ISSN:0365-6217    

DOI:10.1039/AR95249FP001

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

ERRATA.VOL. 46, 1949.Page. Line.VOL. 48, 1951.3347265For or to that at the nucleus read or to a 2 v / W at the nucleus.For 0.8 f 2 kcal. read 0.8 f 0.2 kcal.21 1 5 For 3-chloro-2-hydroxy-5 : 6-dimethoxybenzoic acid read3-chloro-2-hydroxy-4 : 6-dimethoxybenzoic acid

ISSN:0365-6217    

DOI:10.1039/AR9524900006

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.GENERAL AND PHYSICAL CHEMISTRY.1. BOND INTERACTIONS.THERE are two main methods of obtaining information about bond inter-actions in polyatomic molecules. The first is to compare bond properties indifferent molecules. Thus the C-Cl bond is shorter in ClCN (1.67 A) 1 thanin CH&l (1.781 showing the effect of an adjacent triple bond (there isalso an increase in the force constant).4 The second is to study these inter-actions in a molecule as it vibrates; the usual way of doing this is to deter-mine from the vibration frequencies the function governing the variation ofpotential energy with distortion. For example Slawsky and Denni~on,~ andLinnett 6 found that, in the methyl halides, the C-X bond interacts withthe inter-bond angles in the methyl group, the potential-energy functionshowing that, as the C-X bond is lengthened, the HCH angle tends to in-crease. Analogous interaction effects have been found in ethylene,' formalde-hyde,8 keten,8 and dia~omethane.~ Recently other spectroscopic methods ofinvestigating bond interactions have been used.In this Report methods ofthe second kind will be specially considered.Potential-energy Functions.-Of the two basic force fields the Centralhas proved less useful than the Valency.lo In its simplest form the potential-energy function based on the latter involves squared terms in the bondlength and inter-bond angle changes but, in its complete form, " crossterms '' which take account of the interactions between different parts ofthe molecule are also included.Thus for the water molecule the completevalency force field (V.F.F.) potential-energy function is l1V = gkl(Ar12 + AvZ2) + *kaAuz + kla(Arl + AvZ)A# + klIAylAy2 . (1)where AY,, Ar2, and Act are the changes in the bond lengths and H-0-Hangle, k , and k, are the respective constants, k,, measures the interactionJ. Y . Beach and A. Turkevich, J . Amer. Chem. Soc., 1939, 61, 299.L. E. Sutton and L. 0. Brockway, ibid., 1935, 57, 473; S. L. Miller, L. C. Aamodt,A. D. Walsh, Trans. Faraday Soc., 1947, 43, 60.J. W. Linnett and H. W. Thompson, J., 1937, 1399.2. I. Slawsky and D. M. Dennison, J . Chem. Phys., 1939, 7, 509.J. W. Linnett, ibid., 1940, 8, 91.H. W. Thompson and J. W. Linnett, J., 1937, 1376.B. L.Crawford, W. H. Fletcher, and D. A. Ramsay, J . Chem. Phys., 1951, 19, 406.lo G. Herzberg, " Infra-red and Raman Spectra of Polyatomic Molecules," Vanl1 D. F. Heath and J. W. Linnett, Trans. Furaday SOL, 1948, 44, 550.G. Dousmanis, C . H. Townes, and J. Kraitchman, J . Chem. Phys., 1952, 20, 1112.Idem, ibid., p. 1384.Nostrand, New York, 1945, pp. 169-1868 GENERAL AND PHYSICAL CHEMISTRY.between the bonds, and k,, the interaction between the bonds and the angle.There are four independent constants in the complete quadratic potential-energy function. If there are n fundamentalvibrations in a symmetry class, the general potential-energy functiongoverning distortions of that symmetry will contain &n(n + 1) independentconstants.To obtain the number of independent constants for all distortionsof the molecule these must be summed over all symmetry classes. Thus, forwater, there are two fundamental symmetric vibrations ; for these distortionsthere are three constants. There is one fundamental antisymmetricvibration; for this there is only one constant. There are therefore fourconstants in all [cf. (l)].Determination of Force Constants.-The molecule H,O has only threevibration frequencies, so, from them alone, the four constants cannot befound. This difficulty may be overcome by using isotopes. Thus, for water,deuterium oxide which also has three fundamental frequencies may be used.However, for any pair of isotopic molecules, the Teller-Redlich productrule12 states that the ratio of the product of the frequencies of all thevibrations of a given symmetry class for one isotopic molecule to the corre-sponding product for the other is independent of the force field and equalto a function involving the atomic masses and molecular dimensions only.So, since the vibrations of H,O and D,O fall into two symmetry classes,D20 provides only one new independent frequency.This with the three ofH,O makes possible the determination of all four constants. The vibrationfrequencies of DOH might also be used but, because of relationships betweenthe frequencies of isotopic molecules , they provide no additional inform-ation. Decius and Wilson l2 have deduced certain sum rules relating thevibration frequencies of isotopic molecules.the summations being over all vibration frequencies.Decius l4 has alsoexamined what isotopic substitution is necessary in linear molecules toobtain a unique solution for the force constants.Hence, if the frequencies of a sufficient number of isotopic molecules areavailable all the constants may in principle be determined. However theuse of isotopic substitution is not always well suited for the accurate deter-mination of force constants. This may be illustrated with hydrogen cyanide.The valency vibration frequencies of HCN are 3312.0 and 2089.0 cm.'l.15The table lists the frequencies calculated for DCN and HC15N for threevalues of k,, in the functionAs one vibration frequency of DCN is 2629.3,15 k,, must have a small negativevalue.But the figures for HC15N show that it would be necessary toThis is so whatever its form.For example for water;Sv2(HOH) + CvZ(DOD) = 2Zv8(HOD) . . . . * (2)P' = &kl(AVm)' + &(A~CCN)' + ~ I ~ ( A ~ C ' C H ) ( A ~ O N ) * * - - (3)DCN HClSNL r 3 I > k,, ( x 10-6) -0.5 0 +0.5 -0.5 0 +O-5Frequency (crn.-l) 2648.0 2596.1 2548.6 3309-9 3310-8 3311.61881.4 1919.1 1954-9 2056.5 2056-0 2055.4l2 0. Redlich, 2. fibhysikal. Chem., 1935, B,. 28, 371 ; see also W. R. Angus e t aZ.,l4 J. C. Decius, ibid., 1952, 20, 511.J., 1936, 971. l3 J . C. Decius and E. B. Wilson, J . Chem. Phys., 1951, 19, 1409.l6 G. Herzberg, ref. 10, p. 279LINNETT BOND INTERACTIONS. 9determine the frequency shifts from HCI4N to HC15N very accurately tofix the value of kI2.The reason why the substitution of deuterium forhydrogen in hydrogen cyanide is so effective in determining k,, is that,while the CH " group " frequency is much greater than that of the C-Nbond, the CD " group " frequency is close to that of the C-N bond. Thecloseness of the " group " frequencies in DCN causes the effect of varyingk,, on the calculated frequencies to be large. Isotopic substitution shouldtherefore be used for calculating force constants only when it is clear thatit provides a reliable method.For H,O, and other bent AX, molecules, in the absence of isotopic sub-stitution there are only three frequencies to determine four constants. Aconvenient method of representation has been suggested by Duchesne, l6and Glockler and Tung,17 who proposed that the values of three constantsshould be plotted against values of the fourth which is regarded as an inde-pendent variable.It is then found that the graphs are ellipses, and thevalues of the constants are limited to certain ranges. Such graphical repre-sentations have been used by Burnelle and Duchesne,l* Torkington,lgThomas,20 and Linnett and Heath.21 However it is often impossible toselect from such inadequate data the correct set of values for the constantsand it is important that efforts be made to obtain, with complete certainty,all the constants in the general potential-energy function for as many mole-cules as possible so that reliable conclusions may be drawn from the values.Another method that has been used for overcoming the difficulty thatthe number of constants usually exceeds the number of observed frequenciesis that of transferring constants from other molecules containing similarbonds.Thus Crawford and Rrinkley 22 used the same values for the con-stant of the C-N bond in hydrogen cyanide and methyl cyanide. Thismethod has been used by Cleveland and Meister and their co-workers inextensive calculations on the halogen derivatives of methane,23 ethane,24and other molecules.25 However there are often variations in bond lengthsfrom one molecule to another (e.g. from methyl chloride to carbon tetra-chloride) so that there can be no certainty that force constants can betransferred in the above manner. Caution must be used in making suchtransfers.Thomas 26 has used constants from related molecules but hasmade allowance for bond changes on going from one to another. Forl6 J. Duchesne, Mesn. SOC. Roy. Sci., Lizge, 1943, 1, 429.G. Glockler and J. Y . Tung, J . Chem. Phys., 1945, 13, 388.J. Duchesne and L. Burnelle, ibid., 1961, 19, 1191.l9 P. Torkington, ibid., 1949, 17, 357.21 J. W. Linnett and D. F. Heath, Trans. Furaday Soc., 1952, 48, 592.22 B. L. Crawford and S. R. Brinkley, J . Chem. Phys., 1941, 9, 69.33 A. G. Meister, S. E. Rosser, and F. F. Cleveland, ibid., 1950, 18, 346; S. M.Ferigle, F. F. Cleveland, W. M. Bryer, and R. B. Bernstein, ibid., p. 1073; J . P. Zeitlow,F. F. Cleveland, and A. G. Meister, ibid., p. 1076; J. R. Madigan, F. F. Cleveland,W. M. Bryer, and R.B. Bernstein, ibid., p. 1081 ; J. R. Madigan and F. I;. Cleveland,ibid., 1951, 19, 119; C. E. Decker, A. G. Meister, and F. F. Cleveland, ibid., p. 784;P. F. Farlon, A. G. Meister, and F. F. Cleveland, ibid., p. 1561 ; A. Davis, F. F. Cleve-land, and A. G. Meister, ibid., 1052, 20, 454.24 F. F. Cleveland, J. E. Lamport, and R. W. Mitchell, ibid., 1950, IS, 1073; M. 2.El-Sabban, A. G. Meister, and F. F. Cleveland, ibid., 1951, 19, 855; P. 13. McGee,F. F. Cleveland, and S. I. Miller, ibid., 1952, 20, 1044.25 J. S. Ziomek and F. F. Cleveland, ibid., 1949, 17, 578; F. F. Cleveland, K. W.Greenlee, and E. E. Bell, ibid., 1950, 18, 355.26 W. J . 0. Thomas, ibid., 1951, 19, 1162.2o W. J. 0. Thomas, J., 1952, 238310 GENERAL AND PHYSICAL CHEMISTRY.example, the CO force constant in CO, is known exactly, and, from this andthe bond length, using Gordy’s form~lze,~~ Thomas calculated the bond orderin CO,. From the bond length in cyanic acid he calculated the CO bondorder in that molecule, and, from this, using Gordy’s formulz again, heobtained the CO force constant in cyanic acid.So, from the small observedchange in bond length (1-163 to 1.170 A) he determined the small change inthe force constant (from 15-5 to 15.0 x lo5 dynes/cm.). If accurate bondlength tralues are available from micro-wave or other data this probablyprovides the best means of making use of the known value of a force constantof a similar bond in a related molecule. It is to be preferred to transferringthe value uncorrected.With molecules having doubly degenerate vibrations there is a furthermeans of obtaining information about force constants.Such vibrations canpossess angular momenta by virtue of their internal motions, and the magni-tude of the vibrational angular momentum associated with a certain excitedlevel can, in favourable cases, be determined from the structure of the bandsassociated with the transition to that level from the ground state.28 Thisangular momentum is dependent on the force field and may be used todetermine force constants. Formulae for doing this have been publishedby Boyd and Longuet-Higgin~,~~ For the vibrations of a given symmetryclass (say the three of the degenerate class of methyl chloride) the sum ofthe angular momenta associated with all the first excited levels of thatclass has a particular value independent of the force field.Lord and Merri-field 30 and Boyd and Longuet-Higgins 29 have given some examples of themagnitude of this sum. So, for the degenerate vibrations of methyl chloridethere are only two independent angular momenta available for determiningthe force constants.As yet the so-called Coriolis coefficients which measure the angularmomentum associated with the vibration have not been widely used fordetermining iorce constants. Dennison 31 used them with ammonia andhe and Hansen3z used the frequencies of ethane and hexadeuteroethanetogether with values of the Coriolis coefficients to determine all 21 constants(excluding torsion) in the potential-energy function of that molecule. Lordand Venkatcswarlu33 have pointed out that for allene all ten potentialconstants associated with distortions corresponding to the degeneratevibrations could be obtained from the eight degenerate vibration frequenciesof allene and tetradeuteroallene (only seven are independent because of theTeller-Redlich relation) and the eight Coriolis coefficients (only six areindependent because of the sum rules),It has been assumed so far that the potential-energy function is quadratic27 W.Gordy, J . Chem. Phys., 1946, 14, 305; 1947, 15, 305.28 V. &I. McConaghie and H. H. Nielsen, Proc. Nut. Acad. Sci., 1948, 34, 455;D. R. J. Boyd, H. W. Thompson, and R. L. Williams, Discuss. Furuduy Soc., 1950, 9,154; D. R. J. Boyd, H.W, Thompson, and R. L. Williams, Proc. Roy. Sot., 1952, A ,213, 42; D. R. J. Boyd and H. W. Thompson, Trans. Faraday SOC., 1952, 48, 493;H. W. Thompson and R. L. Williams, ibid., p. 502; H. H. Nielsen, J . Chem. Phys.,1952, 20, 759.R. C. Lord and R. E. Mecrifield, J . Chenz. Phys., 1952, 20, 1348; M. Johnstonand D. M. Dennison, Phys. Review, 1935, 48, 868.29 D. R. J. Boyd and H. C. Longuet-Higgins, PYOC. Roy. Soc., 1952, A , 213, 55.3L D. M. Dennison, Review Mod. Phys., 1940, 12, 175.32 G. E. Hansen and D. M. Dennison, ./. Ckem. Phys., 1952, 20, 313.53 R. C. Lord and I?. VenkateswarIu, ibid., p. 1237LINNETT BOND INTERACTIONS. 11and anharmonicity can be neglected. When the aim is to obtain the completepotential-energy function this is not always justifiable.But only in rare cases(e.g. hydrogen cyanide,S5 nitrous oxide 36) can sufficient overtonesbe observed to obtain the zero-order frequencies. In other cases othermethods have to be adopted. For instance Dennison corrected the observedfundamentals of methane by assuming a relationship between the an-harmonicity coefficients of methane and tetradeuteromethane and by usingthe Teller-Redlich product rule. Hansen and Dennison treated ethanesimilarly.Calculating force constants from vibration frequencies is often tedious.Procedures for making such calculations have been proposed by El’yashe-v i ~ h , ~ ’ Wilson,38 and Torkingt~n.~~Results for Interaction Constants.-The simplest type are the bond-bondconstants of linear molecules [ e g .k,, in (3)] for in these the valency vibrationsoccur independently of the bending ones. In most cases the cross-termconstant is positive (e.g. in C0,,8 CS2,40 N3-,4* N,O,41 OCS,42 C1CN,20 BrCN,20ICNIz0 and also, regarding the NH as a unit, in HNC0,20 HNCS,20 and HN, 20).But in HCN,35 and the bent molecules H,O,ll H2SJM and H2Se,40 it is negative.The positive value of this constant has been ascribed to the effect of resonance.Thus in carbon dioxide there is resonance between (i) O=C=O, (ii) 6-C&,and (iii) 0sC-O. The lengthening of the left-hand bond, therefore, favours(ii) and the consequent shortening of the right-hand bond.s The potentialenergy increases less, therefore, when A Y ~ and AY, are opposite in sign thanwhen they are of the same sign and this accounts €or the cross-term constantbeing positive; but, when hydrogen is one of the atoms attached to thecentral atom, the constant is negative.Coulson, Duchesne, and Manne-back4, have suggested that this is due to a charge effect. Hoare andLinnett 40 pointed out that, when the cross-term constant is positive in atriatomic molecule, the diatomic molecule left on dissociating one bondwould be expected to be shorter than the corresponding bond in the triatomicmolecule. This is found to be so (e.g. rCs in CS, is 1.55 and in CS 1.53 A).When the constant is negative the reverse is to be expected; this is alsofound ( e g . roH in H20 is 0-958 and in OH 0-971 A). Thomas has confirmedthis in the molecules studied by him.20 The sign of the cross-term constantsin the mercury halides is still uncertain and more data for these would beinteresting.The positive cross-term constants are always larger than thenegative ones so interaction resulting from resonance effects must be greaterthan that occurring in hydrogen cyanide, water, etc. Heath, Linnett, and34 L. G. Bonner, Phys. Review, 1934, 46, 458; B. T. Darling and D. M. Dennison,ibid., 1940, 57, 128.35 W. Brookes, Trans. Faraday Soc., 1951, 47, 1152.3 6 G. Herzberg, ref. 10, p. 278.3 7 El’yashevich, Compt. rend. Acad. Sci., U.R.S.S., 1940, 28, 604.3 8 E. B. Wilson, J . Chena. Phys., 1939, 7, 1047; 1941, 9, 76; J. C. Decius, ibid.,39 I?. Torkington, ibid., 1949, 17, 357; 1950, 18, 93, 773; 1951, 19, 528, 979.4O M.F. Hoare and J. W. Linnett, Trans. Faraday SOC., 1949, 45, 844.4 1 W. S. Richardson and E. B. Wilson, J . Chem. Phys., 1950, 18, 604.42 H. J. Callomon, D. C. McKean, and H. W. Thompson, Proc. Roy. SOC., 1961,43 C. A. Coulson, J . Duschesne, and J. Manneback, Nature, 1947, 160, 793;+ -1948, 16, 1025.A , 208, 341.“ Contribution a 1’Etude de la Structure Moleculaire,” Liege, 1948, p. 3312 GENERAL AND PHYSICAL CHEMISTRY.Wheatley44 pointed out that in CH,, SiH,, NH,, PH,, H,O, and H,S thebond lengths were always less than in the diatomic molecules AH but,though the cross-term constants are not certain, it seems that they arepositive in the Group IV hydrides and in ammonia but negative in theGroup VI hydrides and in phosphine and arsine. The contrast betweenammonia and arsine has also been noted by Duchesne and Ottelet 45 whosuggest that it may be due to the opposing effects of hybridisation changesand H---H interaction which tend to lead to positive and negative cross-term constants, respectively.They also point out that the bond-bondinteraction constants involving bonds to hydrogen are small.From the three valency vibration frequencies of cyanogen and one ofthe molecule containing one 13C atom, Duchesne and Burnelle 18 have foundthat the (CN)(CC) cross-term constant is positive and the (CN)CN’) cross-term constant negative. The sign of both can be accounted for by theeffect of resonance between NC-CN and double-bonded forms, for a shorten-ing of one C-N bond favours the first canonical form and hence a lengtheningof the C-C bond (positive constant) and a shortening of the other C-N bond(negative constant) (cf.Longuet-Higgins and Burkitt 46).Torkington 47 has suggested a potential-energy function (omitting angleterms) for polyatomic molecules derived from that of Morse for diatomicmolecules. This includes bond-bond interaction terms and, for triatomicmolecules, Torkington relates the sign of the cross-term constant to thedifference between the heat of atomisation and the sum of the bond-dissoci-ation energies (cf. Duchesne 48). He also considers the sign of the higher-order terms in the potential-energy function.In methyl chloride the largest interaction constant is that between theC-Cl bond and the H-C-Cl.angle.It is positive showing that, as the H-C-C1angle is increased the C-C1 bond tends to shorten. It is noteworthy that,in cyanogen chloride, where a similar drawing together of the three pairs ofelectrons opposite to the chlorine atom must also have occurred (relative tomethyl chloride in its near-tetrahedral equilibrium configuration) , theC-Cl bond has become shorter. A similar effect appears to occur in methaneand hydrogen cyanide also.@ In methane the (CHi)(HjCHk) constant isnegative indicating that, as the HjCHk angle is reduced the CHi bond tendsto shorten. Also in hydrogen cyanide (and in acetylene) the C-H bond isshorter than in methane.50 The shortening of the C-Cl bond in cyanogenchloride is often ascribed to resonance, but objections have been made tothis explanation by Burawoy 51 and by D u c h e ~ n e .~ ~ Burawoy suggests thatit is due to changes in electron shielding and other inter-electronic effects,while Duchesne relates it to changes in hybridisation a t the chlorine atom.He has explained in a similar manner increases in bond length from carbontetrachloride to methyl chloride, from silicon tetrachloride to silyl chloride,44 D. F. Heath, J. W. Linnett, and P. J. Wheatley, Trans. Faraday Soc., 1950, 46,137.45 J. Duchesne and I. Ottelet, J . Chem. Phys., 1949, 17, 1354.46 H. C. Longuet-Higgins and F. H. Burkitt, Trans. Faraday Soc., 1952, 48. 1077.47 P. Torkington, J . Chem. Phys., 1952, 20, 1174.48 J. Duchesne, Mew. Acad. Roy. Betg., 1952, 26 (7), 1.4* J. W. Linnett, Proc.Roy. SOC., 1951, A , 207, 30.50 A. D. Walsh, ref, 3 ; J. W. Linnett, Trans. Favaday sot., 1945, 41, 223.6 1 A. Burawoy, Trans. Farnday SOL., 1943, 39, 79; 1944, 40, 537; “ Contribution aI’Etude de la Structure Moleculaire,” Li&ge, 1948, p. 73.52 J . Duchesne, Trans. Faraday Soc., 1950, 46, 187; J . Chem. Phys., 1953, 19, 246LINNETT : BOND INTERACTIONS. 