The active principle of swedes could be extracted into ether from anaqueous extract of the fresh plants and was contained in the water-solublefraction of the evaporated ether phase.In some instances, e.g., swedes andpears, the antithyroid activity is lost on cooking; in others, e.g., peas andground-nuts the antithyroid activity is then retained.33 In 1949, Astwood,Greer, and Ettlinger isolated an active material from aqueous extracts offresh swedes. These extracts gave a pink or purple colour with the Grotenitroprusside reagent 35 and a strong ultraviolet absorption maximum at240 mp ; both these characteristics closely paralleled the antithyroid activity.The active substance was obtained crystalline by high-vacuum distillation,followed by chromatography on alumina; it had m.p. 50", [ a ] ~ -70" inMeOH, and the elementary composition C,H,ONS, No compound of thisformula and having the above properties had been previously described.The structure (4a), (-)-2-thio-5-vinyl-l : 3-oxazolidine, was ascribed to itfrom chemical and physical evidence. It should be noted that, like its6 : 6-dimethyl analogue (2), it may exist also as (4b) 2-mercapto-5-vinyl-A2-oxazoline. The ultraviolet spectrum of the 5-vinyl compound is virtuallyidentical 54 with that of its 5 : 5-dimethyl analogue. (Astwood, Greer, andEttlingera state that the spectrum of the latter given by Hopkins29 isXI C. Y. Hopkins, Canad. J. Res., 1939, 16, B, 341.80 H. A. Bruson and J . W. Eastes, J. Amer. Chem. SOC, 1937, 59, 2011.81 E. B.Astwood, A. Bissel, and A. M. Hughes, Endocrinology, 1945, 37, 456.8% M. A. Greer and E. B. Astwood, ibid., 1948, 43, 105.88 M. A. Greer, M. G. Ettlinger, and W. B. Astwood, J. Clin. Endocrinol., 1949, 9,84 E. B. Astwood, M. A. Greer, and M. G. Ettlinger, J. Biol. Chem., 1949, 181, 121.88 I. W. Grote, ibid., 1931, 93, 25; B. H. Chase and J . Walker, J., 1955, 4443.1069294 BIOLOGICAL CHEMISTRY.incorrect.) It seems to the Reporter that it has not been finally settledwhether these two compounds, when crystalline, exist as thiols (2a and 4b)H HH @C 0 HC"'C 0 H7C-C H. c H: cH, H 2C -CH* C H: C H,I ! I I A ' 'Qn i SH(3 0 ) (3 6) (4 0) (46)HN\ /NH N + / J H H N , p - ior thiones (2b and 4a). It is to be regretted that (-)-2-thio-5-vinyl-l : 3-oxazolidine is now appearing in the literature with the designation " L "since no evidence of the configuration of the asymmetric centre at hasso far been presented (the error is improper use of L for the I originally usedto indicate laevorotation).(-)-2-Thio-5-vinyl-l : 3-oxazolidine was synthesised by Ettli~~ger.~G3 : 4-Epoxybut-1-ene (5), on ammonolysis, gave 37 a mixture of l-amino-but-3-en-2-01 (6) and 2-aminobut-3-en-1-01 which were separated by meansof their hydrogen oxalates. The former, on treatment with carbon disulphideand alkali in 45% dioxan,3O yielded the racemic compound (an or b) whichwas resolved, to afford its (-)-enantiomorph, by (+)-a-bromocamphor-x-sulphonic acid.This synthesis has been improved by Raciszewski et aZ.38who have also recorded analyses for rape seed meal.- (44 H zC,-,CH.CH:CHa NHJ_ H z ~ - ~ . ~ ~ : ~ ~ z CszI IHaN OH 0(5) ( 6 )Astwood et aZ.,34 using the absorption maximum at 240 mp, assayed anumber of Brassica species and obtained the results in the annexed Table;they assumed the absorbing material to be the thione (4a). No such absorp-Material (g./kg.) absorbing at 240 mp :Plant giving extract range meanSwede ....................................... 0.8-8.6 2.5Turnip .................................... 0.3-2.5 1.0Cabbage .................................... 0.24.7 1.5Rape ....................................... 1.8-2.1 1.9Brussels sprouts ........................ 0.5-0.8 0.7Kale ....................................... 0.9-6.3 4.4Broccoli .................................... 1.6Kohlrabi ....................................0.7-1.4 1.1Cauliflower & mustard .................. - 0tion was found in plant extracts from Raphanus (radish), Lobularia,Matthiola, Iberis, Nasturtium, Lepidum, Avabis, Cheiranthus, and Lunaria.The possibility that acetylenic and ethylenic constituents (cf. section onNatural Long-chain Fatty Acids) of plants might have an antithyroidaction through their capacity to bind iodine should not be overlooked.The natural occurrence of nitriles is another possibility since some nitrilesare known to be goitrogenic.Origin of Plant Heterocyclic Goitrogens.-It seems that neither compound(2) nor compound (4) exists as such in the plant's tissues. On the other341 M.G. Ettlinger, J . Amer. Chem. SOC., 1950, 72, 4793.37 R. G. Kadesah, i b i d . , 1946, 88, 41.38 2. M. Raciszeweski, E. Y. Spencer, and L. W.Trevoy, Canad. J . Tech., 1955,33,129~-MERCAPTO-A~-~ : 3-OXAZOLINES (2-THIO-1 : 3-OXAZOLIDINES) . 295hand, plants, especially members of the Cruciferze, are known to contain" mustard oil glycosides " (" thioglycosides "),39 which are isothiocyanatederivatives of the general structure (7). The mustard oils apparently donot exist free in the plant's tissues, but arise by enzymic breakdown of theglycosides. R is usually ethylenic or arylalkyl. E.g., compounds areknown in which R is ally1 and crotonyl, and a butenyl isothiocyanate was firstobtained by Sjollema40 in 1901 who suggested that it was the but-3-enylderivative.Ter Meulen 41 proposed the name '' gluconapin " for the hypo-thetical parent glycoside but did not obtain the substance in a state ofpurity. " Gluconapin " 26 is frequently met in literature relating to mustardoils, but, as far as the Reporter can find, the substance has never been isolated.Sjollema's isothiocyanate is also referred to as a " crotonyl " d e r i ~ a t i v e , ~ ~a name which would ordinarily be applied to the but-2-enyl compound.The inference by J. M. Bellx that Matet, Montagne, and Buchy26 haveisolated " gluconapin " from rape seed is incorrect. It has therefore beensuggested that the 2-thio-1 : 3-oxazolidines (or 2-mercapto-A2-1 : 3-oxazol-ines) might originate by cyclisation of alkenyl isothiocyanates liberated onhydrolysis of the parent glycosides.hop kin^,^^ assuming the existence of a2-methylallyl isothiocyanate glycoside, giving the mustard oil (8), hassuggested the annexed mechanism for the formation of 2-mercapto-5 : 5-(7) (8)dim et hyl- A2- 1 : 3-oxazoline. However, since ( + ) -sec. -but yl isot hiocyanat ehas been obtained from plant ~ o u r c e s , ~ ~ ~ ~ ~ this substance might form theprecursor of (2a or b) by oxidative ring-closure (see below). Liebermann(personal communication to Pitt-Rivers) 44 has suggested an analogous,but oxidative, ring closure of but-3-enyl isothiocyanate (9) to (-)-2-thio-5-vinyl-1 : 3-oxazolidine. This mechanism produces an asymmetric centre atSince the chemical mechanisms in biological systems frequently followpaths quite different from those of classical organic chemistry there is afairly strong possibility that the above suggestions may prove to be invalid.Synthetical Oxazoline Derivatives of Monosaccharides.-It will be ofinterest if the 2-mercapto-oxazoline derivatives of sugars 45 have anti-thyroid activity, since their solubilities in oily tissues should be much lessthan those of the compounds (2) and (4).The sulphur atom in these mono-saccharides, and presumably also in the thio-oxazolines (2) and (4), isremoved by mild ~ x i d a t i o n . ~ ~it therefore appears to require an enzyme to carry it out.D. J. B.39 Cf. A. L. Raymond, Adv. Carbohydrate Chem.. 1945,l. 129.40 B. Sjollema, Rec. Trav. chim., 1901, 20, 237.4 1 H.ter Meulen, ibid.. 1905, 24, 444.42 Cf. E. Andre and M. Kogan-Charles, Comfit. rend., 1944, 218, 1002; 1946, 222,43 W. Bottomley and D. E. White, Roy. Austral. Chem. Inst. J . Proc., 1950, 17, 31.44 R. Pitt-Rivers, Physiol. Rev., 1950, 30, 194.4L J. C. P. Schwarz, J., 1954, 2644.4 8 G. ZemplCn, A. Cerecs, and M. Rados, Ber., 1936, 60, 748.201 ; E. Andre and P. Delaveau, ibid., 1950, 231, 872; cf. refs. 26, 32296 BIOLOGICAL CHEMISTRY.4. NATURAL LONG-CHAIN FATTY ACIDS: SATURATED AND UNSATURATED.Though aspects of the chemistry of natural long-chain fatty acids arereferred to annually in the “ Organic Chemistry ” section of these Reports,and fatty-acid metabolism in animal tissues was reviewed two years ago,lthe topic as a whole has not been treated in these Reports for many years.While attention is focused on progress during the past year, it has beennecessary to make many references to earlier work, particularly that of thepreceding five years.Progress towards a more precise knowledge of complexlipids depends on building a sound foundation of chemical information oncomponent fatty acids and on the perfection of rapid and accurate methodsfor separation, identification, and estimation. The present report concen-trates particularly on these aspects and includes reference to some of themost recent papers on the metabolism and function of long-chain fatty acids.Recent Literature.-Three volumes of the series ‘‘ Progress in theChemistry of Fats and Other Lipids ” and a second volume of Deuel’s newwork3 are now to hand.Vegetable oils and fats have been dealt withunder a biological clas~ification.~ Meara discusses fats and other lipids ;a small but admirable volume by Lovern is available, as is Piskur’s compre-hensive annual review of the literature on fats.’ Progress in fatty acidchemistry was reviewed by Hilditch in 1953. Hutt proposes a classifica-tion scheme for lipids.General Methods and Separation Techniques.-Fractional distillation ofesters lo and low-temperature crystallisation l1 continue to be’much usedas analytical and preparative tools, and useful information on fatty acidsolubilities at low temperature is available. l2 Urea complexes for segre-gation, and protection from oxidation, of fatty acids and glycerides havebeen reviewed l3 and are widely emp10yed.l~ Fractionation of fatty acidcyclohexyl esters as their thiourea complexes is feasible.15 Adducts of1 4nn.Reports, 1953, 50, 301.2 Progress in the Chemistry of Fats and Other Lipids,” Pergamon Press, London,a H. J. Deuel, “ The Lipids. Their Chemistry and Biochemistry,” Interscience Publ.4 E. W. Eckey,6 M. L. Meara i:“‘ Modern Methods of Plant Analysis,” Springer, Berlin, 1954.6 J. A. Lovern,7 M. M. Piskur, J . Amer. Oil Chemists’ SOG., 1955, 32, 255, 319.8 T. P. Hilditch, Awn. Rev. Biochem., 1953, 22, 125.s H. H. Hutt, Nature, 1955, 175, 303.10 K. E. Murray, ref. 2, Vol. 111, p. 243; E. W. Jones and M. A. Maclean, J . Amer.11 J. B. Brown and D. K. Kolb, ref. 2, Vol. 111, p. 57.1.2 D. K.Kolb and J. €3. Brown, J . Amer. Oil Chemists’ SOC., 1955, 52, 357.l3 H. Schlenk, ref. 2, Vol. 11, p. 243.14 E.g.. J. S. Heckles and L. H. Dunlap, J . Amer. Oil Chemists’ SOG., 1955, 32, 224;0. E. McElroy, W. Jordan, J. McLaughlin, and M. E. Freeman, ibid., p. 286; C. Domart,D. T. Miyauchi, and W. N. Sumenvell. ibid., p. 481 ; Y. D. Karkhanis and N. G. Magar,ibid., p. 492; W. F. Shipe, J . Assoc. OBc. Agvzc: Chemzsts, 1955,38, 156; J. M. Martinez-Moreno, F. Mazuelos, and C. Janer, Fette u. Sezfen, 1955, 57, 652; T. N. Mehta, C. V. N.Rao, B. Y. Rao, and K. S. Rao, J . Indian Chem. SOC., I n d . News, 1954,17, 177; T. N.Mehta, B. Y . Rao, G. S. Prabhu, and G. S . Sihota, ibid., p. 182; T. N. Mehta, B. Y.Rao, and S. M. Abhyankar, ibid., 1955,18, 1 ; K.D. Pathak, and J. S. Aggarwal, J . Sci.I n d . Res., India, 1955, 14, B, 229; K. T. Achaya, B. P. Baliga, S. A. Saletore, andS. H. Zaheer, ibid., p. 348; R. Rigamonti and W. Riccio, Gazzetta, 1955, 85, 521.16 H. Schlenk, J. A. Tillotson, and B. G. Lamp, J . Amer. Chem. SOG., 1955, 77,5437.Vol. I, 1952; Vol. 11, 1954; Vol. 111, 1955.Inc., New York, Vol;,I, 1951 ; Vol. 11, 1955.Vegetable Fats and Oils,” Reinhold, New York, 1954.The Chemistry of Lipids of Biochemical Significance,” Methuen,London, 1954.Oil Chemists’ SOG., 1954, 31, 473CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS. 297linoleic acid, linolenic acid, or methyl linolenate formed with “ a-dextrin ”(cyclohexa-amylose), “ p-dextrin ” (cyctohepta-amylose) , or deoxycholicacid are resistant to oxidation l6 and less toxic than urea adducts in feedingexperiments.Protection is due either to the crystal lattice’s offering abarrier to free penetration of oxygen, or to its preventing operation of aradical-chain oxidation.Separations of fatty acids 1’ and related substances by countercurrentextraction were reviewed 18 in 1954 and there is present interest in glyceride~eparati0ns.l~ Chromatography of fatty acids has presented difficulties,but recent progress has been made by methods involving columns or papersheets; column methods may be considered as (a) elution, (b) displacement,or (c) partition chromatography. Some work has been done on frontalanalysis.20 Elution methods 21 applied to preparative separations of fattyacids or esters are of limited value : the coloured 2 : 4-dinitrophenylsulphenylchloride addition products of unsaturated acids can be chromatographed onmagnesium sulphate.22 Methods for displacement and carrier chromato-graphy have been perfected by H ~ l m a n , ~ ~ but, though powerful and welltested, they require expensive ancillary equipment.Nonnal-phase partitionsystems have had marked success (cf. Nijkamp 24), though perhaps the mostuseful at the present time are the reversed-phase partition systems. Anumber of these are based on fundamental work by Howard and Martin 25who use paraffin-loaded non-wetting kieselguhr as the stationary phase, andalcohol-water or acetone-water mixtures as the mobile phase. Rubber 26or Polythene powder 27 may be used as stationary phase (Polythene is usefulfor long-chain acids) : hydroxy-acids are best chromatographed on non-wetting kieselguhr impregnated with castor Reversed-phase partitionmay be employed for saturated even-chain acids from C, to CZ4; the be-haviour of a wide variety of unsaturated acids has also been examined.29This technique is useful for ascertaining the selectivity of hydrogenationduring preparation of cis-long-chain fatty acids, as the acetylenic, ethenoid,and saturated acids are usually separable.30 Combined with hydrogen-ation31 and controlled the method is valuable for analysis ofl6 H.Schlenk, D. M. Sand, and J. A. Tillotson, J . Amer. Chem. SOL, 1955,77,3587.1’ E. H. Ahrens and L. C . Craig, J . Biol. Chem., 1952, 195, 299.18 H.J. Dutton, ref. 2, Vol. 11, p. 292.lQ E. S. Perry and G. Y . Brokaw, J . Amer. Oil Chemists’ SOC., 1955, 39, 191; J. J.Taber, Diss. Abs., 1955, 15, 727.20 Ref. 2, Vol. I, p. 110.21 H. G. Cassidy, J . Amer. Chem. SOC., 1941, 83, 2735; R. W. Riemenschneider,S. F. Herb, and P. L. Nicols, J . Amer. Oil Chemists’ SOC., 1949, 26, 371; H. J. Duttonand C. L. Reinhold, ibid., 1948, 25, 117, 120; M. M. Graff and E. L. Skau, Ind. Eng.Chem. Analyt., 1943, 15, 340.22 R. 0. Simmons and F. W. Quackenbush, J . Amer. Oil Chemists’ Soc., 1953,30,614.as R. T. Holman, ref. 2, Vol. I, p. 104.2c H. J. Nijkamp, Nature, 1953, 172, 1102; Analyt. Chim. A d a , 1954, 10, 448.25 G. A. Howard and A. J. P. Martin, Biochem. J., 1950, 48, 532.27 T. Green, F. 0.Howitt, and R. P. Preston, Chem. and Ind., 1955, 591.28 P. Savary and P. Desnuelle, Bull. SOL chirn. France, 1953, 939.aQ W. M. L. Crombie, R. Comber, and S. G. Boatman, Natare, 1954, 174, 181;Biochem. J.. 1955. 59, 309.so L. Crombie, J., 1955, 3510.s1 G. Popjak and A. Tietz, Biochem. J., 1954, 56, 46; M. H. Silk and H. H. Hahn,ibid., 1954, 67, 677; J. Boldingh in “ Biochemical Problems of Lipids,’’ Internat.Coll., Brussels, 1953.J. A. Boldingh, Experientia, 1948, 4, 270; Rec. Trav. chim., 1950, 69, 247TABLE 1. Column chromatography.Methoddetection Ref. Class22 AStationary phaseA1,0, (40)-" Celite " (7)MgSO,SiO,-MeO*[CHJ ,*OH-H,O (9 : 1)Si0,-furfuryl alcohol-2-aminopyridineSi0,-MeOHCellulose powder-hypophaseKieselguhr-liq. paraffinMobile phaseC,H6-Etz0 (95 : 5 )n-C,H 1Z-EtzOSkellysolve B-Bun,On-C6H 14" isoOctane "Species chromatd.derivs.of 2 : 4-( NO,),C,HS*SHalMe estersAcidI, (salt)ColourWeighingTitrationI,Bromothymol-(on column)Fe (C10,) 3Titration32 A33 N.P.P.34 N.P.P.24 N.P.P. 8 1Hydroxamic acidAcid35 N.P.P. EpiphaseCOMe,- or EtOH-C OMe,-H ,OH2O25 R.P.P.28 R.P.P. Kieselguhr-liq. paraffinKieselguhr-castor oilKieselguhr-liq. paraffinor -cycZohexaneI 8 I,I,28 R.P.P. I J I ,36 R.P.P.29 R.P.P.,II,MeOH<OMe,-C,H 6-COMe,-H,OHZO26 R.P.P.27 R.P.P.23, 37 D.A.23,38 D.A.23,39 C.S.Rubber powder" Polythene " powderDzrco G. 60 tubon (1) :Supercel (2)I,,I Interferometry EtOHI-Hab, etc.E t OH-H 2OEtOH-H,O (95 : 5) +carrier (fatty acidesters)8 1I D I, 8 1a A, adsorption ; N.P.P., normal phase partition ; R.P.P., reversed phase partition ; D.A., displacementb Be., behenolic; Bs., brassidic; El., elaidic ; Er., erucic; Es., elaeostearic; Ey., erythrogenic;leic ; LInc., linolenic ; Oc., octadec-2-enoic ; Ol., oleic ; Ps., petroselinic ; Pto., palmitoleic ; Rl.,stearic ; Un., undecylenic ; Xm., ximenynic ; C,-C,4 denotes saturated even-chain acids of chainc From water-acetic acid-methanol-hexane ( 5 : 1 : 50 : 50).Also dihydroxy- and dibromoTABLE 2. Paper chromatography.Ref.2641424344454647484950515253545569Stationary phase +paper Mobile phaseRubber latex MeOH-COMe, (1 : 1)Petroleum MeOH-H,OPetroleum (b.p. 190- AcOH-H,O (9 : 1)Paraffin Pentanol, hexanol, orOlive oil (or tristearin,chloronaphthalene,etc. )Paraffin AcOHParaffin (Nu jol) MeOH or EtOH-H,OPetroleum (b. p. 140- MeOH-petrol or -ace-Footnote 1 EtOH-tetrahydrofuran-Olive oil EtOH-H,O (3: 1) orParaffin AcOH-H,O (9 : 1)Footnote 2 CC1,-MeOH-NH,Footnote 3Tetralin or petroleum 90% MeOH-AcOH-2200)octanolLower alcohols(9 : 1)170") tone (3 : 1)-petrolH,O (0.6 : 3 : 5 )Pr'OH-H,O (4 : 1)(81 : 18 : 1) (epiphase)MeOH-H,O (4 : 2 to 9 : 1)satd. with decalintetralin (60 : 20 : 11) orMeOH-AcOH- petro-leum(b. p. 140-170")Petroleum (b. p. 190- AcOH-H,O (9 : 1)Paraffin or rubber MeOH-H,O ( 4 : 1 tolatex 19 : l ) , MeOH-H,O(4 : 1) saturated withcyclohexane220O)Silicone AcOH-H,O (17 : 3)Species chromatd.EstersAcidJ .NH,Me or NH,EtsaltAcid,I t? JHydroxamic acidAcidJ JJ JI ,AcOHg-derivAcidAcid or esterSudan IVCu(OAc), + eriochrom-Rhodamine B, Cu(OAc),-IndicatorsDetection of spotcyanin, etc.K,Fe(CN),, etc.AgN0,-NH,-(NH,),Scuso,AgN03-NH3-(NH4)Cu(OAc),-K,Fe(CN),Bromocresol-green,Ferric saltAgNO, (renewedAgN03-(NH4)2SNa,S, etc.)Cu (OAc) ,-K,Fe (CN)Rhodamine BBromothymol-blueMeO*[CH,] ,*OHDiphenylcarbazone-0.05N-HNOSCu(OAc),-K,Fe(CN),Pb(OAc),-H,S or rhodi-zonic acid, or bromo-th ymol-bluePb(OAc), or iodinea-Dextrin-iodine or0 Unsaturated acids also examined as hydroxylated compounds or iodine monobromide derivatives.b See footnote to Table 1.1, Acetylated paper. 2, Alum-treated paper + hypophase. 3, Cellulos300 BIOLOGICAL CHEMISTRY.natural mixtures of saturated and unsaturated acids. The more importantcolumn chromatographic methods are summarised in Table 1.Vapour-phase partition chromatography has been successfully applied 4*to even-numbered saturated fatty esters from C,, to Czz; it should beapplicable to some unsaturated fatty esters but it remains to be seen whetherit is suitable for the sensitive polyunsaturated compounds.Paper chromatography of fatty acids is rapidly developing and itsimportance need hardly be stressed. Methods are summarised in Table 2.Most of them involve a reversed-phase system with filter paper impregnatedwith liquid paraffin, petroleum hydrocarbon, silicone, olive oil, rubber,tristearin, etc., as the stationary phase.Baker 52 uses an octadecyloxy-methyl ether of cellulose, supporting decalin. Spot development is not easyand a number of methods have been employed : besides those in the Table,alkaline permanganate will detect 1 pg. of unsaturated acid, osmium tetr-oxide 5 pg., and Kaufmann’s foam test 56 5-10 pg. (the acid is convertedinto its copper salt and a foam is produced when it is treated with hydrogenperoxide in ammonia). If the paper is treated with 6oCo ions, these are fixedby the acid spots which can then be detected by a radi~autograph.~’ Re-tention analysis is successful with larger quantities (0-2-1.0 mg.) of acid.s8Photometric determination of fatty acids on paper, using the copper acetate-potassium ferrocyanide method for spot-development, has been achieved.54Recently the use of ‘‘ a-dextrin ” followed by treatment with iodine has beenrecommended for locating saturated and unsaturated acids or esters.59The reagent gives an inclusion compound with the fatty acid spot which,unlike free “ a-dextrin,” gives no colour with iodine. Lead tetra-acetate oriodine vapour may be used to detect unsaturated acids.59 Inouye and his32 D. R. Howton, Science, 1955, 121, 704.33 V. Zbinovsky, Analyt. Chem., 1955, 27, 764.34 L. L. Ramsey and I. Patterson, J . Assoc. O@c. Agric. Chemists, 1948, 31, 441.35 J. B. Davenport, Chem. and Ind., 1955, 705.36 M. H. Silk and H. H. Hahn, Biochem.J . , 1954, 56, 406.37 R. T. Holman and L. Hagdahl, J . Biol. Chem., 1950, 182, 421.38 R. T. Holman and W. T. Williams, J . Amer. Chem. Soc., 1951, 73, 5285.30 R. T. Holman, J . Amer. Chem. SOC., 1951, 73, 1261.40 F. R. Cropper and A. Heywood, Nature, 1953, 172, 1101;G. Dijkolra, J. G. Keppler, and J. A. Schols, Rec. Trav. chim., 1955, 74, 805.41 H. P. Kaufmann, J. Budwig, and C. W. Schmidt, Fette u. Seifen, 1952, 54, 10.42 H. P. Kaufmann and W. €3. Nitsch, ibid., 1954, 56, 154; 1955, 57, 473.43 L. A. Liberman, A. Zafarronia, and E. Stotz, Fed. Proc., 1951, 10, 216.44 G. Nunez and J. Spiteri, Compt. rend., 1952, 234, 2603; Bull. SOC. Chim. biol.,45 J. Spiteri, ibid., 1954, 36, 1355.46 P. F. Ceccaldi, R. Wegmann, and J. Biez-Charreton, ibid., p.415; Fette u.47 Y. Inouye and M. Noda, J . Agric. Chem. SOC. Japan, 1952,26, 634; 1953, 27, 50.48 F. Micheel and H. Schweppe, Angew. Chem., 1954, 66, 136.49 V. Kobrle and R. Zahradnik, Chem. Listy, 1954, 48, 1187, 1703.60 0. Perila, Acta Chem. S a n d . , 1955, 9, 864.61 A. Holasek, Angew. Chem., 1954, 66, 330.63 R. G. Baker, Biochem. J . , 1953, 54, xxxix.63 Y. Inouye, M. Noda, and 0. Hirayama, J . Amer. Oil Chemists’ SOL, 1955, 32, 132.64 H. Wagner, L. Abisch, and K. Bernhard, Helv. Chim. Acta, 1955, 38. 1536.65 B. D. Ashley and U. Westphal, Arch. Biochem. Biophys., 1955, 56, 1.66 H. P. Kaufmann and J. Budwig, Fette u. Seifen, 1950, 52, 555.57 Idem, ibid., 1951, 53, 69.68 H. P. Kaufmann, ibid., 1950, 52, 331, 713.69 H. K. Mangold, B.G. Lamp, and H. Schlenk, J . Amer. Chem. SOC., 1955,77, 6070.1954, 174, 1063;1953, 35, 851.Seijen, 1954, 56, 159CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS. 301co-workers have studied the paper chromatography of hydroxamic deriv-atives of unsaturated acids.60 Paper electrophoresis (Table 3) has not beenparticularly useful as yet.61968Ultraviolet spectrophotometric methods 63 for determining (in con-junction with alkaline isomerisation) methylene-interrupted conjugatedfatty acids * have been further examined.65 Infrared spectra arevaluable for estimation and detection of functional groups, but homologousfatty acids are not readily distinguished and different crystal farms havedifferent spectra: 67 the spectra of the sodium salts are sometimes morediagnostic.68 Various X-ray studies are reported.ggTABLE 3. Paper electrophoresis.Ref. Mobile Species Detn. of Approx. of acidTypesClo-Clephase chromatd. spot range (pg.) examined61 Aq. NH, Salt Methyl-red-bromothymol- 80blue62 0-2N-NaOH in glycerol ,, Cu(OAc),-Rhodamine B - c6-c16(90”)Methods for determining lipoperoxides are availableD70 and Bolley 71reports on the chemical determination of unsaturation in fats : Mukherjee 72uses hypochlorous acid for the latter purpose and, with Chowdhury, describesconditions for evaluating a “ true iodine number ” for conjugated acids.73An analytical method for component acids of oils containing epoxy- orhydroxy-acids is available.’* Small quantities of fatty esters (0.2-3.0ymole) may be estimated by treatment with alkaline hydroxylamine andferric perchlorate, followed by photometric measurement at 520 mp.75Reviews of the autoxidation of unsaturated fatty acids and related* Methylene-intzrrupted conjugation refers to systems of type *CH:CH*CH,*CH:CH*.6o Y.Inouye and M. Noda, J . Agric. Chem. SOC. Japan, 1950, 23, 368; 1952, %,61 A. J. G. Barnett and D. K. Smith, Nature, 1954, 174, 659; J . Sci. Food Agric.,62 0. Perila, Acta Chem. Scand., 1955, 9, 1231.ti3 R. T. O’Connor, J . Amer. Oil Chemists’ SOG., 1955, 32, 616, 624.64 W. J. Gensler and A. P. Mahadevan, J . Amev. Chem. SOC., 1955, 77, 3076.6s S. F. Herb, J. Amer. Oil Chemists’ Soc., 1955, 32, 153; J. Moretti and R. .I.Cheftel, Bull. SOC. Chim. biol., 1955, 37, 699; D. Firestone, J .Assoc. Ofic. Agrzc.Chemists, 1955, 38, 657; K. A. Narayan and B. S. Kulkami, J . Indian Chem. SOC., Ind.News Edn., 1964, 17, 79.a6 D. H. Wheeler, ref. 2, Vol. 11, p. 268.6 7 R. G. Sinclair, A. F. McKay, and R. N. Jones, J . Amer. Chem. Soc., 1952, 74,2570, 2575; E. von Sydow, Acta Chem. Scand., 1956, 9, 1119.68 E. Childers and G. W. Struthers, Analyt. Chem., 1955, 27, 737.6Q E. von Sydow, Acta Cryst., 1955, 8, 557; J. Fridrichsons, Austral. J . Chem.,1955,8, 339; A. R. Verma, Proc. Roy. SOG., 1955, A , 227, 34; D. Swern, L. P. Witnauer,S. A. Fusari, and J. B. Brown, J . Amer. Oil Chemists’ SOC., 1955,32, 539; T. R. Lomer,Nature, 1955, 175, 653; T. Malkin, ref. 2, Vol. I, p. 1.70 J. Glavind and S . Hartmann, Acta Chem. Scand., 1955, 9, 497; A.M. Siddiqi andA. L. Tappel, Chemist-Analyst, 1955, 44, 6 2 ; C. B. Kenaston, K. M. Wilbur, A. Otto-lenghi, and F. Bernheim, J . Amer. Oil Chemists’ Sot., 1955, 52, 33.71 D. S. Bolley, ibid., p. 235.72 S. Mukherjee, ibid., p. 351.73 R. B. Chowdhury and S. Mukherjee, ibid., p. 484.74 K. E. Bharucha and F. D. Gunstone, J. Sci. Food Agric., 1955, 6, 373.75 M. H. Hack, Arch. Biochew. Biophys., 1955, 58, 19; R. Nailor, F. C. Bauer, andGensler et al. 64 use491 (Chem. Abs., 1952, 48, 6408).1955, 6, 63.skipped double bonds.”E. F. Hirsch, ibid., 1955,5;4, 201302 BIOLOGICAL CHEMISTRY.substances are available; 76 while it is not possible here to deal adequatelywith this subject there is much current intere~t.~' Monohydroxystearicacids can be obtained by catalytic hydrogenation of peroxidised methyloleate and oleic acid.78 Under certain conditions of hydrogenation, migra-tion of the double bond of oleic acid occurs equally in each direction to givea 1 : 2-cis-trans-equilibrium mixture of positional isomers : 79 a partial-hydrogenation-dehydrogenation theory is used to explain the results.Sodamide in liquid ammonia reacts with methyl linoleate producing acomplex mixture of conjugated and non-conjugated esters and amides :the conjugated compounds are cis-trans with a little trans-trans.80 Linolenategives the cis-trans-diene and stereoisomeric trienes.Long-chain Saturated Fatty Acids.-Until recently it was assumedthat unbranched acids with odd-numbered chains rarely occurred in mam-malian or fish lipids.A number of examples have now come to light,though the acids occur only in small amount and failure to detect them has,at least in part, been due to inadequate techniques for separation. n-Nona-decanoic acid can be obtained from hydrogenated ox perinephric fat.81rt-Heptadecanoic (margaric) and pentadecanoic acid are found in shark liveroil : 8, butter fat also contains the latter acid, together with n-tridecanoicand rt-undecanoic acids. 83 Hydrogenated mutton fat has yielded rt-hepta-decanoic and pentadecanoic acid,s4 and odd-numbered acids from C, to C,can be detected in hydrogenated ox tallow.85 An unsaturated odd-numberedacid, n-heptadec-9-enoic acid occurs in lamb-caul fat. 86Besides the even- and odd-numbered straight-chain acids, branched-chain acids having iso- (Me,*CH*CH,*) or anteiso- (MeEt-CHCH,.) endgroups are probably widely distributed in animal fats, usually in only smallconcentrations.Weitkamp's pioneer work 87 on wool wax resulted in theisolation of thirty-two acids from this source, ten being iso-acids, eleven(+)-artteiso-, and the remainder hydroxy- and normal acids. His work hasstimulated synthetic investigations in these groups.8876 W. Kern and H. Willersinn, Angew. Chem., 1955, 67, 573; R. T. Holman, ref. 2,Vol. 11, p. 51.77 Intev alia, N. A. Khan, J . Chem. Phys., 1954, 22, 2090; Biochim. Biophys. Ada,1955, 16, 159; N. A. Khan, W. E. Tolberg, D. H. Wheeler, and W. 0. Lundberg, J .Amer. Oil Chemists' SOC., 1954, 31, 460; D.H. Saunders, C. Ricciuti, and D. Swern,ibid., 1955, 32, 79; J. E. Coleman, H. B. Knight, and D. Swern, ibid., p. 135; A. L.Tappel, ibid., p. 252; S. S. Kalbag, K. A. Narayan, S. S. Chang, and F. A. Kummerow,ibid., p. 271 ; 0. S. Privett, C. Nickell, W. 0. Lundberg, and P. D. Boyer, ibid., p. 505;W. Kern, A. R. Heinz, and J. Stallmann, Makromol. Chem., 1955, 16, 21; W. Kernand H. Willersinn, ibid., 1955, 15, 1, 15, 36; Y . Toyama and K. Suzuki, J . Chem. SOC.Japan, Ind. Chem. Sect., 1955, 58, 52.'8 J. E. Coleman and D. Swern, J . Amer. Oil Chemists' SOC., 1955, 32, 221.79 R. R. Allen and A. A. Kiess, ibid., p. 400.81 R. P. Hansen, F. B. Shorland, and N. J. Cooke, Nature, 1955, 176, 882.82 I. M. Morice and F. B. Shorland, Biochem. J ., 1955, 81, 453.83 F. B. Shorland, T. Gerson, and R. P. Hansen, ibid., 1955, 59, 350; R. P. Hansen,84 Idem, Biochem. J . , 1954, 58, 513, 516.85 R. P. Hansen and A. G. MacInnes, Nature, 1954, 173, 1093.86 F. B. Shorland and A. S. Jessop, ibid., 1955, 176. 737.87 A. W. Weitkanip, J . Amer. Chem. Soc., 1945, 67, 447; S. F. Velick, ibid., 1947,J. R. Nunn, J., 1951, 1740; F. W. Hougen, D. Ilse, D. A. Suttpn, and J. P.A. M. Abu-Nasr and R. T. Holman, ibid., p. 414.F. B. Shorland, and N. J. Cooke, Chem. and Ind., 1955, 92.69, 2317.de Villiers, J . , 1953, 98; A. H. Milburn and E. V. Truter, J . , 1954, 3344CROMBIE : NATURAL LONG-CHAIN FATTY A4CIDS. 303Hansen, Shorland, and their collaborators have made extensive searchesfor branched-chain acids in a number of animal fats.By use of low-temper-ature crystallisation, distillation, chromatography, and hydrogenation,butter fat has been shown 89 to contain (+)-12-methyltetradecanoic,* 13-methyltetradecanoic, and 12-methyltridecanoic acid, two acids isomeric withheptadecanoic acid (one apparently of the iso- and the other the anteiso-series), and other branched-chain acids. The isolation of these acidsinvolved a hydrogenation step, but objections that the acids may be artefactsderived from unsaturated or cyclopropane acids have been met in part byisolation of (+)-12-methyltetradecanoic (0.43y0), 13-methyltetradecanoic(0.37y0), and n-pentadecanoic acid (O-82y0) by distillation and chromato-graphy on1y.m (+)-lO-Methyldodecanoic (0.01 %) and 1 l-methyldodecanoicacid (0.05%) also occur in butter fat.91Carcass fats of sheep yield small amounts of (+)-14-methylhexadecanoic(+)-l Z-methyltetradecanoic, 13-methyltetradecanoic, 10-methyldodecanoic,and a liquid saturated branched C,, acid.92 Ox perinephric fat gives (+)-14-methylhexadecanoic, 15-methylhexadecanoic (0.06y0),93 and 14-methyl-pentadecanoic a ~ i d .~ 4 Branched-chain acids occur in the preen glands ofducks 95 and in shark liverThe alzteiso-compounds (+)-14-methylpalmitic acid (1 ; n = 12) 97 and(+)-6-methyloctanoic acid (1 ; n = 4) 98 have been related to natural(-)-2-methylbutanol (" active amyl alcohol ") (2) and there is little doubtthat all the natural (+)-alzteiso-acids are configuratively of the " L-"series tand are related to natural isoleucine (3) as shown.99 Little is as yet knownCOiH CO2H --rH CHiOH I+& IMr-C -H Mc-C-H Mr-C-HI I IEt Et Et(441) (-)-(4 (+)-PIof the biosynthesis of the odd-numbered and branched-chain acids, thoughthe .addition of acetate units to propionate (known to be converted intovaleric acid in the rumen) loo would give the former,g0 and addition of acetateunits to isovalerate (or isobutyrate) and (+)-2-methylbutyrate would yield,F.B. Shorland, R. P. Hansen, and N. J. Cooke, Biochent. J . , 1954, 5S, 358;1953,53,374; Chem. and Ixd., 1951,839; R. P. Hansen and F. B. Shorland, Biochem.J . , 1952, 50, 207, 358.F. B. Shorland, T. Gerson, and R. P. Hansen, ibid., 1955, 59, 350.Idem, ibid., 1955, 61, 702.82 F. B. Shorland, R.P. Hansen, and N. J. Cooke, ibid., 1952, 52, 203; 1953, 58,93 Idem, Biochem. J., 1955, 61, 141.95 G. Weitzel and K. Lennert, 2. physiol. Chem., 1951, 288, 251.O 6 I. M. Morice and F. B. Shorland, Chsm. and Ind., 1952, 1267.O 7 S. F. Velick and J. English, J . Biol. Chern., 1946, 160, 473.88 L. Crombie and S . H. Harper, J . , 1950, 2685.loo F. V. Gray, A. F. Pilgrim, H. J. Rodda, and R. A. Weller, Nature, 1951,167, 954. * Geneva nomenclature (C02H = 1) is used in this Report.-f For the significance of D and L see R. P. Linstead, J. C. Lunt, and B. C. L. Weedon,374; Chem. and Ind., 1953, 516; 1954, 1229.Idem, ibid., p. 547.Idem, Chem. and Ind., 1950, 757; W. Klyne, Biochem. J., 1953, 53, 378.J . , 1950, 3333, and W. Klyne, Chem. and Ind., 1951, 1022304 BIOLOGICAL CHEMISTRY.respectively, the iso- and anteiso-seriesW, lol These acids may arise fromdeamination of the corresponding amino-acids.101An interesting study of human sebum waxes is reported : sebum containslong-chain alcohols of three types-saturated normal, saturated iso-, andunsaturated normal.lo2 Hougen points out that in many natural waxes theacids and alcohols are structurally related, suggesting a common biosyntheticprocess (thus wool wax contains both acids and alcohols of the n-, iso-,artteiso-, and u-hydroxy-series) .lO3 This relation does not exist between thecombined alcohols of sebum and the free fatty acids though the combinedacids have not yet been examined.A useful review of bacterial fattyacids,lo5 and studies of the lipids of typhus and diphtheria bacteria lo6and of a group C Strefitoco~czcs,~~~ are available.Mycoceranic acid fromtubercule bacilli lipids is provisionally regarded as 2 ( 0 ) : 4(0) : 6(D)-tri-methyloctacosanoic acid and the 2 : 4 : 6(D)-compound has been syn-thesised.1O8 In connexion with mycolipenic acid [(+)-2 : 4 : 6-trimethyl-tetracos-2-enoic acid], isolated from the same source, syntheses of a numberof long-chain 2-methylalk-2-enoic acids are described : lo9 1 : 2- and 1 : 3-diglycerides of 2-methyloctadec-2-enoic acid are available.110 Mycolicesters and amides from amino-sugars 111 are of interest in connexion withBloch’s toxic lipid “ cord factor ” 11, and palmitic 113 and mycolic 114 esters ofsugars have been synthesised.There is synthetic interest 115 in mycolicacids of the general formula R*CH,-CH(OH)*CHR*CO,H, and anothersynthesis of (-j-)-tuberculostearic acid has been carried out.116Thioctic (c4poic) acid occurs as a conjugate in the lipid fraction fromScenedesmus obliqztus : l 1 7 several syntheses of this and related compounds,including the preparation of the 35S acid, are reported.118Long-chain Unsaturated Fatty Acids.-Unsaturated fatty acids presentan outstanding problem to the biochemist since little is known about their101 F. €3. Shorland, ref. 2, Vol. 111, p. 276.102 F. W. Hougen, Biochem. J., 1955, 59, 302; see also Shkng-Lieh Liu, J . Chinese103 H . W. Knoll, J . Amer. Oil Cltemists’ SOC., 1954, 31, 59.104 A. W. Weitkamp, A. M. Smiljanic, and S.Rothman, J . Amev. Chem. SOL, 1947,106 J. Asselineau and E. Lederer, “ Fortschritte der Chemie organischer Natur-106 S. Cmelik, 2. physiol. Chem., 1955,299,227; 1955,300,167; 1955,302,20.107 K. Hofmann and F. Tausig, J . Biol. Chem., 1955, 213, 415.108 G. S. Marks and N. Polgar, J., 1955, 3851.10s J. Cason and M. J. Kalm, J . Org. Chem., 1954, 19, 1836, 1947; A. S. Bailey,110 G. I. Fray and N. Polgar, J., 1955, 1802.111 J. Asselineau and E. Lederer, Bull. Soc. chim. France, 1955, 1232.112 H. Bloch, J . Exp. Med., 1950, 91, 197; H. No11 and H. Bloch, J . Bid. Chem.,113 J . Asselineau, Bull. Soc. chim. France, 1955, 937.114 U. Eisner, J. Polonsky, and E;,Lederer, ibid., 1955, 212.115 J. Asselineau and E. Lederer, Experimental Tuberculosis,” Colloquium, Ciba116 M.Sy, Ng. Ph. Buu-Hoi, and Ng. D. Xuong, Compt. vend., 1954, 239, 1813.117 R. C. Fuller, H. Grisebach, and M. Calvin, J . Awzer. Chem. Soc., 1955, 77, 2659.118 E. A. Braude, R. P. Linstead, and K. H. R. Wooldridge, Chem. and Ind., 1955,508; A. Campbell, J., 1955, 4218; L. J. Reed and Ching-I Niu, J . Amer. Chem. SOL,1955, 77, 416; A. F. Wagner, E. Walton, C. H. Hofmann, L. H. Peterson, F. W. Holly,and K. Folkers, ibid., p. 5140; E. Walton, A. F. Wagner, F. W. Bachelor, L. H. Peter-son, F. W. Holly, and K. Folkers, ibid., p. 5144; P. T. Adams, ibid., p. 5357; R. C.Thomas and L. J. Reed, ibid., p. 6446.Chem. Soc. (Formosa), 1954, Ser. 2, 1, 71.69, 1936.stoffe,” Springer, Wien, 1953, Vol. X, p. 170.N. Polgar, F.E. G. Tate, and A. Wilkinson, J., 1955, 1547.1955, 214, 251.Foundation, London, 1955CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS. 305metabolism and much has yet to be learnt about the specific roles which someof them play in biological processes. Synthetic work is of basic interest inthat it offers the means of testing biochemical hypotheses by 14C-labelling atselected points in the chain.Useful anodic routes 119 have been added to existing syntheses of oleicacid : in one, adipic half-ester is cross-coupled with an acetylenic acid andthe product semihydrogenated :MefCH,],GC*[CH2J3*C02H + HO,C*[CH,],*CO,MeC Me*[CH,],*GC-[CH,],*CO,Me Me*[CH2],*CH=CH*[CH2],*C0,H(In such formulz, c denotes cis, and t trans.)Octadec-cis- and -trans-1 l-enoic acid have been prepared by anodicmethods 120 and are of interest in that the cis-acid is the hzemolytic factorfrom horse-brain 121 and is also the principal unsaturated fatty acid inLactobacillus arabinosus and L.casei.122 “ Vaccenic acid ” is believed to bea mixture in which octadec-trans-1 1-enoic acid predominates. Hufrnannand Tausig 123 make the interesting suggestion that the l 1 vaccenic acid ’’ ofanimal fats may arise from absorption of octadec-cis-1 l-enoic acid elabor-ated by intestinal bacteria, stereomutation occurring during absorption ortransport. The recent work of Hartman and his collaborators 1% is relatedto this suggestion; using infrared analysis they find that ruminants havesubstantial amounts (3.5-1 102%) of tram-unsaturated acids in their fatsbut non-ruminants have less than 0.9%.Marsupial fats contain 18.1-2100% of trans-acid. According to Hartman et al. the trans-acids arisemainly from hydrogenation of dietary unsaturated acids by bacteria in therumen, or in the rumen-like stomach of the marsupials.The above synthetic method for octadec-trans-1 I-enoic acid employsprotection of the olefinic linkage as a dihydroxy-derivative. The anodictechnique is used in the anodic synthesis of tetracos-cis- and -trans-15-enoicacid (the cis-compound is nervonic or selacholeic acid) : 125 here the startingmaterials are oleic and elaidic acid. Tariric, petroselinic, erucic, and brassidicacid can be prepared by the anodic route, and natural eicos-ll-enoic acid isshown to have the Synthetic cis- and trans-isomers ofmyristoleic, palmitoleic, gadoleic, octadec-4-enoic, undec-9-enoic acid, aswell as erucic, brassidic, oleic, and elaidic acid, are accessible by Ames andBowman’s general methods.127The gross structure of stillingic acid (deca-2 : 4-dienoic acid) from theseed oil of Sapium sebiferum (stillingia oil) 128 has been confirmed by syn-llo 13.W. Baker, R. P. Linstead, and B. c. L. Weedon, J., 1955, 2218.120 D. G. Bounds, R. P. Linstead, and B. C. L. Weedon, J., 1954, 4219.121 I. D. Morton and A. R. Todd, Biochem. J., 1950, 47, 327.lZ2 K. Hofmann, R. A. Lucas, and S. M. Sax, J . B i d . Chem., 1952, 195, 473; K.l Z 3 K. Hofmann and F. Tausig, ibid., 1955, 213, 425.124 L. Hartman, F. B. Shorland, and I. R. C .McDonald, Biochem. J . , 1955, 61, 603.125 D. G. Bounds, R. P. Linstead, and B. C. L. Weedon, J., 1954, 448,1g6 R. P. Linstead, B. C. L. Weedon, and B. Wladislaw, J., 1955, 1097; B. W. Baker,127 R. E. Bowman, J., 1950,177; B. W. Boughton, R. E. Bowman, and D. E. Arnes,128 A. Crossley and T. P. Hilditch, J., 1949, 3353.Hofmann and S. M. Sax, ibid., 1953, 205, 55.R. W. Kierstead, R. P. Linstead, and B. C. L. Weedon, J., 1954, 1804; 1953, 2393.J., 1952, 671; D. E. Ames and R. E. Bowman, J., 1951, 1079; 1952, 677306 BIOLOGICAL CHEMISTRY.thesis. Four possible stereoisomers have been prepared 129 and the trans-2 : cis-4-acid is identical with the natural acid. Stillingic acid is the firstpolyethenoid acid containing less than sixteen carbon atoms to be isolatedfrom a glyceride.Its homologue, dodeca-2 : 4-dienoic acid (stereochemistryunknown), has recently been found in the seed oil of Sebistiana lingustrina.lmA cis9 : trans-1 1 : trans-13-configuration was recently proposed 131 fora-elzeostearic acid (4) from an infrared study of the maleic anhydride adduct(in conjunction with earlier oxidation work and other evidence). Thisconfiguration, and the structure of the acid, have now been established bythe annexed synthesis132 Isomerisation with iodine and ultraviolet lightgives the all-iruns-(p)-form.Me*[CH,],-CH=CH*CHO + Rr*CH,*CCH -- Me*[CH,],*CH=CH*CH (OH) -CH,*CCHtPBr,.d Me.[CH,],*CH=CH*CH=CH*GCH __tMefCH,] ,*CH=CH*CH=CH*GC*[CH,] ,*C1 -KOHNaI- t t ,-+ Me*[CH,],.CH=CH*CH=CH-GC*[CH,],*CO,HKCN-OH- t t C Me*[CH,],*CH=CH*CH=CH*CH=CH,I,.CO,HUseful methods for marking the 1-carboxy-group of natural unsaturatedfatty acids are available. [l-14C]Oleic acid is prepared by Hunsdiecker(silver salt-bromine) degradation of er-ythro-9 : 10-dihydroxystearic acid(from natural oleic acid) to the nor-1-bromo-compound, followed by[14C]nitrile synthesis and stereospecific elimination to regenerate the cis-9 : 10-double bond.133 Linoleic acid is brominated and the carboxyl replacedby bromine by the Hunsdiecker reaction : debromination removes thecontiguous bromine substituents.The monobromide is then converted intoits Grignard reagent and carboxylated with 14C0,. 134A number of syntheses of the essential fatty acid, linoleic acid, appeareda few years ago 135 and a formal synthesis of linolenic acid has now beena~hieved.1~~ The route is as shown.The hexabromostearic acid ( 5 ) , m. p.180-181", was equated with material derived from natural linolenic acid.It can be debrominated to a-linolenic acid from which the natural all-cis-acidcan be obtained by crystallisation.Evidence is repeatedly obtained for the presence in Nature of unsaturatedfatty acids containing methylene-interrupted conjugation, other than thewell-known examples such as linoleic, linolenic, and arachidonic acid. ThelZg L. Crombie, J., 1955, 1007; Chem. and Iizd., 1952, 1034.130 D. P. Hanks and W. M. Potts, J . Amer. Oil Chemists' SOC., 1951, 28, 292; R. T.Holman and D. P. Hanks, ibid., 1955, 32, 356.131 R.F. Paschke, W. Tolberg, and D. H. Wheeler, ibid., 1953, 30, 97; W. G. Bick-ford, E. F. DuPr6, C. H. Mack, and R. T. O'Connor, ibid., p. 376; N. H. E. Ahlers,R. A. Brett, and N. G. McTaggart, J . Appl. Chem., 1953, 3, 433.l32 L. Crombie and A. G. Jacklin, Chem. and Ind., 1955, 1186.13, S . Bergstrom, K. Paabo, and M. Rottenberg, Acta Chem. Scand., 1952, 8, 1127.134 D. R. Howton, R. H. Davis, and J. C . Nevenzal, J . Amer. Chem. SOC., 1952, 74.1109.135 R. A. Raphael and I;. Sondheimer, J., 1950, 2100; W. J. Gensler and G. R.Thomas. J . Amer. Chem. SOC., 1951, 73, 4601; H. M. Walborsky, R. H. Davis, andD. R. Howton, ibid.. p. 2590; R. A. Raphael, " Acetylenic Compounds in OrganicSynthesis," Butterworths, London, 1955, p. 89.(4)136 S. S . Nigam and B.C. L. Weedon, Chem. and Ind., 1955, 1665CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS. 307acids are highly unstable and difficult to purify but there is little doubt thatthey are biologically important, and intensification of effort in this exactingfield is much to be desired. The techniques employed for isolation ofhexadeca-6 : 9 : 12 : 15-tetraenoic acid from pilchard oil are worthy ofMC.CH~*C=C*CH~B~ + HCaC=CHpPy MC-EH~*C=C]~*CH~P~ &,O-CH2,O-CH2 O-CH2Me *EH2.CIC], .CH2Br ?, Me*[CHI.C~],.[CH,],*C~ I &Me *[CH2-CH+CH], *[CH&-CH I & Me .CtH2gCHBr.CHB33*EH,];C02H'O-CHa ( 5 )Py = tetrahydropyranyloxy.Reagents : 1, CuC1. 2, Hf-PBr,. 3, X.Mg*CZC*[CH,],*CH 'O-p'. 4, H,-Lindlar.5, Br,; oxidn.\O-CH,st~dy.13~ In the past year Klenk and Dreike 138 have found evidencefor eicosa-5 : 8 : 11- and -8 : 11 : 14-trienoic, eicosa-5 : 8 : 11 : 14- and-8 : 11 : 14 : 17-tetraenoiq docosa-7 : 10 : 13 : 16 : 19-pentaenoic, and docosa-4 : 7 : 10 : 13 : 16 : 19-hexaenoicacid, as well as linoleic and linolenic acid, in liver phosphatides.Theglycerophosphatides of brain contain eicosa-5 : 8 : 11 : 14-tetraenoic (ara-chidonic) acid and eicosa-5 : 8 : ll-and -8 : 11 : 14-trienoic acid, togetherwith eicosa-1 1 : 14-dienoic acid.139 Considerable quantities of docosa-4 : 10 : 13 : 16-tetraenoic and docosa-4 : 7 : 10 : 13 : 16 : 19-hexaenoic acidhave been isolated by counter-current distribution from the mixture of C,,polyene-carboxylic acids from glycerophosphatides of brain.140 Smallamounts of docosa-4 : 7 : 10 : 13 : 16-pentaenoic acid, and probably adocosatrienoic acid are present.Natural Hydroxy-acids.-There is current interest in natural hydroxy-acids. 18-Hydroxyoctadec-9-enoic acid is obtainable from cork 141 and anew synthesis of phloionic acid (9 : 10-dihydroxyoctadecanedioic acid), alsoZnMe*[CH,],.CHO + Br*CH,*CZCH __t Me*[CH,],CH(OH)*CH,*C~CH *eicosa-5 : 8 : 11 : 14 : 17-pentaenoic,__t Me.[CH,],*CH(OH)CH,-CZCfCH,],Cl+Me-[CH,],CH (OH) *CH,*CH=CH*[CH,] ,*CO,H (6)C* Hydroxy-group protected as the pyranyloxy-derivative during chain extension.obtainable from cork, has been pub1i~hed.l~~ A series of even-numberedw-hydroxy-acids of chain lengths 18-30 inclusive, together with even-numbered ao-diols of chain lengths 22-28, occur in carnauba wax.143 Fulldetails of a synthesis of (-+)-ricinoleic acid (6) have appeared.lU A second13' M.H. Silk and H. H. Hahn, Biochem. J., 1964, 57, 582.138 E. Klenk and A. Dreike, 2. j?&ysioZ. Chem., 1955, 300, 113.139 E. Klenk and F. Lindlar, ibid., 1955, 301, 156.I4O Idem, ibid., 1955, 299, 74.1 4 1 I. Ribas and E. Seoane, Anales Fis. Quim., 1954, 50, B, 963.14% W. J. Gensler and H. N. Schlein, J . Amer. Chem. SOC., 1955, 77, 4846.143 K. E. Murray and R. Schoenfeld. AustraZ. J. Chem., 1955, 8, 432, 437.144 L. Crornbie and A. G. Jacklin, Chem. and Ind., 1954, 1197; J., 1956, 1740308 BIOLOGICAL CHEMISTRY.synthesis of the racemic acid has been briefly rep0rted.1~~ It seems likelythat natural (+)-ricinoleic has the D-~onfiguration.1~~ As ricinoleic acid issimply converted into octadec-trans-1 l-en-9-ynoic acid,147 these synthesesalso give a total synthesis of ximenynic acid which is obtained from seed fatsof Ximenia and Santalum genera (Olacacea) .148 An isomer of ricinoleicacid, 9-hydroxyoctadec-12-enoic acid, is present in the seed oil of Strofihanthussarmentosus 149 and 8-hydroxyoctadec-trans-1 l-en-9-ynoic acid in that ofXimeniar caffra.150 The structure and stereochemistry of the a- and the@-form of kamlolenic acid from the nuts of Mallotus phiZip+inensis (Euphor-biacea) seems clear : the a-form is 18-hydroxyoctadec-cis-9 : trans-11 : trans-13-trienoic acid and the @-form the all-trans-isomer.151 Vernolic acid fromVernonia anthelmintica (Compositeae) is 12 : 13-epoxyoctadec-9-enoic (anepoxylinoleic) a ~ i d .1 ~ ~cycEoAlkane Acids.-The lipids of the plant pathogen, Agrobacterium(Phytomonas) tumefaciens, contain a liquid fatty acid long thought to be 10-or ll-methylnonadecanoic acid : it is in fact the cyclopropane compoundlactobacillic acid (7) The latter had previously been isolated from Lacto-bacillus arabinosus and L. casei : 122 there is a speculation on its bio-synthesis.153 A . tumefaciens is also the richest natural source of octadec-cis-1 l-enoic acid.Closely related to lactobacillic acid is sterculic acid from the kernel oil ofSterculia fatida. Nunn 154 proposes a cyclopropene structure (8) but thishas been challenged by Indian workers 155 who prefer structure (9).Theseauthors do not explain Nunn’s evidence, obtained by ozonisation (whichgives a 1 : 3-diketone), and some of their criticisms are open to objection.Mat *EHJ7 HC -CH$H,I, * CO2HM ~ + H J ~ * c,=,c EH~],*co~H(7)(8)\ ICH2CH2Me *EH& * HC -CH*CH=CH pHd7 CO2H (9)\ /Chaulmoogric acid (10) can be synthesised by anodically cross-coupling(+)-cyclopent-2-enylacetic acid with methyl hydrogen bra~sylate.1~~ De-gradation of the (+I-cyclopentenylacetic acid (11) gives the (-)-tricarboxylic145 V. G. Kendall, P. B. Lumb, and J. C. Smith, Chem. and Ind., 1954, 1228.146 K. Serck-Hanssen and E. Stenhagen, Acta Chem. Scand., 1955, 9, 866.147 J. Grigor, D. M. MacInnes, J. McLean, and A. J. P. Hogg, J., 1955, 1069.148 S. P. Ligthelm and H. M.Schwartz, J. Amer. Chem. Soc., 1950, 72, 1868; S. P.Ligthelm, H. M. Schwartz, and M. M. von Holdt, J., 1952, 1088; M. H. Hatt and A. 2.Szumer, Chem. and Ind., 1954, 962; F. D. Gunstone and M. A. McGee, ibid., p. 1112.149 F. D. Gunstone, J., 1952, 1274.150 S. P. Ligthelm, Chem. and Ind., 1954, 249.151 Ifiter alia, S. D. Gupta and J. S. Aggarwal, J. Amer. Oil Chemists’ Soc., 1955,32, 501; R. C. Caldenvood and F. D. Gunstone, Chem. and I n d . , 1953, 436; N. H. E.Ahlers and F. D. Gunstone, ibid., 1954, 1291 ; R. C. Calderwood and F. D. Gunstone,J. Sci. Food Agric., 1954, 5, 382; L. Crombie and J. L. Tayler, J., 1954, 2816; J. D.von Mikusch, Deut. Farben. 2.. 1954, 8, 166.lS2 F. D. Gunstone, J., 1954, 1611.153 E . M . Kosower, Science, 1951, 113, 605.J.R. Nunn, J.. 1952, 313; cf. G. DijkstraandH. J. Duin, Nature, 1955,176, 71.1 S 6 1. P. Verma, B. Nath, and J. S. Agganval, ibid., 1955, 175, 84; 1955, 176, 1082.166 K. Mislow and I. V. Steinberg, J. Amer. Chem. Soc., 1955, 77, 3807CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS. 309acid (12) which can be configuratively correlated, through shikimic acid,with glyceraldehyde. The (-)-acetic acid (11) was also correlated withglyceraldehyde, through (+)-Z-ethylglutaric acid, by the displacementprinciple. It seems reasonable to suppose that gorlic acid and the naturallower homologues have the same configuration as chaulmoogric acid, and thatthe correlation with glyceraldehyde is valid for the whole g r 0 ~ p . l ~ ~fA synthesis of (&)-dihydrohydnocarpic acid (13), a s shown, is re~0rted.l~'( -J-)-Dihydrochaulmoogric acid is obtained by a similar route.Alepresticacid has also been ~ynthesised.1~~Reagents : 1, SnC1,-thiophen. 2, Wolff-Kishner. 3, AIC1,-(CH,*CO),O.4, Wolff-Kishner ; Raney Ni.Natural Acetylenic Acids.-Some chemical aspects of this subject havebeen reviewed.159 A group of methyl esters of related acetylenic acids occursin the Compositeae; Sorensen and his school have greatly extended ourknowledge of them. cis-Lachnophyllum ester (14) is found in manyplants of the Erigeron genus and it is believed that all true Erigerons containthis and lor, matricaria ester.161 trans-Lachnophyllum ester is found 162in the root oil of the common daisy (Bellis perennis) and has been synthesisedby Glaser c0up1ing.l~~ Its isomer methyl dec-cis-8-ene-4 : 6-diynoate (15) isconsidered to be present in the flower oil of Matricaria inodora and probablyother plants.164Pr*C-=CH + HEC.CH=CH*CH,-OH ~_t PrGC*EC*CH=CHCH,.OHPr=CGC*CH=CH.CO,Me (14)Two of the four possible stereoisomers of matricaria ester (16) are knownin Nature-the cis : cis- in Matricaria inodora and the cis-2 : trans-8- inM . inodova and Amellus stvigosus.164 The trans-trans- and the trans-2 : cis-8-compound are synthetically available by coupling tram-pentenynol with15' Ng. Ph. Buu-Hoi', M. Sy, and Ng. D. Xuong, Compt. vend., 1955, 240, 785.16* B. Wladislaw, J . , 1955, 4227.lB0 W. W. Wiljams, V. S. Smirnov, and V. P. Goljmov, J. Gen. Chem. (U.S.S.R.),lB1 G.M. Tronvold, M. Nestvold, D. Holme, J . S. Sorensen, and N. A. Sorensen,lBa D. Holme and N. A. Sorensen, ibid., 1954, 8, 280.163 T. Brunn, C. M. Haug, and N. A. Sorensen, ibid., 1950, 4, 851.164 K. S. Baalsrud, D. Holme, hl. Nestvold, J. Pliva, J. S. Sorensen, and N. A.F. Bohlmann, Angew. Chem., 1955,67. 389.1935, 5, 1195; N. A. Sarensen and J. Stene, Annalen, 1941, 549, 80.Acta Chem. Scand., 1953, 7 , 1375.Sorensen, ibid., 1952, 6, 883; P. K. Christiansen and N. A. Sorensen, ibid., p. 893310 BIOLOGICAL CHEMISTRY.trans- and cis-pentenyne.166 Jones and his collaborators 1G6 have recentlyshown that trans : trans-matricaria methyl ester occurs in Polyporus anthra-cophilus cultures : deca-2 : 8-diene-4 : 6-diynedioic acid occurs in the samematerial.A dehydromatricaria ester (17) or (18) is obtainable fromArtemesia vulgaris : 167 investigation of the spectra of model compoundsMe*CH=CH*CC.C=C*CH,*CH,*CO,Me (1 5)Me*CH=CH*GC*CEC*CH=CH*CO,Me (1 6)Me*CH=CH*GC*CEC*CC*CO,Me (17)Me*CC*CEC*CC*CH=CH*CO,Me (18)n-C,H ,,*CH=C=C=CH*CO,Me (19)suggests that it is cis-form (18).lG8 The trans-isomer, synthesised by oxid-ative coupling,169 has also been found in Nature (M. oreades and M.i n o d ~ r a ) . ~ ~ ~ A cumulene ester, believed to have structure (19) occurs in thetMeGC-CCH + HEC*CH=CH.CO,Me __t trans-( 18)essential oil of M. inodora 171 and probably in other C o m p o ~ i t e a . ~ ~ ~ Re-lated acetylenic alcohols, ketones, and hydrocarbons occur in this family butdiscussion is outside the scope of the present Report, The distribution ofacetylenic compounds amongst the tribes of the Compositeze, and species ofthe Erigeron genus is summarised by Sorensen 173 and a study of this aspecthas use in botanical classification.The antibiotic amide agrocybin, recognised by Anchel174 as a poly-yne,occurs in the culture liquid of Agrocybe dura and is known by synthesis 175to have structure (20). From Clytocybe diatreta a half amide (21) is ob-tained : 176 synthesis 176 confirms its structure.The corresponding nitrile(22) also occurs n a t ~ r a l l y . 1 ~ ~ A remarkable acid, mycomycin (23), has beenisolated from the culture fluid of Norcardia acidophilus : on treatment withdilute alkali an allene-acetylene rearrangement sets in to give the isomer(24),178 the structure of the latter having been confirmed by synthesis :179HEC-Li + OHC*CH=CH*CH=CHa HEC*CH(OH)CH=CH*CH=CH,PBr, CU-HC5C*CH=CHCH=CH*CH2Br HCEX*CH=CH.CH=CH*CHa.CNHCNHCzCGC-Me MeOH--w MeGC-CZC*EC*CH=CH*CH.CH,.CN __Q (24)H+~~ ~165 T.Bruun, P. K. Christiansen, C. M. Haug, J. Stene, and N. A. Sorensen, Acla.166 J. D. Bu’Lock, E. R. H. Jones, and W. B. Turner, Chem. and Ind., 1955, 686.187 K. Stavholt and N. A. Sorensen, Aclu Chem. Scand., 1950, 4, 1567.168 F. Bohlmann and H.-J. Mannhardt, Chem. Ber., 1955, 88, 429.P. K. Christiansen and N. A. Sorensen, Acta Chem. Scand., 1952, 6, 602.170 J. S. Sorensen, T. Bruun, D. Holme, and N. A. Sorensen, ibid., 1954, 8, 26.1 7 1 N. A. Sorensen and K. Stavholt, ibid., 1950, 4, 1080.1 7 2 Idem, ibid., p. 1575.1 7 3 N.A. Sorensen, Chem. and Ind., 1953, 240.174 M. Anchel, J . Amer. Chem. SOC., 1952, 74, 1588.1 7 5 E. R. H. Jones and J. D. Bu’Lock, J., 1953, 3719; J. D. Bu’Lock, E. R. H.Jones, G. H. Mansfield, J. W. Thompson, and M. C. Whiting, Chem. and Ind., 1954, 990.1 7 6 M. Anchel, J . Amer. Chem. SOC., 1953, 75, 4621; M. Anchel and M. P. Cohen,J . Biol. Chem., 1954, 208, 319.1 7 7 M. Anchel, Trans. N . Y . Acad. Sci., 1954, 16, 337; Science, 1955, 121, 607.1 7 8 W. D. Celmer, and I. A. Solomons, J . Amer. Chem. Soc., 1952, 74, 1870, 2245,3838; 1953, 75, 1372.1711 F. Bohlmann and H. G. Viehe, Chem. Bey., 1954, 87, 712.Chem. Scand., 1951, 5, 1244CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS. 31 1Nemotinic acid is found to be the hydroxy-acid (25) ; 180 it occurs togetherwith the corresponding lactone, nemotin.HOCH ,-CC* C-=C.C-=C *CO*NH ,HO,C*CH=CH*CXGC.CO.NH,HO,C*CH=CH*GC-CCCNC tHC-CGC*CH=C=CH*CH=CH-CH=CH.CH,-CO,H (23)t tMeC*EC*CC*CEC*CH=CH CH=CH *CH,*CO,H (24)HEC*EC*CH=C=CH*CH (OH) -CH,*CH,*CO,H (25)Besides these acetylenic acids, others occur as glycerides in the seed fatsof higher plants : tariric acid (26) was in fact the first acetylenic substanceto be recognised in Nature.181 Its structure is confirmed by twosyntheses.182.126 Ximenynic and 8-hydroxyoctadec-trans-1 l-en-9-ynoic acidhave already been referred to (p.308). The structure for the conjugateddiyne, erythrogenic (isanic) acid (27), found in the seed fats of Onguekoaspecies, is now on a firm basis since its synthesis 183 by cross-coupling ofdec-9-ynoic acid with octa-l-ene-7-yne.Natural erythrogenic acid is knownto contain an incompletely described enediyne impurity named bolekicacid.184 An acetylenic acid, isanolic acid, has been isolated 185 from thesame oil ; the ascribed structure (28) 186 requires confirmation.MefCH,] lo*~C~[CH2],*C02H (26)CH,=CH.[CH2]4*CC*CC*[CHz],*C0,H (27)Pr~CH=CH*CC*G~C*CH,*CH(OH)*[CH,],*CO,H (28)In the past, acetylenic acids have tended to be regarded as mere curiosi-ties. The steadily mounting list, and their occurrence in the highest andlowest groups of plants, indicate that more serious biochemical attentionmust be paid to them. In particular, work on the metabolism of theacetylenic linkage is overdue and its relation, if any, to the olefinic linkage, isin need of study.Natural isoButy1amides.-A distinct group of plant acids occur asisobutylamides : the latter have insecticidal and sialogogue properties buttheir role in plant metabolism is not known. Jacobson 187 has shown thatsynthetic N-isobutyldeca-tram-2 : trans-6 : trans-8-trienamide is identicalwith the isomerisation product of affinin (from HeZzoPsis Zongipes) whichmust be one of the stereoisomers (29).The structure originally proposed 188for herculin (from Zanthoxylzcm claraherculis bark), N-isobutyldodeca-1 : 8-dienamide (30), is incorrect as all four stereoisomers have been synthesisedand none is identical with the natural product.la9 neoHerculin (probably a180 J.D. Bu’Lock, E. R. H. Jones, and P. R. Leeming, J., 1955, 4270.181 A. Amaud, Compt. rend., 1892, 114, 79; Bull. SOC. cham. France, 1892, 7 , 233.182 P. B. Lumb and J. C. Smith, J., 1952, 5032.183 H. K. Black and B. C. L. Weedon, J., 1953, 1785.184 E. R. H. Jones, M. C. Whiting, J. B. Armitage, C. L. Cook, and N. Entwistle,185 H. P. Kaufmann, J. Baltes, and H. Herminghaus, Fette u. Seifen, 1951, 53, 537.l a 6 A. Seher, Annalen, 1054, 589, 222.187 M. Jacobson, J . Amer. Chem. Sot., 1954, 76, 4606; 1955, 77, 2461.189 R. A. Raphael and F. Sondheimer, J., 1950, 115; 1951, 2693; L. Crombie, J.,Nature, 1951, 168, 900.Idem, ibid., 1948, 70, 4234.1952, 2997; N. A. Dobson and R. A. Raphael, J., 1955,3558312 BIOLOGICAL CHEMISTRY.purer specimen of herculin) has been isolated from the same source andstructure (31) proposed.lW Echinacein (from Echinacea angustifolia) maybe similar to, or identical with, neoherculin.191 The proposed lg2 structure(32) for pellitorine from Anacyclus Pyrethrum root has also been disproved lg3by synthesis of the four stereoisomers.It is a mixture of at least threedifficultly separable substances of the type R*CH=CHCH=CH*CO*NHBui inwhich R is a C,, C,, and C, saturated or unsaturated unit.lgP A dienediyneisobutylamide anacyclin (33), isolated from the same r00t,194 is not insecti-cidal but becomes so on partial hydrogenation of the diyne system. Thecompound N-isobutyldeca-trans-2 : trans-4-dienamide is insecticidally activeagainst Musca domestica but the other three stereoisomers are less thanone-tenth as active.129, lg5t tMe*[CH=CH] aCH2CHa*CH=CH CO *NH Bu~Pm*CH=CH*[CH,] ,CH=CH *CO*NHBdMe*[CH=CH]s*CHaCHa*CH=CHCO*NHBu~Prn*CH=CH.[CH,]a.CH=CH*CO.NHBulPrn*[EC],*CH,*CH,*[CH=CH] ,*CO*NHBd (33)Pm.CH=CH CH,*CH,* [CHZCH] ,*CO*NHBu* (34)Me,CH*CH=CH*[CH,],*CO*NH*CH,.C,H,(OH)~OMe-l : 4 : 3 (35)Since N-isobutyldeca-trans-2 : trans-4 : trans-8- and -trans4 : trans-4 : cis-8-trienamide (34) have been synthesised,lg5 there is no doubt that sanshool I(from ZanthoxyZum pi$erit.um) does not possess the structure proposed byAiharalg6 or has never been obtained in a state approaching purity.Asynthesis of the branched-chain vanillin derivative capsaicin (39, the activeprinciple of red peppers, is reported.lQ7Analysis of Component Acids of Fats and Waxes.-This work occupiesinvestigators in many parts of the world and, apart from its commercialinterest, yields information useful for correlation with biological classification:if carried out critically it can lead to detection of new types of fatty acids.However, there is scope for the employment of newer and more searchingmethods of investigation.Chromatography seems promising and has beenapplied with good results to palm-kernel oil and watermelon-seed oil.29Hydrogenation, in conjunction with a chromatographic method, is anexcellent way of determining the distribution of chain lengths in a mixtureof acids.s1 Unsaturated acids may be separated and determined by hydr-oxylation with performic acid, followed by reversed-phase chromatographyon a rubber 1g8 or castor-oil column.199recently investigated are those from Hedera japonica Among plant oils190 L.Crombie, J., 1955, 995.1 9 1 M. Jacobson, Science, 1964, 120, 1028.192 Idem, J . Amer. Chem. Sac., 1949, 71, 366.193 R. A. Raphael and F. Sondheimer, J., 1950, 120; L. Crombie, J., 1952, 4338.104 Idem, J., 1955, 999.195 L. Crombie and J. D. Shah, J., 1955, 4244.197 L. Crombie, S. H. Dandegaonker, and K. B. Simpson, J., 1955, 1025.108 K. Hofmann, C.-Y. Yuan Hsiao, D. B. Henis, and C. Panos, J . Bid. Chew.,109 S . Bergstrom and K. Paabo, A d a Chem. Scand., 1954, 8, 1486.zoo See also T. Kashimoto, J . Chern. Sac. Japan, 1954, 75, 1110.T. Aihara, J . Pharm. SOC. Japan, 1950, 70, 405, 409.1955, 217, 49CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS.313fruits,201 acorns,2o2 coconuts,2~ palm-kernelsJm and the seeds of AnamirtaC O C C U ~ U S , ~ ~ Mucuna @wiens,206 Courupita g u i a n e n ~ i s , ~ ~ Culophyllumwightianum ,208 Elletaria cardarnom~m,~~~ Hippopha rhamnoidesJ210 Hal-optella integrifolia,211 Desmodium gangeticum,212 Bombax s e ~ s i l e , ~ l ~ andLupinus terrnis.213 Analysis of oils from Aspergillus nidulans,214 fresh-waterplants,215 and seeds of the Crucifer= 216 and Cucurbitace~~~l~ as well as twowild Arachis species,218 are reported and there is new information on waxes(~arnauba,l*~ j~te,~19 hinoki leaf ,220 espa.rto,221 and onion-bulb 222).Acids from ckloroplast lipids have been investigated.2BReports are available on fats of the chimpanzee,224 puma,225 tiger,225snake,226 and and the rnesenteric fats of Leporinus o@nis 228and Pimelodus a l b i ~ a n s .~ ~ ~ Lipids of Ascaris lumbricoides,230 as well asshark the body fats of some marine fish,232 Clupea Pilchard~s,~3~Corbicula ~ a n d a i , ~ ~ ~ Lamonema r n o ~ o s u m , ~ ~ ~ and a number of aquaticinvertebratesJB6 have been investigated.and the ovarian dermoid cyst have been examined.238Lipids of globe-fish ovariesG. Kurono, T. Sakai, and I. Seki, Report. Fac. Pharm. Kanazawa Univ., 1954,4, 1.202 N. F. de Castro, Diss. Abs., 1955, 15, 44.203 A. P. Dale and M. L. Meara, J . Sci. Food Agric., 1955, 6, 162.204 Idem ibid., p. 166.205 2’. R. Kasturi and B. H. Iyer, J . Indian Chem.SOC., 1954, 31, 623.206 P. V. Nair and K. S. M. Pillai, Bull. Central Res. Inst., Univ. Travancore, 1954, A ,207 N. S. Bai, ibid., p. 114.208 K. V. Nair and N. S. Varier, ibid., p. 161.209 T. V. Kasturi and B. H. Iyer, J . Indian Inst. Sci., 1955, 37, 106.210 H. P. Kaufmann and A. V. Roncero, Grasas y Aceites, 1955, 6, 81, 129.211 M. 0. Farooq and M. S. Siddiqui, Fette u. Seijen, 1955, 57, 389.B. K. Avasthi and J. D. Tewari, Arch. Pharm., 1955, 288, 272.213 D. N. Grindley and A. A. Akour, J . Sci. Food Agric., 1955, 6, 461.214 J. Singh, T..K. Walker, and M. L. Meara, Biochem. J., 1955, 61, 85.215 M. I. Chechinkin, BioRhiuniya, 1955, 20, 249.a16 E. Andre and M. Maille, Compt. rend., 1954, 239, 1531.217 M. M. Chakrabarty, D. K. Chowdhury, and B.K. Mukherji, Naturwiss., 1955,42, 344; J . Amer. Oil Chemists’ SOG., 1955, 32, 384.218 T. A. Pickett. ibid., p. 521.219 W. G. Macmillan, A. B. Sen Gupta, and A. Roy, J . Indian Chew. Soc., 1955,32,79.220 T. Kariyone and K. Isoi, J . Pharm. SOC. Japan, 1955, 75, 316.221 A. SoIer and G. GuzmAn, Publ. Inst. Quim. Alonso BaYba, 1954, 8, 245.222 M. Okajima, J . Sci. Res. Inst., Tokyo, 1954, 48, 281.223 K. L. Zirm, A. Pongratz, and W. Polesofsky, Biochenz. Z., 1955, 326, 405.224 F. D. Gunstone, Biochem. J., 1955, 59, 454.225 Idem, ibid., p. 455.226 Y. D. Karkhanis and N. G. Magar, ibid., 1955, 60, 565.227 S. P. Pathak and G. D. Pande, J . Sci. Food Agric., 1955, 6, 48.228 R. R. Brenner, S. A. Quaglia, and P. Cattaneo, Anales Asoc. quim.argentina,229 R. R. Brenner, W. H. E. Reinke, and P. Cattaneo, ibid., 1955, 43, 67.230 D. Fairbairn, Canad. J . Biochem. Physiol., 1955, 33, 31, 122.231 S. P. Pathak and G. D. Pande, J . Amer. Oil Chemists’ SOC., 1955, 32,.7; S. P.Pathak and P. N. Suwal, ibid., p. 229; G. G. Kanath and N. G. Magar, J . Indzan Chem.SOC., 1955, 32, 455.232 Y. D. Karkhanis and N. G. Magar, J . Amer. Oil Chemists’ SOC., 1955, 32, 492.233 R. I. Cheftel, J. Moretti, and J. Polonovski, Bull. SOC. Chim. biol., 1955, 37, 709.234 T. Hori, J . Chem. SOG., Japan, 1954, 75, 1144.235 S. Komori and T. Agawa, Technol. Reports Osaka Univ., 1954, 4, 405.236 Y. Toyama and T. Takagi, J . Chem. SOC. Japan, 1955, 76, 237, 240, 243.as7 R. Umezawa, J . Pharm. SOC. Japan, 1955, ‘95, 494.238 Y .Takata, T. Matsuda, and Y . Takata, ibid., 1954 .74, 1401.3, 83.1954, 42, 1923 14 BIOLOGICAL CHEMISTRY.Metabolism and Function of Long-chain Fatty Acids.*-Excellent reviewsof recent advances in fatty-acid metabolism are available; 239 only a fewnew developments will be mentioned. Agreed systematic names for enzymesinvolved in the fatty-acid cycle are listed.239dThe sequence of events in the Lipmann-Lynen '' cycle " has been dupli-cated,m irreversibly, without the use of enzymes, but the chemical methodsemployed are remote from those possible under physiological conditions.They are summarised below. Steps in the (irreversible) chemical sequence12R*C0.NH*CH,*CH2-S.COMe z, R*CO*NH-CH,*CHz*S*CO*CH9*COMeR*CO.NHCH,*CH,*S.COCH,CH,Me[ + R-CO*NH*CH,*CH,*SH]3R*CO-NHCH,CH,*S*CO*CH=CHMe .% R*CO-NH*CH,CH,*S*CO*CH,*CHMe*OH[R = Me] are : 1, Claisen condensation with mesitylmagnesium bromide ;2, sodium borohydride ; 3, thermal dehydration on distillation ; 4, catalytichydrogenation.Enzymes of (reversible) biological " cycle " [R = APP(3-adenylpyrophosphoryl-4'-pantothenyl)] are : 1, p-ketoacylthiolase ; 2, p-hydroxyacyldehydrogenase ; 3, crotonase ; 4, acyldehydrogenase. (Donorsand acceptors are omitted.)A sequence of reactions analogous to the reversible CoA cycle, butinvolving pantetheine thioesters in place of those of CoA, has been an-n0unced.~~1 An interesting feature is the slow speed of hydration of trans-or cis-crotonylpantetheine under the influence of crystalline liver crotonase(0.013% and 0.0023% respectively of the rate for the corresponding reactionsinvolving CoA derivatives).Unlike the CoA cycle, the pantetheine cycle isnot directly linked to the citric acid cycle : it may be concerned in isoprenoidsynthesis.More information about the stereospecificity of two steps in the fatty-acidcycle is available. According to Stem and his colleagues,N2 crystallinecrotonase hydrates both cis- and trans-crotonylCoA to (+)-3-hydroxy-butyrylCoAc (as identified by enzymic assay) in the step :A stereospecific dehydrogenase from pig liver or rat heart oxidises (+)- butnot (-)-3-hydroxybutyrylCoA according to :Me*CH(OH)CH,*CO*CoA + DPN+ e, Me-COCH,*CO*CoA + DPNH + H+However, a racemase occurring in ox and rat liver can racemise (-)-3-hydr-oxybutyrylCoA, and the (+)-isomer is then oxidised.Crystalline crotonase239 ( a ) Ref. 1 ; (b) D. E. Green, Biol. Rev. Cambridge Phil. Soc., 1954, 29, 330;(c) F. Lynen, Ann. Rev. Biochem., 1955, 24, 653; ( d ) idem, Angew. Chem., 1955, 67,463; (e) E. R. Stadtman. Record Chem. Progress (Kresge-Hooker Sci. Lib.), 1954, 15, 1.Z4O J. C. Sheehan and C. W. Beck, J . Amer. Chem. SOC., 1955, 77, 4875.241 J. R. Stern, ibid., p. 5195.242 J. R. Stern, A. del Campillo, and A. L. Lehninger, ibid., p. 1073. * Abbreviations used are : CoA. coenzyme A ; AcCoA, S-acetyl-coenzyme A ;ATP. adenosine triphosphate ; DPN+ and DPNH, oxidised and reduced coenzyme I ;TPNH reduced coenzyme 11.MeCH=CH*CO*CoA + HzO MeCH(OH)*CH,-CO*CoA (+)-(36)( +)- (36CROMBIE : NATURAL LONG-CHAIN FATTY ACIDS.315can dehydrate (+)- but not (-)-(36) : the latter must first be treated withracemase. On the other hand, Wakil 243 reports that a fraction from beef-liver mitochondria (A) catalyses a DPN+ specific oxidation of (-)-3-hydroxy-butyrylCoA, and formulates the apparent racemisation as :A (-)-(36) + DPN+- - Me*CO*CH,*CO*CoA + DPNH + Hf(+)-(36) + DPN+ <B is the dehydrogenase specific for (+)-isomers.The hydration product of trans-crotonylCoA is oxidised by DPN+ in thepresence of B, whilst the hydration product of cis-crotonylCoA is not.However, in the presence of A, the latter product is oxidised by DPN+.Popj&k and Tietzw report that a soluble enzyme system, involvingneither mitochondria1 nor microsomal fractions, can be obtained from themammary glands of lactating rats; it effects synthesis of long- and short-chain fatty acids from acetate, has an absolute requirement for ATP, and isstimulated by oxaloacetate, a-oxoglutarate, succinate, and, particularly,malonate.The effect of poisons has been investigated and presence of apyruvic oxidase is inferred. A similar system synthesising fatty acids hasbeen obtained 245 from rabbit mammary glands where the rate-limitingprocess is one or both of the steps (i) from 3-hydroxyacylCoA to un-saturated acylCoA, (ii) from unsaturated acylCoA to saturated acylCoA.Experiments with a rat-liver preparation indicate that, in the bio-synthesis of fatty acids, TPNH may be needed as a specific electron donor inthe reduction of unsaturated acylCoA derivativesa6An enzyme preparation (solubilised by sodium choleate) from peanutcotyledon microsomes, having the same co-factor requirements as themicrosomal enzymes in sit%, has been made." No co-factor is needed forproduction of 14C0, from [l-14C]palmitic acid, but DPN+ is required forproduction of 14C0, from internally labelled palmitic acid.The oxidativemechanism does not involve CoA or the tricarboxylic acid cycle. Heat-stable substances, from cotyledons of germinating seeds, which catalyse theoxidation of [l-14C]palmitic acid to 14C0,, are identified as glycollic andL-lactic acid (the D-acid is inactive).248 The system is equally active forlabelled stearic, palmitic, and myristic acid, but weakly active for lauric,and inert for lower acids.Carboxy-labelled 2-hydroxypalmitic acid isunaffected, but the 2-oxo-acid is rapidly attacked. Geyer and his co-workers 249 now state that in non-enzymic experiments [l-14C]-palmitic and-stearic acid are converted, under mild conditions, by ascorbic acid andoxygen into 14C0,. Short-chain acids are not responsive. The authorscomment that the ascorbic acid content of germinating seeds reaches >60 mg. 1100 g. of tissue a few days after germination starts.243 S. J. Wakil, Biochim. Biophys. Acta, 1955, 18, 314.244 G. PopjAk and A. Tietz, Biochem. J., 1955, 60, 147, 155.246 P. Hele and G. Popjbk, Biochim. Biophys. Acta, 1955, 18, 294; Biochem. J.,246 R . G. Langdon, J . Amer.Chem. Soc., 1955, '77, 5191.247 T. E. Humphreys and P. K. Stumpf, J. Biol. Chewz., 1955, 213, 941.248 P. Castelfranco, P. K. Stumpf, and R. Contopoulou, ibid., 1955, 214, 567.24a R. P. Geyer, L. Marshal1,M. Ryan, and S. Westhaver, Arch. Biochem. Biophys.,1955, 80, xxxii.1955, 56, 549316 BIOLOGICAL CHEMISTRY.Positive evidence for fatty acid oxidation occurring in tumour mito-chondria has now been obtained.250 Speculative schemes for the formationof plant waxes through acylCoA intermediates are prop0sed.~51More has been published on the effects of the enzyme lipoxidase whichcan be obtained crystalline from soya-bean : it catalyses the peroxidation oflinoleic, linolenic, and arachidonic acid and their e~ters.25~ The principalproducts are optically active cis-trans-conjugated monomeric hydroperoxidesat 0” or 26” in either the dark or daylight; some optically active polymer isalso f0rmed.~53 The enzyme is believed to be involved in the formation ofeach peroxide molecule : 254 it is inactive towards the cis-9 : trans-12- andtrans-9 : trans-12-stereoisomers of linoleic acid.A coupled oxidation ofglutathione and an unsaturated acid of the linoleic type, under the influenceof lipoxidase (two reactions at least are involved, one cyanide-sensitive andone insensitive), has been reported 255 for germinating peas. Extracts fromungerminated peas show no lipoxidase activity but it is initiated by smallamounts of alcohol. The lipoxidase enzyme and substrate are associatedwith the soluble part of the cytoplasm and are absent from the mitochondria.Lipoxidase activity has been studied 256 in maize seedlings at pH 5.0 and 7-2.Recent work shows that linoleic, linolenic, and lauric acid are consider-ably more active as plant-wound hormones than traumatic acid : theiraction is enhanced by cytochrome-C, CoA, and ascorbicL.c.5. THE ENZYMIC HYDROXYLATION OF STEROIDS.Some aspects of the biochemistry of steroid hormones were reviewed inthese Reports 1 in 1951. Advances in this field continue to be so varied andnumerous that a too general survey is liable to be superficial : so this Reportdeals solely with enzymic hydroxylations of steroids.0x0- and hydroxy-groups are the principal substituents in the steroids ofanimal origin. Almost all of them have an oxygen substituent at position 3.In addition, hydroxyl groups are commonly found at positions 7, 11, 12,16, 17, 20, and 21, and less commonly at 6, 18, and 19.Certain physio-logically active plant steroids and toad-venom steroids have hydroxylgroups at other positions, notably 5 and 14; nothing is known regarding thebiological introduction of such groups.Hydroxyl groups may apparently be introduced directly into the mole-cule, as in the formation of 17a-hydroxyprogesterone from progesterone, orthey may arise by reduction of ketones formed on the removal of side chainsat position 21 or 17: such hydroxyl groups will not be considered.1 1 -Hydroxylation.-The dramatic clinical effects of cortisone discovered250 P. Emellot and C.J. Bos, Experientia, 1955, 11, 188.351 G. G. Wanless, W. H. King, and J. J. Ritter, Biochem. J., 1955, 59, 684.2S2 R. T. Holman and S. Bergstrom in J. B. Sumner and K. Myrback’s “TheEnzymes,” Vol. 11, Academic Press, New York, 1951.253 0. S. Privett, C. Nickell, W. 0. Lundberg, and P. D. Boyer, J . Amer. Oil Chemists’Suc., 1955, 32, 505; 0. S. Privett, F. J. Pusch, and R. T. Holman, Arch. Biuchem.Biophys., 1955, 57, 156.zs4 A. L. Tappel, P. D. Boyer, and W. 0. Lundberg, J . B i d . Chern., 1952, 199, 267.255 L. W. Mapson and E. M. Moustafa, Biochem. J., 1955, 60, 71.25~3 G. Fritz and H. Beevers, Arch. Biochem. Biophys., 1955, 55, 436.257 A. J. Haagen-Smit and D. R. Viglierchio, Rec. Trav. chim., 1955, 74, 1197.1 Ann. Reports, 1951, 48, 297GRANT : THE ENZYMIC HYDROXYLATION OF STEROIDS.317by Hench and his co-workers2 in 1949 provided a powerful stimulus toorganic chemists interested in natural steroids. Especial efforts weredirected towards the production of steroids having an 11-oxygen function.Apart from the purely chemical approaches (reviewed by Rosenkranz et d3),biochemical methods have been extensively investigated. As a result moreis known about hydroxylation at the 11-position than at any other. Usingorgan perfusion, Hechter et aL4 demonstrated 11 P-hydroxylation of a numberof steroids by ox adrenals. The authors were careful to point out that theywere concerned to find only whether a reaction could take place in the adrenaland, if so, at what rate. They were less interested in the physiologicalstate of the adrenal glands, which actually gave greater yields of steroidafter rough handling, and they did not claim that the reactions observedwere of physiological importance.These limitations have not always beenborne in mind when the results obtained have been discussed by others inrelation to the biosynthesis of adrenocortical steroids. Ascorbic acid,which disappears from the adrenal glands during steroid hormone secretion,and the adrenocorticotrophic hormone (ACTH) were added to the perfusionmedium in order that the gland might be working at maximum capacity.Neither substance, however, had any effect on llp-hydroxylation of thesteroids investigated, and the opinion was expressed that ACTH influencesRI coR’H(1) R = CH,*OH; (4) R = :O;R’ = H.(6) R = -OH, R’ = * OH.(2) R = CH,*OH ; . * * H . (5) R = :O;R’ = OH. (10) R = -OH, R’ = -OH.(7) R =Me; (9) R’ = :O;R‘ = H. (11) R = -CH(OH)*CH,*OH, R = -CO*CH,*OH.(8) R =Me:R’ = OH.(3) R = :O.- - - CHXH,.* - * OH.[Throughout this section, rings omitted from fornuke are those of the first formulaabove.]adrenocortical steroid biosynthesis at some point before the 11 P-hydroxyl-ation reaction. Crystalline 11 8-hydroxy-derivatives were isolated andcharacterized after perfusion of 1 1-deoxycorticosterone 49 (l), 17a-hydroxy-deoxycorticosterone 4y (2), androst-4-ene-3 : 17-dione (3), androsterone 4P. S. Hench, E. C. Kendall, C . H. Slocomb, and H. F. Polley, Proc. Mayo CZin.,1949, 24, 181.3 G.Rosenkranz, F. Sondheimer, A. Mancera, J. Pataki, H. J. Ringolo, J. Romo,C . Djerassi, and G. Stork, Recent Progr. Hormone Research, 1953, 153, 8, 1.4 0. Hechter, A. Zaffsroni, R. P. Jacobsen, H. Levy, R. W. Jeanloz, V. Schenker, andG. Pincus, ibid., 1951, 6, 215.5 H. Levy, R. W. Jeanloz, C. W. Marshall, R. P. Jacobsen, 0. Hechter, V. Schenker,and G. Pincus, J . Bid. Chem., 1953, 203, 433.Q R. W. Jeanloz, H. Levy, R. P. Jacobsen, 0. Hechter, V. Schenker, and G. Pincus,ibid., p. 453318 BIOLOGICAL CHEMISTRY.(4), epiandrosterone (5), testosterone * (6), progesterone (7), l7a-hydroxy-progesterone (8), and 21-hydroxy-5a-pregnane-3 : 20-dione (9) through oxadrenals. The transformation of progesterone was very poor (<l%). Noreaction occurred with vinyltestosterone (10) or with 17a : 20 : 21-trihydr-oxypregn-4-en-3-one (1 1).11 p-Hydroxylation did not occur when steroidswere perfused through human placenta or through rat liver.* The questionof 11 P-hydroxylation by the liver has given rise to some controversy. Kahntand Wettstein lo claimed to have obtained 1-5% conversion of 17~~-hydr-oxydeoxycorticosterone into cortisol (1 1 p : 17% : 21-trihydroxypregn-4-ene-3 : 20-dione) (12) with homogenates of rabbit or ox liver or kidney : Dorf-man et aL6> l1 and Grant l2 have not been able to confirm this. A claim tohave converted 17a-hydroxydeoxycorticosterone into cortisol with liver wassubsequently withdrawn by Hubener et al. ; l3 the substance confused withcortisol was 17a : 20 : 21-trihydroxypregn-4-en-3-one (11).This is anRI coexcellent example of the result(12) R = CH,*OH; R’ = OH.(13) R = CH,*OH; R‘ = H.(14) R =Me; R’ = H.of inadequate characterisation of a steroidtransformation-product, a fault to be giarded against in facile, uncriticaluse of paper chromatography.Following Hechter et aL4 several groups have made detailed investigationsof 11 p-hydroxylation. Hayano et aZ.14 incubated ox adrenal slices, minces,and homogenates with deoxycorticosterone and observed an increasedglycogenic activity which they ascribed to the formation, from deoxy-corticosterone, of an 11 p-hydroxy-steroid, later identified l5 as corticosterone(13). Subsequently they obtained a residue on centrifuging adrenal homo-genates at 5000 g ; after washing this with saline or water, they referred toit as a purified llp-hydroxylase ~reparati0n.l~ Using this residue theydemonstrated the “ specificity and absolute necessity for fumarate andmagnesium ions and the stimulating capacity of adenosine triphosphate(ATP) and diphosphopyridine nucleotide (DPN+) ” for 11 P-hydroxylation ofsteroids.They suggested that fumarate might play some part in an energy-yielding system for the regeneration of ATP or might function as a hydrogenacceptor in steroid hydroxylation. Dorfman et al. reviewed this work andreported a number of llp-hydroxylations with the “ washed residues.’’ l17 A. S. Meyer, 0. G. Rogers, and G. Pincus, Endocrinology, 1953, 53, 245.L. R. Axelrod and G. Arroyave, J . Amer.Chem. Soc., 1953, 75, 5729.A. S. Meyer, unpublished work cited by 0. Hechter and G. Pincus, Physiol. Rev.,10 F. W. Kahnt and A. Wettstein, Helv. Chim. Acta, 1951, 34, 1790.11 R. I. Dorfman, M. Hayano, R. Haynes, and K. Savard, Ciba Foundation Colloquial 3 H. J. Hiibener and J. Schmidt-Thorn& 2. physiol. Chem., 1955, 299, 126.14 M. Hayano, R. I. Dorfman, and E. Y. Yamada, J . Biol. Chem., 1951,193, 175.l5 M. Hayano and R. I. Dorfman, ibid., 1953, 201, 175.1954, 34, 459.on Endocrinology, 1953, Vol. VII, p. 191.J. K. Grant, Unpublished workGRANT THE ENZYMIC HYDROXYLATION OF STEROIDS. 319Similar results were obtained by others.lO, 16~ 1 7 9 l8 has shown thatthe production of corticosterone and cortisol by 11 p-hydroxylation in hogadrenal homogenates is possible on a commercial scale. After a detailedstudy of co-factor requirements Kahnt et aZ.19 concluded that 11 p-hydroxyl-ation involved synthesis of ATP linked to oxidation of members of theKrebs tricarboxylic acid cycle.Credit for showing that 11 p-hydroxylatingenzymes are associated with adrenal-cell particles, which by their method ofpreparation were mainly mitochondria, is due to Sweat.20 Brownie andGrant 21 drew attention both to the unsatisfactory nature of the enzymepreparations and to the methods of steroid analysis used in earlier studies.Employing ox-adrenal cortical mitochondria, with careful exclusion of othercell components, and improved methods of steroid analysis, they confirmedthe requirement for concurrent oxidative phosphorylation for which addedcitric acid cycle intermediates are oxidisable substrates.It was not neces-sary to add DPN+, ATP, or Mg2+ to such mitochondrial preparations. a-OXO-glutarate was the best “activator” of llp-hydroxylation, and it wasdemonstrated that the “ intact ” mitochondria showed no specific fumaraterequirement for 11 P-hydroxylation. This disagreement with Hayano et aZ.15was explained when Brownie and Grant 22 showed that their mitochondrialpreparations developed a requirement for fumarate when treated withhypotonic media. Such preparations were unable to use a-oxoglutarate tosupport ” 11S-hydroxylation and, in addition to fumarate, required tri-phosphopyridine nucleotide (TPN+) or DPN+ + ATP. (The requirementfor TPN+ had also been shown by Hayano et u Z ., ~ ~ using glands stored a t 0”for long periods.) This suggested that Mg2+ and ATP are required for thephosphorylation DPN _+ TPN in the “ damaged ” particles of Hayano’senzyme preparation. The requirement for oxidative phosphorylation tosupport steroid hydroxylation, as observed by Brownie and Grant withintact ” mitochondria, is not, however, explained. The latter workershave suggested that entry of deoxycorticosterone into mitochondria may bean ‘‘ active ” energy-requiring process ; with the disappearance of penne-ability barriers (protein films ?) on washing of the mitochondria, this energyprovision would become unnecessary.The role of TPN+ and fumarate has been further investigated by Sweatand Lipscomb24 and by Grant and Brownie.25 The former showed thatglucose 6-phosphate and its dehydrogenase together can replace fumarate inan adrenal enzyme system which will 11 p-hydroxylate deoxycorticosteronein presence of TPN’.They concluded that the role of added members ofthe Krebs tricarboxylic acid cycle was to maintain TPN+ in the reducedstate (TPNH) according to the reactions (1) fumarate I) malate, (2)HainesD. A. McGinty, G. N. Smith, M. L. Wilson, and C. S. Worrel, Science, 1950, 112,K. Savard, A. Green, and L. A. Lewis, Ejzdocrinology, 1950, 47, 418.W. J. Haines, Recent Progr. Hormone Res., 1952, 7, 255.F. W. Kahnt, C. Meystre, R. Neher, E. Vischer, and A. Wettstein, Experientia,506.1952, 8, 422.2o M. L. Sweat, J . Amer. Chem.SOC., 1951, 73, 4056.21 A. C. Brownie and J. K. Grant, Biochenz. J . , 1954, 57, 255.22 Idem, ibid., 1956, 62, 29.23 M. Hayano, M. Weiner, and M. C. Lindberg, Fed. PTOC., 1953, 12, 216.24 M. L. Sweat and M. D. Lipscomb, J . Amer. Chem. SOC., 1955, ‘77, 5185.2 6 J. K. Grant and A. C. Brownie, Biochim. Biophys. Acta, 1955, 18, 433320 BIOLOGICAL CHEMISTRY.malate + DPN+ -+ oxaloacetate + DPNH, DPNH + TPN+ --+DPN+ + TPNH , involving the transdehydrogenase described by SanPietro, Kaplin, and Colowick.26 Grant and Brownie 25 produced evidencefor the reduction of TPN+ in a soluble enzyme system extracted from acetone-dried ox-adrenal mitochondria according to reactions (1) and (4) malate +TPN+ + pyruvate + TPNH + CO, or (5) isocitrate + TPN+ _+ a-oxoglutarate + TPNH, and they observed the ll @-hydroxylation of deoxy-corticosterone in dialysed preparations of the soluble enzyme to which2-amino-2-hydroxymethylpropane-1 : S-diol(" Tris ") buffer and TPNH werethe only additions.Hayano et have prepared a soluble enzyme, byextracting acetone-dried adrenal preparations, which requires TPN+ butnot fumarate for 11 p-hydroxylation. Sweat and Lipscomb 24 confirmed thisbut remarked that the slight activity observed in such extracts, withoutfumarate, represents the same small degree of activity observed in mito-chondrial preparations without added fumarate. Soluble enzyme prepar-ations are unlikely to be less dependent upon co-factor-generating systemsthan more highly organised particulate preparations. It may be concludedthat TPNH and oxygen alone are required for llp-hydroxylation of steroids.The availability of TPNH in cells in physiological steady states has beendemonstrated by Chance and Williams ,** and the high TPNH concentrationsin adrenal tissue found by Glock and McLean 29 may be of some significance.The requirements for TPNH and oxygen are remarkably similar to thosefound necessary by Brodie et aL30 for the hydroxylation of certain drugs byliver microsomes.These particles contain no cytochrome oxidase, but willoxidise TPNH via the autoxidation of flavoproteins, a reaction which resultsin the production of hydrogen peroxide. Brodie has suggested that hydrogenperoxide is the hydroxylating agent but was unable 31 to replace TPNH byenzyme systems generating hydrogen peroxide.32 He suggests that theH,02 formed by such systems does not enter the micros0mes.~1 Grant 33has shown independently that hydrogen peroxide generated by the uricacid-uricase system in the presence of his soluble adrenal-enzyme preparationis unable to replace TPNH for 11P-hydroxylation of deoxycorticosterone ;this system contains no permeability barriers to hydrogen peroxide.More-over an increase in oxygen concentration in the reaction mixture increasesthe rate of oxidation of TPNH but inhibits llp-hydroxylation. It thereforeappears unlikely that TPNH is required for production of hydrogen peroxide.A consideration of possible mechanisms for 11 p-hydroxylation of steroidsmay help to throw light on the role of TPNH.The proposal that the hydroxyl is introduced in the hindered Ilkposition of an ll-deoxysteroid (A) by way of the lla-hydroxy- (B) andll-oxo-compound (C) is discounted by the failure to reduce ll-oxo- to11 p-hydroxy-steroids by adrenal enzymes.% By analogy with the reactions,26 A.San Pietro, N. 0. Kaplan, and S. P. CoIowick, J . Bid. Chew., 1955, 212, 941.27 M. Hayano, R. I. Dorfman, and E. Rosenberg, Fed. Pruc., 1955, 14, 224.28 B. Chance and G. R. Williams, Nature, 1955, 176, 250.20 G. E. Glock and P. RlcLean, Biochem. J., 1955, 61, 388.30 B. B. Brodie, J. Axelrod, J. R. Cooper, L. Gaudette, B. N. LaDu, C. Mitoma, and31 B. B. Brodie, personal communication.32 D. Keilin and E. F. Hartree, Proc. Roy. Soc., 1038, B, 125, 171.33 J.K. Grant, unpublished work.34 A. Meyer, J . B i d . Chew., 1953, 203, 469.(3)S. Udenfriend, Science, 1955, 121, 603GRANT : THE ENZYMIC HYDROXYLATION OF STEROIDS. 321succinate + fumarate _.t malate, it has been suggested that steroid11 p-hydroxylation might proceed via an ethenoid intermediate (D). Dorf-man et aZ.11 and Brownie and Grant 22 produced evidence that the A9(11)- and(A 1 ( c )All-compounds are not intermediates. The former suggested that thesecompounds may give small amounts of the parent deoxy-steroid and thatthis will undergo 11 p-liydroxylation and so account for the report by Miescheret ~ 1 . ~ 5 that ethenoid compounds can act as intermediates. g-Jq or )pHOq(0)Fieser 36 proposed the reaction sequence (E) _j (F) , for which there is,Levy et aL5 suggested a mechanism involving however, as yet no evidence.R R0: (yp o:@(F)free hydroxyl radicals in the direct oxidation of deoxycorticosterone. Oneradical would remove and combine with the lla-hydrogen atom, and anotherwould enter the a-position and subsequently undergo inversion to the @-con-figuration.Again there is no evidence in support of this. Hayano andDorfman 37 showed that deuterium does not enter a stable position in thesteroid molecule when the 11P-hydroxylation reaction is carried out in 95%D20. Subsequently they38 and Sweat and Mason39 found that 1 8 0 didnot enter the ll@-hydroxyl group when the hydroxylation was performed inH21*0, but did enter there when the gas phase contained 1802.Theseobservations support the hypothesis that a steroid does not undergo dehydro-genation during 11 p-hydroxylation but is directly oxidised by molecular35 K. Miescher, A. Wettstein, and F. W. Kahnt, Acta Physiol. Latinoarnerican, 1953,3, 144.S c L. F. Fieser, Ciba Foundation Colloquia on Endocrinology, 1953, Vol. VII, p. 288.37 M. Hayano and R. I. Dorfman, J . Biol. Chem., 1954, 211, 227.38 M. Hayano and R. I. Dorfman, personal communication.39 M. L. Sweat and H. S. Mason, personal communication.REP.-VOL. LII 322 BIOLOGICAL CHEMISTRY.oxygen. Such a direct oxidation can occur non-enzymically at C(7) incholesterol, catalysed by traces of heavy metals. It has been formulatedby Bergstrom and Wintersteiner 40 as (G) _+ (H), (I), and (J).It is thusHo [“o&:.J -::&o (H 1L/\ (G 1HO &* (1 1 “omw ( J )Cholesterol derivatives.possible that steroid 11 p-hydroxylation proceeds via a peroxide (K).are, however, few analogies between the two formulations.cholesterol is presumably activated by the neighbouring double bond.TherePosition 7 inNOsuch activation is available for position 11 in deoxycorticosterone. Hydr-oxylation of deoxycorticosterone does not occur if enzymic activity isdestroyed by heat. Transformation of adrenocortical steroids to more polarsubstances when they are shaken in air with solutions of ferrous sulphate,ascorbic acid, or ethylenediaminetetra-acetate has been reported *l butthere is no indication that such reactions involve 11 p-hydroxylation.In seeking an explanation of the requirement for TPNH it may be ofinterest that certain phenolases show high selectivity towards hydrogendonors required for the formation of water in the reactions which they~atalyse.*~ It is possible that the llp-hydroxylase, which appears to catalysethe direct introduction of oxygen into the steroid molecule, requires TPNHfor the subsequent elimination of one oxygen atom as water.Thus the final details of the mechanism of llp-hydroxylation remainunsettled.The interesting possibility has, however, arisen that this reaction,which is probably the last step in the biosynthesis of adrenal hormones, isinfluenced by those processes 43 which control the level of reduced pyridinenucleotides in the cell.No general rules have been evolved regarding the type of steroid whichmay undergo 1 lp-hydroxylation in adrenal tissue.Neither the 17-sidechain nor the A4-3-oxo-grouping appears to be essential since androsterone(4) and ePiandrosterone 7 (5) have been transformed into the corresponding11 fi-hydroxy-derivatives by adrenal perfusion. Hydroxylation is , however,rather less readily achieved with these reduced steroids.40 S. Bergstrom and 0. Wintersteiner, J . Biol. Chem., 1941, 141, 597; 1942, 143,ti03 : 1942, 145, 309, 327.41 A. S . Keston and M. Carsiotis, Arch. Biochem. Biophys., 1954, 52, 282.42 H. S. Mason, Adv. Enzymol., 1965, 16, 105.43 B. Chance, “ Mechanisms of Enzyme Action,” Johns Hopkins Press Baltimore,1954, p. 399GRANT THE ENZYMIC HYDROXYLATION OF STEROIDS.323Clinical demands for cortisone led to an intensive study of the trans-formation of steroids by micro-organisms , which has proved both interestingand rewarding; this has been reviewed by Fried et aL4 and by Wettstein.&Of special interest are the observations which led to a valuable combinedmicrobiological and chemical synthesis of cortisone from readily availableprogesterone. Peterson and Murray 45 found that Rhizofius spp. convertedprogesterone (7) into the lla-derivative in yields up to 85-95%, it beingoften possible to recover the product by direct crystallisation from mycelialextracts. It was particularly fortunate that the lla-epimer was formed,since the A4-3-oxo-group of this substance may be reduced in good yield toa compound of the normal (5p) series suitable for subsequent introductionof 17- and 21-hydroxyl groups.Steroids with l l p - or ll-keto-groups giveaZZo(5a)-reduction products, and these are less readily reoxidised to A4-3-oxo-steroids in the final stages of the synthesis.46 Later 47 it was found possibleto obtain e+i( 11 a)-cortisol in good yield from 17a-hydroxydeoxycortico-sterone (2) by fermentation with Rh. nigricans, thus avoiding the necessityof eliminating and re-introducing the A4-3-oxo-group. It was also found 48that this versatile organism showed a high specificity for hl6-progesterone (la),readily available from steroid sapogenins such as diosgenin, giving 1 la-hydr-oxy-17a-progesterone (16) and thus unexpectedly giving a compound withthe side-chain in the t hermodynamically labile a-position.@ COMc ---+ HO.@-coMe fl(‘61(15)HO(14)Nothing is known of the co-factor requirements or enzymic mechanismsof these mould hydroxylations.Closely related species show remarkablespecificity with regard to direction of attack on the steroid nucleus.49 Sub-stituents in the nucleus have a profound effect on the nature of the trans-formation products. The steroids transformed are not natural substratesfor the mould enzymes, and it is possible that the reactions are attempts at‘‘ detoxication.” It is sometimes necessary to limit the amount of steroidsubstrate or to use deoxycorticosterone acetate on account of inhibitoryeffects of the free alcohol.4917a- and 21-Hydroxylation.-Hydroxylations at positions 17a and 21 are44 J.Fried, R. W. Thoma, D. Perlman, J. E. Herz, and A. Borman, Recent Progr.Hormone Res., 1955, 11, 149.44a A. Wettstein, Experientia, 1955, 11, 465.45 D. H. Peterson and H. C . Murray, J . Amer. Chem. SOL, 1952, 74, 1871 ; D. H.Peterson, H. C . Murray, S. H. Eppstein, L. M. Reinelre, A. Weintraub, P. D. Meister,and H. M. Leigh, ibid., p, 5933.46 0. Mancera, A. Zaffaroni, B. A. Rubin, F. Sondheimer, G. Rosenkranz, andC. Djerassi, ibid., p. 3711; T. H. Kritchevsky, D. L. Garmaise, and T. F. Gallagher,ibid., p. 483.47 D. H. Peterson, S. H. Eppstein, P. D. Meister, B. J. Magerlein, H. C . Murray,H. M. Leigh, A. Weintraub, and L. M. Reineke, ibid., 1953, 75, 412.48 P. D. Meister, D. H. Peterson, H.C. Murray, G. B. Spero, S. H. Eppstein, A.Weintraub, L. M. Reineke, and H. M. Leigh, ibid., p. 55.*O S. H. Eppstein, P. D. Meister, D. H. Peterson, H. C. Murray, H. M. Leigh, D. A.Lyttle, L. M. Reineke, and A. Weintraub, ibid., p. 408324 BIOLOGICAL CHEMISTRY.considered together because they are concerned in the formation of theadrenocortical hormone cortisol, and because there is evidence that thepresence of a hydroxyl group in one or other of these positions influences theease with which the other may be introduced. Early observations 50 thatcortisol (12) was formed when progesterone (7) was incubated with wholeox-adrenal homogenates suggested that 17- and 21-hydroxylating enzymeswere removed during the preparation of 1 l-hydroxylating enzymes.Plagerand Samuels 51 confirmed this; the supernatant fluid obtained on centri-fuging ox-adrenal homogenates for 0.5 hr. at 20,000 g contained enzymeswhich catalysed the 17a- and 21-hydroxylation of progesterone and possessedno 11 p-hydroxylating ability. Some 21-hydroxylation occurred on additionof DPN+, but 17a-hydroxylation appeared to require both ATP and DPN+,possibly for the formation of TPN+. Alternatively, ATP might " activate "the steroid molecule by forming a water-soluble phosphate. There is nosatisfactory evidence in favour of either suggestion and it is not clear whetherthe above enzyme preparation contained microsomes. If in fact it did,then ATP might be concerned in overcoming permeability barriers. Sexhad no effect on 21-hydroxylation, as judged by formation of deoxycortico-sterone from progesterone.The enzyme from heifer adrenals was, however,2-3 times more active in the formation of 17a-hydroxydeoxycorticosteronethan that from steer adrenals, and bull adrenals had intermediate effect.Dehydroepiandrosterone (3p-hydroxyandrost-5-en-17-one) (16), addedin vitro, suppressed formation of deoxycorticosterone and increased that ofits 17a-hydroxy-derivative (2) from progesterone (7). Dehydroepiandro-sterone (16) is itself oxidised to androst-4-ene-3 : 17-dione (3) by the sameenzyme preparation, but it would be difficult to explain the effect on 17- and21-hydroxylation by competition for some co-factor.11 p-, 17a-, and 21-Hydroxylation of steroids has been demonstrated withhuman tissues in d r o 52 and in v ~ v o .~ ~The order in which 1 1 p-, 17a-, and 2 1 -1tfydroxyl Groups are introduced.-In the scheme of adrenocortical steroid biogenesis advanced by Hechteret aZ.4 llp-hydroxyprogesterone is shown as a possible intermediate in theformation of corticosterone (13) or cortisol (12) from progesterone (7). Thestatus of 11 P-hydroxyprogesterone (17) as possible intermediate has beendiminished by the following facts. This steroid has been isolated in yieldsonly of less than 1% after perfusion of progesterone through adrenal glands,and has not been found among the products obtained on incubation ofadrenocortical tissue preparations with progesterone. Finally it has notbeen further hydroxylated to corticosterone or cortisol in significant yields.It was therefore suggested 54 that llp-hydroxylation sets the seal of a com-pleted product on the steroid.In view of the negative nature of the evidencethis suggestion may not be of great significance, especially since Brownie,Grant, and Davidson were able to effect llp-hydroxylation of progesteronein fair yield by using adrenal mitochondria. When the ll-hydroxyl group60 J. E. Plager and L. T. Samuels, Fed. Proc., 1952, 11, 383.ti1 Idem, Arch. Biochem. Biophys., 1953, 42, 477; J . Biol. Chem., 1954, 211, 21.62 G. Pincus, Ciba Foundation Colloquia on Endocrinology, 1955, Vol. VIII, p. 97.53 €1. Werbin, G. V. Le Roy, and D. M. Bergenstal, J . Lab. Clin. Med., 1955, 46,64 0. Hechter, Ciba Foundation Colloquia on Endocrinology, 1953, Vol.VII, p. 161.55 A. C. Brownie, J. K. Grant, and D. W. Davidson, Biochem. J.. 1954, 58, 218.964GRANT : THE ENZYMIC HYDROXYLATION OF STEROIDS. 326has the unnatural cc-configuration further hydroxylation at and C&l)can 0ccur.5~Hayano and Dorfman l6 found that washed homogenate residue prepar-ations were unable to use progesterone (7) or 17a-hydroxyprogesterone (8)as substrates for 11 p-hydroxylation and claimed that a 21-hydroxyl groupwas required for 11 P-hydroxylation. The formation of 11 p-hydroxy-progesterone already referred to 55 refutes this idea.In their perfusion studies Hechter et aZ.* noted the conversion of pro-gesterone (7) into corticosterone (13) and cortisol, whereas deoxycortico-sterone (1) gave corticosterone alone.In confirmation of this Plager andSamuels found no 17a-hydroxylation of deoxycorticosterone with theirsupernatan t-fract ion enzyme. Apparently 17 a-hydroxylat ion can onlyprecede 21-hydroxylation.The question of which compounds may or may not be hydroxylatedmust await detailed knowledge of co-factors required and the preparationof pure enzymes. Only in this way can the influence of steroid substrateson reactions supporting hydroxylations be eliminated.The annexed scheme summarises present knowledge of the individualsteps in 11P-, 17a-, and 21-hydroxylation.Progesterone 17a : 2 1 -Dihydroxyprogesterone I2 1 -Hydroxyprogesterone(deoxycorticosterone)1, 2, 3,4 1 11s : 21 -Dihydroxyprogesterone(corticosterone)1, 2, 3, 4 1 I 1 l&Hydroxyprogesterone 118 : 17a : 21-Trihydroxyprogesterone (cortisol)I-+ 1 lg : 17a-Dihydroxyprogesterone.1, By adrenal perfusion.2, By adrenal homogenate.3, By adrenal homogenate washed residue.4, By adrenal mitochondria.5, By supernatant fluid from centrifuged adrenal homogenate.6-HydroxyIation.-The first isolation of a 6p-hydroxylated steroidfrom mammalian tissue was reported by Haines l8 who obtained 6p-hydroxy-deoxycorticosterone (17) on incubation of deoxycorticosterone with hog-66 A.Zaffaroni and J. Hendrichs, Abs. 122nd Meeting, Amer. Chem. SOC., 1952,-1oc326 BIOLOGICAL CHEMISTRY.adrenal homogenate. Subsequently Hayano and Dorfman 57 obtained6p-hydroxycortisol (1 8) and Meyer et aZ.5s obtained 6p-hydroxyandrost-4-ene-3 : 17-dione (19) with ox-adrenal homogenate preparations. YieldsCH,*OHI0(17) R = H(18) R = OHwere increased by addition of ATP and DPN+.Others reported the form-ation of 6p-hydroxy-steroids in adrenal perfusion experiments.4~ 59 6p-Hydroxylation is not, however, confined to the adrenal gland, as 11 p-hydroxyl-ation appears to be. Hayano et aZ.60 obtained 6~-hydroxydeoxycortico-sterone on incubation of deoxycorticosterone with ox corpus luteum homo-genates, and Miller and Axelrod claim to have found 68-hydroxydeoxy-corticosterone among the transformation products of cortisone perfusedthrough cirrhotic rat livers; but, on finding no 6p-hydroxy-steroids on per-fusion of normal rat livers, they suggested that this occurrence of the 6p-hydroxy-compound might be related to the abnormal electrolyte metabolismoccurring during cirrhosis.The 6-hydroxy-steroids, however, have little orno effect on electrolyte metabolism. Although their physiological signi-ficance is obscure, 6-hydroxy-steroids appear to take some part in the steroidmetabolism of intact animals. They have been isolated from the normaland pathological urines of guinea-pigs 62 and human subjects. Grantfound that 6p-hydroxylation of deoxycorticosterone by adrenal preparationsappeared to have the same co-factor requirement as 11 p-hydroxylation ; 64the 11 p-and 613-hydroxy-steroids were formed in the approximately constantratio of 3 : 1. There was no evidence of the formation of 6p : llp-dihydroxy-compounds. Various steroids have given 6p-hydroxy-derivatives on incub-ation with micro-organisms.6516-Hydroxylation.-Various steroids are known to possess 16-hydroxylgroups, almost exclusively in the a-configuration. It is widely held that theintroduction of hydroxyl groups into the steroid nucleus in the positions 68,l l p , and 17a may be regarded as anabolic reactions. By contrast the 16-hydroxy-steroids have been thought to represent stages in the catabolism5 7 M. Hayano and R. I. Dorfman, Arch. Biochem. Bi@hys., 1954, 50, 218.5 8 A. S. Meyer, M. Hayano, M. C. Lindberg, M. Gut, and 0. G. Rogers, Acta Endo-5 o L. R. Axelrod and L. L. Miller, Arch. Biochem. Biophys., 1954, 49, 248.60 M. Hayano, M. C. Lindberg, M. Wiener, H. Rosenkrantz, and R.I. Dorfman,61 L L. Miller and L. R. Axelrod, Metabolism, 1954, 3, 438.62 S. Burstein, unpublished observation cited in ref. 60.133 S. Lieberman, K. Dobriner, B. R. Hill, L. F. Fieser, and C. P. Rhoads, J . Biol.Chem., 1948, 172, 263; S. Burstein, R. I. Dorfman, and E. M. Nadel, Arch. Biochern.Bioplzys., 1954, 53, 307.64 J. K. Grant, unpublished work.6 5 H. C. Murray and D. H. Peterson, U.S. P. 2,602,769/1952.crinol., 1955, 18, 148.Endocrinolog.y, 1954, 55, 326GRANT : THE ENZYMIC HYDROXYLATION OF STEROIDS. 327of steroids, preceding ring opening and the formation of more highly degradedproducts. Pregn-5-ene-3p : 16% : 20a-trio1 66 (20) 5a-pregnane-3p : 16% : 20p-trio1 67 (21), androst-5-ene-3P : 16a : 17P-triol 68 (22), androstane-3p : 16a : 17p-trio1 69 (23), and testane-3a : 16a : 17p-triol 69 (24) are typicalMeIH-C-OHMaIHO-C-HOHHO @--OHof the 16-hydroxy-steroids which have been isolated from urine and maypossibly be derived from adrenal or testicular hormone precursors.Thesuggestion that compound (22) arises from dehydroefiandrosterone (6) issupported by the observed transformation of the compound (6) into (22)in vitro by rabbit-liver slices.70Ofner 71 suggested that 16-hydroxy-steroids may be formed on incubationof testosterone with minced rat liver. It would be useful to have furtherevidence for the formation of 16-hydroxy-steroids in vitro and to investigatethe sites and mechanisms of hydroxylation in order to throw more light onthe origin of the urinary 16-hydroxy-steroids. (Estriol (25) is, of course, animportant 16a-hydroxy-steroid.Marrian and Bauld 72 isolated the 16p -epimer (26) from human pregnancy urine and suggested that ‘‘ 16-oxo-cestra-dio1-17p ” [3 : 17p-dihydroxycestra-1 : 3 : 5(10)-trien-16-one] might be acommon metabolic precursor of cestriol and epicestriol. Watson andMarrian 73 have since reported the detection of the 16-oxo-derivative (27) of6 6 H. Hirschmann and F. B. Hirschmann, J . Biol. Chern., 1950,184, 259.6 7 G. A. D. Haslewood, G. F. Marrian, and E. R. Smith, Biochem. J., 1934, 28, 1316.H. Hirschmann, J . Biol. Chem., 1943, 150, 363; H. L. Mason and E. J. Kepler,69 S. Lieberman, B. Praetz, P. B. Humphries, and K. Dobriner, Abs. 117th Meeting70 J. J. Schneider and H.L. Mason, J . Bid. Chem., 1948, 172, 771.72 G. F. Marrian and W. S. Bauld, Biochem. J.. 1955, 59, 136.73 J. Watson and G. F. Marrian, Biochem. J., 1955, 61, xxiv.ibad., 1945, 160, 265; 1947, 168, 73.Amer. Chem. SOC., 1950, 19c.P. Ofner, Biochem. J., 1955, 61, 287328 BIOLOGICAL CHEMISTRY." cestradiol-178 " in human pregnancy urine. There is no evidence, however,that oxidative attack of the steroid nucleus at position 16 differs from thatat position 6, 11, or 17a, where the primary product appears to be ahydroxy- and not an oxo-steroid.CH2*OH1R (25) R = * * OH, -H.(26) R = -OH, . * . H .(27) R = :O.0: HOProbably because of the lack of satisfactory methods for the extractionand determination of estrogens in tissues, no reliable study of the conversionof cestrone or estradiol into estriol has been reported.Until such methodsare available the nature of the 16-hydroxylation in these compounds willremain obscure.Considerable interest has been shown in the 16-hydroxylations readilyachieved by micro-organisms, since it was erroneously thought 74 at one timethat the adrenocortical hormone aldosterone (28) might be a 16~-hydroxy-deox ycort icost eron e derivative.18- and 19-Hydroxylations.-Stimulated by the discovery of aldosteroneand with growing experience in handling minute traces of steroids present intissues much interest has recently centred on the hydroxylation of theangular 18- and 19-methyl groups. During an investigation of the bio-synthesis of aldosterone Wettstein and his collaborators 75 obtained, amongother products, the 19- (29) and the hitherto unknown 18-hydroxy-derivative(L) of deoxycorticosterone by the action of ox-adrenal homogenates on thissteroid. Final proof of the identity of the 18-hydroxydeoxycorticosterone(L) involved its conversion to the 18-hydroxy-3-oxoeti-4-en-20-oic lactone(M). The homogenates were supplemented with ATP, DPN+, TPN+, andfumarate.No hydroxylation occurred on omission of fumarate. Wett-stein et aZ.75 also concluded that deoxycorticosterone is superior to cortico-sterone (13) as a precursor of aldosterone in their enzyme preparation.Although the oxidation of 18-hydroxydeoxycorticosterone (L) to aldosterone(28) is possible, it cannot be assumed that deoxycorticosterone and its1 8-hydroxy-derivative are the natural precursors of aldosterone.Onedifficulty to be reconciled would be the fact that deoxycorticosterone isderived from steroids, the production of which is stimulated by ACTH. Inthis way ACTH controls the production of further hydroxylated products,74 A. Wettstein, Experientia, 1954, 10, 397.7 5 F. W. Kahnt, R. Neher, and A. Wettstein, Helv. Chim. Acta, 1955, 38, 1237GRANT THE ENZYMIC HYDROXYLATION OF STEROIDS. 329i.e., of the hormones corticosterone and cortisol. It appears, however, thatsecretion of aldosterone in man is uninfluenced by ACTH.76The scale of working necessary to produce 19-hydroxydeoxycortico-sterone (30), which according to Wettstein 75 is found in amounts up to fourtimes that of 18-hydroxydeoxycorticosterone, may be judged from thefollowing reports.Mattox 77 isolated 10 mg. of the 19-hydroxy-derivativefrom 2060 Ib. of ox-adrenals; this was about one-fifth of the amount ofaldosterone obtained. Zaffaroni et al. 7* obtained 365 mg. on incubation of10 g. of deoxycorticosterone with a homogenate of 2.5 kg. of ox adrenals.Small quantities were isolated after perfusion of 90 g. of progesterone through600 ox adrenal^.^^ The best yield was obtained by Hayano and Dorfman 8owho isolated 5 mg. after incubation of 1 g. of deoxycorticosterone withwashed residues from ox adrenal homogenates. The 19-hydroxy-derivativehas only 4% of the activity of deoxycorticosterone in the sodium retentiontest and (2% of the activity of cortisol in the Ingle work test.mby81The biological significance of 19-hydroxy-steroids may, however, lie elsewhere.Meyer 82 has identified 19-hydroxyandrost-4-ene-3 : 17-dione (31) among theproducts obtained on incubating dehydroePiandrosterone (16) with ox0 00: "P 0:oadrenal homogenate, in an excellent piece of work which is a model of itskind.The dione (31) has little biological activity. It readily yields form-aldehyde from the CH,*OH group under mild basic conditions,= to give19-norandrost-4-ene-3 : 17-dione (32) ; this may be of considerable signi-ficance in connection with the production of estrogens by the adrenal gland,the introduction of the 19-hydroxyl group being the first step in the oxid-ative removal of the 19-methyl group, a prerequisite for the aromatisationof ring ~ .~ ~ 9 82* The relative ease of aromatisation of 19-hydroxy-steroidsby chemical means has been shown by Ehren~tein.~~ Meyer 86 recentlydemonstrated the formation of aestrone (33) from 19-hydroxyandrost-4-ene-3 : 17-dione by endocrine tissues. Identification of the product in thiscase rested upon a colour reaction and the absorption spectra of the sub-stance in sulphuric acid. These very interesting findings offer an explanationof the observed conversion of [14C] testosterone (6) into labelled cestradiol-17 p76 For reviews, see: S. A. Simpson and J. F. Tait, Recent Progr. Hormone Res.,1955, 10, 204; R. Grant, A. A. Renzi, and J. J. Chart, J . Clin. Endocrinol. Metabol.,1955, 15, 621.77 V.R. Mattox, Proc. Mayo Clin., 1955, 30, 180.7 8 A. Zaffaroni, V. Troncoso, and M. Garcia, Chem. and Ind., 1955, 634.79 H. Levy and S. Kushinsky, Arch. Biochem. Biophys., 1955, 55, 290.M. Hayano and R. I. Dorfman, ibid., p. 289.8Do Q. B. Deming and J. A. Luetscher, Proc. SOC. Exp. Biol. N.Y., 1950, 73, 171.D. J. Ingle, Endocrinology, 1944, 34, 191.81 G. W. Barber and M. Ehrenstein, J. Amer. Chem. SOC., 1954, 76, 2026.82 A. S. Meyer, Ex$erientia, 1955, 11, 99.83 D. H. R. Barton and P. de Mayo, J . , 1954, 887.84 G. W. Barber and M. Ehrenstein, J . Org. Chem., 1955, 20, 1253.85 M. Ehrenstein, ibid., 1950, 15, 264; 1951, 16, 335.a6 A. S. Meyer, Biochim. Biophys. Acta, 1955, 17, 441330 BIOLOGICAL CHEMISTRY.(34) by human ovarian the isolation of cestradiol-l7@ froma testicular tumour,88 and many similar observations including the biologicalanomaly of the stallion which produces relatively huge amounts of estrogenin its urine.18- and 19-Hydroxylation have not been achieved by micro-organisms.7- and 12-Hydroxylations.-The transformation of cholesterol (35) into(36) R = C02H.(40) R = CH,Pri.(42) R = CO*NH*[CH,],*SO,H.(38) R = OH.(39) R = H.(37) R = OH.(41) R = NH*[CHJ,*SO,H.CHI 9 0 1 1 CH2.W & I o:& Iw)f43) (44)cholic acid (36) was demonstrated in dogs by the classical work of Blochet ~ 1 .~ ~ in 1943. This involved epimerisation of the 3p-hydroxyl group andthe introduction of new 7a- and 12a-hydroxyl groups, among other changes.Similar observations were made later in rats,g0 rabbit~,~l and man.92 Berg-8 7 B.Baggett, L. L. Engel, K. Savard, and R. I. Dorfman, Fed. PYOC., 1955, 14, 175.8 8 M. Marti and H. Heusser, HeZv. Chim. Acta, 1954, 37, 327.8B K. Bloch, B. N. Berg, and D. Rittenberg, J . Bid. Chem., 1943, 149, 511.S. 0. Byers and M. W. Biggs, Arch. Biochem. Biophys., 1952, 39, 301.Dl P. H. Ekdahl and J. Sjovall, Acta Physiol. Scnnd., 1955, 34, 1.s2 R. S. Rosenfeld, L. Hellman, and T. F. Gallagher, Fed. Proc., 1955, 14, 271GRANT THE ENZYMIC HYDROXYLATION OF STEROIDS. 331strom et ~ 1 . ~ 3 found that 7a-hydroxylation of deoxycholic acid (37) occurredin rats. The 12a-hydroxyl group was not, however, readily introduced intochenodeoxycholic acid 94 (38), nor was lithocholic acid (39) converted intocholic acidg5 (36) in rats. It thus appears that the hydroxyl groups ofcholic acid (36) have to be introduced in a certain order.Since Bergstromet aLg6 have shown that coprostane-3a : 7a : 12a-trio1 (40) is rapidly con-verted into cholic acid (36) on intraperitoneal administration to rats withbile fistulz, hydroxylation may occur before degradation of the cholesterolside chain. 7a-Hydroxylation has been achievedg7 in vitro by using rat-liver slices and homogenates. Microsomes and the particle-free supernatantfluid obtained by centrifuging the liver homogenates were together requiredfor the 7a-hydroxylation of taurodeoxycholic (41) to taurocholic acid (42).Only slight activity was found in the supernatant fluid alone in presence ofATP.98 It should be noted, however, that such experiments with traceramounts of radioactive steroid as substrate cannot be expected to indicateco-factor requirements.The small amount of steroid may be transformedwith the help of co-factors already present in undialysed enzyme preparationsor by means of concentrations of coenzymes maintained by substrates in thesupernatant fluid in the presence of microsomal enzymes. Bergstrom 99 hasrecently shown that there is no incorporation of the isotope in a stableposition in the molecule when biological 7a-hydroxylation is performed intritium-labelled water. It is therefore possible that 1 lp- and 7a-hydroxyl-ation are achieved by the same mechanism. From a study of the effects ofX-rays on steroids in solution Weiss loo claims that 7-hydroxylation ofcholesterol may proceed by abstraction of hydrogen and addition of a hydr-oxyl radical, a proposal which is not in agreement with the previous evidence.The conversion of cholesterol into 7-hydroxycholesterol reported byKritmli and Hon-5th,lo1 using Proactinomyces yoseus, is not completely freefrom the doubt that the reaction may have been effected by molecularoxygen without the intervention of enzymes.Kahnt et uZ.lo2 have reported7p-hydroxylation of 3p : 21-hydroxy-5a-pregnan-20-one (43) by an un-identified species of Rhizopus.12a-Hydroxylation has not yet been achieved by microbiological methods.Some interest in such a reaction might be expected since it has been claimedthat 12a : 17a-dihydroxydeoxycorticosterone (44), a position isomer ofcortisol, is an antagonist of the hormone.lO3Hydroxylations at Other Positions in the Steroid Nucleus.-Introductionof a 3-oxygen atom into the steroid nucleus has excited no comment, possibly93 S.Bergstrom, M. Rottenberg, and J. Sjovall, 2. $hysiol. Chem., 1953, 295, 278.s4 S. Bergstrom and J. Sjovall, Acta Chem. Scand., 1954, 8, 611.95 S. Bergstrom, J. Sjovall, and J. Voltz, Acta Physiol. Scand., 1953,30, 22.s6 S. Bergstrom, K. Paabo, and J. A. Rumpf, ibid., 1954, 8, 1109.O7 S. Bergstrom, A. Dahlquist, and U. Ljungquist, Kgl. Fysiogr. Sallskap. Lund.,1953, Forh., 23, No. 12; S. Bergstrom and U. Gloor, Acta Chem. Scand., 1954, 8, 1373;1955, 9, 34; U. Gloor, Helv. Chim. Acta. 1954, 37, 1927.O 8 S. Bergstrom and U.Gloor, Acta Chem. Scand., in the press.O9 S. Bergstrom, personal communication.lo0 J. Weiss, Ciba Foundation Colloquia in Endocrinology, 1953, Vol. VII, p. 142.l01 A. KrAmli and J. Horv&th, Nature, 1949, 163, 219.lo2 F. W. Kahnt, C. Meystre, R. Neher, E. Vischer, and A. Wettstein, Experientia,lo3 W. J. Adams, B. G. Cross, A. Davies, F. Hartley, D. Patel, V. Petrow, and I. A.1952, 8, 42.Stewart, J . Pharm. Phavmacol., 1953, 6, 861332 BIOLOGICAL CHEMISTRY.because of its ubiquitous occurrence and its apparent association with earlystages of biosynthesis of the steroid nucleus, knowledge of which is of recentorigin. After an early suggestion of Channon’lw Langdon and Bloch105showed that squalene (45) is an efficient precursor of cholesterol in the animalorganism.About the same time Woodward and Bloch lo6 suggested thatsqualene cyclises to an intermediate having the structure of a 4 : 4 : 14-trimethylcholestane derivative (cf. 46), a scheme which would also explainCOMe COMethe formation of lanosterol (47) as an intermediate in the biosynthesis ofcholesterol from ~qualene.10~ Since lanosterol already possesses a 39-hydroxyl group the 3-hydroxylation must have occurred at some earlierstage, possibly before cyclisation. Bucher and McGarrahaw lo* claimedthat DPN+ is essential for the overall reaction of acetate + cholesterol byrat-liver homogenates. Tchen and Bloch lo9 recently found that the super-natant fraction of rat-liver homogenate, supplemented by the microsomalparticles disrupted by ultrasonic vibration, will transform [14C]~qualene intolanosterol, a reaction sequence which includes the hydroxylation step.The authors’ claim that DPN+ had no effect is of limited significance in anexperiment with undialysed enzyme preparation and minute amounts ofradioactively labelled substrate.Microbiological hydroxylations of progesterone in the 14~t-~~O and in thelo4 H.J. Channon, Biochem. J., 1926, 20, 400.lo6 R. B. Woodward and K. Bloch, J. Amer. Chem. SOC., 1953, 75, 2023.lo’ R. B. Clayton and K. Bloch, Fed. PYOC., 1955, 14, 194.lo8 N. L. R. Bucher and K. McGarrahaw, ibid., p. 187.Io9 T. T. Tchen and K. Bloch, J. Amer. Chem. Soc., 1955, 77, 6085.R. G. Langdon and K. Bloch, J. Bid. Chew., 1953, 200, 135.P. D.Meister, S. H. Eppstein, D. H. Peterson, H. C. Murray, H. M. Leigh,A. Weintraub, and L. M. Reineke, Abstr. 123rd Meeting Amer. Chem. SOL, 1953, 5cBELL : OLIGOSACCHARIDES OF MILK. 33315a- ll1 and 15p-position have been achieved. These 14- and 15-hydroxy-derivatives (48, 49) have no known place in mammalian steroid metabolism.J. K. G.6. OLIGOSACCHARIDES OF MILK : THEIR RELATION TO THE “ BIFIDUSFACTOR ” AND TO BLOOD-GROUP SUBSTANCES.The following abbreviations are used in this section :Lb = Lactobacillus bi$dus.LbP = Lactobacillus b<fidus var. Penn.BF = “ Bifidus factor.”BG == Blood-group.The intestinal flora of the normal breast-fed infant is characterised bythe prevalence of Lactobacillus bifidus,1~2~2~ in contrast to the mixed floraof infants fed on cow’s milk.The nutritional requirements of Lb as isolatedfrom the stools of both breast- and bottle-fed infants have been studied byNorris, Flanders, Tomarelli, and G ~ o r g y . ~ During this work,* an apparentlyspecific variant of Lb, named Lactobacillus bifidus var. Pen~z,~ was en-countered ; it showed scant or undetectable growth on the regular Lb medium.If, however, whole or skimmed human milk [containing I ‘ bifidus factor@) ”1was added, vigorous growth followed.Oligosaccharides of Milk.-Recent researches have revealed a number ofhitherto unsuspected and interesting carbohydrates in human milk. Gyorgy,Norris, and Rose 5 showed that BF (virtually absent from cow’s milk) wasthermostable ; a large number of organic compounds including knownmicrobiological growth-factors, yeast extract, vitamins not present in theoriginal Lb growth medium, carbohydrates, and several vegetable extracts,were all ineffective in replacing BF.studied the BF activity of milks of species other than man and found averageactivities highest for human colostrum,* followed, in order, by rat colostrum,human milk, rat milk, and cow colostrum.The milk of ruminants (cow, ewe,goat) on the other hand showed only very slight activity. Somewhat higheractivity appeared in the milk of cat, monkey, dog, rabbit, mare, and sow.High concentrations of BF were shown to be present in various humansecretions, e.g., saliva, semen, amniotic fluid, meconium, and tears. Piggastric mucin, which is a rich source of BG substances, proved to be rich inBF; a number of other nitrogenous polysaccharides, ovomucin, a- andp-heparin, ovomucoid, chondroitin sulphate, urinary glucoprotein, hyaluronicGyorgy, Kuhn, Rose, and ZillikenUnpublished work, cited by J.Fried, ef aZ., ref. 44.H. Tissier, “ Recherches sur la flore intestinale normale et pathologique du nourri-son,” Thesis, Paris, 1900.E. Moro, Wien. klin. Wochenschr., 1900, 13, 114.2a For recent critical remarks on changes in morphological character of Lb see :H. G. Gyllenberg, J . Gen. Microbiol., 19t5:. 13, 394; A. C. Hayward. C . M. F. Hale,and K. A. Bisset, ibid., p. 292 ; E. Olsen, Studies on the Intestinal Flora of Infants,”Ejnar Munksgaard, Copenhagen, 1949.R. F. Norris, T. Flanders, R.M. Tomarelli, and P. Gyorgy, J . Bacteviot., 1950,80, 681.P. Gyorgy, R. Kuhn, R. F. Norris, C. S. Rose, and F. Zilliken, Arner. J . DiseasesChildren, 1952, 84, 848; 1953. 85, 632.P. Gyorgy, R. F. Norris, and C. S. Rose, Arch. Biochem. Biophys., 1954, 48, 193.P. Gyorgy, R. Kuhn, C. S. Rose, and F. Zilliken, ibid., p. 202. * Colostrum is the secretion of the mammary gland which precedes the secretion ofmilk proper in animals commencing lactation334 BIOLOGICAL CHEMISTRY.acid, chitin, ‘‘ 0 ” somatic antigen (Shigella s h i p ) , and gonadotrophin wereall inactive. On the other hand, polysaccharides from Pneumococci typesIV, V, VI, VII, XVIII, and XIX had growth-promoting properties whilethese from types I , 11, 111, and XIV were virtually inactive.Ammoniumsalts in high concentration, N-acetyl-D-glucosamine and N-acetyl-D-galact-osamine were active growth-promoters, the authors suggesting thesesubstances as precursors of BF.then found that the BF activity ofhuman milk and colostrum could be separated into diffusible and non-diffusible fractions and that the BG (A, 13, 0) of the donor had little effecton this fractionation. By adsorption on charcoal or fractional precipit-ation, a mixture of oligosaccharides was obtained from deproteinised,defatted, and desalted human milk; this was resolved into inactive carbo-hydrates, including lactose, and active ones which contained nitrogen ; thelatter may correspond with the “gynolactose” of Polonovski and Les-pagnoLg The allolactose of these authors was not found.The activematerials gave, on hydrolysis, acetic acid, D-glucosamine, L-fucose, D-glucose,and D-galactose. Acetylation gave inactive products from which activenitrogenous oligo- and poly-saccharides could be regenerated. By chromato-graphy on charcoal, and on paper, at least four active components werefound ; all contained N-acetyl-D-glucosamine and were lzvorotatory. Inaddition, a trisaccharide without BF activity was found in human milk(150-300 mg. /l.) ; it is absent from cow’s milk or colostrum. By classicalmethods, Kuhn, Baer, and Gauhe lo have established its structure as ana-L-fucopyranosyl-lactose (1) where the fucosyl radical substitutes position 2of the galactose moiety. The BF-active substances have been structurallyGyorgy, Hoover, Kuhn, and RoseH,O H\ - rHO ’examined by Kuhn and his collaborators; to date they have been char-acterised as follows (where Gal = a D-galactopyranose, G = a D-glUC0-pyranose, GNAc = a N-acetyl-D-glucosamine, and Fuc = a L-fucopyranoseresidue) :(a) Lacto-N-tetraose 8- 119 l 2 ~ l3 (2 ; R = R’ = H) :/&Gal 1-3 /?-GNAc 1-3 /3-Gall-4 G7 P.Gyorgy, J. R. E. Hoover, R. Kuhn, and C. S . Rose, Arch. Biochem. Biophys.,* A. Gauhe, P. Gyorgy, J. R. E. Hoover, R. Kuhn, C. S. Rose, H. W. Ruelius, and9 M. Polonovski and A. Lespagnol, BUZZ SOC. Chim. biol., 1933, 15, 320.lo R. Kuhn, H. H. Baer, and A. Gauhe, Chem. Ber., 1955, 88, 1135.l1 R. Kuhn, A. Gauhe, and H. H. Baer, ibid., 1953, 86, 827.l2 Idem, ibid., 1954, 87, 289.l3 R.Kuhn, Angew. Chem., 1955, 67, 184.1954, 48, 209.F. Zilliken, ibid., p. 214BELL : OLIGOSACCHARIDES OF MILK. 335(b) Lacto-N-fucopentaose I (Morgan-Elson positive) (2 ; R = H,R’ = a-L-fucopyranosyl) :/?-Gall-3 /?-GNAc 1-3 /3-Gall-4 G21a-FucI(c) Lacto-N-fucopentaose I1 (Morgan-Elson negative)l2, 137 (2 :R = a-L-fucopyranosyl, R’ = H) :/?-Gall-3 /?-GNAc 1-3 / ? - G a l l 4 G41a-FucI(a) Lacto-N-difucohexaose l3 (2 ; R = R’ = ct-L-fucopyranosyl) :/?-Gal 1-3 /?-GNAc 1-3 ,%Gal 1-4 G4 2I Ii ia-Fuc a-FucThese four compounds are therefore closely related, the pentaose and thehexaose being formed by addition of a-L-fucosyl radicals at appropriatepositions of the tetraose molecule, which acts as a backbone.Graded hydrolysis of lacto-N-tetraose has yielded two disaccharides andtwo trisaccharides as follows :Lacto-N-biose I : l2* l5 3-U-(/3-~-galactopyranosyl)-N-acetyl-~-glucosamineLacto-N-biose I1 : 12.14 6-GNAc 1-3 GalLacto-N-triose I : 12. l4 P-Gal 1-3 GNAc 1-3 GalLacto-N-triose I1 : 12* l4 p-GNAc 1-3 /?-Gal 1-4 GRecently, two acidic carbohydrates 16 having BF activity have beenadded to the neutral substances mentioned above. These “ acid saccharidesI and 11,” both yield, on hydrolysis, D-galactose, D-glucose, N-acetyl-D-glucosamine, L-fucose, and “ gynaminic acid.” The last is crystalline andgives a deep purple colour with Bial’s reagent.16@have shown the presence of seven carbo-hydrates in addition to lactose on paper chromatograms of charcoal-adsorbedTrucco, Verdier, andl4 R.Kuhn, A. Gauhe, and H. H. Baer, Chenz. Ber., 1954, 87, 1187.l5 R. Kuhn, H. H. Baer, and A. Gauhe, ibid., pp. 1138, 1553.F. Zilliken, G. A. Braun, and P. Gyorgy, Arch. Biochem. Biophys., 1955, 54,564; cf. E. Klenk and H. Langerbeins, 2. physzol. Chem., 1941,270, 185; E. KIenk andK. Lauenstein, ibid., 1952, 291, 147; E. Klrnk acd H. Faillard, ibid., 1954, 298, 230.16a Cf. R. Caputto and R. E. Trucco, Nature, 1952, 189, 1C61; Ciencia e Invest.(Buenos Aires), 1953, 12, 567 ; R. E. Trucco and R. Caputto, J. Biod. Chem., 1954, 206.901 ; R. Heyworth and J. S. D. Bacon, Biochem. J., 1954, 58, xxiv.R. E .Trucco, P. Verdier, and A. Rcga, Biochim. Biophys. Ada, 1954, 15, 582336 BIOLOGICAL CHEMISTRY.material from deproteinised cow’s milk.These substances differ chromato-graphically from the saccharides of human milk; two compounds had BFactivity, two were inactive, and two have not been described. None con-tained L-fucose, but in two instances (BF-active) mannose (presumably theD-isomer) was present. The Table summarises their properties.Substances * Acid hydrolytic products BF activity1 & 2 Galactose, glucose, mannose, N-acetylglucosamine +3 Neuraminic acid, lactose t4 ,# ,D BS 5 Lactose, galactose, glucose -6 & 7 ,D J , 8 8 t-* Numbers indicate relative positions on chromatogram from start-line.f Not described.BF-Active Substances of Non-lacteal Origin: BG Substances.-Theobservation that BF materials from human milk had structural factors incommon with the BG substances, although the molecular sizes of the latterare very much greater than diffusible BF saccharides, led Springer, Rose, andGyorgy l7 to examine the water-soluble BG substances from human andsome animal tissues as growth factors for LbP.BG substances are secretedby “ goblet-cell ” structures and are widely distributed in animals, frommen to molluscs. These authors found that high BG activity was alwaysaccompanied by high BF content. While precipitation by alcohols tendedto destroy BG activity, BF potency remained. Differences in the latterwere noted between different sources of BG substances, Highly purified“ intrinsic factor ” (from gastric mucin) was noted to have high activity ofboth kinds.BG ’polysaccharide materials from the following human sources werefound to have BF activity : colostrum, milk, gall-bladder mucus, mecon-ium ,I* pseudo-mucinous ovarian cyst mucus, cervix uteri mucus, bronchialmucus, nasal mucus, mucocele of appendix, and amniotic fluid.Wateryextracts from the following human tissues were also active : salivary glands,stomach, small intestine, transverse colon, kidney, lung, spleen, pancreas,prostate, and “ intrinsic factor.” Carcinomas sometimes yielded activematerial, sometimes not. Preparations from animal tissues, pig gastricmucin, cattle small intestine and abomasum, frog spawn mucin,lg and wholeoyster tissue contained BF-active material.The above survey indicates the wide distribution in the animal kingdomof material containing fundamentally similar chemical groupings ; itssignificance is therefore wider than is indicated by microbiological study alone.Some Enzyme Activities of LbP Preparations.-Enzymes capable ofinactivating BG substances, as measured by change in their specific sero-logical properties, have been studied from time to time.20 P.Gyorgy et aL2117 G. R. Springer, C. S. Rose, and P. Gyorgy, J . Lab. and Clin. Med., 1954, 43,532; cf. ref. 4.l* D. J. Buchanan and S. Rapport, J . Bio?. Chem., 1951,192, 251.l@ B. F. Folkes, R. A. Grant, and J. K. N. Jones, J., 1950, 2136.2o F. Schiff and G. Weiler, Biochem. Z . , 1931, 235, 454; 1931, 239, 489; F. Schiffand A. Bur6n, Klin. Wochenschr., 1935, 14, 710; F. Schiff, ibid., p. 750; Amer. J.Infect. Diseases, 1939, 65, 127; K. Landsteiner and M. W. Chase, PYOC. SOC. Ex$. BioZ.and Med., N.Y., 1936, 32, 713; W. T. J. Morgan, Natwe, 1946,158, 759; M . V. Stackand W. T. J. Morgan, Brit. J . Exp. Pathol., 1949.80, 470.P. Gyorgy, C. S. Rose, and G. F. Springer, J . Lpb. CEin. Med., 1954,4$, 643BELL OLIGOSACCHARIDES OF MILK. 337found that crude extracts of LbP, culture filtrates of CZostridizm welchii typeB (ATCC No. 7905), and human saliva are all capable of inactivating bothBG and BF activity; no similar enzymes were found in regular strains ofLactobacillus bifidus. BF substances of either low or high molecular weightwere inactivated ; at the same time, N-acetyl-D-glucosamine, L-fucose, andD-galactose were set free. Crude, but not purified, meconium substanceappears to contain an inhibitor to the CZ. welchii enzyme; the salivaryenzyme is not inhibited.Two isomeric crystalline disaccharides were synthesised by a crudeenzyme from LbP acting on lactose and N-acetyl-D-glucosamine, pre-sumably by transgalactosylation.22 One which gave a Morgan-Elsonreaction 23 was slightly BF-active, while the other, which was Morgan-Elsonnegative, was identified with a BF-active substance obtained by Tomarelliet aZ.24 by graded hydrolysis of pig gastric mucin. The constitution of thissugar has now been established as 4-0-((3-~-galactopyranosyl)-N-acetyl-~-gl~cosamine,~~ which has also been obtained from meconium 26 and has beenchemically syn the~ised.~'The following disaccharides of N-acetyl-D-glucosamine are also BF-active,presumably because they are enzymically hydrolysed or have their radicals" transferred " ; 3- 28 and 6-0-( ~-D-galactopyranosyl)-N-acety~-~-glucos-mine ; 22, 29* 3o NN'-diacetylchitobio~e.~~ The last substance was obtainedcrystalline by chromatography of the crude material by gradient elution(waterlethanol) on a charcoal column; it is Morgan-Elson negative with orwithout prior treatment with sodium carbonate (1 mg. was equivalent to30 pg. of N-acetylglucosamine owing to slight alkaline hydrolysis to themonosaccharide). A crude LbP extract 21 hydrolysed the disaccharide togive two mols. of N-acetyl-D-glucosamine.With regard to the Morgan-Elson reaction,= Kuhn, Gauhe, and Baer l5observed that N-acetylglucosamine substituted in position 4 gives no colour.N-Acetylglucosamine gives, with alkali, a chromogen chromatographicallyidentical with anhydro-N-acetylglucosamine. l2 Alkyl glucosaminides giveno colour unless concomitant alkaline hydrolysis liberates a reducing N-acetylglucosamine unsubstituted in position 4.The above-mentioned disaccharides, along with synthetic 6-CQ-2-acetamido-2-deoxy-D-gIucopyranosyl) -D-galactose 32 and 6-0-( P-2-acet-amido-2-deoxy-D-g~ucopyranosy~)-~-g~ucose~~ all possess BF activity,although in differing degrees. LbP enzymes therefore appear to include a@-D-galactopyranosidase and a (3-D-ghcosaminidase. The latter enzyme is22 F. Zilliken, P. N. Smith, C. S. Rose, and P. Gyorgy, J . Biol. Chem., 1954, 208,299. See also ref. 29.2s W. T. J. Morgan and L. A. Elson, Biochem. J., 1934,28,988; D. Aminoff, W. T. J.Morgan, and W. M. Watkins, ibid., 1952, 51, 379.24 R. M. Tomarelli, J. B. Hassinen, E. R. Eckhardt, R. H. Clark, and F. W. Bernhart,Arch. Biochem. Biophys., 1954, 48, 225.25 F. Zilliken, P. N. Smith, R. M. Tomarelli, and P. Gyorgy, ibid., 1955, 54, 398.26 R. Kuhn and W. Kirschenbohr, Chem. Ber., 1954, 87, 560.28 Quoted by P. Gyorgy and C. S. Rose, Proc. SOC. Exp. Biol. Med., N.Y., 1955,2s F. Zilliken, P. N. Smith, C. S. Rose, and P. Gyorgy, J . Biol. Chem., 1955, 217, 79.so R. Kuhn, H. H. Baer, and A. Gauhe, Chem. Bey., 1955, 88. 1713.*l F. Zilliken, G. A. Braun, and P. Gyorgy, J . Amer. Chem. SOC., 1955, '77, 1296.82 R. Kuhn and W. Kirschenbohr, Chem. Ber., 1954, 87, 384.Idem, ibid., p. 1547.90, 219338 BIOLOGICAL CHEMISTRY.capable of hydrolysing a number of alkyl and aryl N-acetyl-p-D-glucos-aminides but not their ~c-anomers.~~ These p-glycosides were found to haveconsiderable, but varied, BF activity. The a-anomers were inactive al-though the activity of methyl N-acetyl-p-D-glucosaminide was greatlyenhanced by addition of its a-anomer. Gyorgy and Rose 33 state that it isnot yet possible to identify the bifidus factor with any specific compound.The dlolactose Question.-Kuhn, Baer, and G a ~ h e , ~ ~ using a crudep-D-galactosidase from E. coli strain VV (ATCC No. 9637), obtained 6-0-(p-~-galactopyranosy1)-D-glucose ( I ' allolactose ") by the action of the enzymeon phenyl p-D-galactopyranoside in presence of glucose. The disaccharidehad previously been synthesised by purely chemical means.35 Kuhn et aL34suggest that the allolactose found by Polonowski et aZ.9936 originated inbacterial contamination ; they were unable to find any allolactose in milk(cf. ref. 3).Lactobacillus bifi dus from Avian Sources-Micro-organisms, classifiedas Lb, have been isolated from the caecal flora of normal 38$ 39 fromthe faeces of turkeys,h* 40 and the czcal flora of turkey poults.39 In the chick,Lb was found in greatest numbers when 16yo of lactose was incorporatedin the diet. Various of these avian strains failed to grow on a chemicallydefined medium ; luxuriant growth was, however, obtained on the additionof a commercial preparation of " papain-hydrolysed casein." This prepar-ation could not be replaced by BG substances A and €3 or by 4-0-(p-D-galactopyranosyl) -N-acetyl-D-glucosamine.D. J. B.D. J. BELL.L. CROMBIE.J. K. GRANT.33 P. Gyorgy el al., see ref. 28.34 R. Kuhn, H. H. Baer, and A. Gauhe, ibid., 1955, 88, 1713.s5 B. Helferich and G. Sparmberg, Ber., 1933, 68, 806.3O M. Polonovski and J. Montreuil, Comtp. rend., 1954, 238, 2263.37 G. L. Romoser, M. S. Short, G. F. Combs, and M. J. Pelczar, Antibiotics and313 R. E. McCarthy, Thesis, Maryland, 1953.3s F. A. Veltre, M. S. Short, and M. J. Pelczar, Proc. SOG. Exp. Riol. Med., N . Y . ,40 A. P. Harrison and P. A. Hansen, J . Bact., 1949, 59, 197.Chemotherapy, 1952, 11, 42.1953, 83, 284