13and from carbon tetrafluoride to methyl fluoride, giving nuclear quadrupolecoupling data in various molecules in support of this hypothesis. Thoughthe above effects in methyl chloride and cyanogen chloride correspond withthose in methane and hydrogen cyanide the bond-bond cross-term constantin the two triatomic molecules are different.The calculations by Hansen and Dennison32 for ethane are valuablebecause they provide a complete treatment of a relatively large molecule.The bond-angle are the largest interaction constants ; all the bond-bondconstants are small.As with the methyl halides the (CC)(CCH) constantis quite large and positive, but the biggest interaction constant is thatassociated with the term (CHi)(CCHi+,), the bond and angle being in thesame methyl group. It is negative, indicating that, as the C-Hi bond islengthened, the CCHi+ angle tends to increase. The constant associatedwith the (CHi)(Hi+ ,CHi-J cross-term is also negative, indicating that, asthe C-Hi bond is lengthened, the Hi+ ,CHi-, angle tends to increase. Thus,as the CHi bond is lengthened, the angles on the opposite side of the carbonatom tend to increase, so the effect is analogous to that produced by thelengthening of the C-C bond (and the C-Cl bond in methyl chloride 5).The interactions between the separate methyl groups are of interest becauseit may be possible to link these to the effects restricting rotation.Themolecule being in the staggered form, it is found that increasing one HCCangle tends to cause the opposite one in the other methyl group to increase,and that increasing a C-H bond length in one methyl group tends to causethe adjacent CCH angles in the other methyl group to decrease. The lattercould be due to repulsion between non-bonded atoms or between bonds butthe former is more difficult to explain, though it might be accounted for byhyperconj ugation effects.Torkington has studied ethylene 53 and its derivatives 54 extensively.Many of his conclusions are unaffected by modifications made to the fre-quency assignment by Arnett and C r a ~ f o r d , ~ ~ and Rank, Shull, and A ~ f o r d .~ ~For instance he finds that the interaction constant between adjacent C-Hbonds is negative (as in water, etc.) and between the trans-C-H bonds isprobably positive. The latter suggests that as one C-H bond is lengthenedthe C-H trans to it tends to contract. The (C=C)(C-H) interaction constantis positive, and Torkington suggests that this may be a consequence ofrepulsion between non-bonded hydrogen and carbon atoms (cf. Heath,Linnett, and Wheatley 57). Torkington also studied the out-of-planebending constant of the CH, group in CH,=CH,, CH,=CHX, and CH,=CX,,where X = methyl, halogen, cyano, etc.= He found that the effect onthe constant is twice as great for the CH,=CX, molecules as for the corre-sponding CH,=CHX molecules (using ethylene as the reference molecule)and also that ortho- and para-directing groups lower the constant whilewta-directing ones increase it.This surprising result appears to show that,1s electrons are drawn from the double bond, the constant increases. In alater paper 53 Torkington links this effect to the conclusion of Heath, Linnett,63 P. Torkington, Proc. Phys. SOL, 1951, A , 64, 32.54 Idem, Nature, 1949, 163, 96; Proc. Roy. Soc., 1950, A , 206, 17.5 6 R. L. Arnett and B. L. Crawford, J . Chew. Phvs., 1950, 18, 118.56 D. H.Rank, E. R. ShuII, and D. W. E. Axford, ibid., p. 116.6 7 D. F. Heath, J . W. Linnett, and P. J . Wheatlcy, Trans. Fnvadny .TOC , 19*9. 45. 114 GENERAL Ah’D PHYSICAL CHEMISTRE’.and Wheatley 57 that the out-of-plane bending of the ethylene molecule iseasier because the constant associated with the x-bond is negative. Tork-ington also studied the out-of-plane bending constant of the CH group inCH,=CHX molecules and found that the order was that of the electro-negativities of the attached groups X.%An important factor causing deviations from the simple valency forcefield is undoubtedly repulsion between non-bonded atoms as has been shownby Urey and Bradley 58 for various AX, molecules and ions, and by Sima-nouti 59 in a variety of substituted derivatives of methane and silane.Heathand Linnett also showed the importance of such repulsions in boron halidesJ6*various hexafluoridesJ61 Group IV halides,62 and such ions as SO,”, NO3-,e t ~ . ~ ~ (see also Coulson, Duchesne, and Manneba~k,~~ and Sehon andSzwarc 6*). Both Simanouti, and Linnett and Heath compared the repulsionconstants with those to be expected from the known van der Waals repulsionbetween inert gas atoms as calculated by Lennard- Jones.G5 Linnett andHeath,,l in a general survey, showed that the repulsion constants for a givenpair of non-bonded atoms varied regularly in a series of molecules with thedistance separating them. Wilson and Polo 66 find that the bond-bondconstant in nitrogen trifluoride is probably positive. This could be due torepulsions between the fluorine atoms.Caunt, Short, and Woodward 67have examined similar repulsion effects in germanium tetrafluoride.Dennison has determined the five potential constants of methane.31For those governing bending only, the main HCH constant is 0.42 x lo5(in dynes/cm.) and the (HfCHj)(H&Hz) interaction constant is -0.075 x lo5.The negative sign of the latter suggests that reducing one HCH angle tends tocause the opposite one to close up also. This would be an erroneous con-clusion, for the six HCH angles cannot be varied independently. Suppose(AHiCHj) = - (AH,CH,) and the distortion is symmetrical, the other HCHangles will not change, but if (AHiCHj) = + (AH,CH,) the other four anglesdecrease by an angle equal to half the increase in the other two.From thisit is easy to show that the potential energy increases more rapidly withchange in angle for the distortion in which (AH&Hj) = + (AH,CH,) thanfor the distortion in which (AHfCHj) = - (AHkCHz). So the closing of oneHCH angle favours the opening of the opposite one. This can be explainedby electron correlation effects 68 or by, what is essentially equivalent,hybridisation changes. Difficulties like the above provided one of thereasons for Heath and Linnett’s modifying the ordinary valency force fieldto their orbital force field (0.V.F.F.) in which the central atom is imagined5~3 H. C. Urey and C. A. Bradley, Phys. Review, 1931, 38, 1919.5s T. Simanouti, J . Chem. P h y s . , 1949, 17, 245, 734, 848; D.F. Heath and J. W.6o D. F. Heath and J. W. Linnett, Trans. Faraday Soc., 1948, 44, 873.61 I d e m , ibid., 1949, 45, 264.62 I d e m , ibid., 1948, 44, 561, 878.64 A. H. Sehon and M . Szwarc, Proc. Roy. Soc., 1951, A , 209, 110.65 J. E. Lennard-Jones, ibid., 1924, A , 106, 463; (‘R. A. Buckingham, ibid., 1938,Statistical Thermodynamics,”6 6 M. K. Wilson and S. R. Polo, J . Chem. Phys., 1952, 20, 1716.O 7 A. D. Caunt, L. N. Short, and L. A. Woodward, Nature, 1951, 168, 557; Trans.68 (Sir) J . E. Lennard-Jones, J . Chem. Phys., 1952, 30, 1024; H. Margenau, “ TheLinnett, ibid., 1950, 18, 147.63 I d e m , ibid., p. 884.A , 168, 264; R. H. Fowler and E. A. Guggenheim,C.U.P., 1939, p. 285.Faraduy SOC., 1952, 48, 873.Nature of Physical Reality,” McGraw-Hill, 1950, p.434LLNNETT : BOND INTERACTIONS. 15to have its valencies directed in particular directions relative to one another,and the angular deviation of each bond from their directions is used in thepotential-energy function.60 Force fields of the same type had been usedby Urey and Bradley 58 and by Howard and Wilson 69 but had never beendeveloped. By this approach difficulties like that for methane will notexist because the impossibility of varying angles independently does notoccur in using the O.V.F.F. In terms of cross-terms, a simple O.V.F.F.with no cross-terms, will correspond, in certain cases, to an ordinary V.F.F.including finite angle-angle cross-terms (and vice versa).Some wave-mechanical calculations of force constants and interactionconstants have been made.Examples are provided by W a r h u r ~ t , ~ ~ Coulsonand L~nguet-Higgins,~~ Parr and C r a w f ~ r d , ~ ~ Parr and Taylor,73 Wheatleyand L i ~ ~ n e t t , ~ ~ and Longuet-Higgins and Burkitt.46Intensities of Infra-red Bands.-Since 1945 an active start has beenmade in determining the intensities of infra-red bands and in using the dataobtained. The procedure is to determine the intensities of the fundamentalabsorption bands of the molecule and from these to calculate the rate ofchange of dipole moment with each normal co-ordinate, +/aQ (see Wilsonand Wells 7 5 ; Thorndike, Wells, and Wilson 7 6 ; Callomon, McKean, andThompson 77; and Penner and Weber 78). After a normal co-ordinatetreatment these may be converted into values for the rate of change of p withbond lengths and angles (+/h and ap/&).In most treatments the ap/&values have been related to a change of moment of a particular bond withlength and the &L/& values used to calculate bond moments supposing that,as the molecule bends, the bonds retain their constant moments whichremain directed along the line joining the atoms. The justifiability of thesefar-reaching assumptions seems to be doubtful. T h ~ r n d i k e , ~ ~ for example,stated that his results for ethane ‘‘ cast some doubt upon the whole conceptof additivity of bond dipole moments ” (see also Bell, Thompson, andVagoDipole-moment changes on distortion can also be obtained from measure-ments of refractive indices using infra-red radiation, as has been done byRollefson with RollefsonJ81 with Havens,sZ and with Kelly and Schurin.833ne important difficulty in the interpreting of the change of p on distortionis that the magnitude, but not the sign, can be deduced from the datalbtained from both refractive-index and absorption measurements.For carbon dioxide Thorndike 79 found that all‘/& for the C=O bond was6s J. B. Howard and E. B. Wilson, J . Chenz. Phys., 1934, 2, 630.70 E. Warhurst, Trans. Faraday Soc., 1944, 40, 26.7 1 C. A. Coulson and H. C. Longuet-Higgins, Proc. Roy. Soc., 1948, A , 193, 447.78 R. G. Parr and B. L. Crawford, J . Chem. Phys., 1948, 16, 526; 1949, 17, 726.73 R. G. Parr and G. R. Taylor, ibid., 1951, 19, 497.74 P.J. Wheatley and J. W. Linnett, Trans. Faraduy Sot., 1949, 45, 897.7 5 E. B. Wilson and A. J. Wells, J . Cltern. Phys., 1946, 14, 578.7 G A. h4. Thorndike, A. J. Wells, and E. B. Wilson, ibid., 1947, 15, 157.7 7 H. J. Callomon, D. C. McKean, and H. W. Thompson, Proc. ROT. Soc., 19517 8 S. S. Penner and D. Weber, J . Chem. Phys., 1951, 19, 807, 817, 974.79 A. M. Thorndike, ibid., 1947, 15, 868.8o R. P. Bell, H. W. Thompson, and E. E. Vago, Proc. Roy. Soc., 1048, A , 192, 498*l R. Rollefson and A. H. Rollefson, Phys. Review, 1935, 48, 779.82 R. Rollefson and R. Havens, ibid., 1940, 5’9, 710.83 R. L. Kelly, R. Rollefson, and B. S. Schurin, J . Clzeiw. Phys., 1951, 19, 1595.4 , 208, 33216 GENERAL AND PHYSICAL CHEMISTRY.+6.0 D/A (p and p’ are used for the dipole moments of molecules and bonds,respectively).This is much bigger than ap’/& for the C-H bond in methane(&0.55).82 He suggests that the large value in carbon dioxide arises be-cause, during the antisymmetric distortion, which is used in the measure-ment, there is a change in the relative contributions of the various canonicalforms which results in a large swing of charge across the molecule (cf. theearlier explanation of the cross-term constant 8). Such an effect will notoccur in methane. In effect, therefore, he ascribes the large value of ap‘/arto aE interaction between the two C=O bonds. Eggers and Crawford 84have investigated the intensities of some combination and overtone bandsof carbon dioxide and, by using Crawford and Dinsmore’s 85 theoreticaltreatment, have deduced the coefficients of higher-order terms in the expres-sion for the dipole moment.They find that “ electrical anharmonicityseems definitely the predominant factor accounting for the observed intensityof the 3614 and 3716 cm:l bands ” which is further evidence for interactionbetween the bonds. Unfortunately the sign of the coefficients of thesehigher-order terms cannot be fixed so that the data do not yet providedefinite information regarding the nature of the interaction, An examinationof the intensities of the bands of molecules like l60C18O might help in dis-coilrering more about electrical interactions between the bonds.86 Nitrousoxide has been studied by Thorndike, Wells, and Wilson 76 and by Callomon,McKean, and Thompson 77 who found that the values for in this mole-cule are large also.The explanation is probably similar to that for carbondioxide. Eggers and Crawford have measured the intensities of overtoneand Combination bands of nitrous oxide (see also Fraser and Price *’).Robinson 88 concluded that ap/arc, in carbonyl sulphide is -6.7&0-5compared with -6.0&0.6 in carbon dioxide and that i?p/arcs is --4.3,tO.r>in the iormer compared with -5.6&0.5 in carbon disulphide. He com-mented on the relative constancy of both these values. Callomon, McKean,and Thompson 42 give a higher value (8-55) for dp/drco in carbonyl sulphide.Hyde and Hornig 89 studied band intensities in hydrogen cyanide anddeuterium cyanide and found that p& and ap’/laruH are much greater inthe former than in methane.They ascribe this to changes in hybridisationof the bond orbitals. Kelly, Rollefson, and Schurin 83 also found pbTJ tobe greater in acetylene than in methane. However they found that ap’larcn:had about the same value in the two molecules (see Callomon, McKean, andThompson 42). Hyde and Hornig found that arc^ in hydrogen cyanidewas similar to that found by Nixon and Cross in cyanogen but much lessthan that found by them in cyanogen chloride. They ascribed the largevalue in the latter to the greater polarisability of the C-C1 bond; in effect,to interactions between the bonds (cf. interaction constant). They con-cluded that pbH in hydrogen cyanide decreases with bond length just asfor ~ H C I in hydrogen chloride (Bell and Coop 91),84 D.I;. Eggers and €3. L. Crawford, J . Chew. Phys.* p. 1554.85 B. L. Crawford and H. L. Dinsmore, ibid., 1950, 18, 983, 1682.B 6 B. L. Crawford, abid., 1952, 20, 977.R. D. B. Fraser and W. C. Price, Nature, 1952, 170, 490.D. 2. Robinson, J . Chenz. Phys., 1951, 19, 881.89 G. E. Hyde and D. F. Hornig, ibid., 1952, 20, 647.OO E. R. Nixon and P. C. Cross, ibid., 1950, 18, 1316.O1 R. P. Bell and I. E. Coop, Trans. Faraday SOC., 1938, 34, 1209LINNETT : BOND INTERACTIONS. 17Barrow and McKean92 have examined the methyl halides in detail.Only some of their results can be reported here. They found that ap’/aroxdecreases from the fluoride to the iodide, as would be expected, but that thevalues are surprisingly large especially for the C-F bond (4.7 D/A).Suchlarge values have only been observed previously in resonating systems.Robinson 93 has found that the dipole moment of hydrogen chloride dependscritically on the hybridisation of the bonding orbitals of the chlorine atom,and they suggest that a similar explanation may account for the large valuesof &L’/~Y,, in the methyl halides (cf. Duchesne 52). Barrow and McKeanalso deduce values for &L‘/&~H from the symmetric and degenerate vibrationsassuming no interaction between the bonds. In all the halides the valuesobtained from the symmetric are greater than those from the degeneratevibrations. The lack of agreement between the two values shows that, inall cases, bond interactions must occur.This is similar to the conclusionreached by Thorndike 79 from his study of ethane (cf. Francis 94). Theassumption of additivity of bond dipoles and an independent linear variationof bond dipoles with bond length seems to provide only a poor approxim-ati0n.9~ There is great need for some further theoretical developments inthis field.Other Possible Methods of Studying Bond Interactions.-The intensityand depolarisation factors of Raman lines may be used, together withmolecular polarisabilities, for calculating bond polarisabilities and theirchanges with bond length. This has been done by Wolkensteing6 for sub-stituted methanes. Cabannes and Rousset 97 have, however, approachedthe problem differently and regard changes of polarisability during molecularvibrations as resulting from changes in the interactions between centres ofpolarisability caused by changes in their separation.Further progress hererequires an extension of our knowledge of the intensities and depolarisationfactors of Raman lines.The determination of the quadrupole coupling constants provides avaluable means of obtaining information about the electron configurationaround a nucleus and changes in this from molecule to molecule caused bychanging environment. Examples of important applications o€ this methodhave been given recently by Townes and Dailey 98; Mays and Dailey *9;Westenberg, Goldstein, and Wilson loo ; Goldstein and Bragg 101 ; Gordy 102 ;Tetenbaum lo3 ; Simmons and Goldstein 104 ; and Duchesne.105J.W. L.9z G.93 D.94 s.95 J.207, 03;O 6 N835, 88397 J.9 8 c.99 L.loo A.lol J.102 w103 s.104 J.Io5 J .M. Barrow and D. C. McKean, PYOC. Roy. SOC., 1952, A , 213, 27.. 2. Robinson, J . Chem. Phys., 1949, 17, 1022.A. Francis, ibid., 1950, 18, 861.A. Pople, PYOC. Roy. SOC., 1950, A , 202, 323; C. A. Coulson, ibid.“ Valence,” O.U.P., 1952, p. 207.. V. Wolkenstein, Acta Physicochem, U.R.S.S., 1945, 20, 161, 174,; J . Exp. Theor. Phys., U.S.S.R., 1948, 18, 138.Cabannes and A. Rousset, J . Phys. Radium, 1940, 1, ( 8 ) , 138.H. Townes and B. P. Dailey, J . Chem. Phys., 1949, 17, 782.M. Mays and R. P. Dailey, ibid., 1952, 80, 1693.A. Westenberg, J. H. Goldstein, and E.B. Wilson, ibid., 1949, 17, 1H. Goldstein and J. D. Bragg, Phys. Review, 1949, 75, 1453.. Gordy, J . Chem. Phys., 1951, 19, 792.J. Tetenbaum, Phys. Review, 1952, 86, 440.W. Simmons and J. H. Goldstein, J . Chem. Phys., 1952, 20, 122.Duchesne, ibzd., p. 1894., 1951, A ,525, 544,31918 GENERAL AND PHYSICAL CHEMISTRY.2. SURFACE CHEMISTRY.The solid-liquid interface is the main theme of this section, and sincethis has not been reported on previously it is necessary to sketch in themain investigations of a decade and a half. Reasons of space have excludedreference to kinetic aspects, to flotation, and adsorption isotherms forsolutions. Two monographs, by Gregg la and Bikerman,l* have appearedin recent years, and there is considerable research in progress.Thermodynamics of the Solid-Liquid Interface.-The basis of modernwork remains the relations due to Young, Duprd, Gibbs, Hardy, and Lang-muir, set out in the textbooks on surface chemistry by Rideal 2a and Adam.2bHere we shall start with the work of Harkins and Dahlstrom and Banghamand R a ~ o u k , ~ who pointed out that arguments based on contact anglesmust take account of the adsorbed film of liquid on the free surface of thesolid.This consideration clarified many thermodynamic quantities,especially the work of adhesion. The equations of surface thermodynamicshave been systematically reviewed in numerous papers by hark in^,^* 6* 7¶ *and the following summary largely follows this author, using his nomen-clature. Let ysFo denote the surface free energy of the solid surface coveredwith an adsorbed film in equilibrium with the saturated vapour (pressure Po),yLV0 that of the liquid-vapour interface, and y y ~ that of the solid-liquidinterface.If a t equilibrium the liquid makes a contact angle eE with theplane surface of the solid, regarded as insoluble in the liquid, thenIf the solid surface has an adsorbed film corresponding to a pressure p < Po,the free energy isysv = y s t + yLv cos 0The work of adhesion is defined here as the work required to separate 1 cm.2of solid-liquid interface in vucuo,Here ys and yL denote surface tensions in zlacuo of solid and liquid, re-spectively. If (la) is substituted in (2), and if yLvo = 'yr; (except for liquidmetals, yL, the surface tension in vucuo, is equal to the usual value measuredin air), thenThe spreading pressure of an adsorbed film on a solid is defined byor for the adsorbed film at saturation pressure. .. . . . ysvo = ysL + y L v o ~ ~ ~ eE - (la). . . . . . . (1b)wA(8Z) = y8 + YZ - y8L - * - - * * - (2)w A ( S L ) = YS - YSV" + yL(1 + cos 8,) * * * * (3)l$ = ys - ysv . . . . . . . - (4a)t$h! = y&! - ysv" . . . . . . . - (4b)(a) S. J. Gregg, " Th?,Surface Chemistry of Solids," Chapman and Hall, London,1951 ; ( b ) J. J. Bikerman,( a ) E. K. Rideal, " An Introduction to Surface Chemistry," Cambridge Univ. Press,1930; ( b ) N. K. Adam, '' Physics and Chemistry of Surfaces," Oxford Univ. Press, 1941.W. D. Harkins and R. Dahlstrom, Im.d.Eng. Chem., 1930, 22, 897.D. H. Bangham and R. I. Razouk, Trans. Faraday SOC., 1937, 33, 1458.G. E. Boyd and W. D. Harkins, J . Amer. Chem. Soc., 1942, 64, 1190, 1195.W. D. Harkins, J . Chem. Phys., 1941, 9, 552.W. D. Harkins and H. I<. Livingston, ibid., 1942, 10, 342.W. D. Harkins and G. Jura, " Colloid Chemistry," Vol. VI, Chapter I (Ed., J .Surface Chemistry," Academic Press, New York, 1948.Alexander), Reinhold Publ. Corpn., New York, 1946ELEY : SURFACE CHEMISTRY. 