ISSN:0365-6217    

DOI:10.1039/AR9555200285

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.IN this year's Report, absorptiometric and radiochemical methods, whichwere not considered in the last Report, are now reviewed. All reference tospectroscopic methods has been omitted, but will be dealt with in the nextReport. Research on absorptiometric methods has been so extensive thatit has only been possible to cover the inorganic applications. It is hopedthat it will be possible to review organic applications in the next Report.The most notable events of general interest to analytical chemists in thiscountry during 1955 were the lectures, sponsored by the Society for AnalyticalChemistry, and given at various centres in England, by Professor Schwarzen-bach of Zurich1 and Professor J. Heyrovskjr of Prague.2 The speakersdealt in general terms with the subjects each had pioneered, complexonesand polarography, and which have had such a great impact on the develop-ment of analytical chemistry in recent years.In July a Symposium on Microchemistry was held in Vienna under theauspices of the Austrian Microchemical Society.About 600 delegates frommost parts of the world were present and some 90 papers were read.3 Atthe opening ceremony, the Feigl Prize was awarded to Dr. H. Weisz for hiscontribution to microchemistry in developing the new ring-oven technique.*GeneralThe design and functioning of various components are discussed and methodsfor assessing the sharpness and fineness of knife edges and their adjustmentare described. Reference is also made to balances used for special purposes.Ulbricht has described a detailed mathematical investigation concerningthe effect of air buoyancy on the accuracy of weighing.Corrections forbuoyancy are recommended which can be calculated from curves andformulze. Pfundt has described a riderless microbalance. A mechanicaldevice is used for adding weights from 1 mg. upwards and a projection scalegives the 0 - 1 mg. readings. The left-hand pan may be removed for addingsmall objects. Two models have been made, for maximum loads of 20 g.and 10 g. respectively. The latter balance has an automatic tare device, aseparate rider for checking sensitivity, and an external sensitivity adjustment.Both models have separate beam compartments.Corrosion tests have been carried out on brass weights coated with twodifferent thicknesses of tin-nickel alloy, and the results have been comparedwith those obtained when other materials were used.8 The weights with theA useful paper has been published which deals with analytical balances.G. Schwarzenbach, Analyst, 1955, 80, 713.J.Heyrovskf, ibid., in the press.Mikrochimica Acta, 1956, in the press.A m . Reports, 1954, 51, 336.D.S.I.R. (N.P.L. Notes Appl. Sci., 1954, No. 7).H. Ulbricht, 2. analyt. Chem., 1955, 145, 161.P. H. Bigg and F. H. Burch, Brit. J . Appl. Phys., 1954, 5, 382.' P. Pfundt, Mikrochim. Acta, 1954, 539340 ANALYTICAL CHEMISTRY.heavier coating (25 p) showed the same resistance as highly polished stainless-steel weights. The stability of mass was about the same as that of austeniticstainless-steel and rhodium-plated brass weights.Weights made from 80120nickel-chromium showed slightly less resistance in highly corrosive atmo-spheres. For the fractional weights austenitic stainless-steel was the best,followed by zirconium, tantalum, aluminium, and titanium.The factors which must be considered when preparing standards forvolumetric glassware have been detailed.g The units of volume, standardtemperature, construction and checking of apparatus, delivery procedure,drainage time, and the delivery of non-aqueous liquids are discussed.Kawamura lo has found that hydrogen peroxide mixed with variousmineral or organic acids effects the rapid dissolution of steels and ferro-alloys which are normally resistant to attack.For example, ferro-tungsten,rapidly dissolves in hydrogen peroxide-hydrofluoric acid, and stellite andferro-vanadium in hydrogen peroxide-oxalic acid. Rapid methods of steelanalysis are discussed using this new opening-out treatment.A new apparatus for wet oxidation with sulphuric and nitric acid hasbeen described l1 in which the volatile products are condensed and returnedto the flask. A great saving in time and reagents is claimed.DeFord l2 has discussed the reliability of calculations based on the lawof chemical equilibrium and has indicated the factors which must be con-sidered in order to avoid serious errors.A historical account of the development of organic elementary analysishas been given by van der Wal.13The problems which arise when complexing agents are used in titrimetricanalysis have been disc~ssed.1~ From potentiometric and colorimetricstudies of the reactions involved, it is concluded that, unless polydentatereagents are used, the formation of lower complexes, particularly near theend-point when the ligand concentration is low, leads to significant errors.Various methods for detecting the end-point are considered.Kuznetsov 15 has studied the theory involved in selecting organicco-precipitants. In certain cases it was found possible to predict suitablereagents, e.g., in the precipitation of zinc thiocyanate with methyl-violet,but it was necessary to select non-salt forming organic compoundsempirically.A systematic study of several metal-diethyldithiocarbamate complexeshas been made by Bode.16 He examined the spectra and the effect of pHand masking agents on the distribution between carbon tetrachloride andthe aqueous phase.Several selective determinations are suggested as aresult of this work.Irving and Rossotti 17 have discussed the factors which determine theanalytical usefulness of reagents, with particular reference to the effect of0 D.S.I.R. (N.P.L. Notes Appl. Sci., No. 6).lo K. Kawamura, Jap. Analyst, 1953, 2, 347, 417.l1 J. Pien, Ann. Fals. Fraudes, 1954, 47, 266.l2 D. D. DeFord, J. Chern. Edztc., 1954, 31, 460.l3 A. A. van der Wal, Chem. Weekblad, 1954, 50, 829.14 A. E. Martell and S. Chaberek, Analyt. Chern., 1954, 26, 1692.l5 V. I. Kuznetsov, Zhur. analit. Khim., 1954, 9, 199.l6 H.Bode, 2. analyt. Chem., 1954, 143, 182.l7 H. Irving and H. S. Rossotti, Analyst, 1955, 80, 245BELCHER, BEVINGTON, STEPHEN, AND WEST. 341structural modifications on reagents of low selectivity. Since insufficientphysicochemical information is available, it is concluded that sensitivitytests are the best approach to assessing the potentialities of a reagent.Thiosemicarbazones of several aldehydes and ketones have been examinedas reagents for all the common metals at various pH levels.l* Silver,mercury, and copper formed coloured precipitates in all cases and cobaltgave red solutions. Some of the compounds were found suitable for thedetermination of mercury and copper.Several substituted dithiocarbamates have been examined as analyticalreagents.lg The most interesting appears to be ammonium tetramethylene-dithiocarbamate, for much smaller amounts of buffer are required to main-tain the correct pH range than with the sodium compounds. This enablesthe total volume to be considerably reduced.The properties and applications of the eight known reagents availablefor the gravimetric determination of nitrate have been reviewed byWilliams .mThe properties of derivatives of ' oxine lD continue to arouse interest.Sensitivity tests on 8-hydroxy-5-nitroquinoline indicated that it should bemore selective than oxine, but unsatisfactory results were obtained whenquantitative experiments were carried out.21 The behaviour of the reagentis discussed from the standpoint of its absorption spectrum and otherphysical characteristics .The analytical properties of 8-hydroxy-5-, -6- , and -7-trifluoromethyl-quinolines have been examined and acid dissociation constants of the firsttwo have been determined.22 Their behaviour is similar to that of thecorresponding methyl compounds, but the 7-compound does not form aprecipitate with any of the ions which have been tested.It is concludedthat this anomalous behaviour is due to ortho-effects. The 5-methyl-7-nitroso-, Z-methy1-5-nitroso-, 7-allyl-5-nitroso-, and 5-bromo-7-(2 : 3-di-bromopropy1)-derivatives of 8-hydroxyquinoline have been examined asanalytical reagents.% Some of these derivatives are more selective thanoxine and the factors which may be responsible are discussed.ReagentsPrecipitants.-A new reagent, purpureocobaltic chloride, for the gravi-metric determination of tungsten has been proposed by Dupuis.% Theparatungstate is formed at pH 5-1-64, and the metatungstate at pH24-3*1.The paratungstate gives more accurate results and can be dis-solved in ammonia solution for colorimetric measurement. However, wheniron is present it is necessary to precipitate the metatungstate to avoidinterference. At other pH ranges other tungstates are precipitated, butare not suitable for gravimetric analysis since their composition is not alwaysconstant.S. S. G. Sircar and S. Sathpathy, J. Indian Chem. SOC., 1954, 31, 450.l9 H. Malissa and E. Schoffman, Mikrochim. Acta, 1955, 187.2o M. Williams, Ind. Chemist, 1954, 30, 594.21 H.Irving, R. G. Hollingshead, and G. Harris, Analyst, 1955, 80, 260.22 R. Belcher, A. Sykes, and J. C. Tatlow, J., 1955, 376.23 R. G. W. Hollingshead, Analyt. Chim. Ada, 1955, 12, 201; Chevn. and I n d ,24 T. Dupuis, Mikrochim. Acta, 1955, 851.1954, 1260; Research, 1955, 8, 9342 ANALYTICAL CHEMISTRY.McCune and Arquette 25 have examined hexamniinocobaltic chloride asa reagent for the separation of triphosphoric and pyrophosphoric acids, butprecipitation occurred at all pH ranges. With trisethylenediaminecobalticchloride, however, only the triphosphate was precipitated at pH 3.5, whilstat pH 6-5 only pyrophosphate was precipitated. Trimetaphosphate andtetrametaphosphate are not precipitated. Unfortunately, it was notpossible to precipitate triphosphate in the presence of pyrophosphate, forrecoveries were incomplete and co-precipitation occurred.An examinationof similar complex precipitants, however, might yield useful results and helpto solve this old problem in analytical chemistry.Arsanilic acid has been proposed as a reagent for the gravimetric deter-mination of bismuth.26 Only sodium, potassium, ammonium, and acetateions are mentioned as not interfering. Chloride, phosphate, and tartratemust be absent.Duval and Wadier 27 recommend 5 : 5-dimethylcyclohexane-1 : 3-dioneas a specific reagent for univalent mercury. The composition of the pre-cipitate is variable, however, and it is necessary to redissolve it in nitric acidand complete the determination by one of the usual methods.Diallyldithiocarbamidohydrazine has been examined as a reagent for thedetermination of nickel and copper.28 Nickel is precipitated in the pH range8-1-8.7, and copper at 2-5-36, hence it is possible to determine both metalsin mixtures.The nickel complex is weighed, but that with copper is ignitedto the oxide, dissolved in acid, and determined iodometrically.Nickel and copper can be determined gravimetrically after precipitationwith resorcylaldoxime.29 Although precipitation of the metal complexesoccurs at different pH ranges, separation is not possible. Many other ionsdo not interfere, however, and the reagent has been used successfully for thedetermination of copper in brass.o- and 9-Chlorophenoxyacetic acid and p-chloro-m-tolyloxyacetic acidhave been used for the gravimetric determination of thorium.30 Separationfrom cerite earths can be achieved with one precipitation, the first being themost effective of these reagents.Thorium may also be determined in thepresence of small amounts of rare earths and bismuth by using benzene-phosphonic acid as reagent.31 Precipitation is quantitative at a very lowpH range. The reagent is not very selective, however, and appears to havelittle advantage over the host of existing reagents now available.Colorimetric.-Solochrome Brilliant Blue B (B.C. Index No. 723) hasbeen proposed for the colorimetric detennination of beryllium.32 It issuitable for the range 0.2-1.6 pg. per ml. A method has been developedfor the determination of beryllium in air.Bromoanilic acid (3 : 6-dibromo-2 : 5-dihydroxy-$-benzoquinone) hasbeen examined as a reagent for the colorimetric determination of calcium.3325 H.W. McCune and G. J. Arquette, Analyt. Chem., 1955, 27, 401.26 A. Musil and R. Pietsch, 2. analyt. Chem., 1955, 144, 347.27 C. Duval and C . Wadier, Compt. rend., 1955, 240, 433.28 N. K. Dutta and K. P. S. Sarma, Science and Culture, 1956, 20, 397.29 A. K. Mukherjee, Analyt. Chim. Acta, 1955, 13, 334.30 N. Eswaranarayana and Bh. S. V. R. Rao, J . Sci. Ind. Res., India, 1954, B, 13,657.a1 C. V. Banks and R. J. Davis, Analyt. Chim. Acta, 1955, 12, 418.32 J. H. Wood, Mikrochim. Acta, 1955, 11.33 L. Erdey and I. Jankovits, Acta Chim. Acad. Sci. Hung., 1954, 4, 245BELCHER, BEVINGTON, STEPHEN, AND WEST.343After addition of a known amount of the reagent the precipitate is filteredor centrifuged off and the residual colour of the solution is measured at530 my in a Pulfrich photometer.Michal and Zyka 34 have used tetraethylthiuram disulphide as a colori-metric reagent for the determination of copper. An intense yellow-browncolour is produced with an absorption maximum at 445 my. The methodis highly selective. Mercury(@ also forms a complex and in its presenceexcess of reagent should be used but there is no interference since themercury complex is colourless.as areagent for the colorimetric determination of copper, an intense yellow colourbeing produced in neutral or hydrochloric acid solutions. Only metalswhich give colours in a hydrochloric acid medium interfere ; nitrates,chlorides, acetates, tartrates, and phosphate have no effect even in a 1000-fold excess.Copper has also been determined colorimetrically by the formation of achloroform-soluble complex with 2-isatoxime methyl ether.36 The methodis highly selective.Mukherjee 37 has proposed the use of ethylenediaminebis-sulphosalicyl-aldehyde and p-aminosalicylic acid as sensitive reagents for the colorimetricdetermination of ferric iron.The latter is the more sensitive but severalions, notably uranyl, copper, nickel, chromate, and molybdate, interfere.The reagent can be used over a wide pH range and the colour is very stable.Thorium may be determined colorimetrically by means of the intenseviolet colour produced when it is treated with ~armine-red.~~ Of the usualelements associated with thorium, only ferric iron interferes. A pH of 2.5and wavelength of 560 mp are the most suitable conditions for measurement.Thiobenzamide has been recommended by Gagliardi andR.B.Inorganic Qualitative AnalysisThe use of thioacetamide in place of hydrogen sulphide, particularly insemimicro-qualitative analysis, continues to gain favour and many papershave been published in recent years extolling the advantages which accruefrom the use of this reagent. However, in a timely paper, Lehrman andSchneider point out that the indiscriminate replacement of hydrogensulphide by thioacetamide in conventional qualitative schemes can lead todifficulties which have not been considered in earlier studies of the reagent.Thus, if oxidising agents like iron(m), arsenate, or nitric acid are present,some reagent may be destroyed, leaving an insufficient concentration insolution to effect complete precipitation of the metal sulphides; the oxid-ation of thioacetamide gives rise to sulphate ions which favour the loss ofthe alkaline-earth cations.During the hydrolysis of thioacetamide, acetateions are formed which lower the hydrogen-ion concentration of the solutionby buffer action. Under these conditions, the Group IV cations may be34 J. Michal and J. Zyka, Chem. Listy, 1954, 48, 1043.35 E. Gagliardi and W. Haas, Mikrochim. Acta, 1954, 593.36 L. Divis and J. Skoda, Chem. Listy, 1954, 48, 539.37 A. K. Mukherjee, Analyt.Chim. Acta, 1955, 13, 268, 273.38 N. Eswaranarayana and Bh. S . V. R. Rao, 2. analyl. Chem., 1955,146, 107.39 L. Lehrman and P. Schneider, J . Chem. Educ., 1955, 52, 474344 ANALYTICAL CHEMISTRY.precipitated as sulphides. Then, before the Group I11 cations can beprecipitated as hydroxides, the excess of thioacetamide must be removed insuch a way that no objectionable ions (e.g., sulphate) are formed in solution.Each disadvantage has been studied experimentally and a procedure hasbeen developed to overcome them; the only unsatisfactory feature of themethod is that about 25% of the zinc is precipitated along with the Group I1sulphides. Of the Group IV cations, only zinc behaves in this way. Thelithium hydroxide reagent recommended by Holness and Trewick for theseparation of the copper and arsenic groups has been criticised by Jamesand Wo~dward.~~ They claim that if the activity of the hydroxyl ion is themain consideration in the choice of a suitable reagent, then lithium hydroxidehas no advantage over sodium or potassium hydroxide. This point isproved in a critical study of the factors affecting the separation, and in place .of the lithium hydroxide reagent, a 06N-SOhtiOn of potassium hydroxide isrecommended.It is not necessary to have potassium nitrate present in thereagent solution if the sulphides are precipitated from hot solution with useof a low flow-rate of hydrogen sulphide; sulphides precipitated in this waydo not readily form colloids. If mercury and the Group IIB cations arepresent together, some mercuric sulphide dissolves in the alkali, and merccrymust be looked for in both sub-groups.Tin@) must be oxidised beforeprecipitation with hydrogen sulphide because of the low solubility of tin@)sulphide in 06N-pOtaSSiUm hydroxide. Heath 41 describes an alternativeto the conventional procedure for the separation and identification of theGroup I1 cations. The precipitate of metal sulphides is treated with hydro-chloric acid which gives an initial separation. Further sub-groups areobtained which make the identification of the elements present an easymatter.Weisz 42 has applied his versatile ring-oven technique to a qualitativeexamination of the materials used in the fabrication of some Egyptianarchaeological specimens.By a suitable sampling procedure, sufficientmetal is removed from the specimen to provide a drop of solution whichcan be analysed by the ring-oven methods. Bank and van der Eijkaconfirm Weisz’s results for the qualitative examination of a drop of solutionby the ring-oven method. Arsenic and mercury are now included in thescheme of analysis. Verma and Paula have developed a spot-test pro-cedure for the detection of cadmium in the presence of copper, lead, and tin.This test is more effective when ring-oven techniques are used.Smith and Shute45 have made a critical study of the separation andidentification of aluminium in the normal scheme of qualitative analysis.Difficulty was experienced in obtaining a satisfactory test for aluminium byusing ammonium aurintricarboxylate (“ aluminon ”) because of incompleteseparation of the aluminium from iron and chromiym.A modified schemehas thus been recommended which uses NN-di(hydroxyethyl)glycine(“ Versene, Fe3+ specific ”) to overcome interference from iron. Highlysatisfactory results are obtained.40 C. F. James and P. Woodward, Analyst, 1955, 80, 825.41 P. Heath, ibid., 1954, 79, 781.42 H. Weisz, J . Chem. Educ., 1955, 32, 70.43 C. A. Bank and W. van der Eijk, Chern. Weekblad, 1955, 51, 351. ** M. R. Verma and S. D. Paul, AnaZyst, 1955, 80, 399.45 S. B. Smith and J. M. Shute, J . Chem. Educ., 1965, 32, 380BELCHER, BEVINGTON, STEPHEN, AND WEST. 345Numerous qualitative tests have been proposed during the year. Holz-becher 46 described the fluorescence reaction of aluminium with salicyl-aldehyde and 2-hydroxy-1-naphthaldehyde and 18 derivatives of thesecompounds.With salicylidene-o-aminophenol, 0-005 pg. of aluminium isdetectable at a limiting concentration of 1 in lo8. Patrovsky4' uses thisreagent for the detection of gallium. The fluorescence due to aluminium ismasked by addition of sodium fluoroborate. Rhodamine-B is also used forthe detection of gallium ; 48 conditions are obtained which make the reactionspecific for as little as 0.01 pg. of Ga2+. Gagliardi and Theis 49 have examinedseveral simple monoazo-dyes derived from 1-naphthol as reagents for thedetection of magnesium in alkaline solution. Benzoin is used as a fluorescentreagent for the detection of germanium; the reaction is not particularlysensitive.Pribil and Michal 51 use quercetin for the identification of vanad-ium; the reagent is sensitive to 2 pg. of vanadium in 5 ml. of solution.Cobalt is identified in the presence of nickel 52 by means of the deep bluecolour formed with a solution containing the monothiophosphate ion,P0,S3-. The test is applicable to the solution of cobalt and nickel obtainedby normal group analysis. Theis 53 describes a spot test for beryllium,using Chromazurol-S, which is sensitive to 1 pg. of beryllium in 5 ml. ofsolution; Chloroplumbic acid 54 has been used for the direct detection ofpotassium in the presence of a large number of cations, including sodiumand lithium ; rubidium and caesium interfere. Sodium tetraphenylboron isrecommended for the detection of potassium in systematic qualitativeanalysis ; 55 ammonium salts, which interfere, are completely removed by asuitable procedure before carrying out the test.Rush and Rogers 56 haveexamined the effect of the substrate (filter-paper) on two catalytic spot-tests for copper. A 10-fold variation in sensitivity is observed between22 grades of paper, the ashless grades in general being the most sensitive.Seely 57 has used modified spot-test techniques to detect several commonions in dust particles of 10-10 to 10-15 g.Little new work has been published in the field of qualitative anionanalysis. A systematic scheme based on Feigl's separation into soluble andinsoluble zinc salts has been recommended for use on the micro- and semi-micro-~cales.~~ Wendlandt and Bryant 59 describe a more reliable test forcarbon dioxide than the conventional one using lime-water.The reagentis a solution of sodium methoxide in methanol, which gives a voluminouswhite precipitate of sodium methyl carbonate with carbon dioxide. Wirth46 S. Holzbecher, Coll. Czech. Chem. Comm., 1954, 19, 241.(7 V. Patrovsky, Chem. Listy, 1954, 48, 537.H. Onishi, Analyt. Chem., 1955, 27, 832.49 E. Gagliardi and M. Theis, 2. analyt. Chem., 1955, 144, 264.N. Appala Raju and G. Gopala Rao, Nature, 1955, 175, 167.51 R. Pribil and J. Michal, Chem. Listy, 1954, 48, 621.52 S. K. Yasuda and J. L. Lambed, J . Chem. Educ., 1954, 31, 572.53 M. Theis, 2. analyt. Chem., 1955, 144, 192.64 W.Rodziewicz and J. Szychlinski, Roczniki Chem., 1954, 28, 657.55 R. F. Muraca, H. E. Collier, J. P. Bonsack, and E. S. Jacobs, Chemist-Analyst,6 6 R. M. Rush and L. B. Rogers, Mikrochim. Ada, 1955, 821.6 7 B. K. Seely, Analyt. Chem., 1955, 27, 93.6 8 F. de Leo, R. Indovina, and A. Bellino, Ann. Chim. (Italy), 1954. 44, 859.69 W. W. Wendlandt and J. M. Bryant, Chemist-Analyst, 1955, 44, 52.6O C. M. P. Wirth, zbid., 1954, 43, 101.1954, 43, 102346 ANALYTICAL CHEMISTRY.has developed a colour test for borates using polyvinyl alcohol; the reagentis added to an acidic solution of the borate and a drop of iodine is introduced ;a deep blue colour results. Feigl and Hainberger 61 have developed a spot-test for the detection of sodium dithionite, using an ethanolic solution of9-dinitrobenzene ; in the presence of strong aqueous ammonia an immediateorange coloration is produced with 3 Fg.of dithionite.Inorganic Gravimetric AnalysisThe discovery of sodium tetraphenylboron as a reliable precipitant forpotassium is one of the most important advances in inorganic analysis inrecent years. Titrimetric procedures are available for the evaluation ofpotassium tetraphenylboron but the gravimetric method is the generallypreferred one. Sykes 62 has reviewed most of the important analytical usesof sodium tetraphenylboron. Sporek and Williams have made a criticalexamination of the published procedures for the precipitation of potassiumtetraphenylboron ; readily filterable precipitates are obtained when thereaction mixture has a final acidity greater than 0 * 2 ~ , but it is then necessaryto keep the temperature at 0" to prevent decomposition of the reagent.Cluley 64 has also studied the available methods for the determination ofpotassium with sodium tetraphenylboron, and he recommends two methods,involving precipitation at pH 2 and pH 6.5 respectively. The proceduresare applied to the determination of potassium in glasses and refractories.The direct determination of potassium by use of fluoroboric acid isdescribed by Mana~evit,~~ who has investigated the effect of temperature,solvent, and foreign ions on the precipitation of potassium fluoroborate.High results are obtained in the presence of ammonium, barium, and sulphateions; calcium and aluminium interfere when present together, but notsingly. A 25-fold excess of sodium can be tolerated in determinations of20-200 mg.of potassium.Conditions for an accurate gravimetric determination of micro-amountsof sodium as antimonate in the presence of large amounts of potassiumhave been worked out ; 66 the precipitation is effected in 25-30% ethanol.Lithium in small amounts is determined in the presence of other alkalimetals by extraction of lithium chloride with n-pr~panol.~~ The residueobtained after removal of the solvent is dissolved in a mixture of hexamine,acetone, and water, and the mixture is treated with a reagent containingpotassium ferricyanide. A yellow precipitate of a complex lithium potassiumhexamine ferricyanide is obtained.Two papers of interest in the field of gravimetric analysis deal with thehygroscopic properties of precipitates 68 and the thermogravimetry ofrhodium.69 Methods have been described for the rapid determination of61 F.Feigl and L. Hainberger, Mikrochim. Acta, 1955, 105.A. Sykes, I n d . Chem. Mfr., 1955, 31, 245, 305.63 K. Sporek and A. F. Williams, Analyst, 1955, 80, 347.134 H. J. Cluley, ibid., p. 354.6s H. M. Manasevit, Analyt. Chem., 1955, 27, 81.66 K. S. Cheshev, Zhur. analit. Khim., 1954, 9, 239.6 7 C. F. Forster, Analyst, 1954, 79, 629.68 H. Amano, J . Chem. SOC. Japan, 1954, 75, 499.6s C. Duval, P. Champ, and P. Fauconnier, Analyf. Chim. Acta, 1955, 12, 138BELCHER, BEVINGTON, STEPHEN, AND WEST. 347thorium in 0re~,70 the determination of chromium as K,CrpF5,H,0,7f andthe determination of bismuth as the 8-hydroxyquinolme complex.72Japanese workers 73 have investigated numerous binary and tertiary systemsin the application of quantitative procedures without preliminary separations.Conductivity measurements have shown 74 that barium sulphate is notprecipitated from aqueous solutions until a concentration product of1.59 x lo-* (about 160 times the solubility product) is reached; spon-taneous formation of nuclei then occurs. The morphology of bariumsulphate has been studied by means of electron micro~copy.~~ Reactiontemperature and concentration of reagents have a considerable effect on theform of the precipitate which is characteristic for any set of reaction con-ditions.Benedetti-Pichler 76 considers that the rate of precipitation and theparticle size of a precipitate may be appreciably affected by trace impuritiesin the reagent.His investigations on the precipitation of barium sulphatehave been prompted by the work of B0gan,~7 who claims that the particlesize of barium sulphate varies according to the age of the solution used asprecipitant.Two papers presented at a Symposium on the role of reaction rates inanalytical chemistry are of interest. O’Rourke and Johnson 78 discuss thekinetics and mechanism in the formation of slightly soluble ionic precipit-ates; they consider that precipitation occurs in two stages, involving firstnucleation and growth, and secondly only the growth of the precipitate.Barium sulphate is taken as experimental model in this study of the entireprocess of precipitation.Gordon 79 discusses slow precipitation processesfrom the standpoint of precipitation from homogeneous solution. Thismethod makes it possible to study the nature and extent of coprecipitationunder very favourable conditions. Methods for the precipitation of silverchloride from homogeneous solution have been used to study the coprecipit-ation of thallium(1) with silver chloride.80Inorganic Titrimetric AnalysisIndicato~s.-~A search of the literature failed to provide any informationon the chemical nature of “ methyl-purple,” an acid-base indicator men-tioned in last year’s Report, and recommended again this year in a titri-metric procedure for phosphorus.81 Correspondence with the manu-facturers has revealed that “ methyl-purple ” is a trade name for an aqueoussolution of methyl-red sodium salt and patent-blue dyestuff (British ColourIndex No.714) in such proportion as to give sharp colour changes in the70 M. M. Tillu and V. T. Athavale, Analyt. Chim. Acta, 1954, 11, 324.71 Sh. T. Talipov and T. I. Fedorova, Trudy Sredneaziatskogo Gosudarst. Univ. Khim.72 A. Jilek and M. KiivBnek, Chem. Zvesli, 1953, 7 , 563.73 N. Unohara, J. Chem. SOC. Japan, 1954, 76, 287.74 W. G. Cobbett and C. M. French, Discuss. Faraday SOL, 1954, 113.7 5 S. Okada and S. Magari, Analyt. Chem., 1955, 27, 1481.7 6 A. A. Benedetti-Pichler, ibid., p. 1505.7 7 E. J . Bogan, ibid., p. 1505.78 J . D. O’Rourke and R.A. Johnson, ibid., p. 1699.79 L. Gordon, ibid., p. 1704.81 I). M. Zall, E. Wagman, and N. Ingber, ibid., p. 277.Nauk, 1953, 40, 57.L. Gordon, J. I. Peterson, and B. P. Burtt, ibid., p. 1770348 ANALYTICAL CHEMISTRY.range pH 44-54. The indicator is described in a U.S. patent specific-ation.82 Nitrazine-yellow & is claimed to give a much sharper end-pointand much better results than methyl-orange in acid-base titrations, but nocomparison is made with newer mixed and screened indicators changingover the same pH range. A two-step mixed indicator containing bromo-cresol-green, New Coccine (B.C.I. No. 185), and p-nitrophenol is recommendedfor the Kjeldahl titration of ammonia in boric acid.@ The colour change isfrom blue (alkaline) through grey to yellow (acid), the grey end-point atpH 4.6 being very sharp and easily seen.The cerous-ceric redox system inthe presence of ferroin or nitroferroin can be used as a pH indicator in thetitration of weak bases; 86 the thallous-thallic system in the presence ofstarch and potassium iodide behaves similarly,86 responding to transitions ofpH around 3-2 and 8.2. The indicator can be used for the titration ofcarbonate as a mono-acid base.Acid-violet 87 (a triphenylmethane dye) and brilliant-yellow 88 arerecommended as argentimetric adsorption indicators for halides and thio-cyanate. Both are not without some of the disadvantages usually associatedwith this type of indicator. Aniline-blue and alltali-blue have also beenused as argentimetric indicator^.^^have used triphenylmethylarsonium chloride asindicator in redox titrations of highly coloured solutions. Triphenylmethyl-arsonium permanganate and dichromate are both soluble in ethylene di-chloride, forming yellow solutions, and the end-points are denoted byextraction of these substances into the organic layer.Few new indicators have been recommended for the ever-widening fieldof complexometry, despite the fact that the recent literature on titrimetricanalysis shows an overwhelming preference for complexometric methods.Gerlach 91 uses a mixture of dimethyl-yellow (or methyl-orange) and Erio-chrome Black T for titrations with E.D.T.A.; the colour change is fromgrey to wine-red.Taylor 92 recommends hzmatoxylin as indicator for thedirect complexometric determination of aluminium.This overcomes thenecessity for a back-titration procedure involving other metal solutions.Morin 93 is used as fluorescent indicator in the direct complexometnc titrationof gallium and indium. Catechol-violet is a useful indicator in complexo-metric analysis, forming coloured complexes with cations not only in alkalinebut also in acidic solution. Malat, Suk, and Ryba have developed selectiveand accurate methods for the titrations of bismuth 94 and thorium 95 usingGibson and White82 U.S.P. 2,416,619, 1947.83 W. Buss and G. Schmidt, Lebensmitt., 1954, 5, 56.84 I. H. Sher, Analyt. Chem., 1955, 27, 831.85 E. Ranke-Madsen, H. Skarbye-Nielsen, and K. Ostergaard, A d a Chem. Scand.,87 G. Muller and A.Detter, Deutsch. Apoth.-Ztg., 1954, 94, 1119.8 8 J. BognAr and J. Vereskoi, Ada Chim. Acad. Sci. Hung., 1954, 5, 91.89 N. F. Dobrovol'skii, Soobshch. Nauk Rabot. Vsesoyuz. Khim. Obshchei im Mende-O0 N. A. Gibson and R. A. White, Analyt. Chim. Acta, 1955, 12, 116, 413.O1 K. Gerlach, Angew. Chem., 1955, 67, 178.92 M. P. Taylor, Analyst, 1955, 80, 153.93 V. Patrovsky, Chem. Listy, 1953, 47, 1338.O4 V. Suk, M. Malat, and 0. Ryba, ibid., 1954, 48, 203.* 5 Idem, Coll. Czech. Chem. Comm., 1954, 19, 079.1954, 8, 1414.E. Ranke-Madsen and T. KjaergArd, ibid., 1955, 9, 293.leeva, 1953, 12BELCHER, BEVINGTON, STEPHEN, AND WEST. 349this indicator. Nickel, cobalt, manganese, zinc, magnesium, cadmium, andcopper also form coloured complexes with catechol-violet in alkaline solution,enabling these metals to be accurately determined by direct complexometrictitration.96 Flaschka and Franschitz 97 have applied the ferrocyanide-ferricyanide-3 : 3'-dimethylnaphthidine system as a general indicator incomplexometry.The method is based on an earlier procedure of Brownand Hayes.98 Musil and Theis use Chromazurol S as indicator for thedirect titration of iron, aluminium, and zirconium gs9 100~101 with E.D.T.A.Kinnunen and Merikanto lo2 have used " Zincon," as a colorimetric reagentfor zinc, in place of Eriochrome Black T as indicator in the direct titrationof zinc with E.D.T.A. and in back-titration procedures using standard zincsolutions. A similar approach may lead to the development of other selec-tive indicators for the complexometric determination of metals.Standardisation.-GAlvez Laguarta lo3 recommends using saturatedsolutions of certain substances as analytical standards where the concen-trations are accurately known from the solubility of the solute.Suitablesubstances for acidimetric and alltalimetric standards are calcium hydroxide,borax, boric acid, and tartaric acid. Pierson and Gantz lo4 prefer to usepotassium dichromate for the standardisation of titanium(@ solutions, andthey carry out the titration under carbon dioxide, using conventionalredox indicators. The titanium(II1) solution is best prepared from thehydride, which can be obtained in a very pure state.Van Hall and Stone lo5 describe the properties of 4-aminopyridine as astandard in acidimetry.There are few bases which can be used as analyticalstandards and the introduction of this base is a matter of some interest.The substance behaves as a monoprotic base, dissociation constant,1.6 x 10-5; its equivalent weight is thus 94-12 4-Aminopyridine appearsto satisfy most of the requirements for a primary standard : it is a stablecolourless solid (m. p. 161') which is easily purified by recrystallisation orsublimation and is non-hygroscopic. The reagent is readily synthesised andcan be recovered from titration residues. Used in the standardisation ofhydrochloric acid, sharp end-points are obtained with methyl-red as indi-cator. The relatively high equivalent weight is another desirable feature ofthis substance.Smith lo6 describes a convenient method for the preparation and stan-dardisation of small quantities of perchloratoceric acid solutions in per-chloric acid, thus making an important analytical reagent of very highoxidation potential readily available.The standardisation of ammoniumvanadate solutions with oxalic acid is described by West and Skoog.lo7Duval lo8 has studied the thermal stability of twelve analytical standards96 V. Suk, M. Malat, 0. Ryba, Coll. Czech. Chem, Comm., 1955, 20, 158.97 H. Flaschka and W. Franschitz, 2. analyt. Chem., 1955, 144, 421.O 8 E. G. Brown and T. J. Hayes, Analyt. Chim. Acta, 1953, 9, 6.9g A. Musil and M. Theis, 2. analyt. Chem., 1955, 144, 351.loo Idem, ibid., p. 427.lol M. Theis, ibid., p.106.lo2 J. Kinnunen and B. Merikanto, Chemist-Analyst, 1955, 44, 50.lo3 E. M. GAlvez Laguarta, I n f . Qukm. Anal., 1954, 8, 153.lo4 R. H. Pierson and E. St. C. Gantz, Analyt. Chem., 1954, 26, 1809.lo5 C. E. van Hall and K. G. Stone, ibid., 1955, 27, 1580.lo6 G. F. Smith, ibid., p. 1142.lo' D. M. West and D. A. Skoog, Analyt. Chim. Ada, 1955, 12, 301.log C. Duval, ibid., 1955, 13, 32350 ANALYTICAL CHEMISTRY.by thermogravimetry ; hydrated salts show large irregularities in watercontent, and anhydrous forms are preferred.Methods.-Numerous procedures have been recommended for titrimetricdetermination of the sulphate ion. Wilson, Pearson, and Fitzgerald 109describe improvements to the complexometric method for the determinationof 1-20 mg.amounts of sulphate; after the precipitation of barium sul-phate, the excess of standard barium chloride is titrated with E.D.T.A. Asimilar method is described by Tettweiler and Pilz 110 for the determinationof 0-01-50 mg. of sulphur in biological material; the excess of barium isreplaced by zinc on addition of a small amount of the zinc-E.D.T.A. complexand the liberated zinc ions are titrated with E.D.T.A. Belcher, Gibbons,and West ll1 apply their complexometric evaluation of barium sulphateprecipitates to the determination of sulphur in steel. Geyer 112 describesthe titration of sulphate, using a solution of barium chloride as titrant andalizarin-red S as indicator. The procedure does not differ appreciablyfrom that of Fritz and Kirkland,l13 who have made a much fuller study ofthe titration and have published a rapid titrimetric procedure for the deter-mination of macro-amounts of sulphate.A subsequent paper by Fritz andYamamura 11* deals with the titration of micro-amounts of sulphate ; thetitration is carried out in 80% ethanol, an ethanolic solution of bariumperchlorate being used as titrant and " Thorin '' [2-(2-hydroxy-3 : 6-di-sulpho-l-naphthy1azo)benzenearsonic acid] as indicator. These methodsare satisfactory only with pure sulphate solutions ; the microtitration isused for the determination of sulphate in raw and treated water after removalof cations by ion exchange.Much has been published during the year on complexometric methodsfor the determination of many metals.It is not possible to include all thepublished methods in this Report, but a critical selection of the more originalmethods is given. The literature on the analytical applications of the com-plexones is becoming confusing and some attempt must shortly be made toreview developments since Schwarzenbach's original publications on a reallycritical basis.An interesting paper 115 describes the complexometric titration ofultramicro-amounts of calcium and magnesium in 5-20 pl. of insect hzmo-lymph. Bond and Tucker 116 give three methods for the titration of calciumin the presence of magnesium. Harris and Sweet 117 determine cobalt withE.D.T.A., excess of reagent being titrated with zinc. In solutions containingonly nickel and cobalt,lls the sum of both metals is determined on onealiquot part and nickel only on another aliquot part after extraction of thecobalt as the a-nitroso-P-naphthol complex.Pribil 119 determines nickel inthe presence of cobalt by forming the E.D.T.A. complexes of both metals;lo9 H. N. Wilson, R. M. Pearson, and D. M. Fitzgerald, J . A$pl. Chem., 1954, 4, 488.110 K. Tettweiler and W. Pilz, Naturwiss., 1954, 41, 332.ll1 R. Belcher, D. Gibbons, and T. S. West, Analyst, 1955, 80, 751.112 R. Geyer, 2. analyt. Chem., 1955, 146, 174.113 J. S . Fritz and M. Q. Freeland, Analyt. Chem., 1954, 26, 1593.11* J. S . Fritz and S. S. Yamamura, ibid., 1965, 29, 1461.115 K. van Asperen and I. van Esch, Nature, 1954, 194, 927.118 R. D. Bond and B. M. Tucker, Chem. and Ind., 1954, 1236.117 W.F. Harris and T. R. Sweet, Analyt. Chem., 1954, 28, 1648.118 Idem, ibid., p. 1649.R. Pribil, Chem. Listy, 1954, 48, 825BELCHER, BEVINGTON, STEPHEN, AND WEST. 351nickel ions are then liberated by addition of potassium cyanide to thesolution. Numerous direct and indirect procedures are recommended forthe titration of aluminium.120-124 Bismuth is titrated with E.D.T.A. in thepresence of thiourea; 125 the effect of numerous ions on this titration isdescribed. An indirect procedure 126 and a method suitable for metallurgicalproducts 127 are also described for the complexometric determination ofbismuth. Other methods have been recommended for the determination ofgal1ium,l2* magnesium in the presence of aluminium,129 palladium,13* zincin aluminium alloys,131 and zirconium.132Pribil 133 has continued his studies of 1 : 2-diaminocyclohexane-NNN‘N‘-tetra-acetic acid as a titrimetric reagent; iron and manganese are titratedstepwise, and copper is determined indirectly in the presence of iron, cobalt,nickel, and manganese. Pribil has also described a modified iodometricmethod for manganese in ores and alloys, based on the titration of themanganese (111) -E . D .T. A. complex.Methods are given for the masking of iron,135 iron, aluminium, andmanganese,l36 and lead, bismuth, and other heavy metals 137 in titrationswith E.D.T.A. Collier 138 discusses the interference of phosphate in thetitration of calcium and magnesium with E.D.T.A.Among the newer and lesser-known titrants, ascorbic acid, sodiummetavanadate (vanadic acid), and chloramine-B deserve some mention.Erdey and his co-workers 139 have used ascorbic acid as a reducing titrant inthe determination of silver in alloys, plating baths, and spent “ hypo ”solutions.The neutral or slightly acid silver solution is titrated with astandard solution of ascorbic acid, Variamine Blue (4-amino-4’-methoxy-diphenylamine) being used as indicator. A procedure for the determinationof oxygen in water 140 depends on the oxidation of iron(I1) to iron(m)hydroxide, which is then dissolved in acid, and the iron(II1) titratedwith ascorbic acid. Ascorbic acid as reductant and Variamine Blue asindicator have been compared with thiosulphate and starch in severaliodometric titrations ; 141 good results are obtained in most of the titrationsexamined.120 M.Theis, 2. analyt. Chem., 1955, 144, 106.121 1. Saj6, Magyar Kern. Folybirat, 1954, 60, 268.122 Idem, ibid., 1953, 59, 319.123 H. Flaschka and H. Abdine, Mikrochim. Acla, 1955, 37.124 E. Wanninen and A. Ringborn, Analyt. Chim. Acta, 1955, 12, 308.1Z5 J. S. Fritz, Analyt. Chem., 1954, 26, 1978.1Z6 K. Lu Cheng, ibid., p. 1977.127 J. Kinnunen and B. Wennerstrand, Chemist-Analyst, 1954, 43, 88.125 G. W. C. Milner, Analyst, 1955, 80, 77.1Z9 J. A. Ritchie,,ibid., p. 402.130 W. M. MacNevin and 0. H. Kriege, Analyt. Chem., 1955, 27, 535.132 A. Musil and M. Theis, 2. analyt. Chem., 1955, 144, 427.133 R. Pribil, Coll. Czech. Chem. Comnz., 1955, 20, 162.134 R. Pribil and J.Vulterin, Chern. Listy, 1954, 48, 1132.135 H. Flaschka and R. Puschel, 2. anaZyt. Chem., 1954, 143, 330.136 R. Pribil, Chem. Listy, 1953, 47, 1333.137 R. Pribil and 2. Roubal, ibid., 1954, 48, 818.135 R. E. Collier, Chem. and I d , 1955, 587.140 L. Erdey and F. Szabadvery, ibid., p. 325.141 L. Erdey, E. Bodov, and M. Papay, ibid., 1955, 5, 235.J. C. Sergeant, Metallurgia, 1954, 50, 252.L. Erdey and L. BuzAs, Acta Chim. Acad. Sci. Hung., 1954, 4, 195352 ANALYTICAL CHEMISTRY.Singh and Sood 142 have reported further on the uses of the Chloramine-B-iodine monochloride system. In strongly acidic solution, iodide, arsenite,antimonite, mercurous chloride, stannous chloride, iron (II), hydrazine, andquinol are determined by direct titration. Indirect titrations are describedfor hydrogen peroxide, lead and manganese dioxides, and seleniumdioxide.143Vanadatometry has received considerable attention during the past yearand may prove useful in some titrimetric processes. The reduction ofvanadium(v) to vanadium(1v) proceeds smoothly and quite rapidly in mostof the recommended procedures and visual end-points with established redoxindicators are sharp. In a paper published in 1947, Willard and Manalo 1 4stated that the formal potential of the system, V0,-/V02+ is 3-1-02 v inlhl-sulphuric acid, rising to +la30 v in 8M-sulphuric acid. The high acidconcentration necessary in most vanadatometric procedures and the almostexclusive use of N-phenylanthranilic acid as indicator may thus be explained.Molybdenum is determined by reduction to molybdenum(1v) in a bismuthreductor ; 146 the reduced solution is titrated with a solution of ammoniummetavanadate, N-phenylanthranilic acid being used as indicator.Rao,Murty, and Gopala Rao 146 find that oxalic acid catalyses the indicatorreaction in the titration of uranium(1v) with vanadate solution ; diphenyl-benzidine or N-phenylanthranilic acid may be used as indicators. Hypo-phosphite and phosphite are both oxidised by an excess of vanadic acid inthe presence of silver ~u1phate.l~~ The excess of vanadic acid is titrated withstandard iron (11) and N-phenylanthranilic acid as indicator. The oxidationof thiosulphate to tetrathionate and to sulphate by vanadic acid has beenre-examined and suitable procedures for the titration of thiosulphate havebeen deve10ped.l~~ Singh and Singh titrate numerous substances directly 149and indirectly with vanadic acid in strongly acidic solutions, using iodinemonochloride as indicator.These procedures are almost identical withthose using Chloramine-B as titrant, described by Singh and So0d.1~~ Thevanadatometric determination of copper, zinc, cobalt, and mercury afterprecipitation of the metals as complex thiocyanates is described : lead iodidecan also be titrated.The direct titrimetric determination of carbon dioxide is described byBlom and Edelhausen.151 This important method involves the absorptionof the gas in pyridine or acetone and the titration of the solution withstandard sodium methoxide in methanol, thymol-blue being the indicator.The method is applied to the determination of carbon dioxide in air andin gaseous products obtained by combustion of micro- and semimicro-amounts of organic compounds.142 B.Singh and K. C . Sood, Analyt. Chim. Acta, 1954, 11, 313.143 Idem, ibid., p. 317.144 H. H. Willard and G. D. Manalo, Ind. Eng. Chem. Anal., 1947, 19, 462.145 E. V. Ankudimova, Trudy Komissii analit. Khim. Akad. Nauk S.S.S.R., Otdel.146 V. P. Rao, B. V. S. R. Murty, and G. Gopala Rao, 2. analyt. Chem., 1955, 147,147 G. Gopala Rao and H. S. Gowda. ibid., 1955, 146, 167.148 H. S. Gowda, K. B. Rao, and G. Gopala Rao, Analyt. Chim. Acta., 1955, 12, 504.140 B. Singh and S. Singh, ibid., 1954, 10, 408; 1954, 11, 412.150 Idem, ibid., 1955, 13, 405.1 5 1 L.Blom and L. Edelhausen, ibid., p. 120.khim. Nauk, 1954,5, 197.161BELCHER, BEVINGTON, STEPHEN, AND WEST. 353A simple and elegant method is described by Flaschka 152 for the titri-metric evaluation of potassium tetraphenylboron. The precipitate is dis-solved in acetone containing acetic anhydride, and the solution is titratedwith standard perchloric acid in glacial acetic acid, crystal-violet being theindicator.An interesting titrimetric procedure has been developed for the deter-mination of hypophosphite in the presence of phosphite.lm Cerium(1v)oxidises both substances quantitatively in boiling solution after 15 minutes,but at 60°, only hypophosphite is oxidised after 30 minutes. The method isaccurate and precise.w. r. s.Classical Organic AnalysisThe development of rapid methods of ultimate and functional groupanalysis has been reviewed,lM and the various methoas are compared.The effect of saving time by proper organisation of the laboratory and theuse of riderless damped balances and of calculating machines is also discussed.An alternative tube packing has been recommended for the determinationof carbon and hydrogen to avoid radio-active cross-contamination betweenconsecutive samples of 1%-labelled compounds. 155 This consists of 7 cm.of platinum gauze, 11 cm. of granular quartz (both kept at 900-950"),4 cm. of manganese dioxide mounted on platinised asbestos, and 3 cm. ofsilver-wool heated at 175".It has been found that low carbon values are obtained with certain sugarphosphates unless the boat is heated with the full blast of the flame.15sThis causes rapid deterioration of the combustion tube.If, however, thesample is covered with tungstic oxide, decomposition proceeds normally.Some glazing occurs at the junction of the tube with the long furnace becauseof attack by volatile phosphorus compounds, but this effect can be reducedby placing a boat containing tungstic oxide at this point.Wilzbach and Sykes 15' have described a procedure for the determinationof isotopic carbon in which the sample is heated with copper oxide in a sealedtube and the carbon dioxide is isolated by fractional condensation in vacuo.The results agree well with those obtained by less simple methods.The rapid high-temperature method 158 for determination of carbonand hydrogen in coal has been subjected to further examination by inde-pendent workers.'@)* It is concluded that the method is more rapid andaccurate than the Liebig method.Ammonium sulphamate has been recommended as a substitute for leaddioxide for the absorption of nitrogen oxides.161 More than 100 analysescan be carried out with one filling.It is not stated, however, if this reagent152 H. Flaschka, Chemist-Analyst, 1955, 44, 60.153 D. N. Bernhardt, Analyt. Chew., 1954, 26, 1798.15* W. Schoniger, Angew. Chern., 1955, 67, 261.155 J. D. Gabourel, M. J. Baker, and C. W. Koch, Aflalyt. Chenz., 1055, 27, 795.lS6 R. Belcher, J. E. Fildes, and A. J. Nutten, Analyt. Chiin. Acta, 1955, 13, 431.15? K.E. Wilzbach and W. Y. Sykes, Science, 1954, 120, 494.15* R. Belcher and C . E. Spooner, Fuel, 1941, 20, 130.159 R. A. Mott and H. C . Wilkinson, ibid., 1955, 34, 169.160 L. J. Edgcombe, ibid., p. 185.161 A. S . Hussey, J. H. Sorensen, and D. D. DeFord, AnaZyt. Chew., 1965, 27, 280.REP.-VOL. LII 364 ANALYTICAL CHEMISTRY.has any advantage over other alternatives to lead dioxide reviewed in thelast Report.Sources of error in the method for the direct determination of oxygenhave been investigated.162 The quartz of the combustion tube and thecarbon black must be of good quality and the temperature of the carbonmust be kept constant. A simple method of purifying carbon black isproposed.A modified method for the direct determination of oxygen has beendescribed lrn based on the Oita-Conway method.By incorporating thefillings in one tube only one furnace is required. This method appears tobe a distinct advance over the previous rather cumbersome assemblies whichhave been described.A study has been made of the reaction of copper oxide with carbondioxide in the Dumas method.lM It is claimed that a significant amountof oxygen is formed under the usual conditions of the determination and iscarried over into the azotometer. The effect is overcome by modifying boththe packing of the tube and the heating arrangements.A submicro-Kjeldahl method has been developed for amounts of nitrogenof the order of 30 pg.165 After distillation of ammonia a colorimetric methodis applied using ninhydrin as reagent.The factors influencing sealed-tube decomposition have been studiedby Kirk and his co-workers.166 When the temperature exceeds 500"ammonium hydrogen sulphate is decomposed, yielding elementary nitrogen,and also ammonia is oxidised by sulphur trioxide or oxygen.The amount ofsulphuric acid and the time of digestion may also have an influence on lossof ammonia. When a little water is added, the stability of ammonia insulphuric acid is markedly increased. Most organic compounds are decom-posed completely during 30 minutes' digestion.Baker 16' has shown that compounds which normally do not respond tosealed-tube digestion (e.g., nitro-compounds) can be analysed by mixingthem with 50 mg. of glucose or o-mercaptobenzoic acid.A digestion tem-perature of 4 2 0 4 0 " for about 45 minutes is recommended.For microgram amounts of nitrogen, Dixon 168 recommends sodiumhypobromite-sodium thiosulphate titration after digestion and distillationin the usual way, owing to the more favourable equivalent which is obtained.A new method has been described 169 in which the compound is decom-posed by heating with iodic and phosphoric acids. Nitrogen is then measuredin an azotometer. However, many types of compound, particularly hetero-cyclic compounds, yielded poor results and the general accuracy was inferiorto that of the Kjeldahl or the Dumas method.Mikl and Pech170 have extended a method developed some few yearsago for the rapid determination of chlorine, to the determination of sulphur.L.J. Moelants and W. Wesenbeck, Mikrochim. Acta, 1954, 738.163 F. H. Oliver, Analyst, 1955, 80, 593.164 T. Mitsui, Jup. Analyst, 1953, 2, 117.166 Y . Okada and H. Hanafusa, Bull. Chcm. SOC., Japan, 1954, 27, 478.166 B. W. Grunbaum, P. L. Kirk, L. G. Green, and C. W. Koch, Analyt. Chem.,lg7 P. R. W. Baker, Analyst, 1955, 80, 481.168 J. P. Dixon, Analyt. Chim. Acta, 1955, 13, 12.16@ S. Ohashi, Bull. Chem. SOC. Japan, 1955, 28, 177.170 0. Mikl and J. Pech, Chem. Listy, 1953, 47, 904.1955, 27, 384BELCHER, BEVINGTON, STEPHEN, AND WEST. 355The sample is wrapped in filter-paper which is ignited and lowered into aflask filled with oxygen, acid gases being absorbed in hydrogen peroxide.The sulphuric acid formed is titrated with standard alkali.If chlorine ispresent it is determined by titrating the neutralised solution with mercuricnitrate.A similar method has been described by Schoniger 171 for the determin-ation of chlorine and bromine, which are finally determined by the mercuricoxycyanide method.Sulphur has been determined by combustion in an empty tube withchromic oxide as ~ a t a l y s t . 1 ~ ~ Sulphur oxides are absorbed on sodiumsilicate contained in a boat which presumably is then weighed. Vecera 173claims to have improved the so-called Zinneke method by using a 10-cm.length of silver shavings kept at 450480" to absorb sulphur oxides, thesample being burnt in the usual way over a platinum contact. Silversulphate is extracted with water and titrated potentiometrically with0.01 N-pot assium iodide solution.To overcome low results due to the fixation of sulphur when metals arepresent, Sirotenko 17* recommends covering the residue in the boat after thecombustion, with boron oxide and re-igniting it.The sulphur oxidesproduced are absorbed and titrated in the usual way.A method has been described 175 for the determination of 1-100 p.p.m.of sulphur in organic liquids, in which the sample is decomposed in a verticalfurnace packed with vanadium pentoxide and the sulphur formed is measuredby a conductometric method.Chlorine in certain chlorinated aromatic compounds has been determinedby hydrolysis in a solution of potassium hydroxide in tetrahydrofurfurylalcohol.176 The alcohol is distilled off and the residual solution is titratedby Volhard's method.Brown and Musgrave 1 v 7 determine fluorine, chlorine, and nitrogensimultaneously by decomposition with sodium in a nickel bomb.Whenoxygen is absent from the compound, nitrogen is converted quantitativelyinto cyanide. Fluorine is determined on one aliquot part by means of athorium nitrate titration, chlorine on another part by argentometric titrationusing Rhodamine-BS indicator, and cyanide on a further part by the Liebig-Deniggs method. In a later paper 178 an ion-exchange method is reportedfor chlorine and fluorine after masking cyanide with formaldehyde. Thetotal acidity of the eluate is determined, and chloride then titrated argento-metrically or by the mercury oxycyanide method.Raney nickel in an alkaline medium or zinc-sulphuric acid in the presenceof palladised charcoal has been recommended as an alternative to the usualmethods of decomposition for the determination of hal0gens.17~ Theparticular reagent to be used depends on the nature of the compound.Fluorine has also been determined on the semimicro-scale after171 W.Schoniger, Mikrochim. Ada, 1955, 123.172 P. N. Fedoseev and R. M. Lagoschnaya, Zhur. analit. Khim., 1954,9,224.M. VeEefa, Chem. Listy, 1954, 48, 613.174 A. A. Sirotenko, Mikrochim. Acta, 1955, 153.175 J. A. Hudy and R. D. Mair, Analyt. Chem., 1955, 27, 802.E. H. Searle and E. Bell, J. Appl. Chem., 1954, 4, 430.177 F. Brown and W. K. R. Musgrave, Analyt. Chim. Ada, 1955, 12, 29.178 R. E. Banks, F.Cuthbertson, and W. K. R. Musgrave, ibid., 1955,13, 442.L. Simonyi, G. TokAv, and G. GBI, Magyar Kkm. Folybirat, 1954, 60, 97356 ANALYTICAL CHEMISTRY.decomposition in a Pam bomb by passing the leachings through an ion-exchange resin before titration with thorium nitrate in the usual way.lmFluorine and carbon have been determined simultaneously by decom-position in a silica tube in the presence of moist oxygen at 1100".181 Thehydrofluoric acid produced is titrated with standard alkali and the carbondioxide is determined gravimetrically after absorption in a soda-asbestostube.Burton and Riley lS2 have described a rapid method for the determin-ation of phosphorus in which the samples are decomposed in a Parr micro-bomb and then determined spectrophotometrically by the molybdenum-bluemethod.Arsenic can be determined rapidly by heating in a sealed tube for 5minutes with magnesium and magnesium oxide.lB The contents of thetube are decomposed with dilute acid and the evolved arsine is trapped in asolution of silver diethyldithiocarbamate in pyridine.The colour producedis measured spectrophotometrically . Pietsch decomposes by wetdigestion, adds barium nitrate, and determines arsenate in the filtrate bythe Volhard method. It is claimed that the method can be applied in thepresence of many metals and halogens.A modified wet oxidation method for 10-mg. samples has been developedwhich avoids the low results sometimes obtained when sulphuric-nitric acidoxidation is used.186 The sample is dissolved in sulphuric acid and oxidisedwith potassium permanganate, the excess of which is removed with hydrogenperoxide. After evaporation to fumes of sulphuric acid, the conventionaliodometric titration is applied.A new combustion procedure to determine mercury when halogens arepresent, which eliminates possible loss as mercury halide, has been de-scribed.ls6 The combustion tube is packed with calcium oxide, and mercuryis collected in a bubbler containing nitric acid.It is finally titrated withpotassium thiocyanate, ferric alum being used as indicator.Methoxyl and ethoxyl groups have been determined selectively by thetrimethylarnine method, isopropanol being used as solvent in place of theusual ethan01.1~' No solubility correction for tetramethylammonium iodideis then necessary.The latter is filtered off and ethoxyl is then determinedin the filtrate.A critical study of the methoxyl determination has been carried out.18*Erratic results were traced to the use of sodium thiosulphate in the scrubber.When 25% sodium acetate solution was used instead, satisfactory resultswere obtained. In an independent study lS9 sodium antimony1 tartrate wasfound to be the best of several scrubbing solutions which were examined.A new improved apparatus has been described by Kirsten and Ehrlich-180 C. Eger and A. Yarden, Bull. Res. Council Israel, 1954, 4, 305.181 H. E. Freier, 13. W. Nippoldt, P. B. OIsen, and D. G. Weiblen, AnaZyt. Chem.,182 J. D. Burton and J. P. Riley, AnaZyst, 1955, 80, 391.183 M.JureEek and J. Jenik, Coll. Czech. Chem. Comm., 1955, 20, 550.184 R. Pietsch, 2. analyt. Chern., 1955, 144, 353.187 G. Gran, Suensk. Papperstidning, 1954, 57, 702.188 A. E. Heron, R. H. Read, H. E. Stagg, and H. Watson, AnaZyst, 1954, 79, 671.189 R. Belcher, J. E. Fildes, and A. J. Nutten, Aszalyt. Chim. Ada, 1966, 13, 16.1955, 27, 146.G. Bahr, H. Bieling, and K. H. Thiele, 2. analyt. Chern., 1954, 143, 103.T. Sudo, D. Shimoe, and F. Miyahara, Jap. Analyst, 1955, 4, 88BELCHER, BEVINGTON', STEPHEN, AND WEST. 357Rogozinsky.lW The sample is first heated with the reaction mixture in astoppered tube for 30 minutes at 100" and is then transferred to the apparatusto distil off the methyl iodide. The determination is completed iodo-metrically.R.B.Polarography.Inorganic.-During the period covered by this Report, considerableattention has been paid to the selection of electrode systems for use inpolarographic analysis. A vibrating platinum electrode has been chosenfor the determination of oxygen in water.lgl The diffusion current varies asthe square root of the amplitude, and is greater than that obtained with arotating electrode. Platinummicro-electrodes and automatic recording have been used for polarographyin fused salts, and the effects of variation in speed of rotation, electrodearea, and temperature on the rate of polarisation have been studied.192 Anew type of mercury electrode which has a pinhole small enough to preventmercury (kept at constant pressure level) from falling has been described.193The sensitivity is comparable to that of the dropping electrode, and thepolarograms are smooth with considerably less slope than those obtainedwith the streaming electrode.Yet another form of dropping-mercurycathode, in which the end is bent into a horizontal position, has been devised.The advantage claimed is that the mercury drop has minimum size andmaximum stability. Reduction in dropping time minimises galvanometeroscillation.lM The dropping-gallium electrode has been found entirelyunsuitable. lg5 The advantages of replacing the calomel and other conven-tional reference electrodes by electrodes such as antimony, molybdenum,tungsten, graphite, etc., when the limiting current rather than the half-wavepotential is being measured, have been discussed.These electrodes simplifyvessel design, and give excellent waves.1g6 A nomogram for determiningthe characteristics of capillaries has been constructed. lS7 Japaneseauthors 198 have described a polarograph in which a small alternating currentis superimposed on the directly applied potential, and the alternatingcurrent is recorded directly on photographic paper. The method wasapplied to several analyses and theoretical implications were considered.A general discussion of the various methods of oscillographic polarographyhas been published,lg9 and its application in quantitative analysis has beentreated.200 The excellence of the Barker '' Square Wave " polarograph hasbeen demonstrated, particularly in respect to sensitivity and selectivity.mlA value of 50 C.P.S.was chosen as normal.190 W. Kirsten and S. Ehrlich-Rogozinsky, Mikrochim. Acta, 1955, 786.l*l W. Dirschel and K. Otto, Chem.-Ind.-Tech., 1954, 26, 321.IQ2 E. D. Black and T. De Vries, Analyt. Chem., 1955, 27, 906.193 Y. Yashiro, Bull. Chem. SOC. Japan, 1954, 27, 564.194 J . Smoller, Coll. Czech. Chem. Conzm., 1954, 19, 238.lS5 P. A. Gigdre and D. Lamontagne, Science, 1954, 120, 390.lQ8 L. JensovSk9, Chem.-Tech., Berlin, 1955, 7, 159.197 D. P. Schcherbov, Zauodskaya Lab., 1955, 21, 246.lS8 M. Senda, M. Okuda, and I. Tachi, Bull. Chenz. SOC. Japan, 1955, 28, 31, 37.lQ9 Ya. P. Gokhshtein and Yu. A. Surkov, Zhur. analit. Khim., 1954, 9, 319.2oo R. Kalvoda and J . Macku, Chem. Lisly, 1954, 48, 378.201 D.J. Ferrett and G. W. C. Milner, Analyst, 1955, 80, 132358 ANALYTICAL CHEMISTRY.Attention has been drawn to the non-proportionality between concentrationand maximum current in derivative polarography.a2 The effect of adsorp-tion on the anodic polarographic wave has been studiedJ203 and attention hasbeen paid to selection of the zero line in cases where an incomplete wave isobtained.204 Methods have been specified for the purification of supportingelectrolytes for use in p~larography.~~Very many analytical methods have been described during the past year.Few outstanding applications have appeared and it is only possible tomention some of the more interesting methods. The suitability of ascorbicacid, phthalic acid, and benzoic acid media for the determination of uraniumhas been examined.m6 Ascorbic acid appears to be the most efficient baseelectrolyte.rn7 Others have used an ammonium carbonate medium contain-ing ‘‘ Tiron ” (1 : 2-dihydroxybenzene-3 : 5-disulphonic acid) and com-plexone I11 (E.D.T.A.) for the same analysis.Methods for the determinationof zinc in various electrolyte media and in various alloys, ores, etc., havebeen investigated.208 The polarography of niobium has been described 204-211and also that of 213 gallium,214 indiumJ2I5 palladiumJ216and 218 The polarographic determination of copper 219 and ofcadmium and zinc 220 in cyanide solution has been investigated, and alsogeneral applications of the method to the analysis of electroplating solu-tions.221 The polarographic method is well suited to the analysis of minorconstituents in titanium alloys.222 m-Nitrophenylarsonic acid has beendescribed as a polarographic reagent for the latter After precipit-ation of the titanium compound, it is dissolved and the nitro-group ispolarographed.The polarographic behaviour of chlorides ,224 bromides,225chlorates,226 sulphate,227 sulphite,228 nitrate and nitrite,229, 230 fluoride,=l202 T. Isshiki, Y. Mashiko, and S. Tsukagoshi, Pharm. Bull., Japan, 1954, 2, 263.203 P. Zuman, Chem. Listy, 1954, 48, 1025.204 N. 2. Bruja, Rev. Chim., 1953, 4, 30.205 L. Meites, Analyt. Chem., 1955, 27, 416.208 M. V. SuSiC, Bull. Inst. Nuclear Sci. Belgrade, 1954, 4, 57, 59.207 M. V. SuSiC, I. Gal, and E. Cuker, Analyt.Chim. Acta, 1954, 11, 586.208 I. A. Korshunov, Uch. Zap. Gor’kovskogo Un-Ta, 1953, 24, 15.20s S. K. Dhar, Analyt. Chim. Acta, 1954, 11, 289.210 D. J. Ferrett and G. W. C. Milner, Nature, 1955, 175, 477.211 E. I. Krylor, U. S. Kolevatova, and V. A. Samarina, Doklady Ahad. Nauk212 A. A. Vleck, Chem. Listy, 1954, 48, 189.213 G. W. Smith and F. Nelson, J . Amer. Chem. Soc., 1954, 76, 4714.214 H. E. Zittel, Diss. Abs., 1954, 14, 1303.215 M. Bulovova, Chem. Listy, 1954, 48, 655.216 R. F. Wilson and R. C . Daniels, Analyt. Chem., 1955, 27, 904.217 J. Cihalik, J. Dolezal, V. Simon, and J. Zyka, Chem. Listy, 1954, 48, 28.218 J. Kracek, Cesk. Sklar a Keramik. 1953, 3, 183.219 J. V. Petrocelli and G. Tatoian, Plating, 1955, 42, 550.z2O T.A. Downey, ibid., p. 267.z 2 l R. Diaz, ibid., p. 415.2g2 J. J. Mikula and M. Codell, Analyt. Chem., 1955, 27, 729.2z3 E. Van Dalen and R. P. Graham, Analyt. Chim. Acta, 1955,12, 489.224 A. A. Vleck, Coll. Czech. Chem. Comm.. 1954. 19, 221.228 J. Koryta and J. Tenygl, ibid., 1954, 48, 407.227 0. A. Ohlweiler, Analyt. Chim. Acta, 1954, 17, 590.228 V. B. Aulenbach and J. L. Balmat, Analyt. Chem., 1955, 27, 562.22s R. Pletikha and E. Krzhizhova, Zhur. analit. Khim., 1954, 9, 366.Z3O Idem, Prumysl. Potravin, 1953. 4, 383.231 C. E. Shoemaker, Analyt. Chem., 1955, 27, 552.S.S.S.R., 1954, 98, 593.M. Hemala, Chem. Listy, 1953, 47, 1323BELCHER, BEVINGTON, STEPHEN, AND WEST. 359iodine and iodides 232 has been studied. Methods have been described formanganese in air,= tin in dissolved oxygen and hydrogen p e r ~ x i d e , ~ ~and for minute amounts of carbon monoxide.236Amperometric methods have been proposed for several analyses, e.g.,of ferricyanide with silver nitrate,%? of thorium with fluoride,%* of zirconiumin fluoride medium with c~pferron,%~ of calcium and fluoride (indirectlyvia calcium), and also of lead 241 with ferrocyanide, of .heavy metals withsodium hydroxide by use of a rotating platinum electrode,a2 of arsenite,ammonia, and thiocyanate with hypochlorite,243 of copper and nickel inalloy steel by means of rubeanic acid,% of copper, zinc, nickel, and cobaltwith sodium anthranilateIa5 of copper with sodium carbonate by use ofcopper electrodes (this procedure is said to be superior to the use of thedropping-mercury cathode or rotating platinum cathode) .246 Perhaps themost interesting amperometric method to be suggested during the period isthat for the determination of potassium.247 The potassium is precipitatedwith sodium tetraphenylboron, and the excess reagent is then titrated withthdous nitrate.Apart from the similar behaviour of rubidium, cxsium,and ammonium, chloride is said to interfere.Organic.