19Substituting (4b) in (3) yieldswAcsL, = $rc + yL(i + case,) . . . . . * ( 5 )w2(8L,) = y L ( 1 f coS6,) . . . . . . (6)The equationyields the work required to separate 1 cm.2 of solid and liquid and leave anadsorbed film on the solid. Greg la calls this the work of adhesion, but inthe Reporter's opinion it is preferable to use (5).$E is appreciable for metalsand oxides, although for solids such as paraffin it may be very small.Eqn. (1) is Young's equation, (2) Duprk's equation, and eqn. (5) has beencalled the corrected Young-Duprk relation.Further definitions concern the spreading coefficient of a liquid on asolid to give thick (Harkins " duplex " 6, films. For the initial spreadingof a liquid on the clean solid surfacesL/S = ?'8 - y8,5 - Y& = $E e . . - * - (7a)Since the film adsorbed at saturation is a duplex film, i.e., has a lowersurface with energy ySL and an upper one with energy yL, S L , ~ is of courseequal to +E. The final spreading coefficient refers to the film-covered solid.s&,8i = ySVo - YSL - YL .- * * * . - (7b)As noted originally by Hardy, if SLIs is positive, the liquid will spread onthe solid.These equations may be adapted to the case where the solid is slightlysoluble in the liquid, if one puts the appropriate values ~ L ' V O and ~ S L 'into eqn. (1).for liquids and, with qualifications, for solids."free energy which omits the y A term, viz., G = U + PV - TS.Helmholtz free energy is F = U - TS.The surface tension may be equated to the free surface energy perHarkins employs a GibbsTheIn terms of these functions, we have eitherwhere small letters denote thermodynamic functions for 1Harkins usesf where the British use g, and E where the British use u.solid from a liquid into a vacuum isof surface.The Gibbs free energy change of emersion (reverse of immersion) of agE(SL) = g 8 - gSL = YS - y8L - * * * - (9)Physically Adsorbed Films on Solids.-Two topics of immediate interestare 4~ and the surface-area problem.In addition, the discussion of physicaladsorption is continued from the Annual Reports for 1950 and 1951.Bangham 10 suggested application of the Gibbsadsorption equation for calculating the spreading pressure of an adsorbedThe spreading pressure.@ W. D. Harkins, " Techniques of Organic Chemistry," Vol. I (Ed., A. Weissberger),lo D. H. Bangham, Trans. Faraduy SOC., 1937, 33, 805.* Thus, surface free energy is correct in eqn. ( ~ ) ( c f . R. Shuttleworth, Proc. phys.Intersci. Publ., New York, 1945.SOC., 1949, ea, A , 167)20 GENERAL AND PHYSICAL CHEMISTRY.film on a solid.adsorbed per cn~.2 of surface, thenIf I? is the " surface excess," i.e., the number of moles+ = p P 0and, if the perfect gas law can be assumed, then, (10a)where z, C.C.of gas are adsorbed on area A at pressure p , and V is the molarvolume of the gas. To obtain #E, the integration is taken up to the saturationvapour pressure PoRT *'v h =ml0 jjdp . . . . . . . . ( l o b )Bangham suggested that 4~ can only be regarded as a true lateral pressurewhen the film is mobile. Bangham and Razouk 11 applied graphical inte-gration to Coolidge's data for charcoal in order to evaluate +E. Harkins andJura have used this method extensively, and their +E values are listed in theTable on p. 25. A comparison of the third and the fifth column in thisTable show that +E may be 50% or more of the work of adhesion.Bafigham and Razouk11 found a dis-continuity when +a was plotted against ?/Po for water on charcoal, whichthey attributed to formation of a condensed phase.Here a = l/I' is thearea per molecule in the adsorbed film, assumed unimolecular. Gregg,12and later Harkins and Jura,*, 13914 have extended this analysis, findingcurves analogous to those found for monolayers on water.2* l5 FollowingDervichian, phase changes were classified according to Ehrenfest, viz., afirst-order change is a discontinuity in the v-$ isotherm, a second-orderchange a discontinuity in (%) -p, etc. First-order phase changes werereported for water on graphite, and for n-heptane on silver, ferric oxide, orgraphite.Smith l6 has repeated the work on the last two systems andfailed to find the transition points, so the matter is still open. However,as originally shown by R. H. Fowler, a first-order condensation processmay occur if attractive forces exist between neighbouring molecules in amonolayer. The theoretical aspects of phase changes in adsorbed filmshave been reviewed by Hi1l.l'Gregg and Maggs 18 plot the function p' against log p to reveal moreclosely the nature of the phase changes involved. p' is proportional to thecompressibility of the monolayer and isPhase changes in monolayers.av[Pl 1 D. H. Bangham and R. I. Razouk, Trans. Faraday SOC., 1937, 33, 1463.l2 S. J . Gregg, J., 1942, 696.l4 G. Juraetal., J .Chem. Phys,, 1945, 13, 535; 1946, 14, 117, 344.l5 W. D. Harkins, " Colloid Chemistry," Vol. V (Ed., J . Alexander), Reinhold Publ.l6 R. N. Smith, J . Amer. Chem. SOC., 1952, 74, 3497.3 7 T. L. Hill, Adv. i~ Catalysis, 1952, 4, p. 21 1,le S . J. Gregg and F. A. P. Maggs, Trans. Faruduv Soc., 1048, 44, 123.W. I). Harkins and G. Jura, J . Chem. Phys., 1944, 12, 112; J , Amer. Chem. SOC.,1944, 68, 1356.Corpn., New York, 1944ELEY : SUKPACE CHEMISTRY. 21where na& molecules are adsorbed per g. of solid. This method shows a veryfew true first-order changes, e.g., for n-heptane on silver, but most of thechanges occur over a range of pressure and fall into Mayer and Streeter’sclass of diffuse first-order ~hanges.1~ The changes are shown to occurbefore multi-layer formation sets in.Tompkins suggests that the changesare truly of first order, but blurred by surface heterogeneity.Coulter and Candela 21 attributed a phase transition, observed for wateron silver iodide, to the formation of a hydrate by an impurity. After sub-traction of this effect, a type I11 isotherm was obtained. Bowden andThrossel 22 found that a platinum foil, cleaned in V ~ C U O by electron bombard-ment, adsorbed only a unimolecular layer of water at PIPo = 0.9. Thethirty or so layers taken up before cleaning were attributed to traces ofhydrophilic impurities.Harkins and Jura 8 discuss empirical equations of state of adsorbedmonolayers, and use that for a condensed phase, 4 = a - bcc, as the basisfor their well-known surface area method (H.J. relative method 23).Thermodynamics and Surface Areas.-The theoretical aspects of physicaladsorption have been reviewed by Hill.17 He advocates 17¶ 24 the usefulnessof “ adsorption thermodynamics,” treating the adsorbed film as a pseudo-one-component system, yielding integral values of energies and entropiesof adsorption. Everett 25 discusses solution thermodynamics, treatingadsorbed gas and solid as a two-component system, which leads to differentialenergies and entropies. The thermodynamics of the solid-liquid interfaceyielding integral energies and entropies of immersion form a third system.Hill and Everett have clarified relations between the solution and adsorptionthermodynamics, and a discussion of immersion data has been promisedby Hill and Jura.17 The present approach to adsorption is predominantlythermodynamic. Thus, Hill, Emmett, and Joyner 26 have calculated fromisotherms differential and integral energies and entropies of adsorption fornitrogen on graphon. Drain and Morrison 27 have made similar calculations,using calorimetric data, for argon on rutile.The integral entropy of adsorp-tion goes through a minimum a t 0 = 1, an effect predicted by the Brunauer-Emmett-Teller (B.E.T.) equation for large c values, and considered by theauthors as justification for use of the B.E.T. equation for determinationof surface areas.I t is well known that the B.E.T. equation predicts too high an adsorptionfor $/Po > 0.35. Casse128 showed a related effect, that substitution of theB.E.T. isotherm into eqn.(10) yields + E = co. Hill 17 attributes thiscatastrophe to the configuration partition function, and stresses that a properapproach to multilayer theory can only be made through the difficult modernFurther work of this kind is urgently needed.Is J. E. Mayer and S. F. Streeter, J . Chem. Phys., 1939, 7, 1019.2o F. C. Tompkins, Tyans. Favadccy Soc., 1950, 46, 580.21 L. V. Coulter and G. A. Candela, 2. Elektrochem., 1952, 56, 449.22 F. P. Bowden and W. R. Throssel, Nature, 1952, 167, 601, 1038.23 W. D. Harkins and G. Jura, J . Amer. Chem. SQC., 1944, 66, 1366.24 T. L. Hill, J . Chem. Phys., 1949, 17, 520; 1950, 18, 246; Trans. Faraday SOC.,26 D. H. Everett, ibid., 1950, 46, 453.26 T.L. Hill, P. H. Emmett, and L. G. Joyner, J . Amel.. Chem. SOC., 1951, 73, 5102,27 L. E. Drain and J. A. Morrison, Trans. Faraday SOC., 1952, 48, 840.t 8 H. M. Cassel, J . Chem. Phys., 1944, 12, 115; J , Phys. Chem., 1944, 48, 195.1951, 47, 376.593322 GENERAL AND PHYSICAL CHEMISTRY.theory of liquids. He concludes I ‘ that, bearing in mind the confirmatorywork of Harkins and J ~ r a , , ~ B.E.T. areas are the best available at present.”The most recent papers do not disturb this conclusion. B.E.T. theory hasbeen applied to water on montmorillonite.30 Molecular cross-sectionalareas O’ have been obtained by determination 31 of VM for anatase of knownarea (H. J. absolute method 29) and their deviations from the liquid density anoted, e.g., CO, -8-1%, CO, +43.5%.The k of the H. J. relative methodwas found to be 0.2510. Anderson and Emmett 32 compare the B.E.T.method, its modifi~ation,3~ and the H. J. relative method 23 for variousgases on a range of carbon blacks. Barrer et aZ.* have produced a numberof modified B.E.T. equations which fit data up to higher pressures and giveconsistent Vrm values. Corrin, using a solid of known area, has comparedH.J. relative areas and B.E.T. a r e a ~ , ~ 5 and Huttig and B.E.T. areas.36Theimer3’ proposes a semi-empirical equation of the B.E.T. type. Achemisorbed film, depending on its nature, may reduce,38 or leaveunchanged,39 the isotherm for physical adsorption.The thermodynamic properties of argon on rutile upto 8 = 0.6 may be satisfactorily interpreted on the basis of a localisedmonolayer on a heterogeneous surface without interaction^.^^ The plot ofheat of adsorption against 8 for argon on the (1 11) face of potassium chlorideagrees with calculations, and differs markedly from the values for the (100)face.*1 This supplements data on the effect of crystal face on adsorptionalready advanced by Rhodin 42 for nitrogen on copper.Halsey43 notesthat a comparison of Rhodin’s data for single crystal faces and polycrystallinecopper, points to intercrystalline boundaries as an important source ofheterogeneity. In a review, Halsey43 concludes that the usual B.E.T.nitrogen isotherm with the well-marked point B corresponds to a state ofintermediate heterogeneity. The Sips distribution is different for nitrogenon rutile from that for oxygen and argon.a4 Huttig and Theimer45 havediscussed lateral interactions and heterogeneity, using the expanded Lang-muir equation.Porous Solids.-The pore-size distribution is generally measured 46 byapplication of Kelvin’s equation to the desorption branch of the isotherm.Thus, if the saturation vapour pressure of a liquid be Po, molar volume V ,Heterogeneity.29 W.D. Harkins and G. Jura, J. Amer. Chem. SOC., 1944, 66, 1362, 1366.3o R. W. Mooney, A. G. Keenan, and L. A. Wood, ibid., 1952, 74, 1367,3 l H. L. Pickering and H. C . Eckstrom, ibid., p. 4775.32 R. B. Anderson and P. H. Emmett, J. Phys. Chem., 1952, 56, 753, 756.33 R. B. Anderson, J. Amer. Chem. SOC., 1946, 68, 686.34 R. M.Barrer, N. Mackenzie, and D. McLeod, J.. 1952, 1736.35 M. L. Corrin, J . Amer. Chem. Soc., 1951, 73, 4061.313 Idem, J . Phys. Colloid Chenz., 1951, 55, 612.37 0. Theimer, Trans. Faraday Soc., 1952, 48, 326.38 F. S. Stone and P. F. Tiley, Nature, 1951, 167, 654.sS A. S. Joy and T. A. Darling, ibid., 1951, 168, 433.*O L. E. Drain and J . A. Morrison, Trans. Farnday SOC., 1952, 48,316; J. A. Morrison,J . M. Los, and L. E. Drain, ibid., 1951, 47, 1023.41 D. M. Young, ibid., 1952, 48, 548.42 T. N. Rhodin, Jr., J. Amer. Chem. SOC., 1950, 72, 5692.43 G. D. Halsey, Adv. Catalysis, 1952, 4, 259.44 J . M. Honig and L. H. Reyerson, J. Phys. Chenz., 1952, 56, 140.46 G. F. Hiittig and 0. Theimer, 2. EEektrochem., 1952, 56, 490.413 A. G. Foster, Trans.Faraday SOC., 1932, 28, 645; Proc. Roy. SOC., 1934, A , 146,129ELEY : SURFACE CHEMISTRY. 23and surface tension y, across a plane surface, then across a meniscus in acapillary, of radius r and with a contact angle 8,Foster 47 assumed that 8 = 0, and that a bimolecular layer of thickness 20is adsorbed on the capillary, so that Y = ro - 2 ~ , where yo is the actualradius of the capillary. Some success has been achieved in applying thistheory to data for ferric oxide gel, where seven liquids lie on a commonr0-v curve (v = volume adsorbed). Pore-distribution curves, dvldr against r,are disc~ssed.~7 Wheeler 48 has proposed a theory combining B.E.T.muitilayer and capillary-condensation viewpoints with Y = ro - t, t beingthe multilayer thickness at pressure p .Shul149 points out that B.E.T.theory predicts excessively thick multilayers for gases on plane surfacesand recommends obtaining t from experimental data on non-porous solids.This procedure has been followed recently by Juhola, Palumbo, and Smith ;they compare pore-size distribution for carbon blacks (1) from nitrogendesorption data 51 and (2) from water desorption data.52 Since the carbonblacks are free from hydrophilic groups, it is assumed adsorption is negligible,t = 0, and 0 = 60". The distributions agreed approximately over the22-300 A range, and method (2) was found applicable to the whole rangeof pores. The importance of pore-distribution in catalytic work has beenstressed in an important article by Wheeler.53The open-pore theory of hysteresis 46 has been developed by Cohan,54who considers condensation to start by formation of a cylindrical meniscusradius ro - G, at pressure pa, and desorption at pressure p, to follow theusual Kelvin equation with Y = yo.ThusHysteresis commences a t pd = pa, and thus a t ro = 2s. This theoryhas been discussed by Brunauer 55 and again recently by F0ster.~6 Cohan'stheory does not consider an adsorbed layer in desorption (eqn. 13b), andFoster 56 endeavours to improve this. He considers the adsorption potentialas made up of a term for capillary condensation and one for multilayeradsorption. The theory predicts that hysteresis will occur when productVylRTo for the adsorbed liquid exceeds unity. Pierce and Smith 57 haveconsidered hysteresis in charcoal adsorption, where adsorbed patches areformed on active spots.Everett and Whitton 58 consider the properties ofa mechanical model for hysteresis similar to the well-known bimetallic-strip4 7 A. G. Foster, Discuss. Faraday SOC., 1948, 3, 4.48 A. Wheeler, Catalyst Symposia, Gibson Island A.A.A.S. Conference, June, 1945,49 C . G. Shull, J . Amer. Chem. SOC., 1948, 10, 1405.50 A. J. Juhola, A. J. Palumbo, and S. B. Smith, ibid., 1952, 74, 61.51 E. P. Barrett, L. J. Joyner, and P. P. Halenda, ibid., 1951, 73, 373.52 A. J. Juhola and E. 0. Wiig, ibid., 1949, 71, 2069.53 A. Wheeler, Adv. Catalysis, 1951, 3, 249.E4 L. H. Cohan, J . Amer. Ckem. Soc., 1944, 66, 98.s5 L. Brunauer, " The Adsorption of Gases and Vapours," Vol.I, Oxford Univ.56 A. G. Foster, J., 1952, 1806.57 C . Pierce and R. N. Smith, J . Phys. Chenz., 1950, 54, 784.5 9 D. H. Everett and W. I. Whitton, Trans. Faraday SOC., 1952, 48, 749.June 1946.Press, London, 194524 GENERAL AND PHYSICAL CHEMISTRY.thermostat control (cf. also Gregg la). Freezing-point depressions have beenmeasured for liquid held in capillaries.59y60 The Kelvin equation has beenapplied to the contact zones of anatase powder.61Bartell and Bower 62 have applied eqn. (9a) to a porous gel (silica gel).They evaluated A+ by graphical integration and plotted log A# against-log$/$,. They obtained a curve which was interpreted as two straightlines cutting at a point fib, where liquid was formed in the capillaries. Thearea of the gel was determined bywhere everything except A was known.Contact Angle and Work of Adhesion.-To calculate work of adhesionone must insert the equilibrium contact angle eE into eqn.( 5 ) , and frequentlyvery large differences have been found between advancing and recedingangles, making evaluation of 8 3 impossible. Adam and Jessop 63 ascribethe difference formally to a frictional force opposing motion of the interface.Adam,2b and Bartell and Cardwell,6* suggest that the relatively largeadvancing angle arises from the need for the liquid to displace lyophobicadsorbed films from the surface. An additional factor is the roughness ofthe surface.2 Wenzel 65 writes a modified version of Young’s equation fora surface of roughness factor v (ratio true : apparent areas),and a thermodynamic proof has recently been advanced for eqn.(15) byGood.66 An analysis has been made of porous surfaces.67 Shuttleworthand Bailey 68 show that, on solids whose roughness is formed by isolated pits,subsidiary minima exist apart from that given by eqn. (la), and so hysteresisof the contact angle arises. Cassie G9 attributes hysteresis to a number ofpossible states of the adsorbed multilayer, which must be in the form ofmolecular clusters rather than a continuous film. Adam, in the discussionfollowing the last two papers, considered that factors other than roughnessmust cause hysteresis with varnished surfaces. Hysteresis of the contactangle has been reported at the mercury-benzene-water interface. 70 Soh-tions of surface-active agents show a unimolecular change of 8 with time,associated with adsorption of the agent.‘1Fowkes and Harkins 72 claim true equilibrium 83 values, using a develop-ment of Adam’s tilting-plate method.63~ 73 Harkins and Livingston59 M. J. Brown and A. G. Foster, Nature, 1952, 169, 37.6o I. Higuti and M. Shimizu, J. Phys. Chem., 1952, 56, 198; I. Higuti and Y. Iwa-61 I. Higuti and H. Utsugi, J. Chem. Phys., 1952, 20, 1180.62 F. E. Bartell and J. E. Bower, J . CoZZoid Sci., 1952, 7 , 80.O3 N. K. Adam and G. Jessop, J., 1925, 1863.O4 F. E. Bartell and P. H. Cardwell, J. Amer. Chem. Soc., 1942, 64, 494.O 5 R. N. Wenzel, Ind. Eng. Chem., 1936, 28, 988.O 6 R. J. Good, J . Amer. Cltem. Soc., 1962, 74, 5041.6 7 A. B. D. Cassie and S.Baxter, Trans. Favaday SOC., 1944, 40, 546.O 8 R. Shuttleworth and G. L. T. Bailey, Discuss. Faraday Soc., 1948, 3, 16.O9 A. B. D. Cassie, zbzd., p. 11.7O F. G. Bartell and C. W. Bjorklund, J. Phys. Chem., 1952, 56, 453.71 G. A. Wolstenholme and J. H. Schulman, Trans. Faraday Soc., 1950, 46, 488.72 F. M. Fowkes and W. D. Harkins, J. Amer. Chem. Soc., 1940, 68, 3377.7 3 N. K. Adam and R. S. Morrell, J. Soc. Chenz. Ind., 1934, 53, 2 5 5 ~ .v(ysvo - y8L) = y A v ~ ~ s e . . . . . . - (15)gami, ibid., p. 921ELEY : SURFACE CHEMISTRY. 25:alculated values of W(alsL from eqn. (5), and showed the importance of + E .The most modern data are in the annexed Table.Free energies of solid-liquid interaction, erg/cm.2 (Harkins)Solid Liquid,, * ............Nitrogen,, 8 ............ %-Butane,, * ............ n-HeptaneAnatase 8 ............ WaterCopper 74 ............Silver 7* ...............Lead 71 ............... ,Iron 7 x ............... I ,Graphite ‘I ............ , t>Spreadingcoeff.190564346293749534 E-Free energyof emersionfiE(8-L)26264586649576973-Work ofadhesionWAWL)3347273866977897369Low-energy Surfaces.-Fox, Zisman, and their co-workers are publishingm important series of papers on “ The Spreading of Liquids on Low EnergySurfaces.” To date, the following have appeared : I, Polytetrafluorethylene(TFE) 75; 11, Copolymers of TFE 7 6 ; 111, Hydrocarbon surfaces 77; IV,Monolayer coatings on platinum 78 ; V, Perfluorodecanoic acid monolayers.79In each case a very large number of pure liquids was found to give finitevalues of OB, measurable by the sessile-drop method to &2” or better. Itwas found that the contact angle was unchanged, whether measured in air,3r in air saturated with the vapour of the liquid, at least for the less volatileliquids. Thus it was concluded that these low-energy solids did not appre-ziably adsorb the vapours concerned, i e . , that +E = 0 in eqn. (5). It wasEurther found that for each homologous series of liquids and a given solid,EOS Ox decreased linearly with the surface tension of the liquid yLvo. Extra-polation to 0 = 0 yielded a parameter ye, regarded as the critical surfacetension, below which spreading of the liquid occurred on the solid concerned,typical values being 33 dynes/cm.for Polythene, and 17-5-206 dynes/cm.€or TFE. The following order of wettability of groups in the solid surfacewas found, @OF, > OGF, > OCH, > &H,. Another interesting result wasthat a monolayer of a long-chain compound effectively changed platinuminto a “ low-energy ” (non-spreading) surface ‘‘ demonstrating beyond doubtthe short-range nature of the forces involved in wetting.’’Elton has suggested combining Antonoff’s lawwithto givewhere ysa, y L A , refer to the surfaces mutually saturated with respect toEach other in air. Thus he calculated a value of Y ~ A for paraffin wax of74 W. D. Harkins and E. H. Loeser, J . Chew. Phys., 1950, 18, 556.75 H.W. Fox and W. A. Zisman, J . CoEloid Sci., 1950, 5, 514.7 6 Idem, ibid., 1952, 7, 109.78 E. G. Shafrin and W. A. Zisman, ibid., p. 166.79 F. Schulman and W. A. Zisman, ibid., p. 465.8o G. A. H. Elton, J . Chem. Phys., 1951, 19, 1066.7 7 Idem, ibid., p . 42826 GENERAL AND PHYSICAL CHEMISTRY.27 dyneslcm., values for water, glycerol, and ethylene glycol agreeing verywell. Fox and Zisman 76 point out that the correct equation isYS = 4~ + + Y L F O ( ~ + cos 0x1but since +E z 0 for their solids, presumably this introduces little error.They note that ys varies from 18 to 30 ergs/cm.2 for TFE, and reject themethod. Elton 81 concludes that evidence for mutual saturation of phases islacking and in any case that real differences in ys may exist.Fowkes andSawyer 82 assume that y8vn and y8L are the same for a solid perfluorinatedoil as for liquid fractions of the same material. Using Young's equation,they calculate OE values for the solid in good agreement with those observedfor a number of liquids. They also test the use of Antonov's rule, calculatingvalues of ysvg of 18.3-23.5 erg/cm.2 compared with 22.4 experimentally.Displacement Pressure.-The rate a t which a liquid penetrates a capillaryis of course determined by yL cos 8, but since this quantity is no longergenerally equal to yx - ysL, but toys - ysL - +E, Harkins and Livingstonsuggested that the use of Freundlich's term, adhesion tension, should beabandoned. Bartell and his co-workers 83 have described a method forrelating the pressure required to stop liquid 1 from displacing liquid 2 froma solid, which assumes that= ys - ysl = y1 cos eW .. . . . - (16)As2 = ys - ys2 = y2 cos osa- = ys2 - ysl = y 1 2 c 0 s e12 . . . . . (17)for the separate liquids displacing air from the powder, andfor liquid 1 displacing liquid 2.the correct equation derived from (5) isHarkins and Livingston have shown thatAS1 - A82 = (YSV," - Y S V z o ) + (YSl - 782)= y1 cos esl + yz COS eS2 . . . . . * (1st.- In one case, eqn. (17) gave 242 ergs/cm.2 while the correct eqn. (18) gave51 ergs/cm.2 for the difference of two adhesion tensions. Again, the equationy12 cos el, = 242 is impossible since y12 for the system concerned is 51.The experimental aspects of the method have also come under 85and a recent worker reports unfavourably on it.86 A D.C.potential isreported to affect adhesion tension.8'Heats of Wetting.-The heat of immersion per cm.2 qi(Ls) of a solid fromvacuo into a liquid, which is the enthalpy change of emersion, h,,, is *3 53 *G. A. H. Elton, J . Colloid Sci., 1952, '4, 450.F. M. Fowkes and W. M. Sawyer, J . Chem. Phys.. 1952, 20, 1650.See, e.g., F. E. Bartell and H. J. Osterhof, I n d . Eng. Chem., 1927, 19, 1277;Symposium on Wetting and Deter-F. E. Bartell and H. Y. Jennings, J . Phys. Chem., 1934, 38, 495.gency," Harvey, London, 1937, p. 19.84 N. S. Davies and H. A. Curtis, Ind. Eng. C k m . , 1932, 24, 1137.85 S. H. Bell, J. 0. Cutter, and C. W. Price,8 6 N. J. de Lollis, J. Phys. Chem., 1952, 56, 193.87 2.Laszlo, J . Chew. Plays., 1952, 20, 1807ELEY : SURFACE CHEMISTRY. 27If the solid has an adsorbed filmTo determine qi(L4 an evacuated bulb of solid is broken under the liquid,whereas if the solid is first equilibriated with vapour at pressure 9 and thenimmersed, qi(LJlf) results. In modern work the surface area of the powderis determined, usually by the B.E.T. method, and results are given inergs/cm.2. Laporte gives a bibliography.88 Most modern data are due toHarkins, who neglects PV and classifies results as zt~(s~) (he writes zE(s~)).*The liquids examined may be arranged in order of decreasing uE(gL), which isthe same for all the solids examined. If I z ~ ~ ~ a , ) is the enthalpy change ofdesorption of the adsorbed film containing n moles, the heat of evaporationfrom liquid being A, then 8,89an equation of use in linking heat of wetting to heats of adsorption.Harkinsand Jura 89 have plotted h,(S,L) for water on anatase as a function of filmthickness. There is an exponential decrease of 3 2 ~ ( a ~ ~ ) , which becomes con-stant after five molecular layers. At this stage, i.e., for the saturated film,the heat of emersion is just the surface enthalpy hL of the bulk liquid, forwater 118.5 ergs/cm.2 at 25". This forms the basis of the H.J. absolutemethod of surface area determinati0n.~3~~ It gives the specific area of asolid non-porous powder as the ratio of Qi(Ls,), heat of wetting per g. ofsolid with saturated film, to hL, Le., A = QqLalfIihL. Incidentally, themethod seems to have been foreseen in a way by Patrick and GrimmWin their work on the heat of wetting with silica gel, but the method is now-adays not recommended for porous solids.Heats of wetting for water-graphite confirm discontinuities observed on isotherrn~.~lHeats of wetting on alumina and silica gels have been reported to changewith absorbability of the and with molecular size.93 The effectsmay be associated with the failure of larger molecules to penetrate pores(cf. Gregg la). Stowe 94 examined the effect of surface coverage with alumina,and displacement of hydrocarbons by water. The heat of wetting of somesurfaces by water is high enough to suggest chemical reaction.95 The tem-perature of outgassing of the solid is important, and a balance is usuallystruck between removal of adsorbed layers and sintering of the internalsurface, e.g., with silica gel.96 It seems that many of the miscellaneousdata on heats of wetting apply to porous solids and therefore are difficult tointerpret.hUCVSf) = h[E)SL - h E ( S f S +D.D. E.8 8 F. Laporte, Ann. Physique, 1950, 5, 5 .89 W. D. Harkins and G. Jura, J . Amer. Chem. SOC., 1944, 66, 919.90 W. A. Patrick and F. V. Grimm, ibid., 1921, 43, 2144.91 P. R. Basford, G. Jura, and W. D. Harkins, ibid., 1948, 70, 1444.92 L. Robert, Compt. rend., 1951, 233, 1103.93 J . G. Miller, H. Heinemann, and W. S. W. McCarter, Ind. Eng. Chem., 1950, 42,84 V. M. Stowe, J . Phys. Chem., 1952, 56, 484, 487.g6 F. Howard and J . 0. Culbertson, J .Amer. Ckem. SOC., 1952, 72, 1185.g6 D. T. Ewing and B. T. Bauer, ibid., 1937, 59, 1648.* hE(8Z) = ~ ~ ( 8 5 ) + PV, where V is the associated volume change of emersion.15128 GENERAL AND PHYSICAL CHEMISTRY.3. ELECTROLYTES.Strong Electrolytes.-GeneraZ theory. In the Debye-Hiickel theory ofelectrolytic solutions, the calculation of the ionic atmosphere surroundingan ion is based on a Boltzmann distribution : nr = n exp(- ze+?/kT),where nr and $r are respectively the number of ions per unit volume andthe potential at a distance r from the central ion. According to this, thecharge density increases indefinitely with potential, but Wicke and Eigenpoint out that the space requirements of the ions cannot be neglected exceptin very dilute solution, and, taking account of these, they derive a newdistribution function which departs from Boltzmann’s at moderate concen-trations, bending over to a limiting saturation value for the charge density.The effect can account for the observed minima in activity data and, withreasonable assumptions concerning ion-hydration, gives good agreementwith experiment up to 1~ for the alkali halides in water.Falkenhagen isreported as having explained the conductance curves of some alkali halidesup to IM on the same basis, and extensions of the theory to multivalentelectrolytes are promised.Kramers’s derivation by statistical mechanics of the Debye-Hiickellimiting laws has been modified by Berlin and M~ntroll,~ and the new treat-ment eliminates the low critical concentration a t which Kramers’s derivationbroke down.has derived a relationbetween concentration (c) and the velocity (u) of sound in electrolytes; bycombining the equations of the interionic-attraction theory for the apparentmolar volume and isothermal compressibility of the dissolved salt, he obtainsfor very dilute solutions a relation of the form u = G~ + Fc - Gc4.Thecomparison of this with experimental results is reminiscent of the findingstwenty years ago with apparent molar volumes : plots of Au/c are linearagainst c* even up to 4 ~ , but F and G must be replaced by empiricalconstants. As the experimental data are not accurate below 0.3h1, nocomparison with the theoretical slope is yet possible. A substantial contri-bution on polarisation 5 extends Jaffk’s earlier theory 6 to electrolyticsolutions, and presents results for water and salt solutions with variouselectrode metals over a wide range of frequencies.The properties of purerare-earth salts should be of great interest owing to the close similaritiesbetween the compounds ; the predominating variable in their electroIyticproperties will be the radius of the ion.have now published a number of papers on the subject, giving data for theconductivities, transport numbers, and activity coefficients of many of thechlorides and bromides.The equivalent conductances conform with theOnsager limiting slope, and the mobilities derived for the rare-earth ionsE. Wicke and M. Eigen, Naturwiss., 1951, 38, 453; 2. Ebktrochem., 1952, 56, 551.H.A. Kramers, Proc. Roy. Acad. Amsterdam, 1927, 30, 148.T. H. Berlin and E. W. Montroll, J. Chem. Phys., 1952, 20, 76.S . Barnartt, ibid., p. 278.5 H. C. Chang and G. Jaff6, ibid., p. 1071; G. Jaffk and J. A. Rider, ibid., p. 107’7.G. JaffC, Ann. Physik, 1933, 16, 217, 249.F. H. Spedding, P. E. Porter, and J. M. Wright, J , Amer. Chem. SOC., 1952, 74,For graph summarisingTurning to more specialised topics, BarnarttCoizductivity, tvansport, and dzj@sion phenomena.Spedding and his associates2055,2778,2781 ; F. H. Spedding and I. S. Yaffe, ibid., p. 4751.mobility data, see p. 4753DAVIES AND MONK : ELECTROLYTES. 29increase regularly with decrease in atomic number up to a flat maximum forcerium, with the value for lanthanum slightly lower.The direction of thecurve implies that the effective hydration number is the larger the smallerthe ion; the maximum suggests that the larger radius of the first membersof the series enables them to accommodate an additional molecule of waterin the first hydration sphere, a view to which crystallographic and calorimetricdata * offer some support.Gordon and his co-workers have made precision transport-number andconductivity measurements on sodium chloride and potassium chloride inpure methanol at 25" and derive the limiting mobilities : C1-, 52.38; Na+,45.22 ; K+, 52-40. Moving-boundary studies have been made by Dismukesand King,lo and by Spiro and Parton l1 who have investigated and improvedBrady's 12 analytical boundary method.MacInnes and Dayhoff l3 havemodified the E.M.F. centrifuge and record new results for sodium iodideand potassium iodide. Measurements continue to appear both of saltdiffusion l4 and of tracer-ion diffusion; l5 a novel method has been intro-duced by Wall, Grieger, and Childers.16 For a review of the field up to1950 see Harned.1'The Wien effect 18 was discovered twenty-five years ago and, althoughsince then the theory of the increase in conductivity at high field strengthshas been worked out, the experimental data remain meagre.l9 Fortunately,new work in the field has now begun at Yale,20 taking advantage of the recentgreat advances in techniques a t high voltages, and systematic study by thenew method should make valuable contributions to electrolyte theory.Acompletely dissociated electrolyte undergoes a conductivity increase a thigh voltages because the normal ionic atmosphere, with its retarding effects,virtually disappears at the high ionic velocities engendered. With weakelectrolytes there is an additional mass-action increase, since the localconcentration of oppositely charged ions is reduced for each ion by the dis-appearance of its atmosphere, and dissociation proceeds further.21 Pattersonand his co-workers 20 have shown that new results for magnesium, zinc, andcopper sulphates are incompatible with the theory for completely dissociatedelectrolytes, but are in gratifying agreement with theory when the knowndissociation constants of the sulphates are taken into account.F.H. Spedding and C. F. Miller, J . Amer. Chem. SOC., 1952, '94, 3158.J . A. Davies, R. L. Kay, and A. R. Gordon, J . Chem. Phys., 1951, 19, 749; J. P.lo E. B. Dismukes and E. L. King, J . Amer. Chew. Soc., 1952, 74, 4798.l1 M. Spiro and H. N. Parton, Tram. Furuday Soc., 1952, 48, 263.l2 A. P. Brady, J . Amer. Chem. Soc., 1948, 70, 911.Is D. A. MacInnes and M. 0. Dayhoff, J . Chem. Phys., 1952, 20, 1034.l4 R. A. Robinson and C. L. Chia, J . Amer. Chem. Soc., 1952, 74,2776; H. S. Hamerl6 JI M. Nielson, A. W. Adamson, and J. W. Cobble, ibid., 1952, 74, 446; J. TI.l7 H. S. Harned, Ann. Rev. Phys. Chem., 1951, 2, 37.l8 M. Wien and J. Malsch, Ann. Physik, 1927, 83, 305.lS For review and references see H. C. Eckstrom and C . Schmelzer, Chem. Reviews,1939, 24, 367.2o J.A. GledhilI and A. Patterson, Jr., J . Phys. Chem., 1952, 56, 999; F. E. Bailey,Jr., and A. Patterson, Jr., J . Amer. Chem. SOC., 1952, 74, 4426, 4428; D. Berg andA. Patterson, Jr., ibid., p. 4704.21 G. S. Hartley and J. W. Roe, Tvans. Favaday Soc., 1940, 36, 101.Butler, H. I . Schiff, and A. R. Gordon, ibid., p. 752.and R. S. Hudson, ibid., 1951, 73, 5083.Wang, zbzd., p. 1182; J. H. Wang and S. Miller, ibid., p. 1611.P. T. Wall, P. F. Grieger, and C . W. Childers, ibid., p. 356230 GENERAL AND PHYSICAL CHEMISTRY.Thermodynamic $ro$erties. Partial molal heat capacities and heatcontents have been recorded by Spedding and Miller * for aqueous solutionsof cerium trichloride and neodymium trichloride at 25". MacInnes and hisco-workers 22 have developed the magnetic float method of density deter-mination, and report partial molal volumes of potassium chloride and iodideand sodium iodide in water at 25".Salt effects for various organic gasesand liquids have been studied,23 and current theories are analysed in a reviewby Long and McDevit 23; the solvation of uranyl nitrate has been examinedby both distribution 24 and calorimetric methods,25 and the activity co-efficients in aqueous silver nitrate-nitric acid mixtures have been measuredby Davidson and his collaborators 26 using a cell with silver and glass elec-trodes. E.M.F. measurements have also been used to obtain activities inliquid ammonia 27 and liquid hydrogen fluoride 28 as solvents.Incomplete Dissociation in Salt Solutions.-The applicability of mass-action considerations to ionic association in salt solutions is now widelyaccepted and a considerable amount of work in this field is being reported,partly filling gaps in the data previously accumulated for the commonersalts and partly supplying information about salts of the new or rarerelements.There is no major theoretical advance to report, but it is clearthat the experimental results now being derived from a wide variety ofdifferent properties will add to our understanding of the short-range forcesbetween ions. Measurements, unfortunately, are still being largely confinedto one temperature, and some, being made in mixed electrolytes at highnominal ionic strengths, cannot be safely used for theoretical comparisons.Most of the methods so far used are exemplified in the results underreview.Conductivity measurements on dilute solutions have yieldeddissociation constants for barium thiosulphate 29 and for SrI03+.30 Con-ductivities on mixed solutions are applicable where extensive association isexpected, and this method and the solubility method have both been appliedto a number of ferricyanides 31 and tri- and tetra-metaph~sphates.~~ Parryand Dubois 33 have used E.M.F. measurements, with copper and glasselectrodes, to investigate the interactions of cupric and citrate ions ; concen-tration cells have been used to study the association of stahnous with C1-and Br- ions 34 at a nominal ionic strength of 3.0 ; and equilibrium constantsof many bivalent cations with iminodiacetic and related acids 35 have beenB1 D.A. MacInnes, M. 0. Dayhoff, and B. R. Ray, Rev. Sci. Instr., 1951, 23, 642;D. A. MacInnes and M. 0. Dayhoff, J. Amer. Chern. SOC., 1952, 74, 1017.23 T. J . Morrison, J., 1952, 3814, 3819; W. F. McDevit and F. A. Long, J. Amev.Chem. Soc., 1952, 74, 1773; A. P. Altshuller and H. E. Everson, J. Phys. CoZZoid Chem.,1951, 55, 1368; H. A. C. McKay, Trans. Faraday SOL, 1052, 48, 1103; J . H. Saylor,A. I. Whitten, I. Claiborne, and P. M. Gross, J. Awzev. Chew. SOC., 1952, 74, 1778.For review see F. A. Long and W. F. McDevit, Chem. Reviews, 1952, 51, 119.24 A. W. Garner, H. A. C. McKay, and D. T. Warren, Trans. Faraday SOC., 1952,48,997.25 L. I. Katzin, D. M. Simon, and J.R. Ferraro, J. Amer. Chem. SOC., 1952, 74, 1191.26 0. D. Bonner, A. W. Davidson, and W. J. Argersinger, Jr., ibid., p. 1047.2 7 J . Sedlet and T. de Vries, ibid., 1951, 73, 5808.z 8 G. G. Koerber and T. de Vries, ibid., 1952, 74, 5008.2s T. 0. Denney and C. B. Monk, Trans. Paraday Soc., 1951, 47, 992.30 C. A. Colman-Porter and C. B. Monk, J., 1952, 1321.31 C. W. Gibby and C. B. Monk, Trans. Faraday Soc., 1952, 48, 632.32 C. B. Monk, J., 1952, 1314, 1317.33 R. W. Parry and F. W. Dubois, J , Amer. Chem. SOC., 1952, 74, 3749.34 C. E. Vanderzee and D. E. Rhodes, ibid., pp. 3552, 4806.35 S. Chabarek, Jr., and A. E. Martell, ibid., pp. 5052, 5057, 6021DAVIES AND MONK ELECT-ROLYTES. 31determined by J. Bjerrum’s method. A new departure is the use of cellswithout transference for studying ion-pair formation in salts.36 The methodis well adapted for work over a range of temperature and should lead to theaccumulation of reliable data for the entropy and heat content changes(AS, AH) of the dissociation process.The values so obtained, with thoseof some related compounds are (Ma1 = malonate) :MgSO, MgMal ZnMal37 LaSO,+ LaFe(CN), 38AH, kcal. ....,....... -5.7 - 3.2 -3.1 -2.5 -2.0AS, cal./deg. . . . . . . . . . -31.0 -23.9 -27.5 - 26.0 - 23.9Spectrophotometric measurements in the visible and ultra-violet regionsare being increasingly employed to study ionic equilibria. The method isexperimentally simple and the interpretation straightforward so long as it isremembered that foreign ions which do not affect the absorption may never-theless interact with the system being studied, especially at high ionicstrengths.By measurement of optical densities, Gordon and Schreyer 39have shown that the deep blue colour given by cobalt in concentrated alkaliis due to Co(OH),-, and by a similar method Yaffe and Voigt 40 find thatRU(III) and (IV) both give RuCNS2+, RU(IV) being reduced by the thiocyanate.They determine an equilibrium constant for the ion-pair at an ionic strengthof approximately 1, and Farrington,4l in a similar way and a t the same ionicstrength, has measured the extent of CuBr+ formation. King and Pandow 42have carried out further work on the ionic state of Ce(1v) in perchloric acidsolutions; Beer’s law is not obeyed a t H+-ion concentrations of 1-2.5~,and the spectra give evidence of polymerisation-presumably dimerisationthrough oxide or hydroxyl bridging.Anderson and his co-workers 43 haveused the method of continuous variations to study the interaction of sulpho-salicylic acid with aluminium, nickel, and chromium ; a maximum in opticaldensity is given for the 1 : 1 ratio. The copper salt was used as indicatorwith aluminium, and in a rather similar way Wilson and Taubea havestudied the interaction of chromium and gallium with the fluoride ion,using ferric ion as indicator.Raman spectra have been used45 to study the aluminate and zincateions; the experimental data are found to be in good agreement with cal-culations for the tetrahedral ions Zn(OH),2- and Al(OH),-.The interactionbetween thorium and various anions has been studied by distributionmeasurements using the thenoyl-trifluoroacetone complex.46 Finally,Schubert 47 has continued his application of ion-exchange resins, utilisingradio-tracers, to the determination of equilibrium constants, and his most36 H. W. Jones and C. B. Monk, Trans. Fwaduy SOC., 1952, 48, 929; J . I. Evans38 C. W. Davies and J. C . James, Proc. Roy. SOC., 1948, A , 195, 116.39 S. Gordon and J . M. Schreyer, J . Amer. Chem. SOC., 1952, 74, 3169.40 R. P. Yaffe and A. F. Voigt, ibid., p. 2500.4 1 P. S. Farrington, ibid., p. 966. 