-A general review of the polarographic method and instrumentsin general has been madea8 and particular attention has been paid toorganic applications of the technique.xg Studies have been made of thepolarography of steroids,2m sulphur ~ompounds,~~1 aromatic heterocyclicethers and esters.253 Many workers continue to pursue theline of functional group analysis by means of polarography and amperometrictitration.Examples are the determination of the carbonyl group,254aliphatic nitro-gro~ps,~~~ dis~lphide,~~6 ~ u l p h o n e s , ~ ~ ~ and t h i o l ~ . ~ ~ ~ Exten-sive surveys have been made of the polarography of several compounds :232 J. V. A. NovAk, Chem. Listy, 1953, 47, 903.233 I. B. Kogan and S. L. Makhover, Gigiena i Sanit., 1954, 2, 52.234 L. Bouberlova-Kosinova, Vest. Ustred Ustav. Geol., 1954, 29, 13.235 J. C. Fittipaldi, Rev. Fac. Ing. Quim. argentina, 1953, 21-22, 123.236 J. Vykoukal and K. Linhart, PaZiva, 1953, 33, 236.237 B. Khosla and H. C. Gaur, Current Sci., 1954, 23, 216.238 M. Sundaresan and M. D. Karkhanavala, ibid., p. 258.230 E.C. Olson and P. J. Elving, Analyt. Chem., 1954, 26, 1747.240 0. A. Songina, A. P. Voiloshnikova, and M. T. Kozlovskii, Izvest. Akad. Nauk241 B. Khosla, H. C. Gaur, and N. P. Ramaiah, Current Sci., 1954, 23, 361.242 J. Kamecki and M. Slabon, Roczniki Chem., 1955, 29, 107.243 H. A. Laitinen and D. E. Woerner, Analyt. Chem., 1955, 27, 215.244 Kh. Ya. Levitman and 2. A. Krivchik, Zavodskaya. Lab., 1955, 21, 397.a45 A. K. Zhdanov, R. I. Tseitlin, and A. M. Yakubov, ibid., p. 7.246 J. Kamecki and L. Suski, Roczniki Chem., 1955, 29, 115.247 W. Kemula and J. Kornacki, ibid., 1954, 28, 635.248 W. van Tongeren, Chem. Weekblad, 1954, 50, 769.249 F. Freese, ibid., p. 781.250 M. Brezina, V. Volkova, and J. Volke, Chem. Listy, 1954, 48, 194.251 P.Zuman, R. Zumanova, and J. Teisinger, Coll. Czech. Chem. Comm., 1955, 20,252 J. Volke and V. Volkova, Ckem. Listy, 1954, 48, 1031.253 M. I. Bobrova and A. N. Matregeva, Zhur. obshlhi Khim., 1954,24, 1741.264 Ch. Pr6vost and P. Souchay, Chim. analyt., 1955, 37, 3.255 R. Miquel and A. Condylis, Bull. Soc. chim. France, 1955, 236.256 J. R. Carter, Science, 1954, 120, 895.257 E. S. Levin, A. P. Shestov, Doklady Akad. Nauk S.S.S.R., 1954, 98, 999.258 M. D. Grimes, J. E. Puckett, B. J. Newby, and B. J. Heinrich, Analyt. Chem..Kazakhstan S.S.R., 1953, Ser. Khim. [6], 69.139.1955, 27, 152360 ANALYTICAL CHEMISTRY.barbituric acid derivatives,259, 260 penicillin,261 papaverine,262 chloro-p h y l l i n ~ , ~ ~ ~ cystine,264 dithiocarbamic oxalic acid,266 maleic an-h ~ d r i d e , ~ ~ ~ formaldehyde,268 aureomycin and terramycin ,26B the loweralkyl, dialkyl, and acyl peroxides,270 alkyl phthalate e s t e r ~ , ~ ~ l amaranth,272cyclohexyldini tr~phenols,~'~ diethyldithio~arbamate,~~a and di- and tri-phosphopyridine n u ~ l e o t i d e s .~ ~ ~ In addition, the polarographic assay oftechnical malathion 276 (S-1 : 2-dicarbethoxyethyl-00-dimethyl dithio-phosphate), trypsin ethyl alcohol content of bl00d,~~8 thio-compounds in blood and serum,279 and of carbon oxysulphide 280 has beendescribed. The role of polarography in biochemistry 281 and of oscillo-graphic polarographv in pharmacy has been reviewed generally.282Potentiometric Titration.-The selection of the inflection point on potentio-metric titration curves by the concentric-arcs method using a simply madetransparent template is described by Tubbs.2s The well-known abilityof a platinum electrode to respond to changes of silver-ion concentration hasbeen examined.284 The response was found to be due to a layer of silverformed at the interface and it varied with the previous treatment of theelectrode.The discussion also covers the similar behaviour of gold andcarbon electrodes. I t has been shown 285 that, in the titration of ferrousiron with ceric sulphate, a platinised platinum electrode may function partlyas an oxygen electrode when the concentration of ferrous ion is less than0.001~. A study 286 has been made of the response of a silver electrode topH, with the conclusion that it is not suitable for the determination of pHalthough a linear relationship between potential and pH was obtainedfrom pH 2 to 9.The precipitation of halides with silver nitrate has beenstudied with a glass electrode.287 The curves for direct titration againstsilver nitrate have maxima at the equivalence point and the reverse titrationZ59 P. Zuman, Chem. Listy, 1954, 48, 1006.260 Idem, ibid., p. 1020.z6l E. Krejci, Cesk. Farm., 1955, 4, 73.962 V. D. Bezuglyi, Zhuv. obshchei Khim., 1954, 24, 2190.263 W. L. Waggatzer and J. E. Christian, J . Amev. Phavna. Assoc., Sci. Ed$z., 1955,94,30.Z64 hl. Kalousek, 0. Grubner, and A.Tockstein, Coll. Czech. Ckem. Comm., 1954,19,1111.265 I<. Zahradnik and L. JenSovskv, Chem. Listy, 1954, 48, 11.246 G.F. Reynolds and R. C. Smart, Anal-yt. Chim. Acta, 1954, 11, 487.267 E. Barendrecht, Chem. Weekblad, 1954, 50, 755.Z68 L. SCrAk, Chem. Listy, 1954, 48, 272.269 0. Ti5lupilovA and V. MaSinovA, Cesk. Favm., 1953, 2, 226.270 H. Briischweiler and G. J. Minkoff, Analyt. Chim. A d a , 1955, 12, 186.271 G. C. Whitnack, J . Reinhart, and E. S t . Clair Gantz, Analyt. Chenz., 1055, 27, 359.272 G. C. McKeown and J. L. Thompson, Canad. J . Chem., 1954, 32, 1025.273 M. Maruyama and K. Maruyama, Jap. Analysl, 1964, 3, 11.274 J. Davis, A. J. Easton, and J. Freezer, Chem. and Ind., 1955, 241.275 C. Carruthers and J . Tech, Arch. Riochem. Biophys., 1955, 56, 441.276 W. H. Jura, Analyt. Chem., 1955, 27, 525.277 5 . Stokrova, Chem. Listy, 1954, 48, 1082.278 D.Monnier and W. F. Riiedi, Helv. Chim. A d a , 1955, 38, 402.279 L. Jirousek and M. Petrackova, Chenz. Listy, 1954, 48, 260.280 V. Sedivec and V. VaSAk, ihid., p. 19.281 J. de Wael, Chem. Weekblad, 1954, 50, 778.282 J . Heyrovskq, Cesk. Farm., 1953, 2, 403.283 C. I;. Tubbs, Anadvt. Chem., 1954. 26, 1670.284 I-'. L. Allen and A. Hickling, Anal.vt. Chim. Acta, 1954, 11, 467.265 T. de Vries, Chem. Weekblad, 1954, 50, 533.I-I. Khalifa and I. M. Issa, J . Indian Chem. SOC., 1954, 31, 426.287 W. Hubicki, Ann. Univ. M . Cztrie-Sklodowska, 1953, 8, 149BELCHER, BEVINGTON, STEPHEN, AND WEST. 361curves have minima. The addition of indifferent electrolytes decreases stepheight. Potentiometric titrations with controlled current input have beendescribed by Adams,28* but he has concluded that the new method is fre-quently no better than conventional potentiometry except that sometimeslarger inflexions are obtained.It has been found that a platinum electrodeimmersed in a solution containing hydrogen peroxide changes its potentiallinearly with pH.2S9 The electrode can be used for the titration of acids,bases, and certain salts and was applied to the determination of activechlorine, alkali, and carbonate in hypochlorites and chlorites. It wassubsequently used for the titration of dichromate ions and strong acidswhen present together.B0Potentiometric methods have been described for the titration of lowconcentrations of boric acid in water and deuterium oxide. The titrationwas carried out with carbonate-free potassium hydroxide with addition ofmannitol.Helium gas was used for stirring.291 Blannitol was preferred toglycerol. Other authors have confirmed that invert sugar, fructose, propane-1 : 2-diol, and ethylene glycol can also replace glycerol. These authors 298preferred ethylene glycol to mannitol. Maltose, lactose, starch, dextrin,etc., were ineffective. Quadrivalent selenium can be titrated with potassiumpermanganate in a sodium hydroxide medium.293 A new potentiometricmethod has been described for cadmium in which the latter is precipitatedas (C22H240,N4)2HB[CdBr4] by addition of diantipyrinylmethane in thepresence of a known amount of 0-%-potassium bromide. The excess ofbromide ion is then determined argent~metrically.~~~ A potential drop ofapproximately 400 mv was recorded by others for the potentiometrictitration of hydrogen peroxide with 0.1 N-potassium ferricyanide in alkalinemedium.2g5 Singh et aZ.Zg6 have continued their studies on the use ofchloramine-B by describing the potentiometric determination of ferro-cyanide, hydrazine, ferrous sulphate, iodide, arsenic(w), antimony(m),quinol, and quinhydrone.The titrations were carried out in dilute mineralacid. The potentiometric determination of sulphur in a wide variety ofmaterials has been described,2g7 and the titration of thiols and disulphidesby means of silver nitrate has been critically examined, errors in previouswork being disclosed.298 Others have described the automatic pH titrationof soluble phosphates and their mixtures.299 A mean-square error of&l*9% has been recorded for the potentiometric determination of sodiumfluoride by titration against an aluminium salt with the quinhydronee l e c t r ~ d e .~ ~ Deschamps’s method for the potentiometric titration ofa s s R. N. Adams, Analyt. Chem., 1954, 26, 1933.28g I. E. Flis, Zkur. analit. Khim., 1954, 10, 38.eeo I. E. Flis and Zh. L. Vert, ibid., p. 44.291 L. Silverman and W. Bradshaw, Analyt. Chim. Acta, 1955. 12, 177.292 J. J. Sciarra and J . A. Zapotocky, J . Amer. Pltarm. Assoc., Sci. Edn., 1955,44,370.2g3 I. M. Issa, S. A. Eid, and R. M. Issa, Analyt. Chim. Acta, 1954, 11, 275.2g4 V. P. Zhivopistsev, Uch. Zap. Molotovskogo, Gos. Un-ta, 1953, 8, 141.2B5 J. Vulterin and J .Zgka, Chem. Listy, 1954, 48, 619.2g8 B. Singh and G. Singh, Analyt. Chirn. Acta, 1954, 11, 569.2g7 G. Graus and A. Zohler, Angew. Chem., 1954, 66, 437.2B* R. Cecil and J. R. McPhee, Biochern. .J., 1955. 59, 234.2gg J. R. van Wazer, E. J. Griffith. and J. F. McCullough, Analyf. Chem., 1954,300 Sh. T. Talipov and I. L. Teodorovich, Doklady Akad. Nauk Uzbekhistan S.S.R.,26, 1755.1953, 32362 ANALYTICAL CHEMISTRY.chlorides in sea water in an aqueous acetone medium has been favourablyreviewed by Denam~r.~Ol A copper indicator electrode has been used forthe potentiometric titration of xanthates with standard copper sulphatesolution.302Conductometric Titration.-During this period relatively little workhas been done on the application of conductometric titration techniques toanalytical problems.The design of cells for precision conductometry hasbeen d i s c u s ~ e d . ~ ~ Japanese authors have reported on the conductometrictitration of copper with a O.OEiM-solution of 8-hydroxyquinoline in ethanol,=and another worker305 has determined the chloride content of serum bytitration with silver nitrate after precipitation of protein with alcohol.Higuchi et d 3 0 6 have titrated hydrochloric and sulphuric acids and theirmixtures in anhydrous acetic acid, with a standard lithium acetate reagent.The curves showed distinct breaks corresponding to C1-, SO,-, and HSO,-.The relative merits of lithium, sodium, potassium, and tripentylammoniumacetates as titrants were examined. Conductometric and potentiometrictechniques have been compared €or the titration of free acids and of acidsliberated by hydrolysis from nickel@) salts at high temperatures.307 Theconductometric titration of anabasine and lupinine mixtures in acetonesolution against 0*05~-mineral acid or naphthalene-2-sulphonic acid has beenreported. The latter titrant gave the most satisfactory results.308High-frequency Titration.The fundamentals of high-frequency titration and specifically theproperties of analysers " without electrode contact " have been discussedparticularly with reference to measurements with a heterodyne apparat~s.~O~A study has been made of the mechanism of high-frequency titrationmethods by means of a " Q meter " 310 and the relationship between the resist-ance and the concentration of the solution and its application to the explan-ation of titration curves, have been discussed in detaiL311 The same authorhas also examined the general theory of high-frequency tit ration^.^^^ Otherauthors 313 have independently examined the change in electrical character-istics of solutions during titration.Ethylenediaminetetra-acetic acid has been used as a titrant for the high-frequency determination of several cations. Hara and West 314 have usedthe Sargent Model V Oscillometer for chelation studies of several ions,301 J.Denamur, Compt. rend., 1955, 240, 1223.302 M. Oktawiec, Prace Inst. Minist. Hutnic, 1954, 5, 184.903 J. C. Nichol and R. M. Fuoss, J . Phys. Chem., 1954, 58, 696.304 K. Shinra, K.Yoshikawa, T. Kato, and Y . Nomizo, J . Chern. SOC. Japan, 1954,SO6 H. A. Teloh, Amer. J . Clin. Path., 1954, 24, 1095.306 T. Higuchi and C. R. Rehm, Analyt. Chem., 1955, 27, 408.307 F. Cuta, 2. Ksandr, and M. Hejtmhnek, Chem. Listy, 1954, 48, 1341.308 V. V. Udovenko and L. A. Vvedenskaya, Trudy Sredneaziatskogo GosudarstUniv. Khim. Nauk, 1953, 40, 3.30g K. Cruse and R. Huber, Angew. Chem., 1954, 86, 625.310 M. Honda, K. Nakano, and A. Satuka, J . Chem. SOC. Jafian, 1954, 75, 1299.311 K. Nakano, ibid., p. 773.312 Idem, ibid., p. 776.313 V. A. Zarinskii and D. I. Koshkin, Zhur. analit. Khim., 1955, 10, 110.314 R. Hara and P. W. West, Analyt. Chim. Acta, 1954, 11, 264.75, 46BELCHER, BEVINGTON, STEPHEN, AND WEST. 363particularly uranyl ion at pH 3-5-4.0,315 and bivalent metals such as nickel,cobalt, manganese, zinc, cadmium, and lead.Calcium was titrated success-fully in the presence of a phosphate buffer, but magnesium and the otheralkaline earths gave erratic results.316 Large concentrations of electrolytedisturbed these titrations. High-frequency titrations of the salts of variousorganic acids in non-aqueous solvents have been reported.317 Sodium saltswere directly titrated with perchloric acid, and potassium salts were back-titrated by using sodium acetate in glacial acetic acid.Coulometric Titrations.Coulometric determinations at constant current in unstirred solutionshave been described by Gierst et aL31* In this method only the transitiontime is measured, i.e., the interval between the establishment of capacitycharge on the electrode and the increase in potential that occurs when theconcentration of the substance at the surface of the electrode falls to zero.The subject is treated mathematically, and two transitometers are describedfor providing the necessary electrical and timing devices.Determinationsoccupy less than one minute and the accuracy is approx. 0.2%. Lingane 319has described a method and electrode assembly for the automatic coulometrictitration of acids, Another author 320 has examined the various stages inthe titration of a solution of hydrochloric acid by coulometry at constantintensity. Salicylic acid has been determined coulometrically by bromin-ation and amperometric titration of the excess generated with cuprousion.321 Electrically generated bromine has also been used for the titrationof phenols.322 Here, however, the reaction was sufficiently rapid to permitdirect determination. Selenium( rv) has been determined coulometricallywith iodide and thio~ulphate.3~ Chloride, bromide, and iodide have beentitrated coulometrically with electrically generated silver ion, dichloro-fluorescein being used as i n d i ~ a t o r .~ ~ Concentrations of lead down to10e8hil have been analysed by coulometric technique.325 Various dyes havebeen titrated coulometrically with externally generated titanous andelectrically generated permanganate 327 has been used to determine oxalate,ferrous iron, and arsenite.Photometric Titration.Underwood 328 has discussed the technique, apparatus, and applicationsThe applications are discussed in a general way of photometric titrations.s15 R.Hsra, and P. W. West, Analyt. Chim. Acta, 1955, 12, 285.316 Idem, ibid., p. 72.817 M. Ishidate and M. Masui, Pharm. Bull., Japan, 1954, 2, 50.s18 L. Gierst and P. Mechelynik, Analyt. Chim. Acla, 1955, 12, 79.320 J. Badoz-Lambling, Chim. analyt., 1954, 36, 291.321 B. Kawamura, K. Momoki, and S. Suzuki, Jap. Analyst, 1954, 3, 29.322 C. N. Van Zyl and K. A. Murray, S. African Ind. Chemist, 1954, 8, 243.s23 K. Rowley and E. H. Swift, Analyt. Chem., 1955, 27, 818.324 P. S. Tutundzic, I. Doroslovacki, and 0. Tatic, Analyt. Chim. Ada, 1955, 12, 481325 T. L. Marple and L. B. Rogers, ibid., 1954, 11, 574.826 J.S. Parsons and W. Seaman, Analyt. Chem., 1965, 27, 210.327 P. S. Tutundzic and S. Mladenovic, Analyt. Chim. Acta, 1955, 12, 390.A. L. Underwood, J. Chem. Educ., 1954, 31, 394.J. J. Lingane, ibid., 1954, 11, 2833 M ANALYTICAL CHEMISTRY.in respect of acid-base, redox, precipitation, and complexometric titrations.Stress is laid on the use of ethylenediaminetetra-acetic acid in complex-f onnation tit rat i ons. Automatic spec trophotomet ric tit rations with coulo-metrically generated titanous ion have been used for the determination ofvanadium in titanic chloride.329 Bobtelsky et al. have continued theirstudies of the heterometric technique by using quinaldic acid for the titrationof copper in the presence of sundry other and l-nitroso-%naphtholfor the determination of ferric iron and cobalt.332* 333 Other workers 334have described the automatic photometric titration of calcium and mag-nesium in carbonate rocks, using ethylenediaminetetra-acetic acid with theusual murexide and Eriochrome-black T indicators.Frame Photometry.As would be expected, during the period of the Report, the bulk ofpapers having the use of the flame photometer as their main subject matterare concerned with the analysis of small amounts of the alkali and alkaline-earth metals. A few papers deal with the determination of other ions.Thus, attention has been paid to the determination of copper in gasoline,after extraction with hydrochloric acid ; 335 to the determination of boron 336by using an aqueous methanol solvent (1 : 1) which is 0 .5 ~ in hydrochloricacid, to the determination of lanthanum 337 by use of the band spectra ofLao, and to the determination of amino-nitrogen by the ingenious device ofshaking the amino-acid solution with a suspension of copper phosphate andsubsequently determining the chelate-bound copper by the flame photo-meter .%*Vm-ous workers have reported on the determination of sodium : in puresolution,33g and in alumina in the presence of calcium 3p1 and the otheralkaline earths,342 in glass and ores,343 and in rocks.% Potassium has beendetermined : in fertilisers after ion-exchange separation 345 of interferinganions, in the presence of sodium,346* 3433 344 and in the presence of alkaline-earth metals.342 Methods have been described for lithium 342*343 and forrubidium and c ~ e s i u m . ~ ~ Methods for overcoming interference in the329 H.V. Malmstadt and C. B. Roberts, A m l y l . Chem., 1955, 27, 741.330 M. Bobtelsky and B. Graus, Analyt. Chim. Acta, 1954, 11, 253.331 M. Bobtelsky and E. Jungreis, ibid., 1955, 12, 351.333 Idem, ibid., p. 248.35a Idem, ibid., p. 263.334 L. Shapiro and W. W. Brannock, Analyt. Chem., 1955, 27, 725.as5 J. H. Jordan, Petrol Refining, 1954, 33, 158.336 J. A. Dean and C. Thompson, Anulyt. Chem., 1955, 27, 42.337 R. Ishida, J . Chem. SOG. Japan, 1955, 76, 60.338 R. E. Beauchene, A. D. Berneking, W. G. Schrenk, H. L. Mitchell, and R, E.339 F. Hegemann, V. Caimann, and H. Zoellner, Ber. deufsch. Keram. Ges., 1954, 31,340 A.Hegedas, F. K. Fukker, and M. Dvorszky, Magyar Kkm. FoZyda’rat, 1953, 59,341 F. Hegemann and B. Pfab, Glaslechn. Ber., 1954, 27, 189.342 W. Schuhknecht and H. Schinkel, 2. analyt. Chem., 1954, 143, 321.843 J. P. Williams and P. B. Adams, J . Amer. Ceram. SOC., 1954, 37, 306.344 L. Jenkins, U.S. Atomic Energy Comm., TEI-453, 1954.345 C. W. Gehrke, H. E. Affsprung, and E. L. Wood, J . Agric. Food Chem., 1955,34~1 R. Neumann, Gas Lek Ces., 1954, 93, 1229.Silker, J . Biol. Chem., 1955, 214, 731.315.334.3, 48BELCHER, BEVINGTON, STEPHEN, AND WEST. 365determination of sodium and potassium due to overIapping spectra, radi-ation, and anions have been discussed.a7 The interference of chlorohydro-carbons owing to flame quenching has been reported by Milton and Duffield.34sAnother worker 34~1 has reported on the influence of the stability of the lightsource and the mutual effects of sodium and potassium on each other.Methods have been reported for the determination of calcium in the presenceof the other alkaline earths?= in natural ~ a t e r s , ~ ~ l and in serum.352 Anacetylene flame has been used for the photometric determination of stront-ium 353 without interference from iron, sodium, calcium, and magnesiumwhen present separately.Strontium has also been determined simultane-ously with sodium, potassium, calcium, and magnesium with a multi-channelphotometer 354 and its determination in sea water 355 and in cement 356has also been reported. Flame photometry has been used for the deter-mination of trace metals in wine a57 and for the determination of inorganicsulphate358 in serum after precipitation of this anion with an excess ofbarium chloride.Absorp tiometry .Inorganic.-The development of absorptiometric methods during 1954has been re~iewed.35~ During 1955 many methods were reported in theliterature, but few of these can be regarded as outstanding contributions.Mehler 360 has reviewed potential errors in spectroyhotometry withoptically dense solutions, stressing the need for a truly monochromatic lightsource.The principles of precision colorimetry have been discussed, and ithas been shown how variations in slit width, sensitivity, and dark currentsetting affect precision. Two new photometric procedures were proposed,which offer a possible increase in precision, but require more time and effortthan normal methods.361Copper has been determined photometrically with several reagents :tetraethylthiuram disulphide which forms a yellow-brown copper complexin acid solution ; sodium di-2-hydroxyethyldithiocarbamate 362 which issaid to possess many advantages over sodium diethyldithiocarbamate ;ethylenediaminetetra-acetic acid 363 and nitrilotriacetic acid ; 364 8-hydroxy-and 8-hydro~y-2-methyl-quinoline,~~~ the latter being more suitable ;347 P.Porter and G. Wyld, Analvt. Chenz., 1955, 27, 733.348 R. F. Milton and W. D. Duffield, Chem and Ind., 1955, 280.s4Q R. Ishida, J . Chem. SOC. Japan, 1955, 76, 56.350 A. Hegedus, T. Millner, and E. Pungor, Magyar KLm.FoZy6iral, 1953, 59, 304.351 E. G. Will and B. Schwarzkopf, J . Amer. Waterworks Assoc., 1955, 47, 253.352 R. W. R. Baker, Biochem. J., 1955, 59, 566.353 A. E. Taylor and H. H. Paige, Analyt. Chem., 1955, 27, 282.s56 T. J. Chow and T. G. Thompson, Analyt. Chem., 1955, 27, 18.358 R. D. Strickland and C. M. Maloney, Amer. J . Clin. Path., 1954, 24, 1100.35Q Anon., Chemical Age, 1955, 71, 527.360 A. H. Mehler, Science, 1954, 120, 1043.361 C. N. Reilley and C. M. Crawford, Analyt. Chem., 1955, 27, 716.s62 J. E. Delaney, SanitaZk, 1954, 2, 11.a68 W. Nielsch and G. Boltz, 2. analyt. Chem., 1954, 143, 1.364 Idem, ibid., 1954, 142, 406.s65 J. Bernal-Nievas and L. Serrango Berges, Anales F k Qulm., 1954, B, 50, 459.B. L. Valee, Nature, 1954, 174, 1050.J.J. Diamond, ibid., p. 913.M. J. Pro and A. P. Mathers, J . Assoc. Ofic. Agric. Chem., 1954, 37, 945366 ANALYTICAL CHEMISTRY.guaiacol in ammonia solution; 366 hydrobromic acid (which cannot be usedin the presence of iron) ; 367 diquinolol 368, 369 and sodium diethyldithio-arba am ate.^^^^^^ Uranium has been determined by use of 1 : 3-dipentyl-propanedi-1 : 3 - 0 n e , ~ ~ ~ ammonium thi~glycollate,~~~ dibenzoylmethane(using ethyl acetate extraction), and by the thiocyanate method with 377and without 378 extraction. Iron has been determined by using variousreagents : ethylenediaminetetra-acetic acid,379, 3a0 tartaric acid 381 in thepresence of a periodate stabiliser, salicylaldehyde-glycinehydroxamicacid 382 over the pH intervals 2.35-3.34 or 5.06--10*26, phenazone-thio-cyanate, the pink complex being extracted with amyl acetate at pH 2.5,383cupferron (methanol or butane-2 : 3-dio1 being used to keep the complex ins ~ l u t i o n ) , ~ ~ dimethylglyoxime 385 but with use of pyridine rather thanammonia, with or without extraction by chlor0form,~8~ o-phenanthrol-ine,387, 388 and dipyridyl 389 and with sulphosalicylic acid 390 and variationsof the t hiocyanate meth0d.~~1-393Bismuth has been determined colorimetrically by use of thio~rea,~9~-3~~hydrobromic acid,397 sodium diethyldithio~arbamate,~~~ and phenazone-potassium iodide.399 Manganese has been determined by using sodiumdiethyldithio~arbamate,~~ the intense colour of the permanganateor that of the manganic ion following oxidation by bromate in 8N-nitricacid.m2 Ethylenediaminetetra-acetic acid 403 and dimethylglyoxime have366 M.Ya. Shapiro and V. G. Lupina, Vinodelie i Vinogradstvo S.S.S.R., 1953, 6.367 W. Nielsch and G. Boltz, 2. analyt. Chem., 1954, 142, 427.368 L. Ghyssaert, Bull. Cent. Belge Etud. Docum. Eaux, 1954, 56.369 H. Jerome and H. Schmitt, Bull. SOC. Chim. biol., 1954, 36, 1343.370 A. L. Shinkarenko, E. A. Gryaznova, and L. A. Podkolzina, Attechnoe Delo, 1954,3,21.371 H. J. Cluley, Analyst, 1954, 79, 561.373 R. H. Rush, Diss. Abs., 1954, 14, 1521.373 J. A. S. Adams and W. J. Maeck, Analyt. Chem., 1954, 26, 1635.374 L. Kosta, Sloven. Acad. Sci. Arts Ljubljana Rep., 1953, 1, 12.375 R. Piibil and M. Jelinek, Chem. Listy, 1953, 47, 1326.376 F.Will, Diss. Abs., 1954, 14, 761.377 L. Silverman and L. Moudy, Nucleonics, 1954, 12, 60.378 V. S. JovanoviC and E. F. Zucker, Bull. Inst. Nuclear Sci., Belgrade, 1954,4,111.379 W. Nielsch and G. Boltz, Mikrochim. Acta, 1954, 481.380 Y. Uzumasa and M. Nishimura, Bull. Chem. SOC. Japan, 1955, 28, 88.381 W. Nielsch and G. Boltz, Metall, 1954, 8, 374,382 A. Mukherjee, Naturwiss., 1955, 42, 127.383 E. Sudo, J . Chem. SOC. Japan, 1954, 75, 968.384 F. Buscarons and J. L. M. Malumbres, Anales Fis. Qufm., 1955, B, 51, 117.385 N. Oi, J . Chem. SOC. Japan, Pure Chem. Sect., 1954, 75, 1067.386 Idem, ibid., p. 1069.387 A. E. Harvey, jun., J. A. Smart, and E. S. Amis, Analyt. Chem., 1955, 27, 26.388 G. Nonvitz and M. Codell, Analyt. Chim. Acta, 1954, 11, 350.389 M.Schnitzer and W. A. Delong, Canad. J . Agric. Sci., 1954, 34, 324.390 L. Erdey and E. Banyai, Acta Chim. Acad. Sci. Hung., 1954, 4, 315.391 F. G. Zharovskii, Ukrain. Khim. Zhur., 1953, 19, 548.392 L. Aconsky, T. Asami, and hl. Mori, J . Amer. Waterworks Assoc., 1954, 49, 894.393 M. Gral-Cabanac, Analyt. Chim. Acta, 1955, 12, 50.394 W. Nielsch and G. Boltz, 2. analyt. Chem., 1954, 143, 13.395 N. N. Aleshkina, Sk. Stud. Nauchn Rabot Rostovskogo, Gos. Un-ta, 1953, 92.306 W. Nielsch and G. Boltz, 2. analyt. Chem., 1954, 143, 168.397 Idem, Analyt. Chim. Acta, 1954, 11, 438.398 K. L. Cheng, R. H. Bray, and S. W. Melsted, Analyt. Chem., 1955, 27, 24.399 E. Sudo, J . Chem. Sac. Japan, 1954, 75, 1291.400 E. Specker, H. Hartlramp, and M.Kuchtner, Z . analyt. Chem., 1954, 143, 425.401 A. Kozawa, M. Tanaka, and K. Sasaki, Bull. Chem. SOC. Japan, 1954, 27, 345.402 W. C. Purdy and D. N. Hume, Analyt. Chem., 1955, 27, 256.403 W. Nielsch and G. Boltz, Analyt. Chim. Acta, 1954, 11, 367BELCHER, BEVINGTON, STEPHEN, AND WEST. 367been used in the determination of nicke1,4w,405 and the former also for thatD f cobalt.N6 Other workers have used the terpyridyl,a7 nitroso-R-salt,N8and thiocyanate 409 methods. Eriochrome-black T,410 m~rexide,~ll bromo-anilic acid,% and pyrazole-blue412 have been used for the colorimetricdetermination of calcium, in addition to the alizarin413 method. Bariumhas been determined in the presence of equal amounts of calcium andstrontium by precipitation with ammonium molybdate 414 and subsequentdetermination of the molybdenum by the thiocyanate procedure.Thelatter procedure has been employed by some authors for the determinationof molybdenum itself 4 1 5 3 416 but others prefer to use the dithiol 417 procedureor the colour of the molybdoferrocyanide complex.418 Two papers havereported on the tungsten thiocyanate 420 Vanadium has beendetermined : by reduction to the quadrivalent state, reaction with ferricchloride and formation of colour of the ferrous iron thus produced withdimethylglyoxime,421 by a catalytic effect based on the enhanced oxidationof aniline in the presence of complex-forming oxalate ions,422 through theacceleration by vanadium of the oxidation of aniline by chlorates activatedwith 8-hydroxyquinoline,423 by the colour produced with catechol 424 andalso with molybdophosphate or tung~tophosphate.~~~ Ethylenediamine-tetra-acetic acid 426 and diphenylcarbazide 427 have been used as reagentsfor the absorptiometric determination of chromium.The stereotypedrhodamine-B 42*9 429 and thiourea 430 methods have been used for the deter-mination of antimony, whilst arsenic has been determined turbidimetricallyafter reduction to elementary arsenic by hypophosphorus acid 431 or by the useof silver diethyldithiocarbamate after evolution as a r ~ i n e . ~ ~ ~ Thiourea 433-436404 W. Nielsch, Z. analyt. Chern., 1954, 143, 272.405 H. Specker and H. Hartkamp, ibid., 1955, 145, 260.406 H. Goto and J. Kobayashi, J . Chem. SOC. Japan, 1954, 75, 964.407 R.R. Miller and W. W. Brandt, Analyt. Chem., 1954, 26, 1968.408 Y. Oka and M. Miyamoto, J a p . Analyst, 1953, 2, 322.409 S. Hirano and M. Suzuki, ibid., p. 316.(lo A. Young, T. R. Sweet, and B. B. Baker, Analyt. Chem., 1955, 27, 356.411 T. T. Gorsuch and A. M. Posner, Nature, 1955, 176, 268.412 L. Erdey and L. Jankovits, A c f a Chim. Acad. Sci. Hung., 1954, 4, 235.413 S. Natelson and R. Penniall, Analyt. Chem., 1955, 27, 434.414 T. Nozaki, J . Chem. SOC. Japan, 1954, 75, 168.415 Methods of Analysis Committee, B.I.S.R.A., J . Iron and Steel Inst., 1954,178, 356.418 B. Ricca and G. D’Amore, Ann. Chim. (Italy), 1955, 45, 69.420 H. Nishida, Jap. Analyst, 1954, 3, 25.421 N. Oi, J . Chem. SOC. Japan, 1954, 75, 841.422 G.Almassy and 2. Nagy, Magyar Kkm. Folydivat, 1954, 60, 118.423 V. A. Nazarenko and E. A. Birycik, Zhur. analit. Khim., 1955, 10, 28.424 V. Patrovsky, Chem. Listy, 1954, 48, 622.425 L. Erdey, K. M. Vigh, and L. Mazor, Acta Chim. Acad. Sci., Hung., 1954, 4, 259.426 R. F. Cellini and E. A. Valiente, Anales Fis. Quim., 1955, 51, B, 47.427 L. Erdey and J. Inezedy, Acta Chim. Acad. Sci. Hung., 1954, 4, 289.428 H. Onishi and E. B. Sandell, Analyt. Chim. Acta, 1954, 11, 444.42Q W. Nielsch and G. Boltz, Z. analyt. Chem., 1954, 143, 264.43O Idem, ibid., p. 81.431 S. Hirano and D. Ishii, Jap. Arzalyst, 1953, 2, 28.432 M. JureEek and J. Jenik, Coll. Czech. Chem. Comm., 1955, 20, 550.433 A. Jilek and J. Vrestal, Chem. Zvesti, 1953, 7, 33.434 W. Nielsch, Z.anal-vt. Chem., 1955, 144, 191.435 W. Nielsch and G. Boltz, 2. Metallkunde, 1954, 45, 380.436 W. Nielsch and L. Giefer, 2. analyt. Chem., 1955, 145, 347.K. Protiva, Chem. Listy, 1954, 48, 779.C. H. Williams, J . Sci. Food Agric., 1955, 6, 104.Methods of Analysis Committee, B.I.S.R.A., J . Iron and Steel Inst., 1954,178, 356368 ANALYTICAL CHEMISTRY.has been used extensively in the absorptiometric determination oftellurium, and phosphorous acid has been employed to reduce it to metallictellurium before measurement of the absorption in the ultraviolet region.3 : 3'-Diarninobenzidine yields an intense yellow piazselenol with selenitesolutions; this has been used in the determination of selenium.&* Thestructure of the alumjnium-morin complex has been examined, and what isclaimed to be a new method has been proposed on this ba~is.43~ In thealuminon method, precipitation of the aluminium lake has been preventedby formation of the aluminon-aluminium-sulphosalicylic acid complex.440Others 841 prefer Eriochrome-cyanine to aluminon.Ferroin 442 and thefluorescence of alurninium-8- hydrox yquinoline 443 under carefully controlledconditions have also been employed in absorptiometric methods for alu-minium. Various reagents have been used in the absorptiornetric deter-mination of titanium : salicylhydroxamic acid * (yellow coloiir in diluteacid solution), " Tiron " in the presence of E.D.T.A.,446 sulphosalicyljc acid,446hydrogen p e r o ~ i d e , ~ ' ~ and t h i o ~ y a n a t e . ~ ~ Many authors report onvariations of the silicomolybdate procedure for the determination of silicatein various 8-Hydroxyquinoline has been used for thedirect colorimetric determination of magnesium 457 and also indirectlyafter treatment with sulphanilic acid and sodium 459 Titan-yellow 460 and Eriochrome blue-black B 461 have also been used as colori-metric reagents for determination of the same metal.The variables in thethiourea method for tin have been closely examined.462 The tetrabromo-chrysazin463 and dianthrimide464 methods for boron have been re-investigated.437 R. A. Johnson and B. R. Andersen, Analyt. Chem., 1955, 27, 120.438 J. Hoste and J. Gillis, AnaZyt. Chim. Acta, 1955, 12, 158.4313 2. G. Szabo and M. T. Beck, Acta Chim. Acad.Sci. Hung., 1954, 4, 211.440 D. Eckerdt, L. Hartinger, and L. Holleck, Angew. Chem., 1955, 67, 178.441 K. Wacykiewicz, Prace Inst. Minist. Hutnic, 1955, 7 , 35.442 M. Delevaux, R. Smith, and F. S . Grimaldi, U.S. Atomic Energy Comm., TE1-450,443 J. W. ColIat and L. B. Rogers, AnaZyt. Chem., 1955, 27, 961.444 J. Xavier, A. K. Chakraburtty, and P. Ray, Science and Cztltuve, 1954, 20, 146.4d5 P. Szarvas and B. Csiszar, Magyar Kbm. Folybirat, 1955, 6l, 50.4413 K. Saarni and S. Suikkanen, 2. analyt. Chem., 1954, 143, 112.447 J. R. Simmler, K. H. Roberts, and S . M. Tuthill, Analyt. Chew., 1954, 26, 1902.448 G. AlmfLssy and P. Szarvas, Magyar Tud. Akad. Kbm. Tztd. Oszt Kozl., 1953,449 C. E. Crouthamel, B. E. Hjette, and C. E. Johnson, Analyt. Chern., 1955,450 Glasgow Absorptiometry Panel, MetaZZurgia, 1954, 50, 145.451 B.E. Remik, G. P. Fedorova, and G. N. Veritennikova, Nauk Zapisk. Denepr.452 P. Enghag, Jernkontorets Ann., 1954, 138, 404.453 J. Celechovskjl, Chem. Listy, 1954, 48, 391.454 J. B. Mullin and J. P. Riley, Analyt. Chi?%. Acfa, 1955, 12, 162.455 H. Wolk, Arch. Eisenhiittenw., 1954, 25, 333.456 M. Jean, Chim. analyt., 1955, 37, 125.457 C. L. Luke and M. E. Campbell, Analyt. Chem., 1954, 26, 1778.458 N. Yokouchi, J a p . Analyst, 1954, 3, 3.459 M. Suzuki, ibid., p. 93.460 H. J. G. Challis and D. F. Wood, Awlyst, 1954, 79, 762.4 a W. Nielsch and G. Boltz, 2. analyt. Chem., 1954, 143, 161.463 J. H. Yoe and R. L. Grob, Analyt. Chem., 1954, 26, 1466.464 H. Baron, 2. anaZyt.Ckem., 1954, 143, 339.1954.3, 413.27, 507.Gos. Univ., 1953, 43, 79.V. A. Nazarenko and E. A. Biryuk, Zavodskaya Lab., 1955, 21, 20BELCHER, BEVINGTON, STEPHEN, AND WEST. 369Dithizone methods for 466 zinc,467 and mercury 469have been employed. Carmine-red 38 and quinalizarin 470 have been usedfor thorium , and 9-phenetidine 471 and starch-iodine 472 (oxidation ofpotassium iodide) for thallium. Hydrogen peroxide,473 8-hydroxyquinol-ine,474 and thiocyanate-acetone methods 475 have been used to determineniobium, and in the last case, tantalum was determined simultaneously by amodified pyrogallol procedure.Cerium has been determined absorptiometrically with ~eratrole,'?~germanium with diphenyl~arbazone,4~~ gallium with rh0damine-B,4~8zirconium with ali~arin-S,*~~ beryllium by a new method with Solochromebrilliant-blue,32 phosphorus by the molybdenum-blue method using ascorbicacid as r e d u ~ t a n t , ~ ~ sodium by direct colorimetry with violuric acid inanhydrous dimethylformamide 481 and indirectly via uranyl thiocyanatefollowing precipitation of sodium zinc uranyl acetate in the usual ~ a y , * 8 ~the rare earths by aluminon 483 and alizarin-red S,4M platinum by p-nitroso-dimethylaniline,485 and palladium by the same reagent or with ethylene-diaminetetra-acetic fi-nitr~so-cr-naphthol,~~~ or thiourea.48*Hydrogen peroxide has been determined by addition of ferrous iron andt h i ~ c y a n a t e , ~ ~ ~ and carbonyl sulphide by hydrolysis to sulphide and deter-mination by the methylene-blue rneth~d.~~O Atmospheric sulphur di-oxide 491 has been determined by catalytic reduction to hydrogen sulphideand reaction of the latter with ammonium molybdate, and sulphate492has been determined following conversion into sulphuric acid on a cationexchanger by treatment with lanthanum and a measured amount of solidthorium borate-amaranth reagent (the released dye is measured at 621 mp).Nitrogen has been determined in steel by the ammonia-pyrazolone-pyridinemethod:% and in organic compounds following Kjeldahl digestion by reaction465 L.Erdey, G. Y . RCidy, and V. Fclps, Acta Chim. Acad. Sci. Hung., 1954, 5, 133.466 M. Shima, Jap. Analyst, 1953, 2, 96.467 T. Kato and S. Takei, ibid., p. 208.468 A. Petzold and I. Lange, 2. analyt. Chein., 1955, 146, 1.46s A.C. Rolfe, F. R. Russel, and N. T. Wilkinson, Analyst, 1955, 80, 523.470 A. Purushottam, Z . analyt. Chem., 1955, 148, 245.4 7 1 S. Iijima and Y . Kamemoto, J . Chem. SOC. Japan, 1954, 75, 1294.472 V. S. Fikhengol'ts and N. P. Kozlova, Zavodskaya Lab., 1955, 21, 407.473 R. Pickup, Colon. Geol. Min. Resources, 1955, 5, 174.474 J. L. Kassner, A. G. Paratla, and E. L. Grove, Analyt. Chem., 1955, 27, 492.475 A. E. 0. Marzys, AncaZyst, 1955, 80. 194.476 H. N. Antoniades, Chemist-Analyst, 1955, 44, 34.4 7 7 G. S . Desmuk, Zhur. analit. Khim., 1955, 10, 61.478 H. Onishi, Analyt. Chem., 1955, 27, 832.478 E. C. Mills and S. E. Herman, Mefallurgza, 1955, 51, 157.480 L. Erdey, V. Felps, and E. Bodor, Acta Chim Acad.Sci. Hung., 3954, 5, 65.4 8 1 R. F. Muraca and J. P. Bonsack, Chemist-Analyst, 1955, 44, 38.482 P: N. Kovalenko and V. V. Tenkovtsev, Uhrain. khim. Zhur., 1954, 20, 411.483 L. Holleck, D. Eckardt, and L. Hartinger, 2. analyt. Chem., 1955, 146, 103.484 R. W. Rinehart, Analyt. Chem., 1954, 26, 1820.485 J. J. Kirkland. Diss. Abs., 1954, 14, 760.486 W. M. MacNevin and 0. H. Kriege, Analyb. Chem., 1954, 26, 1768.487 K. L. Cheng, ibid., p. 1894.488 W. Nielsch, Mikrochim. Acta, 1954, 532.489 F. Patty and P. B. Maury, Compt. vend., 1954, 289, 976.494 L. A. Pnrsglove and H. W. Wainwright, Analyt. Chenz., 1954, 26, 1835.481 H. Stratmann, Mikrochem. Acta, 1954, 668.492 J. L. Lambert, S . K. Yasuda, and M. P. Grotheer, Analyt. Chem., 1955, 27, 800.499 J.B. Lear, Diss. Abs., 1954, 14, 1520370 ANALYTICAL CHEMISTRY.with phenol and hypochlorite in the presence of a nitroprusside catalyst.494Nitrite has been determined by reaction with thioglycollic acid and extrac-tion with diisopropyl ether-pentanol-a~etone.~~~Chloride has been determined by reaction with silver iodate and liber-ation of iodine from the displaced iodate ion by treatment with acid andcadmium iodide-starch reagent .496 The liberation of red Chromotrope-2Bfrom the blue thorium lake by the fluoride ion has been used as a means ofdetermining the latter.497 It has also been determined after distillation offluorosilicic acid by the bleaching of the thorium-alizarin lake.49* Pyro-phosphate has been determined by the cysteine-catalysed reaction withFiske’s molybdate reagent .499 Hypophosphite has been determined byreaction with molybdic acid.500T.S. W.Radiochemical Methods of Analysis.Radiochemical analysis was very briefly reviewed in Annual Reportsfor 1953,501 but the importance of isotopic methods is now such that a specialsection is devoted to them. Radioactive and enriched stable isotopes arenow generally available 502 and there are facilities for irradiating materialsin high fluxes of thermal neutrons; 502 many laboratories are equipped toundertake isotopic work. Unless special problems are being studied, theassay of radioactive isotopes requires only apparatus which is available com-mercially; a list of equipment manufactured in Great Britain has beenpublished..503 The total cost of fitting a laboratory for simple radiochemicalwork compares favourably with the initial costs for other modern instru-mental methods.For work with stable isotopes, a mass spectrometer isgenerally needed ; commercial instruments are of necessity expensive butof course can be used for analytical purposes besides those involving isotopes.There are now many useful text-books dealing with isotopic methods inChemistry; there has been a series of ten articles dealing with all aspectsof work with radioactive isotopes. The Atomic Energy Authority of GreatBritain has a school in which instruction in the uses of isotopes is given.Two conferences, in 1951 and 1954, on the uses of radioactive isotopeshave been organised by the Atomic Energy Research Establishment andheld at Oxford.At both conferences, there was a very wide range ofsubjects since the only feature common to all the papers presented was theuse of radioactive isotopes. The papers and the discussions on them have494 B. Lubochinsky and J. P. Zalta, Bull. SOC. Chim. biol., 1954, 36, 1363.495 M. Ziegler and 0. Glemser. 2. analyt. Chem., 1956, 144, 187.498 J . L. Lambert and S. K. Yasuda, Analyt. Chem., 1955, 27, 444.497 H. F. Liddell, Analyst, 1954, 79, 752.498 L. Bloch, Ckem. Weekblad, 1955, 51, 65.499 R. M. Flynn, M. E. Jones, and F. Lipmann, J . Biol. Chem., 1954, 211, 791.500 G. Gutzeit, U.S.P. 2,697,651, 1954.501 C. L. Wilson, Ann. Re$orts, 1953, 50, 375.502 “ Radio-active Materials and Stable Isotopes,” Atomic Energy Research Estab-lishment, Harwell, 1954.503 “ Radio Isotope Instrumentation and Accessories,” edited by D.Taylor andA. G. Peacock, Scientific Instrument Manufacturers’ Association of Great Britain,London, 1955.604 F. P. W. Winteringham, Lab. Practice, 1955, 4, 94, 148, 196, 244, 288, 328, 370;411, 449, 493BELCHER, BEVINGTON, STEPHEN, AND WEST. 37 1been In the summer of 1955, a large conference on thepeaceful uses of atomic energy was held at Geneva. A meeting at Edinburghon the use of radioactive materials in biological assays has been r e p ~ r t e d . ~ ~It is evident that workers in the medical and biochemical fields have beenreadier to apply isotopic methods than workers in the physical fields, butthe methods are now being used in investigations of many types, e.g., inresearch in the paint industry.510 An indication of the wide application ofthese methods is the fact that titles of papers now do not always indicatethat isotopic methods have been used in the work described.The most significant point in connection with the use of radioactiveisotopes in analysis is the great sensitivity of detection; depending uponthe isotope being studied, the limit of detection is between 10-l1 and g511Other important features of certain isotopic methods in analysis is theirspecificity, and the fact that the decay of a radioactive isotope is independentof its chemical and physical state.Almost all the chemical applications of radioactive isotopes are analyticalin nature.The topics discussed and the references cited in this Report havebeen selected to show the wide range of problems which can be tackled byisotopic methods; it has been necessary to choose those topics in which theanalytical aspects of the work are stressed.Isotopes as Accessories in Analysis.-The use of radioactive isotopes todetermine the solubilities of sparingly soluble materials is well known; 512labelled materials can also be used to study distribution equilibria, co-precipit -ation , adsorption, and other phenomenaof importance in analytical procedures.Efficiencies of separation can be assessed by labelling one of the com-ponents of a mixture and measuring activities during the course of theseparation ; the measurements can be rapid, non-destructive, and verysensitive.Radioactive isotopes have been used to test the separation byliquid-liquid extraction of the following pairs of elements : niobium andtantalurnJ5l3 cobalt and zincJ514 and protactinium and niobium.515 Thecontrolled-potential electro-separation of copper, bismuth, and lead hasbeen tested 516 with radioactive isotopes. Isotopic methods have beenemployed 517 in a study of the purification of metals by zone melting. Theseparation of tin, antimony, and tellurium with anion-exchange resins,518and paper chromatographic methods for separating inorganic ions 519 and605 “ Radio Isotope Techniques, Vol. I, Medical and Physiological Applications,”H.M.S.O., London, 1953.GO6 “ Radio Isotope Techniques, Vol. 11, Industrial and Allied Research Applic-ations,” H.M.S.O., London, 1952.“ Radio Isotope Conference, 1954, Vol.I, Medical and Physiological Applic-ations,” Butterworths, London, 1954.508 “ Radio Isotope Conference, 1954, Vol. 11, Physical Sciences and IndustriaApplications,” Butterworths, London, 1954.509 R. F. Glascock, Nature. 1955, 176, 427.510 D. F. Rushman, J . Oil Colour Chemists’ Assoc., 1953, 36, 352.511 H. Seligman, ref. 506, p. 1.512 H. K. Zimmerman, Chem. Rev., 1952, 51, 26.613 J. Y . Ellenburg, G. W. Leddicotte, and F. L. Moore, Analyt. Chem., 1954, 26, 1045.514 H. A. Mahlman, G. W. Leddicotte, and F. L. Moore, ibid., p. 1939.515 F. L. Moore, ibid., 1955, 27, 70.516 M. Ishibashi, T. Fujinaga, and Y . Kusaka, J . Chem. SOC. Japan, 1954, 75, 13.517 P.Albert, F. Montariol, R. Reich, and G. Chaudron, ref. 508, p. 75.518 G. W. Smith and S. A. Reynolds, Analyt. Chirn. Acta, 1965, 12, 151.519 M. Lederer, ibid., p. 146372 ANALYTICAL CHEMISTRY.uranium from many metals 520 have been studied with radioactive isotopes.It has been shown 521 by labelling with 35S that cyclohexyl methyl sulphidecan be completely separated from the corresponding sulphoxide by chromato-graphy. Radioactive metallic tracers (in the form of salts) have been addedto petroleums before ashing to see if the metals are completely retained inthe ash.522Isotopic methods have been used 523 to test precipitations in the colori-metric determinations of niobium and tantalum in steels. Procedures forthe micro-determination of beryllium have been tested 524 with 7Be.Methods for precipitating germanium have been examined 525 with ?lGe.Radioactive isotopes have been used 526 in critical studies of methods fordetecting and separating potassium, rubidium, and casium.In very accurate absorptiometric determinations of niobium inminerals 527 and steels,528 addition of 95Nb at an early stage in the deter-mination allows one to make corrections for small losses of the elementduring chemical separations.Isotopic methods have been combined withflame photometry to determine strontium in sea water,529 and with X-rayspectrographic methods in analyses for uranium and thorium.6306OCo has been used 531 for testing the various stages in the assay ofvitamin B12. Evaluations of determinations of iodine in biological materialshave been carried out 5329 533 with 1311.The removal from high polymers ofmaterials of low molecular weight, e.g., unused initiator, present at very lowconcentrations has been tested 534 with labelled materials. Efficiencies offractionations of high polymers can readily be assessed 635 by using mixturesof unlabelled and labelled polymers.Isotope Dilution Analysis.-A well-known and important application ofradioactive isotopes and enriched stable isotopes is in the method of isotopedilution analysis.m6 This method is applied to the analysis of complexmixtures ; it is essential that pure samples of the various components shouldbe recovered from the mixture but the necessity for complete recovery isavoided.The calculations, when using radioactive labels, are simple ; withstable labels the calculations are slightly more complicated because theconcentration of the labelling atoms needs to be such that the molecularweight of the substance is affected.In one method of working, the components of the mixture are unlabelled620 H. P. Raaen and P. F. Thomason, Analyt. Chem., 1955, 27, 936.521 G. Ayrey, D. Barnard, and C. G. Moore, J., 1953, 3179,682 L. 0. Morgan and S . E. Turner, Analyt. Chem., 1951, 23, 978.523 T. F. Boyd and &I. Galan, ibid., 1953, 25, 1568.624 T. Y. Toribara and R. E. Sherman, ibid., p . 1594.525 L. K. Bradacs, 1.-M. Ladenbauer, and F. Hecht, Mikrochirn. Acta, 1953, 229.526 W. Geilmann and W . Gebauhr, 2. analyt.Chem., 1954, 142, 241.527 G. W. C . Milner and A. A. Smales, Alaalyst, 1954, 79, 315.528 Idem, ibid., p . 425.529 A. A. Smales, ibid., 1951, 'SS, 348.530 W. J. Campbell and H. F. Carl, Analyt. Chem., 1955, 27, 1884.531 F. A. Bacher, A. E. Boley, and C. E. Shonk, ibid., 1954, 28, 1146.632 J. W. Decker and H . S. Hayden, ibid., 1951, 23, 798.533 H. Spitzy, Mikrochim. Acta, 1955, 130.534 J . C. Bevington, H. W. Melville, and R. P. Taylor, J . Polymer Sck., 1954, 12, 449.535 J. C. Bevington, G. M. Guzman, and H. W. Melville, Proc. Roy. SOC., 1954, A ,636 See, e.g., M. D. Kamen, " Radio Active Tracers in Biology," 2nd Edition, Academic221, 437.Press, New York, 1951BELCHER, BEVINGTON, STEPHEN, AND WEST. 373and it is necessary to prepare pure labelled samples of the components forwhich analyses are required.This method is likely to be encountered inanalyses of commercial and natural products. Recent applications includeanalyses for substances of biological and biochemical interest, e.p., per+illi ins,^^^, 538s 539 vitamin B,,,5Qo, 531 vitamin D,=l2 : 4dichlorophenoxyacetieacid,M2 y-hexachlor~cycZohexane,~~~ D- and L-glutamic acid,6Q5 ~ - g l u c o s e , ~ ~gentiobiose,5Q6 and t h y r o ~ i n e . ~ ~ Other examples of isotope dilution ana-lysis are the determinations of diethyl ether in mixtures of acrylic acidand ethanol,5q8 triphosphates and pyrophosphates in mixtures,M9 ~ i n c , ~ l % 550lead,551 niobium in mixed oxides of niobium, tantalum, and titanium,552water in s o l i d ~ , ~ u and free sulphur in vulcanised rubber.55qAnother method of working can be applied in research problems requiringthe determination of the various products of a reaction; the products maybe present in very small quantities.The reaction is performed with labelledreactants so that the products are labelled; unlabelled carriers are added.Purity of the isolated samples is extremely important since contaminationby traces of a labelled impurity may seriously affect the results; the onlyconclusive test for efficiency of purification is to perform trials on a mixtureof an unlabelled sample of the substance with labelled samples of all possiblecontaminants. Isotope dilution analysis of this type has recently beenapplied 555 to reactions involving substances of importance in radicalpolymerisations, e.g., initiators, retarders, and inhibitors.Isotope dilution analysis has been used by Grosse, Kirshenbaum, andtheir co-workers for the determination of oxygen in many compo~nds.6~*Molecular oxygen enriched in l80 is added to the material and the conditionsare adjusted so that there is complete exchange between the elementaryoxygen and the oxygen in the specimen; comparison of the l 8 0 contentsof the original oxygen and the equilibriated mixture allows calculation ofthe oxygen content of the specimen.In copper, oxygen contents between0.01 and 0.1% by weight can be determined.557 The method can also beused for other elements.As a result of the development of mass-spectrometric techniques forsolids and the availability of enriched isotopes for many elements, isotope637 J.T. Craig, J. B. Tindall, and M. Senkus, Analyt. Chcm., 1951, 23, 332.538 hI. Gordon, A. J . Virgona, and P. Numerof, ibid., 1954, 26, 1208.538 G. C. Ashton and M. C. Foster, Analyst, 1955, 80, 123.5p0 E. L. Smith, ref. 505, p. 281.5u1 P. Numerof, H. L. Sassaman, A. Rodgers, and A. E. Schaefer, J . Nutrition,6.2 P. Sarensen, Analyt. Chem., 1954, 28, 1581.543 J. T. Craig, 1'. 1;. Tryon, and LV. G. Brown, ibid., 1953, 25, 1661.544 R. Hill, A. G. Jones, and D. E. Palin, Chem. and Ind., 1964, 162.545 C. C. Barker, I. W. Hughes, and G. T. Young, J., 1951, 3047; 1962, 1574.54% J. C. Sowden and A. S. Sprigs, J . Amer. Chem. SOC., 1954, 76, 3539.547 E. P. Reineke, J .Daivy Sci., 1954, 37, 1227.J. G. Burtle and J. P. Ryan, Analyt. Chem., 1955, 27, 1215.548 0. T. Quimby, A. J. Mabis, and €3. W. Lampe, &id., 1954, 26, 661.550 K. Theurer and T. R. Sweet, ibid., 1953, 25, 119.551 €3. von Buttlar, Natuvwiss., 1955, 42, 90.5 5 2 J. Reydon and C. Fisher, AnaZyt. Chim. Acta, 1953, 8, 538.553 R. Viallard and Marchetti, Chinz. analyt., 1954, 36, 214.s54 S. Ikeda and S. Kanbara, J . Chem. SOC. Japan, 1954, 75, 1308.555 J. C. Eevington and H. W. Melville, ref. 508, p. 3.5 5 % See, e.g., A. D. Kirshenbaum and A. G. Streng, Analyt. Chem., 1953, 25, 638.557 A. D. Kirshenbaum and A. V. Grosse, ibid., 1954, 26, 1955.1955, 55, 13374 ANALYTICAL CHEMISTRY.dilution analysis can be applied to many solids. Thorium has been deter-mined 558 in this way.Rocks have been dated 559 by determining the ratioof radioactive s7Rb to stable s7Sr. The use of the technique for traceimpurities in solids has been discussed ; 560 in many cases impurities at 10-10%by weight can be detected.The principle of isotope dilution is applied also in other analyticalprocedures involving isotopes.Labelled Reagents-In a number of cases an element or compound canbe determined by reaction with a labelled reagent; the activity of a pre-cipitate or a derivative can then be used to calculate the quantity of theelement or compound in the sample. The method is capable of greatsensitivity but it requires complete recovery of the pure derivative ; thisdifficulty can be overcome in some cases by a double tracer t e ~ h n i q u e .~ ~ l ~ 562[131I]~-Iodobenzenesulphonyl chloride (" pipsyl chloride ") has beenused as a reagent for amino-acids; 563 it is suitable for any amine whichgives a crystalline pipsyl derivative. This reagent has been used -in analysesfor histamine 564 and pyrimidines,565 and the double labelling technique hasbeen u ~ e d . ~ ~ 1 ~ 562 Acetic anhydride labelled with 3H and 14C has been usedas a reagent for hydroxy- and arnino-compound~.~~~ Compounds of thesetypes have also been determined with 3-chloro-4-methoxybenzoyl chloridelabelled with 36Cl at the 3 - p o ~ i t i o n . ~ ~ ~ Amino-acids on paper chromato-grams have been located with methyl [1311]iodide followed by scanning ofthe paper for activity; 568 the reagent caused some methylation of thecellulose and a consequent increase in background.The positions of fattyacids on paper chromatograms may be fixed by converting the acids intotheir cobalt salts by use of s°C0.510The identification and estimation of the free radicals in reaction mixturescan be performed 569 by adding radioactive iodine to the system. The smallamounts of the corresponding labelled iodides can then be determined byisotope dilution analysis.Potassium has been determined with reagents labelled with 60Co.570-572The same isotope has been used in reagents for the determination of thall-ium 573 and antimony.574 [lloAg]Silver nitrate has been used 575 in the558 G. R. Tilton, L. T. Aldrich, and M. G. Inghram, Analyb.Chem., 1954, 26, 894.559 R. H. Tomlinson and A. K. Das Gupta, Canad. J . Chem., 1953, 31, 909.560 G. P. Barnard, Analyst, 1954, 79, 594.5 6 1 A. S. Keston and J. Lospalluto, Fed. Proc., 1951, 10, 207.662 A. S. Keston, S. Undenfriend, and M. Levy, J. Amer. Chem. Soc., 1947, 69,563 A. S. Keston, S. Undenfriend, and R. K. Cannan, ibid., 1946, 68, 1390; 1949,564 R. W. Schayer, Y. Kobayashi, and R. L. Smiley, J . Biol. Chem., 1955, 212, 593.565 J. R. Fresco and R. C. Warner, ibid., 1955, 215, 751.566 P. Avivi, S. A. Simpson, J. F. Tait, and J. K. Whitehead, ref. 607, p. 313.567 P. Serrensen, Analyt. Chem., 1955, 27, 388.568 F. P. W. Winteringham, A. Harrison, and R. G. Bridges, ref. 505, p. 352.569 G. R. Martin, ref. 506, p. 115.570 E. Sanchez Serrano and I.Lopez Santos, BoZ. radiactividad, 1951, 24, 49.5 7 1 T. Ishimori and Y . Takashima, Bull. Chem. SOC. Japan, 1953, 26, 481.572 I. M. Korenman, F. R. Sheyanova, and 2. I. Glazunova, Zuvodskaya Lab.,579 T. Ishimori, Bull. Chem. SOC. Japan, 1953, 28, 336.574 T. Ishimori and K. Ueno, ibid., 1955, 28, 200.575 C. Barcia Goyanes, E. Sanchez Serrano, and C. Gamis, Bol. radiactividad, 1954,3151; 1950, 72, 748.71, 249.1955, 21, 774.26, 37BELCHER, BEVINGTON, STEPHEN, AND WEST. 3'1 t)formation of Ag,TIPO, and Ag,TlAsO, and the determination of phosphatesand arsenates. Quantitative paper chromatography with traces of metalions has been achieved with the aid of hydrogen ~5S]s~lphide.67s Thesmall amounts of silver in photographic images have been determined 577by converting the silver into silver [131I]iodide ; the method could be adaptedfor the determination of small amounts of silver chloride, bromide, orsulphide. This procedure is similar to one proposed 578 earlier, viz., theconversion of the silver into cobalt ferrocyanide by means of 6oCo.Activation Analysis.-Neutron activation analysis is a powerful methodfor elementary analysis particularly suited for the determination of tracequantities; 579 with certain limitations, it is independent of the chemicalnature of the material. The method depends upon the fact that the atomsof many elements are converted into radioactive isotopes by reactions withslow neutrons ; other bombarding particles---particles, protons, anddeuterons-can be used for activation, but activation by neutrons is generallyfavoured.5rnThe method was described in Annaal Reports of 1949; 581 reviewspublished since 1949 include those by Smales 5rn and Meinke.b882 Usuallythe very high fluxes of thermal neutrons available in nuclear reactors areused, but small neutron sources, e.g., a 25-mg. radium-beryllium source, canbe used successfully in many cases; 583 sources of this kind can be installedin almost any laboratory.Usually it is necessary to add carriers to the irradiated samples and then,following the procedure of isotope dilution analysis, to isolate pure specimensand determine their activities.Recent developments have simplified thechemical manipulations. The activities due to the various isotopes in amixture can be measured by using filters chosen so that they absorb theradiations emitted by certain of the isotopes.The filter technique is notgenerally applicable and results in some loss of sensitivity. y-Spectrometrycan be used for detecting and estimating y-emitters in mixture~,~84-58~provided that the energies of the y-photons are not too close together.Some of the recent applications of the neutron activation technique havebeen concerned with trace impurities in semi-conductors. Analyses forarsenic in germanium copper in germanium,5s8 phosphorus insilic0n,~8~ arsenic in silicon,590 and various impurities in silicon 586 havebeen reported; a typical sensitivity is the determination of 3 x lo4 pg. ofarsenic in a l-g. sample of silicon.576 P.C . van Erkelens, Nature, 1953, 172, 357.677 A. E. Ballard, C . W. Zuehlke, and G. W. W. Stevens, ref. 506, p. 105.578 N. C . Baenziger, J . Chem. Phys., 1948, 16, 1175.579 W. A. Brooksbank, G. W. Leddicotte, and H. A. Mahlman, J . Phys. Chem.,580 A. A. Smales, ref. 506, p. 162.Idem, Ann. Reports, 1949, 46, 285.5a2 W. W. Meinke, Science, 1955, 121, 177.583 W. W. Meinke and R. E. Anderson, AnaZyt. Chenz., 1953, 25, 778.584 R. E. Connally and M. B. Leboeuf, ibid., p. 1095.585 G. H. Morrison and J. F. Cosgrove, ibid., 1955, 27, 810.586 A. A. Smales and L. Salmon, AnaZyst, 1955, 80, 37.5137 A. A. Smales and B. D. Pate, AnaZyt. Chem., 1952, 24, 717.sa8 G. Szekely, ibid., 1954, 26, 1500.589 J. A. J.ames and D. H. Richards, Nature, 1955, 176, 1026.1953, 57, 815.Idem, zbid., 1955, 175, 769376 ANALYTICAL CHEMISTRY.The technique has been applied to the determination of very smaUquantities of impurities in alurnini~m,~~1~ 592 aluminium a l l 0 ~ ~ , 5 9 3 mag-nesium,694 and iron.695 It has been suggested 696 that 6 x by weightof phosphorus in aluminium or aluminium oxide could be detennined quitereadily by this technique.The method is particularly suitable for analysesfor impurities in aluminium since only a negligible activity is induced in thematrix by slow neutrons; with fast neutrons, however, the reaction27Al(n, u)%Na occurs and it can interfere with the determination of sodiumin duminium.Neutron activation analysis has been used to determine sodium andpotassium in mixtures.The method has been applied to single nerve698 in which the sodium content may be only 1 pg. and the potassiumcontent not much greater; it was concluded that the method is about20 times as sensitive as methods with the flame photometer. The techniquehas been applied to the dating of potassium minerals.599 The rubidium andczsium contents of sea water and related materials have been measured; 586for sea water there was a preliminary concentration by means of a cation-exchange resin. The arsenic content of sea water can be measured directlyby neutron activatioamfor mixtures of rare earths byusing a small neutron source; in many cases the method is much superiorto spectrophotometric methods. Other examples of recent applications ofthe technique are the determinations of antimony,602 indi~m,~O~ cerium,604tantalum,528* 552, 60s and thorium.606The analyses considered so far have depended upon the occurrence of(12, 7 ) reactions.With slow neutrons 235U undergoes fission to give 1NBaamong many products, and the yield of 140Ba is a measure of the 235U contentof the original material. Several papers on the determination of uraniumby neutron activation have been p ~ b l i s h e d . ~ 7 - ~ ~ ~ ‘jLi readily undergoesa (aYt, a) reaction with slow neutrons; the tritium produced can be used todetermine 611 the original 6Li. This reaction is also used 632 in a deter-mination of the oxygen content of powdered beryllium; the beryllium isActivation analysis has been used591 R.C. Plumb and R. H. Silverman, Nucteonics, 1954, 12 [12], 29.592 P. Albert, M. Caron, and G. Chaudron, ref. 506, p. 171.593 B. M. Thall and B. Chalmers, J . Inst. Metals, 1950, 77, 79.594 G. J. Atchison and W. H. Beamer, Analyt. Chem., 1952, 24, 1812.595 P. Albert, M. Caron, and G. Chaudron, Compt. rend., 1953, 236, 1030.596 L. M. Foster and C. D. Gaitanis, Analyt. Chern., 1955, 27, 1342.597 P. R. Lewis, ref. 505, p. 381.588 R. D. Keynes and P. R. Lewis, J . Physiol., 1951, 114, 151.509 A. Moljk, R. W. P. Drever, and S. C. Curran, Nucleonics, 1955, 13 [2], 44.600 A. A. Smales and B. D. Pate, Analyst, 1952, 77, 188.601 W. W. Meinke and R. E. Anderson, Analyt. Chent., 1954, 26, 907.602 J. E. Hudgens and P. J. Cali, ibid., 1952, 24, 171.603 J.E. Hudgens and L. C. Nelson, ibid., p . 1472.604 L. E. Glendenin, K. P. Flynn, R. F. Buchanan, and E. P. Steinberg, ibid., 1955,605 A. Kohn, Chimie et Industvie, 1954, 71, 69.E. N. Jenkins, Analyst, 1955, 80, 301.607 A. A. Smales, ibid., 1952, 77, 778.608 A. P. Seyfang and A. A. Smales, ibid., 1953, 78, 394.609 A. P. Seyfang, ibid., 1955, 80, 74.H. A. Mahlman and G. W. Leddicotte, Analvt. Chem., 1955, 27, 823.611 L. Kaplan and K. E. Wilzbach, ibid., 1954, 28. 1797.612 R. G. Osmond and A. A. Smales, Analyt. Clzirn. Ada, 1954, 10, 117.27, 59BELCHER, BEVINGTO”, STEPHEN, AND WEST. 377mixed with 7 times its weight of lithium fluoride and irradiated. Thereaction 6Li(n, a)3H is followed by 160(t, n)l8F. The fluorine isotope isradioactive with a half-life of 112 min.; it is finally precipitated as PbClFfor assay. The oxygen content of the lithium fluoride may be significant inthis analysis.In some cases considerable care is needed in planning the analyses.The determination of arsenic in germanium 687 depends upon the reaction75As(12, but 76As can also be produced from the matrix by thereactions 74Ge(n, ~ ) 7 ~ G e and 75Ge -% 75As. 76As can also be formed frombromine and selenium by the reactions 79Br(n, a)76As and ?%e(n, p)7sAs,so these elements may interfere with the determination of arsenic. I n thedetermination of phosphorus in silicon,589 it must be noted that silicon canbe converted into an isotope of phosphorus thusmSi(n, y)31Si 3lSi B-L 3lpand the phosphorus so produced can contribute to the apparent phosphoruscontent of the silicon.Analyses for sulphur and phosphorus in magnesiumare complicated 594 if the specimen contains chlorine, because of the reactions35Cl(n, p)35S and 35Cl(n, a)32P. In analyses for trace impurities, the possi-bility of the matrix’s being converted into the impurity being studied mustalways be considered.Neutron activation has been used 613 to follow the sniall changes inbromine con tent caused by chemical manipulation of brominated poly-styrene. The technique has also been used in conjunction with paperchromatography. The bromine analogue of D.D.T. was located 568 on achromatogram by exposing the paper to a neutron flux and scanning for*2Br activity; similarly the a-, (3-, y-, and 8-isomers of hexachlorocycb-hexane were located 568 by means of the reaction 35Cl(n, p)35S. In applic-ations of these types difficulties may arise from losses of hydrogen[s2Br]bromide for example, from the unknown and standard, and theseshould be similar both chemically and physically.Ordinarily in activation analysis it is necessary that radioactive isotopesof fairly long half-life should be produced, although a half-life of only 22 min.for 233Th is sufficient to permit the determination 606 of thorium by thismethod.A development 614 in activation analysis is the irradiation togetherof the sample and a nuclear emulsion. The activities of short-lived isotopesmay be detected by the emulsion. In addition, elements which undergonuclear reactions but only to produce stable isotopes may also be detennined,for example 10B undergoes a (12, a) reaction readily and the a-particles canbe detected by the emulsion; this has also been described by Frenchauthors.615Photoneutron Methods.-The reaction 9Be(y, ~2)2~He occurs with y-raysmore energetic than 1.63 mev, and has been utilised 616 in a sensitive methodfor determining beryllium.The emitted neutrons are moderated and thendetected with lOB-enriched boron trifluoride counters. A lNSb source isa s M. H. Jones, H. W. MelvilIe, and W. G. P. Robertson, Nature, 1954, 174, 78;Ricerca sci., in the press.614 G. Mayr, Nucleonics, 1954, 12 [ S ] , 58.616 A. M. Gaudin and J . H. Pannell, Analyt. Chem., 1951, 23, 1261.. 615 H. Faraggi, A. Kohn, and J . Doumerc, Compt. rend., 1952, 255, 714378 ANALYTICAL CHEMISTRY.recommended ; the precautions needed in using a 1-curie y-source are con-siderable, but 1 p.p.m. of beryllium can be detected. The method is specificsince no other element has a photoneutron threshold below 2.04 mev whichcorresponds to the most energetic y-photons from %b; the presence oflithium, boron, or cadmium in the specimen is undesirable since theseelements have large cross-sections for the capture of thermal neutrons.A new method for deuterium analysis uses 617 the reaction 2D(yJ ~z)lH.The threshold is 2.23 mev and 24Na has been used as the y-source. Berylliumis the only element which can interfere, but samples should have similarcompositions so that moderation of the neutrons and absorption of they-rays are similar ; otherwise the purity of the sample is not critical.The reaction l60(y, n)150 forms the basis of a method 618 for determiningoxygen in organic compounds and metals. It is necessary to use y-rays ofenergies greater than 15-5 mev; the short-lived activity of 1 5 0 is measured.Another nuclear reaction involving the release of neutrons, viz. ,14N(d, T Z ) ~ ~ O , has been used G19 for analytical purposes. The mass ofnitrogen in a specimen is calculated from the observed 150 activity and thedeuteron flux; in metals, nitrogen contents as low as 1 p.p.m. have beenmeasured.Other Uses of Isotopes in Analysis.-The natural radioactivity of potas-sium, due to 40K, has been used 620a 621 in methods for determining thiselement; an accuracy of 1% or better is possible.510 The radiations from*7Rb, a naturally occurring isotope, are less penetrating than those fromUK, and the difference has been utilised622 in a method for determiningpotassium and rubidium in mixtures.The uses of labelled substances for analyses of high polymers have beens~mmarised.5~5 Accurate determinations of the amounts of initiators,retarders, and transfer agents incorporated in polymers during their pre-paration are possible ; the technique is valuable for analyses of co-polymersin those cases where the compositions of the monomer units are very similaror when one component is present only in small proportions. It is alsopossible to study similarly reactions between high polymers and materialsof low molecular weight, e.g., the quantity of P-benzoquinone which becomeschemically incorporated with poly(methy1 methacrylate) when mixtures ofthe quinone and the polymer are irradiated, has been found.623The X-ray absorption method for determining traces of heavy elementsin organic materials has been reviewed.624 In some cases there are con-siderable advantages in using radioactive isotopes as the sources of y- orX-rays for this purp0se.~~5 The isotope 55Fe which emits X-rays becauseof K-capture, is regarded G26 as the most suitable for the determination ofsulphur in hydrocarbons.617 C. P. Haigh, Nature, 1953, 172, 359; ref. 508, p. 101.61s R. Basile, J. HurC, P. LbvBque, and C. Schul, Compt. rend., 1954, 239, 422.619 P. Sue, zbid., 1955, 240, 88.620 K. C. Scheel, Angew. Chem., 1954, 66, 102.621 H. Dresia, 2. anaZyt. Chem., 1955, 144, 81.622 0. Gubeli and K. Stammbach, HeZv. Chim. Ada, 1951, 34, 1245, 1253.623 J. C. Bevington and A. Charlesby, Ricerca scz'., in the press.624 D. H. Whiffen, Ann. Reports, 1954, 51, 365.625 M. B. Leboeuf, D. G. Miller, and R. E. Connally, Nucleonics, 1954, 12 [8], 18.626 H. K. Hughes and J. W. Wilczewski, Analyt. Chem., 1954, 26, 1889BELCHER, BEVINGTON, STEPHEN', AND WEST. 379A neutron-scattering method for determining soil moisture has beendescribed.627 It depends upon the fact that hydrogen atoms are particu-larly effective in slowing down neutrons. A source of fast neutrons and adetector for slow neutrons are required. The method actually determinesthe hydrogen content of the soil, but practically all the hydrogen in mineralsoils is in the form of water.The amount of 8-radiation scattered from a sheet of material dependsupon the atomic number of the scatterer. This fact forms the basis for amethod for analysis of chromium-niobium alloys ; G28 the amount of radiationscattered is compared with that scattered from standards. The methodcan be extended to other alloys provided that the atomic numbers of thecomponents differ appreciably.Other applications of radioactive isotopes which are of some significancein analysis are the use of isotopes for calibrating m i ~ r ~ - ~ a l o r i m e t e r ~ , ~ 630the use of a radioactive falling-ball viscometer for opaque viscous liquids 631and the use of p-sources for dispersing static electricity on films andpowders.632J. C. B.R. BELCHER.J. C. BEVINGTON.W. I. STEPHEN.T. S. WEST.627 A. H. Knight and T. W. Wright, ref. 508, p. 111.63e P. Boivinet and E. Calvet, Comfit. rend., 1954, 238, 1995.6so W. B. Mann, J. Res. Nat. Bur. Stand., 1954, 52, 177.N. A. Bogdanov and V. F. Funke, Zavodskuyu Lub., 1955, 21, 181.J. GuCron, ref. 506, p. 6.See, e.g., P. S . H. Henry, ref. 506, p. 150