42 E. L. King and M. L. Pandow, ibid., p. 1966.4s A. M. Liebman and R. C. Anderson, ibid., p. 2111 ; M. B. Lasater and R. C.4 5 E. R. Lippincott, J .A. Psellas, and M. C. Tobin, J . Chem. Phys., 1952, 20, 536.46 E. L. Zebroski, €3. W. Alter, and F. K. Heumann, J . Amer. Chem. Soc., 1951, 73,47 J . Schubert, ibid., p. 113.and C. B. Monk, ibid., p. 934.J . C. James, J., 1951, 153.Anderson, ibid., p. 1429.5646; W. C. Waggener and R. W. Stoughton, J . Phys. Chem., 1952, 56, 1.44 A. S. Wilson and H. Taube, ibid., p. 350932 GENERAL. AND PHYSICAL CHEMISTRY.recent contribution also reviews earlier work in this field. This completes thelist of methods used in the period under review, but, varied as the list is, it isworth noting in addition that conductivities at high field strengths promiseto provide a sensitive method of detecting and estimating ion-pairs, and thatthe same applies, to a lesser degree, to diffusion rneas~rernents.~~In the main, the measurements enumerated fall well into line with earlierwork. In the summary below, numerical values quoted are equilibriumconstants for the dissociation process.Some recent writers give the reci-procals of these, but this seems a pity even in cases where it may be themore logical procedure, partly because it is confusing in relation to all theearlier literature and partly because it creates an artificial distinction betweenacids and other electrolytes.Ion-pair formation is appreciable but not extensive in cupric bromide,41in agreement with data for the chloride.49 It is somewhat more marked, asmight be expected, in RU(III) thiocyanate; K, = 0.017 for RuCNS2+ a t 40an ionic strength of approximately 1.An approximate value, K = 0.04, forThCP+ is quite high for this valency type 46 and suggests ion-pair formationof the Bjerrum kind between hydrated ions. At M-chloride concentrationand an ionic strength of 4.0, however, Waggener and Stoughton46 reporthigher association products to be present in the following proportions :Th4+, 33.8; ThCP+, 57.5; ThC122+, 4.7; ThC13+, 3.4; ThCl,, 0.6%. Therelative figures are not what would be expected from electrostatic theory,and suggest that the further association of C1- ions is governed rather byconsiderations of co-ordination chemistry ; this conclusion must be treatedwith reserve however, in view of our complete ignorance of the activitycoefficients and the sensitivity of the results to small experimental errors.The fluorides of metals of high valency are weaker than the other halides,and the dissociation constant 44 of GaF2+ is about the same as that of FeF2+ ;the corresponding chromium complex is about five times as strong, so thedifficulty in removing water from the hydrated Cr3+ ion has no discernibleinfluence here.The dissociation constants of a number of bivalent metal thiosulphatesare normal,29 being somewhat higher than those of the sulphates, but thecadmium salt is weak (K = 1.2 x and complex-anion formation isappreciable even in dilute solutions.The sulphosalicylates 43 of copper(K = 0.0022), aluminium (K = 5 x and chromium (K are ofthe order of magnitude to be expected for normal ion-pair formation, butthe nickel salt (K = 4 x The dissociation constantsfor the ion-pairs of the ferricyanides 31 and tri- and tetra-metaphosphates 32of the alkaline earths are given in the following Table :is distinctly weak.Mg Ca Sr BaFerricyanides ( x los) .....................1.63 1-47 1.41 1-32Trimetaphosphates ( x lo*) ............... 4-89 3-56 4.43 4.50Tetrametaphosphates ( x 106) ......... 6.7 3.9 7.0 10.3It seems that the trimetaphosphate ion, unlike the ferricyanide ion, isable to replace hydration water from the cation, thus giving much smaller4 8 H. S. Harned and R. M. Hudson, J. Anzev. Chem. SOC., 1951, 73, 3781.49 W. H. Banks, E. C. Righellato, and C. W. Davies, Tuuns. Furaday SOL, 1931,27, 621DAVIES AND MONK : ELECTROLYTES. 33K's, and reversing the order Ca, Sr, Ba.The magnesium trimetaphosphateis still the strongest salt, presumably because the inner hydration shell ofthis small ion is particularly stable. This further emphasises the importanceof geometrical considerations in any final analysis. Lanthanum trime ta-phosphate 32 (K = 2-0 x(K = 1-82 x lo-*) and again the non-hydrated cation may be involved.The dissociation constant 32 of the lanthanum tetrametaphosphate ion-pairis 2.2 x lo-'; this valency product of twelve is the highest yet studied.Analogous considerations concerning the stabilities of complexes involvingorganic ligands have received active consideration over the past few years.Williams,5o who has taken the alkaline-earth cations for detailed discussion,shows that the relation between the pK values and ionization potentials,which has so far provided the most satisfactory explanation, fails for mag-nesium.He considers that short-range repulsion forces must also beconsidered. In a study of the alkaline earth monocarboxylates by Colman-Porter and Monk,51 magnesium is again found to be anomalous, and it issuggested that, as detailed above for inorganic salts, the hydration ofmagnesium may account for this difference.has re-moved a former discrepancy between the dissociation constant at varioustemperatures obtained by this method and by other methods ( K = 0.0103at 25"); the Bureau of Standards 53 have added tartaric and 5 : 5-diethyl-barbituric acids to their series of precise E.M.F. data; sulphamic acid hasbeen carefully examined by King,54 and Jones and Parton 55 have obtainedsatisfactory results for benzoic acid by using the quinhydrone in place of thehydrogen electrode.A further article on an individual acid is that ofWaring,56 who reviews the thermodynamic properties of formic acid, andtwo papers devoted to a study of series of acids have been given by Bother-Byand Medalia 57 on some substituted benzoic acids and by Peek and Hill 58on some dicarboxylic acids in 20% methanol; both of these interpret theirresults in terms of current theories. As opposed to these E.M.F. methods,a spectrophotometric method has been developed for determining the over-lapping constants of dibasic acids 59; this has been applied to severalexamples and the results are compared with previous data.In the field ofnon-aqueous solvents, formamide, which is a good solvent of higher dielectricconstant than water (109 at room temperature), has been used by Dawsonand Griffith 6o for freezing-point studies of several organic acids. Theirsemi-quantitative calculations suggest that ionization is roughly 10% greaterin this solvent than in water.Two further contributions to the study of base equilibria are those ofis also much weaker than the ferricyanideAcids and Bases.-A recent E.M.F. study of the HSO, ion50 R. J. P. Williams, J., 1952, 3770.5 1 C. A. Colman-Porter and C. B. Monk, ibid., p. 4363.5% C. .W. Davies, H. W. Jones, and C. B. Monk, Trans. Faraduy SOC., 1952, 48, 921.63 R. G. Bates and R.G. Canham, J . Res. Nut. Bur. Stand., 1951, 47, 343; G. C .Manov, K. E. Schuette, and F. S. Kirk, ibid., 1952, 48, 84.64 E. J. King and G. W. King, J . Amer. Chew. SOC., 1952, 74, 1212.5 5 A. V. Jones and H. N. Parton, Trans. Faraday SOC., 1952, 48, 8.5G W. Waxing, Chem. Reviews, 1952, 51, 171.5 7 A. K. Bother-By and A. I. Medalia, J . Amer. Chem. SOC., 1962, 74, 4402.58 H. M. Peek and T. L. Hill, ibid., 1951, 73, 5304.69 B. J. Thanier and A, F. Voigt, J . Phys. Chem., 1952, 66, 226.Go L. R. Dawson and E. J. Griffith, ibid., p. 281.RE P,-VOL. XLIX . I34 GENERAL AND PHYSICAL CHEMISTRY.Everett and Wynne- Jones who used a hydrogen electrode for temperaturestudies of the ammonium and methylammonium ions in 60% aqueousmethanol, and a solubility investigation of strontium hydroxide ; 30 here(K = 0.11 for SrOH+) the value fits an equation 62 which relates crystallo-graphic cation radii with the pK’s of strong hydroxides.Redox Systems.-Potentials of some of the valency systems ofneptunium,m americium and praseodymium,64 and ruthenium 65 havebeen reported during 1952, and an interesting system, namely, that of the2 : 2’-dipyridyl derivatives of OS(II-111) has been investigated.66 The effectof varying the ionic strength ( I ) by indifferent electrolytes gave plots ofE.M.F.against I* which deviate from those predicted by the Debye-Huckeltheory. The authors suggest that the changing nature of the ligand-metalbonds with ionic eiivironment can explain this; however, a consideration ofthe possible ion-pairs present may well provide a more logical interpretation.C.W. D.C. B. M.4. THE KINETICS OF HOMOGENEOUS REACTIONS.There has been no substantial change in the theory of rate processes.Most of the published work has been based on experiment and Concernedeither with the elucidation of the mechanisms of various reactions or with thedetermination of the specific rate constants and energies of activation ofsimple unimolecular or bimolecular reactions involving ions, molecules, andradicals. The ready availability of suitable radioactive isotopes of most ofthe common elements has led to an increased understanding of electron- andgroup- or atom-transfer processes in solution, and also of the nature of thechemical reactions which ensue when nuclear radiations are absorbed bymatter. A noteworthy conference has been held on each of these twosubjects and the large amount of work which has been carried out is reflectedin the size of the appropriate sections of this Report.Three other symposiaconcerned with (1) the reactivity of free radicals (see ref. 56), (2) combustionand flame, and (3) ionic polymerisation (see ref. 300) have also taken placebut the Proceedings of none of these have yet been published.We have presented the topics in order of increasing complexity of mechan-ism, and have deliberately omitted any mention of certain fields of work.Thus, oxidation and combustion have not been referred to, but it is hopedthat this subject will be covered in next year’s Report when the paperssubmitted to the Boston conference (no.2 above) will have been printed.Work on reactions in the solid phase and investigations relating to the morephysical or dosimetric aspects of radiation chemistry have been omitted asbeing of only minor interests to chemists.General and Theoretical.-Most reactions which have been reported havebeen investigated by conventional experimental methods, or by slight61 D. H. Everett and W. F. K. Wynne-Jones, Trans. Faraday Soc., 1952, 48, 531.62 C. W. Davies, J . , 1951, 1256.63 D. Cohen and J . C. Hindman, J . Anzer. Chem. SOC., 1952, 74, 4679, 4682.64 L. Eyring, H. R. Lohr, and B. B. Cunningham, ibid., p. 1186.65 R. E. Connick and C. R. Hurley, ibid., p. 5012.6 6 G. T. Barnes, F. P.Dwyer, and (Miss) E. C . Gyarfas, Trans. Faruduy Soc., 1962,48, 269BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 35variants of these. One new method is that of Heitler who used a modifiedCottrell apparatus, with a suitably aged thermistor in place of a thermometerto detect the changes of boiling point of the solvent accompanying the chang-ing concentration of a dissolved reactant. By using acetone as the solvent itwas possible to record the course of reactions with half-lives of less than oneminute. A number of authors developed the mathematical treatmentappropriate to the kinetics of complex reactions, such as those involving twoconsecutive second-order steps,2 accompanied by diff u ~ i o n , ~ and auto-synthetic reaction^.^The principal difficulty in the calculation of velocity constants a priori,by the methods of the transition-state theory, is that of obtaining an accuratevalue for the increment in internal energy at absolute zero in passingfrom the reactants to the complex.At best the calculation is semi-empiricaland can only be carried through to completion for the simplest systems.There is therefore considerable incentive to find good empirical relationsbetween measured energies of activation and experimentally accessibleproperties of the reactants. Eyring and Smith have recently shown thatthere is a linear relation between the activation energy of the reaction ofsodium atoms with chlorinated hydrocarbons and the ratio of the net chargeon the halogen atom to the polarisability of the carbon-halogen bond whichis broken.It has often been pointed out that there is a simple proportion-ality between the change in activation energy (AE) and the change in bonddissociation energy (AD) for certain series of simple bimolecular reactions.Bernstein has pointed out, for the case of the reactionCX* - + M +M-X + CX, -- , t Y nwhere TZ = 0, 1, 2, or 3, and X is a halogen, that, if all the bonding andnon-bonding contributions to the heat of atomisation of the substitutedmethane CX, - ,Y, are additive, and if the same is also true for the activatedcomplex, then not only is AE proportional to ADc-x but both are proportionalto changes in the heat of formation and in the heat of atomisation of thesubstituted methane.It is a feature of the transition state theory that, since In A = aAS*,variations of the frequency factor (A) can be associated with variations of theentropy of activation (AS*).Rollefson has drawn attention to the factthat the A values of many bimolecular gas and solution reactions are within-loll or =lo7 1. mole-l min.-l, corresponding to AS* values of 21-10and --30 cal. deg.-l mole-l respectively. The second value of A S isof the same order as the translational entropies of many molecules at roomtemperature, and it is therefore suggested that in the first case the two mole-cules comprising the activated complex are only loosely bound and that theonly condition for formation of the complex is approach of the molecules towithin a certain distance, so that only one degree of vibrational freedom islost; however, in the second case the molecules are tightly bound in the1 C.Heitler, Chem. alad I n d . , 1952, 875.2 H. G. Higgins and E. J. Williams, Australian J . Sci. Res., 1952, 5, A , 572.3 F. J . W. Roughton, Proc. Roy. SOC., 1952, A , 214, 564; J. Crank, Phil. Mag., 1952,5 H. Eyring and R. P. Smith, J . Amer. Chem. Soc., 1952, 74, 229.6 R. B. Bernstein, J . Chem Phys., 1952, 20, 524.7 G. K. Rollefson, J . Phys. Chem., 1952, 56, 976.43, 811. 4 (Sir) Cyril Hinshelwood, J., 1952, 74536 GENERAL AND PHYSICAL CHEMISTRY.complex and all three degrees of translational freedom have gone. Thechemical nature of the reactions in the two groups is considered to be broadlyin accord with this view.Another simple deduction from transition-statetheory which can readily be demonstrated concerns equilibria.8 When areversible reaction is displaced from equilibrium so slightly that the free-energy change is less than the value of RT, the rate of approach to equili-brium is directly proportional to the free-energy difference between thereactants and the products.The transition-state theory has little of quantitative value to offerconcerning the pressure dependence of the rate constant of unimolecularreactions, and in the attempts to refine the Lindemann collision theory thereare signs of a revived interest in this field and in the problems which underliethis theory. Johnston9 has carried out a general summation over allquantum states of the individual steps in the Lindemann scheme, whence heobtains the expression.where ai, bi, and ci are respectively the average values of the rate constantsin proceeding from any quantum state of the molecules on the left-handside of reactions (l), (2), and (3) below, to any quantum state of the moleculeson the right-hand side :.. . . . . M + M A M + A * (1)M + A & M + - M . - (2)A 4 C . . . . . . . . * (3). . . . .and A denotes an activated molecule, C a product molecule, and N thereactant molecule. By assuming these averages to be constant it is possibleto set a limit on the value of the rate constant a t low concentrations of Mfrom data on the value of the rate constant at high concentrations and viceversa. Theory and experiment have been compared for the pyrolyses of nitrousoxide and nitrogen pentoxide.Benson lo has combined Slater's theory 11with the Lindemann hypothesis and concludes (a) that for molecules con-taining more than 6 atoms the rate constant is unlikely to change withdecreasing pressure until at least 1 mm. Hg is reached and (b) that formolecules of identical atomicity but differing shape the fall in rate constantwill occur at pressures higher for linear than for non-linear molecules.First-order and Unimolecular Gas Reactions.-Several pyrolytic andisomerisation reactions have recently been shown to be non-chain first-orderhomogeneous reactions. Notable amongst these are the dehydrohalogen-ation reactions of halogenated hydrocarbons. Howlett l2 has shown thatethyl chloride, 1 : I-dichloroethane, isopropyl chloride, and isobutyl chloridedecompose in this manner. Furthermore, below a certain pressure (5 mm.Hg for ethyl chloride a t 456') the order of reaction exceeds unity, but in thepresence of sufficient quantities of either product, or added inert gases suchas nitrogen and helium, the first-order character can be maintained down to8 V51.R. Gilkerson, M. M. Jones, and G. A. Gallup, J . Chem. Phys., 1952, 20, 1188.H. S. Johnston, zbid., p. 1103. lo S. W. Benson, ibid., p. 1064.l1 N. B. Slater, Proc. Roy. Soc., 1948, A , 184, 112.l2 K. E. Howlett, J . , 1952, 3695, 4487; Chem. and Ind., 1952, 1176XETTS ct a/. THE KINETICS OF HOMOGENEOtTS REACTIONS. 37lower pressures. The pyrolysis of 1 : 2-dichloroethaneJ though a chainreaction, shows similar effects below 20 mm.Hg pressure.13 This author hasexamined the results in the light of Rice and Ramsperger's theory and hasshown that they are in agreement with the idea that the transformationprobability of an activated molecule is a function of the energy possessed inexcess of the minimum required for reaction. The relations between thefrequency factors and energies of activation of these reactions are regarded asbeing in accord with the notion that the slow step is the localisation of theenergy in the activated molecules. By employing carbon-coated reactionvessels Barton, Head, and Williams l4 have succeeded in suppressing anyheterogeneous reaction in the decomposition of (-)-menthy1 chloride anddemonstrated the unimolecular nature of the residual homogeneous reaction.The usual stereospecificity was observed, the ratio of A2- to A3-olefin in theproducts being about 0.3.The isomerisation of diisopropenyl ether to allylacetone has been followedspectrophotometrically by Stein and Murphy.15 At temperatures between143" and 194" and pressures between 20 and 760 mm.the first-order rateconstant has the value 5.4 x loll exp (-29.3 kcal./RT) sec.-l, very closeto the value which they obtained earlier for ally1 vinyl ether. A preliminaryaccount has been given of the kinetics of the isomerisation of cyclopropaneto propylene between 10 and 0.1 mrn.l6 The reaction is quasi-unimolecular,and reasonably good agreement of the data with the predictions based onKassel's equation l7 is obtained, if in applying the latter, it is assumed thatthe collision diameter is 3.94 A and 13 oscillators are involved.Sir Cyril Hinshelwood and his collaborators have published a series ofpapers l8 on the decomposition of various straight-chain and branched-chainparaffins in the presence of sufficient nitric oxide to suppress the concurrentchain reaction, and their results are summarised in a final paper.lQ Re-actions of hydrocarbons such as ethane, propane, isobutane, isopentane,neopentane, and neohexane show a single transition from first to secondorder as the pressure is reduced, and the energy of activation is independentof pressure.Reactions of other hydrocarbons, including n-butane, PZ-pentane, n-hexane, 2 : 3-dimethylbutane, and 2- and 3-methylpentane,change from first to second order, return to first order and finally becomesecond order as the pressure is reduced from 1600 to 0.1 mm.This effectcould be ascribed to the coexistence of two unimolecular reactions withdifferent pressure dependence, and in agreement with this two distinctactivation energies are observed, but the products of these two reactionsappear to be the same in the case of n-butane. Hydrocarbons in the firstcategory have a frequency factor for decomposition in the normal range ofl O l a to 1014 sec.-l, as also do the hydrocarbons in the second category whenthe pressure is high. The low-pressure first-order frequency factors for thel3 K. E. Howlett, Tram. Furaday Soc., 1952, 48, 25.l4 D.H. R. Barton, A. J . Head, and R. J. Williams, J , . 1952, 453.l5 L. Stein and E. W. Murphy, J . Amer. Chem. Soc., 1952, 74, 1041.l6 H. 0. Pritchard, R. G. Sowden, and A. F. Trotman-Dickinson, J . Amer. Chena. SOC.,1952, 74, 4472.l7 L. S. Kassel, " Kinetics of Homogeneous Reactions," Chem. Catalog. Co., NewYork, 1932, p. 93.F. J. Stubbs, K. U. Ingold, B. C. Spall, C. J. Danbv, and (Sir) Cyril Hinshelwood,Proc. Roy. SOG., 1952, A , 214, 20; M. G. Peard, F. J . Stubbs, and (Sir) Cyril Hinshelwood,ibid., p. 330, 339. I* Idem, ibid., p. 47138 GENERAL AND PHYSICAL CHEMISTRY.latter group of hydrocarbons are however very much higher. A similarhigh-frequency factor is suggested for the dissociation of vinylcyclohexene intobutadiene.20 A comparative study of the pyrolysis of nine olefins has beenmade by Molera and Stubbs21 All these reactions are of first order duringthe initial stages.Marcus 22 has surveyed existing data on atomic crackingreactions and on the deuteration of free radicals, and has deduced thevelocity constants for the dissociation of various vibrationally excited alkanes.As would be expected, the rate constant increases with increasing number ofdegrees of freedom of the decomposing molecule.The kinetics of decomposition of diethyl peroxide have been investigatedin a flow system in the presence of excess of toluene.23 The products aremainly ethane and formaldehyde with smaller amounts of methane anddibenzyl. The results are interpreted in terms of a non-chain, radicalmechanism and the overall first-order constant [=2.1 x 1013 exp (-31.7kcal./RT) sec.