ISSN:0365-6217    

DOI:10.1039/AR9555200339

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

CRYSTALLOGRAPHY.PROTEINS, NUCLEIC ACIDS, AND VIRUSES.Introduction.-The study of these complex structures has greatlyadvanced since it was last fully reported,l owing to the convergence of anumber of lines of attack both chemical and physical. The analyticalchemical methods of Sanger and others have succeeded in revealing thesequence of amino-acid residues in a number of complex peptides and ininsulin as well as indicating the position of -S-S- bridges. Thus it may besaid that the structure of all pure proteins is, in the purely chemical sense,in principle, determinable. This information, though essential, is not,however, sufficient to explain the physical, colloidal, and biochemicalproperties of such complicated bodies. It is necessary also to form someidea of how the long and relatively flexible polypeptide chains are coiledand folded in both fibres and discrete molecules.It is now apparent that large aliphatic heteropolymeric molecules canbe considered as arranged in a succession of levels of ordering of which thechemical structural formula giving the topology of the covalent bonds isonly the first or primary structure. The secondary structure refers to themutual stereochemical relations of sequences of residues along each chain.These are determined in the first place by conditions of steric hindrance andfurther among configurations sterically possible by the presence of hydrogenbonds.These can stabilise various types of coiled or folded chain struc-tures according to the arrangements of bonds between residues of the samechain (intracatenary hydrogen bonds) or of neighbouring chains (inter-catenary hydrogen bonds).The knowledge of primary and secondary structure serves in general todescribe adequately those of synthetic polypeptides, but for naturallyoccurring fibres and for globular or crystalline proteins it is insufficient.Itis necessary in addition to know the tertiary structure, namely the lengths ofthe coils and the way in which they are grouped or folded together, forexample as a coiled coil as has been proposed for keratin (p. 386) or inreversed parallel coils in one model of insulin (p. 384).Even higher orders of structure can now be discussed, namely in thearrangements of small protein molecules to form larger, relatively stable,aggregates.The unit molecule of insulin of molecular weight 6000 is, itseems, rarely found in solution. In crystals it appears in groups of six, infibres in groups of t ~ e n t y , ~ and in solution in groups of two to eight.The protein coating of virus particles seems to be composed of such high-order aggregates .So far the chief advances have been made in determining the secondarystructure of proteins and nucleic acids, though information on the tertiarystructure is beginning to accumulate. The crystallographic attack has been1 Ann. Reports, 1951, 48, 238-248, 362-382.a Cf. Ann. Reports, 1953, 50, 268-280.8 D. F. Waugh, D. F. Wilhelmson, S. L. Commerford, and M. L. Sackler, J. Amer.Chem. SOC., 1953, 75, 2592BERNAL AND CARLISLE.381pressed from both within and without, that is, by starting with molecularmodels and verifying their correctness with X-rays or starting from X-rayanalysis and interpreting the results by means of molecular models. Nocomplete analysis of the type carried out by Mrs. Hodgkin on vitamin B,,(p. 403) has yet been carried out for a protein but it is not unlikely thatthis may be done soon.the idea of a hydrogen-bonded spiral first put forward by Huggins * and refined by Pauling et aZ.6has proved most fruitful. Especially valuable was Pauling’s conceptionof a non-integral spiral allowing the greatest freedom for packing andhydrogen bonding. To verify this by X-rays involved the development byCochran, Crick, and Vand of the theory of the scattering by spiral structuresexpressible in terms of Bessel functions and leading to very rapid inductionsof plausible structures from simple inspection of fibre photographs. Com-bined with the optical method perfected by Taylor, Hinde, and Lipson 7of producing Fourier transforms similar to X-ray photographs from molecularmodels, this method has led to the elucidation of many extremely complexstructures such as collagen (p.388), nucleic acids (p. 395), and tobacco-mosaic virus (p. 400).The value of these methods has been greatest in the case of fibroussubstances, especially synthetic fibres which lack the complication of vanedside groups. The interplay between the study of corresponding syntheticand natural proteins has been most fruitful.Thus poly(methy1 glutamate)provided the key to the a-keratin structures (p. 385), poly-L-alanine tothat of silk (p. 387), and polyproline to that of collagen (p. 388). The useof polarised infrared absorption has enabled conclusions to be drawn as tothe orientation of hydrogen bonds in synthetic polymers which would bedifficult to determine for natural fibres owing to the influence of side groups.The structures of three main types of protein fibres distinguished by Ast-bury have been determined in main outiine. The a-type (keratin, myosin,epidermim, fibrin) seems to conform, with variations, to the Pauling a-helix(p. 385) in which all hydrogen bonds are within the chain. The p-type(silk) consist of extended chains linked by hydrogen bonds in pleated sheets(p.387). The most intractable form, that of collagen, now seems to berevealed (p. 389) as a twinning of three partially extending chains mutuallyheld together by hydrogen bonds and thus intermediate between CL and p.The most spectacular advance of fibre analysis, already briefly reported,ghas been in the structure of the polynucleotides. Here a number of workersin Cambridge and London, notably Crick, Watson, Wilkins, and Franklin(p. 397), have co-operated to determine a structure for deoxyribose nucleicacid. This structure involves a double spiral of linked phosphate and sugargroups stabilised by the piling of sheets of hydrogen-bonded purine andpyrimidine pairs lying at right-angles to the axis. This structure is likelyto prove of considerable biochemical and even of genetic importance.In the structure of crystalline proteins the degree of complexity has4 M.L. Huggins, Chem. Rev., 1943, 32, 195.6 L. Pauling, R. B. Corey, and H. R. Branson, Proc. Nut. Acad. Sci., 1951, 37, 206. * W. Cochran, F. H. C . Crick, and V. Vand, Acta Cryst., 1962, 5, 581.7 C. A. Taylor, R. N. Hinde, and H. Lipson, zbid., 1951, 4, 458.8 W. T. Astbury, J . Inst. Soc. Leather Trades’ Chemists, 1940, 24, 69. * Ann. Reports, 1954, 51, 270-279.In the prediction of the structure of protein382 CRYSTALLOGRAPHY.made both approaches from models or from diffraction data extremelydificult. Indeed, despite much observation the most that could be deduceddirectly from unaltered proteins was something of the size, shape, andmutual relations of protein molecules in crystals.A decisive advance onthe crucial problem of the determination of the phases of X-ray diffractionwas made when Perutz et aZ.1° (see p. 392) used heavy atoms attached tothe protein molecule for this purpose. Since then work has gone rapidlyforward on a number of protein crystals with promising results, though thesheer labour of observation and calculation makes it unlikely that completestructures will be determinable for some years.The papers of four discussions l1 on the structure of proteins are avail-able : the first, initiated by Astbury, centres on the theme of the newly borna-helklla The second lib is that of the Institut International de ChimieSolvay, held at Brussels in April, 1953.This is an excellent review of theposition concerning chemical and structural information of the globularproteins up to 1953. The third is the “ Nature and Structure of Collagen,’’held at King’s College, London, 1953, and the fourth is that of the Symposiaof the Society of Experimental Biology,lld No. IX on “ Fibrous Proteinsand their Biological Significance.” The emphasis throughout the latter ison the significance of chemical, X-ray diffraction, and electron-microscopicalstudies on the interpretation of structure. Current knowledge in thesestudies is reviewed as it concerns collagen, keratin, and muscle, and theirbiological , biophysical, and biogenetic implications.An excellent survey has been given l2 by Kendrew of the position in thestudy of the crystalline proteins up to 1954, with particular reference tostructural hypothesis; Springall’s book l3 is an attempt to portray ourpresent knowledge on proteins to honours students reading chemistry.Thelatter is an excellent survey of the subject covering the chemical and physico-chemical aspects of protein structure. Another outstanding contributionin this field is “ The Proteins ” l4 (two volumes, four parts) ; it containsvaluable surveys of many aspects of proteins and nucleoproteins by peopleactively engaged in research in their fields. Another contribution l5 con-stituting a valuable survey is “ The Nucleic Acids,” in which the attempt ismade to collect all the information at present available on this subject intoa single comprehensive work.General and Theoretical.-In addition to the proposed configurations forpolypeptide chains, the u- and y-helices,s Huggins l6 claimed the existenceof a 306,~ helix, and Low and Baybutt l7 suggested a 4*4,, helix, with an10 D.W. Green, V. F. Ingram, and M. F. Perutz, Proc. Roy. Soc., 1954, A , 225, 287.11 (a) Proc. Roy. Soc., 1953, B , 141, 1 : (b) Proceedings of April Meetings, 1953, ofthe Institut Internatiqyal de Chimie Solvay, ed. R. Stoops, Brussels; (c) ‘‘ NFFure andStructure of Collagen, ed. J. T. Randall, Butterworths, London, 1953 : ( d ) FibrousProteins and their Biological Significance,” Symposia of the Society of ExperimentalBiology No. 9, Cambridge Univ. Press, 1955.12 J. C. Kendrew, Frogy. Bio9hysics Biophys.Chem., 1954, 4.13 H. D. Springall, The Structural Chemistry of Proteins,” Butterworths, London,1954.14 “The Proteins,” ed. H. Neurath and K. Bailey, Accademic Press, NewYork, 1955.15 “ The Nucleic Acids,” ed. E. Chargaff and J. N. Davidson, in “ Chemistry andBiology,” Vols. I and 11, Academic Press, New York, 1955.16 M. 1;. Huggins, J. Amer. Chem. SOL, 1962, 74, 3963.17 B. W. Low and R. B. Raybutt, ibid., p. 5806BERNAL AND CARLISLE. 383axial translation of 1-15 A per residue parallel to the axis.has made an assessment of six hydrogen-bonded helix configurations, namelythe a- and y-helices and the 4.416, 4-3,,, 3.010, and 2.2, helices. The last isthe 2,b originally put forward by Huggins* but the flattened ribbon has atwist which gives the chain a super-helix effect.Quantitative estimates ofbond energies show that proposed structures are decreasingly stable in theorder 3.6,,, 4.416, 2*2,, 3.0,,, 5.1,,, and 403,~. A combination of a favourablehydrogen-bond system and unknown external influences may allow poly-peptide chains to fold in one or another of the configurations which at firstglance seem to be rather less reasonable than the 3-6,, (a)-helix.In a subsequent paper Donohue 1M calculated the radial distributionfunctions for the 3.6,,, 413, 3.010, and 4 ~ 4 , ~ helices for the @-carbon atoms inboth position 1 and 2, and also that for the 2.2, helix with the @-carbon atomin position 1. The 41, helix was originally suggested by Bragg, Kendrew,and Perutz19 which closely resembles that of the 3*6,, helix.At smallradial distributions (0-2.0 A) there is little to distinguish one curve fromany of the others, but for spacings greater than 2.7 A it is possible to distin-guish the 2.2, and 3.OlO helices from the others which are quite similar toone another-the latter all show a marked peak in the vicinity of 5 A, withlittle to choose between those with the @-carbon atoms in positions 1 or 2.The stereochemical uncertainties in such calculations can only lead to verygeneral considerations concerning protein structure.Arndt and Riley20 have examined the X-ray scattering of thirty amor-phous proteins and two synthetic polypeptides, and suggest that there is asingle polypeptide chain common to all as a predominant constituent.Furthermore, they claim that it is possible to distinguish from such scatteringdata, for instance, in which position the @-carbon atom is to be found inserum albumin.Small-angle X-ray investigations 21 have been carried outon bovine serum albumin, human mercaptalbumin, and mercaptalbumin-mercury dimer, which are shown to have radii of gyration of 29.8, 31-0, and37-2 A respectively. I t is suggested that the molecules have internaland external hydrations of 0.37 and 0.11 g. of water per g. of proteinrespectively.Complete theoretical treatments of the X-ray diffraction to be expectedare available for the single strand a-helix and for " coiled coil " arrange-ments of a-helices in two and three strand ropes.22 The form factors havebeen calculated for the 18-residue 5-turn y-helix, without the inclusion oftemperature, Lorentz, or polarisation fact01-s.~~ A description of the theoryof X-ray fibre diagrams suitable for biologists is given by Stokes.24 Harker 25discusses the inapplicability of Wilson's statistical procedures 26 to thediffraction data of protein crystals, and Luzzati 27 has further indicated theDonohueJ.Donohue, PYOC. Nut. Acad. Sci., (a) 1953, 39, 470; ( 6 ) 1954, 40, 377.W. L. Bragg, J. C . Kendrew, and M. F. Perutz, Proc. Roy. SOL, 1951, A , 203, 321.2o U. W. Arndt and D. P. Riley, Phil. Trans., 1955, 24'4, A , 409.z1 J. W. Anderegg, W. W. Beemen, C . Shulman, and P. Kaesberg, J . Amer. Chew.22 F. H. C . Crick, Acta Cryst., 1953, 6, 685.23 L.Pauling, R. B. Corey, H. L. Yakel, jun., and R. E. Marsh, ibid., 1955, 8, 853.24 A. R. Stokes, Progr. Biophysics Biophys. Chem., 1955, 5.25 D. Harker, Actu Cryst., 1953, 6, 731.26 A. J. C. Wilson, Nature, 1942, 150, 152.27 V. Luzzati, Acta Cryst., 1955, 8, 795.SOL, 1955, 77, 2927384 CRYSTALLOGRAPHY.limitations inherent in Wilson’s statistical method and has derived newtheoretical laws more applicable to protein crystals.Low and Grenville-Wells 28 have constructed nornographs relating theatomic co-ordinates of atoms on a helix to the vertical translation of the coilper residue. Lindley 29 has shown that there are simple ways of modifyingthe rigidity of the or-helix by incorporating a sense of change in the chain.This can result in side-chains participating in main chain bonding, henceleading to the masking of groups.Lindley and RoHett 30 have, on the basisof the known amino-acid sequence of its four chains, put forward a proposedstructure for insulin based on a-helices. They conclude that it is possible tobuild a satisfactory model of a globular protein on the a-helix, and the factthat such a possibility can exist is all the more important in view of thedoubts expressed about the presence of the a-helix in globular proteins,Techniques-Single-crystal X-ray work on proteins requires the carefulindexing and the measuring of intensities of thousands of reflections. Thisis a tedious operation and Furnas and Harker31 have made the first stepstowards designing a Geiger-counter diff ractometer that permits of theaccurate location of reflections and the measurements of their integratedintensities.The heart of the apparatus is a “ Eulerian cradle ” permittingrotation of the crystal about each of the Eulerian axes. This eliminates theneed to raise the counter out of the equatorial plane and thus enables thereciprocal lattice to be surveyed by a “ zone ” or “ cone ” scheme.One difficulty in determining the molecular weights of proteins by theX-ray method is that of obtaining accurate and reliable density measure-ments of the crystals. Law and Richards32 have described a gradientcolumn technique for the measurement of densities and a microbalancewhich combines the procedures of weighing the crystal and simultaneouslyenabling the operator, by taking suitable photomicrographs, to determinethe dimensions of the crystal and hence its volume by optical means.Increasing use is being made of the Lipson-Taylor diffractometer origin-ally suggested by Bragg in the study of the diffraction intensities of helicalstructures. A recent modification of this instrument has been successfullyused34 in the study of synthetic polypeptides, and Hooper, Seeds, andStokes 35 describe a photographic process for the preparation of masks forthe Lipson-Taylor diffractometer in their studies of the larger molecules likedeaxyribonucleic acid and collagen.has shown two methods ofproducing fibre diagrams of a given structure by means of t h e opticaldiffractometer by superposing a number of diffraction patterns of theprojections of the structure.An expression is obtained for the minimumnumber of projections required for a faithful representation of the fibrediagram.New types of space-filling atomic model for use in building organic28 B. W. Low and H. J. GrenviHe-Wells, Proc. Nal. Acad. Sci. , 1953, 39, 785.29 H. Lindley, Biochim. Biophys. Ada, 1955, 38, 194.SO H. Lindley and J. S. Rdlett, abid., p. 183.32 B. D. Low and F. M. Richards, J . Amer. Chem. SOL, 1952, 74, 1660; Nature,33 W. L. Bragg and A. R. Stokes, Nature, 1945, 156, 332; see also ref. 7.34 A. Elliott and P. Robertson, Actu Cryst., 1955, 8, 736.35 C. W. Hooper, W. E. Seeds, and A. R. Stokes, Nature, 1955, 175, 679.313 A. R. Stokes, Actu Cryst., 1955, 8, 27.T. C.Furnas and D. Harker, Rev. Sci. Instv., 1955, 26, 449.1952, 170, 412BERNAL AND CARLISLE. 385structure models and polypeptide chains are de~cribed.~' These are nowessential aids in organic and protein-structure X-ray analysis.Artificial and Natural Fibrous Proteins.-In this section is given a briefaccount of the advances in knowledge of the structure of the three maintypes of fibrous protein : (1) the a, or helical keratin, type; (2) the p, orextended silk, type; and (3) the twined, or collagen, type. In each casethe evidence provided by the relatively simple synthetic polymers is firstpresented followed by that for natural products.There is good evidence from the use of X-rays andpolarised infrared rays that synthetic polypeptide chains with neutral residuestake up the a-helix configuration.New measurements are available 38for better oriented films of poly-(y-methyl L-glutamate) with cell dimensionsa = 11-95 A, b = 20-70 A, c = 43.2 A (fibre axis), which are closely related tothe hexagonal cell previously described.39 This work shows that the generalpattern of non-meridional reflections is in at least qualitative agreement withthat calculated by Cochran and In line with these conclusions isthat of the work carried out on poly-(c-benzyloxycarbonyl-L-lysine) and acomplex of a form of poly-(y-methyl ~-glutamate).*l The former crystalliseswith one molecule in a simple hexagonal cell and gives an X-ray diffractionpattern that is almost identical with the latter. There appears to be someuncertainty about the correct choice of unit cell for poly-(7-methyl L-glutamate) , but its cylindrical Patterson function 42 shows qualitativeagreement with a theoretical cylindrical Patterson projection for the 3:6-residue a-helix.The interpretation of the polarised infrared absorption bands for syntheticpolypeptides can still only be applied in a qualitative manner owing to lackof information concerning the precise nature of the atomic motions associatedwith certain absorption bands.43 Particularly is this so for the molecularmotion concerned with the CEO band which is known to be complex.Nevertheless, the method has been useful in distinguishing between the a- andthe @-form of polypeptides, particularly where orientation is difficult, bynoting the differences in the characteristic frequencies of the N-H deform-ation mode.44 Elliott 45 has used the characteristic frequencies of the C=Oband to distinguish between optically active a-polypeptides and the meso-forms.A recent study of poly-L-alanine46 shows that the fibres exist inthe a- and the @-form. The a form is similar to poly-(y-methyl L-glutamate),but there appear to be 47 residues in 13 turns of the helix. A detailedreport 47 of the investigations on this synthetic polypeptide has shown that37 G. S. HartIey and C. Robinson, Trans. Faraday SOC., 1952, 48, 847; C. Robinsonand E. J. Ambrose, ibid., p. 854; R. B. Corey and L. Pauling, Rev. Sci. Instr., 1953,84, 621.38 C. H. Bamford, L. Brown, A. Elliott, W. E. Hanby, and I.F. Trotter, Proc.Roy. Sot., 1953, A , 141, 49.39 C. H. Bamford, W. E. Hanby, and F. Happey, PYOC. Roy. Soc., 1951, A, 205, 30.40 W. Cochran and F. H. C. Crick, Nature, 1952, 169, 234.41 H. L. Yakel, jun., Acta Cryst., 1953, 6, 724.42 H. L. Yakel, jun., and P. N. Schatz, ibid., 1955, 8, 22.4s R. D. B. Fraser and W. C. Price, Nutwe, 1952, 170, 490.44 E. J. Ambrose and A. Elliott, Proc. Roy. SOL, 1951, A , 205, 47.45 A. Elliott, ibid., 1953, A , 221, 104.46 C. €1. Bamford, L. Brown, A. Elliott, W. E. Hanby, and I. F. Trotter, Nutwe,4? L. Brown and I. F. Trotter, Trans. Furuday Soc., 1956, in the press.HeZicaZ type (E).1954, 173, 27.REP.-VOL. LII 386 CRYSTALLOGRAPHY.some distortion in methyl side-groups is necessary in the helical structure toaccount for the presence of meridional reflections not supposed to exist onthe basis of the a-helix with equivalent residues.No significant major discoveries concerning the keratin-myosin-epi-dermin-fibrin group have been made since the last Rep0rt.l It was alwaysdifficult to explain the 5.1 A meridional reflection for a-keratin in termsof a single-chain a-helix although the presence of a 1.49 %i reflection recordedby MacArthur 48 supports Pauling and Corey's suggestion that a-keratincan be interpreted in terms of their helix.Both Pauling and Corey49 andCrick M, suggested that the polypeptide chains of a-keratin might assumecompound helical configurations. By this Pauling and Corey mean thatthe straight a-helix is now to be replaced by an a-helix that is itself a super-helix repeating after about 35 turns of the a-helix (126 residues in 190A),and in assuming this configuration it is possible for six such super-helices tosurround a straight-chain helix in such a manner as to give rise to a 7-strandcable of the " coiled coil " type, having a diameter of 30 A.The sense ofthe outer strands of the 7-strand cable must be opposite to that of thecentral strand in order that the compound a-helices may pack around thecentral cable. The 5.1 A meridional arc is explained by this proposedstructure. Crick 51 has shown that when a-helices of the same sense packtogether they will probably do so about 20" out of parallel. Two simplemodels, the 2- and 3-strand rope, are described and used to illustrate thediffraction theory already developed for such structures.6, 22Astbury and Haggitt 52 have shown that before the a-p transformationa-keratin shows a stretching of the 5.1 A and 1.5 spacings which takes placereversibly over a range of 2%. This experiment demonstrates that the twospacings must be intimately related although the authors point out thatthere is no suggestion that these reflections are not orders of the samediffraction series.The low infrared dichroism of the natural fibrous proteins is accountedfor 53 by the presence of a relatively large component not possessing di-chroism. Fraser 54 has studied side-chain orientation in fibrous proteinsand Malcolm 55 has shown that only 15% of muscle can be oriented parallelto the muscle axis, the remainder being folded in secondary folds oramorphous, giving zero dichroism.The proteins from flagella of Proteus vulgaris and BaciZZus subtilis showthe normal a-type diagram together with that of a cross-B-type.11ds56 Inaccordance with other proteins of the keratin group, the meridional 5.1 Aand 1-(5 The fibres are about 120 A thick, witha microperiod of 410 %i which corresponds very closely to the 411 A fibreperiod observed for skeletal muscle by Philpott and>zent-Gyorgyi 584 8 I .MacArthur, Nature, 1943, 152, 38.4s L. Pauling and R. B. Corey, ibid., 1953, 171, 59.F. H. C. Crick, ibid., 1952, 170, 882.f 1 Idem, Acta Cryst., 1952, 5, 381.f2 W. T. Astbury and J . W. Haggitt, Biochim. Biophys. Acta, 1953, 10, 483.53 K.D. Parker, ibid., 1955, 17, 148.j4 R. D. B. Fraser, Nature, 1955, 176, 358.f b B. R. Malcolm, in ref. l l ( d ) .5 6 W. T. Astbury and N. N. Saha, Nature, 1953, 171, 280.5 7 R. S. Bear, J. Amer. Chew. SOC., 1943, 65, 1784.reflections are observed.D. E. Philpott and A. G. Szent-Gyofgyi, Biochini. Biophvs. Acfa, 1954, 15, 165BERNAL AND CARLISLE. 387have recently shown that one of the components of myosin, light mero-myosin, obtained by tryptic digestion shows cross-striations of about420 A. Such close correlation between these periods cannot pass unnoticed.Suggestions are made by Astbury and his co-workers 56 for the geometry ofthe arrangement of subfibrils in flagella and the explanation of the helicalmovements of the flagella in motion.Elliott and Malcolm 59 have been investigating water-soluble silks whichare obtained by dissolving the fibroin in aqueous inorganic salts, followed bydia1ysis.M Infrared and X-ray evidence, in the case of water-soluble Bombyxsilk, points to the existence of a folded configuration for the polypeptidechains.More definite conclusions on chain configuration appear to befound in the water-soluble Anaphe nzoloneyi silk which to a large extent isa copolymer of glycine and alanine. By comparison with poly-L-alanine 46whose configuration is shown to be that of the a-helix and with the copolymerL-alanine-glycine (2 : 1) it is suggested 59 that Anaphe moloneyi silk castfrom trifluoroacetic acid takes up the cc-helix configuration. Freeze-driedAnaphe silk, however, seems to resemble water-soluble Bombyx silk, whereinfrared and X-ray data are not conclusive enough to point in favour of theu-helix.Kratky, Sekora, and Pilz 62 give evidence for the existence of a-helices insolutions of natural silk gel from small angle X-ray scattering.Pleated sheet structures (p).In this category there are two main types,the extended synthetic polypeptides and the natural silks. The X-raypattern of P-poly-L-alanine 469 47 can be indexed on an orthorhombic unit cellcontaining two chains which are hydrogen bonded into sheets in a mannersimilar to that observed 63 in nylon 66. There are interesting comparisonsbetween the fibre diagrams of this polypeptide and silk structures. Marsh,Corey, and Pauling 64 point out that the unit cell dimensions indicated byBamford et al.for p-poly-L-alanine 46 are in good agreement with the pseudo-unit cell of tussore silk based on antiparallel-chain pleated sheets.The early X-ray work on fibroin has been s ~ m m a r i s e d . ~ ~ ~ 66 Warwickerhas based his suggested structure for Bombyx mori silk on an orthorhombicunit cell containing four residues. This is a pleated sheet structure resem-bling that first put forward by Pauling and Corey 67 to account in generalfor the P-type proteins. Marsh, Pauling, and Corey 68 have since putforward alternatives which are still not fully established. They have,however, indicated discrepancies 68 that arise as a result of Warwicker’schoice of atomic co-ordinates and they propose instead a structure that hasa pseudo-monoclinic unit cell, with space group P2,.The four chains packin the cell so that the extended polypeptide chains are held together bylateral N-H . . . 0 hydrogen bonds to form antiparallel-chain pleated sheets,5g A. Elliott and B. R. Malcolm, Trans. Faraday Soc., 1956, in the press.6o P. P. von Weimarn, “ Colloid Chemistry,” Chemical Catalog Co., New York,1932, p. 363; D. Coleman and F. 0. Howitt, Proc. Roy. Soc., 1947, A , 190, 145; E. J.Ambrose, C. H. Bamford, A. Elliott, and W. E. Hanby, Nature, 1951, 168, 264.62 0. Kratky, A. Sekora, and I. Pilz, 2. Naturforsch., 1954, 9b, 803.63 C. W. Bunn and E. V. Garner, Proc. Roy. SOC., 1947, A , 189, 37.64 R. E. Marsh, R. B. Corey, and L. Pauling, Acta Cryst., 1955, 8, 710.6 5 J.0. Warwicker, ibid., 1954, 7, 567.66 R. E. Marsh, R. B. Corey, and L. Pauling, Biochim. Biophys. Acta, 1955, 16, 1.L. Pauling and R. B. Corey, Proc. Nut. Acad. Sci., 1951, 37, 251.68 R. E. Marsh, L. Pauling, and R. B. Corey, Acta Cryst., 1955, 8, 62388 CRYSTALLOGRAPHY.the sheets in turn being staggered with respect to each other. The sequenceglycyl-alanyl(or sery1)-glycyl-alanyl(or seryl) predominates throughout thestructure, so that adjacent sheets pack parallel together at distances ofabout 3.5 A and 5.7 A.In light of this work, Marsh, Pauling, and Corey 68 consider it is un-necessary to suggest an amorphous phase for silk. Yet according to Am-brose and Elliott 69 and Elliott, Hanby, and Malcolm '* there is strongspectroscopic evidence for the existence of such a phase.Further con-firmation that silk fibroin is an extended polypeptide chain comes from thework of Andreeva and Iveronova 71 on Bombyx mori silk. An investigationon tussore silk reveals that the pseudo-unit cell is orthorhombic with aspace group P2,2,2, containing 8 amino-acid residues. This space groupdiffers from that of the Bonabyx mori silk pseudo-unit cell which is P2,. Thisdifference is due to the method of packing of adjacent sheets in Bombyxmori silk which are separated alternately by 3.5 and 5.7 A, whereas in tussoresilk all sheets are at equally spaced intervals 5.3 A apart. Within eachpleated sheet adjacent polypeptide chains are held in antiparallel sense byhydrogen bonds.The principal difference accordingly between the pseudo-structures of the two sheets is in the method of packing pleated sheets. * InBombyx silk the alternation of intersheet distances of 3.5 and 5.7 A corre-sponds to back-to-back and front-to-front packing of the sheets-thisappears to be necessary for the location of larger residues like tyrosine. Intussore silk the regular spacing of pleated sheets implies the lack of residueswith large atomic grouping and is in keeping with chemical evidence thatabout 85% of the silk contains glycine, alanine, and serine, in the cruderatio 2 : 1 : 1.Interhelical hydrogen- bonded collagenous ,types. Although collagen 72was long known to give a diffraction pattern different from the a- andp-type proteins it is only recently that a scheme of classification has beenfound for its constituent polypeptide chains. This has arisen largely as aresult of the X-ray study uf the synthetic polypeptides, poly-L-proline andpolyglycine 11, which indirectly have led to a suitable structure for collagen.Polyproline 73 as prepared by Berger, Kurtz, and Katchalski 74 contains anaverage of 20 residues in the chain and the X-ray powder pattern can beindexed on a hexagonal lattice with indications that there is a three-foldscrew axis parallel to c.There are three proline residues in the unit cell andthe structure consists of polypeptide chains situated at trigonal positions,each having three equivalent residues related by an exact three-fold screwaxis, the residue repeat along the c axis being 3.12 A.It is possible to builda three-fold helix with a repeat of 3.12 using planar amide groups if somedistortion is allowed at the a-carbon atom and it is found that the helix isleft-handed if the absolute configuration at the carbon atom is assumed.An observed perpendicular dichroism for the infrared G O stretching fre-quency is in keeping with such a model.The original X-ray diffraction effect of polyglycine obtained by Meyer69 E. J. Ambrose and A. Elliott, Proc. Roy. Soc., 1951, A , 206, 206.'O A. Elliott, W. E. Hanby, and B. R. Malcolm, Brit. J. AppZ. Phys., 1954, 4, 377.71 N. S. Andreeva and V. J. Iveronova, Doklady Akad. Nauk S.S.S.R., 1954,99,991.7a W. T. Astbury and W. R. Atkin, Natuve, 1933, 152, 348.73 P.M. Cowan and S . McGavin, Nature, 1955, 116. 501.7 4 A. Berger, J. Kurtz, and E. Katchalski, J . Anzer. Chem. SOC., 1954, 76, 5552BERNAL AND CARLISLE. 389and Go 75 has been reinvestigated by Bamford et Using infrared andX-ray methods they have identified two forms of the synthetic polypeptide.Form I, which shows spacings of 4.4,3.45, and 1-16 A, is identified as a (3-typestructure in agreement with Astbury's earlier findings on this syntheticpolypeptide.77 Form 11, precipitated from water by lithium bromidesolution, shows strong reflections at 4-15 and 3.10 A. No satisfactoryexplanation could be put forward for these spacings except that they clearlycould not be explained on the basis of an a-helix type structure. Crick andRich 78 connected the existence of this 3-10 A reflection in polyglycine I1with the residual repetition of 3-12A observed in poly-L-proline and haveconsequently suggested a close similarity in structure for these two syntheticpolypeptides.The polyglycine chains are packed in hexagonal array, eachchain being hydrogen-bonded to each of its six neighbours, forming an infinitesequence of hydrogen bonds running from one cell to the next. The planarpeptide groups in each chain are inclined at about 35" to the fibre axis.The structure contains three residues in 9.3 A and can be described asa = 4.8 A, c = 9.3 Owing to the fact that thereis no asymmetric carbon atom the mirror-image structure P3, is equallypossible. As there are no bulky side groups, interchain hydrogen bondingis dictated by the interaction between neighbouring chains.This is thefirst example reported of interchain hydrogen bonding between helical typepolypeptide chains and it is a warning that no rigid demands are made, inthe case of the natural and globular proteins that all hydrogen-bonds areinternally satisfied in the folded configuration of their respective chains.A cylindrical Patterson function 79 has been calculated €or collagen.There is some difficulty in interpreting the function in terms of the a-helix.In the attempt to maintain planar amide groups and to account for infrareddichroism Randall et al. suggested a sheet-type structure for collagen whoseconfiguration was formally similar to that for a 2,b chain earlier suggestedby Bamford, Hanby, and Happey.81 This structure, like those previouslysuggested,4Ssa failed for the simple reason that it could not account for thestrong meridional reflections at 2.8-3.1 A.Cohen and Bear 83 and Cowan,McGavin, and North 8Q have provided strong arguments based on X-rayevidence that collagen must be a helical type structure. A structure pro-posed by Ramachandran and Kartha,*5 being a revision of an earlier 3-chainmodel based on a 3-chain coiled coil does account for the meridionalspacing of collagen. Rich and Crick 86 found that Ramachandran andKartha's structure was stereochemically unsatisfactory and was incom-75 K. H. Meyer and Y. Go, Helc. Chim. Acta, 1934, 17, 1488.76 C. H. Bamford, L. Brown, E. M. Cant, A. Elliott, W.E. Hanby, and B. R. Malcolm,77 W. T. Astbury, Natuve, 1949, 163, 722.'@ H. L. Yakel, jun., and P. N. Schatz, A d a Cryst., 1955, 8, 22.with space group P3,.Nature, 1955, 176, 396.F. H. C. Crick and A. Rich, Nature, 1955, 176, 780.J. T. Randall, R. D. B. Fraser, S. Jackson, A. V. W. Martin, and A. C. T. North,C. H. Bamford, W. E. Hanby, and F. Happey, Proc. Roy. Soc., 1961, A , 205, 308a W. T. Astbury and F. 0. Bell, Nature, 1940,145, 421 ; L. Pauling and R. B. Corey,1 3 ~ C. Cohen and R. S. Bear, J . Amer. Ckem. SOC., 1953, 75, 2783.84 P. M. Cowan, C. S. McGavin, and A. C. T. North, Nature, 1955, 176, 1062.85 G. N. Ramachandran and G. Kartha, Nature, 1954, 174, 269; 1955,178, 59.Nature, 1952, 169, 1029.Proc. Nat. Acad. Sci., 1951, 37, 272.A.Rich and F. H. C. Crick, Nutuve, 1955, 175, 915390 CRYSTALLOGRAPHY.patible with recent chemical evidence 87 which shows that the amino-acidsequence glycine-proline-hydroxyproline occurs very frequently. Startingfrom the structure of polyglycine I1 78 they showed that if three adjacentchains were twisted as in the Ramachandran-Kartha structure, ie., themajor helix is right-handed while the minor ones are left-handed, two stereo-chemically completely satisfactory structures could be obtained dependenton the two different ways it is possible to select three chains in polyglycine 11.Both structures have one systematic set of hydrogen bonds lying approxim-ately perpendicular to the fibre axis, in agreement with infrared data 88 andthe effect of super-coiling permits room for residues like proline and hydroxy-proline. In one of the structures the hydroxyproline residues are internallyhydrogen-bonded to a G O group of one of the three chains, while in the otherthe hydroxyproline is able to form a hydrogen bond to an adjacent set ofthree chains which appears to be in keeping with the suggestion made byGustavson 89 that hydroxyproline is largely responsible for stabilising thecollagen structure. Although this model has not as yet been established asa correct structure it does broadly satisfy the requirements of the wide-angle X-ray data of collagenous type fibres.The swelling of collagen has been investigated by X-ray diffraction byRougvie and Bear.go Water adsorption gives rise to the straightening ofchains for dry collagen resulting in parallel alignment.Further adsorptionresults in lateral separation of the fibrillar groups with further straighteningof the chains. At low and high adsorption values the sorbed water contri-butes to the increase of the apparent molecular volume in the expectedmanner. Low-angle X-ray diffraction studies on the ultrastructure ofbone 91 of perch and pike indicate rod-shaped particles approximately65 A wide and 200 A long, with the long axis aligned parallel to the fibreaxis of collagen. A close relation was shown to exist between the form ofcrystallisation of the apatite and the structure of collagen. It is interestingto point out that Cowan et aLg2 from improved wide-angle X-ray photo-graphs of collagen have definite evidence of a layer line spacing of 200 A.Vitrosin, prepared from vitreous humour of cattle has been charac-terised from wide- and small-angle X-ray diffraction, electron diffraction,and chemical analysis as a member of the collagen group.It is a fibrousprotein, 100-150 A in diameter, containing an axial periodicity of 640 A.The hydroxyproline and glycine contents are 11.7 and 19% respectively,indicating the ratio of these two residues to be higher than for most verte-brate collagens. X-Ray investigations of the changes with age in thestructure of the human intervertebrate disc have been carried Ageingof the disc, in general, results in fibrillation and precipitation of the collagen.On the basis of X-ray investigations Astbury and Bellg6 placed elastin in87 W.A. Schroeder, L. M. Kay, J. Le Gette, L. Homer, and F. C. Green, J . Amer.Chem. SOC., 1954,76,3556; T. D.Kroner, W.Tabroff, and J. J. McGarr.ibid., 1955,77,3356.88 G. B. B. M. Sutherland, K. N. Tanner, and D. L. Wood, J . Chem. Plzys., 1954,22, 1621 ; G. N. Ramachandran, ibid., 1955, 22, 600.wo M. Rougvie and P. S. Bear, J. Amer. Leather Chemists' Assoc., 1953, 48, 735.w 1 D. Carstrom and J. B. Finean, Biochim. Biophys. Acta, 1954, 13, 183.v2 P. M. Cowan, A. C. T. North, and J. T. Randall, Nature, 1954, 174. 1143.g3 J . Gross, A. G. Matolsty, and C. Cohen, J . Biophys. Biochenz. Cvtol., 1955, 1, 21.5.g4 F. Happey, T. P. Macras, and K. Naylor, ref. l l c , p. 66.v 5 W. T. Rstbury and F. 0.Bell, Tabah Biologic@, 1939, 17, 90.K. H. Gustavson, Nature, 1955, 175, 90BERNAL AND CARLISLE. 891the collagen group, and now recent electron-micrograph studies, combinedwith biochemical and histological studiesF6 have shown the apparenttransformation of collagen fibrils into elastin. Randall and his collaborators’pertinent observations 97 on native and precipitated collagen are worthnoting. Attempts are made (1) to correlate electron-micrograph studies ofcollagen fibrils with low-angle X-ray scattering, (2) to examine the im-portant factors in fibrinogenesis of collagen from solution, both experi-mentally and theoretically, and (3) to define the conditions of formation oflong-spacing fibrils and segmented fibrils more closely. It is found as resultof these studies (1) that the 640 A periodicity arises from a single proteinconstituent, (2) that neither fibrous nor segmented long-spacing materialhas been observed in connective tissues in vivo, and (3) that there is insuffi-cient evidence to decide whether or not structures of collagenous type arebuilt up of units of short length. Their most recent observations show thatthe structure factors calculated from density functions along the fibril axisof different tendons derived from electron micrographs can be successfullycompared with the corresponding structure factors derived from low-angleX-ray photographs of dry fibres.Globular Proteins.-The chief crystalline globular proteins now underX-ray investigations are various hzemoglobins (molecular weight 66,700) andmyoglobins (14,000), insulin (12,000), ribonuclease (13,400) and lysozyme(14,000).For the purpose of this Report it is convenient to deal withhzemoglobins, which have been most intensively investigated, and myo-globins together, although it is fully recognised that there is no necessarystructural connection between these two proteins. Of the remaining three,ribonuclease has so far been examined in most detail.These three groups have been studied by the heavy-atom technique, butonly in the case of hzmoglobins and myglobins has this led to informationon the internal structure of the molecules. For the rest all that is known istheir shape and size, and some tentative hypotheses as to the possiblealignments of their polypeptide chains.Hwmoglobins and myoglobins.The names of these are put in the pluralas many crystalline varieties derived from horse, sheep, whale, seal, ox,tortoise, penguin, carp, and man have been studied. Though differing indetail, these show a common basic structure.Six papers entitled “ The Structure of Hzmoglobin ” Qg describe the firststeps in the attempt to solve the structure of the haemoglobin moleculeusing direct methods. It has been possible, by following lattice changes andconsequent changes in the modulus of the molecular transform at the latticepoints in crystals at different shrinkage stages using absolute measurements,to give reliable dimensions for the hemoglobin molecule, treated as a spheroidof 53 X 53 X 71 A and 45 x 45 x 65A for the hydrated and the dry96 D.Burton, D. A. Hall, M. K. Keech, R. Reed, H. Saxl, R. E. Tunbridge, andM. J . Wood, Nature, 1955, 167, 1966.s7 J . T. Randall, F. Booth, R. E. Burge, S. F. Jackson, and F. C. Kelly, ref. lld,p. Ig27; R. E. Burge and J . T. Randall, Proc. Roy. Soc., 1955, A , 223, 1.(Sir) L. Bragg and M. F. Perutz, Proc. Roy. Soc., 1952, A , 213, 425; (Sir) L.Bragg, E. R. Howells, and M. F. Perutz, ibid., 1954, A, 222, 33 ; (Sir) L. Bragg andM. F. Perutz, ibid., 1954, A , 225, 264; D. W. Green, V. M. Ingram, and M. F. Perutz,ibid., p. 287; E. I<. Howells and M. F. Perutz, ibid., p. 308; (Sir) L. Bragg and M. F.Perutz, zbid., p. 315392 CRYSTALLOGRAPHY.molecule, respectively. By observing these lattice changes an attempt hasbeen made to obtain the absolute signs of reflections for h and I up toA M = 0.24 for that part of the crystal transform which is real.The absolutesigns of layers with h > 2 are left in doubt, but the number of alternativecombinations has been reduced from 296 to 213.Confirmation of the sign determination by application of transformprinciples has come from a study of haemoglobin crystals containing p -mercuribenzoate and silver ions severally, which are isomorphous withnormal monoclinic methzemoglobin. The changes in F(h0I) were used todetermine the x and z parameters of the pair of heavy atoms attached toeach haemoglobin molecule. This was carried out for the normal wet latticeand for one of the acid expanded lattices. The positions of the heavy atomsproved to be slightly different in each case, and this allowed just over two-thirds of the signs to be found with certainty. All the sign relationsestablished by the transform method were confirmed and uncertaintiescleared up.In this way the signs of 87 out of 94 reflections were foundwith certainty. A further check on the signs was made by the study ofglyoxaline-methzemoglobin where there is a close correlation in the alignmentof the molecules in these crystals which are orthorhombic with the orientationof the molecules in the monoclinic form.This work has now resulted in the calculation of an electron-density mapof a single row of molecules on the (010) projection. This is shown inFig. 1 for hzemoglobin molecules suspended in salt-free water.It has beencalculated with terms whose interplanar spacings are larger than 7.0 A ;hence one is looking at a poor resolution of a molecule some 50 A thick.Nevertheless, the picture must be substantially correct and it is also thefirst picture of a protein molecule derived without chemical or physicalassumptions. The broken lines running across the positive regions of themap indicate the outline of the molecule along the a direction.Although the internal structure of the molecule is still obscure the mapis in general agreement for a tilted spheroid 71 x 54A and much greaterresolution is needed to confirm or refute the arguments put forward for thepresence of parallel polypeptide chains in the molecule.X-Ray studies on crystalline myoglobin are being actively pursued byKendrew 99 at Cambridge.Intense activity at the moment is being centredon the isomorphous replacement technique, so successful in the case ofhamoglobin. The crystal symmetry and Patterson projection of a mono-clinic, pseudo-orthorhombic form of horse myoglobin has been described byKendrew and Trotter.lW The unit cell is very closely related to the mono-clinic form of the protein previously described. lol Interesting speciesspecificities of myoglobin in relation to antigen-antibody reactions have beendescribed by Kendrew, Parrish, Marrack, and Ostens.lo2 It is of interestthat crystallographic and immunological techniques have been used inconjunction for the first time in an attempt to gain a deeper insight into thedifficult field of immunochemistry.fie J.C . Kendrew, personal communidation.loo J . C . Kendrew and I. F. Trotter, Acta Cryst., 1954, 7, 347.Io1 J. C. Kendrew, R o c . Roy. SOL, 1950, A , 201, 62.lo2 J. C. Kendrew, R. G. Parrish, J. R. Marrack, and E. S. Ostens, Nalzwe, 1954,174, 946BERNAL AND CARLISLE. 393Other publications have included the demonstration of an improvedtechnique for studying the discontinuous lattice changes in haemoglobincrystals,lW the study of the form birefringence of the ha3moglobin moleculeand the possible application of such a method to the determination of the10 20 30 40 50 a =109*2I t r r r l i i i i l r r ~ r l i i r i l ~ i r ~ lFIG. 1. Fouvier projection of u YOU of hawtoglobin molecules in salt-free water.The zerocontour corresponds to the density found where the whole depth of the unit cell is fclledwith water. The other contours are drawn at intervals of I eZectron/A4 above or belowthat level. (Reproduced, with permission, from Bragg and Perutz, Proc. Roy. Soc.,1954, A , 226, 315.)form of other protein molecules,lw the study of polarisation dichroism, formbirefringence, and molecular orientation in crystalline haemoglobins lo5 andan X-ray study of reduced human haemoglobin,lo6 showing its similaritiesto horse methzmoglobin.The X-ray work on globular proteins may now be divided into (a) thatwhich deals with the direct analysis of the structure, the isoxnorphousheavy-atom replacement technique being used with the minimum of chemicalassumption, and (b) attempts to interpret the Patterson functions of thesecrystals. Critical analyses of the latter have been of use in rejecting hypo-theses of very simple models for globular proteins.has suggested from a study of the three-dimensional Patterson functions ofhaemoglobin that the molecule cannot be regarded as a simple alignment ofFor instance, Crickl** H.E. Huxley and J. C. Kendrew, Acta Cryst., 1953, 6, 76.lo4 W. L. Bragg and A. B. Pippard, ibid., p. 865.lo6 M. F. Perutz, ibid., p. 859.lo6 M. F. Perutz, I. F. Trotter, E. R. Howells, and D. W. Green, zbid., 1955, 8, 241.F. H. C. Crick, Pi1.D. Thesis, Cambridge, 1953; Acta Cryst., 1952, 5, 381;1953, 6, 600394 CRYSTALLOGRAPHY.polypeptide chains folded backwards and forwards on themselves, but it isonly by postulating irregularities such as parallel alignment of chains overshort lengths that an explanation can be given for the low vector density ofthe Patterson functions.Furthermore, from a study of the strength of the10-A reflections it is possible that hzmoglobin could consist of a-helices notnecessarily parallel to one another. Caution is expressed that this must notbe taken to mean that the molecule is largely composed of a-helices. Argu-ments that hzmoglobin is made up of globulite molecules are put forward byWrinch lo* who has further concluded from a study of the three-dimensionalvector maps of hzmoglobin that there is no evidence for the existence ofparallel polypeptide chains in this molecule.lo9 Arguments against theexistence of parallel polypeptide chains in myoglobin have been putforward.lloInsuligt. The anomalous situation exists that for this protein moleculethe sequence of amino-acids in the sub-unit of 6000 comprising 2 chains iscompletely known.lll Yet no model so far built involving the four chainscoiled in the a-helix configuration 112 has satisfactorily accounted for theX-ray crystal data. A preliminary account has been published of theorientation of polypeptide chains in orthorhombic air-dried crystals of acidinsulin sulphate. 113 A complete three-dimensional Patterson synthesis hasbeen calculated by using 96 reflections, which shows marked ridges of vectordensity in approximately hexagonal packing at about 10-13 A from oneanother running parallel to the a axis.I t is suggested that these ridges ofhigh vector density might correspond with possible chain directions of themolecules in the crystal.The amino-acid composition of this enzyme has beenrecently determined by Hirs, Stein, and Moore 114 who find that the moleculeis composed of 128 amino-acid residues, and preliminary studies by Afinsen,Redfield, Choate, Page, and Carroll 115 have shown that the molecule consistsof one chemical chain.reports the preparation of ribonuclease crystals containingdyes with and without heavy atoms, and the cell dimensions and space groupsof at least four different protein dye complex crystals. Crick and Magdoff 117have described a crystalline form of ribonuclease containing iodophenolblue, and details are given 118 of a new type of shrinkage phenomenon inthese crystals involving appreciable alterations in the intensities of theX-ray diffraction by the crystal. Attention is drawn to the obtaining ofaccurate measurements of cell dimensions in the light of solvent effects onRibonuclease.Harkerlo* D.Wrinch, J . Chem. Phys., 1952, 20, 1332; Acta Cryst., 1952, 5, 694.lo* Idem, ibid., 1953, 6, 562, 638.110 Idem, ibid., 1952, 5, 694.ll1 F. Sanger and H. Tuppy, Biochem. J . , 1951, 49, 463, 481; F. Sanger andE. 0. P. Thompson, ibid., 1953, 53, 353, 366.112 D. P. Riley and U. W. Arndt, Nature, 1953, 172, 245 i C. Robinson, $bid., p. 27;H. Lindley and J. S . Rollett, Biochim. Biophys. Acta, 1955, 18, 183.113 B.W. Low, Nature, 1952, 189, 955.114 C . H. W. Hirs, W. H. Stein, and S. Moore, J . B i d . Chem., 1954, 211, 941.lt5 C. B. Anfinsen, R. R. Redfield, W. L. Choate, J. Page, and W. R. Carroll, ibid.,116 D. Harker, Progress Report of Protein Structure Project, 1-3-1954 to 28-2-117 F. H. C . Crick and B. Magdoff, ibid., 1955, 8, 468.llB Idem, ibid., p. 461.1954, 207, 201.1955; Acta Cryst., 1954, 7, 654BERXAL AND CARLISLE. 395the crystal. A third paper 119 describes the three-dimensional Pattersonvectors of the monoclinic form of ribonuclease they call 11. This Pattersonvector distribution is calculated with reflections having spacings greaterthan 3 A and the authors point out that there is no apparent evidence forany polypeptide chain direction in the crystal.have calculated a second three-dimensional Pattersonvector distribution of the monoclinic form of ribonuclease based on a new setof X-ray results, and find that the Patterson vector maps are in substantialagreement with a previous three-dimensional Patterson calculation of thecrystal for which a smaller number of terms was used.This has been con-sidered to supply more evidence to justify the original suggestion that thepolypeptide chains of the molecule are lying in or near the c axis direction ofthe crystal, in agreement with infrared dichroic measurements 121 and insupport of the earlier findings by Carlisle, Scouloudi, and Spier 122 that it isexceedingly difficult to interpret the X-ray data of this crystal in terms of ahexagonal packing of ct-helices.Wrinch has put forward evidence forglobular units, with low-density interiors, as forming the basis of the ribo-nuclease molecule.Lysozyme. Corey, Donohue, and Trueblood 124 have calculated thethree-dimensional Patterson function of air-dried tetragonal lysozymechloride crystals. Only 198 observed reflections from the air-dried crystalbeing used, it is not surprising that the authors saw no distinctive character-istics in the vector distribution that would support the presence of eitherIX- or y-helices in the molecule.In his attempts to find proteins of low molecular weight suitable fordetailed study Crick 125 has given the cell dimensions for lysozyme nitrate.King 126 has recently completed a measurement of the wet and the dry celldimensions of lysozyme nitrate and iodide which are isomorphous in bothstates.The wet crystals contain 4 molecules per unit cell and the driedcrystals 2 molecules per unit cell; Carlisle has found I2O that lysozymebromide behaves similarly.Nucleic Acids.-The unravelling of the structure of deoxyribonucleicacid has been a triumph of combined chemical and crystallographic attack.(A good general account 127 is given in Chargaff and Davidson’s book,‘‘ TheNucleic Acids.”) The 3’ : 5’-diester linkage proposed by Brown and Toddfor a method of joining nucleotides through phosphates has been amply con-firmed,128 but X-ray analysis was required to bring out the stereochemistryof this arrangement. Deoxyribonucleic acid can be made in the form oforiented fibres.These were studied by Astbury f29 who, noting the strongmeridional reflection at 3.4A, concluded that the structure consisted of aCarlisle et al.ll0 F. H. C. Crick and B. Magdoff, Acta Cryst., 1956, 9, in the press.lZo C. H. Carlisle, M. Ehrenberg, G. S. D. King, RI. Levy, and H. Scouloudi,121 A. Elliott, Proc. Roy. Soc., 1952, A , 211, 490.122 C. H. Carlisle, H. Scouloudi, and M. Spier, Proc. Roy. Soc., 1953, B, 141, 85.123 D. Wrinch, Biol. Bull., 1953, 105, 354.12* R. 13. Corey, J , Donohue, and K. N. Trueblood, Acta Cryst., 1952, 5, 701.125 F. H. C. Crick, Acta Cryst., 1953, 6, 221.lzG G. S. D. King, personal coniinunication.lZ7 Ref. 15, p. 461lea Cf. - 4 n n . Reports, 1952, 49, 246; 1954, 51, 275.lz9 W.T. Astbury, Sywip. SOL. Exp. Biol., 1947, 1, 66pcrsonal com munication396 CRYSTALLOGRAPHY.pile of purine and pyrimidine groups at right angles to the fibre axis whichwould also serve to explain the strong negative birefringence. Next Fur-berg,130 studying the crystal structure of the nucleoside cytidine, showed thatthe plane of the sugar molecule was roughly at right angles to that of thepyrimidine base. He accordingly put forward two alternative structures(Fig. 2) for nucleic acid, both involving a pile of purine pyrimidine basesQ nf4- 3-4AI 3.4A3 , 4 i i I0 C,N,OModel I @ p 0&3A ModelIIFIG. 2. Two models of thymonucleic acid based on nucleotides of the “ standard ” conjigura-The planes of the $urine and pyrimidine rings are perpendicular to the p2ane of(Reproduced, with permission, from Furberg, Acta Chenz.Scand., 1952,tion.?he paper.6, 634.)in one of which the phosphate sugar groups were peripheral, in the othercentral. The second alternative was further developed by Pauling andCorey,131 who introduced the concept of a helical structure, but this led tocontradictions. The first led to a structure of unexpected complexity butof great beauty and ultimate significance. Its establishment was the resultof the combination of careful X-ray study of good preparations of nucleicacid and the impetus of the ideas of helical structures already developed forproteins. It arose out of consultations between workers at King’s College(London) and at the Cavendish Laboratory (Cambridge) and has led in turnto a deeper appreciation of the part helical systems play in biologicalstructures (see section on Plant Viruses).Franklin and Gosling 132 foundthat sodium deoxyribonucleate fibres can occur in two reversible statesA and B, and that in both states the phosphate groups are accessible towater and hence must lie on the outside of any roposed structure. StatesA and B show layer line spacings of 28 and 34 x respectively : the formerexists at about 75% relative humidity and possesses a high degree ofcrystallinity ; the other exists at higher humidities and its X-ray diffraction130 S. Furberg, Acta Claeni. Scatid., 1952, 6, 634.131 L. Pauling and R. B. Corey, Pvoc. Nut. Acnd. Sci., 1953, 39, 84; Natzrre, 1953,133 R.E. Franklin and R. G. Gosling, Acta Cryst., 1953, 8, 073.171, 346397 BERNAL AND CARLISLE.pattern shows a lower degree of crystallinity but is even inore characteristicof the type of diffraction pattern given by a helical structureeS6Watson and Crick, 133 considering this ex perimen tal evidence, arrived a tthe conclusion that deoxyribonucleic acid was not composed of piles ofsingle nucleotides as previously supposed but of pairs of nucleotides (Fig. 3)0 1 2 3 4 5 i t ' " " ' FIG. 3. The $airing of adenine and guanine in deoxyribonucleic acid. Hydrogen bondsThe arrow vepresents(Reproduced, with permission, from Crick and Watson,are shown dotted.the crystaZZograph.ic diad.Proc. Roy. SOL, 1954, A , 223, SO.)One carbon atom of each sugar is shown.formed by hydrogen bonding.Each pair was composed of a pyrimidine anda purine residue, and consequently were either thymine-adenine or cytosine-guanine. This idea suggested in turn that a double instead of a single helicalphosphate sugar chain (Fig. 4) was coiled around the same axis, repeatingFIG. 4. This Figure i s purely diagrammatic. The two ribbons symbolise the two phosphate-sugar chains, and the vertical rods the $airs of bases holding the chains together.The horizontal line marks the fibre axis. (Reproduced, with permission, fromWatson and Crick, Nature, 1953, 171, 737.)10 nucleotides a t 34 intervals. This model provided an explanatione X-ray and titration observations of sodium deoxyribonucleate fibres133 J.D. Watson and F. El. C. Crick, Nature, 1953, 171. 737; Proc. Roy. Soc., 1954,A, 223, 80398 CRYSTALLOGRAPHY.of different h~1nidities.l~~ It also had other implications for biochemistryand genetics. The two chains postulated follow right-handed helices butrun in opposite directions; consequently if one chain has the sequence :adenine-cytosine-thymine-adenine, then the corresponding sequence on theother chain must be thymine-guanine-adenine-thymine. This is in keepingwith the chemical evidence 134 that the ratio of purine to pyrimidine basesare usually close to unity. Furthermore, the structure is compatible lZ99 135with X-ray and optical evidence for structure B. Further detailed workdGfining the geometry of deoxyribonucleic acid has been published.1367 13iA cylindrically symmetrical Patterson function and a three-dimensionalPatterson function have been calculated for the sodium salt of form A. Itis shown that the P-P vectors in these Patterson functions indicate a slightlymodified form of the model proposed by Watson and Crick,133 viz., that thephosphorus atoms form two coaxial helical strands of 9 A radius and 28.1 Apitch, with 11 phosphorus atoms spaced equally along each turn of eachstrand, and the separation of the helical strands in the direction of theircommon axis is 14 A. This model suggests that ionic links between phos-phate groups are primarily responsible for maintaining order in the three-dimensional crystal. I n structure A, the sodium ions hold the chainstogether and, as the relative humidity increases, the additional water insome way weakens the directional property of the phosphate link andstructure B then appears.Water absorption leads ultimately to gel fonn-ation and solution. These X-ray data give no direct evidence for the locationof the sugar and base rings in the structure but it is clear that they mustpoint inwards towards the helical axis and that the diameter of the helix ofstructure B should be about 20 A with a pitch of 34 A. A radial distributioncurve for the air-dried sodium salt 138 has been reasonably interpreted interms of the two-strand helix model.I n their studies of nucleoprotein, Wilkins and Randall 139 have pointedout that there is a similarity between the X-ray photographs of sperm headsand those of the fibres of pure sodium thymonucleate. Watson andCrick 140 suggest that there is room between the pair of polynucleot ide chainsfor a polypeptide chain in the p-configuration to wind around the same axis,and this argument is based on their interpretation of the relevant publishedX-ray pictures.129$ 139 Riley and Arndt,l*l in investigating the X-rayscattering of the air-dry compacts of nucleoprotein specimens from herringsperm and calf thymus together with the corresponding separated proteinsand nucleic acids, conclude that the nucleoproteins are simple additionproducts rather than the type of complex suggested by Watson and Crick.130 E.Chargaff, C. F. Crampton, and R. Lipschitz, Nature, 1953, 172, 289; G. R.Wyatt, “ The Chemistry and Physiology of the Nucleus,” Academic Press, New York,1952.135 R.E. Franklin and R. G. Gosling, Nature, 1953, 171, 740; M. H. F. Wilkins,A. R. Stokes, and H. R. Wilson, ibid., p. 738; M . H. F. Wilkins, R. G. Gosling, andW. E. Seeds, ibid., 1951,167, 759.136 R. E. Franklin and R. G. Gosling, Acta Cryst., 1953, 6, 67; Nature, 1953, 172,156; Acta Cryst., 1955, 8, 151.13’ M. H. F. Wilkins, W. E. Seeds, A. R. Stokes, and H. R. Wilson, Nature, 1953,172, 759.13* U. W. Arndt and D. P. Riley, Nature, 1953, 172, 803.130 M. H. F. Wilkins and J . T. Randall, Biochim. Biophvs. Acta, 1953, 10, 193.l40 J . D. Watson and F. H. C . Crick, Nature, 1953, 171,-964.141 D. P. Riley and U. W. Arndt, ibid., 1953, 172, 249BERNAL AND CARLISLE. 399Recently Feughelman et ~ 1 .l ~ ~ have shown that in the synthetic deoxyribosenucleoptrotein, made by combining nucleic acid and protamine, the X-rayphotograph can be reasonably well interpreted in terms of an extendedpolypeptide chain wound helically around the nucleic acid helix. Thisevidence obtained from oriented wet fibres is absent when the fibres areexamined in the dry unoriented state.Feughelman et aZ.142 have put forward a modified structure for deoxy-ribonucleic acid, in that it is a tighter two-chain helix conforming to dimen-sions suggested by Franklin and G0sling.13~ This reduces the generaldiameter of the molecule, so moving each pair of purine-pyrimidine basestowards the helix axis.Rich and Watson 143 have pointed out that the X-ray patterns of ribo-nucleic acid from different sources appear to be similar, implying that theunderlying three-dimensional configurations of these nucleic acids are possiblysimilar in spite of large differences in their respective purine : pyrimidineratios.Drawn fibres show negative birefringence, like deoxyribonucleic acid,suggesting a similar orientation of nucleotide groups with respect to the fibreaxis. As the water content increases the fibres swell, losing birefringenceand becoming amorphous. The fibres show " necked " regions on extensionand become positively birefringent in contrast to the rest of the structure;similar effects were previously noted in deoxyribonuclease by Wilkins,Gosling, and Seeds. 135Plant Viruses.-Following the success of the chemically feasible structurefor deoxyribonucleic acid based on a helical structure, Watson turnedto an interpretation of the wide-angle diffraction photographs of tobacco-mosaic virus which had earlier been studied by Bernal and F a n k ~ c h e n .~ ~ He suggested, on the basis of the theory of X-ray diffraction by helicalstructures,6 that the virus particle was one giant helical molecule, composedof a large number of equivalent protein sub-units helically arranged arounda core of ribonucleic acid. The proposed helix is repeated after 3 turns in68 It is considered that n isof the order of 10. By using this value and a molecular weight 146 of 5 x lo7,it was found that the weight of a protein building unit was 35,000, a figureabout twice that found by chemical methods.147 Schramm and Braunitzer 14*believe there is N-terminal proline.A detailed analysis by Franklin 149 of the X-ray pattern of tobacco-mosaic virus, by using a cylindrical Patterson function, has revealed thatWatson's preliminary considerations about the virus particle's being ahelical structure are essentially correct, but should be modified in detail.Forinstance, A value of 12 was suggested but 16 now seemsand contains (3n + 1) sub-units per repeat.is larger than 10.142 M. Feughelman, R. Langridge, W. E. Seeds, A. R. Stokes, H. R. Wilson, C. W.Hooper, M. H. I?. Wilkins, R. K. Barclay, and L. D. Hamilton, Nature, 1955, 175, 834.143 A. Rich and J. D. Watson, ibid., 1954, 173, 995; Proc.Nut. Acad. Sci., 1954,40, 759.144 J. D. Watson, Biochim. Biophys. Acta, 1954, 13, 10.145 J. D. Bernal and I. Fankuchen, J. Gen. Physiol., 1941, 25, 111.146 R. C. Williams, R. C. Backus, and R. L. Steere, J . Anzer. Chem. Soc., 1951, 73,14' J. L. Harris and C. A. Knight, Nature, 1952, 170, 613; C. A. Knight, Adv.148 G. Schramm and G. Braunitzer, 2. Natzwforsch, 1963, 8b, 61.149 I<. E. Franklin, Nutwe, 1955, 175, 379.2062.Vivus Research, 1954, 2, 153400 CRYSTALLOGRAPHY.more probable,l50 giving 49 building units in 3 turns of the helix of pitch23 A. There is evidence from both the cylindrical Patterson function anda detailed study of the X-ray pattern that there is an important structuraldiscontinuity between one turn of the helix and the next and this appears tobe associated with an external grooving of the particle.This groovingresults in the virus particle's having a larger surface area than that associatedwith a cylinder of 150 A diameter.145 Since the mean radius of the tobacco-mosaic virus particle is only about 75 A and, of this, the ribonucleic acidcore must occupy the inner 15-20 151 it is clear that a substantial partof the virus protein must lie in the proximity of the surface. The cylindricalPatterson function shows a double row of peaks about 11 A apart, consistentwith the idea that the protein units have a double layer of polypeptide chainsrunning perpendicular to the axis of the particle. Here there is agreementwith infrared measurements 152 which suggest that the protein may be inthe form of %-helices lying perpendicular to the axis of the virus.The helical groove in a mild U2 strain of tobacco-mosaic virus has beenshown 153 to be approximately 30 A deep and it is suggested that the groovein fact may be a common feature in all strains, being more marked in somethan in others.The existence of the groove implies some form of helicalridge around the particle and it is suggested that this takes the form of ahelical array of protuberances, one for each protein sub-unit. The form ofthe groove and ridge is such as to permit a high degree of interlockingbetween neighbouring particles. In further investigations it has beenshown that the X-ray diagrams of three strains of tobacco-mosaic virus anda cucumber virus are closely similar in their main features but differ signi-ficantly from one another in points of detail.A noticeable feature of theseX-ray diagrams is that the intensity maxima do not lie exactly on a set ofequally spaced layer lines. They are displaced to small distances on eitherside of the mean layer line position for layer lines of the type I = (3n + 1)and (3n + 2). The extent of the effect varies with the strain of the virusand this means that there must be a slight variation from the (3n + 1)protein sub-units in 3 turns of the helix.155 In the mild U2 strain there are,for instance, 31.05 &- 0.01 protein units in 3 turns of the helix if n = 10.In the other strains examined, such as U1 and the Rothamsted strain thereare approximately 31.02 units in 3 turns of the helix.Investigations aimed at determining the radial structure of tobacco-mosaic virus have been carried out by Caspar 156 who has studied the radialdistribution curves of the equatorial intensity maxima for the virus and thevirus soaked in lead acetate.It is found that the lead is located at sites25 A and 84 A from the axis of the particle, there being two lead atoms perprotein sub-unit. It is not clear yet what specific residues bind the leadatoms to the protein. Crystallographically, the importance of the work isthat, in noting the difference in intensities of the equatorial intensity maxima150 R. E. Franklin, unpublished work.151 G. Schramm, G. Schumacker, and W. Zillig, Nature, 1955,175,549; R.G. Hart,152 R. D. B. Fraser, Nature, 1952, 170, 491.153 R. E. Franklin and A. Klug, Biochim. Bioplzys. Actu, in the press.15* €3. E. Franklin, ibid., in the press.lS5 R. E. Franklin and A. Klug, Acta Cryst., 1955, 8, 777.156 D. Caspar, Ph.D. Thesis, Yale, 1955.PYOC. Nut. Acad. Sci., 1955, 41, 261BERNAL AND CARLISLE. 401for tobacco-mosaic virus and for the lead-bound virus, it has been possibleto give the first ten maxima their correct signs. A calculation of the radialdensity shows regions of high density at 24 and 40 A from the axis with aneffective radius of 84 A for the virus particle in solution.Watson,157 in suggesting that the ribonucleic acid forms a central coresome 35 A in diameter, drew his ideas from the study of turnip yellow-mosaicvirus,158 where X-ray and chemical evidence suggests that the ribonucleicacid component is situated within the virus particle.Beautiful confirm-ation of this comes from the electron-micrograph studies by Hart on theone hand and by Schramm et al. on the other 151* 159 who show very clearlyin their studies on degraded particles of tobacco-mosaic virus that the ribo-nucleic acid exists as a fibrous central core, some 40A thick. Equallyinteresting are their observations of a hole down the centre of the virusparticle when the ribonucleic acid has been removed.X-Ray studies on an abnormal protein associated with tobacco-mosaicvirus have been carried out by Rich, Dunitz, and Newark 160 and Franklinand Commoner.lG1 The material studied by Rich et al.is non-infectious,nucleic-acid free, and virtually identical with the protein component of thevirus, and at its isoelectric point forms rod-like structures, which are some5’3, shorter than the usual value of 68A associated with tobacco-mosaicvirus. Franklin and Commoner’s studies are connected with an abnormal(B8) non-virus protein polymerised in rods which differs little in chemicalconstitution from that examined by Rich et al. The particle has a repeatunit of 65A, but the protein sub-units are possibly not arranged helicallyaround the particle axis but rather stacked one above the other to form astructure which is grossly similar to that of the tobacco-mosaic virus protein.In further studies Franklin 162 shows that there is a marked structural re-semblance between a repolymerised protein freed from ribonucleic acid,known as Schramm’s A protein,163 and tobacco-mosaic virus.The gel has alower positive birefringence than the virus of the same concentration, whilethe birefringence of dry oriented polymerised A protein is weakly negative.This shows that the ribonucleic acid makes a positive contribution to thebirefringence of the virus and therefore has a structure which is unlike thatof deoxyribose nucleic acid 135 which is strongly negative. The protein gelshows an axial repeat of 69 A as in tobacco-mosaic virus and 62 in thedry state. It seems that when the nucleic acid core is replaced by waterthe structural arrangement of the protein in the virus particle remainsstable, but when this water is removed by drying the particle shrinks andbecomes partially disordered.Small-angle X-ray scattering measurements have been made on southernbean-mosaic virus, tobacco-necrosis virus and tomato-bushy stunt virus.164These nearly spherical viruses are found to have diameters of 286A for157 J. D. Watson, Biochim. Biophys. Acta, 1955, 13, 10.15* J. D. Bernal and C . H. Carlisle, Nutwe, 1948, 162, 139; R. Markham, Discuss.15D G. Schramm, G. Schumacker, and W. Zillig, 2. Naturforsch., 1955, lob, 481.160 A. Rich, J. D. Dunitz, and P. Newark, Nature, 1955, 175, 1074.lel R. E. Franklin and B. Commoner, ibid., p. 1076.162 R. E. Franklin, Biochim. Biophys. Ada, 1951, 18, 313.163 G. Schramm, 2. Naturforsch., 1947, 2b, 112, 249.164 B. R. Leonard, J. W. Anderegg, S. Shulman, P. Kaesberg, and W. W. Beeman,Faraduy SOC., 1951,11, 221.Biochim. Biophys. A d a , 1953, 12, 499402 CRYSTALLOGRAPHY.southern bean-mosaic virus, 280 for tobacco-mosaic virus, and 309 A fortomato-bushy stunt virus. A similar investigation has been carried out onsolutions of turnip-yellow mosaic virus. 165 Measurements of the virus andthe associated nucleic acid-free protein indicate that both particles are nearlyspherical and about 140tf in radius. It is suggested that all these virusparticles have large internal hydrations.* B c P. Schmidt, P. Kaesberg, and W.W. Beeman,Biochim., Biophys. A d a . , 19.54,14, 1 BERNAT, AND CARLISLE. 403Vitamin B1,.-Although vitamin B,, is not mainly a polypeptide thiswork is relevant both as a landmark in X-ray crystallography and as pro-viding information on the packing of residues in complex molecules. Whatis probably the most important X-ray investigation being carried out at themoment is that by Dr. Crowfoot Hodgkin and her schoo1.166 Almost thecomplete structure of a degradation product of the vitamin, a hexacarboxylicacid,I67 has now been determined. The 73 atoms in the molecule (Fig. 5)have been located from three-dimensional structure analyses and althoughit is not possible at this early stage to pick out double bonds it is neverthelesspossible to suggest a likely chemical formula for the degradation product,which provides a solution of the larger part of the chemical structure ofvitamin B,, now in progress. Main points arising so far are : (1) the cobaltatom at the centre of the molecule is attached to chlorine on one side andcyanide group on the other and surrounded by a nucleus of 63 atoms some-what characteri3tic of type I11 porphyrins. (2) The main nucleus consistsof 4 five-membered rings, two of which are directly linked, forming an almostplanar unit. The outer ring of atoms lie alternately above and below theplane of the minor ring ; they are reduced and carry side-chains which appearto be alternately acetic acids, lying on the same side of the ring as thechlorine atom, and propionic acids on the other. Not all the substituentshave been unequivocally located but sufficient is known for the structureanalysis to be carried to a satisfactory conclusion. There is confirmation ofthe same nucleus being present in vitamin BIZ. It appears that an exchangereaction occurs during the formation of the acid, the nucleotide in thevitamin being at the site of the cyanide group in the degradation product.With this reorientation it has been possible to identify the same groupingsin the vitamin, except for the lactam ring in the acid, which is representedby a free acetamide residue. A tentative complete structure correspondingto the empirical formula C,,H,oOl,N,,PCo has been put forward.168J. D. BERNALC. H. CARLISLE.D. C. Hodgkin, J. Peckworth, J . H. Robertson, K. N. Trueblood, R. J. Prosen,and J. G. White, Nature, 1955, 176, 326; Cf. J. C . Speakman, Ann. Reports, 1954, 51,399.16' J. R. Cannon, A. W. Johnson, and A. R. Todd, ibid., 1954, 174, 1168.168 D. C. Hodgkin, A. W. Johnson, and (Sir) A. R. Todd, Chem. SOC. Special Publ.,1956, No. 3, p. 109