-lJ is shown to refer to the initial break into two ethoxy-radicals.However, the value 31.7 kcal. is rather smaller than the expectedvalue of the bond dissociation energy DE~o-oE~. The possibility that thisreaction may be more complicated than has hitherto been supposed has beensuggested by Style and Jenkins; 24 and Mortlock and Style 25 have drawnattention to the fact that diethyl peroxide reacts with nitric oxide to formethyl nitrite. Clearly the nitric oxide method cannot be used to isolateany non-chain decomposition products of this peroxide. The pyrolysis ofdi-terf.-butyl peroxide has been studied mass spectrometrically by Lossingand Tickner at very low pressures (approx.2 p) and temperatures up t o350°.26 These results were combined with those obtained by Vaughan andSzwarc at lower temperatures, and the first-order constant was calculatedto be 7.1015 exp (-38 kcal./RT) sec.-l. Brinton and Volman 27 havecarried out the reaction at much lower temperatures and higher pressuresin the presence of ethyleneimine and give values for the rate of fission ofthe peroxide link in fair agreement with those of Lossing and Tickner.Szwarc and his co-workers have continued their measurements of bonddissociation energies by pyrolysis of the parent compound in a flow system,using toluene as a carrier gas and radical reagent.28 An interesting pointwhich has emerged from studies of this kind on alkyl and aryl bromides isthat, although the rate constants of two C-Br bond dissociation processesmay be in the ratio lo5 : 1, the frequency factors are of the same order ofmagnitude.29Bimolecular Gas Reactions.-Many bimolecular association reactions are“ slow,’’ i.e., have a P factor very much less than unity, and this is attributedto a loss of entropy during formation of the activated complex.Anotherexample of this behaviour is the simple reactions between olefins and ozone20 N. E. Duncan and G. J. Janz, J. Chem. Phys., 1952, 20, 1644.21 M. J. Molera and F. J . Stubbs, J., 1952, 381.22 R. A. Marcus, J . Chem. Phys., 1952, 20, 352, 359, 364.23 R. E. Rebbert and K. J . Laidler, ibid., p. 574.24 A. D. Jenkins and D. W. G.Style, Nature, 1952, 170, 706.25 H. N. Mortlock and D. W. G. Style, ibid., p. 706.26 F. P. Lossing and A. W. Tickner, J. Chem. Phys., 1952, 20, 907.2 7 R. K. Brinton and D. H. Volman, ibid., p. 25.M. Ladacki, C . H. Leigh, and M. Szwarc, Proc. Roy. SOC., 1952, A , 214, 273;C. H. Leigh and M. Szwarc, J . Chenz. Phys., 1952, 20, 403, 844; M. Szwarc and D.Williams, ibid., p. 1171. 29 M. Szwarc and D. Williams, Nature, 1952, 170, 290RETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 39which are characterised by frequency factors of the order lo3 to lo4 1. mole-lsec.-1.30 The dimerisations of tetrafluoro- and chlorotrifluoro-ethylene arealso “ slow,” with frequency factors similar to those for the dimerisation ofdienes, viz., -lo7 1. mole-1 ~ec.-l.~l In marked contrast to these are theaddition of butadiene to cyanogen : 32and the addition of boron trifluoride to the mono-, di-, and tri-methyl-amines33 for which the frequency factors are respectively 1.6 x lo1, and - 1013 1.mole-l sec.-l. The latter reactionis particularly interesting in that noenergy of activation is required, and it is therefore as rapid as the combinationof two methyl radicals.34The expectation for bimolecular metatheses is that the P factor should beclose to unity. This appears to be almost the case in the very rapid reactionNO,C1 + NO + NO, + NOCl which was investigated over the widerange of pressure, 0-2 to 384 mm. Hg, by Freiling, Johnston, and Ogg 35 andfor which the velocity constant is lo9 exp (-6.9 kcal./RT) 1.mole-l sec.-l.This is a particularly interesting reaction in that it is not known whether achlorine or an oxygen atom is transferred.Atomic and Free-radical Reactions.-Some atomic and free-radicalreactions are dealt with in the section on photochemistry. In many casesthe photolysis of a compound has been used as a source of free radicals forthe purpose of studying the kinetics of inter-radical, and radical-moleculereactions.Much attention continues to be devoted to the reactions of hydrogenatoms and simple alkyl radicals. Berlie and LeRoy 36 claim to have elimi-nated the difficulties inherent in previous investigations of reaction (1) andgive preliminary values of El = 6-2 & 0.1 kcal. and P, = 3-3 xThe energy of activation is consistent with the work of Wijnen and Steacie 37on the reverse reaction (2), where deuterium is used in place of hydrogen.They find that the value E, = 13.3 & 0.5 kcal./mole, which after allowancefor the difference in zero-point energy of deuterium and hydrogen, leadsto El = 7 & 1 kcal./mole.Wijnen and Steacie did not detect any C,H,D,in their products, but in another system it is claimed3* that the exchangereaction CH,*CH,* + D, + CH,*CHD- + HD can occur.30 R. D. Cadle and C. Schade, J . ‘4mer. Chem. SOC., 1952, 74, 6002.31 J. R. Lacher, G. W. Tompkin, and J. D. Park, ibid., p. 1693.32 P. J. Hawlrins and G. J. Jam, ibid., p. 1790.33 D. Garvin and G. B. Kistiakowsky, J . Chem. Phys., 1952, 20, 105.34 R. Gomer and G. B. Kistiakowsky, ibid., 1951, 19, 85.35 E.C. Freiling, H. S. Johnston, and R. A. Ogg, ibid., 1952, 20, 327.38 M. R. Berlie and D. J. LeRoy, ibzd., p. 200.37 M. H. J . Wijnen and E. W. R. Steacie, ibid., p. 205.3* V. V. Voevodskii, G. K. Lavrovskaya, and R. E. Mardalekhvili, Dokl. Akad.Nauh. S.S.S.R., 1951, 81, 215; Cham. Abs., 1952, 46, 1852.Such reactions are reported mainly in this section.H +C2H6-+C2H5 + H, . . . . . * (1)CZH, + D,--+C2H5D + D . . . . . * (240 GENERAL AND PHYSICAL CHEMISTRY.Conflicting values continue to be reported for the energy of activation ofthe reactionMajury and Stea~ie,,~ using the photolysis of acetone as source of radicals,find E, = 9.7 & 0.6 kcal./mole; Davidson and Burton,m using photolysisof acetone and acetaldehyde as sources, find E, >13 kcal./mole; andAnderson and Taylor,41 using the photolysis of dimethylcadmium as source,find E, = 13 & 2 kcal./mole. It is assumed by all the authors that theenergy of activation for the combination of two methyl radicals is zero.Majury and Steacie have shown that substitution of D, for H, in reaction (3)causes an increase in activation energy of the order to be expected from thedifferent zero-point energies, while replacement of CH,.by CD,* causes arelatively slight reduction in rate.Lossing and Tickner 26 have developed a mass-spectrographic method formeasuring the partial pressure of methyl radicals in thermally decomposinggases. The method differs from previous similar methods in that relativelyhigh-voltage electrons (50 ev) are used, the effect of ionisation of speciesother than methyl being allowed for by assuming a 100% carbon balance.The combination reaction of methyl radicals was studied and the collisionefficiency at 850" estimated as 2-3 x 1W2.A redetermination of thecollision efficiency of the reaction between methyl radicals and nitric oxidehas been made,42 by using a radioactive tellurium mirror method. This leadsto a collision efficiency of for the combination of methyl radicals atroom temperature. Durham and Steacie conclude, from a comparison of theavailable data, that the true value is between 0-5 and 0.05. The problem hasalso been discussed theoretically.22The thermal decomposition of di-tert.-butyl peroxide has been used as asource of the methyl radical in studies of its reactions with acetone,43 acet-aldehyde, and acraldehyde.44 The energy of activation of the reaction withacetone was found to be 9.5 & 1.5 kcal./mole in agreement with otherwork, while for the reaction with acetaldehyde E = 7-5 & 0.3 kcal./mole.Acraldehyde polymerises as well as decomposing in the presence of radicals.The hydrogen abstraction reactions of methyl radicals with various halo-genated methane derivates have been found 45 to have the following activ-ation energies : CH,F, 8.7 ; CH2F2, 6.2 ; CH,Cl, 9.4 ; CH2CI2, 7.2 ; CHCl,, 5.8 ;CH3Br, 10.1; CH2Br2, 8.7 kcal./mole.The steric factors lie in the range10-2 to 10-4. The reactions of methyl radicals with oxygen46 and withsec.-butyl chloride 47 have also been studied.The Combination, disproportionation, hydrogen-abstraction, and de-composition reactions of the ethyl radical have been reviewed.48 Thereappears to be a real discrepancy between the relative extent of dispropor-tionation and combination of ethyl radicals produced by different methods.CH,-+H,-+CH,+H .. . . . . (3)39 T. G. Majury and E. W. R. Steacie, Canad. J . Chem., 1952, 30, 800.40 S. Davidson and M. Burton, J . Amer. Chem. SOG., 1952, 74, 2307.4 1 R. D. Anderson and H. A. Taylor, J. Phys. Chem., 1952, 56, 498.42 R. W. Durham and E. W. R. Steacie, J. Chem. Phys., 1952, 20, 582.43 M. T. Jaquiss, J. S. Roberts, and M. Szwarc, J . Amer. Chem. SOL, 1952, 74, 6005.4 3 D. H. Volrnan and R. K. Brinton, J. Chem.Phys., 1952, 20, 1764.4 5 F. A. Raal and E. W. R. Steacie, ibid., p. 578.4fi F. B. Marcotte and W. A. Noyes, J . Amer. Chem. Soc., 1952, 74, 783.4 7 A . S. Kenyon, ibid., p . 3372.4 5 K. J. Ivin, M. H. J. Wijnen, and E. W. R. Steacie, J. Phys. Chem., 1952, 56, 967BETTS d fll. THE KINETICS OF HOMOGENEOUS REACTIONS. 41Bevington 49 has calculated the differences in the heat content, entropy,and free energy of the products resulting from the disproportionation andcombination of ethyl and other radicals. It does not follow that the reactionleading to the greatest decrease of free energy will necessarily predominate,since it follows from the work of Wijnen and Steacie185 that the two reactionsare quite independent and do not proceed via the same transition complex.Paneth and Hollis 5O have shown by a radiochemical method that ethylradicals react a t every collision with a bismuth mirror.The frequency factors for a number of hydrogen-abstraction reactionshave been calculated 5 l from the theory of absolute reaction rates and shownto be in fair agreement with experimental values.The reactions of sodium vapour with ethyl chloride 52 and trifluoro-halogenomethanes 53 have been studied by the diffusion flame method andthe following energies of activation found : C,H5Cl, 10.2 & 0.5 ; CF,I, 1.7 ;CF,Br, 2.3; CF,Cl, 7-4 kcal./mole.In the CF,X compounds it is the X atomwhich is preferentially removed. In the case of ethyl chloride the stericfactor is unity within experimental error.In solution the phenyl radical reacts with aromatic compounds to givediphenyl derivatives :Ph- + PhX --+ PhC,H4X + Hbut in the gas phase at high temperature and low pressure, hydrogen ab-straction is preferred in the case of compounds such as toluene :This difference in behaviour has been investigated by Jaquiss and Szwarc 54who conclude that the effect is real and advance a tentative explanation.Kooyman and Farenhorst 55 hgve given a preliminary account of anexperimental study designed to provide a broad test of the predictions ofCoulson ct al.that the free valence number calculated for a given carbonatom in a compound should be related to its ability to interact with a freeradical. The correlation is found to be remarkably good for velocity con-stants varying over a range of more than lo5.A summary of the Toronto conference on the Reactivity of Free Radicalshas been published.56Reactions in Solution.-General.-Kacser 57 has given a theoreticalaccount of the probability factor in uncomplicated ion-dipole reactions. Anequation for the " effective shape " of a polar molecule in the field of an ionis developed, which determines the success of reactive approaches of the ionfrom any given direction. If the field around the molecule is markedlyanisotropic, there will be favoured directions of approach for the ion, whichwill be reflected in the non-exponential factor of the Arrhenius equation,When these concepts are applied to exgerimentaI data (reactions of methylPh. + PhMe --+ PhH + PhCH,.-> (PhCH,),43 J . C. Bevington, Trans. Faraday SOC., 1952, 48, 1045.60 F. A. Paneth and A. Hollis, Nature, 1952, 169, 618.j1 S. Bywater and R. Roberts, Canad. J . Chenz., 1952, 30, 773.j2 R. J . Cvetanovic and D. J. LeRoy, J . Chem. Fhys., 1952, 20, 1016.53 J. W. Hodgins and R. L. Haines, Canad. J , Chem., 1952, SO, 473.64 M. T. Jaquiss and M. Szwarc, Nature, 1952, lY0, 312.55 E. C. Kooyman and E. Farenhorst, ibid., 1952, 169, 153.56 H. W. Melville, zbzd., 1952, 170, 819.5 7 I-I. Kacser, J . Phys. Chem., 1952, 58, 110142 GENERAL AND PHYSICAL CHEMISTRY.halides with halide ions), they yield the approach distance of reacting mole-cules, and give infomation concerning the steric course of the reaction.The differential rate equations for the kinetics of competitive reactions ofthe type A + B + C + E, and A + C + D + E have been integrated forthe special case where [A] = [B].58 Measurements of the rates of hydrolysisof ethyl adipate and ethyl succinate were made and used as an illustration ofthe theory.Pearson 59 has made a theoretical study of the influence of the solvent onthe heats and entropies of reactions in which ions are formed from neutralmolecules. Changes in the entropy term appear to be decisive in relatingthe rates of similar reactions in different solvents.Curme and Rollefson 6o have compared the rate of quenching of fluor-escence of p-naphthylamine by carbon tetrachloride in the gas phase, and insolution in isooctane and cyclohexane. Values of the entropy of activationfor the process in these three media are essentially identical.They concludethat the rate a t which these molecules come together and react is not greatlydifferent in solution in an inert solvent, from what it is in the gas phase.Franklin has calculated the entropy and heat of formation of alkyl-carbonium ions in solution from corresponding values for the gaseous ions,using Latimer's method. These values are used for calculations of ASsand AHs for hydrolysis of alkyl halides in aqueous ethanol, and also of therate of hydration of isobutene and dehydration of tert.-butanol. The cal-culations of the rates of these processes are in good agreement with experi-mental values.IsotoPic Exchange Reactions in Solution. Many reactions in solutioncan be detected only by the use of suitably labelled isotopic species.Theincreasing availability of both radioactive isotopes of many of the elements,as well as stable isotopes, e.g., l 8 0 and 15N, has led to a considerable expan-sion in the number and variety of studies in this field.Adamson 63 has suggested that a relationexists between the rate of one-electron transfer and the magnetic propertiesof the ions concerned. The criterion of this correlation is that if the productof the sum and the difference of the magnetic moments of the couple is high,electron transfer between the couple will be slow. The theoretical basis forthis relation is admitted to be obscure.Libby 64 has considered the probability of isotopic electron transfer fromthe point of view of the Franck-Condon principle.He suggests that thehydration atmospheres around the ions are unable to move in the time re-quired for electron transfer, thus causing formation of ions in incorrectenvironment. This requires the later movement of hydration energy fromone site to another, and thereby constitutes a barrier which inhibits electrontransfer. For large co-ordinated ions such as the ferro- and ferri-cyanides,the energies of hydration are smaller, and the barrier is greatly reduced.Catalysis by small negative ions is explicable on the basis of formation of alinear complex with the anion between the two exchanging cations. This will(a) Electron-transfer processes.6 8 A. A. Frost and W. C. Schwemer, J . Amer. Chem.Soc., 1952, 74, 1268.59 R. G. Pearson, J . Chem. Phrvs., 1952, 20, 1478.60 H. G, Curme and G. K. Rollefson, J . Amer. Chern. Soc., 1952, 74, 3766.6 1 J. L. Franklin, Trans. Furaday Soc., 1952, 48, 443.62 W. M. Latimer, K. S . Pitzer, and C. M. SIansky, J . Chem. Phys., 1939, 7, 108.63 A. W. Adamson, J . Phys. Chem., 1952, 56, 858. 64 W. F. Libby, ibid., p. 863BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 43result in a sharing of the water molecules in the hydration spheres of thecations, with a consequent reduction in height of the energy barrier forelectron transfer. As an example of this predicted catalytic effect of smallanions, Hornig and Libby 65 have shown that concentrations of fluoride ionas low as 1 0 - 6 ~ exert an accelerating effect on the rate of electron transferbetween Ce(II1) and Ce(1v) in 6~-nitric acid.Silverman and Dodson 66 have published a definitive paper on thekinetics of electron transfer between ferrous and ferric ions in aqueousperchloric-hydrochloric acid media.In perchloric acid, the main contri-bution to exchange comes from the ions FeOH2+ and Fe2f ; the rate constantfor exchange between Fe3+ and Fe2' is about 1000-fold less. Chloride ionproduces a slight catalytic effect, and rate constants were measured forelectron transfer between the couples FeCT+-Fe2+, and FeC12+-Fe2+.Perchlorate ion plays no specific part in any of the reactions. Molecularoxygen 67 does not affect the rate of electron transfer, and the mechanismsuggested by Weiss 68 therefore cannot be operative.Furman and Garner 69 have found that the rate of electron transferbetween V(III) and V(IV) is given by :The mechanism suggested is : Vf3 + H20 VOH2+ + H+, VOH2+ +*VO2+ + Z4+ --+ *VOH2+ + V02+, where Z4+ is a quadruply chargedactivated complex of unspecified structure.The exchange between VII andVIII is complete within one minute at 2" c . ~ *Bonner and Hunt 71 have reported that the half-time for electron transferbetween CO(II) and CO(III) in aqueous perchloric acid a t 0" varies from 4.8 to22 minutes, depending on the molarity of the solution in the region 0.7to 3.0 x 10-3~. The exchange is not catalysed by glass surfaces or byordinary daylight.The electron transfer 72 between EU(II) and EU(III) in perchloric-hydro-chloric acid solutions is of first order in each of the valency states of euro-pium, and also of first order in chloride ion.The over-all energy of activationis 20.8 kcal./mole.Wolfgang and Dodson 73 have confirmed earlier work that exchangebetween Hg(1) and Hg(I1) is very rapid in perchloric acid solution. Theyfind, however, that addition of cyanide causes the exchange to become slowand measurable. Preliminary kinetic data suggest that the rate-controllingstep may be reaction between Hg22+ and a cyanide complex of Hg(I1).Electron transfer between K,Mo(CN) and K,Mo(CN), has been invest-igated with 99Mo as the radioactive tracer.74 The exchange is complete atall pH values between 1 and 11, and at total molybdenum concentrations aslow as lo-".R = 4.5 x 1012 exp (- ~O,~OO/RT)[V(III)][V(IV)~/[H+] mole 1.-1 sec.-l6 6 H.C. Hornig and W. F. Libby, J . Phys. Chem., 1952, 56, 869.6 7 L. Eimer, A. I. Medalia, and R. W. Dodson, J . Chem. Phys., 1952, 20, 743.6 8 J. Weiss, ibid., 1951, 10, 1066.70 W. R. King, Jr., and C . S. Garner, ibid., p. 3709.'1 N. A. Bonner and J. P. Hunt, ibid., p. 1866.'2 D. J . Meier and C . S. Garner, J . Phys. Chem., 1952, 56, 853.73 R. L. Wolfgang and R. W. Dodson, ibid., p. 872.74 R. L. Wolfgang, J . Anzer. Chem. SOC., 1952, 74, 6144.J . Silverman and R. W. Dodson, ibid., p. 846.S . C. Furman and C. S . Garner, J . Atner. Chem. SOC., 1952, 74, 233341 GENERAL AND PHYSICAL CHEMISTRY.By separating Cr(n) from Cr(m) by an ion-exchange resin, Haissinsky 75has shown that electron transfer between these ions is complete in hydro-chloric acid in the time taken for separation (3-7 minutes).There aresome indications that the exchange may not be complete in sulphuric acidin the same time.The electron transfer between the tris-5 : 6-dimethyl-1 : 10-phenanthro-line complexes of ferrous and ferric ions is complete within 15 seconds atO", a t concentrations 2 x 1 0 - 5 ~ in each species.76Jenkins and Yost 77 have investigated thekinetics of exchange of tritium between hypophosphorous acid and water,and their results indicate that in solution, two forms of this compoundexist which differ in position of the hydrogen atom in the H,PO, molecule.lPC-Labelled acetate has been used in a study of the exchange reactionsamong sodium acetate, acetic acid, and acetic anhydride in anhydrousacetic acid solutions. 