ISSN:0365-6217    

DOI:10.1039/AR9555200380

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

INDEX OF AUTHORS’ NAMES.Abdine, €3.. 351.Abe, T., 67.Abe, Y., 92, 192, 193.Abeck. W., 120.Abel, E., 8, 28.Abell, J., 184.Abhyankar, S. M., 296.Abisch, L., 300.Abraham, E. P., 278, 279.Abricosova, I. I., 57, 69.Abugov, D. I., 15.Abu-Nasr, A. M., 302.Achaya, K. T., 296.Acheson, R. M., 239.Achtzehn, G., 160.Aclter, L., 264.Ackman, R. G., 241.Aconsky, L., 366.Acquista, N., 83.Adair, D., 67.Adams, G. A,, 260, 261,262, 267.Adams, J. A. S., 366.Adams, P. B., 364.Adams, P. T., 304.Adsms, R., 137.Adams, R. N., 361.Adams, W. J., 209, 210,Adcock, D. S., 65.Addor, R. W., 181.Adler, D. G., 13.Adler, S. J., 28.Aebi, A., 194.Aeschlimann, J. A.. 233.Affsprung, H. E., 364.Agawa, T., 313.Agganval, J. S., 165, 296,Agius, P.J., 10.Agnello, E. J., 209.Agnew, W. G., 89.Agren, A., 96.Ahlers, N. H. E., 306, 308.Ahrens, E. H., 297.Ahrland, S., 96.Aignesberger, A., 113, 11 8.Aihara, T., 312.Ainsworth, C., 233.Aitken, €3. A. A., 291.Akabori, S., 277.Akerlind, L., 75.Akour, A. A., 313.Albert, A., 234, 240.Albert, P., 371, 376.Alberti, C . G., 218, 219.331.308.Albrecht, A. C., 78.Albrecht, A. M.. 240.Alder, B. J., 62, 63, 64, 90.Alder, K., 184.Aldrich, L. T., 374.Aldrich, P. E., 248.Aleshkiaa, N. N., 366.Alexander, B. H., 269.Alexander, P., 49.Alexander, W. J., 42.Alfrey, T. A., 150.Aliyev, A. A., 15.Allan, G. G., 200, 205.Allan, J. L. H., 137, 164.Allen, A. O., 44, 47.Allen, C. E., 291.Allen, G., 86, 87.Allen, P.L., 360.Allen, P. W., 36,Allen, R. R., 302.Allen, W. S., 157, 209,212, 214, 219, 220.Allerton, R., 258.Allin, E. J., 88.Allinger, N. L., 184.Allinson, R., 48.Allison, H. W., 52.Almassy, G., 367, 36b.Alper, T., 48.Alpert, N. L., 83.Alt, G. H.. 207.Amano, H., 346.Ambrose, E. J., 385, 387,Ambrose, J., 48.Ames, D. E., 306.Ames, S. R., 164.Amiard, G., 226, 230, 280.Amin, El S., 267.Aminoff, D., 337.Amis, E. S., 31, 366.Amstutz, E. D., 136.Ananchenlco, S. N., 229.Anatol, J., 280.Anbar, M., 29.Anchel, M., 310.Anderegg, G., 96.Anderegg, J. W , 401.Andersen, R. B., 368.Andersen, W., 283.Anderson, A. B., 263.Anderson, A. G., 180.Anderson, D. M. W., 265.Anderson, J. H., 91.Anderson, J. R., 54.Anderson, L., 257.388.40.5Anderson, L.C., 49.Anderson, R. A , 275, 277.Anderson, R. C., 18, 43.Anderson, R. E., 375,Anderson, R. W., 291.And&, E., 295, 313.Andreeva, N. S., 388.Andrews, A. C., 96.Andrews, E. B., 75.Andrews, L. J., 138.Andrews, P., 263, 267,Andreyev, D. N., 45.Anet, E. F. L., 162.Anet, F. A. L., 249.Anfinsen, C. B., 394.Angell, C. L., 87.Angier, D. J., 38.Angyal, S. J., 185, 257.Ankudimova, E. V., 352.Anliker, R., 215, 216, 217,Anner, G., 215, 229.Anthony, W. C., 238.Antler, M., 108.Antoniades, H. N., 369.Antony, V., 120.Anziani, P., 139.Aparicio, F. L. J., 138.Araki, C., 267.Archer, R., 279.Arcus, C. L., 139,189.Ard, W. S., 42.Arigoni, D., 184, 202, 203,Arima, K., 213.Ariya, S.M., 121.Arlman, E. J., 37.Armen, A., 236.Armitage, J. B., 311.Armstrong, D. A., 23.Armstrong, R., 253,Arnaud, A., 311.Arnaud, P., 167.Arndt, U. W., 383, 394,Arnold, C.. 155.Arquette, G. J., 342.Arroyave, G., 318.Arth, G. E., 216, 228.Arthington, W., 272.Asahina, Y., 235.Asai, M., 85.Asami, T., 366.Ashley, B. D. 300.376.268.221.225.398406 INDEX OF AUTHORS’ NAMES.Ashley, J. N., 286.Ashmore, P. G., 12, 16.Ashton, G. C., 373.Asmis, H., 246.ASperger, S., 32.Aspinsll, G. O., 262, 263,Asselineau, J., 304.Astbury, W. T., 381, 386,Astle, M. J., 232.Astrup, T., 282.Astwood, E. B., 290, 292,Atchison, G. J., 376.Athavale, V. T., 347.Atkin, W. R., 388.Aubert, J. P., 270,Aubry, A., 139.Audrieth, L.F., 110, 111.Aulenbach, V. B., 358.Ausloos, P., 21, 22.Avaluan, S., 274.Avasthi, B. K., 313.Avivi, P., 374.Avrahami, M., 32.Axelrod, J. , 320.Axelrod, L. R., 318, 326.Ayant, Y., 91.Ayer, W. A., 190.Aylett, B. J., 106.Aymonino, P. J., 25.Aynsley, E. E., 119.Ayres, G. H., 128.Ayrey, G., 372.Ayscough, P. B., 22.Biiik, T., 99.Baalsrud, K. S., 309.Babanova, N. P., 220.Babko, A. K., 96.Bach, N., 48.Bach, S. R., 166, 230.Bachelor, F. W., 304.Bacher, F. A., 372.Back, R., 35.Backus, R. C., 399.Bacon, J. S. D., 264, 335.Bacon, R. G. R., 36.Badami, G. N., 14.Baddeley, G., 134, 135,136, 141, 142, 143.Bader, F. E., 248.Badger, G. M., 231.Badoche, M., 230.Badoz-Lambling, J., 363.Badran, N., 237.Rachli, E., 246.Bahr, G., 96, 103, 356.Baehr, H.D., 60.Baenziger, N. C., 127, 375.Baer, H. H., 255, 256,258, 334, 335, 337.I3agg, J., 51.Raggett, B., 330.Sagnall, K. W., 119.Baguley, M. E., 241.264, 266, 268, 270.388, 389, 390, 395.293.Bai, N. S., 313.Bailey, A. S., 304.Bailey, G. C., 53.Bailey, J. L., 278.Bailey, K., 382.Bailey, T. L., 43.Bailey, W. G., 172.Bailey, W. J., 161, 163,167, 181.%in, O., 84.Bak, B., 81.Baker, A. W., 84.Baker, B. B., 367.Baker, B. R., 250.Baker, B. W., 165, 305.Baker, E. B., 90.Baker, L. C. W., 121.Baker, M. J., 353.Baker, M. McD., 51, 52.Baker, P. R. W., 354.Baker, R. G., 300.Baker, R. W. R., 365.Baker, W., 173, 174, 176,Bakhareva, I. F., 8.Balch, C., 238.Baldridge, R.C., 287, 289.Baldwin, E., 263.Baldwin, R. R., 16.BalenoviC, K., 275.Baliga, B. P., 296.Ball, D. H., 267, 268.Ballard, A. E., 375.Ballard, D. G. H., 40, 282.Ballass, J. I., 108.Ballhausen, C. J., 80.Balloffet, G., 73.Ballou, E. V., 67.Balmat, J. L., 358.Baltazzi, E., 232.Baltes, J., 311.Ralz, G., 118.Bsmford, C. H., 33, 40,91, 282, 385, 387, 389.Banerjee, A. K., 97.Banerjee, M. K., 90.Bank, C. A., 344.Banks, C. V., 96, 342.Banks, R. E., 355.Bannard, R. A. B., 211.Bannister, B., 228.Banus, M. D., 97.Banyai, E., 366.Baran, J. S., 243.Baranauckas, C. F., 175.Barb, W. G., 29, 37. 39.Barber, G. W., 329.Barbour, J. B., 225.Barcelb, J. R., 83.Barcia Goyanes, C., 374.Barclay, R. K., 399.Bardwell, J., 14.Barendrecht, E., 360.Barger, G., 286.Barkemeyer, H., 240.Barkenbus, C., 231.Barker, C.C., 373.233.Barker, G. R., 256.Barker, J . A,, 62, 64.Barker, M. H., 292.Barker, S. A., 85. 147, 264,Barkley, L. B., 227.Barnard, D., 372.Barnard, G. P., 374.Barnard, K. A., 239.Barnes, C. S., 225.Barnes, R. A., 170.Barnes, R. G., 92.Barnett, A. J. G., 301.Barney, D. L., 112.Baron, C., 213.Baron, H., 368.Barr, C. E., 39.Barraud, G., 139, 185.Barriault, R. J., 59.Barron, T. H. K., 57.Barrow, G. M., 83.Barrow, R. F., 74, 75, 76.Barry, C., 270.Barry, V. C., 256, 257,Barsh, M., 30.Bartlett, A. F. I?., 54.Bartlett, M. F., 253.Bartlett, P. D., 145, 167.Bartlett, R. G., 289.Barton, A. D., 272.Barton, B. S., 291.Barton, D.H. R., 146,156, 173, 190; 193, 194,199, 203, 204, 207, 212,225, 237, 329.Basile, L. J., 100.Basile, R., 378.Basolo, F., 27, 98.Batchelor, F. W.. 231.Bates, T. H., 45.Batres, E., 219.Batten, J. J., 14.Battersby, A. R., 238.Baudler, M., 85, 1 13.Bauer, A. W., 265.Bauer, E., 8, 234.Bauer, F. C., 301.Bauld, W. S., 218, 327.Baum, G., 258.Baum, H. A., 265.Baumann, E. J., 291.Baumann, W., 190.Baumgarten, H. E., 240.Baumgartner, G., 215.Baurer, T., 45.Bautze, M., 257.Bawn, C. E. H., 29, 35.Baxendale, J. H., 28, 29.Baxter, J. G., 164.Baxter, J. N., 85.Bayer, E., 96.Bayliss, N. S., 88.Beal, P. F., 208, 214.Beamer, W. H., 376.Bear, P. S., 390.Bear, R. S., 386, 389.269.260INDEX OF AUTHORS’ NAMES.407Beaton, J. M., 200, 203,Beattie, J. A., 59.Beatty, P. M., 22.Beauchene, R. E., 364.Beaussier, J., 24.Beaven, G. H., 136.Beavers, L. E., 239.Becher, H. J., 87.Bechlars, F.. 233.Bechtold, M. F., 39.Beck, C. W., 314.Beck, M. T., 368.Becker, E. I., 150, 175.Becker, E. J., 211.Becker, H., 114.Becker, H. J., 102, 274.Becker, J. A., 52.Becker, R. S.. 79.Beckert, O., 130.Beckett, A. H., 171.Beckmann, P., 172.Beecher, L., 85.Beeman, W. W., 383, 401,Beer, R. J . S., 238.Beevers, H., 316.Behre, J. A., 288.Behrens, H., 114, 125.Belcher, R., 341, 350, 353,Belemans, A., 64.Belf, L. J., 107.Bell, D. J., 256, 263, 266,Bell, E., 355.Bell, F., 137.Bell, F. O., 389, 390.Bell, J. M., 292.Bell, P.H., 280.Bell, R. P., 26.Bell, T. N., 12.Bellamy, L. J., 84, 85.Bellino, A., 345.Bello, J., 161.Ben-Aim, R., 17.Bendas, H., 199.Bender, P., 83.Benedetti-Pichler, A. A.,Benedict, S. R., 287, 288.Benedict, W. S., 89.Bengough, W. I., 33, 35.Bengtsson, E. B., 234.Benjamin, B., 82.Benkeser, R. A., 155, 156,Rennet, J. M., 73.Bennett, A. L., 15.Bennett, G. J., 189.Bennett, J. E., 91.Bennett, W., 46.Benoist, S., 74.Benoiton, L., 273.Benson, S. W., 8, 61.Bentley, K. W., 242, 264.Bentley, R., 148.204, 205.402.356.269.347.168, 180.Benton, D. P., 57, 66, 68,Berding, C., 282.Berenson, G. S., 260.Berg, A.-M., 272, 273.Berg, B. N., 330.Berganstal, D. M., 324.Bergelson, L. D., 229.Bergeon, R., 59, 60.Berger, A., 40, 281, 388.Berger, A.W., 60.Berges, L. S., 365.Bergh, A., 8.Bergstrom, S., 213, 306,312, 316, 322, 331.Beringer, F. M., 169.Berlinguet, L., 274.Bernal, J. D., 399, 401.Bernal-Nievas, J., 365.Bernard, W. J.. 107.Bernauer, K., 236.Berneking, A. D., 364.Bernhard, K., 300.Bernhardt, D. N., 353.Bernhart, F. W., 337.Bernheim, F. , 30 1.Bernier, J. P., 44.Bernstein, H. J., 8, 84, 87.Bernstein, R. B., 11, 83.Bernstein, S., 157, 209,210, 212, 214, 218, 219,220.Bernstein, W., 44.Beroza, M., 237.Berry, P. J., 49.Berse, K., 197.Berson, J. A., 234.Berthet, G., 91.Berthold, H. J., 116.Berthold, W., 121.Beton, J. L., 202, 236.Bett, K. E., 59.Bettelheim, F. K., 284.Bevilacqua, E. M., 42.Bevington, J. C., 35, 36,372, 373, 378.Beydon, J., 373.Beyerman, H.C., 243.Beyler, R. E., 209, 216,Bezuglyi, V. D.. 360.Bhar, B. N., 90.Bhargava, P. M., 171.Bharucha, K. E., 301.Bharucha, K. R., 213.Bhatnagar, M. P., 99.Bhattacharya, A. K., 69.Bhattacharyya, S. C., 195.Bianchi, G. C., 291.Bianco, E. J., 160.Bickel, H., 246.Bickford, W. G., 306.Bieber, T. I., 174, 233.Bieler, A., 151.Bielig, €1. J,, 96.Bieling, H., 356.Bierman, A., 69.69.220.Bies, D. A., 25.Biez-Charreton, J., 300.Bigeleisen, J. , 11.Bigg, P. H., 339.Biggs, M. W., 330.Bijl, A., 62.Bijvoet, J. M., 275.Bill, P. T., 88.Billeter, J. R., 215.Binks, R., 238.Binte, H.- J., 257.Birch, A. J., 170, 190,Birch-Andersen, A., 282.Bird, C. W., 140, 211.Bird, G.R., 136.Bird, R. B., 56, 60.Birdsall, C. M., 60.Birdwhistell, R. K., 98.Birkinshaw, J. H., 162.Birmingham, J. M., 130,Birnbaum, S. M., 275.Biryuk, E. A., 367, 368.Bischoff, I?., 212.Biserte, G., 277.Bishop, C. T., 261, 262,Bissel, A. , 293.Bisset, K. A., 333.Bissot, T. C., 101.Bitner, J. L., 85.Bittker, D. A., 11.Bjerrum, J., 27, 80.Blacet, F. E., 20.Black, E. D., 357.Black, H. K., 311.Blackall, E. L., 147.Blackburn, P. E., 106.Blackwell, D. E., 86.Blades, A. T., 11.Bladon, P., 213.Blair, A. E., 48.Blair, J., 170, 236.Blakely, R. M., 291.Blank, R. H., 209.Blanz, E. J., 183.Blatz, P. S., 13.Bleaney, B., 91. .Blevins, G. S., 82.Bloch, H., 304.Bloch, K., 330, 332.Bloch, L., 370.Block, B.P.. 97.Blamer. J., 108.Blom, L., 352.Blomeyer, F., 218.Blomquist, A. T., 163,Bloom, A. L., 90.Bloom, B. M., 209.Blout, E. R., 86, 282.Bluhm, H. F., 159.Blum, F., 291, 292.Blum, W. P., 164.Blumer, O., 113.Blumrich, W., 106.195, 237.180.267.181, 183408 INDEX OF AUTHORS’ NAMES.Boardman, N. K., 283.Boarland, M. P. V., 175.Boarland, V., 156, 171,Boatman, S. G., 297.Boaz, H., 232.Boaz, H. E., 248.Bobrova, M. I., 359.Bobtelsky, M., 105, 113,Bockris, J. O’M., 66.Bode, H., 340.Bode, K., 195.Bodor, E., 351, 369.Boedtker, H., 284.Boekelheide, V., 242, 249.Boltz, G., 366, 367, 368.Boerboom, A. J. H., 60.Bottcher, R., 130.Bogan, E. J., 347.Bogdanov, N. A., 379.Bogert, M. T., 146.Bogle, G. S., 91.Bognhr, J., 348.Bohlmann, F., 162, 163,Boissonnas, R.A., 277,Boit, H.-G., 252.Boivinet, P., 379.Bokelmann, E., 281.Boldingh, J., 297.Boldingh, J. A., 297.Boley, A. E., 372.Bolgiano, N. C., 163.Bolley, D. S., 301.Bolt, G. H., 66.Boltz, G., 365.Bond, G. C., 50, 63.Bond, R. D., 350.Bonet-Maury, F., 48.Bonitz, E., 103.Bonnet, R., 242.Bonsack, J. P., 345, 369.Boord, C. E., 180.Booth, F., 67, 70, 391.Boozer, C. E., 35.Boreham, G. R., 180.Borland, J. R., 291.Borlaug, E. T., 162.Borman, A., 207, 209,Borrows, E. T., 37.Bos, C. J., 316.Bose, S., 154, 246.Boser, H., 276.Bosshard, H., 203.Bosworth, R. C. L., 51.Bothner-By, A. A., 182.Bottenbruch, L., 259.Bottle, R. T., 265.Bottomley, W., 196, 296.Botzen, A., 62.Bouaziz, R., 97.Bouberlova-Kosinova, L.,Bouby, L., 48.182.364.309, 310.279.323.359.Boudart, M., 7, 54.Boughton, B.W., 305.Bounds, D. G., 165, 305.Bourne, E. J., 85, 147,255, 256, 264, 269.Bourns, A. P., 230.Bouthillier, L. P. 264,Bouveng, H., 257.Bovey, F. A., 32, 38.Bowen, E. J., 79.Bower, J. D., 239.Bowers, K. D., 91.Bowers, S. D.; jun., 30.Bowman, R. E., 305.Boyd, D. R. J., 83.Boyd, F. R., 113.Boyd, T. F., 372.Boyer, J. I%, 232, 234.Boyer, N. E., 232.Boyer, P. D., 302, 316.Boyle, J. W., 47.Brackman, W., 158.Bradacs, L. K., 372.Brade, H., 135.Brading, J. W. E., 267.Bradley, D. C., 108, 115.Bradlow, H. L., 221.Bradshaw, W., 361.Bradsher, C. K., 221, 239.Bragg, (Sir) L., 391.Bragg, W.L., 383, 384,Branch, R. F., 85.Brand, J. C. D., 76, 87.Brandes, R. G., 52.Brandt, C. W., 189, 196.Brandt, W. W., 98, 127,Brannock, W. W., 364.Branscornb, L. M., 43.Bratoi, S., 89.Braude, E. A., 133, 134,161, 167, 226, 231, 304.Brauer, G., 106. 109, 114.Braun, G. A., 335, 337.Braunitzer, G., 399.Bray, P. J., 92.Bray, R. H., 366.Bree, A., 79.Breil, H., 38.Breitenbach, J. W., 34.Bremson, H. R., 381.Brenner, M., 280.Brenner, R. R., 313.Bresadola, S., 30.Brett, R. A., 306.Brewer, G. A., 232.Brezina, M., 359.Brice, C., 148, 256.Bridges, R. G., 374.Bridgman, P. W., 111.Briegleb, G., 79.Brierley, J. S., 59.Briggs, L. H., 180.Brignani, G., 126.Brink, N. G., 216.273.393.367.Briner, E., 46.Brini, M., 84.Brinton, R.K., 20.Brintzinger, H., 27.Bristow, G. M., 42.Britton, D., 59.Brix, P., 73.Brixner, L., 99, 121.Broadhead, G. D., 180.Brocklehurst, B., 79.Brockmann, H., 164, 256.Brodersen, P. H., 74.Brodie, B. B., 320.Brodskii, A. I., 24.Broida, H. P., 115.Brokaw, G. Y., 297.Brook, M., 74.Brooks, C. J. W., 205.Brooks, R. V., 217.Brooks, W. V. F., 86.Brooksbank, W. A.. 375.Broquist, H. P., 240.Brough, J. N., 169.Brout, R., 64.Brown, B. R., 153.Brown, C., 60.Brown, C. A., 101.Brown, D. J., 235.Brown, D. W., 38, 41.Brown, E. G., 349.Brown, F., 118, 122, 366.Brown, H. C., 135, 140,141, 145, 154, 155, 234.Brown, I., 66.Brown, J. A., 184.Brown, J. B., 296, 301.Brown, J. J., 170.Brown, J.K., 87.Brown, L., 385, 389.Brown, L. A., 41.Brown, L. O., 43.Brown, R. F. C., 244, 245.Brown, S. C., 34.Brown, W. G., 373.Brown, W. H., 241.Brownie, A. C., 319, 324.Brownlie, G., 205.Brubaker, C. H., 110.Bruce, D. B., 174.Bruce, G. T., 269.Bruce, J. M., 170.Bruckner, V., 282.Bruckner, K., 218, 226,Bruesch, J., 153.Briigel, W., 81.Bruschweiler, H., 360.Bruja, N. Z., 358.Brunisholz, G., 104, 113.Brunneck, E., 118.Brunner, R., 246.Brunnstrom, G., 174.Bruno, M., 30.Bruson, H. A., 293.Bruun, T., 162, 194, 205,206, 309, 310.Bryant, J. M., 345.227INDEX OF AUTHORS’ NAMES. 409Buchanan, A. S., 68.Buchanan, D. J., 336.Buchanan, R. F., 376.Bucher, N. L. R., 332.Buchschacher, P. , 255.Buchy, A., 292.Buckingham, A.D., 58,Budwig, J., 300.Biichele, F., 232.Buchi, G., 182.Buchi, W., 269.Bues, W., 88.Buff, F. P., 64.Buhs, R. P., 232.Bukata, S. W., 83.Bulmer, F. M. R., 287.Bu’hck, J. D., 162, 173,Bulovova, M., 358.Bumpus, F. M., 278, 279.Bundersmann, H., 147.Bunker, D. L., 136.Bunn, C. W., 387.Bunnett, J. F., 150.Bunton, C. A., 30, 147.Burch, F. H., 339.Burge, R. E., 391.Burgstahler, A. W., 153,Burgoyne, J. H., 14, 16.Burke, D. C., 166.Burke, H. J., 90, 181,Burkhard, D. G., 82.Burnett, G. M., 34, 38.Burn, D., 198.Burns, J. F., 43.Burns, W. G., 44.Burbn, A., 336.Burris, C. T., 31.Burrus, C. A., 82.Burstein, S., 209, 326.Burtle, J. G., 373.Burton, C. A., 24.Burton, D., 39. €3;3~;: & D., 356.., 45, 47, 40.Burtt, B.P., 45, 347Burwasser, H., 14.Burwell, R. L., 53, 54.Buscarons, F., 366.Bush, I. E., 207.Busing, W. R., 86.Buss, w., 348.Butenandt, A., 164.Butler, K., 270.Buu-Hoi, Ng. Ph., 168,304, 309.Buyle-Bodin, M., 91.BUZ~S, L., 351.Byers, S. O., 330.Bywater, S., 35, 42.Cadbury, W. E., 97.Cadle, I<. D., 71.Cahn, A., 141, 234.62.310, 311.184, 104.185.Cahn, R. S., 191.Caimann, V., 364.Cala, J. A., 83.Calas, R., 188.Caldenvood, R. C., 308.Caldin, E. F., 26.Cali, P. J., 376.Callear, A. B., 19, 21.Callis, C. F., 90.Callomon, J. H., 76.Callow, R. K., 222.Calvet, E., 379.Calvin, M., 281, 304.Camerino, B., 218, 219.Cameron, A. F. B., 223.Campbell, A., 304.Campbell, I. G. M., 171.Campbell, J.A., 213.Campbell, M. E., 368.Campbell, P. N., 276.Campbell, W. G., 263.Campbell, W. J., 372.Canjar, L. N., 59.Cannan, R. K., 374.Canning, J. , 65.Cannon, C. G., 85.Cannon, J. R., 242, 403.Cant, E. M., 389.Canter, F. C., 234.Caputto, R., 335.Cardinaud, R., 31.Cardwell, H. M. E., 191,Carl, H. F., 372.Carlisle. C. H.. 395. 401.242, 254.Carlsmith, L. A., 160.Carmack, M., 243, 250.Carnahan, J. E., 151.Carnmalm, B., 237.Caron, M., 376.Carpenter, F. H., 277.Carrick, W. L., 31.Carrington, H. C., 236.Carrol, P. K., 74.Carroll, W. R., 394.Carruthers, C., 360.Carsiotis, M., 322.Carstrom, D., 390.Carter, J. R., 359.Case, I;. H., 133.Casey, J. J., 105.Casimir, H. B. G., 57.Cason, J., 304.Caspar, D., 400.Cass, R.C., 96, 174.Cassidy, H. G., 297.Castelfranco, P., 315.Casu, B., 208.Cattaneo, P., 313.Caughey, W. S., 241.Cava, M. P., 175.Cavalca, L., 105.Cavard, R., 270.Cave-Brown-Cave, J .Cawley, J. D., 164.Cawthon, T. M., 87.270.E.,Ceccaldi, Y. F., 300.Cecil, R., 361.Celechovskq, J., 368.Cellini, R. F., 367.Celmer, W. D., 329, 310.Cerar, D., 275.Ckrecs, A., 295.Cermak, J., 32.Cerny, V., 224.Ceschino, F., 60.Chabbal, R., 82.Chabarek, S., 96, 340.Chadha, M. S., 246.Chadha, R. N., 37.Chadwick, J., 135, 142,Chaiet, L., 232.Chakrabarty, M. M., 313.Chakrsburtty, A. K., 368.Challenger, F. , 272.Challenger, G. E., 47.Challinor, S. W., 268.Challis, H. J. G., 368.Chalmers, B., 376.Chambers, G., 24.Chambers, R.W., 277.Champ, P., 346.Champetier, G., 39.Chance, B., 320, 322.Chancel, P., 85.Chang, S. S., 302.Channon, H. J., 332.Chapiro, A., 48, 49.Chaplen, P., 162.Chapman, J. H., 216.Chapman, N. B., 234.Chargaff, E., 398.Charlesby, A., 33, 42, 49,Charlson, A. J., 267, 268.Charney, W., 208.Charnley, A., 60.Chart, J. J., 329.Chase, B. H., 293.Chase, M. W., 336.Chatt, J,, 94, 96, 128.Chatterjee, A., 246.Chatterjee, S. R., 37.Chatterji, A. C.. 120.Chattoraj, D. K., 67.Chaudhuri, N., 229.Chaudron, G., 371, 376.Chauvet, J., 279.Chechak, A. J., 164.Chechinkin, M. I., 313.Cheesman, G. H., 65.Cheftel, R. I., 301, 313.Chemerda, J. M., 200.Chen, C. T.. 213.Chen, C. Y., 71.Chen, W. T., 113.Chen-Chuan Tu, 42.Cheng, K.L., 351, 366,Cher, M., 28.Cheshev, K. S., 346.Chesney, A. M., 291, 292.143.378.369410 INDEX OF AUTHORS’ NAMES.Choate, W. L., 394.Chopin, J.. 213.Chopra, N. M., 192, 193.Chow, T. J., 365.Choudhury, B. K., 67.Chowdhury, D. K., 313.Chowdhury, R. B., 301.Childers. E., 301.Childs, E. C., 66.Ching-I Niu, 304.Chinn, L. J., 228.Chirkov, N. M., 16.Christensen, B. E., 85.Christensen, G. M., 238.Christian, J. E., 360.Christian, R. H., 59, 74.Christiansen, J. A., 28.Christiansen, P. K., 309,Christie, M. I., 23.Chupka, W. A., 106.Cifonelli, J, A., 264.Cihalik, J., 358.Cipera, J. D., 274.Cipra, A., 291.Claff, C. E., 168.Clagett, C. O., 170.Clandon, M. M., 139.Clar, E., 171, 172.Clark, A., 53.Clark, H.C., 95.Clark, I:, 215.Clazk, L. C., 279.Clark, M. T., 138, 150.Clark, R. H. 337.Clarke, E. M., 43.Clarke, F. H., 195.Clarke, N., 233.Clarke, R. L., 209.Clark-Lewis, J. W., 236.Clauson-Kaas, N., 230.Clawson, T. A., 291.Clayton, R. B., 332.Cleare, B. E., 180.Cleaver, C. S., 232.Cleaver, G. C., 32.Clegg, H. P., 59,Clement, R. A., 151.Clemente, J . , 2 12.Clemo, G. R., 194.Clerc-Bory, G., 238.Clerc-Bory, M., 238.Cleveland, F. F., 83, 84.Cluley, H. J., 346, 366.Clusius, K., 30, 75.Cmelik, S., 304.Coates, G. E., 96, 103.Coats, F. H., 43.Cobb, R. L., 238.Cobbett, W. G., 347.Cocker, W., 191, 192, 193,Cochran, W., 381, 385.Codell, M., 358, 366.Coffey, R. S., 177.Cohen, C., 389, 390.Cohen, D., 27, 122.310.194, 198.Cohen, E.G. D., 62.Cohen, M. H., 91.Cohen, M. P., 310.Cohen, T., 234.Cohen, V. W., 91.Cohn, H., 87.Colclough, T., 102.Cole, A. R. H., 88, 196.Cole, S., 46.Cole, W., 210.Cole, W. E., 147.Cole, W. F., 99.Coleby, B., 48.Coleman, D., 387.Coleman, G. H., 172, 181.Coleman, J. E., 302.Collat, J. W., 368.Collier, H. E., 345.Collier, R. E., 351.Collin, J., 43, 88.Collins, I?. D., 164.Collins, R. F., 238.Collinson, E., 46, 40.Colombi, L., 167.Colowick, S. P., 320.Colpa, J. P., 88.Colvin, J. R., 260.Combe, A., 13.Comber, R., 297.Combs, G. F., 338.Comings, E. W., 60.Commerford, S. L., 380.Commoner, B., 401.Compagnon, P., 230.Conbere, J. P., 274.Condylis, A., 359.Connally, R.E., 375, 378.Conrad, H. E., 262, 269.Constantin, J. M., 220.Contopolou, R., 315.Cook, C. L., 311.Cook, D., 58.Cook, J. W., 242.Cook, W. H., 260.Cooke, A. H., 91.Cooke, N. J., 302, 303.Cooke, R. G., 172.Cookson, R. C., 140, 170,184, 208, 211.Cooley, G., 218.Cooley, S. D., 18.Cooper, C. D., 78.Cooper, J. R., 320.Cope, A. C., 182, 183.Copeland, C. S., 61.Copestake, T. B., 27.Copp, F. C., 240.Corbett, J. D., 105.Corbett, W. M., 265.Corbridge, D. E. C., 85,112.Corcoran, J. W., 218.Zorcoran, W. H., 33.Zordes, J . F., 99.Cordon, M., 156.Corey, E. J., 90, 181, 184,185, 191, 200, 202, 205,213.Corey, R. B., 381, 383,385, 386, 387, 389, 395,396.Corish, P. J., 84.Cormack, D. V., 44.Cormier, M., 139, 185.Cornforth, J.W., 227.Cornubert, R., 139, 185.Corrodi, H., 178, 255.Corson, B. B., 53.Corval, M., 84.Corwin, A. H., 241.Cosgrove, J. F., 375.Costanza, A. J., 34, 37.Cotter, R. J., 182.Cottin, M., 46.Cotton, E., 110.Cotton, F. A., 87, 94, 130,Cotton, K. J., 58.Coulon, R., 88, 89.Coulson, C. A., 57, 132.Courtoy, C. P., 83.Cowan, P. M., 388, 389,Cowles, E. J., 180.Cox, R. A., 42.Coyle, T. D., 11.Cozzi, D., 115.Crabbe, P., 188.Crabtree, J. M., 97.Craig, D. P., 24, 77, 78.Craig, J. T., 373.Craig, L. C., 278, 297.Craighead, P. W., 107.Cram, D. J., 156, 184.Crampton, C. F., 398.Crandall, J. L., 36.Craubner, H., 30.Crawford, B., 83, 86.Crawford, C. M., 365.Crawford, G. H., 123.Crawford, M., 139.Crawhall, J.C., 278.Crawshaw, A., 214.Cremlyn, R. J. W., 214.Crew, M. C,, 144.Crick, F. H. C., 381, 383,385, 386, 389, 393, 394,395, 397, 398.Crimmin, W. R. C., 96.Cnstol, S. J., 31, 184.Croall, I. F., 50.Crombie, L., 162, 164, 165,166, 297, 303, 306, 311,312.Crombie, W. M. L., 297.Cropper, F. R., 300.Cross, B. E., 193, 194, 198.Cross, B. G., 331.Zross, P. C., 81.3ossley, A., 164, 305.Srosswhite, H. M., 73.zrouthamel, C. E., 368.Zrow, W. D., 243.Srowfoot, D., 227.3uickshank, A. J. B., 56.180.390Cruse, K., 362.Csendes, E., 281.Csiszar, B., 368.Cuker, E., 358.Cullis, C. F., 13, 28.Culvenor, C. C. J., 253.Cummings, G. A. McD., 8.Cunningham, G. L., 123.Curd, F. H. S.. 235.Curl, R.F., 61.Curran, C., 95.Curran, S. C., 376.Cuta, F., 362.Cuthbertson, F., 355.Cutler, R. A., 146.Curti, R.. 126.Curtin, D. Y., 144.Curtis, R. F., 175.Curtiss, C. F., 56, 60.Cvetanovid, R. J., 19, 21.Cymerman-Craig, J . , 85.Czekalla, J., 79.&ern?, V., 152.Daascli, L. W., 87.Dacey, J. R., 20.Dadson, R. S.. 59.Dagron, C., 119.Dahler, J. S., 62.Dahlquist, A., 331.Dahmen, H., 123.Dailey, B. P., 82.Dainton, F. S., 16, 22, 42,Dakin, H. D., 273, 288.Dale, A. P., 313.Dale, H., 286.Dale, W. M., 48.Dalibor, H , 257.DallaValle, J. M., 72.Dalma, G., 15, 196.Damm, I<., 100.D’Amore, G., 367.Danby, C. J., 9, 18, 24.Dandegaonker, S. H., 208,Danforth, J. D., 56.Daniels, F., 9.Daniels, M., 48.Daniels, R.C., 358.Dannley, R. L., 153.Danusso, F., 35.Darnell, A. J., 108.Darwent, B. deB., 19, 21.Das, D. B., 261.Das, M. N., 11.Das, S. K., 37.Das, T. P., 90.Das Gupta, A. K., 374.Datz, S., 25.Dauben, W. G., 183, 193,Daum, K. W., 116, 124.Dautravaux, M., 277.Davenport, J. B., 300.Davenport, S. J., 71.David, H. G., 31, 59, 62.46, 49.312.194.INDEX OF AUTHORS’ NAMEDavidson, D. W., 324.Davidson, E. A., 271.Davidson, N., 28, 59.Davies, A., 331.Davies, D. S., 280.Davies, J. E., 174.Davies, M., 84.Davies, N. R., 27.Davies, P. L., 57.Davies, R. R., 239.Davis, J., 360.Davis, R. H., 306.Davis, R. J., 342.Davis, S. P., 73.Davison, W. H. T., 84, 85.Dawson, J. AI., 57, 59.Dawson, M. C., 226.De, P. K., 67.Dean, C., 92.Dean, D.O., 229.Dean, F. At., 173, 237.Dean, J. A., 364.Deatherage, F. E., 276.Deatherage, W. L., 266.Debell, A. G., 83.Debiais, L., 144.de Boer, J., 62.de Boer, N. H., 51, 66, 61,de Castro, N. F., 313.Decius, J. C., 81, 85, 86.Decker, J. W., 372.de Deken, R. H., 284.De Deken-Grenson, M., 284.Dedonder, R., 269, 270.Deflorin, A. M., 173, 237.DeFord, D. D., 340, 353.de Gaudemaris, G., 167.de Graaff, W., 59.de Groot, S. R., 62.de Hemptinne, M., 83.Dehm, H. C., 228.Dehn, J. S., 134.de Jonge, J., 39.Delahay, P., 25, 51.de la Mare, P. B. D., 30,Delaney, J. E., 365.Delaveau, P., 295.Delbourgo, R., 15.del Campillo, A., 314.de Leo, F., 345.Delbpine, M., 230.Delevaux, M., 368.Dell, R. M., 52.Della Morte, D., 220.Delong, W.A., 366.Delwaulle, M. L., 88.de Maeyer, L., 25.de Mayo, P., 212, 329.Demediuk, T., 99.Deming, Q. B., 329.Dempsey, J. N., 127.Denamur, J., 362.Denney, D. B., 178.Deno, N. C., 86.Dent, C. E., 273.62.141.41 1Denton, I. N., 26.de Paulet, A. C., 213.Derevenskikh, L. V., 12.Derfer, J. M., 180.Derjaguin, B. V., 57, 68,de Ruggieri, P., 220.Descharmes, M., 139, 185.Desmuk, G. S., 369.Desmyter, A., 64.Desnuelle, P., 277, 297.Despas, J., 39.DeTar, D. F., 8.Detoni, S., 85.Detter, A., 348.Deuel, H., 269.Deuel, H. J., 296.Devanathan, M. A. V., 65.de Villiers, J. P., 302.de Vogelaere, R., 7.de Vries, G., 161.De Vries, T., 357, 360.de Waal, H. L., 253.de Wael, J., 360.Dewar, M.J. S., 176, 238.Dewhurst, H. A., 47.de Witt, T. W., 38.D’Eye, R. W. M., 109,Dhar, S. K., 358.Diamond, J. J., 365.Diassi, P. A., 248.Diaz, R., 358.Dibeler, V. H., 43.Dick, G. P. G., 240.Dicke, R. H., 81.Dickel, D. F., 248.Dickson, D. H. W., 208,Diehl, H. W., 258.Dieke, G. H., 73, 74.Diemair, W., 264.Dienes, G. J., 50.Diepen, G. A. M., 56.Dieterle, J. M., 164.Dietrich, P., 198.Dijkolra, G., 300.Dijkstra, G., 165, 308.Dijkstra, R., 39.Dille, K. L., 85.Dillon, T., 268.Dingledy, D. P., 106.DiPaulo, F. S., 60.Dippy, J. F. J., 140, 141.Dirschel, W., 357.Dische, Z., 260.Divis, L., 343.Dix, G., 15.Dixon, A. S., 276.Dixon, J. P., 354.Dixon, R. N., 83.Djerassi, C., 153, 191, 199,203, 205, 208, 210, 211,313, 217, 248, 254, 317,323.69.119.222.Dmitriev, M.T., 24, 45.Doak, G. O., 168, 234412 INDEX OF AUTHORS’ NAMES.Dobriner, K., 209, 326, 327.Dobriner, S 222.Dobrovol’skh, N. F., 348.Dobson, N. A., 156, 311.Dodd, R. E., 21, 22.Dodonova, N. Y., 89.Dodson, R. W., 27.Dodsworth, P. G., 74.Doering, W. von E., 26,Doisy, E. A., 221.Dokoupil, Z., 61.Dokunikhin, N. S., 88.Dolezal, J. , 358.Domagk, G. F., 226.Domart, C., 296.Domb, C., 57.Donaldson, D. M., 44, 46.Donavanik, T., 238.Dondes, S., 45.Done, J., 273.Dania,. R. A., 213.Donn, H. V., 159.Donnelly, H. G., 60.Donohue, J., 383, 395.Donovan, F. W., 191.Donovan, R. E., 89.D’Or, L., 88.Dorfman, A., 260.Dorfman, L., 247, 248.Dorfman, L. M., 43, 45.Dorfman, R.I., 209, 313,318, 320, 321, 326, 329,330.Dornow, A., 153.Doroslovacki, I., 363.Dose, K., 276.Dostrovsky, I., 30.Doty, P., 282, 284,Douglas, A. E., 73, 74,Douglas, B., 243.Douglas, H. W., 67.Douglas, J. E., 25.Doumerc, J., 377.Dow, D. S., 291.Dowden, D. A., 50.Downey, T. A., 358.Downie, A. R., 83.Downie, T. C., 180.Downing, G., 232.Dows, D. A., 84, 86, 89.Doyle, F. P., 232.Draganic, I., 44,Drago, R. S., 110.Drawert, F., 232.Dreesen, G., 65;.Dreiding, A. S., 183, 185,Dreiding, J., 203.Dreike, A., 307.Dresia, H., 378.Dressler, K., 74.Dreux, J., 230.Drever, R. W. P., 376.Drexler, M., 169.Drummond, A. Y., 28.178.75.210.Dry, L. J., 253.Duchesne, J., 77, 92,Duckworth, A., 158.Dudman, W.F., 270.Duff, R. E., 74.Duff, S. R., 198.Duffield, W. D., 365.Duffin, G. F., 230.Duffus, H. J., 91.Duffus, R. J., 91.Duggen, D. E., 163.Dugger, G. L., 15..Dugleux, P., 17.Duin, H. J., 165, 308.Duke, F. R., 28.Dulin, C. I., 67, 68.Dulou, R., 188.Duncan, A. B. F., 77.Duncan, N. E., 83,Duncanson, A,, 128.Dunitz, J. D., 93, 227,Dunlap, L. H., 296.Dunn, T. M., 78.Dunstan, S., 269.Dupont, G., 188.DuprC, E. F., 306.DuPuis, T., 341.Dupuy, P., 119.Dutler, H,, 206.Dutta, N. K., 342.Dutta, R. L., 98.Dutton, F. B., 108.Dutton, G. G. S., 238.Dutton, H. J., 297.Duval, C., 342, 346, 349.Du Vigneaud, V., 274, 279.Dvoi-Ak, K., 17.Dvorszky, M., 364.Dwyer, F. P., 27.Dyer, E., 34.Dylion, C. M., 248.Dzurus, M., 101.Eadon, €3.G., 270.Eagles, B. A., 287, 288,Easter, J. W., 293.Eastham, A. M., 147.Easton, A. J., 300.Easton, J. D., 203.Ebert, J., 116.Eccot, E. N., 167.Eckardt, D., 368, 360.Eckey, E. W., 206.Eckhardt, E. R., 337.Economy, J., 163.Eddinger, C. C., 164.Eddy, C. R., 222.Eddy, L. B., 101.Edelhausen, L., 352.Edgcombe, L. J., 353.Edgell, W. F., 84, 125.Edlen, B., 73.Edsall, J. T., 284.Edward, J. T., 134, 148,192, 193, 198.401.289.Edwards, A. E., 60‘Edwards, E. G., 36.Edwards, H. D.. 82.Edwards, J. A., 253, 254.Edwards, 0. E., 173, 237.Edwards, T. E., 266.Effenberger, E., 30.Efimov, A. F., 114.Eger, C., 356.Egerton, (Sir) A., 14.Eggert, H. G., 139, 185.Eggers, D. F., 86.Ehrenberg, A., 284.Ehrenberg, L., 44.Ehrenstein, M., 320.Ehrenthal, I., 262.Ehrlich, G., 50, 52, 85.Ehrlicli, R., 208, 211.Ehrlich-Rogozinsky, S.,Eich, S., 291.Eichel, A., 244.Eid, S. A., 361.Eigen, M., 25.Eigner, E. A., 280.Eischens, R. P., 52, 66,Eisenmann, E., 125.Eisenschitz, R., 56.Eisner, U., 241, 304.Ekdahl, P. H., 330.Eley, D. D., 53.Eliel, E. L., 153, 185.Elkeles, H., 30.El Khadem, H. S., 270.Elks, J., 215, 222.Elleman, T. S., 27.Ellenburg, 3. Y., 371.Ellert, H. G., 230.Ellinger, F. H., 99.Elliott, A., 86, 384, 385.387, 388, 389, 305.Elliott, D. F., 275, 278.Elliott, W. H., 221.Ellis, B., 210, 218.Ellison, F. O., 72.Elming, N., 230.Elson, L. A., 337.Elton, G. A. H., 66, 68,Elvidge, J. A., 241.Elving, P.J., 25, 359.Elyash, L. J., 38.Emanuel’, N. M., 17.Emelkus, H. J., 84,’ 106,EmelCus, K. G., 74.Emellot, P., 316.Emerman, S. L., 183.Emery, D. J., 85.Emmett, P. H., 50.Emmons, W. D., 158, 161.Emschwiller, G., 27.Endres, G. F., 38.Endres, H., 278.Engel, B. G., 197.Engel, C. R., 210.367.87.72.113INDEX OF AUTHORS’ NAMES. 413Engel, L. L., 330.Engelbrecht, A., 113, 118.Enghag, P., 368.Englert-Chwoles, A., 64.English, J., 303.English, J. L., 113.English, W. D., 108.Entwistle, N., 311.Eppstein, S. H., 323, 332.Epstein, L. F., 60.Ercoli, A., 220.Erdey, L., 342, 351, 366,367, 369.Erdmann, H. M., 226.Erdtman, H., 189, 237.Erlanger, B. F., 274.Erlenmeyer, H., 27.Ernstein, N. E., 14.Eqhenmoser, A., 149, 176,184, 202, 208.Estok, G. K., 134.Eswaranarayana, N., 342,343.Etingof, Ye.I., 21.Ettlinger, M. G., 293, 294.Eugster, C. H., 174.Evans, D. E., 152, 213.Evans, D. F., 79.Evans, D. O., 39, 85.Evans, D. P., 143.Evans, E. A., 167.Evans, J. C., 84.Evans, J. M., 266.Evans, M. W., 14.Evans, R. B., 60.Evans, R. M., 222, 223.Everest, D. A., 109, 110.Everett, D. H., 56.Everett, G. W., 25.Ewald, A. H., 61.Ewins, A. J., 286.Exner, O., 152.Eyring, H., 26, 52, 53.Eyring, L., 105.Fabitschavitz, H., 282.Faillard, H., 335.Fairbairn, D., 313.Fairbrother, F., 42, 104.Fajkos, J., 217.Fales, H. M., 158.Falkmer, S., 291.Fallab, S., 27.Fankuchen, I., 399.Faraggi, H., 377.Farber, M., 108.Farrington, J.A., 281.Farkas, E., 203, 292.Farmer, J. B., 19.Farnham, N., 145.Farnworth, A. J., 284.Farooq, M. O., 313.Farrer, M. W., 227.Farringer, L. D., 91.Fassel, V, A., 84.Fateley, W. G., 84.Fauconnier, P., 346.Fava, A., 30.Fawcett, J. S., 22%.Fedneva, E. M., 100.Fedorov, I. A., 100.Fedorova, G. P., 368.Fedorova, T. I., 347.Fedoseev, P. N., 355.FehCr, F., 116, 117.Feigl, F., 346.Feklisov, G. I., 13.Feldman, I., 99.Feldman, L. I., 209.Feldman, T., 82.Felps, V., 369.Felton, D. G. I., 85.Feng, P. Y., 49.Ferington, T. E., 36.Fernandez, J., 82.Fernelius, W. C., 97.Fernholz, H., 207.Ferrari, A., 105.Ferraro, J. R., 109.Ferrett, D. J., 357, 358.Ferriso, C. C., 88, 115.Feuer, H., 1’53.Feughelman, M., 399.Feurer, M., 216, 228.Fiallrov, Y.A., 32, 123.Ficken, G. E., 241.Field, B. O., 157, 170.Field, F. H., 43.Fields, E. K., 231.,Fieser, L. F., 212, 213, 217,224, 321, 326.Fieser, M., 212, 213, 217,224.Figdor, S. K., 254.Fikhengol’ts, V. S., 369.Filcek, M., 114.Fildes, J. E., 353, 356.Finan, P. A., 258.Finch, F. C., 246.Fine, J., 82.Finean, J. B., 390.Finholt, A. E., 152.Firestone, D., 301.Fischer, D., 124.Fischer, E., 169.Fischer, E. O., 94, 128, 129,Fischer, W., 243.Fischer-Wasels, H., 80.Fisher, C., 373.Fishman, J., 47, 211, 248.Fittipaldi, J. C., 359.Fitts, D. D., 172.Fitzgerald, D. M., 23.5,Fitzgerald, J. S., 39, 106.Fitzgerald, W. E., 87.Fitzmaurice, W. E., 235.Flahant, J., 122.Flanders, T., 333.Flaschka, H., 349, 351,Flatt, R., 113.Flavin, M., 384.130.350.353.Fleeman, J., 50.Flengas, S.N., 25.Fletcher, H. G., jun., 258,Flis, I. E., 361.Florey, K., 209.Floyd, N. F., 276.Flynn, K. P., 376.Flynn, R. M., 370.Fock, W., 65.Fodor, G., 243.Foering, L., 12.Forland, T., 104.Fogg, P. G. T., 59.Folkers, K., 231, 232, 242,Folkes, B. F., 336.Foltz, E. W., 208.Fones, W. S., 275.Fonken, G. S., 157, 211.Forbes, E. J., 178.Forbes, J. W., 248.Forbes, W., 133.Forbes, W. F., 236.Ford, T. A., 151.Forneris, R., 83.Forrest, H. S., 240.Forster, C. I?., 346.Forsyth, G., 270.Forsyth, P. F., 48.Foster, A. B., 256, 260.Foster, G., 121.Foster, J. F., 16.Foster, L. M., 376.Foster, M. C., 373.Fowden, L., 30, 141, 229,Fowler, D.I., 273.Fox, D., 78.Fox, J. H. P., 60.Fox, M., 49.Fox, R. E., 43.Fox, R. P., 279.Fox, S. W., 277.Fraenkel, G. K., 91.Frainnet, E., 188.France, H., 241.Francis, P. G., 60.Frank, G., 105.Frank, H., 17.Franke, K. W., 289.Franke, W., 159.Frankel, M., 169, 281,Frankel, S. P., 63.Frankenburg, W. G., 55.Frank-Komenetskii, D. A.,Franklin, E. C., 110.Franklin, J. L., 43.Franklin, R. E., 396, 398,399, 400, 401.Franschitz, W., 349.Franz, J. , 274.Franze, C., 14.Franzen, V., 151.Fraser, M. M., 259.259.304.273.282.7414 INDEX OF AUTHORS' NAMES.Fraser, R. D. R., 385, 386,Fray, G. I., 304.Frazza, E. J., 161.Freed, S., 80.Freedman, L. D., 168.Freeland, M. Q., 350.Freeman, G.R., 23.Freeman, J. H., 119.Freeman, J. P., 149, 168,Freeman, M. E., 296.Freese, F., 359.Freezer, J . , 360.Freier, H. J., 65.Freir, H. E., 356.FrCling, E., 17.French, C. M., 347.Fresco, J. R., 374.Freudenberg, K., 160.Friclte, H., 46.Fridrichsons, J., 30 1.Fried, J., 207, 209, 217,Friedel, K. A., 87, 124,Friedman, H. L., 11.Friehl, P. J., 24.Friend, J . P., 82.Frieschi, R., 63.Friess, S . L., 145.Frisch, K. C., 146.Fritsch, W., 220.Fritz, G., 106, 107, 316.Fritz, J. S., 350, 351.Fritzsche, H., 199.Frombling, K., 40, 112.Fronaeus, S., 29.Frost, D. C., 43, 77.Frumkin, A. N., 65.Fry, A., 31.Fry, E. J. S., 270.Fuchs, L. H., 45.Fuchs, O., 154.Fuchs, W., 154.Fiichtenbusch, F., 122.Fueno, T., 36.Fugger, J., 234.Fujii, S., 275.Fujinaga, T., 371.Fujita, H., 66.Fujita, J., 87.Fuke, T,, 91.Fukker.F. K.. 364.389, 400.161.224, 323, 333.125.Fukush'ima, i>. I<., 208,221. 222.Fuller; R. C., 304.Fulmer, R. W., 156.Funk, H., 107, 108.Funke, V. E., 379.Fuoss, R. M., 362.Furberg, S., 396.Furnas, T. C., 384.Furukawa, J., 36.Fusari, S. A., 301.Fushtey, S. G., 285.Vyfe, W. S., 98.Gzibor, V., 154.Gabourel, J . D., 353.Gaensslen, H., 8.Gage, C. L., 241.Gagliardi, E., 343, 345.Gaitanis, C. D., 376.Gal, A. E., 274.Gal, D., 17.Gzil, G., 355.Gal, I., 358.Galan, M., 372.Gale, W. A., 97.Galetti, R., 35.Galinovsky, F., 243.Gallagher,- T. F., 208, 215,221, 323, 330.Gallo. G. G.. 86.Gallup, G., 125.Gamboni, G., 167.Gamis, C., 374.Gantz, E.St. C., 349, 360.Garcia, M., 329.Gardner, H. J., 14.Gardner, P. D., 190.Gardner, W. E., 184.Garifyanov, N. S., 91.Garmais.e, D. L., 323.Garner, C. S., 26.Garner, E. V., 387.Garner, W. E., 50.Garoti, G., 208.Garrison, W., 46.Garsou, J., 92.Garvin, D., 21.Gascoigne, R. M., 224.Gash, V. W., 156.Gassmann, L., 265.Gassner, I?. X., 291.Gastinger, E., 105, 116.Gates, S., 213.Gaudette, L., 320.Gaudin, A. M., 377.Gaudry, R., 274.Gauhe, A., 256, 258, 334,Gaur, H. C., 359.Gautschi, F., 223.Gaydon, A. G., 76.Gaze, R., 108.Gazith, M., 30.Gebauhr, W., 372.Gebhardt, G., 97.Gee, D. W., 285.Gee, G., 42.Geerdes, J. D., 262.Gehatia, M., 40.Gehlen, H., 32.Gehrke, C.W., 364.Geilmann, W., 372.Geissman, T. A., 236.Gelfand, S., 145.Gell, R. J., 244, 245.Geller, L. E., 203.Geller, S., 92, 107, 114.Gellerstadt, N., 291.Gellert, H. G., 104, 15.5,335, 337.159.Gelles, E., 31.Gellrich, M., 153.Gensler, W. J., 301, 306,Gentile, P. S., 123.George, M. H., 38.George, P., 28, 29, 91, 115.George, T. H., 51.Georg-Plant, M. M. T.,Gerber, M. I., 13.Gerber, N. N., 170.Gerding, H., 83, 85, 88.Gerhard, E. R., 20.Gerischer, H., 25.Gerlach, K., 348.Gerliczy, G., 151.Gerok, W., 276.Gerold, C., 154, 159, 211,Gerrard, W., 102, 161.Gerris, V., 219.Gerson, T., 302.Geselle, P., 1 11.Gesser, H., 20.Geyer, R., 350.Geyer, R. P., 315.Ghanem, N. A., 36.Ghigi, E., 198.Ghormley, J.A., 46, 47.Ghosh, B. N., 67.Ghosh, S., 67.Ghosh, S. P., 97.Ghyssaert, L., 366.Gibbons, D., 350.Gibbons, G. C., 265.Gibson, C. S., 195.Gibson, G., 109.Gibson, N. A., 348.Giefer, L., 367.Gierst, L., 363.Giesbricht, E., 246.Gigubre, P. A., 84, 357.Gilbert, G. A., 265.Gillam, A. E., 72.Gillespie, D. T. C., 187.Gillespie, G. R., 71.Gillespie, T., 71, 72.Gilliam, 0. R., 91.Gillis, J., 368.Gindler, E. M., 169.Ginsburg, D., 159.Gittos, M. W., 231.Gish, D. T., 279.Glascock, R. F., 371.Glaser, D. V., 74.Glass, R. A., 122.Glasser, L., 114.Glavind, J., 301.Glazener, M. R., 272.Glazman, Y. M., 71.Glazunova, 2. I., 374.Sleason, E. H., 33.Slemser, O., 103, 114, 117,Slendenin, L. E., 376.;lock, G.E., 330.307.267.214, 220.370INDEX OF AUTHORS’ NAMES. 41 6Glockling, F., 98.Glogger, I., 135.Gloor, U., 331.Glover, T., 289.Glushkova, V. B., 121.Glusker, D. L., 88.Gmelin, R., 168.Go, Y., 389.Godfrey, J. C., 249.Godson, D. H., 197.Goehring, M., 111, 116,117, 124.Goerdeler, J., 233.Goff, J. A., 60.Goffinet, B., 226.Goggin, D., 180.Gokhshtein, Ya. P., 357.Gold, V., 26, 31.Goldberg, E. P., 151.Goldemberg, J., 18.Gol’denberg, S. A., 15.Goldschmidt, S., 280.Goldstein, A., 183.Goldstein, J. H., 82.Goldstein, R., 114.Goljmov, V. P., 309.Gollan, F., 279.Golub, A. M., 98.Gomer, R., 51.Gonikberg, M. G., 12.Good, W., 28.Goodenow, E. L., 26.Goodman, E. I., 83.Goodman, I., 42.Goodman, M., 282.Gordon, A.S., 16, 22.Gordon, J. P., 81.Gordon, L., 347.Gordon, M., 34, 136, 373.Gordon, P. L., 150.Gordon, S., 47, 48.Gordy, W., 42, 82.Gore, P. H., 171.Goring, D. A. I., 267.Gorman, M., 153, 211.Gornick, F., 33.Gorrod, A. R. N., 262.Gorski, R. A., 60.Gorsuch, T. T., 367.Gorvin, J. H., 168.Goryacheva, I. A., 98.Gosling, R. G., 396, 398.Goss, F. R., 180.Goto, H., 367.Goto, R., 14.Goubeau, J., 84, 301, 102Gould, D., 208, 219.Goutarel, R., 24.5, 248.Gowan, J. E., 235.Gowda, H. S., 352.Gowenlock, B. G., 11.Goyer, G. G., 72.Graff, M. M., 297.Gragson, J. T., 180.Graham, R. P., 358.Graham, W. A. G., 100.Grahame. D. C.: 65.kal-Cabanac, M., 366.;ran, G., 356.Grant, J. K., 207, 319, 320,324, 326.Grant, L.R., 101, 123.;rant, R., 329.;rant, R. A., 336.;rantham, L. F., 27.Srassmann, W., 278.Graus, B., 105, 364.;ram, G., 361.haver, R. P., 209.Sray, F. V., 303.;ray, L. H., 44, 46.;ray, P., 7, 13, 17, 32.Sraziotti, R., 17.;reen, A., 319.Sreen, A. A., 279, 280.Sreen, D. E., 314.Sreen, D. W., 382, 291,Sreen, F. C., 390.Sreen, H. S., 56.Sreen, J . H. S., 10.Sreen, L. G., 354.keen, R., 36.Sreen, T., 297.Zreenberg, D. M., 275.Sreenberg, S. A., 39.Sreene, E. F., 59.Sreene, T. W., 212.Sreenlee, K. W., 180.Sreenler, R. G., 82. .Sreenspan, F. P., 158.Sreenstein, J. P., 275.Greenwood, C. T., 265.Greenwood, I?. L., 153.Greer, M. A., 293.Grenville-Well, H. J., 384.Gresham, W. F., 151.Greuell, E., 243.Grewe, R., 178.Gnehl, W., 39, 40.Griesbach, W., 292.Griesbach, W.E., 291.Griffith, E. J., 112, 361.Griffith, J. F., 277.Griffith, J . S., 91.Grigor, J., 165, 215, 308.Grigsby, W. E., 151.Grimaldi, F. S., 368.Grimes, M. D., 359.Gnmshaw, J., 236.Grinberg, A. A., 27.Grindley, D. N., 313.Grisebach, H., 257, 304.Griswold, E., 98, 104.Grob, A., 203.Grob, C. A., 190, 229.Grob, R. L., 368.Grobbelaar, N., 272.Grodsky, G., 276.Gross, D., 276, 277.Gross, J., 390.Gross, M. D., 34.Grosse, A. V., 18, 373.Grossman, J., 213.393.Srossnickle, T. T., 211.Srote, I. W.. 293.Jroth, W., 20.Srotheer, M. P., 369.;rove, E. L., 369.;roves, W. O., 108.Srubb, W. T., 40.Srubner, O., 360.Sruber, W., 230.Jriin, A. E., 74, 76.Sruen, R,, 72.Sriindel, R., 226, 227.Srumer, J., 15.kunbaum, B. W., 354.jrundmann, C., 84, 112,164, 230, 235.Srundy, J., 157, 170.Srunwald, E., 31.Zryaznova, E.A , , 366.Sryder, J. W., 112.Sucker, F. T., 71.Siibeli, O., 378.SuCnoche, H., 17.Siinthard, H. H., 84, 86,Giinther, P. L., 111.Guenther, W. B., 12.Guerillot-Vinet, A., 213.GuQon, J., 379.Guggenheim, E. A,, 56, 61.Guha, P. C., 195.Gulland, J. M., 288.Gunn, R., 72.Gunning, H. E., 11, 20.Gunstone, F. D., 166, 192,245.301, 308, 313.Gupta, S., 308.Gurnani, S . U., 275.Gustafsson, C., 262.Gustavson, K. H.,Gustavson, R. G., 291Gut, M., 326.Gutman, J . R., 54.Gutmann, V., 108,Gutowsky, H. S., 90,Guttmann, S., 279.Gutzeit, G., 370.Guyer, A., 17, 55, 151Guyer, P., 17, 55.GuzmAn, G., 313.Guzman, G.M., 372.Gwinn. W. D.. 82.390.114.284,112,36.Gyllenberg, H. G., 333.Gyorgy, P., 271, 333, 334,335, 336, 337, 338.Haagen-Smit, A. J., 316.Haar, R. W. V., 96.Haas, C. G., 97.Haas, H. C., 39.Haas, W., 343.Hack, M. H., 301.Hackerman, N., 66.Hades, W., 134.Hadler, H. I., 151416 INDEX OF AUTHORS’ NAMES.Hadni, A., 83.Hadorn, E., 240.Hadii, D., 85.Haede, W., 220.Haefele, L., 153.Haendler, H. M., 83.Haeseler, H., 103, 117.Hafner, K., 178, 179.Hafner, W., 129, 130.Hagdahl, L., 300.Hagenbach, W. P., 60.Hager, G. F., 151.Hager, G. P., 281.Haggitt, J. W., 386.Hagstrum, €3. D., 43.Hahn, H., 105.Hahn, H. H., 297, 300, 307.Hahn, H. T., 106.Haigh, C. P., 378.Hainberger, L., 346.Haines, W.J., 319.Haissinsky, M., 46, 48.Hale, C. M. F., 333.Halevi, E. A., 24.Halewood, P., 237.Halford, R. G., 35.Hall, A. R., 17.Hall, D. A., 391.Hall, D. M., 136.Hall, J. A., 166.Hall, R. M., 274.Hallam, B. F., 130, 180.Halleux, A., 8.Halpern, J., 29.HalsaU, T. G., 202, 224, 226.Halsey, G. D., 50.Halvarson, K., 26.Ham, E. A., 216.Hamaker, H. C., 69.Hamann, S. D., 31, 58, 59,Hamer, J., 232.Hamill, W. H., 45.Hamilton, L. D., 399.Hamilton, P. B., 275, 277.Hamlet, J. C., 223.Hamm, R. E., 27.Hammel, E. F., 60.Hammond, G. S., 8, 35,Hampton, A., 95, 133.Hanafusa, H., 354.Hanby, W. E., 385, 387,Hance, P. D., 193, 194,Hanks, D. P., 306.Hanks, P. A., 59.Hansen, J.L., 33.Hansen, P. A., 338.Hansen, R. P., 302, 303.Hanze, A. R., 208, 214.Happe, J. A., 28.Happey, F., 385, 389, 390.Hara, R., 362, 363.Hardegger, E., 178, 255.Harden, C. D., 10.60, 62.140.388, 389.248.Hardy, D. M., 267.Hare, W. F. J., 88.Hargitay, B., 282.Hargreave, I<. R., 29.Hargreaves, G., 28.Hariharan, K. V., 195.Haring, H. G., 85.Harington, C. R., 286.Harker, D., 383, 384, 394.Harley-Mason, J., 238.Harman, R. E., 216.Harned, R. L., 232.Harner, D. E., 49.Harnik, E., 132.Harper, S. H., 180, 303.Harrell, L. L., 189.Hams, F. E., 62.Harris, G., 273, 341.Harris, G. C., 196.Harris, G. F. P., 36.Harris, G. M., 31.Harris, J., 103.Hams, J. I., 280.Harris, J. L., 399.Harris, M. E., 15.Harris, P.L., 164.Harris, W. F., 350.Harrison, A., 374.Harrison, A. J., 23.Harrison, A. P., 338.Hamson, G. R., 73.Harrison, I. T., 226.Harrison, L. G., 55.Hart, E. J., 46, 47.Hart, K. R., 65.Hart, R. G., 400.Hart, V. E., 41.Harteck, P., 45.Hartinger, L., 368, 369.Hartkamp, H., 366, 367.Hartley, F., 210, 218, 331.Hartley, G. S., 385.Hartman, J. A., 213.Hartman, L., 305.Hartmann, H., 80, 81.Hartmann, S., 301.Hartough, H. D., 238.Hartree, E. F., 320.Hartung, W. H., 281.Hartwimmer, R., 102.Harukawa, T., 192.Harvey, A. E., jun., 366.Harwood, V. D., 264.Haselhorst, M., 257.Haslam, E., 237. .Haslewood, G. A. D., 327.Hasselmann, R., 15.Hassid, W. Z., 263.Hassinen, J. B., 337.Haszeldine, R. N., 85, 88,Hatch, L.F., 163.Hatt, M. H., 305.Haug, C. M., 309, 310.Hause, C. D., 83.Hauser, C. R., 149.Hausmann, W., 278.113, 117.Haust, P. L., 79.Havill, J. R., 99.Havinga, E., 158, 226, 227.Haward, R. N., 34, 37.Hawkins, E. G. E., 191.Haworth, R. D., 177, 198,211, 224, 236, 237.Haworth, W. N., 261, 264,268.Hay, A. S., 156.Hayakawa, T., 282.Hayano, M., 213, 318,319, 320, 321, 326, 329.Hayao, S., 239.Hayatsu, R., 213, 214.Hayden, H. S., 372.Hayden, P. M., 235.Hayek, E., 99, 113, 118.Hayes, D. H., 193.Hayes, P. F., 59.Hayes, T. J., 349.Hayes, W., 75.Hayes, W. K., 194.Haymond, H. R., 46.Haynes, R., 318.Hayter, R. G., 96.Hayward, A. C., 333.Hayward, B. J., 272.Heal, H. G., 50.Heath, H., 286, 287, 289,Heath, P., 344.Heath, R.L., 264.Hecht, F., 372.Hechter, O., 213, 317,Heck, R., 145.Heckelsberg, L. F., 53.Hecker, E., 164.Heckles, J. S., 296.Heffler, M. S., 222.Heftmann, E., 207.Hegedus, A., 364, 365.Hegemann, F., 364.Heidelberger, C., 171.Heidelberger, M., 260.Heikens, D., 40.Heilbronner, E., 176.Heilmann, R., 167.Heimel, S., 15.Heinke, J., 117.Heinrich, B. J., 369.Heinz, A. R., 302.Hejtmhek, M., 362.Helbling, R., 221.Hele, P., 315.Helferich, B., 259, 338.Heller, M., 210, 218, 220.Heller, W., 71.Hellman, L., 330.Hellmann, H., 273, 274.Hellwig, K., 18.Helvenston, E. P., 123.Hemala, M., 358.Henbest, H. B., 164, 165,Hench, P. S., 317.290.324.214INDEX OF AUTHORS' NAMES. 417Henderson, I. H. S., 18.Hendley, E.C., 138, 150.Hendrichs, J., 325.Hendrickson, J. B., 237.Hendrie, J. M., 74.Henglein, A., 38, 42.Henglein, E., 34.Henis, D. B., 312.Henley, A., 67.Hennaut-Roland, 57.Hennebutte, L., 60.Henrici, G., 37.Henry, D. C., 67.Henry, J. A., 205.Henry, I?. S. H,, 379.Henseke, G., 257.Hentz, R. R., 43.Hepworth, h4. A., 127.Herak, J., 70.Herb, S. F., 297, 301.Herbst, R. L., jun., 37.Hercus, C. E., 291.Herington, E. F. G., 87,Herling, F., 86, 208, 222.Hermanie, P. H. J., 67, 71.Herman, R., 86.Herman, S. E., 369.Hermans, J. J., 68.Hermans, P. H., 40.Herminghaus, H., 311.Heron, A. E., 356.Herout, V., 189.Herr, M. E., 209.Herran, J., 191, 254.Hersh, C. K., 60.Hershberg, E. B., 154,159, 211, 214, 219, 220,221.Hershberg, P.L., 208.Hertz, S., 292.Henvig, W., 175.Herz, J. E., 209, 323.Herz, W., 180.Herzberg, G., 73, 75, 76,Herzog, H. L., 208, 221.Hess. E. L., 282.124.82, 83.Hess, G. P., 281.Hess, K., 244.Hesse, G., 146, 181.Hetherington, G., 1Heuschkel, G., 240.Heusler, K., 218.Heusner, A,, 243.Heusser, H., 215, 2Hewgill, F. R., 185.Hewitt, J. J., 181.Hev. D. H.. 250.221, 330.1, 119.6, 217,HeGding, R. D., 187.Heyl, F. W., 209.HeymGs, R., 280.Heyns, K., 272, 273, 276.Heyrovskf, J., 339, 360.Heywood, A., 300.Heyworth, R., 335.REP.-VOL. LIIHibbert, C. J., 60.Hickam, 147. M., 43.Hickling, ..4., 360.Hidy, P. H., 232.Hieber, W. H., 120.Hiestand, A., 225.Hietala, P. K., 273.Higgins, T.H. S., 102.Higginson, W. C. E., 28.Higgs, P. W., 89.High, L. B., 211, 217.Highet, R. J., 157, 251.Higuchi, I., 52.Higuchi, J., 77.Higuchi, T., 362.Hildebrand, J. H., 65.Hilditch, T. P., 164, 296,Hill, B. R., 326.Hill, G. R., 55.Hill, R., 373.Hilsenrath, J., 56.Hinaga, Y., 92.Hinde, R. N., 381.Hindin, S. G., 55.Hindman, J. C., 27, 123.Hine, J., 184.Hine, M., 184.Hinkle, B. L., 72.Hinshelwood, (Sir) C. N., 9.Hinz, G., 155.Hippchen, H., 234.Hipple, J. A., 43.Hirai, N., 14.Hirano, S., 367.Hirarta, Y., 272.Hirase, S., 267.Hirayama, 0.. 300.Hirohata, R., 275.Hirs, C. H. W., 277, 394.Hirsch, E. F., 301.Hirsch, H., 16.Hirschfelder, J. O., 56, 57,Hirschler, F. G., 68.Hirschmann, F. B.. 218.Hirschmann, H., 207, 218,Hirschmann, R.F., 209,Hirshon, J. &I., 91.Hirst, E. L., 261, 262, 263,264, 265, 266, 268, 269,270.Hisar, R. S., 32.Hisatsune, I. C., 56.Hjette, B. E., 368.Hoare, M. I?., 15.Hobbins, P. C., 78, 79.Hobbs, J. J., 244.Kobbs, &l. E., 134.Hobkirk, R., 260.Hobson, J. D., 246.Hoch, D., 255.Hoch, J., 134.Hoch, M., 106, 108.Hochanadel, C. J., 46, 47.305.62.327.215.Hochstein, F. A., 256.Hodge, E. B., 232.Hodges, D., 60.Hodgkin, D. C., 248, 254,Hodkin, A., 169.Holemann, P., 15.Hoerger, E., 235.Hormann, H., 278.Hosli, H., 203.Hoey, G. B., 229.Hoey, G. R., 20, 22.Hoffenberg, D. S., 149.Hoffman, A. K., 26.Hofman, K., 286.Hofmann, A., 242, 245,Hofmann, C. H., 304.Hofmann, K., 280,305,312.Hofreiter, B.T., 266.Hogg, A. J. P., 165, 308.Hogg, J. A., 208, 209.Holasek, *4., 300.Holden, J. S., 31.Holden, N. E., 159.Holder, B. E., 90.Holland, D. O., 232, 230.Holleck, L., 368, 369.Holley, C. E., 99.Holley, R. W., 281.Holley, T. F., 198.Hollingshead, R. G. W.,Hollstein, U., 243.Holly, F. W., 231, 232,304.Holman, R. T., 297, 300,302, 306, 316.Holme, D., 162, 309, 310.Holmes, A., 129.Holmes, F., 96.Holmes, R. R., 140.Holness, N. J., 204.Holt, G., 136.Holt, S. J., 161.Holt, T., 34.Holtschmidt, U., 105.Holtzberg, F., 114.Holyer, N. F., 165.Holysz, R. P., 213.Holzbecher, S., 345.Holzer, K., 264, 265.Holzkamp, E., 38.Honda, M., 362.Honig, A., 82.Hooge, F. N., 88, 89.Hooper, C.W., 384, 399.Hoot, W. F., 14.Hoover, J. R. E., 334.Hopkins, C . Y., 293.Hopson, E. M., 291.Horan, H. A., 97.Horeau, A., 230.Hori, T., 313.Horner, E. C. A., 13.Horner, L., 36, 173.403.246, 248.214.341.41 8 INDEX OF AUTHORS' NAMES.Horner, W. H., 287.Hornig, D. F., 59, 86, 88,Homing, R. H., 136.Horowitz, R. H., 140.Horstman, P., 144.Horswill, E. C., 257, 258.Horton, W. J., 190.HorvAth, J., 331.Hoskin, N. E., 66.Hosking, J. R., 196.Hoskins, R., 91.Hossenlopp, I. A., 59.Hoste, J., 368.Hougen, F. W., 302, 304.Hough, L., 154, 262, 263,Hough, W. V., 101.Hoult, T. G., 239.Houner, L., 390.Houtgraaf, H., 83, 88.Howard, G. A., 297.Howard, K. S., 280.Howe, E., 232.Howe, J. P., 32.Howe, P. G., 57, 69.Howe, R., 190.Howells, E.R., 391, 393.Howitt, F. O., 297, 387.Howton, D. R., 300, 306.Hoyle, D. H., 140.Hromatka, O., 250.Hu, K. H., 106.Huber, G., 148.Huber, R., 362.Hubicki, W., 360.Hudgens, J. E., 376.Hudy, J. A., 365.Hiibener, H. J., 318.Hueber, H . V., 99.Huebner, C. F., 160, 247,Hiickel, W., 146, 156, 190.Hiirzeler, H., 30.Hiittel, R., 232.Huffman, E. F., 109.Huffman, G. W., 255.Huffman, M. N., 217, 218.Huffstutler, M. C., 18.Huggins, C. M., 61, 88, 90.Huggins, M. L., 381, 382.Hughes, A. M., 293.Hughes, E. D., 30, 141.Hughes, E. 0.. 267.115.270.248.Hume, D. N., 366.Humphreys, T. E., 315.Hund. F., 121.i Isaac, R., 59.j Isherwood, F. A., 256, 264.Hunnewell, B. D., 232.Hunsberger, I.M., 136, 234.Hunt, J. P., 27.Hunt, J. S., 223.Hunt, R. &I,, 247.Hunter, G., 285, 286, 287,Hunziker. F., 199, 213.Hurd, C. D., 171, 233, 234,Hur6, J., 378.Hurst, T. L., 277.Hussey, A. S., 353.Hutchison, C. A., '31.Hutchison, D. A., 43, 47,Hutchison, H. P., 193.Hutt, H. H., 296.Huxley, H . E., 393.Huyberechts, S., 8.Hybart, F. J., 265.Hyde, E. K., 165.288.230.Ibarz AznArez, J., 32.Ichishima, I., 87.Iddings, G. M., 101).Idol, J . D., 175.Igarashi, K., 213.Iijima, S., 369.Ikeda, S., 373.Ikeda, T., 251.Ikegami, Y., 177.Iliceto, A., 30.Ilse, D., 302.Use, F. E., 80.Imaeda, Y., 92.Imoto, M., 36, 38, 42.Inamoto, N., 159.Indovina, R., 345.Inezedy, J.. 367.Ingber, N., 347.Inghram, M. G., 106, 374.Ingle, D. J., 329.Ingold, C.K , 30, 76, 78,87, 141, 145.Ingold, W.. 204.lngram, D. J . E., 33, 81,91.Ingram, V. F., 382.Ingram, V. M., 391.Inhoffen, H . H., 165, 218,Inn. E. C. Y., 73.226, 227.Huihes; F. J., 29.Hughes, G. K., 244, 345. , Innes, K. K.,.76.Hughes. H. K., 378. I Inoue, E., 24, 45.Hughes; I. W.,.373.Hughes, M. F., 55.Hughes, S. C. R., 140,Hugo, T. J., 74.Huhn, P., 8.Huisgen, R., 135, 160.Hulburt, H . M., 53.Huldt, L., 75.Hulme, A. C., 272.Humber, L. G., 197.Tnoue, N., 92.Inouye, \-., 300, 301. ji1I Ipatieff, V N , 168.Iriarte, J., 211. 1 Irmscher, K., 226. 1 Irvin, J, C., 82., Irvine, D. S., 226.1 Irving, H. M. N. H., 95,141. i Iofa, 2. A , , 66.i 133, 340, 341.Ishida, R., 364, 365.Ishidate, M., 363.Ishii, D., 367.Ishikawa, H., 192.Ishimori, T., 374.Islam, A.M., 183.Isles, G. L., 60.Isoi, K., 313.Issa, I. M., 28, 360, 361.Issa, R. M., 28, 361.Isshiki, T., 358.Ito, T., 272.Itoh, T., 82.Iveronova, V. J., 388.lves, D. A. J., 156, 203.Ivin, K. J., 42.Iwai, I., 192.Iyer, R. H., 313.Izatt, R. M., 97.Izumiya, AT., 25.3.Jach, J.. 9.Jache, A. W., 82.Jacklin, A. G., 16.3, 306,'ackman, L. PI., 238.'ackson, A. H., 238..ackson, J., 268..ackson, R. W., 209, 214..ackson, S., 389..ackson, S. F., 391.-acobs, E. S.. 345.'acobs, G., 68.'acobs, S., 276.acobs, S. J., 59..acobs, W. .\., 254..acobsen, R. P., 317.acobson, E. C., 152.acobson, M., 166, 311, 312.acques, J., 230.acquinot, P., 73, 82.affC, H.H., 234.affe, J. H., 82.ahn, A., 153.ahn, E. L.. 84.ahn, W., 99.ailer, J. W., 221.ames, C. F., 344.ames, C. G., 16.ames, D. K.. 213.ames, J. A., 375.ames, V. H. T., 222.ameson, R. F., 121.ander, J., 85, 104, 110.laner, C., 296.iang, G. I., 234.iankovits, I., 348.Fankovits, L., 367.ranot, M.-M., 245, 248.'ansen, L., 57, 62.'anssen, R., 67..am, G. J., 8, 83, 87.aquenoud, P. A,, 279.'&rboe, C. H., 230.307INDEX OF AUTHORS' NAMES. 419Jaroslavsky, N. G., 87.Jarrel, R. F., 73.Jaruzelski, J. J., 26.Jeacocke, G. J., 161.Jean, M., 368.Jeanes, A., 269.Jeanloz, R. W., 317.Jefferies,P.R., 185,187,206.Jeffrey, I. G. A., 111.Jeger, O., 184, 201, 202,203, 204, 206, 223, 255.Jelinek, M., 366.Jellinek, H.H. G., 41.Jenik, J., 356, 367.Jenkins, A. C., 60.Jenkins, A. D., 33, 91.Jenkins, E. N., 376.Jenkins, G. I., 51, 52, 53.Jenkins, L., 364.Jensen, A. O., 213.JenSovSkq, L., 367, 360.Jepson, J . B., 232.Jepson, W. B., 61.Jerchel, D., 234.Jerome, H., 366.Jessop, A. S., 302.Jevnik, M. A., 208.Jilek, A., 347, 367.Jira, R., 129.Jirousek, L., 360.Jonassen, H. B., 98.Jochum, P., 232.Johl, A., 280.Johns, H. E., 44.Johns, R. B., 177, 241.Johns, R. H., 25.Johns, 1%'. F., 157, 216,Johnson, A. W., 176, 177,Johnson, B. A., 213.Johnson, C. E., 368.Johnson, E. A., 136.Johnson, E. R., 11.Johnson, G. R. A., 48.Johnson, J . L., 213.Johnson, O., 55.Johnson, P., 48.Johnson, R. A., 347, 368.Johnson, S., 97.Johnson, T.B., 288.Johnson, W. S., 227, 228.Johnston, H. L., 106, 108.Johnston, H. S., 9, 12.Johnston, J. D., 205.Johnstone, H. F., 20, 71.Jolly, W. L., 110.Jonas, H., 123.Jones, A. G., 373.Jones, D. N., 212.Jones, E. R. H., 124, 137,162, 164, 200, 214, 224,226, 310, 311.Jones, E. W., 296.Jones, J. K. N., 154, 255,255, 262, 263, 267, 268,336.220, 228.242, 403.Jones, M. E., 370.Jones, M. H., 377.Jones, M. M., 110.Jones, P. G., 223.Jones, R. G., 231.Jones, R. L., 84.Jones, R. N., 86, 208, 301.Jonker, G. H. , 70.Jordan, J. H., 364.Jordan, W., 296.Jergensen, C. K., 80.Jori, M., 115,Joshi, R. M., 37.Josien, M.-L., 85, 88.Joska, J., 211.Jost, W., 14.JovanoviC, V. S., 366.Jubb, A. H., 198.Jucker, E., 243.Judina, N.D., 291.Juel, L. H., 171.Julian, P. L., 210.Jungreis, E., 364.Jura, W. H., 360.JureCek, M., 356, 367.Just, G., 210.Justisz, M., 278.Kadesah, R. G., 294.Kaesberg, P., 383, 401, 402.Kagan, F. E., 32.Kagarise, R. E., 85, 87.Kahnt, F. W., 217, 318.319, 321, 328, 331.Kaizumi, M:, 36.Kalbag, S. S., 302.Kalm, M. J., 304.Kalousek, M., 360.Kalvoda, J., 255.Kalvoda, R., 367.Kamecki, J., 359.Kamemoto, Y., 369.Kamen, M. D., 372.Kanath, G. G., 313.Kanbara, S., 373.Kancko, S., 60.Kanda, Y,, 275.Kaplan, J., 74.Kaplan, L., 31, 149, 376.Kaplan, N. O., 320.Kapur, S. L., 37.Kariyone, T., 313.Karjakin, A. W., 87.Karkhanis, Y., D., 296,Karkhanavala, M. D., 359.Karlson, R. H., 282.Karrer, P., 153, 174, 240,242, 246, 255.Kartha, G., 389.Kasha, M., 79.Kashimoto, T., 312.Kaspar, H., 111.Kassel, L., 9.Kassner, J.L., 369.Kasturi, T. R., 313.Katagiri, K., 37.313.Katchalsky, E., 40, 281,Kath, J., 226.Kath, J. F., 227.Kato, T., 362, 369.Katritzky, A. R., 233, 238.Katsoyannis, P. G., 279.Katz, D. L., 60.Katz, L., 105.Katzenellenbogen, E. , 86,Katzin, L. I., 109.Kauder, O., 227.Kaufman, F., 12.Kaufmann, H. P., 300, 311,Kawahara, F., 37.Kawamura, B., 363.Kawamura, K., 340.Kay, J. C., 17.Kay, L. M., 390.Kaye, W., 83.Kebrle, J., 246.Keech, M. K., 391.Keefer, R. M., 138.Keii, T., 53.Keil, B., 243.Keilin, B., 100.Keilin, D., 320.Keller, F., 248.Keller, W. E., 59, 60.Kelly, F.C., 391.Kelso, J. R., 12.Kemball, C., 54.Kemp, A. D., 227.Kemula, W., 359.Kenaston, C. B., 301.Kendall, E. C., 317.Kendall, F. E., 212.Kendall, J . D., 230.Kendall, V. G., 308.Kendrew, J. C., 382, 383,Kennard, W., 84.Kennedy, J. W., 49.Kennedy, T. H., 291.Kenner, G. W., 155, 170,Kenner, J., 265.Kenney, H. E., 223.Kent, P. W., 50.Kepler, E. J., 327.Keppler, J. G., 300.Kern, F., 11.Kern, R. J., 36.Kern, W., 302.Kertes, S., 113.Kessler, V., 289.Keston, A. S., 322, 364.Ketelaar, J . A. A., 88, 89.Ketley, A. D., 31.Keyes, F. G., 62.Keynes, R. D., 376.Khaibullin, I. Kh., 61.Khalafalla, S. E., 28.Khalifa, H., 360.Khan, N. A., 302.388.208.313.392, 393.281.0 420 INDEX OF AUTHORS’ NAMES.Kharasch, M.S., 23, 37.Khitrin, L. N., 15.Khorana, H. G., 281.Khosla, B., 359.Kice, J. L., 36.Kickhofen, B., 239, 240.Kidd, J- M., 85, 117.Kieffer, W. F., 47.Kieffler, J., 59.Kiepert, K., 137.Kierstead, R. W., 184,Kieslich, K., 163.Kiess, A. A,, 302.Kihara, T., 56, 57, 60.Kikuchi, C., 91.Kilb, R. W., 82.Kilpatrick, J. E., 60.Kimitsuki, M., 275.King, C., 167, 181.King, C. V., 66.King, E. L., 121.King, F. E., 174, 197, 236.King, G. W., 76.King, T. J., 197, 236.King, R. O., 15.King, W. H., 316.Kinnunen, J., 349, 351.Kiprijanow, A. I., 161.Kirby, A. F., 135.Kirchner, K.-D., 257.Kiriyama, S., 42.Kirk, D. N., 209.Kirk, P. L., 354.Kirkland, J. J., 369.Kirkwood, J. G., 62, 63,Kirrmann, A., 85.Kirschenlohr, W..271, 337.Kirshenbaum, A. D., 18,Kirsten, W., 357.Kitagawa, T., 252.Kitai, R., 283, 284.Kiyama, R., 15.Kjaer, A., 168, 273.Kjaergard, T., 348.Klager, K., 154.Klass, D. L., 217.Klein, D., 224.Klein, F. S., 30.Klein, G., 292.Klein, M. P., 90.Kleinberg, J., 104.Kleinspehn, G. G., 231.Kleman, B., 75.Klemm, L. H., 133.Klemm, W., 97, 127.Klemperer, W. A., 84.Klenk, E., 307, 335.Klohs, M. W.. 248.Klosterman, H. J., 170.Klug, A., 400.Klyne, W., 200, 208, 217,Knabe, J . , 153.Knight, A. H., 379.305.64, 172.373.303.Knight, C. A., 399.Knight, H. B., 302.Knight, S. A., 146.Knight, S. B., 238.Knipe, R. H., 16.Knoll, €3. W., 304.Knoller, Y., 29.Knorre, D. G., 8.Knoth, P., 243.Knowles, W. S., 227.Koba, S., 57.Kobayashi, J., 367.Kobayashi, M., 87.Kobayashi, Y., 374.Kobe, K.A., 14, 56.Kober, E., 230.Kobrle, V., 300.Koch, C. W., 353, 354.Koch, 0. G., 124.Kochi, J. K., 32, 97.Koefoed, J., 28.Koehler, R. C., 159.Koekemoer, M. J., 253.Koelmanns, H., 67, 71.Koevoet, A. L., 226, 227.Kofranyi, E., 276.Kogan, I. B., 359.Kogan-Charles, M., 2 95.Kogl, F., 173.Kohler, F., 64.Kohn, A., 376, 377.Kohn, E. J., 160.K6i, Y., 91.Kojima, S., 92.Kojima, T., 82.Kolb, D. K., 296.Kolditz, L., 113.Kolevatova, U. S., 358.Kollonitsch, J., 154.Kolthoff, I. M., 32, 33, 37,Komaki, C., 87.Komeno, T., 213.Komori, S., 313.Konasiewicz, A., 30.Kondo, Y., 79.Kondrashev, Y. D., 98.Kooyman, E. C., 143.Korenman, I.M., 374.Korman. J., 208.Kornacki, J., 359.Korotun, M. V., 96.KorsHk, V. V., 39.Korshunov, I. A., 358.Korte, F., 230, 240.Kortum, G., 65.Korvezee, A. E., 65.Koryta, J., 358.Koshkin, D. I., 362.Koskenkyla, M., 182.Kosower, E. M., 308.Kosta, L., 366.Kostic, R. B., 214, 222.Kotai, A., 282.Kottenhahn, G., 121.KovAcs, J. , 282.KOVACS, K., 282.96, 125.Kovalenko, P. N., 369.Kovalenko, V., 289.Kowkabany, G. N., 256.Kozawa, A., 366.Kozlova, L. I., 27.Kozlova, N. P., 369.Kozlovskii, M. T. , 359.Kozlowski, M. A., 209.Kozyrev, B. M., 91.Kracek, J., 358.Kraemer, J., 117.Kraft, R., 159.Kraitchman, K., 82.Kramer, D. N., 281.Kraml, M., 264.ICrAmli, A., 331.Kratky, O., 387.Krauch, H., 151, 156, 163.Krause, E., 155.Kraut, M., 213.Krebs, H., 111, 112.Kreevoy, M.M., 30.Krehbiel, G., 146, 181.Krejci, E., 360.Krenz, F. H., 49.Kressman, T. R. E., 276.Kretschmer, C. B., 59.Kreutzberger, A., 84, 235.Knege, 0. H., 351, 369.Krieger, A. L., 240.Krieger, H., 184.Krimm. S.. 85.Kritchevsky, T. H., 221,222. 323.K?iv&ek, M., 347.Krivchik, 2. A., 359.Kroger, C., 108.Krohnke, F., 239, 240.Kron, N., 126.Kroner, T. D., 390.Kropman, M., 253.Krupp, F., 159.Kruse, H.-H., 80.Kruys, P., 8.Kruyt, H. R., 70.Krylor, E. I., 358.Krzhizhova, E., 358.Ksandr, Z., 362.Kucera, T. J., 153.Kuchen, W., 107, 161.Kuchtner, M., 366.Kuehl, F. A., 232, 242.Kuhn, R., 156, 163, 164,224; 255, 256, 258, 271,333, 334, 335, 337, 338.Kuivila, H.G., 151.Kulkarni, B. S., 301.Kummer, J. T., 50.Kummerow, F. A,, 302.Kumta, U. S., 275.Kupchan, S. M.. 224.Kuratani, K., 87.Kuri, Z., 20.Kurono, G., 313.Kurtz, J., 388.Kurz, P. F., 15.Kurzer, F., 233INDEX OF AUTHORS’ NAMES. 421Kusaka, Y., 371.Kushida, T., 92.Kushinsky, S., 329.Kusserow, G. W., 248.Kutschke, K. O., 20.Kuzina, L., 86.Kuznetsov, V. I., 340.Kwan, T., 52.Kyburz, E., 223.Kynaston, W., 87.Labianca, T.. 98.Labler, L., 152, 211, 224.Lacher, J. R., 85.Ladbury, J. E., 136, 172.Ladbury, J. W., 28.Ladenbauer, 1.-M., 372.Ladner, W. R., 65.LaDu, B. N., 320.Laffitte, P., 15, 17.Lafleur, S., 64.La Force, R. C., 90.Lagerqvist, A., 75.Lagoschnaya, R. M., 355.Laguarta, E. M. G., 349.Laidlaw, R.A., 264.Laidler, K. J., 31.Laird, R. K., 75.Laitinen, H. A., 359.Lake, S. J., 31.Lakritz, J., 25.Lakstigala, M., 42.Lal, J., 36.Lambert, J. A., 58, 60.Lambert, J, D., 58, 59, 60.Lambert, J. L., 369, 370.Lambert, R. F., 155.Lamberton, A. H., 26.LaMer, V. K., 72.Lamm, C. G., 27.Lamontagne, D., 357.Lamp, B. G., 296, 300.Lampe, H. W., 373.Landel, A. M., 257.Landmann, W. A., 280.Landsberg, P. T., 51.Landsteiner, K., 336.Lane, E. S., 169.Lang, K., 123.Lang, K. F., 171.Langdon, R. G., 315, 332.Lange, I., 369.Langemann, A., 176.Langer, A,, 43.Langerbeins, H., 335.Langmuir, I., 72.Langridge, R., 399.Lanyon, M. A. H., 51.Lapin, H., 223.Lapitskii, A. V., 114.Lapkin, M., 36, 183.Lappert, M.F., 102.Lapworth, A., 159.Lardon, A., 207.Lardon, F., 198.Larsen, I., 168.Larson, E. B., 264.Laruelle, P., 100.Lascombe, J., 85, 88.Latham, H. G., jun., 224.Latremouille, G. A., 147.Laubach, G. D., 209, 221.Laubengayer, A. W., 101,Lauenstein, K., 335.Laurie, C. M., 11.Lavie, D., 224.Lavigne, J. B., 178.Lavine, T. F., 276.Lavit, D., 168.Law, J. T., 51.Lawley, H. G., 266.Lawrence, A. S. C., 69.Lawrie, W., 226.Lawson, A., 232, 239, 286,Lawson, G. J., 270.Lawson, W. B., 181.Lawton, V. D., 232.Laxton, J. W., 140, 141.Lazard, B., 31.Leach, S., 46.Leake, W. W., 160, 170.Leanza, W. J., 274.Lear, J. B., 369.Leavitt, F., 138.Leboeuf, M. B., 375, 378.Le Boulch, N., 213.Lecamp, M., 14.Lecomte, J., 84, 85.Lechner, M., 147.Leddicotte, G.W., 371,Leden, I., 98, 128.Lederer, E., 198, 304.Lederer, M., 371.Lednicer, D., 136, 161,Lee, R. J., 12.Leech, J. G., 261.Leeds, N. S., 221.Leeming, P. R., 311.Lees, C. S., 97.Leese, C. L., 240.Lefferts, E. B., 167.Lefort, M., 46.Legagneur, C. S., 73.Le Gette, J., 390.Legrand, L., 231.Legros, J., 27.Le Hir, A., 245, 248.Lehmkuhl, W., 104, 155.Lehninger, A. L., 314.Lehrman, L., 343.Leigh, C. H., 11.Leigh, H. M., 323, 332.Leipfinger, H., 128.Leising, E., 281.Lemay, A., 14.Lemin, A. J., 203, 205.Lemmon, R. M., 48.Lenhard, R. H., 209, 214Lennert, K., 303.Lenormant. H.. 86.108.287, 290.375, 376.172.Leonard, B. R., 401.Leonard, N. J., 145, 156.Leonard, W., 97.Leone, E., 287, 289.Lerner, R.G., 82.Le Roy, D. J., 22.Le Roy, G. V., 324.Lesemann, K. J., 14.Lesher, G. Y., 232.Lespagnol, A., 334.Lesslie, M. S., 136.Lester, C. T., 229.Lestyan, J. , 243.Letort, M., 13, 39, 144.Lettre, H., 207.LBveque, P., 378.Levesley, P., 28.Levi, G. R., 126.Levin, B. Y., 88.Levin, E. S., 359.Levin, R. H., 157, 208, 214.Levine, R., 160, 170, 234.Levine, S., 68.Levitan, P., 221.Levitman, Kh. Ya., 359.Levitt, B. P., 12.Levitt, L. S., 29.Levy, A., 15, 16.Levy, A. L., 277.Levy, H., 317, 329.Levy, M., 132, 138, 374.Lewbart, M. L., 221.Lewin, M., 32.Lewinson, V. A., 63.Lewis, B. A., 255.Lewis, E. S., 169.Lewis, H. B., 287.Lewis, J. R., 139, 161,Lewis, J. W., 166.Lewis, L.A., 319.Lewis, M. S., 272.Lewis, P. R., 376.Lewis, T. A., 147.Li, C. H., 280.Li, K., 59.Li, N. C., 96.Liao, C., 172.Liao, C.