78 Rapid exchange occurs between sodium acetateand the solvent, by direct proton transfer.Only slow exchange occursbetween acetic anhydride and acetic acid. Rapid acetate exchange isfound between both Pb(I1) and Pb(1v) acetates and the solvent. However,contrary to earlier results,79 no electron exchange occurs between Pb(11) andPb(1v) in acetic acid at 80" in four hours.Bonner and Bigeleisen *ci report no exchange of l80 between water andN20 in either concentrated alkali or concentrated acid media. No exchangewas found between water and sodium hyponitrite a t pH above 7.0, or inacid solution, in which this salt slowly decomposes.Similarly, no exchangewas observed during the decomposition of sodium " nitrohydroxylamite ' '(oxyhyponitrite) (Na2N20,) in either acid or alkaline media.Two independent investigations have shown that there is no exchangebetween either CN- or S= with CNS- in the pH range 0-5-12-7.81Based on the observations that ozone, H,O,, and 0, do not exchange1 8 0 with water, but that addition of hydrogen peroxide to water in presence ofozone causes exchange between water and ozone, Forchheimer and Taube 82suggest that OH radicals probably undergo exchange with water. Thisconclusion is reached from a consideration of the mechanism of interactionbetween hydrogen peroxide and ozone, according to which oxygen atoms inOH radicals finally emerge as oxygen gas.Atkins and Garner 83 have investigated the exchange of radioactive zincbetween zinc ions and seven zinc chelate complexes in pyridine.All " non-fused ring " complexes (e.g., the complex with 8-hydroxyquinoline) showedcomplete exchange in less than 0-5 minute, while the only " fused ring "complex examined (zinc phthalocyanine) showed no exchange in 35 days.This behaviour is in agreement with earlier predictions relating to theexchange lability of metallo-organic complexes.(b) Atom and group transfer.7 5 M. Haissinsky, J . Chim. Phys., 1952, 40, C 133.7 6 L. Eimer and A. I. Medalia, J . Apner. Chew. SOC., 1952, 74, 1692.7 7 W. A. Jenkins and D. M. Yost, J . Chem. Phys., 1952, go, 538.7 8 E. A. Evans, J . L. Huston, and T. H. Norris, J .Amer. Chem. Soc., 1958, 74, 4985.79 G. von Hevesy and L. Zechmeister, 2. EEektrochem, 1920, 26, 151.80 F. Bonner and J. Bigeleisen, J . Amer. Chem. SOC., 1952, 74, 4944.8l A. W. Adamson and P. S. Magee, ibid., p . 1590; G. E. Heisig and K. Holt, ibid.,83 D. C. Atkins, Jr., and C. S. Garner, ibid., p. 3627.84 S . Ruben, M. D. Kamen, M. B. Allen, and P. Nahinsky, ibid., 1942, 84, 2297.p. 1597. 82 0. L. Forchheinier and H. Taube, ibid., p . 3705BETTS et U l . THE KINETICS OF HOMOGENEOUS REACTIONS. 45Exchange of radio-chromium between the ion Cr( H20)63+ and thecomplexes (Cr en3)3t, Cr(~rea),~+, and CrF,(H,O), were found to be veryThe complex with fluoride ion showed some exchange whichincreased a t lower acidities.West 86 has continued his studies on the relation between bond type andrate of exchange for cobaltous and cobaltic complexes of the bidentate type.The results in general support the view that covalent bonds display slowexchange of the central metal atom with cobalt ion, and ionic complexesshow rapid exchange.Jones and Long 87 have investigated several exchange reactions betweenferrous and ferric ions and their complexes with ethylenediaminetetra-aceticacid (H4Y).Fey= and Fe2+ exchange instantaneously, while the corre-sponding ferric couple Fey- and Fe3+ exchange slowly. The pair FeOH2+-Fey- exchange a t a rate tenfold slower than the couple Fe3 '-Fey-.14C has been used by Harris and Stranks 88 to follow the kinetics ofexchange between carbonate ion in solution and the carbonate ion in thecomplex [Co (NH,) ,CO,]+.Exchange occurs by two mechanisms, dependingon the concentration of carbonate (or bicarbonate) ion in solution. Onemechanism involves the ions [CO(NH,)~,HCO,,H,O]~+ and HC0,-, and theother the equilibrium :H,O + [CO(NK,),HCO,H,O]~~ G+ CO(NH,),(H,O),+~ + HC0,-In a later paper, the effects of ionic strength on the rate of the ion-dipolemechanism and the ion-ion mechanism were in~estigated.~~ In the con-centration range for which the ion-dipole reaction is operative, the equationof Amis and Jaff6 accurately described the results up to ionic strength 1.0.For the ion-ion interaction, the Bronsted relation did not describe the effectof the ionic strength on the rate of reaction.The exchange reaction between water as H2180 and Cr(H20),+, is firstorder in Cr(IrI), and the rate increases with concentration of the anionpi-e~ent.~l With C1- as the only anion present, the rate of exchange of watergreatly exceeds the rate of formation of the complex ion [Cr(W20),C1]2+.The rate of exchange is markedly increased by Cr2+, and only slightly byCr,0,2-, and is induced by the reaction between Ce(1v) and Cr(r1r).Theresults suggest that electron transfer between Cr(I1) and Cr(1rI) is rapid, andthat exchange of water takes place a t the Cr(I1) stage. The exchangebetween free and bound water in the complex ion [Co(NH,),H20I3+ wasfound to be of first order with respect to the complex ion, and was independentof acidity. A dissociation mechanism is favoured over a bimolecularmechanism involving water as the second reacting speciesg2Bernstein and Katz 93 have measured the gas-phase exchange betweenfluorine and the interhalogen compounds ClF,, BrF,, and IF,.Homo-geneous exchange occurs at a measurable rate about loo", probably by$ 5 W. R. Icing, Jr., and C. S. Garner, J . Amer. Chem. SOC, 1952, 74, 5534.b G B. West, .I., 1952, 3116.8 7 S. S. Jones and F. A. Long, J . Phvs. Chacin., 1952, 56, 25. ** G. M. Harris and D. R. Stranks, Tians. Faraday SOC., 1952, 48, 137.89 D. R. Stranks, Trans. Faraday Soc., 1952, 48, 911.99 E. S. Amis and G. Jaffe, J. Chem. Phvs., 1952, 10, 598.91 R. A. Plane and H. Taube, J. Phys. Chew., 1952, 56, 33.9: A. C. Rutenberg and H. Taube. J. Chenz. Phys., 1952, 20, 825.KI R.I3. Bernstein and J. J. KaEz, J . Phys. Chem., 1952, 66, 88646 GENERAL AND PHYSICAL CHEMISTRY.reversible dissociation for the chlorine and iodine compounds, and by anassociation mechanism for BrF,.The exchange of 1311 as sodium iodide has been investigated for the follow-ing compounds : (i) ally1 iodide in ethyl alcohol; 94 (ii) iodobenzene insec.-octyl alcohol ; 95 (iii) 9-iodophenol in octan-2-01; 96 (iv) 2-iodo-naphthalene in acetyl alcohol; 97 (v) ethyl iodide in acetonitrile 9* and9-iodonitrobenzene in octan-2-01 and in acet~nitrile.~~Exchange between periodate and iodine loo is slow compared with thatreported lol for exchange between iodate and iodine. The rate varies withacidity in the same way as the chemical reaction between iodide ion andperiodate, and the temperature coefficients for the two processes are similar,suggesting similar mechanisms.The exchange between iodate and periodateis very slow and is catalysed by molecular iodine.Non-isoto9ic Reactions in Solution.- (a) Electron transfer reactions inaqueozcs solution. Dainton lo2 has reviewed both thermal and photochemicalelectron transfers between various cations and anions, on the one hand, andwater, hydrogen peroxide, and formic acid, on the other.Two independent studies have been made of the kinetics of the reactionTI(III) + 2Fe(11) ---+ Tl(1) + 2Fe(111).lo3 The hydrolysed forms T10H2+and TIOf take part in rate-controlling electron transfers from Fe(I1). T~(II)is suggested as an intermediate in the process.Carter and Davidson lo4 have shown that the oxidation of ferrous ion bybromine in a two-stage process involves the radical-ion Br2-.The kineticsof the reaction agree with the scheme :Fez+ + Br,-Br,- + Fe2-b +Fe+3 + 2Br-Fe3+ + Br- + Br2-Fudge and Sykes lo5 have shown that the thermal electron transfer betweenFe(m) and iodide ion probably occurs by the sequence : Fe3+ + I- FeI2+,FeI2+ + I- Fe2+ + I,-, and Fe3 + I,- Fe2+ + I,. Ferrous ioninhibits the reaction, by competition with ferric ions for the radical-ion 1,.In a second paper, Sykes loG relates the retarding effects of various anionson the process to complex-ion formation with Fe(m), and from the kineticdata, deduces the association constants for formation of the complex ionsFeOH2+, FeSO,+, and FeNO,,+.Adamson G3 has examined the kinetics of oxidation of cyanide ion byFe(CN)G3-, and suggests a mechanism involving the radical ion (CN),-.A preliminary account has appeared of the reactions of Hg(1) and Hg(r1)with formic acid.lo7 The rate-controlling steps involve electron transferfrom formate ion to Hg(1) or Hg(II), with formation of the free radical94 S.May, P. Daudel, J. Schottey, M. Sarraf, and A. Vobaur6, J . Chiin. phys.,1952, 49, 64.96 S. May, M. Sarraf, A. Vobauri., and P. Daudel, Compt. rend., 1951, 233, 744.913 S. May and B. Girandel, ibid., 1952, 234, 326.97 I. EstellCs and S. May, ibid., p. 433.98 S. May and B. Girandel, ibid., 1952, 235, 953.100 M. Cottin, M. Haissinsky, and D. Peschanski, J. Chirn. phys., 1951, 48, 500.101 0.E. Myers and J . W. Kennedy, J . Amer. Chem. SOL, 1950, 72, 89.102 F. S, Dainton, J . , 1952, 1533.103 C. E. Johnson, Jr., J . Amer. Chem. SOC., 1952, 74, 959; 0. L. Forchheimer and R. P.lo4 P. R. Carter and N. Davidson, J . Phys. Chew., 1952, 56, 877.106 A. J . Fudge and K. W. Sykes, J., 1952, 119.lo6 K. W. Sylres, ibid., p. 124. lo' A. R. Topham and A. G. White, ibid., p. 105.gs I d e m , ibid., 1952, 234, 2280.Epple, ibid., p. 5772BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 47H-CO*O*. Another thermal electron-transfer reaction leading to freeradicals is that between Fe(I1) and the isopropylcumene and tert.-butyl-cumene hydroperoxide.108 The rate-controlling step is Fe2+ + R-O*OH --+ Fe3+ + ROO- + OH-.Evidence for a two-electron transfer process has been given by Haight andSager,lo9 arising from their studies of the molybdate-catalysed reduction ofperchlorate ion by Sn(I1).The reaction is very complex, and appears toproceed via quadrivalent molybdenum formed by two-electron transferfrom Sn(I1).In continuation of his studies ofoxygen-transfer reactions involving the use of l80, Taube and his co-workers 11* have found that only part of the oxygen in HOCl is transferred tosulphite in this reaction to form C1- and SO,2-. He suggests two modes ofattack of the hypohalite on SO,,- : C10- + SO,,- -+ C1- + ;OC1- + SO,,- + Hf + ClSO,- + OH-, followed by ClSO,- + H20 --+SO4,- + 2H+ + 2C1-. In the first, oxygen transfer is direct, whilst in thesecond the oxygen atom transferred to the sulphite is derived from thesolvent.It was also shown that two atoms of oxygen are transferred to502- per molecule of hydrogen peroxide reactinglll When the samereaction is catalysed by molybdate, only one atom is transferred from H20,to SO,2-. In the former case, permonosulphurous acid is postulated as anintermediate. In the other reaction, oxygen atoms may be transferred frompermolybdic acid to SO,,-, with rupture of the 0-0 bonds in the per-molybdate. Transfer of oxygen from Mn0,- to SO,,- is very inefficient, andTaube suggests that pennanganate acts mainly by electron transfer.In alkaline solution, pentathionate ion decomposes to thiosulphate,according to 2S,0,2- + 60H- + 5S2OS2- + 3H20.112 The reaction is offirst order in S,0G2- and OH-, and displays a kinetic salt effect corre-sponding to that predicted for a reaction between a singly and a doublychanged anion.The slow stage in the reaction is postulated as S,0G2- +OH- --+ S2032- + HOS*S,O,-, followed byHOS=S,O,- + OH-+ S(OH), +S2032-.Peschanski 113 has made a detailed study of the kinetics of the oxidationof I, by periodate ion. The mechanism proposed involves successive oxygentransfers from periodate to I-, 10-, 10,- (or HOI and HIO,). Iodide ionis present at low concentrations provided by the hydrolysis of iodine.Abel 114 has discussed the mechanism of the permanganate-oxalatereaction in terms of the relative reactivities of the oxalate ion (C02)?2-and the radical-ion (C02)2-. He suggests that reaction of Mn in oxidationstates 6, 5, 4, and 3 is fast with either reagent, and that reaction of Mn04- isslow with (C02),2-.The ion-radical is thus the main catalyst, which slowlyaccumulates during the induction period. Catalysis by Mn(I1) is due toreaction with Mn04- to give intermediate oxidation states, which then reactrapidly with (C02)22- to give (C02),-. Malcolm and Noyes 115 suggest that(b) Reactions of oxygenated anions.lo8 R. J. Orr and H. L. Williams. Canud. J. Chem., 1952, 30, 985.log G. P. Haight, Jr., and W. F. Sager, J . Amer. Chem. SOC., 1952, '94, 6056.112 J. A. Christiansen, W. Drost-Hansen, and A. E. Nielsen, Acta Chem. Scand.114 E. Abel. Monutsh., 1952, 83, 695.116 J . M. Malcolm and R. M. Noyes, J . Anrev. Chem.SOC., 1962, 74, 2769.J. Halperin and H. Taube, ibid., p. 375. ll1 Idem, ibid., p. 380.1952, 6, 333. 113 D. Peschanski, J. Chim. phys., 1951, 48, 48948 GENERAL AND PHYSICAL CHEMISTRY.the kinetics of the Mn0,--oxalate reaction are consistent with a reactionbetween Mn0,- and an oxalate complex of Mn(II), to give Mn(vz), whichis rapidly reduced to Mn(1Ix) by either Mn(I1) or oxalate. The subsequentreaction involves decomposition of Mn( 111) complex oxalates, according to themechanism suggested by Taube.l16The kinetics of the reaction between Mn(I1) and periodate have beeninvestigated by Waterbury, Hayes, and Martin.l17 The scheme proposed toaccount for some aspects of their kinetic results involves oxidation-reductionequilibria between the pairs Mn(n)-MnO,-, Mn(Iv)-Mn(II), accompanied byreaction between Mn(1r) and Mn(v1) to form Mn(1v).With these postulatedequilibria, together with the assumption that [M~(II)] > [M~(III)] > [Mn(~v)],an expression was obtained which fits the experimental rate law, R =k[Mn0,-]0'5[Mn(~~)][H510,].A study of the reaction between nitrous acid and hydroxylamine to formnitrous oxide and water has been made by Bothner-By and Friedman.l18By examining the isotopic composition of the products formed from I5N-enriched nitrite and l*O-enriched water, they conclude that the earliermechanism involving NOH (nitroxyl) is untenable. Hyponitrous acid(HO-N:N*OH) is proposed as the intermediate in neutral solution, and N-nitrosohydroxylamine (HO-NH-NO) as the intermediate in acid solution.A mechanism based on kinetic studies has been proposed for the de-composition of nitrosyldisulphonate ion in water.lls It involves theformation of OH radicals as an intermediate by reaction of hydrogen-ionwith (S0,)2NO*2-, followed by reaction of OH with nitrosyl disulphonateion to produce N20, nitrous acid, and sulphate ion.Lister 120 has shown that the decomposition of HOCl is a second-orderreaction, and suggests that the rate-controlling step involves dispro-portionation of HOCl to chloride and chlorite ions. The reaction HOCl $-OC1- + C1- + Hf + C10,- also occurs, but is much slower than the reactionbetween un-ionised HOCl molecules. Oxygen is generated by a first-orderreaction, possibly by reaction of HOCl and water to form H,02, followed bya rapid reaction between OC1- and H20,.Taube 121 has published a comprehensivereview of the rates and mechanisms of substitution in inorganic complexes insolution.He stressed the importance in this connection of the electronicstructure of the complex ion.Bjerrum and Poulsen 122 have reported a preliminary study of the rate offormation of several types of complex ions, ,e.g., the reaction of Ni(11) withdimethylglyoxime and the reaction of Fe(II1) with thiocyanate. By usingmethanol as the solvent, they were able to examine the kinetics of suchreactions at temperatures down to 180" K, where the rates are no longer" instantaneous." The results support the idea of a connection betweenthe rate of complex formation and the valency and electron configuration inthe transition elements ; thus for the same electron configuration, e.g.,(c) Reaction of complex ions.116 H.Taube, J . Amev. Chenz. SOC., 1948, 70, 1216; 1947, 69, 1418.11' G. R. Waterbury, A. M. Hayes, and D. S . Martin, Jr., ibid., 1952, 74, 15.118 A. Bothner-By and L. Friedman, J . Chem. Phys., 1952, 20, 459.120 M. W. Lister, Cauaad. J . Chew., 1962, 50, 879.lZ1 H. Taube, Chem. Reviews, 1952, 50, 69.132 J. Bjerrum and K. G. Poulsen, Natwre, 1952, 189, 463.J. H. Murib and D. M. Ritter, J . Amer. Chem. Soc., 1952, 74, 3394BETTS et a2. : THE KINETICS OF HOMOGENEOUS REACTIONS. 49Feat and Mn2+, the higher valency state reacts more slowly. For equalvalency, ions with half-completed or completed electron shells give a muchhigher rate of complex formation.Approximate measurements of thekinetics indicate that most reactions leading to formation of complex ionsare instantaneous at room temperature because of a high value of thefrequency factor rather than a low value of the activation energy.Wilmarth and Baes 123 have shown that the paramagnetic complex ionsof Cr(m) with water, thiocyanate, urea, ammonia, and other ligands willcatalyse the conversion of para- to ortho-hydrogen. By using Wigner'sformula relating the approach distance of the paramagnetic ion to the rateof the conversion, deductions regarding the size of these ions were made. Itappears likely on this basis that hydrogen must penetrate through most ofthe atoms in the ligand groups surrounding the central Cr(m) ion.The mechanism of the acid-catalysed aquation of the complex ionCo(NH,),CO,+ has been investigated, by means of H2180.124 By analysingthe l*O content of the complex ion before and after aquation, it was shownthat at least 99% of the change leaves the Co-0 bond intact.have measured the rates of hydrationand hydrolysis of a series of C-substituted acetato-pentammino-cobalt (111)ions in solution.The rates of both processes were dependent on the basestrength of the acid ligand, but independent of its size. The authors concludethat the incoming groups approach the complex from a position opposite tothe outgoing groups, or that substitution occurs by dissociation. In asecond paper,126 the rate of aquation of the complex ions [Co(AA),Cl,]+were measured, where AA represents compounds of varying complexity,containing two amino-groups.Increased crowding around the centralatom, arising from longer hydrocarbon skeletons in AA, did not retard thereaction, which suggests that aquation does not occur by a seven-co-ordinatedSN2 mechanism, but rather by a S N 1 mechanism in which the activatedcomplex is penta-co-ordinated.Price 127 has examined the kinetics of the metal-ion catalysed decarboxyl-ation of acetonedicarboxylic acid, and has shown that the undissociatedacid, the univalent anionic form, and the bivalent enol anion react at differentrates. Hesuggests that the catalytic activity of cations is due to chelation of theactivated complex by the metal ion.In support of this, a relation was foundbetween the catalytic coefficient and the association constant of the chelatecompounds formed by these ions with nialonate ion. Further, ions whichdo not form chelate compounds display no catalytic effects.Brandt and Gullstrorn 12* have calculated the stabilities of some 5-substituted 1 : 10-phenanthroline-Fe(11) complexes from the rates of forrn-ation and dissociation of the complexes, and also from equilibribium data.The stabilities of the complex formed with Fe(I1) decreases in the ordermethyl, phenyl, chloro, and nitro, Values for the equilibrium constantsdetermined by the two methods for each system were in good agreement.Basolo, Bergmann, and PearsonThe last process is most strongly influenced by metal ions.123 W.K. Wilmarth and C. F. Baes, Jr., J. Chem. Phys., 1952, 20, 116.184 J. P. Hunt, A. C. Rutenberg, and H. Taube, J . Anzer. Chem. SOC., 1952, 74, 268.125 F. Basolo, J. G. Bergmann, and R. G. Pearson, J . Phys. Cheun., 1952, 58, 22.126 R. G. Pearson, C. R. Boston, and F. Basolo, J . Amev. Chem. Soc., 1952, 74, 2943.127 J . E. Prue, J., 1952, 2331.128 W. W. Brandt and D. K. Gullstrom, J . Amer. Chem. SOC., 1952, 74, 353250 GENERAL AND PHYSICAL CHEMISTRY.(d) Reactions of hydrogen peroxide. During the year, a review hasappeared of the reactions of hydrogen peroxides with " donor particles,''e.g., Br03-, IO,, I-.129 At least three papers have been published relatingto the source of oxygen evolved from the decomposition of hydrogen peroxidein aqueous solutions containing a variety of other reagents including Fe(Ir),Fe(m), Ce(Iv), MnO,-, Br2.130-132 In all cases examined, oxygen comescleanly from hydrogen peroxide, indicating that the 0-0 bond in the per-oxide remains intact.Measurements of the relative rates of evolution of1 8 0 and l60 have led to several interesting speculations regarding thedetailed mechanism of some of the reactions; thus, Cahill and Taube 131suggest that a two-electron transfer between Fe(I1) and H202 is an importantchain-carrying step in the Fe( 11) -induced decomposition of this substance.Reactive isomers of H02-, arising from decomposition of FeO*OH2+, havebeen suggested as intermediates in this reaction. 