-W., 181.Liberman, L. A., 300.Liddell, H. F., 370.Lide, D. R., 82.Lieberman, S., 221, 326.Liehr, A. D., 87.Liesegang, E. C., 102.Ligthelm, S. P., 308.Liljeqvist, B., 75.Lin, C. C., 82.Linacre, J. K., 45.Lincoln, F. H., 208, 209,Lindars, F. J., 9, 26.Lindberg, B., 257, 264.Lindberg, H. A., 292.Lindberg, M. C., 319, 326.Linden, C. E., 209, 212.Linderstr~m-Lang, K., 283.212.214422 INDEX OF AUTHORS’ NAMES.Lindlar, F., 307.Lindlar, H., 162.Lindley, H., 283, 384, 394.Lindqvist, S., 75.Lindsey, A. S., 194.Lindstrom, G., 90.Lingane, J. J., 363.Lingens, F., 273, 274.Linhard, M., 95, 121.Linhart, K., 359.Linke, W.F., 99.Linko, P., 273.Linnett, J. W., 15.Linstead, R. P., 165, 167,Lipman, C., 194.Lipmann, F., 370.Lippincott, E. R., 84, 89,Lippman, A. E., 203, 208,Lippman, D. Z., 61.Lipschitz, R., 398.Lipscomb, M. D., 319.Lipsky, S., 49.Lipson, H., 381.Lister, J. H., 174.Littell, R., 157, 214, 220.Little, K., 50, 97.Little, L. H., 88.Littman, J., 83.Liu, L. H., 203, 245.Livasy, J. A., 100.Livingston, D. I., 39.Livingston, R., 82.Liwschitz, Y., 282.Ljungquist, U., 331.Llewellyn, D. R., 30, 147.Lloyd, D., 175, 179, 180.Lloyd, G., 173.Lloyd, P. F., 255.Loan, L. D., 34.Lock, M. V., 256.Locke, D. M., 156.Lockhart, A. I. M., 278,Loclcyer, R., 44.Lodge, J. P., 71.Loeser, E., 240.Low, I., 224, 255, 258.Lohmar, R.L., 269.Loiseleur. J., 49.Lomer, T. R., 301.Londergan, T. E., 234.Long, A. G., 222, 223.Long, G., 26.Long, L. H., 11.Longfield, J. E., 12.Longuet-Higgins, H. C.,Looney, F. S., 25.Lopez, G., 212.Lopez Santos, I., 374.Loprest, F. J., 122.Lord, R. C., 83, 84, 88.Lorktan, M., 104.Loriers, J., 104.231, 241, 304, 305.97.254.279.56, 64.Lospalluto, J., 374.Lossing, F. P., 19.Lott, M: H., 217, 218.Loudon, J. D., 172.Lourens, W. A., 225.Louwerse, P., 59.Lovern, J. A., 296.Low, B. W., 382, 384, 394.Lowe, E. J., 85, 112.Lozac’h, N., 231.Lubochinsky, B., 370.Lubschez, R., 287.Lucas, G. B., 149, 158.Lucas, R., 160.Lucas, R. A., 248, 305.Lucquin, M., 17.Ludsteck, D., 167.Ludwig, R., 161.Luetscher, J.A., 329.Liittringhaus, A., 85, 160.Luft, N. W., 15, 87.Luke, C. L., 368.Lukes, R. M., 216, 220,228.Lukin, M., 153.Lukovnikov, A. F., 13.Lumb, P. B., 308, 311.Lumieux, R. U., 148.Lumpkin, C. C., 169.Lundberg, W. O., 302, 316.Lunde, K., 84, 165.Lunts, L. H. C., 211.Lupien, Y., 59.Lupina, V. G., 366.Lutz, W. B., 161, 172.Luzzati, V., 383.Lymen, F., 314.Lynn, R. E., 56.Lyons, J. A., 35.Lyons, J. E., 232.Lyons, L. E., 78, 79.Lyssy, T., 202.Lythgoe, B., 162, 169, 226.Lyttle, D. A., 208, 323.Mabis, A. J., 373.McAleer, W. J., 209.MacArthur, I., 386.Macarthur, M. M., 203.McArthur, W., 266.McBee, E. T., 175.Macbeth, A. K., 187.McBride, W. R., 110.McCall, D. W., 90.McCallum, K.J., 50.McCarrison, R., 291.McCarthy, R. E., 338.McCasland, G. E., 257,McClellan, A. L., 84.McClure, D. S., 77, 78, 79.McConnell, H. M., 90.McConnell, W. B., 275.Maccoll, A., 10, 11.McCormick, J. E., 256, 260.McCready, R. M., 266.McCubbin, T. K., 83.McCullock, W. J. H., 234.258.McCullough, J. F., 361.McCullough, J. P., 59.McCune, H. W., 342.McCutcheon, T. P., 121.McDaniel, D. H., 135, 141,MacDiarmid, A. G., 84, 106.McDonald, C. C., 20.Macdonald, C. G., 185.McDonald, I. R. C., 305.MacDonald, J. A., 238.Macdonald, R. E., 88.MacDonald, S. F., 231.McDonell, W. R., 47, 48.McDowell, C. A., 43, 55.McDowell, G. A., 77.McElcheran, D. E., 22.McElroy, 0. E., 296.McEvoy, F. J., 250.McEwen, W. E., 238.McGarr, J.J., 390.McGarrahaw, K., 332.McGavin, C. S., 389.McGavin, S., 388.McGee, M. A., 308.McGhie, J. F., 146.McGilvray, D. I., 261, 262.McGinty, D. A., 290, 319.McGlashan, M. L., 60, 65.McGuckin, W. F., 210.McGuire, J. M., 43.Machleidt, H., 230.McHugh, D. J., 257.MacInnes, A. G., 302.MacInnes, D. M., 165, 308.McInteer, B. B., 99.McIntosh, A. O., 132.Mack, C. H., 306.McKay, A. F., 211, 301.Mackay, M., 254.McKellar, A., 82.McKenna, J., 198, 211.Mackenzie, H. A. E., 8.Mackenzie, K. G., 260.McKeown, G. C., 360.Mackie, J. D. H., 30, 141.McKinley, J. D., jun.,Mackor, E. L., 71.Macku, J., 357.McKusick, €3. C., 250.McLaughlin, J., 296.McLean, A. D., 90.McLean, D. C., 183.McLean, J., 165, 308.Maclean, M.A., 296.McLean, P., 320.MacLean, R. L., 183.McManamey, W. J., 59.MacMasters, M. M., 266.Macmillan, W. G., 323.McMullan, R. K., 105.McMurry, T. B. H., 192.McNab, A. S., 226.McNaughton, G. S., 46,McNesby, J. R., 22.234.21.49INDEX OF AUTHORS’ NAMES. 423MacNevin, W. M., 351, 369McNiven, N. L., 190.McOmie, J. F. W., 174,McPhee, J. R., 361.McPherson, J., 257, 264.McPherson, J. F., 242.MacPhillamy, H. B., 160,McQuillin, F. J., 190, 191.Macras, T. P., 390.McRorie, R. A., 272.McSharry, J. J., 97.McTaggart, N. G., 306.Madayeva, 0. S., 220.Madden, R. P., 89.Maddock, A. G., 84, 106.Madhava, I<. B., 291.Madorsky, S. L., 41.Maeck, W. J., 366.Maeda, M., 37.Magar, N. G., 296, 313.Magari, S., 347.Magat, M., 13, 49.Magdoff, B., 394, 395.Magee, J., 28.Magee, J.L., 46.Magerlein, B. J., 208, 214,Magoon, E. F., 164.Mahadevan, A. P., 301.Mahadevan, V., 37.Mahlman, H. A., 371, 375,Mahomed, R. S., 262.Mailander, E., 118.Maille, M., 313.Mair, R. D., 355.Maitlis, P . M., 238.Maizlish, R. S., 65.Maizus, 2. K., 17.Majert, H., 155.Major, A., 257,Majury, T. G., 34.Makansi, M. M., 97.Makhover, S. L., 359.Maki, M., 271.Malaguti, A., 98.Malat, M., 348.Malatesta, L., 127.Malcolm, B. R., 386, 387,Malera, A., 202.Malhotra, 0. P., 23.Malinowski, E. R., 29.Malissa, H., 341.Malkin. T., 301.Malkina, A. D., 57, 69.Malmstadt, H. V., 364.Maloney, C. M., 365.Malumbres, J. L. M., 366.Mamantov, G., 25.Manalo, G. D., 352.Manasevit, H.M., 346.Mancera, A., 317.Mancera, O., 209, 210, 219,175.247, 248.323.376.388, 389.323.Mandel, M., 82.Mangold, H. K., 300.Manion, J. P., 45.Mann, F. G., 127, 169.Mann, T., 287, 289.Mann, W. B., 379.Manners, D. J., 266, 270.Mannhardt, H.-J., 162, 310.Manning, R. A., 96. .Manring, E. R., 92.Mansfield, G. H., 310.Manske, R. H. F., 242, 253.Manson, A. J., 211, 250.Manson, J. E., 71.Mapes, J. E., 56. 87.Mapson, L. W., 316.Marchetti, (Mlle.), 373.Marcus, R. J., 26.Marfurt, H. R., 55.Margeneau, H., 69.Margerison, D., 29, 35.Margoshes, M., 84.Margrave, J. L., 99.Marine, D., 291.Markgraf, H. G., 64.Markham, R., 401.Markley, F. X., 153.Markovskii, L. Y., 98.Markowitz, M. M., 99.Marks, G.S.. 304.Marlatt, V., 209.Marple, T. L., 363.Marrack, J. R., 392.Marrian, G. F., 218, 327.Marriott, J. V. R., 265.Marsden, D. G. H., 19.Marsh, J. K., 105.Marsh, R. E., 383, 387.Marsh, W. R., 45.Marshall, C. W., 317.Marshall, J. R., 220.Marshall, L., 315.Marshall, R . H., 104.Martell, A. E., 80, 96, 340.Marti, M., 330.Martin, A. J. P., 297.Martin, A. V. W., 389.Martin, D. S., jun.,, 27, 28,Martin, E. W., 243.Martin, G. J., 274.Martin, G. R., 374.Martin, H., 38, 159.Martin, J. S., 49.Martin, R. E., 37.Martin, R. J. L., 39, 275.Martin, T. W., 19.Martinez-Moreno, J. M.,Martini, C. M., 209.Maruyama, K., 360.Maruyama, M., 360.Marxer, A., 204.Marzys, A. E. 0.. 369.Masamune, H., 271.Maschka, A., 112.Maschmann, E., 291.29.296.Mashiko, Y., 358.MaSinovA, V., 360.Mason, D.M., 32.Mason, E. A., 57, 58.Mason, H. L., 210, 327.Mason, H. S., 322.Mason, S. F., 235, 237,Massat, H., 119.Masson, C. R., 42.Masson, D. B., 100:Massy-Westropp, R. A.,Masters, B. J., 30, 47.Masui, M., 363.Matet, J., 292.Mathes, A. P., 365.Mathes, W., 234.Matheson, M. S., 46.Matheson, N. K., 257.Mathieu, J .-P., 85.Mathis, P., 39.Mathot, V., 64.Mathur, G. P., 268.Matijevic, E., 70.Matikkala, E. J., 272.Matolsty, A. G., 390.Matoyama, T., 36.Matregeva, A. N., 359.Matsuda, T., 313.Matsumoto, M., 37.Matsumura, H., 192.Matthes, A., 41.Matthews, J. S., 230.Matthias, B. T., 114.Matti, J., 230.Mattox, V. R., 329.Mattsson, G., 189.Matzuk, A.R., 274.Maung, K., 266.Maury, P. B., 369.Maxwell, C. R., 48.May, A., 103.May, H. U., 164.May, K. R., 71.Mayo, D. W., 84.Mayr, G., 377.Mazor, L., 367.Mazuelos, F., 296.Mazur, P., 62.Meacock, S. C. R., 134.Mead, E. J., 154.bleakins, G. D., 164, 201,Means, J. H., 292.Meara, pvl. L., 296, 313.Meares, P., 64.Mechelynik, P., 363.Mecke, R., 84, 85.Medalia, A. I., 27.Medalia, I. A., 32.Medvedev, S. S., 35, 43.Meecham, S., 211.Meehan, E. J., 32, 37.Meeker, R. E., 27.Meenvein, H., 155.Mehler, A. H., 365.240.170.226424 INDEX OF AUTHORS’ NAMES.Mehta, T. N., 296.Meier, H., 118.Meier, J., 221.Meinke, W. W., 375, 376.Meinwald, J., 182.Meisel, S. L., 238.Meisels, A., 180, 202.Meister, A.G., 83.Meister, P. D., 323, 332.Meites, L., 368.Meland&, L., 26.Meldrum, N. U., 288.Mellor, D. H., 95.Melsted, S. W., 366.Melville, D. B., 287, 289,Melville, H. W., 33, 36,Melville, M. H., 241.Menard, E., 225.Mennicken, G., 118.Mentzer, C., 238.Mercier, D., 198.Mergenthaler, E., 135.Merikanto, B., 349.Merrall, G. T., 42.Merrett, F. M., 36.Merritt, P. E., 87, 95.Merton-Bingham, B. E.,Mesrobian, R. B., 38.Mester, L., 257.Metropolis, N., 60, 63.Metz, D. J., 38.Metze, R., 235.Metzler, D. E., 234.Meyer, A., 320.Meyer, A. S., 128, 208,Meyer, D. M., 278.Meyer, E. W., 210.Meyer, H., 246.Meyer, K., 271.Meyer, K. H., 265, 389.Meyer, L. H., 90.Meyer, R. J., 124.Meyers, R. K., 175.Meyer, W., 212.Meystre, C., 208, 319, 331.Michal, J., 343, 345.Micheel, F., 258, 282, 300.Michel, A., 76.Michel, G., 159.Micheli, R.A., 221.Michels, A., 59, 60, 61, 62. .Mickel, B. L., 96.Mickelsen, W. R., 14.Midzuno, Y., 60.Miescher, E., 73.Miescher, K., 199, 229, 321.Migirdicyan, E., 49.Miglioretto, P., 207.Mignolet, J. C. P., 51.Mihm, X. R., 234.Mijovid, M. V., 223.Mikawa, Y., 84.Mikheeva, V. I., 100.291.37, 38, 372, 373, 377.29.212, 318, 326, 329.Miki, T., 192.Mikl, O., 354.Mikovsky, R. J., 54.Mikula, J. J., 358.Milazzo, G., 73.Milburn, A. H., 302.Milburn, R. M., 96, 124.Miles, D., 173.Milhaud, G., 270.Millard, B., 83.Millen, D. J., 82.Miller, C. O., 240.Miller, D. B., 107.Miller, D. G., 378.Miller, F.M., 238.Miller, G. H., 34.Miller, 1. M., 242.Miller, J . G., 60, 62.Miller, J . R., 34.Miller, L. L., 326.Miller, N., 43, 44, 46.Miller, R., 209.Miller, R. R., 101, 127, 367.Miller, S. I., 84.Miller, S. L., 271.Millner, T., 365.Mills, E. C., 369.Mills, G. A., 29, 55.Mills, G. L., 276.Mills, I. M., 83, 86.Mills, 0. S., 69, 129, 130.Milner, G. W. C., 351, 367,Milstone, J. H., 283.Milton, R. F., 365.Minkoff, G. J., 180, 360.Miquel, R., 359.Mirnik, M., 66, 69.Mirvish, S., 162.Mislow, K., 308.Misra, G. S., 37.Mitchell, H. K., 240.Mitchell, H. L., 364.Mitchell, J. W., 66, 68.Mitchell, P. W. D., 256,Mitgau, R., 159, 170.Mitoma, C., 320.Mitra, M. K., 261.Mitsui, T., 354.Miyahara, F., 356.Miyama, H., 45.Miyamoto, M., 367.Miyauchi, D.T., 296.Miyazaki, S., 24, 45.Miyazawa, T., 84, 87.Mizushima, M., 60.Mizushima, S., 85, 87, 95.Mladenovic, S., 363.Mochel, W. E., 36.Moelants, L. J., 354.Moeller, T., 104.Moffitt, W., 77, 180.Morgis, G. G., 71.Molinari, E., 55.Moljk, A., 376.Meller, C. K., 73.358, 372.257, 260.Molnar, G. D., 286, 288,Momoki, K., 363.Monfils, A., 92.Mongkolsuk, S., 237.Monnier, D., 360.Montagne, R., 292.Montariol, F., 371.Montgomery, R., 262.Montreuil, J., 338.Moody, R. W., 262.Mooradian, A., 209.Moore, C. G., 372.Moore, F. L., 371.Moore, G. E., 52.Moore, G. W., 139.Moore, J. A., 224..Moore, M., 242.Moore, S., 272, 276, 277,Moore, W. J., 9.Morath, R. J., 150.Moretti, J., 301, 313.Morey, G.W., 113.Mori, M., 366.Mori, R. I., 233.Morice, I. M., 303.Morimoto, I., 272.hloritani, I., 145.Morley, H. V., 239, 287.Morgan, K., 154, 255.Morgan, L. O., 372.Morgan, W. 33. D., 137.Morgan, W. T. J., 336,Moro, E., 333.Morozova, M. P., 112.Morrison, G. H., 375.Morrison, J. A., 53.Morrissey, C. J., 234.Morton, A. V., 168.Morton, I. D., 305.Morton, M., 33.Morton, R. A., 164.Mosbach, E. H., 212.Moser, C., 73.Mosettig, E., 214, 218, 222.Mosher, H. S., 85, 234.Moss, F. A. J., 104.Mott, R. A., 353.Moudy, L., 366.Moustafa, E. M., 316.Moye, C. J., 170.Muckenfuss, C., 60.Muller, A., 159.Muller, E., 167.Miiller, E. W., 52.Miiller, G., 348.Miiller, G. E., 103.Mueller, G. P., 218.Miiller, M., 216.Miiller, R., 105.Miillner, F.X., 213.Muendel, C. H., 97.Mulley, B. A., 171.Mukai, T., 177.Mukharji, P. C., 229.Mukherjee, A., 366.394.337INDEX OF AUTHORS’ NAMES. 425Mukherjee, A. K., 97, 342,Mukherjee, S., 268, 301.Mukerjee, S. K., 236.Mukherji, B. K., 313.Mulford, R. N. R., 122.Muller, G., 178.Muller, Y. M. F., 243.Mulliken, R. S., 76.Mullin, J. B., 368.Munksgaard, E., 333.Muraca, R. F., 345, 369.Murk, J. B., 71.Murmann, R. K., 98.Murphy, D., 269.Murphy, S. J., 60.Murr, B. L., 229.343.Murray, H. C., 323, 326,332.Murray, K. A., 363.Murray, K. E., 165, 296,Murty, B. V. S. R., 352.Muschlitz, E. E., 43.Musgrave, W. K. R., 355.Musil, A., 342, 349, 351.Myers, R. J.. 82.Mysels, K.J., 67.Nace, H. R., 151, 213.Nadel, E. M., 326.Nagakura, S., 79.Nagamatsu, A., 275.Nagel, K., 159.Nagels, P., 68.Nagy, Z., 367.Nailor, R., 301.Nair, P. V., 313.Nakagawa, I., 84, 87.Nakagawa, M., 145.Nakamura, M., 275.Nakanishi, K., 272.Nakano, K., 362.Naldrett, S. hT., 19.Nandi, U. S., 35, 36.Nanta, W. T., 133.Narayan, K. A., 301, 302.Narayanan, C. R., 224.Nardelli, M., 105.Narita, K., 277.Natelson, S., 367.Nath, B., 165, 308.Nathan, A. H., 208, 214.Natta, G., 38.Nast, R., 120, 126, 127.NaudC, S. M., 74.Nayler, J. H. C., 232, 239.Nayler, P., 137, 163.Naylor, R., 390.Nazarenko, V. A., 367, 368.Nazarov, I. N., 229.Nedenskov, P., 230.Needham, D. P., 18.Neely, W. B., 260, 269.Negita, H., 92.Neher, R., 216, 217, 319,307.328.Neill, K.G., 197.Neiman, M. B., 13.Neish, A. C., 259.Nelan, D. R., 164.Nelson, F., 97, 358.Nelson, L. C., 376.Nelson, N. A., 183.Nelson, R. C., 78.Nelson, R. D., 97.Neptune, J. A., 121.Nes, W. R., 214.Nesbet, R. K., 77.Ness, R. K., 259.Nestvold, M., 309.Nesvadba, H., 243.Nethercot, A. H., 83.Neurnan, F., 210.Neuman, W. F., 99.Neumann, H. M., 27.Neumann, R., 364.Neurath, H., 382.Neuss, N., 248.Nevenzal, J. C., 306.Neville, 0. K., 138, 150.Nevin, E. E., 75.Newark, P., 401.Newbold, G. T., 170, 215,Newby, B. J., 359.Newitt, D. M., 59.Newman, M. S., 132, 161,Newstead, E., 232.Newton, E. B., 288.Newton, G. G. F., 278, 279.Newton-Hearn, P. A., 260.Neyer, R., 331.Nichol, J.C., 362.Nicholls, R. V. V., 264.Nichols, M. J., 111.Nichols, N. L., 83.Nicholson, G. A., 59.Nicholson, W. H., 258,Nickell, C., 302, 316.Nickon, A., 194, 195.Niclause, M., 13, 144.Nicols, P. L., 297.Nielsch, W., 365, 366,367, 368, 369.Nielsen, A. H., 83.Nielsen, J. T., 230.Nigam, S. S., 165, 306.Nightingale, R. E., 83.Nijboer, B. R. A., 63.Nijkamp, H. J., 297.Nikitenkov, V. Ye., 12.Nikol’skaya, L. E., 27.Nikuradse, A., 64.Nineham, A. W., 234.Nippoldt, B. W., 356.Nishida, H., 367.Nishikawa, T., 82.Nishimura, M., 366.Nitsch, W. H., 300.Niu, C., 231.Nobile, A., 208.236.172, 181.268.Noble, R. H., 83.Noda, M., 300, 301.Noguchi, J., 282.Noland, W. E., 238.Nolin, B., 88, 208.Noll, H., 304.Nomizo, Y., 362.Nord, A.A., 88.Nord, F. F., 231.Nord, H., 29.Nordenfeldt, S., 291.Normant, H., 167, 188.Norris, R. F., 333.Norris, T. H., 30.Norrish, R. G. W., 16, 17,North, A. C. T., 389, 390.Northcote, D. H., 260, 266.Norton, L. L., 218.Nonvitz, G., 366.Norymberski, J. K., 153,203, 219.Novak, A., 85.NovBk, J. V. A., 359.Nowotny, H., 108.Noyes, R. M., 28, 30, 46.Noyes, W. A., jun., 19, 21.Nozaki, T., 367.Nozoe, T., 177.Nudenberg, W., 23, 37.Numerof, P., 209, 373.Nunez, G., 300.Nunn, J. R., 165, 267, 268,Nussbaum, A. L., 191.Nutten, A. J., 353, 356.Nyman, C. J., 100.Nystrom, R. F., 153.Obermeier, F., 280.Oblad, A. G., 55.O’Brien, J. L., 33.O’Brien, K. G., 85.O’Brien, M. C. M., 91.O’Ceallachain, D.F., 268.Ockenden, H. M., 122.O’Colla, P. S., 258, 263,O’Connor, D. J., 68.O’Connor, P. R., 33.O’Connor, R. T., 301, 306.Oda, Z., 51, 52.Odell, A. L., 95.olander, A., 99.Dstergaard, K., 348.Ostman, C. O., 29.Oey, T. S., 123.Offenbach, J., 33.Ofner, G., 108.Ofner, P., 327.Ogard, A. E., 152.Ogawa, M., 74.Ogawa, S., 92.Ogg, R. A., 83, 90.Ogimachi, N., 138.O’Hare, J. P., 292.Ohashi, S., 354.23, 75.302, 308.267, 268426 INDEX OF AUTHORS’ NAMES.Ohki, E., 192.Ohlweiler, 0. A., 358.Ohno, A., 60.Ohno, K., 60, 277.Oi, N., 366, 367.Oiwa, M., 33.Oka, Y., 367.Okada, S., 347.Okada, Y., 354.Okajima, M., 313.Okamoto, T., 150.Okamoto, Y., 145.Okamura, S., 36, 37.Oktawiec, M., 362.Okuda, M., 357.Okumura, F.S., 240.Oldenburg, E. B., 163.Oliv6, S., 37.Oliver, F. H., 354.Oliveto, E. P., 154, 159,Ollis, W. D., 233.O’hane, J. K., 83.Olsen, M. E., 275.Olsen, P. B., 356.Olson, E. C., 359.O’Mant, D. M., 256.Oncley, J. L., 62.O’Neill, A. N., 267.Onishi, H.. 345, 367, 369.Ono, T., 275.Onstott, E. I., 105.Onyon, P. F., 33, 36.Onyszchuk, M., 23.Opfell, J. B., 59.Opitz, H. E., 84.Oppenheim, I., 63.O’Reilly, E. J., 84.Orgel, L. E., 79, 80, 81,Ormond, R., 232.O’Rourke, J. D., 347.Orr, C., 72.Orr, R. J., 35, 38.Orr, S. F. D., 85.Orr, W. C., 105.Osberg, W. E., 86.Osborne, C. E., 166.Osborne, R. N., 109.Osdene, T. S., 240.Ositjanskaja, L., 86.Osman, A. M., 173, 237.Osmond, R. G., 376.Ostens, E.S., 392.Osthoff, R. C., 40.Osugi, J., 15.O’Sullivan, J. F., 235.O’SuIlivan, W. I. A,, 235.Oswin, H. G., 21.Otero, C., 83.Otey, M. C., 275.Otken, C. C., 289.Ott, A. C., 213.Ott, D. G., 138.Otting, W., 173, 232.Otto, K., 357.Otto, R., 111.208, 211, 214, 220.93.Ottolenghi, A., 301.Ouellet, C., 14.Oughton, J. F., 222.Ourisson, G., 195, 206.Overbeek, J. T. G., 57,67, 68, 69, 71.Overberger, C. G., 36, 38,134, 183.Overell, B. G., 282.Overend, W. G., 42.Overland, L., 221.Overton, K. H., 199.Owen, L. J., 231.Owen, L. N., 137, 189.Owen, T. C., 164, 165.Owens, H. S., 266.Oxford, A. E., 270.Oza, T. M., 111.Pace, E. L., 83.Pacheco, H., 238.Packham, D. I., 238.Pacsu, E., 261, 265.Paabo, K., 213, 306, 312,Paech, K., 255.Pagano, A.S., 158.Page, I., 394.Page, I. H., 280.Page, J. E., 208, 222.Paige, H. H., 365.Pailthorpe, M. W., 58.Paine, H. H., 67.Pajaro, G., 30.Pakulla, I., 112.Palik, E. D., 82.Palin, D. E., 373.Palit, S. R., 35, 36, 37.Palluel, A. L., 250.Pal’m, V. A., 8.Pammer, E., 123.P’an, S. Y., 221.Panckhurst, D. J., 107.Pande, C. S., 99.Pande, G. D., 313.Pandow, M. L., 247.Pani, S., 115.Pannell, J. H., 377.Pannetier, G., 18.Panos, C., 312.Papay, M., 351.Pappo, R., 227, 228.Paratla, A. G., 369.Parchen, F. R., 28.Parham, W. E., 179.Paris, G., 274.Park, J. D., 85.Parker, K. D., 386.Parlin, R. B., 53.Parr, R. G., 72.Parrish, R. G., 392.Parry, R. W.,, 101.Parsonage, N. G., 64.Parsons, J. S., 363.Parsons, R., 65, 66.Partridge, S.M., 283.Paschke, R. F., 306.331.Pataki, J., 317.Patat, F., 40, 112.Patchornik, A., 281.Pate, B. D., 375, 376.Patel, D., 331.Patel, D. K., 209, 210.Patel, S. A., 111.Pathak, K. D., 296.Pathak, S. P., 313.Patrick, J. B., 249.Patrovsky, V., 345, 348,Patterson, E. L., 240.Patterson, I., 300.Patti, F., 48.Patton, A. R., 291.Patty, F., 369.Paudler, W. W., 240.Paul, L., 252.Paul, R. C., 113.Paul, S. D., 344.Pauling, L., 381, 383, 385,Paulson, J. C., 276.Pausacker, K. H., 146, 168.Pauson, P. L., 94, 129, 130,PavloviC, D., 32.Pavone, D., 99.Payne, C. C., 208, 221.Pchelkin, M. A., 114.Pchelkina, M. A., 114.Peace, J. B., 68.Peacock, J., 26.Peacock, R. D., 124, 127.Peacocke, A.R., 42.Peake, J. S., 84.Pearse, J. F., 62.Pearson, D., 61.Pearson, D. E., 147.Pearson, R. G., 27.Pearson, R. K., 100.Pearson, R. M., 350.Pease, R. N., 14.Peat, S., 264, 266.Pech, J., 354.Pechet. &I. M., 308.Peck, R. L., 232.Peckworth, J., 403.Pederson, R. L., 213.Peetz, U., 121.Pelchowicz, Z., 237.Pelczar, M. J., 338.Pellam, J. R., 115.Pelletier, S. W., 254.Pellon, J. J., 13.Pemsler, J. P., 88.Penasse, L., 278.PCneloux, A., 8.Penna-Franca, E., 27.Pennetier, G., 14.Penniall, R., 367.Pennington, R. E., 59.Pepper, K. W., 276.Peppiatt, E. G.,53. 139,185.Percival, E. G. V., 262,263, 264, 267, 269.367.386, 387, 389, 396.180INDEX OF AUTHORS’ NAMES. 427Peries, P., 65.Perila, O., 300, 301.Perizzolo, C.F., 34.Perkampus, H.-H., 77.Perkins, R. H., 27.Perlin, A. S., 256, 267, 268.Perlman, D., 207, 323.Perlman, P. L., 208.Perlmutter-Hayman, B.,Perrier, M., 230.Perry, E. S., 297.Perry, M. B., 270.Person, W. B., 84, 86.Perutz, M. F., 382, 383,391, 393.Peters, E., 29.Peters, R. A., 288.Peterson, A. H., 71.Peterson, D. C., 48.Peterson, D. E., 61.Peterson, D. H., 207, 323,Peterson, J. I., 347.Peterson, J. L., 36.Peterson, L. H., 231, 304.Peterson, Q. R., 213.Peto, A. G., 137.Petrackova, M., 360.Petrocelli, J. V., 358.Petrow, V., 209, 210, 218,Petrzilka, T., 245.Petit, E. L., 168.Pettit, R., 176.Petzold, A., 369.Peyer, J., 242.Pfab, B., 364.Pfefferle, W. C., 60.Pfister, K., 274.Pflaum, R.T., 98.Pfleiderer, G., 274.Pflugmacher, A., 123.Pfohl, W., 104, 155.Pfundt, O., 339.Philbin, E. M., 235.Phillips, D. D., 246.Phillips, P. C., 226.Phillips, W. D., 90.Phillips, W. F., 232.Philpott, D. E., 386.Philpotts, A. R., 39, 85.Photaki, I., 280.Picon, M., 122.Pickett, T. A., 313.Pickup, R., 369.Pickworth, J., 242.Pien, J., 340.Pierce, J. B., 232.Pierce, J. G., 283.Pierce, J. H., 211.Pierce, L., 83.Pierre, P. D. S., 112.Pierson, R. H., 349.Pierson, R. M., 37.Pietsch. R., 342, 356.Piez. K. A., 275.29.326, 332.282, 331.Piirma, I., 33.Pike, J. E., 227, 228.Pilc, A., 15.Pilgrim, A. F., 303.Pilgrim, F. J., 160.Pillai, K. S. M., 313.Pillar, C., 185.Pilz, I., 387.Pilz, W., 350.Pimentel, G.C., 84, 86,88, 89, 90,Pincus, G., 317, 318, 324.Pinder, A. R., 227.Pinder, J. A., 22.Pindred, H. K., 236.Pines, H., 168.Piper, T. S., 87, 130.Pirie, N. W., 285.Piskur, M. M., 296.Pitt, G. A., 164.Pitt-Rivers, R., 295.Pitts, J. N., jfin., 19.Pitzer, K. S., 31, 61.Plager, J. E., 324.Plane, R. A., 27.Platt, J. R., 77.Plattner, P. A., 197.Platzer, H. K., 120Platzman, R., 42.Pletikha, R., 358.Plieninger, H., 152.Pliskin, W. A., 56.Plouvier, V., 257.Plumb, R. C., 86, 376.Pluyger, C. W., 161.Plyler, E. K., 83, 89.Podkolzina, L. A,, 366.Pohland, A., 232.Pohmer, L., 160.Polanyi, J. C., 11, 22, 24.Polder, D., 57.Polesofsky, W., 313.Polgar, N., 166, 304.Pollard, J. K., 272, 273.Polley, H.F., 317.Pollock, D. J., 38.Polonsky, J., 304.Polonovski , J . , 3 13.Polonovski, M., 334, 338.Polster, R., 161.Polyak, S., 156, 171, 182.Pongratz, A., 313.Poole, H. G., 87.Poos, G. I., 157, 216, 219,220, 228.Popenoe, E. A., 279.PopjAk, G., 297, 315.Pople, J. A., 58, 62.Popov, A. I., 104.Poppelsdorf. F., 161.Porath, J., 278.Porges, J., 37.Porter, A. S., 51.Porter, G., 17, 23, 75, 79.Porter, P., 365.Porter, R. R., 283.Porto, s. P. s., 74.Posner, A. M., 29, 367.Potter, A. L., 266.Potter, I., 232.Potter, R. M., 99,Potter, V. R., 289.Potts, K. T., 238.Potts, W. J., 76.Potts, W. M., 306.Powers, M. D., 60.Powling, J., 18.Prabhu, G. S., 296.Pradhan, M. K., 146.Praetz, B., 327.Prager, J., 183.Pratt, B.C., 232.Pratt, E. F., 161.Pratt, M. W. T., 13.Pravda, Z., 152.Preece, I. A., 260.Prelog, V., 145, 156, 171,182, 223, 242, 245, 248,250.Premaswarup, D., 75.Preston, R. P., 297.Pretorius, V., 18.Prdvost, C., 359.Pr6vot-Bernas, A., 49.Pfibil, R., 345, 350, 351,Price, C. C., 38.Price, W. C., 385.Prigogine, I., 64.Primak, W., 45.Primas, H., 86.Pringsheim, P., 50.Pritchard, G. O., 22.Pritchard, H. O., 8, 22, 23.Privett, 0. S., 302, 316.Pro, M. J., 365.Prokhorov, P. S., 72.Prokof’eva, E. A., 112.Prosen, R. J., 242, 403.Protiva, K., 367.Prue, J. E., 65.Pryce, M. H. L., 91.Pshezhetsky, S. Y., 45.Pucheault, J., 44.Puckett, J. E., 359.Puddington, I. E., 57, 69.Puschel, R., 351.Pujo, A. M., 48.Puke, S.M., 127.Pummerer, R., 173.Pungor, E., 365.Purdon, W. A. B., 28.Purdy, W. C., 366.Pursglove, L. A., 369.Purushottam, A., 369.Purves, H. D., 291, 292.Pusch, F. J., 316.Puttfarcken, H., 173.Pyke, J. B., 23.Pzhezhetskii, S. Ya., 24.Quackenbush, F. W., 297.Quaglia, S. A., 313.Quagliano, J. V., 87, 95.366428 INDEX OF AUTHORS’ NAMES.Quimby, 0. T., 373.Quincey, P. G., 174.Quinkert, G., 226.Quist, J. D., 68.Quitt, P., 280.Raabe, F., 109.Raaen, H. P., 372.RaaI, F. A., 22.Rabben, H. J., 123.Rabinovitch, B. S., 17, 25.Rabinovitz, M. , 275.Raciszewski, 2. M., 294.Rados, M., 213, 295.RAdy, G. Y., 369,Ratz, R., 112.Raffelson, H., 227.Raju, N. A., 345.Rakshit, S. C., 67.Ramachandran, G. N., 85,Ramage, G.R., 194, 239.Ramaiah, N. P., 359.Ramart-Lucas, P., 134.Ramierez, F., 153.Ramirez, F., 135, 144,Ramsay, D. A., 75, 76.Ramsay, H., 189.Ramsey, L. L., 300.Rarnsey, W. J., 32.Randall, J. T., 389, 390,Rank, D. H., 73, 82.Ranke-Madsen, E., 348.Rankin, J. C., 269.Rao, 33. C. S., 154.Rao, Bh. S. V. R., 342, 343.Rao, B. Y., 296.Rao, C. V. N., 296.Rao, G. G., 345, 352.Rao, K. B., 352.Rao, K. S., 296.Rao, V. P., 352.Raoul, Y., 213.Raphael, R. A., 156, 183,Rapoport, H., 178.Rapoport, S., 336.Rapp, W., 135.Rasp& G., 165.Ratusky, J., 243.Rauenbusch, E., 135.Rausser, R., 211, 214.Raw, C. J. G., 102.Rawson, R. W., 292.Ray, P., 368.R&y, P., 97.Raybutt, R. B., 382.Raymond, A. L., 295.Rayson, D., 84.Razdan, R.K., 172.Read, J., 190.Read, R. H., 356.Rebbert, R., 21.Rebentisch, W., 111.Rebers, P. A., 256.389, 390.221.391, 398.259, 306, 311, 312.Reburn, W. T., 97,Redfield, R. R., 394.Reding, F. P., 86.Ree, T., 52.Reed, H. W. B., 180.Reed, J. F., 17.Reed, L. J., 231, 304.Reed, R., 391.Reerink, H., 69.Rees, R. W., 214.Reese, R. M., 43.Reeves, C. G., 59.Reeves, J. M., 257.Reeves, R. E., 98.Rega, A., 335.Regan, B. M., 210.Regan, C. M., 174.Reggiani, M., 208.Register, U. D., 289.Regna, P. P., 256.Rehm, C. R., 362.Reich, H. E., 234.Reich, R., 371.Reichstein, T., 207, 216.Reid, D. H., 179.Reid, R. C., 13.Reid, S. G., 264.Reid, W. W., 255.Reiff, H. E., 179.Reiher, M., 281.Reilley, C. N., 25, 365.Reilly, C.A., 90.Reinebeck, L., 76.Reineke, E. P., 373.Reineke, L. M., 323, 332.Reinhart, J., 360.Reinhold, C. L., 297.Reinisch, L., 49.Reinke, W. H. E., 313.Reiser, R., 243.Reisman, A., 114.Rekker, R. F., 133.Rembaum, A., 11, 138.Remers, W. A., 90, 181.Rempe, G., 117.Renner, H., 109, 114.Rennhard, H. H., 176.Renzi, A. A., 329.Reppe, W., 159, 162.Ressler, C., 279.Restivo, A. R., 209.Reuteler, K. G., 213.Reynolds, G. F., 360.Reynolds, S. A., 371.Reznik, B. E., 368.Rhoads, C. P., 326.Ribas, I., 307.Ricca, B., 367.Ricca, M., 45.Ricci, J. E., 99, 122.Riccio, W., 296.Ricciuti, C., 302.Rice, B., 88, 100.Rice, F. O., 9, 23, 110.Rice, H. L., 234.Rice, R. G., 160.Rice, W. E., 57.Rich, A., 389, 399, 401.Richards, D.H., 375.Richards, E. L., 154.Richards, F. M., 384.Richards, G. N., 147, 256,Richards, H. C., 211.Richards, H. P., 230.Richardson, D. N., 235.Richardson, E. G., 56.Richardson, M. F., 252,Richardson, W. L., 282.Richter, D. E., 102.Rideal, (Sir) E. K., 51, 52,Ridge, M. J., 14, 22.Riedel, L., 61.Riemenschneider, R. W.,Rjenits, K. G., 260.Rigamonti, R., 296.Rigby, W., 198.Rigg, T., 47.Riggs, N. V., 243.Riley, D. P., 383, 394, 398.Riley, J. P., 356, 368.Rimington, C., 286, 287,Rimmer, W. B., 76.Rinehart, R. W., 369.Ringbom, A., 351.Ringolo, H. J., 317.Rios, T., 205.Rist, C. E., 260, 269.Rist, H., 160.Ritchie, E., 244, 245.Ritchie, J. A., 351.Rittel, W., 191.Rittenberg, D., 286, 330.Ritter, J.J., 316.Rivard, D. E., 153.Robb, J. C., 21.Roberts, C. B., 364.Roberts, C. W., 175, 279.Roberts, E. A. H., 236.Roberts, G., 208, 222.Roberts, G. D., jun., 32.Roberts, J. C., 171, 174,Roberts, J. D., 160, 174.Roberts, K. H., 368.Roberts, L. E. J., 52.Roberts, R., 121.Robertson, A., 173, 237,Robertson, H. J., 73.Robertson, J. H., 242, 403.Robertson, J. M., 132, 187,Robertson, J. S. M., 266.Robertson, P., 384.Robertson, W. G. P., 377.Robeson, C. D., 164.Robin, J., 89.Robins, P. A., 135, 184.Robinson, A. M., 58.Robinson, C., 385, 394.265.53, 71.297.289, 290.237.238.194INDEX OF AUTHORS’ NAMES. 429Robinson, C. R., 213.Robinson, F. M., 216, 228,242 .Robinson, P. L., 12, 111,118, 127.Robinson, (Sir) R., 227,238, 242, 246, 249.Robinson, R.E., 155, 168.Robinson, R. W., 292.Robison, B. L., 159.Robison, M. M., 159.Rod, P., 113.Rodda, H. J., 231, 303.Rode, J. A., 18.Rodgers, A., 373.Rodziewicz, W., 345.Roe, D. K., 100.Roe, G. M., 60.Roedig, A., 137.Rogan, J. B., 183.Rogers, D., 208.Rogers, E. F., 274.Rogers, L. B., 345, 363, 368.Rogers, M. A. T., 152.Rogers, 0. G., 318, 326.Rohr, O., 215, 217.Rohr, T. M., 21.Roiter, V. A., 8.Rolfe, A. C., 369.Rolfe, J. A., 83, 88.Rolipoli, A. E. C., 24.Rollefson, G. K., 47.Roller, G. G., 182.Rollet, A. P., 97.Rollett, J. S., 384, 394.Romand, J.. 73.Romanko, J., 82, 83.Romer, R. H., 81.Romero, M. A., 213.Rorno, J., 254, 317.Romoser, G. L., 338.Roncero, A.V., 313.Ronco, A., 197.Rose, C. S., 333, 334, 336,Rose, F. L., 240.Roseman, S., 260.Rosen, W. E., 222.Rosenberg, E., 320.Rosenberg, J., 181.Rosenblum, B., 82.Rosenblum, L., 101.Rosenbluth, A. W., 63.Rosenbluth, M. N., 63.Rosenfeld, R. S., 215, 330.Rosenhead, L., 56.Rosenkrantz, H., 208, 209,Rosenkranz, G., 210, 211,Roseveare, W. E., 60.Rosnati, V., 212.Ross, A., 185.Ross, W. C. J., 169.Rosselet, J. P., 221.Rosser, S. E., 83.Rossmy, G., 84.337.326.219, 317, 323.Rossotti, F. J. C., 27.Rossotti, H. S., 340.ROSSOUW, A. J., 102.Rotenberg, D. L., 83.Roth, M., 217,Rothemund, P., 241.Rothman, E. S., 223.Rothman, S., 304.Rott, E., 64.Rottenberg, M., 306, 331.Roubal, Z., 351.Roudier, A., 262.Rougvie, M., 390.Routley, P.M., 74.Rovery, M., 277.Rowc, F., 179.Rowland, B. I., 147.Rowley, K., 363.Rowlinson, H. C., 53.Rowlinson, J. S., 56, 58,59, 60, 61, 64.Roxburgh, C. M., 259.Roy, A., 313.Royals, E. E., 189.Royen, P., 106.Rozedestvenskaya, G. B.,Rozlovskii, A. I., 15.Rubin, B. A., 323.Rubin, M. B., 153.Rudel, H. W., 221.Rudinger, J., 152.Rudolph, H., 208.Rudorff, W., 106, 114.Ruedi, W. F., 360.Ruegg, R., 201, 202.Ruetschi, R., 51.Ruehrwein, R. A., 108.Ruelius, H. W., 334.Ruetschi, P., 26.Ruiter, L. I-I., 65.Ruka, R. J., 54.Rulfs, C. L., 124.Rumpf, J. A,, 331.Rundel, W., 167.Runge, W. F., 232.Rupp, J. J., 212.Ruschig, H., 219, 220.Rush, R. H., 366.Rush, R. M., 345.Rushbrooke, G.S., 63, 64.Rushman, D. F., 371.Ruske, W., 235.Russel, F. R., 369.Russell, C., 48.Russell, G. A., 143.Russell, K. E., 36.Russell, P. B., 133.Russell, R. A., 86.Russell, W. C., 165.Rutgers, A. J., 67, 68.Rutschmann, J., 245.Ruzicka, L., 184, 185, 190,196, 197, 198, 199, 201,202, 203, 204, 206, 225.Ryan, J. P., 373.Ryan, M., 315.66.Ryason, R., 83.Ryba, O., 348, 349.Rydberg, J., 122.Rydon, H. N., 240, 270,Ryle, A. P., 283, 284.Ryley, J. F., 270.Ryskiewicz, E. R., 159.Saad, K. N., 265.Saarni, K., 368.Saarnio, J.. 262.Sabatier, G., 61.Sabo, E. F., 209, 217.Sacco, A., 126.Sachtler, W. M. H., 51.Sackler, M. L., 380.Saeland, E., 44.Sage, B. H., 59.Sager, W. F., 158.Saha, A. K., 90.Saha, N.G., 35.Saha, N. N., 386.Sahasrabudhe, M. B., 275.Sainsbury, I. E. J., 65.St. BndrC, A. F., 247, 248.St. Garay, A., 289.St. Pierre, P. D. S., 99.Saito, E., 31.Sajb, I., 351.Sakai, T., 313.Saletore, S. A., 296.Salmon, J. A., 121.Salmon, J. E., 109.Salmon, L., 375.Salsburg, 2. W., 62, 64.Salter, W. T., 292.Salutsky, M. L., 105.Salvetti, O., 97.Samarina, V. A., 358.Samhammer, E., 264.Samuel, D., 159.Samuels, L. T., 324.Sanchez Serrano, E., 374.Sand, D. M., 297.Sanday, A. P., 60.Sandberg, C. L., 38.Sandell, E. B., 128, 367.Sandeman, I., 85.Sanderson, T. F., 196.Sandler, S., 15.Sandoval, A., 210.Sands, C. A., 101.Sandstedt, R. A., 102.Sanger, F., 283, 284, 394.Sankaran, G., 291..Sankey, G. B., 173.SanniC, C., 223.San Pietro, A., 320.Santavq, F., 178.Santhappa, M., 37.Santoro, V., 30.Sarett, L.H., 157, 209, 216,220, 228.Sargeant, G. A., 54.Sarma, K. P. S., 342.Sarry, B., 126.282430 INDEX OF AUTHORS’ NAMES.Sartor, D., 72.Sasaki, K., 366.Sassaman, H. L., 373.Sasse, W. H. F., 231.Satchell, D. P. N., 26, 31.Sathpathy. S., 341.Sato, Y., 224.Satterfield, C. N., 13.Satuka, A., 362.Saucier, K. M., 80.Sauer, G. L., 238.Sauerland, H. D., 146.Sauermilch, W., 234.Saunders, D. H., 302.Saunders, K. H., 239.Saunders, M., 39.Saunders, W. H., jun., 145.Sauve, D. M., 155, 156,Savard, K., 318, 319, 330.Savary, P., 297.Sax, S. M., 305.Saxl, H., 391.Sayasov, Yu. S., 8.Sayers, N. D., 74.Sayre, E. V., 80.Scanlan, J., 36.Schaefer, A.E., 373.Schafer, H., 115,Schiifer, O., 332.Schafer, W., 281.Schaeffer, G. W., 100, 101.Schaefgen, J. R., 34.Schaeppi, W. H., 176.Schallenberg, E., 281.Schaltegger, H., 213.Schamp, H. W., 59.Scharfstein, L. R., 66.Schatz, P. N., 385, 389.Schawlow, A. L., 81, 92.Schayer, R. W., 374.Schcherbov, D. P., 357.Scheel, K. C., 378.Scheer, I., 214, 218, 222.Scheer, J. J., 127.Scheer, M. D., 13.Schellman, J. A., 283.Schenk, P. W., 116.Schenker, V., 317.Scherber, F., 110.Scherer, J. R. , 83.Schiff, F., 336.Schilling, K., 240, 282.Schindler, A., 34.Schindler, O., 229.Schinkel, H., 364.Schinz, H., 167.Schissler, D. O., 24.-Schlafer, H. L., 79, 80.Schlamowitz, M., 263,Schlein, H. N., 307.Schleitzer, E., 96.Schlenk, H., 296, 297, 300.Schlesinger, H.I., 155.Schlientz, W., 245.Schlinger, W. G., 59.Schlittler, E., 246, 247, 248.168.Schlogl, K., 277, 282.Schlubach, H. H., 264, 265.Schmeisser, M., 123.Schmerzler, G., 277, 278.Schmid, H., 242, 246.Schmid, R. W., 176.Schmidlin, J., 215, 216.Schmidt, C. W., 300.Schmidt, G., 348.Schmidt, G. M. J., 132.Schmidt, H., 122.Schmidt, H. D., 122.Schmidt, P., 402.Schmidt, 0. T., 236.Schmidt-Thom6, J., 220,Schmit, G. C. A., 51.Schmitt, H., 366.Schmitt, J., 23 1.Schmitz-Dumont, O., 109,Schnapp, O., 84.Schneider, A., 99.Schneider, F., 55.Schneider, J., 155, 159.Schneider, J. J., 221, 327.Schneider, K., 155.Schneider, P., 343.Schneider, W., 96.Schneider, W.G., 39, 59.Schneider; W. P., 208, 209,Schneiders, H., 122.Schnepp, O., 78.Schnitzer, M., 366.Schollkopf, U., 163.Schoen, J., 25.Schonberg, A., 237.Schoenfeld, R., 165, 307.Schoniger, W., 353, 355.Schoon, N. H., 98.Schopf, C., 224.Schoffman, E., 341.Scholder, R., 99, 121, 124.Scholes, G., 48.Scholnick, F., 121.Schols, J. A., 300.Schopflocker, P., 173.Schorygin, P., 86.Schott, G., 59.Schramm, G., 399, 400,Schreffler, R. G., 59.Schreiber, E. C., 175.Schreiber, J., 149, 208.Schreiber, K., 224.Schrenk, W. G., 364.Schreyer, J. M., 122.Schriesheim, A., 26.Schroder, H., 235.Schroeder, R., 89.Schroeder, W. A., 390.Schroll, G., 156, 180.Schubert, W. M., 135, 181.Schubert, K., 160, 227.Schuler, H., 75, 76.Schuettler, C.L., 67.31 8.122, 126.214.401.Schuhknecht, W., 364.Schul, C., 378.Schuler, R. H., 44, 48.Schulte-Hiirmann, W., 259.Schultz, H., 15.Schultz-Grunow, F., 14.Schulz, E. V., 261.Schulz, G. V., 37.Schulz, K., 52.Schulz, K. F., 70.Schulz-Kiesow, H., 171.Schumacher, H. J., 25, 60.Schumacker, G., 400, 401.Schumb, W. C., 107, 109.Schumuckler, S., 144.Schwabe, K., 97.Schwan, T. C., 38.Schwartz, H. M., 308.Schwarz, H. A., 46, 47.Schwarz, J. C. P., 256, 295.Schwarz, R., 94, 107, 161.Schwarzenbach, G., 96,339.Schwarzkopf, B., 365.Schwarzmann, E., 114.Schweppe, H., 300.Sciarra, J. J., 361.Scoins, H. I., 63, 64.Scott, A. B., 106.Scott, N., 104.Scott, R. L., 56, 65.Scouloudi, H., 395.Scrivins, J., 58.Scrocco, E., 97.Scroggie, J.G., 146, 168.Seaman, C. E., 36.Seaman, W., 363.Searle, E. H., 355.Sebban, J., 49.Sedivec, V., 360.Seeds, W. E., 384, 398, 399.Seel, F., 118, 123.Seely, B. K., 345.Seeman, H., 104.Seffl, M. E., 85.Segal, L., 98.Segal, W., 172.Seher, A., 311.Sehon, A. H., 19.Seitzer, W. H., 32.Seki, I., 313.Sekora, A., 387.Sela. M., 40, 281.Seligman, H., 371.Selin, L.-E., 75.Selke, W. A., 97.Sellers, D. E., 97.Sellman, P. G., 109.Semmler, F. W., 195.Semonsky, M., 245.Sen, D. N., 95.Sen, J. N., 35.Senda, M., 357.Senent, S., 132.Sen Gupta, A. B., 313.Sengupta, P., 191, 199.Senkus, M., 373.Senn, H., 96INDEX OF AUTHORS' NAMES. 431Sensi, P., 86.Seoane, E., 307.S&r&k, L., 360.Serck-Hanssen, K., 308.Sergeant, J.C., 351.Serota, S., 222, 223.Servigne, M., 274.Seshadri, T. R., 236.Seyfang, A. P., 376.Seyhan, M., 96.Shabica, A. C., 222.Shagisultanova, G. A., 27.Shah, J. n., 312.Shalimoff, G. V., 109.Shalitin, Y., 40.Shapiro, E. L., 208,219.Shapiro, I., 100.Shapiro, J., 153.Shapiro, L., 364.Shapiro, M. Ya., 366.Sharples, A., 261.Sharpless, G. R., 291.Sharpless, N. E., 48.Shaulov, Yu. Kh., 15.Shaw, A. W., 168.Shaw, B. L., 236.Shaw, J. I., 200, 213.Shchukarev, S. A., 112,Shealy, Y. F., 213.Shearer, J. N., 73.Sheats, G. F., 19.Sheehan, J. C., 281, 282.Sheng-Lieh Liu, 304.Shepherd, D. A., 213.Shepherd, R. G., 280.Sheppard, D. E., 88.Sheppard, E., 67.Sheppard, N., 39, 83, 84,Sher, I.H.. 348.Sheridan, J., 81, 82.Sherman, L. J.. 50.Sherman, R. E., 372.Sherrard, E. I., 82.Shestov, A. P., 359.Sheyanova, F. R., 374.Shibata, S., 235.Sheehan, J. C., 314.Shields, H., 42.Shigorin, D. N., 88.Shih, C.-H., 151.Shima, H., 92.Shima, M., 369.Shimanouchi, T., 85, 87.Shimauchi, A., 92.Shimoda, K., 82.Shimoe, D., 356.Shimomura, K., 92.Shine, W., 272.Shingu, T., 252.Shinkarenko, A. L., 366.Shinra, K., 362.Shipe, W. F., 296.Shipko, F. J., 43, 45.Shizume, T., 60.Shoemaker, C , E., 358.121.85, 87.Shonk, C. E., 372.Shoolery, J. N., 90.Shoppee, C. W., 139, 151,152, 211, 212, 213, 214.Shor, 0. L., 123.Shorland, F. B., 302-305.Short, M. S., 338.Short, W. F., 196.Shu, N.W., 14.Shufler, S. L., 87, 124,Shulman, C., 383.Shulman, S., 401.Shunk, C. H., 242.Shute, J. M., 344.Shyluk, W. I?., 148.Sianesi, D., 35.Sicard, A., 14, 18.Sicre, J . E., 25, 74.Siddiqi, A. M., 301.Siddiqui, M. S., 313.Sidman, J. W., 79.Sidorov, A. N., 87.Sieber, H., 40.Siebert, H., 95.Siebrasse, K. V., 248.Sihota, G. S., 296.Silberman, H., 172.Silk, M. H., 162, 297, 300,Silker, R. E., 364.Silveira, V., 266.Silverman, J., 61.Silverman, L., 361, 366.Silverman, M., 146.Silverman, R. H., 376.Silverstein, R. M., 159.Simamura, 0.. 159.Simeral, W. G., 86.Simes, J. J. H., 224.Simmler, J. R., 368.Simmons, H. E., 160.Simmons, J. W., 82.Simmons, R. F., 16.Simmons, R. O., 297.Simon, A., 112.Simon, K., 282.Simon, V., 358.Simons, J.H., 123.Simonsen, (Sir) J., 189,Simonyi, L., 355.Simpson, D. M., 84.Simpson, K. B., 312.Simpson, S. A., 329, 374.Simpson, T. H., 236.Simpson, W., 34.Simpson, W. T., 78.Sims, H. 3, 159.Sinclair, D., 39.Sinclair, R. G., 301.Singer, F. M., 209.Singer, L. S., 91.Singh, B., 352, 361.Singh, G., 361.Singh, J., 313.Singh, S., 352.125.307.193, 195.Sinha, P. R., 37.Sinnott, K. M., 82.Sircar, S. S. G., 341.Sirotenko, A. A., 355.Sirtl, E., 120.Sisler, H. H., 107, 110.Sivertz, U., 35.Sixma, F. L. J., 133.Sjovall, J., 330, 331.Sjollema, B., 295,Skarbye-Nielsen, H., 348.Skarulis, J. A., 97.Skattebol, L., 162.Skau, E. L., 297.Skinner, G. B., 108.Skinner, M. W., 86.Skirrow, G., 18.Skoda, J., 343.Skogstrom, P., 208.Skoog, D.A., 349.Skoog, F., 240.Slabon, M., 359.Slates, H. L., 211, 215,Slawsky, 2. I., 59.Sloan, C. K., 70.Sloan, J. W., 269.Slocomb, C. H., 317.Slomp, G., jun., 213.Sloth, E. N., 26.Slowinski, E. J., 89.Slowinski, E. J., jun., 32.Smales, A. A., 372, 375,Small, P. A., 32.Smaller, B., 46.Smart, J. A., 366.Smart, R. C., 360.Smeltzer, P. B., 214.Smiley, R. L., 374.Smiljanic, A. M., 304.Smirnov, V. S., 309.Smith, B. B., 213.Smith, C. R., 254.Smith, D. B., 267.Smith, D. C. C., 256, 258.Smith, D. F., 88.Smith, D. K., 301.Smith, E. L., 242, 373.Smith, E. R., 327.Smith, F., 170, 255, 256,262, 264, 268.Smith, G. F., 349.Smith, G. G., 138.Smith, G. N., 319.Smith, G.W., 358, 371.Smith, H. Q., 211.Smith, J. C., 308, 311.Smith, J. W., 22.Smith, L. F., 284.Smith, L. W., 253.Smith, M. J., 22.Smith, N. H. P., 134, 136.Smith, P. A. S., 185.Smith, P. N., 271, 337.Smith, P. W. G., 282.Smith, R., 368.219.376432 INDEX OF AUTHORS' NAMES.Smith, S. B., 344.Smith, S. H., 101.Smith, S. J., 43.Smithies, O., 283.Smoller, J., 357.Smyth, D. G., 139.Smyth, D. M., 109.Sneeden, R. P. A., 157Sneen, R. A., 184.Sneezum, J. S., 175.Snell, E. E., 234.Snell, R. L., 184.Snipes, R. F., 150.Snoddy, C. S., jun., 209.Snow, G. A., 166.Snyder, H. R., 159, 232,Soderberg, B. A., 65.Soderback, E., 161.Sonke, H., 155.Sorensen, J. S., 162, 309,Sorensen, N. A., 162, 309,Solimene, N., 82.Solomon, 0.F., 161.Solomons, I. A., 239, 310.Sommargua, M., 151.Sommer, L. H., 108.Sone, K., 83.Songina, 0. A., 359.Sondheimer, F. , 133, 134,209, 211, 219, 226, 306,311, 312, 317, 323.Sonkin, L. S., 71.Sood, K. C., 352.Sorensen, J. H., 353.Sorensen, P., 373, 374.Sorm, F., 152, 189, 211,217, 224, 243.Sorrie, A. J. S., 178.Sosnovsky, H. M. C., 54.Souchay, P., 359.Soulen, J. R., 99.Sourisseau, G., 88.Sowden, J. C., 373.Spath, E., 250.Spall, B. C., 9.Spandau, H., 118.Sparmberg, B., 338.Sparnaay, M. J., 57, 69.Speakman, J. C., 180, 403.Speakman, P. T., 28.Specker, E., 366.Specker, H., 367.Speeter, M. E., 238.Spencer, E. Y., 294.Spencer, H. E., 47.Spero, G. B., 323.Speziale, A. J., 227,Spicer, S.S., 289.Spier, M., 395.Spillmann, M., 199.Spiteri, J., 300.Spitzy, H., 372.208.238.310.310.' Soler, A., 313.Spoelstra, D. B., 197.Spoerri, P. E., 175.Spohler, E., 256.Sponer, H., 72, 78.Sponer, R., 112.Spooner, C. E., 353.Sporek, K., 346.Sprague, J. W., 133.Spriestersbach, D., 268.Spriestersbach, D. R., 255.Spriggs, A. S., 373.Spring, F. S., 200, 203,204, 205, 215, 226.Springall, H., 174.Springall, H. D., 382.Springer, G. F., 336.Springer, G., R., 336.Srinivasan, R., 8.Srivasta, H. C., 268.Stacey, M., 147, 255, 256,260, 269, 270.Stack, M. V., 336.Stadler, H. P., 111.Stadlmann, W., 99.Stadtman, E. R., 314.Stafford, J. E., 213.Stafford, W. H., 179.Stafiej, S., 144, 221.Stagg, H.E., 356.Stahl, E., 180.Stahl, H. O., 130.Staiger, G., 173.Stallmann, J., 302.Stal'makhova, L. S., 12.Stammbach, K., 378.Stammer, C. H., 232.Stammreich, H., 83.Stange, K., 276.Stanley, M. N., 290, 292.Stanley, R. W., 73.Stannett, V., 138.Stansbury, E. J., 82, 83.Staritzky, E., 99.Starkowsky, N. A., 237.Staveley, H. E., 232.Staveley, L. A. K., 64, 65.Stavholt, K., 162, 310.Steacie, E. W. R., 7, 11,Stedman, G., 30.Stedman, R. J., 231.Steere, R. L., 399.Steger, E., 112.Stein, G., 47, 48.Stein, R. S., 84.Stein, W. H., 272, 276,Steinberg, E. P., 376.Steinberg, H., 184.Steinberg, I. V., 308.Stempel, A., 233.;tender, W., 252.Stene, J., 309, 310.Stenhagen, E., 308.Stephen, A. M., 267, 268.Stephen, M. J..24.Stephens, C. R., 160.19, 21, 22.277, 394.Stephens, J. A., 227.Stephens, K., 147.Stephens, R., 85.Stephens, S. J., 66.Stephenson, R. J., 211.Stepukhovich, A. D., 12,Stern, E. S., 72, 253.Stern, J. R., 314.Stern, M. H., 164.Stern, O., 66.Sternberg, H. W., 87, 124,Stevens, A. B., 60.Stevens, E. R., 13.Stevens, G. W. W., 375.Stevens, K. W. H., 91.Stevenson, D. P., 24, 43,Stevenson, R., 200, 203,Steward, F. C., 272, 273.Stewart, A. C., 101.Stewart, F. H. C., 127, 169.Stewart, I. A., 331.Stewart, J, L., 200, 205.Stewart, R., 28.Sthapitanonda, P., 99.Stidham, H. D., 88.Stiles, M., 145, 167.Stiner, O., 291.Stitch, M. L., 82.Stites, J. G., 105.Stoicheff, B. P., 82.Stok, P., 164.Stokem, M. B., 221.Stokes, A.R., 382, 384,398, 399.Stokes, P. J., 236.Stokes, W. M., 200.Stokrova, s., 360.Stokstad, E. L. R., 240.Stolar, S. M., 210.Stolar, S. N., 218.Stoll, A., 224, 242, 243,245, 246, 248.Stone, B. D., 105.Stone, D., 213.Stone, F. G. A., 94, 100.Stone, F. S., 51, 52.Stone, K. G., 349.Stonner, F. W., 250.Storegraven, H., 104.Stork, G., 184, 195, 317.Stotz, E., 300.Stoudt, T. H., 209.Stout, C. A., 169.jtrachan, A. N., 20.Strachan, W. S., 200, 205.Straley, J. W., 86.Strang, A., 143.Stranks, D. R., 24, 27, 31.;tratmann, H., 369.Straumanis, M. E., 108.Straus, S., 41.Street, J., 37.Street, N., 68.21.125.51.205, 213INDEX OF AUTHORS’ NAMES. 433Streitwieser, A., 174.Streng, A. G., 378.Strickland, R.D., 365.Stricks, W., 125.Stripp, K. F., 63.Strom, R., 15.Strong, F. M., 240.Struck, M., 97.Struthers, G. W., 301.Stuart-Webb, I. A., 209,Stubbs, F. J., 9.Stubblefield, C. T., 105.Stucker, J. F., 175.Stumpf, P. K., 315.Sturdy, G. E., 122.Sturm, K., 173.Sturm, W., 94, 102.Sturtevant, J. M., 30.Stuyts, A. L., 65.Style, D. W. G., 13.Styrikovich, M. A., 61.Sudo, E., 366.Sudo, T., 356.Sue, P., 378.Suehiro, T., 159.Sugden, T. M., 16.Suhrmann, R., 52.Suikkanen, S., 368.Suk, V., 348.Sullivan, E. A., 97.Sullivan, H. R., 232.Sullivan, J. C., 27, 122.Sumenvell, W. N., 296.Sumi, M., 192, 193.Summers, D., 13.Summers, G. H. R., 152,Summers, L., 129.Sumner, F. H., 61.Sumper, W. C., 238.Sundaram, A. K., 128.Sundaresan, M., 359.Sundstrom, K.V. Y., 137.Sundt, E., 223.Suquet, M., 231.Surber, W., 167.Surkov, Yu. A., 357.Surrey, A. R., 146, 232.SuSiC, M. V., 358.Suski, L., 359.Suss, H., 243.Sutcliffe, F. K., 170.Sutcliffe, L. H., 28.Sutcliffe, T., 103.Sutherland, G., 263.Sutherland, G. B. B. M.,84, 85, 86, 390.Sutherland, G. L., 272.Sutherland, I., 242.Sutherland, M. B., 189.Sutton, D. A., 302.Sutton, J., 44, 121.Sutton, J. R., 59, 60, 61,Suwal, P. N., 313.Suzuki, K., 302.210.211, 212.64.Suzuki, M., 24, 45, 367,Suzuki, S., 363.Swain, C. G., 30, 31.Swain, M. S., 145.Swalen, J. D., 82.Swallow, A. J., 48.Swaminathan, S., 159.Swan, G. A., 159.Swan, J. M., 274, 279.Swann, G., 189.Swanson, W. J., 164.Sweat, M.L., 319.Sweeney, W. A., 135.Sweeney, W. Z., 181.Sweet, T. R., 350, 367, 373.Swenker, M. D. P., 61.Swern, D., 301, 302.Swift, E. H., 363.Sworski, T. J., 46, 47.Sy, M., 231, 304, 309.Sykes, A., 341, 346.Sykes, W. Y., 353.Sgkora, V., 189.Symons, M. C. R., 33, 91.Synge, R. L. M., 272.Szabadvery, F., 351.Szabo, 2. G., 8, 368.Szarvas, P., 368.Szarvasi, E., 274.Szckerke, M., 282.Szekely, G., 375.Szent-Gyorgyi, A. G., 386.Szpilfogel, S. A., 219.Szumer, A. Z., 308.Szwarc, M., 11, 79, 132, 138.Szychlinski, J., 345.Taber, D., 175.Taber, J. J., 297.Tabroff, W., 390.Tachi, I., 262, 263, 357.Tada, H., 31.Tait, J. F., 329, 374.Takagi, S., 251.Takagi, T., 313.Takahara, A., 192.Takahashi, S., 24.Takahashi, T., 206.Takahishi, S., 45.Takashima, Y., 374.Takata, Y., 313.Takeda, K., 205, 213.Takei, S., 369.Takemoto, K., 36, 38.Talipov, Sh.T., 347, 361.Talgt-Erben, M., 35.Tallan, H. H., 272.Talley, R. M., 83.Tamaru, K., 54.Tamm, C., 215.Tan, W., 121.Tanaka, M., 366. .Tanaka, N., 125.Tanaka, Y., 73, 74.Tanner, D., 134.Tanner, K. N., 390.368.Tanret, C., 285.Tapley, J. G., 91.Tappel, A. L., 301, 302,Tarbell, D. S., 249.Tarlton, E. J., 190.Tarte, P., 85.Tatarintsev. V. V., 12.Tate, F. E. G., 304.Tatic, O., 363.Tatlow, J. C., 341.Tatoian, G., 358.Tatsuzaki, I., 91.Taub, D., 219, 222.Taube, H., 27, 29.Tausig, F., 304, 305.Taussig, P., 136.Tayler, J. L., 308.Taylor, A. E., 365.Taylor, C. A., 381.Taylor, D., 169.Taylor, E. C., jun., 240Taylor, E.H., 25.Taylor, G. R., 74.Taylor, H., 54.Taylor, H. A., 53.Taylor, H. T., 142, 143.Taylor, M. D., 101, 123.Taylor, M. P., 348.Taylor, R. P., 372.Taylor, W. I., 190, 197, 251,Taylor, W. L., 104.Tchen, T. T., 332.Tech, J., 360.Teichner, S. J., 53.Teisinger, J., 359.Telfer, R. G. J., 264.Teller, A. H., 63.Teller, E., 63.Teloh, H. A., 362.TBlupilovA, O., 360.Tenkovtsev, V. V., 369.ten Seldam, C. A., 62.Tenygl, J., 358.Teodorovich, I. L., 361.Teranishi, H., 15.Terenin, A. N., 87.ter Haar, D., 61.ter Meulen, H., 295.Terrey, H., 115.Tesar, C., 286.Teste, J., 231.Tettweiler, K., 350.Teuber, H. J., 173.Tewari, J. D., 313.Tezak, B., 66, 70.Thacker, R., 64.Thall, B.M., 376.Thaller, V., 164.Thayer, S. A., 221.Theilacker, W., 138.Theis, M., 345, 349, 351.Theorell, H., 284.Thesing, J., 150.Theurer, K., 373.Theus, V., 167.316.252434 INDEX OF AUTHORS’ NAMES.Thiele, K. H., 356.Thieme, G., 161.Thilo, E., 94, 104, 107,Thoma, R. W., 323.Thomaes, G., 58.Thomas, A. F., 254.Thomas, B. B., 42.Thomas, B. R., 156, 189,Thomas, G. H., 203, 210,Thomas, G. R., 306.Thomas, J. R., 12, 35.Thomas, J. W., 71.Thomas, L. F., 82.Thomas, 0. H., 155, 168.Thomas, P. D., 156.Thomas, P. J., 10, 11.Thomas, R. B., 60.Thomas, R. C., 304.Thomas, R. W., 207.Thomas, W. J. O., 233.Thomas, W. M., 33.Thomason, P. F., 372.Thompson, A. R., 277.Thompson, C., 364.Thompson, E.0. P., 394.Thompson, IS. W., 81, 86,Thompson, J. L., 157, 360.Thompson, J. M., 162, 310.Thompson, M. J., 187.Thompson, Q. E., 227.Thompson, R., 152.Thompson, T. G., 365.Thomson, R. H., 174, 178.Thrush, B. A., 17, 75.Thurmond, C. D., 107.Thyagarajan, B. S., 239.Tien, J. M., 234.Tietz, A., 297, 315.Tillotson, A., 218.Tillotson, J. A., 296, 297.Tillu, M. M., 347.Tilton, G. R., 374.Timell, T. E., 261.Timmermans, J., 57.Timmis, G. M., 240.Timmons, C. J.. 134.Tindall, J. B., 373.Ting, Y., 91, 92.Tinker, P. B., 177.Tinkham, M., 91.Tirouflet, J., 138.Tiselius, A., 283.Tishler, M., 209.TiSler, M., 176, 177.Tissier, H., 333.Titijevskaia, A. S., 57, 69.Tobin, M. C., 8, 84.Tobolsky, A. V., 32, 33, 36.Tockstein, A., 360.Toda, T., 177.Todd, (Sir) A.R., 242,305, 403.Todd, G., 194.108, 113.204, 225.213.88.Toennies, G., 290.Toennies, J. P., 16.Tokav, G., 355.Tolberg, W., 306.Tolberg,, W. E., 302.Tolberg, R. S., 20.Tolbert, B. M., 48, 90.Tolksdorf, S . , 208.Tolmatschew, A. I., 161.Tomarelli, R. M., 333, 337.Tomarelli, R. N., 271,Tomasewski, A. J., 183,211.Tomlinson, R. H., 374.Tompkins, F. C., 51.Topie, T. H., 185.Toren, P. E., 96.Torgov, I. V., 229.Toribara, T. Y., 99, 372.Torizuka, I<., 92.Torto, F. G., 165.T6th, J., 243.Touchstone, J. C., 221.Touloukian, Y. S., 56.Touster, O., 287.Tomes, C. H., 81, 82.Townley, J. R., 60.Toyama, Y., 302, 313.Tracey, M. V., 255.Trapnell, B. M. W., 50,Trappeniers, N., 58.Traylor, T.G., 26.Treacy, J. C., 9.Treibs, W., 179.Trenam, R. S., 91.Trenner, N. R., 232.Trenwith, A. B., 12.Trevoy, L. W., 294.Trippett, S., 162, 226.Trischmann, H., 224, 255,Tristram, H., 147.Trivedi, B. N., 23.Troelstra, S. A., 68.Trominel, J., 275.Troncoso, V., 329.Tronvold, G. M., 309.Troshin, Ya. K., 14.Trotman-Dickenson, A. F.,Trotter, I. F., 385, 392, 393.Troxell, H. A., 160.Troxler, F., 242.Trucco, R. E.; 335.Trueblood, K. N. 242, 395,Truter, E. V., 302.Tryon, P. F., 373.Tsatsas, G., 245, 248.Tschamler, H., 84.Tschesche, R., 207, 240.Tseitlin, R. I., 359.Tsiklis, D. S., 59, 61.Tskhvirashvili, D. G., 61.Tsuboi, M., 85.Tsuchiya, T., 43.Tsuda, K., 213, 214.51, 53.258.7.403.Tsuda, Y., 85.Tsujimura, A., 91.Tsukada, K., 92.Tsukagoshi, S., 358.Tsuruta, T., 36.Tsvetkova, V.I., 16.Tsyskovskii, V. K., 13.Tubbs, C. F., 360.Tucker, B. M., 350.Tufts, B. J., 71.Tulloch, A. P., 192.Tully, M. E., 208.Tunbridge, R. E., 391.Tupman, W. I., 65.Tuppy, H., 394.Turner, C. W., 291.Turner, E. E., 136, 172.Turner, R. A., 277, 278.Turner, R. B., 157,208,221.Turner, J. M., 281.Turner, S. E., 372.Turner, W. B., 162, 310.Tuthill, S. M., 368.Tutundzic, P. S., 363.Tuxworth, R. H., 53.Tverdovskii, I. P., 65.Tweit, R. C., 183.Tyle, Z., 230.Ubbelohde, A. R., 8, 24.Uchida, H. S., 88.Udenfriend, S., 320.Udovenko, V. V., 362.Ueda, M., 74.Ueno, K., 374.Ugi, I., 135.Uhle, F. C., 224.Uhler, U., 75.Uhlig, H.H., 51.Uhring, H., 159.Uksila, E., 272.Ulbricht, H., 339.Uloth, R. H., 129.Ulshafer, P. R., 247, 248.Ultee, C. J., 84.Umezawa, B., 313.Undenfriend, S., 374.Underwood, A. L., 363.Underwood, O., 277.Ungnade, H. E., 135.Uno, K., 37.Unohara, N., 347.Urbach, G., 272.Urech, H. J., 182.Uri, N., 27.Urnes, S., 104.Urquiza, M., 219.Ursprung, J. J., 200, 202,Ushakov, S. N., 161.Utkin, L. M., 259.Uyeo, S., 251, 252.Uzumasa, Y., 366.Uzzell, P. S., 238.Vaidhyanathan, V. S., 37.Vaitiekunas, A., 231.205INDEX OF AUTHORS' NAMES. 435\-ale, I?;. li. F., 58.Valee, B. L., 365.Valenta, Z., 250.1-alentine, L., 32, 35, 37,Valiente, E. A., 367.Valks, J. F., 38.van Arkel, A. E., 127.van Asperen, K., 350.Van Cleve, J.W., 255.Vand, V., 132, 381.Van Dalen, E., 358.van den Tempel, M.. 69.van der Eijk, W., 344.van der Kerk, G. J . M.,Van der Krogt, S. M. H.,van der Maesen, I?., 2.van der Minne, J. L., 67,\Tan der Waals, J. H., 71.van der Wal, A. A., 340.van Erkelens, P. C., 376.\Tan Esch, I., 350.van Est, W. T., 67.van Hall, C. E., 349.Vanpee, M., 17.van Riet, R., 83.van Soest, G., 61.\-an Straaten, W., 59.\-an Tamelen, E. E., 166,van Tiggelen, A., 13, 15.van Tongeren, vC7., 359.\-an Veen, A. G., 190.van Velden, P. F., 40.Van Wazer, J. R., 90, 112,van Wessem, G. C . , 173.van Wonterghem, J., 15.Van Zyl, C. N., 363.Varfolomeyeva, Ye. K., 12.Vargha, L., 213.Varier, N. S., 313.Varnerin, R. E., 9, 23.Varney, R.N., 110.Vars, H, M., 289.V&Ak, V., 360.Vasilev, Y. N., 61.Vasil'yeva, A. B., 8.Vaughan, C. W., 160.VeCeka, M., 355.L'elasco, M., 209.Velick, S. F., 302, 303.Velluz, L., 178, 226, 280.Veltre, F. A., 338.Venanzi, L. M., 128.VGne, J., 138.Venkataraman, B., 91.Venkateswarlu, P., 82.Verdier, P., 335.Verdol, J. A., 163, 191.Vereskoi, J., 348.Veritennikova, G. N., 368.Verloop, A., 226, 227.17erma, A. R., 301.39,161.141.71.230, 243, 248.361.Verma, J. I?., 165, 308.Verma, M. R., 344.Vermeil, C., 47.Vernon, C. A., 147.Verschaffelt, J. E., 8.Vert, Zh. L., 361.Venvey, E. J . W., 68, 69.Vescovi, E., 104.Veseley, J. A., 168.Veselovsky, V. I., 48.Vester, K., 126.Vestin, R., 59.Viallard, R., 373.Vickers, M.A., 134.Vickery, R. C., 104, 105.Viehe, H. G., 162, 310.Vielstich, W., 25.Vigh, K. M., 367.Viglierchio, D. R., 316.Vincze, I. W., 243.Vines, R. G., 56.Virgili Vinadk, J., 32.Virgona, A. J., 373.Virtanen, A. I., 272, 273.Vischer, E., 208, 216, 319,Viscontini, M., 207, 240,Viswanath, G., 175.Vivarelli, S., 115.Vleck, A. A., 358.Vodar, B., 59, GO, 73, 88,Voh, R., 283.Voiloshnikova, A. P., 359.Volders, A., 13.Volke, J., 359.Volkova, V., 359.Volman, D. H., 21.Voltman, A,, 211.Voltz, J., 331.Voltz, S. E., 55.von Auwers, K., 147.von Buttlar, H., 373.von Euw, J., 216.von Holdt, M. M., 308.von Klemperer, M. E., 161.von Krakkay, T., 127.von Mikusch, J. D., 308.von Saltza, M. H., 240.von Sydow, E., 301.von Tavel, I?., 283.von Weimarn, P.P., 387.Vorres, K. S., 108.Vosburgh, W. C., 124.Vovet, D., 242.Voyevodskii, V. V., 16.Vrestal, J.. 367.Vuillard, G., 123.Vulterin, J., 351, 361.Vvedenskaya, L. A., 362.Vykoukal, J., 359.Vysotskaya, N. A., 24.Wacykiewicz, K., 368.Waddington, G., 59.Waddington, T. C., 32.331.255.89.Wadier, C., 342.Wadman, W. H., 263.Waelbroeck, F. G., 60.Wanningen, E., 351.Waggatzer, W. L., 360.Wagland, A. A., 214.Wagman, E., 347.Wagner, A. F., 231, 304.Wagner, H., 232, 300.Wagner, H. G., 16.Wagner, P., 15.Wagner, R. L., jun., 256.Wagner, R. S., 82.Wagner, S., 273.Waight, E. S., 161.Wailes, P. C., 124, 273.Wainwright, H. W., 369.Wait, S. C., 8.Wakil, S. J., 31.5.Wal, R.P. V., 96.Walborsky, H. M., 306.Wald, M. H., 292.Walder, W. O., 263.Waldschmidt-Leitz, E.,Walens, H. A,, 222, 223.Waley, S. G., 282.\Talker, J., 135, 184, 220,Walker, R. I\'., 215.Walker, S., 76.\Valker, T. K., 313.Wall, &I. E., 222, 223.Iiallenstein, RI. B., 53.Waller, J. P., 279.Wallick, R. H., 238.TValling, C., 37.Wallis, E. S., 211, 213.Wallis, R. F., 86.Walls, F., 191.Walls, L. A,, 9, 38.Walsh, A. D., 77, 135.Walsh, J . R., 79.Walter, R. I., 91.Walter, ?V., 272, 273.Walters, W. D., 11, 12.Walton, E., 231, 304.Walton, G. N., 50.Walz, H., 135.Wang, T.-C., 92.Wanless, G. G., 316.Wannagat, U., 118.Ward, J. P., 179.Ward, K., jun., 42.JVardlaw, W., 108, 115.Wareham, J . F., 261.Warhurst, E., 11.Wariyar, N.S., 170, 184.Warner, R. C., 374Warren, C. W. H., 237.Warren, F. L., 161, 225,Wartik, T., 100.Warwick, G. P., 169.Warwicker, J. O., 387.Washburn, E. R., 68.Wassenaar, R., 59.283.293.252, 253436 INDEX OF AUTHORS’ NAMES.Watanabe, A., 36.Watanabe, K., 77.Waterhouse, P., 169.Waters, W. A., 28.Waters, R. F., 54.Waters, W. A., 138.Waterstradt, H., 124.WathBn, K., 262.Watkins, W. M., 337.Watling, K. H., 225.Watson, G. M., 60.Watson, H., 356.Watson, J., 327.Watson, J. D., 397, 398,Watson, P. R., 260, 266.Watson, R. H., 119.Watson, W. F., 35, 38.Watt, G. W., 106, 110,Watts, E. D., 147.Waugh, D. F., 380.Wawersich, E., 277.Weast, R. C., 15.Weaver, H. E., 90.Weaver, O., 256.Weaver, W.E., 281.Webb, A. N., 52.Weber, A., 84.Weber, E. N., 48.Weber, L., 211.Webster, B., 291, 292.Wedaa, H. W., 15.Wedlake, D., 210.Weedon, B. C. L., 164, 165,305, 306, 311.Weeks, B. M., 46.Wegmann, R., 300.Wehrmuller, J., 280.Weiblen, D. G., 356.Weichselfelder, T., 126.Weigel, M., 95, 121.Weiler, G., 336.Weinberg, F. J., 14.Weiner, M., 319.Weinmayr, V., 180.Weinstein, A. H., 37.Weintraub, A., 323, 332.Weise, E., 127.Weisenborn, F. L., 248.Weisiger, J. R.. 278.Weisler, L., 164.Weiss, A., 100.Weiss, E., 128.Weiss, H., 98, 184.Weiss, H. D., 163.Weiss, J.. 42, 44, 47, 48,116, 124, 331.Weissmann, H. B., 83.Weisz, H., 344.Weitkamp, A. W., 302, 304.Weitz, H., 111.Weitzel, G., 303.Weizmann, A., 180.Welch, F.J., 234.Welch, G. A., 122.Weldes, H., 178.399, 401.123.Weller, A., 26.Weller, R. A., 303.Weller, S., 29.Weller, S. W., 55.Welsh, H. L., 83.Weltner, W., 84.Wender, I., 87, 124, 125.Wendlandt, W. W., 104,345.Wendler, N. L., 209, 211,215, 219, 222.Wendt, B., 155.Wenkert; E., 196, 245,Wennerstrand, B., 351.Wepster, B. M., 141.Werbin, H., 324.Werner, R. L., 84, 85.Wernet, J., 114.Werst, G., 152.Wesenbeck, W., 354.Wessel-Ewold, M.-L., 138.Wesselly, I?., 277.West, D. M., 349.West, P. W., 362, 363.West, S. F., 111.West, T. S., 350.Westcott, D. T., 211.Westland, C. J., 127.Weston, R. E., jun., 11.Westphal, U., 300.Westshaver, S., 315.Wettstein, A., 199, 207,208, 215, 216, 217, 218,318, 319, 321, 323, 328,248, 251.331.257, 281.Weygand, F., 159, 170,Weymouth, F.J., 40, 282.Whallev. E.. 59.Whalle;; M.’, 241.Whalley, ?V. B., 173, 237.Wheeler, C. M., 102.Wheeler, D. H., 301, 302,Wheeler, D. M. S., 198.Wheeler, 0. H., 226.Wheeler, T. S., 235.Whelan, W. J., 154, 255,306.266.Whiffen, D. H., 81, 84, 85,Whistler, R. L.. 262, 269.147, 378.Whitaker, D. R., 262.Whitaker, J. R., 276.Whitby, G. S., 34.White, D. E., 196, 295.White, E. V., 263, 269.White, J. G., 242, 403.White, J. R., 9, 12.White, J. U., 83.White, R. A., 348.White, W. C., 48.White, W. F., 280.Whitehead, J. K.. 374.Whitehead, L., 194.Whitehead, V. I. E., 292.Whiteman, C. A, 12.Whiting, M. C., 124, 137,162, 163.164, 273, 310,311.Whitley, A., 116.Whitnack, G. C., 360.Whittaker, A. M. B., 65.Whittaker, F. A., 136.Whittle, E., 84, 86, 89.Whytlaw-Gray, R., 56, 59,Wibaut, J. P., 243,Wiberg, E., 94, 102, 103.Wiberg, F., 153.Wiberg, K. B., 28, 31, 147,Wiberley, S. E., 87, 95.Wichterle, 0.. 41.Wicker, R. J., 53, 139,Wickstrom, A., 268.Wideqvist, S., 8.Wiebe, R., 59.Wieland, P., 229.Wieland, T., 274, 276, 280,Wiener, M., 326.Wiesner, K., 25, 250, 253,Wiggins, H. S., 208.Wiggins, T. A., 82.Wight, N. J.. 285, 288.Wijga, P. W. O., 67.Wijnen, M. H. J., 21.Wilbur, K. M., 301.Wilczewski, J. W., 378.Wild, W., 49.Wildman, W. C., 157, 251.Wiles, R. A., 151.Wiley, P. F., 256.Wiley, R. H., 230.Wiley, R. M., 70.Wilgus, H. S., 291.Wilhelmson, D. F., 380.Wiljams, W. W., 309.Wilkins, C. J., 107.Wilkins, M. H. F., 398,Wilkinson, A., 304.Wilkinson, G., 87, 130,Wilkinson, H. C., 353.Wilkinson, J. F., 270.Wilkinson, N. T., 369.Wilkinson, P. G., 73, 76.Wilkinson, R. W., 48.Will, F., 366.Will, E. G., 365.Willard, C., 159.Willard, H. H., 352.Willemart, A., 230.Willersinn, H., 302.Williams, A. F., 346.Williams, C., 169.Williams, C. H., 367.Williams, D., 91, 92.Williams, D. F., 211.Williams, D. G., 86.150.185.281.254.399.180INDEX OF AUTHORS’ NAMES. 437Williams, E. F., 292.Williams, G. R., 320.Williams, €3. L., 35, 38.Williams, H. R., 85.Williams, j. P., 364.Williams, M., 341.Williams, N. R., 155, 170.Williams, R. C., 399.Williams, R. E., 248.Williams, R. R., jun., 45.Williams, T. F., 48.Williams, W. T., 300.Williamson, I. R., 263.Williamson, S. W., 288.Willig, M., 233.Willis, J. B., 85.Willits, C. H., 85.Wiloth, F., 40, 41.Wilson, A. J. C., 383.Wilson, A. N., 232.Wilson, C. L., 370.Wilson, E. B., 81, 82.Wilson, H. N., 350.Wilson, H. R., 398, 390.Wilson, L., 275.Wilson, M. K., 83.Wilson, M. L., 290, 319.Wilson, R. F., 358.Wilson, S., 42.Wilson, W., 231, 240.Wilzbach, K. E., 31, 353,Wingfield, E. C., 86.Winitz, M., 275.Winkler, C. A., 23.Winkler, G., 279.Winstein, S., 26.Winter, E. R. S., 53, 55.Winter, R. W., 39.Winteringham, F. P. W.,Winternitz, F., 213.Winternitz, P. F., 99.Wintersteiner, O., 248, 322.Wirth, C. M. P., 345.Wiseblatt, L., 275.Witkop, B., 244, 249.Witnauer, L. P., 222, 301.Wittig, G., 160, 161, 163,Wladislaw, B., 165, 305,Wodtcke, F., 108.Wolk, H., 368.Worffel, U., 156.Woerner, D. E., 350.Wohl, K., 14.Wohlfahrt, J., 216.Wolf, F. J., 54, 232.Wolf, R., 70.Wolff, I. A., 260, 266,Wolfhard, H. G., 17, 18.Wolfrom, M. L., 260, 263.Wolinsky, J., 183.Wolovsky, R., 169.Wood, D. F., 368.376.370, 374.175.309.269.REP.-VOL. LIIWood, D. L., 390.Wood, E. L., 364.Wood, H. B., jun., 258.Wood, H. C. S., 240.Wood, J. C., 272.Wood, J. H., 342.Wood, J. L., 292.Wood, J. M., 83.Wood, K. H., 233.Wood, M. J., 391.Woodburn, H. W., 158.Woodcock, R. F., 63.Woodger, R., 240.Woods, G. F., 153, 163,Woods, R. J., 259.Woodward, L. A., 83, 88.Woodward, P., 344.Woodward, R. B., 181,223, 256, 332.Wooldridge, K. H. R., 231,304.Wooley, J. G., 289.Woolf, A. A., 123.Woolf, L. I., 287.Wootton, N. F., 71.Work, T. S., 276.Worms, K. H., 111.Worrel, C. S., 319.Worsham, J. E., jun., 134.Wortman, R., 51.Wotiz, J. H., 230.Wozniak, W. A., 185.Wright, F. J., 79.Wright, G. F., 241.Wright, I. S., 67.Wright, J., 45.Wright, J. B., 158.Wright, L., 29.Wright, P., 28.Wright, T. W., 379.Wrigley, T. I., 214.Wrinch, D.. 394, 395.Wuellner, J. A., 231.Wursch, J., 152.Wulf, W., 178.Wutsckel, A., 112.Wyart, J., 61.Wyatt, G. R., 398.Wylam, C. B., 260.Wyld, G., 365.Wyler, H., 226.Wyman, L. J., 215.Xavier, J., 368.Xuong, Ng. D., 304, 300.Yajima, H., 251, 252.Yakel, H. L., jun., 383, 385,Yakubov, A. M., 359.Yalman, R. G., 126.Yamada, E. Y., 318.Yamamori, N., 262, 263.Yamamura, H., 92.Yamamura, S. S., 350.Yamasaki, K., 212.219.389.Yanagita, M., 192.Yang, N. C., 182.Yanovsky, E., 190.Yarden, A., 366.Yarger, F. L., 59, 74.Yashiro, Y., 357.Yasinskene, E. I., 27.Yasnoff, D. S., 282.Yasuda, S. K., 345, 360,Yasumori, I . , 7.Yates, D. J. C., 87.Yatsimirskii, K. B., 27Yeremin, V. V., 12.Yoe, J. H., 368.Yoffe, A. D., 7.Yokouchi, N. , 368.Yokozawa, Y., 91.Yoshikawa, K., 362.Yoshino, T., 87.Yoshizawa, Z., 271.Yost, D. M., 32.Young, A., 367.Young, D. M., 20.Young, E. G., 267.Young, G. T., 373.Young, J. A., 64.Young, J. R., 143.Young, L. J., 181.Young, R. L., 213.Young, R. M., 58.Soung, R. W., 233.Young, W. G., 151.Young, V. V., 232.Youngquist, M., 83.Yuan Hsiao, C.-Y., 312.Yumoto, H., 41.Zachariasen, W. H., 99.Zacharius, R. M., 273.Zachau, H. G., 164.Zafarronia, A., 300.Zaffaroni, A,, 317, 323, 325,Zaheer, S. H., 296.Zahradnik, K., 300, 360.Zalkow, L. H., 184.Zall, D. M., 347.Zalta, J. P., 370.Zanker, V., 79.Zapotocky, J. A., 361.Zapp, K. H., 105.Zappel, A., 101.Zarinslui, V. A., 362.Zbinovsky, V., 300.Zechmeister, L., 84, 137,Zeeman, I?. B., 74.Zeiger, H. J., 81.Zelauskas, J., 233.Zeller, R., 106.Zemann, J., 114.Zernph, G., 295.Zharovskii, 1‘. G., 366.Zhdanov, A. K., 359.Zhivopistsev, V. l’., 361.Ziegler, J. B., 222.370.329.164, 165.438 INDEX OF AUTHORS’ NAMES.Ziegler, K., 38, 104, 155,159, 168, 179.Ziegler, M. , 370.Ziegler, P., 213.Ziffer, H., 133.Zilkha, A., 281.Zilkha, Z., 282.Zillig, W., 400, 401.Zilliken, F., 271, 333, 334,Zimmerman, H. E., 140.Zimmerman, H. K., 371.335, 337.Zimmermann, J. P., 280.Zimmt, W. S., 23.Zirker, G., 116.Zirm, K. L., 313.Zittel, H. E., 358.Zobel, C. R., 77.Zohler, A., 361.Zoellner, H., 364.Zollinger, H., 31, 140.Zook, H. D., 159.Zosel, K., 104, 155, 159.Zschaage, W., 112.Zubler, E. G., 45.Zucker, E. F., 366.Zuehlke, C. W., 376.Ziircher, A., 202.Ziircher, R. F., 84.Ziirn, G.. 112.Zuman, P., 358, 359, 360.Zumanova, R., 359.Zwanzig, R. W., 63.Zwecker, I. T., 291.Zwolinski, B. J., 26, 53.Zyka, J., 343, 358, 361

ISSN:0365-6217    

DOI:10.1039/AR9555200405

出版商:RSC    

年代:1955

数据来源: RSC

摘要:

INDEX OB’ SUBJECTS.Absorptiometry, 365.Acetaldazine, photolysis of, 20.Acetaldehyde, photolysis of, 18.thermal decomposition of, 12.Acetone, photolysis of, 19, 22.Acetone cyanohydrin nitrate as a nitrat-ing agent, 161.Acetylene, acidity of, 43.polymerisation of, to cyclooctatetraene,161.Acetylenes, 161.Acetylenic compounds, natural, 162.Acid catalysts, reactions over, 55.Acids, cycloalkane, 308.hydroxy-, natural, 307.long-chain fatty, metabolism and func-tion of, 314.saturated, 302.unsaturated, 304.synthesis of, 305.natural acetylenic, 309.long-chain fatty, 296.Acidimetric and alkalimetric standards,349.Acridine, bromination of, 239.Acridizinium salts, preparation of, 239.Acridone, 2 : 3 : 4-trimethoxy-lO-rnethyl-,Acrylonitrile, polymerisation of, 33.Actinium, preparation of, 105.Activation analysis, 375.Absorbed molecules, spectra of, 87.Aerosols, 71.Affinin, 311.Agrocybin, structure of, 310.Ajmaline, structure of, 246.Alcohols, preparation of, 159.Aldehydes, preparation of, 158, 170.Aldosterone, total synthesis of, 215.Alicyclic compounds, 180.Aliphatic compounds, 161.Alkali metals, reduction by, 155.Alkaloids, 242.Alkyl radicals, reactions of, 21.Allenes, 163.Allotropy, 93.See also under Phosphorus and Sulphur.Aluniina-silica catalysts, 55.Aluminium, detection of, 345.determination of, 344, 368.Aluminium, triethyl-, uses of, 93.Aluminiums, trialkyl-, synthesis of, 93.occurrence of, 244.filtration of, 71.orp-unsaturated, electronic moments of,134.steroidal, 223.Aluminium alkyls, formation of, 104.preparation of, 155.Aluminium bromide, conductivity of, inethyl bromide, 104.Aluminium chloride in the graphitelattice, 106.Aluminium hydride, reaction of, withammonia, and with amines, 103.Aluminium hydrides, dialkyl-, prepara-tion of, 155.(&)-Ambreinolide, formation of, 187.Americium, separation of, from curium,Amides, conversion of, into nitriles, 160.Amines, preparation of, 160.a-Amino-acid anhydrides, N-carboxy-,polymerisation of, 40.Amino-acids, natural, 271.preparation of, from peptides and pro-teins, 275.synthetic, 273.122.Amino-nitrogen, determination of, 364.Ammonia, mercury-photosensitised de-composition of, 20.slow oxidation of, 13.Ammonia vapour, decomposition of, bysilent discharge, 45.Ammonium sulphamate, use of, in com-bustion analysis, 353.Amperometric methods of analysis, 359.u-Amyrin, 200.Analytical chemistry, 339.Androsterone, partial syntheses of, 21 1.Angiotonin.See Hypertensin.Anilines, 2 : 5- and 3 : 4-dinitro-, formationAnthracene, condensation of, with I-nitro-Antimony, determination of, 367.Antimony compounds, tervalent, pyrami-dal structure in, 17 1.Antimony pentachloride, compound of,with phosphorus oxychloride, 112.Antithyroid substances from vegetablesources, 291, 292.Apionic acid, formation of, 259.(f)-Apiose, formation of, 259.Aricine, structure of, 246.Aromatic compounds, 168.Arsenic, determination of, 356, 367.Arsenic trifluoride, complexes with , 1 13.Artemisin, 193.Ascorbic acid as a reducing titrant, 351.of, 168.naphthalene, 171.crystal spectra of, 78.trisulphide, amino- and imino-deriv-atives of, 113.1440 INDEX OF SUBJECTS.Aspidospermine, structure of, 249.Association phenomena, 88.Atisine and isoatisine hydrochlorides,structure of, 254.Aureothricin, structure of, 239.Aurones, ring expansion of, to flavones,235.Azeotropes, theories of, 64.Azetidine-2-carboxylic acid, occurr$nce of,Azobenzenes, o-carboxy-, fine structure of,Azomethane, photo-oxidation of, 20.cis-Azonaphthalenes, formation of, 169.Azulene, synthesis of, 178.Azulenes, 178.Bacitracin A, amino-acid sequence in,278.Baicalem, formation of, 237.Barium, determination of, 367.Barium dipotassium tetranitrate, 99.Basseol, heterogeneity of, 226.Benzamides, planar structure of, 134.&nzene, crystal spectra of, 78.Benzenes, o-halogenonitro-, absorptionBenzilic rearrangements, 150.Benzo[c]phenanthrenes, methyl-, methylaffinities of, 132.Benzoquinolizinium salts, dehydro-, pre-par?tion of, 239.Benzoquinone as inhibitor in polymeris-ation, 36.3enzoquinone, 2 : 5-dimethoxy-, as anatura!, product, 173.# ' Benzyne intermediates, 160.Beryllium, detection of, 345.determination of, 342, 369.Beryllium-citrate system, 99.Beryllium boride, 98.Bifidns factor, 333.Bifidus-factor active substances of non-lacteal origin, 336.Biological chemistry, 285.Biopterin, isolation of, 240.Bismuth, determination of, 342, 351.Biscyclopentadienylrhenium hydride, 130." Blazed '* gratings, definition of, 73.Block copolymers, 38.Blood-group substances, 333, 336.Borazole, aromatic character of, 101,Boric acid, determination of, 361.Borohydrides, alkali-metal, reactions' of,Boron-sulphur compounds, 102.Boron trihalides. equilibria between, 102.Branching in polymerisation, 38.Bromides, organic, pyrolysis of, 10.Bromination, 168.Bromine trioxide as formula of alleged229, 273.169.phosphides, 11 2.sulphate, precipitation of, 347.intensities of, 135.Borate, detection of, 346.reduction by, 153.100."Br,O,, 123.Bromyl fluoride, preparation of, 123.Burning velocities, 14.Buta-1 : 3-diene, 2-vinyl-, synthesis of,%-Butane, slow oxidation of, 14.thermal decomposition of, 9.cycZoButane, 1 : 2-dimethylene-, prepara-cycZoButanone, thermal decomposition of,isoButylamides, natural, 311.Butyrosperm 01, 226.Cadmium, determination of, 361.Cafestol, structure of, 198.Calciferol and its isomers, 226.Calcium, micro-determination of, 350.Calcium hydrogen silicates, 107.Camphene, 189.Carbohydrates, 255.Carbon, determination of, 356.heat of sublimation of, 106.isotopic, determination of, 353.Carbon dioxide, detection of, 345.determination of, 352.Carbon monoxide, activation energy ofoxidation of, on metal oxide cata-adsorption of, on metals, 52.Carbon monoxide-oxygen mixtures,second explosion limit of, 16.Carbonyl sulphide, determination of,369.Carborundum, adsorption by, 66.Carissone, 190.Carrageenin, K- and X-, 267.Carvenone, formation of, 188.Carvone, enol acetate of, structure of,/I-Caryophyllene alcohol (caryolan-1-01).Caryophyllene oxide, 194.isocaryophyllene oxides, 194.Cassaic acid, 196.Catechin and epicatechin, structure of,236.Caulophylline, synthesis of, 243.Cedrol, 195.Cellulose, 260.Cerin, structure of, 207.Cerium, determination of, 369.Cerium(II1) ion, oxidation of, 29.Cerium(1v) ion, y-ray induced reductionCevine, oxidation of, 223.a-Chaconine, structure of, 258.Chamazulene, structure of, 180.Chamazulenecarboxylic acid, structureCharge-transfer spectra, 79.Chaulmoogric acid, synthesis of, 308.Chemisorption, 50.on metals, 50.on metal oxides, 52.Chloramine, reactions of, 110.Chloranil, copolymerisation of, 36.Chlorination by y-irradiated chlorine, 49.163.tion of, 181.11.lysts, 55.181.194.of, 47.of, 180.(f)-dihydro-, synthesis of, 309INDEX OF SUBJECTS.441Chlorination rates of C,-C, paraffins, 25.Chloride, determination of, 370.Chlorine, determination of, 355.Chloryl fluoride, preparation of, 123.5p-Cholanic acid , 3a-hydroxy-, pyrolysis5/?-Chol-S-enic acid, formation of, 212.Cholestan-3-one oxime, reduction of, 152.Cholest-5-en-38-yl benzoate, 7-bromo-,dehydrobromination of, 213.“ pseuddholesterol,” identity of, 213.Chromatography of amino-acids, 276.Chromium (111) , fluoropentammino-, saltsChromium , azidopentammino-, salts of,hydroxyaquocarbonyl complex of, 120.triamminotricarbonyl-, 120.Chromium acetylide, complexes of, 119.Chromium (VI) oxide, mechanism of oxid-Chromonols, formation of, 235.Cicutol, synthesis of, 163.Cladinose, structure of, 256.Clovene, 194.Cobalt, detection of, 345.determination of, 350.Cobalt, tetra(thionitrosy1)-, 116.Cobalt carbonyl, formation of, 125.hydride, structure of, 125.Dicobalt octacarbonyl, structure of, 125.Cobalt(II1) chloride, purpureo-, as re-agent for tungsten, 341.Cobalt (111) complexes, distinction betweencis- and trans-, 95.Cobalt(rI1) potassium nitride, 126.a- and fl-Codeimethines, structure of, 254.Colchicine, isomerisation of, 178.Collagens, structure of, 388.swelling of, 390.Colloid chemistry, 65.Colloids, lyophobic, stability of, 68.slow coagulation of, 69.Combination, distinction between, andCombustions, explosive, of hydrocarbons,Complexes, inorganic, 94.Compounds, densely branched, 167.Condensation polymerisation, 39.Conductometric titration, 362.Co-ordination complexes of transitionCopolymers, analysis of, 378.Copolymerisation, 37.Copper, detection of, 345.determination of, 342, 343, 351.Copper(1) carbonyl cyanide, 98.ion, atmospheric oxidation of, 29.Copper(I1) fluoride, non-existence of, 97.Coprostan-3-one oxime, reduction of, 152.(A)-Cordycepose, formation of, 259.Correllogenin, 223.Corresponding states, equations of, 60.Corticotropins, amino-acid sequence in,of, 212.ion-exchange, 276.of, 121.121.ation by, 120.disproportionation, 33.17.elements, electronic spectra of, 79.280.Coulometric titration, 363.Coumaran-3-ones, 2-acyl-, mechanism ofsynthesis of, 235.S-arylidene- (aurones) , formation of,235Crystallography, 380.Cuauchichicine, structure of, 253.Cumulene ester, structure and occurraence of a, 310.Cumulenes, 163.preparation of, 156.Curium, separation of, from americium,Cyanogen, para-, 106.paraCyclophanes, 184.a- and /3-Cyperone, 190.Cysteine, L-S-methyl-, sulphoxide, oc-(+) -Cytisine, synthesis of, 243.czs-czs-cycZoDeca- 1 : 3-diene, double bondsDecal-l-one, tram- and cis-9-methyl-,cycZoDecane, conformation of, 182.trans-cycZoDecene, isomerisation of, 183.bicycZo[5 : 3 : O]Dec-l(lO)-en-9-one, pre-paration of, 183.Decomposition in sealed tubes, factorsinfluencing, 354.cycZoDecylamine, reaction of, with nitrousacid, 182.Dehydrocyclisations, 182.Dehydroergosteryl acetate, rearrangementof, 214.Dehydrogenation, 166.Dendroketose, formation and degradationDeoxyribonucleic acid, crystal structureDepolymerisation equilibria, 41.Deserpidine, occurrence and structure of,Desmotroposantonins, acetates of, 192.(f) -8-Desmotropo-+-santonin, 194.Desosamine, 256.Deuterium, exchange reactions of, 53.isoDextropimaric acid, structure of, 196.Dianthronylidene, overcrowding in, 132.Diaryliodonium salts as arylating agents,Diatomic molecules, electronic spectra of,2 : 3a-Diazaindenes, formation of, 239.Diazomethane, lithium derivative of,167.3 : 4-5 : 6-Dibenzophenanthrene, over-crowding in, 132.Diborane, reactions of, 100.Dichlorophosphorous nitride, polymeris-Dictamnic acid, structure of, 244.Dictamnine, structure of, 244.Dielectric effects on reactions, 31.Digitogenin, stereochemistry of, 217.122.currence of, 272.in, 183.equilibration of, 185.in steroid group, 208.of, 259.of, 397.247.169.74.dibu tyl-, 10 1.ation of, 39443 INDEX OF SUBJECTS.Dihydromyrcene, retardation of poly-merisation by, 36.1 : 1’-Dinaphthyl derivatives, opticallyactive, racemisation of, 137.Dinaphthylenes, stability of, 175.2 : 4-Dinitrobenzenesulphonic acid,methyl ester, use of, 161.Dicyclopentadienylmetal compounds, 180.Diphenylene, stability of, 175.Diphenylpicrylhydrazyl, uses of, in poly-1 : 1’-Diisoquinoline, strain in, 133.Disaccharides, reduction of, by sodiumDisproportionation, distinction between,Distemonanthin, structure of, 236.Diterpenes, abietane-type, biogenesis of,1 : 2-Dithiole-3-thiones, preparation of,Dithionite, detection of, 346.Dosimeter, gas-phase, 45.Dosimetry, 44.( (Double bonds, skipped,” 301.Echinacein. See neoHerculin.a-Elaeostearic acid, synthesis of, 165,Electric discharge in gases, 45.Electrokinetic phenomena, 66.Electronic spectra, 72.E,lectrophoresis, 67.of polysaccharides, 260.Elemadienolic acid, epimers yf, 225.Elemane. See “ Tirucallane.Elemol. 189.merisation, 35, 36.borohydride, 255.and combination, 33.196.231.306.Emulsions, coagulation of, 70.End-groups in polypeptides and proteins,determination of.277.Equations of state, of pure and mixedL( -J-)-Ergothioneine, 285.gases, 59.analysis of, 286.functions of, 290.occurrence of, 287.origin of, 289.structure and synthesis of, 285.upoErysopine, structure of, 250.Erythrogenic (isanic) acid, synthesis of,a-Erythroidine, structure of, 249.Esters, fatty, estimation of small quan-tities of, 301.Ethane, thermal decomposition of, 11.Ethoxyl, determination of, in presence ofmethoxyl, 356.Ethyl bromide, thermal decompositionof, 10.Ethyl nitrate, pyrolysis of, in flames, 18,Ethylation, 168.Ethylene, dideutero-, cis-trans-isomeris-ation of, 25.Ethylene, photosensitised hydrogenationof, 22.Ethylene oxide, photosensitised decom-position of.19.311.Eth ylenediaminetetra-acetic acidEthyleneimine, polymerisation of, 39.Eudesmane, 191.Eudesmol, composition of, 190.Euphol, correlation of, with tirucallol, 225.rearrangement of, 146.Euphorbol, epimers of, 225.Europium, separation of, from samarium,Europium(I1) oxide, preparation of, 105.Evolatine, structure of, 244.(E.D.T.A.), uses of, 350.105.Fagarol. See (f)-Sesamin.Farnesic acid, 187.Farnesylacetic acid, cyclisation of, 187.Fats and waxes, analysis of componentFeist’s acid, structure of, 180.Ferrocene, metalation of, 180.Ferrous ion, atmospheric oxidation of,Ferrous sulphate dosimeter, 44.Flame photometry, 364.Flames supported by oxygen or air, 14.slow, velocities of, 14.Flavones, formation of, 235.Flavonoids, rearrangement of, 236.Flavonols, formation of, 235.Flindersine, structure of, 244.Fluoride, determination of, 370.Fluorine, determination of, 355, 356.Fluorine-hydrogen mixtures, burningFluorocurine, partial structure of, 246.Fluorosulphonic acid, ionisation of, 122.Formaldehyde, slow oxidation of, 13.Formaldehyde-oxygen mixtures, thermalinflammation of, 17.Formic acid, activation energy of de-composition of, 54.Fraxinol, formation of, 237,Friedelin, structure of, 205.Fructosans, 264.Fucoxanthin, allenic linkage in, 165.Fulvalene derivatives, 175.Fulvene, 1 : 2 : 3 : 4-tetraphenyl-, re-Furoxans, formation of, 232.Fuscin, structure of, 237.Galactans and galactoarabans, 263.Gallium, detection of, 345.determination of, 369.Gallium (I) chloride, decomposition of,Gallium (11) iodide, preparation of, 105.isoGalloflavin, structure of, 236.Garryfoline (new name for laurifoline),Gdrryine, structure of, 253.Gaseous decompositions, kinetics of, 9.Gaseous reactions, kinetics of, 7.Gases, behaviour of, a t very high pres-acids of, 312.28.mechanism of oxidation of, 47.velocity of, 18.thermal decomposition of, 12.action of, with piperidine, 175.105.254.sures, 58INDEX OF SUBJECTS.443General and physical chemistry, 7.Gentrogenin, 223.Germanium, detection of, 345.determination of, 348, 369.Germanium hydride (germane), decoin-position of, 54.oxychloride, 109.tetrachloride, hydrolysis of, 109." Germanoic acid, penta-," non-existenceof, 109.Germine, structure of, 224.Gitogenin, structure of, 21 1, 217.Gluconapin, 295.Glucosans, 264.D-Glucose, 3-0-methanesulphonyl-, re-action of, with alkali, 258.2 : 3 : 6-trimethyl-, separation from2 : 3 : 6-tri-O-methyl-~-mannose, 256.p-D-Glucose, 2 : 3 : 4 : 6-tetra-O-acetyl-l-0-(2 : 4 : 6-trimethylbenzoyl)-, fissionof, 258.Glucose phenylhydrazone, modificationsof, 257.Glucose phenylosazone, structure of, 257.Glutamic acid, DL-yhydroxy-, prepara-tion of, 273.y-methylene-, occurrence of, 273.preparation of, 274.Glutamine, y-methylene-, occurrence of,273.L-isoGlutamine, synthesis of, 274.Glycogen, 265.Glycopyranosides, relative reactivity ofGlycosides, reaction a t position 1 of, 147.Glycyrrhetic acid, configuration of, 204.Glyoxaline derivatives, preparation of,232.Glyoxalinothiazolium salts, dihydro-, pre-paration of, 239.Gorlic acid, configuration of, 309.Graft copolymers, 38.Haemocorin, structure of, 172.Haemoglobins, 391.Hafnium, solubility of, in acids, 108.Halides, precipitation of, by silver nitrate,Halogen atoms, reactions of, 23.Helices in polypeptide chains, 382.Hemicelluloses, 260.Heptacene, formation of, 172.bicycZo[2 : 2 : lIHeptadiene, isomerisationcis-Hept-3-en-Z-one, 167.Herculin, incorrectness of assigned struc-neoHerculin, possible identity of, withHeterocyclic compounds, 229.Heterogeneous catalysis , 50.Heterogeneous reactions, kinetics andmechanisms of, 53.6-Heteropoly-anions, structure of, 121.Hexacene, formation of, 172.cycloHexadecanone, preparation of, 183.Hexafluoroazomethane, photolysis of, 20.u- and p-, 147.360.of, 184.ture of, 311.echinacein, 312.cycZoHexanecarboxylic acid, cis-( -J-)-3-amino-, conformation of, 185.cycZoHexanecarboxylic acids, stereoiso-meric monosubstituted, strengths of,140.e-Hexanolactam, polymerisation of, 40.cycZoHexene, bond angles in, 184.cycZoHexene, 4 : 5-dimethylene-, 181.Hieracifoline, heterogeneity of, 253.High-frequency titration, 362.Histidine, ~-3-methyl-, occurrence of,Holarrhimine, structure of, 224.Homolycorine, structure of, 251.DL-Homomethionine, preparation of, 273.Homopseudopelletierine methiodide, de-composition, of, 182.D-Homosteroids, 221.Hydnocarpic acid, (f)-dihydro-, syn-thesis of, 309.Hydrazinesulphinic acid, calcium salt,110.Hydrazinesulphonic acid, 11 1.Hydrocarbon radicals, reactions of withnitrogen dioxide, 13.Hydrocortisone, synthesis of, 157.Hydrogen, heats of adsorption of, onmetals, 51.Hydrogen, thermal reaction of, withnitrogen dioxide, 12.Hydrogen-air mixtures, burning velocitiesof, 14.Hydrogen-fluorine mixtures, burning ve-locity of, 18.Hydrogen-oxygen mixtures, ignitions in,16.Hydrogen atoms, reactions of, 21.Hydrogen halide monohydrates, structureof, 115.Hydrogen isotopes, exchange of, in gaseoushydrogen on irradiation, 45.Hydrogen peroxide, determination of, 369.reactions of, with iron salts, 28.use of, in alkaline hydrolysis ofHydrogenation, catalytic, 151,Hydroperoxides, production of, by irradi-ation, 47.6-Hydroxycyclodecanone oxime, trans-annular hydrogen transfer in reduc-tion of, 182.Hydroxyl groups in steroids, llp-, 17a-,and 21-, order of introduction of,324.Hydroxylation of steroids, 316.in the 6-position, 325.7-position, 330.ll-position, 316.12-position, 330.16-position, 326.17a-position, 323.18- and 19-positions, 328.2 1 -position, 323.other positions, 331.Hypertensin, preparation of, 279.Hypochlorous acid, decomposition of, 31.272.nitriles, 150.mechanism of chlorination by, 31444 INDEX OF SUBJECTS,Hypophosphite, determination of, 362,370.Hypophosphorous acid, tautomeric formsof, 32.Ignitions, kinetics of, 16.Indicators, 347.Indium, determination of, 348.Indium(r) chloride, preparation of, 105.Indoles, ring scission of, 238.Inhibition of polymerisation, 36.Initiation of polymerisation, 35.Inorganic chemistry, 93.Inorganic gravimetric analysis, 346.Inorganic qualitative analysis, 343.Inorganic titrimetric analysis, 347.Inositols, 257.Insulin, crystal structure of, 394.Insulin molecule, grouping of, 380.Integerrimine, structure of, 253.Intermolecular forces in gases, 57.Iodine atoms, recombination of, 23.Iodine in biological material, determina-Iodyl fluoride, preparation of, 123.Periodyl fluoride, preparation of, 123.Ionic polymerisation, 38.Ionisation potentials, 77.Ions, adsorption of, from solution, 65.Iresin, structure of, 191.Iron, determination of, 351.Iron(IIx), determination of, 343.Iron, thionitrosyl-, 124.Iron pentacarbonyl, ionisation of, 124.Iron surface, adsorption of sulphate ionsIrradiation of aqueous media, yields ofhydrogen and hydrogen peroxide in,45.Isanic acid.See Erythrogenic acid.Isanolic acid, 311.Isotactic(al), definition of, 38.Isotope effects, 31.Isotopes as accessories in analysis, 371.Isotopic dilution analysis, 372.Isotopic exchange reactions, 24, 30.Isotopic exchanges in presence of nitricJuniperol, identity of, with macrocarpol,tion of, 372.of substituted benzyl ions, 43.by, 66.Ferric ions, hydrolysis of, 124.oxide, 10.189.Kamlolenic acids, u- and 8-, stereo-chemistry of, 308.Ketones, preparation of, 169.Kinetics of chemical change, 7.Kinetin, synthesis of, 240.Kokusaginine, structure of, 245.“ Labelled ” reagents, 374.trans-Lachnophyllum ester, synthesis of,Lactobacillic acid, occurrence of, 308.Lactobacillus bifidus from avian sources,309.338.LactobaciZlus bifidus var Penn.prepara-tions, enzyme activities of, 336.Lactones, 230.Lactose, 2-0-a-~-fucopyranosyl-, as aconstituent of human milk, 258.aZZoLactose question, the, 338.Lanosterol, epimers of, 225.formatioqpf, 186.Lanthanon bisulphite ” solutions, 105.Laurifoline, structure of, 254.See also Garryfoline.Lead tetra-acetate, oxidation of carbo-hydrates by, 256.Lead, tetraethyl-, synthesis of, 104.isoleucines, configurations of, 275.“ Lichenin,” nature of, 264.(&)-Limonene, isomerisation of, 168.Linalool, preparation of, 188.Linocinnamarin, structure of, 170.Linolenic acid, synthesis of, 306.Lipids, 165.a-Lipoic (6-thioctic) acid, synthesis of,231.Lipoxidase, 31 6.Liquids, theory of, 62.Liquid solutions, theories of, 64.Lithium, determination of, 346.Lithium as reducing agent, 168.Lithium aluminium hydride, uses of,Lithium hydroxide, criticism of use of,Lithium silicides, 97.Longifolene, 195.Lumicolchicines, 178.Lupeol, stereochemistry of, 186.Lupin alkaloids, 243.(-J-)-epiLupinine N-oxide, occurrence of,Lycorenine, structure of, 252.Lycorine, structure of, 250.DL-Lysine, synthesis of, 274.Lysozyme, crystal structure of, 395.Lyxose, formation of, from xylose, 268.Machaerinic acid, structure of, 203.Macrocarpol.See Juniperol.Maculine, structure of, 245.Magnesium, detection of, 346.determination of, 368.micro-determination of, 350.Magnesium bromides, alkenyl-, use of, 167.Magnesium carbide, 99.Magnesium hydride, 99.Manganese, determination of, 351.Manganese dioxide, oxidation by, 157.Mannans, 263.D-Mannose, 2 : 3 : 6-tri-O-methyl-, separ-ation from 2 : 3 : 6-tri-O-methyL~-glucose, 256.Markogenin, structure of, 223.Marrubiin, configuration of, 198.Matricaria ester, dehydro-, 310.Matricaria esters, 309.separation of, from sodium, 97.152, 153.344.243.nitride, preparation of, 124.gluco- and galacto-, 263INDEX OFMavacurine, partial structure of, 246.Mellein (ochracin), structure of, 236.p-Menth-l(7)-ene, formation of, 188.Mercury, determination of, 366.Mercury(1).determination of, 342.Mercury, dimethyl-, pyrolysis of, 11.Mercuric oxide, new form of, 100.“ Mesoionic,” use of the term, 233.Metal catalysts, reactions on, 53.Metal halides, anhydrous, preparation of,Metal oxide catalysts, reactions on, 55.Metalation, reagent for, 168,Metallic ions, oxidation by, 27.Methane, di+nitrophenyl-, brominationMethane-air mixtures, lean, combustionMethionine, isolation of, 276.Methoxyl, determination of, in presenceMethylation of carbohydrates, quantit-Methyl borate, rotational isomerism in,Methyl nitrate, rotational isomerism in,123.of, 168.of, 16.of ethoxyl, 356.ative, 255.87.87.pyrolysis of, in flames, 18.nitrite, pyrolysis of, in flames, 18.Methyl neopentytketone, photolysis of, 20.‘‘ Methyl-purple, nature of, 347.Methylsulphonium analogue of methionine,Mexogenin, structure of, 223.Mills-Nixon effect, 136.Mirene, structure of, 196.Molybdenum, determination of, 352.Monosaccharides, 255.Monoterpenes, 187.Morin, use of, in complexometric titration,(-)-Morphine, stereochemistry of, 254.apoMorphine dimethyl ether, synthesis of,250.Mycamhose, 256.Mycarose, 256.Mycobactin, 166.Mycomycin, 310.Myoglobins, 391.Myosimine, structure of, 244.Naphthalene, electronic spectra of, 78.Naphthalene, 1-nitro-, condensation of,2-Naphthol, l-ethylthiomethyl-, as anNemotinic acid, structure of, 311.Neptunium-(v) and -(vI), complexes of,Nickel, determination of, 342, 356.Nickel, tetrathionitrosyl-, 94.Nickel carbonyl, formation of, 125.Nickel hydrides, 126.Nickel-acetylene complexes, 126.isoNicotinic acid, preparation of, 234.Niobium, determination of, 369.Niobium, lower valency states of, 116.272, 276.348.with anthracene, 171.alkylating agent, 161.122.SUBJECTS.446Niobium carbides, 114.Niobium (v)-tantalum (v) oxides, 1 16.Nitramide, base-catalysed decompositionNitrogen, active,” nature of, 110.chemisorption of, on metals, 52.determination of, 355, 369.micro-determination of, 364.Nitrogen atoms, reactions of, 23.Nitrogen molecule, ground-state dis-sociation energy of, 74.Nitrous oxide, activation energy ofdecomposition of, 54.thermal decomposition of, 9.Nitric oxide, oxidation of, by oxygen, 8.thermal decomposition of, 12.Nitrogen dioxide, thermal reaction of,Dinitrogen tetroxide, oxidation by,156, 170.Dinitrogen pentoxide, thermal de-composition of, 9.Nitric acid, thermal decomposition of,32.Nitric acid vapour, thermal decom-position of, 12.Nitriles, alkaline hydrolysis of, 160.formation of, from amides, 160.Nitrite, determination of, 370.reaction of, in acid solution, 29.Nitro-compounds, determination of, 354.Nitrososulphuryl fluoride, 11 8.Nitrosyl hexafluoroiodate, 11 9.Non-benzenoid compounds, 174.trans-cycZoNonene, isomerisation of, 183.Norcaradiene, carboxy-, as source of(A) - and ( -) -1 2-Norsantonin , synthesisNucleic acids, crystallography of, 380, 395.0-0 bond, energy of, in peroxides, 11.Ochracin.See Mellein.cycZoOctadecanone, preparation of, 183.Octadec-12-enoic acid, 9-hydroxy-, occur-rence of, 308.Octadec-trans-1 l-en-9-ynoic acid, 8-hydr-oxy-, occurrence of, 308.A1(Q)-Octalin, 10-ethoxycarbony1-2-oxo-,hydrogenation of, 183.trans-A2-Octalin, stability of, 184.16-epioestriol, occurrence of, 218.Oleic acid, hydrogenation of, 302,synthesis of, 305.Oligosaccharides, 258.of milk, 333.a-Onocerin (a-onocsradienediol), structureof, 199.Oosoporein, structure of, 173.Organic analysis, 353.Organic chemistry, 131.theoretical, 13 1.Orthobenzoic acid derivatives, 259.Osazones, structure of, 257.Oxadiazoles, 1 : 2 : 4- and 1 : 3 : 4-, pre-of, 26;,with hydrocarbon radicals, 13.with hydrogen, 12.tropylium salts, 176.of, 192.paration of, 233446 INDEX OF SUBJECTS.1 : 3 : 4-Oxadiazol-2-ones, preparation of,233.2-Oxaindane-5 : 6-diol hexahydro-, cis-and tvans-, conformation of, 185.Oxalate, oxidation of, by bromine, 29.Oxamycin (cycloserine), structure of,1 : 3-Oxazolidine, ( -)-2-thio-5-vinyl-, syn-1 : 3-OxazolidinesJ 2-thio-, as antithyroidOxazolid-2-ones, preparation of, 232.Oxazolines, 2-aryl-, preparation of, 232.As-1 : 3-OxazolinesJ 2-mercapto-, as anti-Oxetan-3-one, 2 : 2 : 4 : 4-tetraphenyl-,Oxidation, 158.by metallic ions, 27.Oxidations, photochemical, 20.Oximes, N-alkyl, reduction of, 152.O-alkyl, reduction of, 152.Oxygen, atomic, production of, 115.chemisorption of, on metals, 51.determination of, combined, 354, 378.Oxygenations, reactions of, 21.Oxygen-carbon monoxide mixtures,Oxygen-formaldehyde mixtures, thermalOxygen-hydrogen mixtures, ignitions in,Oxygen in slow oxidations, 13.Oxygen molecule, ground-state dissocia-Ozone, production of, in silent discharge,232.thesis of, 293, 294.substances, 291.thyroid substances, 291.preparation of, 229.free, 351.second explosion limits of, 16.inflammation of, 17.16.tion energy of, 74.45.Palladium, chloro-complexes of, 128.determination of, 369.thionitrosyl-, 124.Palladium chloride complexes with ethyl-ene and styrene, structure of, 127.Pantetheine cycle, 314.Pellitorine, disproof of structure of, 312.Pentacene, formation of, 172.cycZoPentadienyls, nitrosyl derivatives of,cycZoPentadienyls and related compounds,cycZoPentadienyliron dicarbonyl, structuren-Pentane, thermal decomposition of, 9.cyclopentanone, thermal decompositionPeptides, biologically active , 2 78.Peroxytrifluoroacetic acid, oxidation by,Persulphate, decomposition of, 29.(f)-Phellandral, synthesis of, 187.Phenanthrene, perhydro-1 : 4-dioxo-, iso-Phenanthrenes, perhydro-1 : 4-dioxo-,heterogeneity of, 166.130.128.of, 129.of, 11.’synthetic, 280.158.meric forms of, 184.stability sequence in, 135.Phenanthro (3’ : 4’-3 : 4)phenanthrene, op-Phenol, 2 : 5-dinitro-, formation of, 168Phenols, polyhydric, reactions of, 170.Phenylsodium-phenyl-lithium, stability ofPhosphides, poly-, 112.Phosphine oxide, tristrifluoromethyl-, 11 3.Phosphinic acid, bistrifluoromethyl-, 11 3.Phosphite, determination of, 352.Phosphonous acid, trifluoromethyl-, 113.Phosphorus, black, preparation of, 11 1.Phosphorus, determination of, 356, 369.Phosphorus hexa-azide, 112.Phosphorus oxychloride, compound of,with antimony pentachloride, 112.Photochemical decompositions, 18.Photometric titration, 363.Photoneutron methods of analysis, 377.Phthalic anhydride, 3-nitro-, use of, 160.Phthiocerol, structure of, 166.Phyllocladene, biogenesis and stereo-Physical properties of gases, liquids, andPimelic acid, a-amino- and a-amino-y-Pinonic acid, rearrangement of, 189.Pipentone, formation of, 188.Plant goitrogens, 291.heterocyclic, origin of, 294.Plant gums and mucilages, 267.Plant viruses, crystal structure of, 399.Platinum, determination of, 369.Platinum(r1) complexes, 128.Platinum electrode, change of potential of,Platinum metals, fluoro-complexes of, 127.Platynecine, structure of, 253.Platyphylline, structure of, 253.Plutonium, isolation of, 122.Plutonium hydrides and deuteride, 122.Polarography, 357.Polonium and its salts, properties of, 119.Polyacenes, electronic structure of, 77.Polyatomic molecules, simple, electronicPolycyclic compounds, 171 , 183.Polyenes, 163.Polymerisation, radical, 33.Polymerisation in solution, 34.Polymers, solid, radiation-induced changesin, 49.Polymethylene chains, conformation of,135.Polysaccharides, 259.algal, 266.muco-, 270.Polysaccharides synthesised by micro-Porphyrins, 240.Potassium, detection of, 345.determination of, 346, 359.Potassium hexafluororhenate, preparationPotassium nitrosodisulphonate, oxidationtically active, 171solutions of, 161.chemistry of, 196.solutions, 56.hydroxy-, occurrence of, 272.with pH, 361.spectra of, 75.organisms, 269.of, 124.by, 173XNDEX OF SUBJECTS.417Potassium tetracyanonickel(I), formationPotassium t e traphen ylboron , evaluationPotentiometric titration, 360.Proline, hydroxymethyl-, occurrence of,L-Proline, synthesis of, 152.cycZoPropanes, monoalkyl-, preparationisoPropy1 alcohol, oxidation of, 29.Proteins, crystallography of, 380.of, 127.of, 363.precipitation of, 346.272.of, 180.fibrous, artificial and natural, 385.globular, 391.isolation and purification of, 282.structure of, 283.Protoanemonin, preparation of, 230.Pteridines, 240.Pterophine, heterogeneity of, 253.Purpurogenone, structure of, 237.Pyrazoles, nitration of, 232.Pyridine, 4-amino-, as acidimetric stand-3-chloro-, formation of, from pyrrole,3-hydroxy-, preparation of, 230.Pyridines, substituted, preparation of, 234.Pyridine-aldehydes and -carboxylic acids,Pyridinium cyclopentadienylide, 175.Pyridocoline, octahydro-, dehydrogenationPyridoxine, preparation of, 231.2-2’-Pyridylethylamines, preparation of,2-Pyridylmercuric chloride, preparationPyrimidines, 2- and 4-hydroxy-, lactamPyrophosphate, determination of, 370.separation of, from triphosphate, 342.Pyrophosphate anions, 113.Pyrosulphuryl fluoride, 11 8.Pyrrocoline system, reactions of, 239.Pyrrole-2-carboxylates, substituted, syn-Pyrrolidines, preparation of, 232.Pyrrolidones, N-alkyl-, preparation of,reactions of, 232.ard, 349.234.preparation of, 234.of, 156.234.of, 234.form of, 235.thesis of, 231.231.Queretaroic acid, structure of, 204.Quinol, reaction of, with maleic anhydrideQuinoline, nitration of, 238.isoQuinoline, dihydro-, isolation of, 238.1-2’-pyridyl-, strain in, 133.Quinones, 173.Quinovic acid, structure of, 202.Radiation chemistry, 42.Radiochemical methods of analysis, 370.Rare-earth ions, paramagnetic, catalys-Reactants, association of, 149.Reactions, acid-base, very rapid, 26.184.ation by, 31.Reactions, exchange, involving net electrontransfer, 26.ionisation, very rapid, 25.neutralisation, very rapid, 25.Reactions in solution, 25.Reorientation by sulphuric acid,.168.Reserpic acid, structure of, 247.Reserpine, stereochemistry and structureResonance, nuclear magnetic, 89.nuclear quadrupole, 91.paramagnetic (electron), 90.Retardation of polymerisation, 36.Rhenium hydride, biscplopentadienyl-,Rhenium(vI1) oxyfluorides, 124.Rhodosamine, 256.Rhombifoline, synthesis of, 243.Ribose, formation of, from arabinose,258.D- and DL-Ribose, 2-deoxy-, formation of,259.j3-D-Ribofuranosyl bromide, tri-U-benzo yl-,hydrolysis of, 259.Ribonuclease, crystal structure of, 394.Ricinoleic acid, (+)-, configuration of, 308.(f)-, synthesis of, 367.Rimuene, structure of, 196.Ring polymerisation, 39.“ Roseonine,” structure of, 272.Rosmarinecine, structure of, 252.Rosmarinine, structure of, 253.Rotational isomerism, 86.Ruscogenin, 223.Ruthenium, use of, as Fischer-Tropschcatalyst, 55.Sagittol, 190.Salicylic acid, 6-methyl-, 170.Samandarine, 224.Samarium, separation of, from europium,Samogenin, structure of, 211, 223.ekaSantalic acid, 195.Santalenes, 195.4-Santonic acid, structure of, 193.Santonin (a-santonin), 191.j3-, a mixtutre, 192.of, 248.130.105.tetrahydro-, a- and y-, 192.9-, 193.Sapogenms, stereochemistry of, 222.Scandium oxalate, hydrates of, 104.Sebum waxes, 304.Selenium, determination of, 368.Selenions acid, rate of oxidation of, byhydrogen peroxide, 29.Senecionine, structure of, 253.Sequence of amino-acids in polypeptidesand proteins, determination of, 277.cycloserine. See Oxamycin.(f)-Sesamin, identity of, with fagarol,237.Sesamolin, structure of, 237.Sesquiterpenes, 189.Silica, fused, adsorption by, 66.Silica-alumina catalysts, 55.Silicic acid, polymerisation of, 39448 INDEX OF SUBJECTS.Silicon monosulphide, formation of, 107.monoxide, formation of, 107.tetrachloride, reaction of, with hydrogensulphide, 107.tetrafluoride, preparation of, 107.Silyl compounds, 106.Silylphosphine, 106.Silks, water-soluble, structure of, 387.spiroSiloxanes, 10 7.Silver, isobut-I-enyl-, 98.Silver azide, complex ions of, 98.Silver complexes, 3-co-ordinate, 96.Silver electrode, response of, to pH, 360.Silver iodide, complex ions of, 98.Silver iodide sols, adsorption by, 60.Silver silicates, 108.Silver sulphate, y-ray induced reductionSkimmianine, structure of, 245,Skimmianinic acid, methyl ester, structureSkimmiol, identity of, with taraxerol, 205.Sodium, determination of, 369.Sodium aluminium hydride, use of, 152.Sodium amalgam, reaction of, with carbonSodium-atom reactions, 17.Sodium formatoborohydride, 100.Sodium manganate, preparation of, 124.Sodium peroxide, commercial, nature of,Solasodine, configuration of, 224.Sols, stability of, 71.Spectra, pure rotation, 81.vibration, 83.vibration-ro tation, 82.Spectra of flames and discharges, 89.Spectral intensities, 86.Spectroscopy and molecular structure,Spermostrychnine, structure of, 248.Standardisation of volumetric solutions,349.Starch, 265.Stearic acids, monohydroxy-, preparationof, 302.Stellatogenin, structure of, 203.Sterculic acid, constitution of, 165, 308.Stereochemistry in alicyclic series, 184.of, 48.of, 245.separation of, from lithium, 97.vapour pressure of, 97.dioxide, 97.115.72.of amino-acids, 274.of steroids and terpenes, 185.of steroids, 207.Steric effects, intramolecular, 142.Steric strain, 132.Steroids, 207.a-5, 11-0x0-, bromination of, 214.9 : 10-seco-, 226.enzymic hydroxylation of, 316.stereochemistry of, 207.trimethyl-, 224.Stevioside, structure of, 268.Stilbene, 2 : 3’ : 4 : 5‘-tetrahydroxy-, oc-Stillingic acid, structure of, 305.Strain, intermolecular, 137.currence of, 170.Strontium hyponitrite, decomposition of,Strychnospermine, structure of, 248.Styrene, polymerisation of, 34.Sulphur, allotropy of, 116.determination of, 354, 355.Sulphur compounds, exchange reactionsSulphur-boron compounds, 102.Sulphur dioxide, determination of, in111.nitrite, decomposition of, 11 1.of, 29.atmosphere, 369.oxidation of, by nitrous oxide, 12.photochemical oxidation of, 21.Sulphur fluoronitrides, 11 7.halides, lower, preparation of, 117.oxyfluorides, 11 8.oxynitride, S,N,O,, 116.tetrafluoride, 11 7.Sulphate, determination of, 350.Sulphides, lower, of metals, 116.Sulphuric acid solutions, y-irradiationSumaresinolic acid , stereochemistry of,Sydnone, 3-3’-pyridyl-, phototropy of,of, 47 .203.234.Talomethylose, formation of, from fucose,Tantalum, determination of, 369.Tantalum alkoxides, 116.Tantalium(v)-niobium (v) oxides, 11 5.Taraxerene, structure of, 205.Taraxerol, identity of, with skimmiol, 205.Tariric acid, 311.Tazettine methine, structure of, 251.Tellurium, determination of, 368.Tellurium(1v) alkoxides, 119.Tellurium(rI) dibromide, 119.Terpenes, 185.Terphenyl, y-ray induced luminescence ofTetra-alkoxyborates of alkaline-earthTetraethylammonium diphenylamide, 1 10.Tetramminosodium ion, stability of, 97.1 : 2 : 11 : 12-TetraphenylcycZoeicosane,Tetraphyllin, structure of, 248.cycZoTetrasiloxane, octamethyl-, polymer-Tetrasulphur nitride, S,N,, 11 6.Tetrazan, 110.Thiadiazoles, 1 : 2 : 4- and 1 : 2 : 3-, pre-Triazole, 2-amino-, preparation of hydro-Thiazol-5-ones, preparation of, 232.Thioacetamide, use of, instead of hydrogenrhiocyanates, antithyroid activity of,I’hiolutin, structure of, 239.rhionitrosyl salts of various metals, 116.rhionyl chloride as an ionisirrg solvent,258.solutions of, 49.metals, 102.preparation of, 183.isation of, 40.paration af, 233.chloride of, 232.sulphide, 343.292.118INDEX OF SUBJECTS.449Thorium, amides and imides of, 108.behaviour of, towards acids, 108.determination of, 342, 343.nitrate, dehydration of, 109.oxalate, dehydration of, 109.D-Threose, 4 : 4-di-C-hydroxymethyl-, pre-Thurberogenin, structure of, 203.Thymonucleic acid , structure of, 396;‘Tirucallaze,” use of, instead of ele-Tirucallol, correlation of, with euphol,Titanium, behaviour of, towards acids,paration of, 259.mane, 226.225.epimers of, 225.determination of, 368.di- and tetra-chlorides, 108.oxyfluoride, 108.tetrakistrimethylsilyloxy-, 10 8.Titanium alloys, analysis of, 358.Toluene, mercury-photosensitised de-Tomatidine, configuration of, 224.Total synthesis of steroids, 227.Transfer in polymerisation, 37.Triazines, 1 : 2 : 4- and 1 : 3 : 5-, prepara-Trichloromethyl polysulphides, 11 6.Tricyclene, 189.Trifluoroacetamido-acids, preparation of,Trifluoromethanesulphonic acid , 11 7.Trifluoromethyl fluorodithioformate, 11 7.Trimethylene oxide, thermal decom-Triphosphate, separation from pyrophos-Triplet states, 79.Triterpenes, 199.Tropinone methiodide, decomposition of,Tropolones, 176.reactions of, with organometallic com-pounds, 177.Tropone, 4-hydroxy-, 177.Tropones, 176.Tropylium cation, the, 174.Tungsten, determination of, 341.108.composition of, 19.tion of, 235.281.trithiocarbonate, 11 7.position of, 11.phate, 342.181.Tungsten, heats of adsorptbn on, 52.Tungstic oxide, use of, in combustionanalyses, 353.Uranium sulphides, 122.Uranyl amide, 122.Urothione, structure of, 240.Usnic acid, synthesis of, 237.(&)-Usnic acid, synthesis of, 173.“ Vaccenic acid,” heterogeneity of, 165,Valeric acid, (+)-y-amino-, formation of,Vanadium, detection of, 345.lower oxides and hydroxides of, 114.Vanadium(1v) , complex chlorides, of, 114.Vanadometry, 352.. Veatchine, structure of, 253.Vernolic acid, structure of, 308.Vinyl acetate, polymerisation of, 33.Vinylene carbonate, use of, 181.4-VinylpyridineJ homopolymerisation of,Virial coefficients, measurements of second ,Viruses, crystallography of, 380.Vitamin B,,, assay of, 372.crystal structure of, 403.structure of, 242.Voacangine, structure of, 245.Vouacapenic acid, methyl ester, structureWater, radiolysis of, 49.Waxes, natural, structural relations in,Weights, coating of, 339.Wool wax, nature of acids of, 302.upuXanthoxyletin, formation of, 237.Ximenynic acid, synthesis of, 308.Xylans, 261.D-Xylose, 2-C-hydroxymethyl-, prepara-305.275.33.59.of, 197.304.tion of, 259.Yohimbine skeleton, formation of, 239.Zirconium, determination of, 369.solubility of, in acids, 108

ISSN:0365-6217    

DOI:10.1039/AR9555200439

出版商:RSC    

年代:1955

数据来源: RSC