1339 134The reaction between nitrous acid and hydrogen peroxide has beenstudied by Halfpenny and R0bins0n.l~~ The scheme proposed to accountfor the kinetics involves peroxynitrous acid (H0,NO) as an intermediate,which decomposes to HO and NO,, followed by reaction of these speciesto form nitric acid.Shilov also suggests peroxynitrous acid as the inter-mediate in this r e a ~ t i 0 n . l ~ ~The reduction of sodiumanthraquinone-2-sulphonate by Ti3+ is a composite reaction involvingsimultaneous reduction of the semiquinone, the semiquinone dimer, and amolecular complex of one molecule of quinone and one of semiquinone.The ratio of reduction of the quinone itself is insignificant compared withthese other react ions. l3Turgeon and LaMer 138 have published a comprehensive account of thekinetics of formation of the carbinol of crystal-violet. The reaction followsquantitatively the Bronsted-Debye law for primary kinetic salt effects.The energy of activation is 0.9 kcal./mole higher in 40% acetone-water thanin pure water.This is contrary to the decrease expected due to the loweringof the coulombic activation energy in a solution of lower dielectric constant.A specific solvent effect may be involved, resulting in preferential solvation ofthe crystal-violet cation by the organic solvent rather than by water.Derbyshire 139 has reviewed recent results relating to the rates of bromin-ation and iodination by hypobromous and hypoiodous acid in acid solutions,and suggests that the active entity in such solutions is the halogen cationco-ordinated with a molecule of water, rather than siinply a cation hydratedby electrostatic solvation.CH,I + Br- have been investigated in ethylene glycol for comparison with(e) Kinetics qf other reactions in sobution.The kinetics of the non-isotopic exchange reaction CH3Br + I-lZ9 J.0. Edwards, J . Phys. Chem., 1952, 56, 279.130 C. A. Bunton and D. R. Llewellyn, Research, 1952, 5, 142.131 A. E. Cahill and H. Taube, J . Amer. Chem. Soc., 1952, 74, 2312.132 M. Dole, D. P. Rudd, G. R. Muchow, and C. Comte, J . Chem. Phys., 1952, 20, 961.133 V. S. Anderson, Acta Chem. S c a d . , 1952, 6, 1090.13p J. A. Christiansen, ibid., p. 1056.135 E. Halfpenny and P. L. Robinson, J . , 1952, 928.1 3 ~ E. A. Shilov, Chem. Abs., 1952, 46, 2946.137 C.E. Johnson, Jr., and S . Winstein, J . Amer. Chem. Soc., 1962, 74, 3105.158 J. C. Turgeon and V. K. LaMer, ibid., p. 5988.139 D. H. Derbyshire, Research, 1952, 5, 240BETTS et Ul. : THE KINETICS OF HOMOGENEOUS REACTIONS. 51earlier measurements of the same system in water, methanol, and acetone.140The rates in this solvent were three times greater than in methanol, andfour times as great as in water. Values of AG and A S for the equilibrium, asreflected in the ratio of the rate constants, are -1-62 kcal./mole and 17.3cal. mole-1 deg.-l, respectively.Glew and Moelwyn-Hughes have investigated the kinetics of the alkalineand acid hydrolysis of methyl fluoride in water.141 The first-order reactionwith water is retarded by hydrogen fluoride and by methanol, and kineticanalysis suggests the scheme CH3F CH3*F CH3*OH + HF. Thealkaline hydrolysis is a second-order process, vix., CH,F + OH-+ CH,*OH +F-.The energy of activation for alkaline hydrolyses of methyl bromide andfluoride are the same within experimental error, and thus the difference inbond energies of some 30 kcal. is not reflected in this quantity. The authorssuggest that the solvent plays an important part in these reactions, and thatthe energy of activation refers to the escape of the ion from its solventsheath. For the first-order reaction, this analysis suggests a simultaneousattack by six water molecules surrounding the methyl halide, with re-organisation necessary for the ionisation of a seventh water molecule.The rate-determining step is then the simultaneous ionisation of water andattack on CH3X by OH- so formed.Bell and Clunie 142 have described a thermal method for following fastreactions in solution, which they have used to investigate the kinetics ofhydration of a~eta1dehyde.l~~ The results do not support the view 144 that thereaction mechanism involves simultaneous attack by acidic and basic species.Meadows and Darwent 145 have shown that in neutral and buffered solu-tions, hemiacetal is the only important product in the reaction betweenacetaldehyde and methanol ; in strongly acid solution, acetal is formed nearlyquantitatively. The former reaction exhibits general acid-base catalysis,whilst the latter is catalysed only by hydrogenSeveral papers have appeared during the year relating to the kinetics ofthe reaction of formaldehyde in aqueous solution with urea 147, 148 N-methyl-urea,149 and phenol.lMBell and Skinner 151 have investigated the kinetics of depolymerisation ofparaldehyde in ethereal solutions of proton acids and Lewis acids.TheLewis acids (e.g., BCl,, SnCl,, TiC1,) showed in general more marked catalyticactivity than even a very strong proton acid such as HBr. Moreover,these substances appeared to act as catalysts without the co-operation ofproton acids. The reactions were initially of first order in paraldehyde andsecond-order in catalyst.Bell and Goldsmith 152 have shown that the iodination of 2-ketocyclo-j4* J. S. McKinley-McKee and E. A. Moelwyn-Hughes, J ., 1052, 838.141 D. N. Glew and E. A. Moelwyn-Hughes, Proc. Roy. SOC., 1952, A , 211, 254.142 R. P. Bell and J . C. Clunie, ibid.. 1952, A , 212, 16. lp3 Idenz, ibid., p. 33.144 C. G. Swain, J . Anter. Chew,. SOC., 1950, 72, 4578.145 G. W. Meadows and B. de B. Dai-went, Canad. J . Chem., 1952, 30, 501.146 B. de B. Darwent and G. W. Meadows, Trans. Faraday SOC., 1952, 48, 1015.147 J. I. de Jong and J . de Jonge, Xec. Tvav. chirn., 1952, 71, 643, 890.148 G. Smets and A. Borzee, J . PoJyiner Sci., 1952, 8, 371.14s L. E. Srnythe, J . Anaey. Chew. Soc., 1952, 74, 2713.150 L. M. Oebing, G. E. Murray, and R. S. Schatz, Igzd. Eng. Chew., 1052, 44, 354, 366.151 R. P. Bell and F. G. Skinner, J . , 1952, 2955.152 R. P. I3ell and H. L. Goldsmith, Pvoc.Roy. Soc., 1958, A , 210, 32252 GENERAL AND PHYSICAL CHEMISTRY.hexanecarboxylic acid is of first order with respect to the ester, and zeroorder in iodine, The reaction is catalysed by water and by anions of carb-oxylic acids. Catalytic constants for four carboxylic acids obey a relationof the Bronsted type. This ester is iodinated 100--400 times more slowlythan the &membered analogue. This result is unexpected on the basis ofring-strain considerations, which suggest that the 6-membered ring should bethe more reactive of the two compounds.Isotope Effects.-At least three papers have appeared during the year,which consider the theoretical aspeets of the effects of isotopic substitutionon the rates of chemical reacti0n.1~~ In some cases, an arbitrary choice ofmodel appears necessary to account for the experimental results.154The isotope effect in the hydrolysis of triphenylsilane in moist piperidinehas been studied with tritium.155 The ratio k ~ / k ~ of the rate constants forthe isotopic reactions was 0.8, whilst earlier work with deuterium gaveThe 12C-12C bond in carboxyl-labelled malonic acid is broken about 10%more frequently than the 12C-14C bond by decarboxylation at 138".15'This is an intramolecular isotope effect.The temperature coefficient of theintermolecular isotope effect for the same reaction is zero 158 in the tempera-ture range 137-196". The intermolecular isotope effect is slightly greaterin the decarboxylation of [C02H-14C]malonic acid than it is for the corre-sponding reaction with [a-14C]-acid.159Stevens, Pepper, and Lounsbury I6O have measured the relative isotopeeffects of 13C and 14C arising from decarboxylation of mesitoic acid.Byusing 0.8 mole-% 14C-compound labelled in the carboxyl position, they wereable to measure W02, 13C02, and 14C02 in a mass spectrometer. The14C isotope effect was more than twice the 13C isotope effect (1.101 and 1.038respectively) which is unexpected in view of current theories. 153The 12C-carboxyl group 154 is lost as 12C02 about 10% more frequentlythan in the %-groups in both a-naphthyl- and phenyl-malonic acid. De-carboxylation of 1%-labelled anthranilic acid,161 either by heating it aboveits melting point, or by boiling it in water, shows no isotope effect.This isconsidered explicable on the basis of the mechanism proposed, which in-volves a proton attack on the a-carbon of the zwitterion.The relative isotope effects in the thermal decomposition of oxalic acidhave been investigated with l4,C and 13C; the isotopes were measured byradiochemical and mass-spectrometric technique, respectively. The 13Cisotope effect was about one-half of the 14C isotope effect. A small tempera-ture coefficient was noted in the region 80-100".162 Bunton and Llew-ellyn have investigated 13C isotope effects in the chemical reactionsKDIFZN = 6.156153 J. Bigeleisen, Canad. J. Chem., 1952, 30, 443; J . Phys. Chem., 1952, 56, S23;H. Eyring and F. W. Cagle, Jr., ibid., p. 589.154 A. Fry and M. Calvin, ibid., p.901.155 L. Kaplin and K. E. Wilzbach, J. Amer. Chem. SOC., 1952, 74, 6152.166 G. E. Dunn, H. Gilmour, and G. S. Hammond, ibid., 1951, 73, 4499.157 P. E. Yankwich, E. C. Stivers, and R. F. Nystrom, J . Chem. Phys., 1952,20,344.158 J. G. Lindsay, A. N. Bourns, and H. G. Thode, Canad. J . Chem., 1952, 30, 163.159 G. A. Ropp and V. F. Raaen, J. Amer. Chem. SOC., 1952, 74, 4992.160 W. H. Stevens, J . M. Pepper, and M. Lounsbury, J. Chem. Phys., 1952, 20, 192.161 Idem, Canad. J . Chem., 1952,30, 529.162 A. Fry and M. Calvin, J. Phys. Chem., 1952, 56, 897.163 C. A. Bunton and D. R. Llewellyn, Research, 1952, 5, 443BETTS et al. : THE KIXETICS OF HOMOGENEOUS REACTIONS. 53between oxalic acid and bromine, hydrogen peroxide, potassium perman-ganate, and KMn0,-Mn2+. Formation of l2CQ, is preferred to that of13C02, but the effect varies from 1-8 to 3-6%, depending an the reagent used,and appears to be related to the mechanism of attack on oxalic acid by thesereagents.The thermal deammoniation of phthalamide shows an isotope effect,14NH, being formed more readily than 15NH,.16, The results are related tothe effect of isotopic mass of the nitrogen atom in the C-N bonds which areboth broken and formed in the reaction.Schmitt, Myerson, and Daniels have shown that an isotope effect existsin the hydrolysis of urea by u r e a ~ e .1 ~ ~ 12C02 is evolved 1% more readilythan 13C0,, and 3.2% more readily than 14C02.Ropp and Raaen 166 have examined the efiect of ring substitution on theisotope effect in hydrolysis of ethyl [C02Et-14C] benzoates.The isotopeeffect may be greatest in the hydrolysis of those esters in which the largestcontributions to the normal state are made by resonance forms of the type+ R:C,H,YC(OEt)*O-. Other organic systems for which isotope effectshave been detected include (i) the reaction between 14C-labelled benzo-phenone and 2 : 4-dinitrophenylhydrazine ; 167 (ii) Cannizzaro reaction of14C-labelled formaldehyde ; 168 (iii) reaction of 14CH20 with dimedone ; 169and (iv) reaction of [l-14C]acetonc with alkaline hypoiodite.170 The lastreaction is of particular interest, since the isotope effect appears to beopposite to that ordinarily found : the I2C-l4C bond is more easily brokenthan the I2C-l2C bond.Yankwich and McNamara 171 find no isotope effects on the equilibriuniCo(en),CO,- + H*CO,- HCO,-- + Co(en),*CO,+, but find that thelighter isotopes of carbon are exchanged more readily than the heavier.Stranks and Harris 172 have observed just the reverse behaviour in thesystem Co(NH,),CO,' : 14C becomes concentrated in the anion at equili-brium, while no discrimination is found between 12C and 14C in the kineticsof the process.Photochemistry.-Light Sources and A ctiizometers.-The influence ofseveral variables on the output of light of wave-length 2537 A from a quartz-mercury vapour lamp of the low-pressure type has been studied by Heidt and130yles,l~~ who conclude that the output is particularly sensitive to theexternal temperature and is a maximum at about 45".The uranyl oxalate actinometer has been shown to be suitable for measur-ing intensities up to 1000 times the highest previously used.174 The quantumyields, at 3650 A, for the photolysis of seven aromatic diazonium salts 175 havebeen accurately measured and found to lie in the range 0.20-0.74.Thel C 4 F. W. Stacey, J . G. Lindsay, and A. N. Bourns, Canad. J . Chon., 1952, 30, 135.165 J. A. Schmitt, A. L. Myerson, and 1;. Daniels, J . Phys. Chem., 1952, 56, 917.166 G. A. Ropp and V. F. Raaen, J . Chenz. Phys., 1952, 20, 1823.167 F. Brown and D. A. Holland, Canad. J . Chem., 1952, 30, 438.168 A. M. Downes and G. M. Harris, J . Chem. Phys., 1962, 20, 196.160 A. M. Downes, Austral. J . Sci. Res., 1952, 5, A , 521.170 A. Roe and E. L.Albenesius, J . Amer. Chem. SOC., 1952, 74, 2402.171 P. E. Yankwich and J. E. McNamara, J . Chem. Phys., 1952, 20, 1325.172 D. R. Stranks and G. W. Harris, J . Phys. Chem., 1952, 56, 906.173 L. J. Heidt and H. B. Boyles, J . Amer. Chem. Sot., 1951, '73, 5728.174 M. I. Christie and G. Porter, Proc. Roy. SOC., 1952, A , 212, 390.175 J. de Jonge, R. Dijkstra, and G. L. Wiggerink, Rec. Trav. chinz., 1952, 71, 84654 GENERAL AXD PHYSICAL CHEMISTRY.photolysis of phenylaminobenzenediazonium sulphate , $ = 0.36, has beenproposed as an actinometer for 3650 A. It has the merits (i) that 100%decomposition gives the theoretical amount of nitrogen, (ii) that the nitrogenproduced may be blown off by a stream of carbon dioxide and used as adirect measure of the light absorption, and (iii) that the diazonium salts havea high extinction coefficient and lOOyo absorption of light is easily achieved.The malachite-green leucocyanide actinometer has been reinvestigated.176An improved method of preparation has been described, and it has beenconfirmed that at all wave-lengths the quantum yield is 1.00, provided theintensity is sufficiently low and the stirring rate sufficiently high.A new type of Draper-Bunsen actinometer has also been described.177Direct Photochemical Reactions.-(a) Ketones and aldehydes.The photo-lysis of keten has been the subject of two papers. By means of 13C0 it hasbeen found that the CH, formed by the rupture of the keten moleculereadily combines with carbon monoxide to re-form keten.A study of theproducts of the reaction between CH, and (CHD), indicates the inter-mediate formation of the trimethylene diradical which then rearranges togive pr0py1ene.l'~ Norrish and his co-workers 179 have investigated theflash photolysis of keten and discuss attempts to obtain the absorptionspectrum of the methylene radical.Further evidence for the complete free-radical photolysis of acetonevapour, at all temperatures, and wave-lengths between 2300 and 3400 A, hasbeen published.180-182 Using radioactive l3lI3 as radical " catcher,"Martin and Sutton have investigated the photolyses of acetone lS2 and ethylmethyl ketone.183 They find that at 3130 A the relative rates of the twopossible primary radical processes, (1) COMeEt I_, MeCO + Et and (2)COMeEt + EtCO + Me, is RJR, = 21 6 2 compared with Blacet andPitts's value of 40, while at 2537 A the ratio is considerably lower.The photolysis of diethyl ketone vapour has been extensively investigatedbetween 25" and300" by Kutschke and by Wijnen and Steacie.Their results,which are in good agreement, are published in a joint paper and supportthe following mechanism :( 1 )( 2 ) 2C2H5. -+ C,Hlo(C,H,),CO + hu 4 C2H5*CO* + C,H,* +X,H,- + CO(3)(4)2C2H5. --+ CZH4 + CzH,CZH,. + (C,H,),CO _3 C&, + .C&4*CO*C&,,( 7 ) .C,H,*CO*C,H, + C2H4 + CO + CZH,.The results indicate that k3/k2 - 0.10 at all temperatures, i.e., E3 - E, = 0,E , - = 7-4 kcal./mole, and that reaction (7) only becomes important athigh temperature and/or low intensity.The photolysis of (CH,*CD,),COhas confirmed this mechanism and has provided the additional inform-176 J. G. Calvert and H . J. L. Rechen, J . Amer. Chem. SOC., 1952, 74, 2011.177 E. Crerner and H. Margreiter, 2. physikul. Chem., 1952, 199, 90.178 G. B. Kistiakowsky and W. L. Marshall, J . Amer. Chem. SOC., 1952, 74, 88.1 7 9 K. Knox, R. G. W. Norrish, and G. Porter, J . , 1952, 1477.180 S . W. Benson and C. ?V. Falterman, J . Chern. Phys., 1952, 20, 201.181 D. H. Volman and W. M. Graven, ibid., p. 919.182 G. R. Martin and H. C . Sutton, Trans. Furaday Soc., 1952, 48, 812.183 Idem, ibid., p. 823.184 K. 0. Kutschke, M. H. J. Wjnen, and E. W. R. Steacie, I . Amev. Chem. SOC. 1952,74, 714. 185 M. 13. J . Wijnen and E. W. R.Steacie, Canad. J . Chefn., 1951, 29, lb92BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 55ation that E , - 17 kcal./mole, that the disproportionation reaction occursby a head-to-tail mechanism :and that the energy of activation for reaction (4) is greater for the abstractionof a methyl hydrogen than that of a methylenic hydrogen atom.In the photolysis of di-n-propyl ketone, Masson lS6 has concluded thatabout 50% of the activated molecules ultimately decompose by one of thefollowing two processes :CH,*CD,. + CH,*CD,* --+ CH,CD,H + CH,:CD,> C,H, + CH,.COC,H,(C,H,*CO*C,H,)*(2) 2C,H, + COFor the reaction C,H, --+ C,H, + CH,, E = 20 kcal./mole was obtained.At 113", 17% of the propyl radicals disproportionate and 83% combine togive n-hexane.The photolysis of propaldehyde has been studied with steady and inter-mittent light,lS7 and Blacet and Pitts lS8 have deduced the relative im-portance of four possible primary processes from the products obtained inthe presence and the absence of iodine.In the photolysis of the hydrogenhalides the energy of the light absorbed may be considerably greater than theenergy required to break the hydrogen-halogen bond.Part of the excess ofenergy will appear as kinetic energy of the hydrogen atom* and might beexpected to affect the rates of the reactions, (1) H + HI -+ H, + I, and(2) H + I, --+ HI + I. However, in the presence of sufficient inert gas theexcess of energy will be removed by collision before these reactions occur.Schwarz and his colleagues 189 have interpreted, on the basis of this theory,their results on the photolysis of hydrogen iodide, deuterium iodide, andhydrogen bromide in the presence of helium and hydrogen.They find that,in the presence of inert gas, k,/k, is reduced to a limiting value which isindependent of the nature of the inert gas, and for thermal hydrogenatoms, E, - El f 4.5 -+ 0.8 l<cal./mole.Burns and Dainton lgo have made a complete investigation of the photo-chemical formation of carbonyl chloride in the presence and absence ofnitrosyl chloride as inhibitor, using light of wave-length 3660 A, between25 and 55". Their results confirm the Bodenstein mechanism and thefollowing values for the individual frequency factors ( A ) and energies ofactivation (E) have been obtained :(b) Reactions involving halogen atoms..,log,, A E(1. mole-* sec.-l) (kcal. mole.-')1% A,IA,- c1, + h v ---j 2CI co -b c1-4- COClCOCl--+ co + c1COCl + c1, --+ coc1, + C1 ............C1 + NOCl-+ XO + C1, ............ 10-06 1-06- ............................................. E, - E ,..................... = 6.31 = 2-8062.96COCl + c1--+ co + c1, ............ 11.6 0.83COCI + NOCl+CO + C1, + NO 10.68 1.14I{9.4> {(or COCI, + NO)186 C. R. Masson, J . Amer. Chent. SOC., 1952, 74, 4731.1 8 7 R. E. Dodd, J . , 1952, 878.188 F. E. Blacet and J . N. Pitts, J . Amey. Chew,. SOC., 1952, 74, 3382.1 8 9 H . A. Schwarz, R. R. Williams, and W. H. Hamill, ibid., p 6007.190 W. G. Burns and F. S.Dainton, Trans. Faraday SOC., 1952, 48, 39, 52. * Such atoms are designated as " hot " by the authors56 GENERAL AND PHYSICAL CHEMISTRY.The results lead to the following heats of reaction :CO + C1+ COCl + 6.3 kcal.COCl + C1-> COC1, + 74.9 kcal.The big difference in thc magnitude of the C-Cl bond strengths is in accordwith the high energy of reorganisation for the change : >C=O --+ lCC0.The authors have discussed their results in terns of the theory of absolutereaction rates.Other photochemical reactions involving halogen atoms which have beeninvestigated are the reaction between iodine monochloride and hydrogen,lglchlorination of toluene, 192 a-deutero toluene , lg3 and 2-deu teroisobu t ane(CH3),CD,lg3 bromination of n-pentane,l94 formation of acyl chlorides fromoxalyl chloride and paraffins,lg5 and reaction of a mixture of chlorine andsulphur dioxide with paraffins.lg6 In the liquid-phase photochlorination of(CH,),CD at -15" equimolar amounts of (CH,),CCl and DC1 are formed,indicating that no significant rearrangement of free radicals or hydrogenexchange between radicals and hydrocarbon occurs during chlorination. lg3Kharasch and his co-workers lg4 dispute Williams and Hamill's claim lg7that lower bromides are formed in the photobromination of ut-pentane.The formation of the H2+ ion has been postulated to explain the effect ofpH in the photochemical reactions of aqueous iodide 19* and ferrous solu-tions 1g9 respectively.(c) Other reactions. A further study of the photolysis of aqueous hydro-gen peroxide has been made at relatively high intensity.2mA mechanism of photolysis of methyl nitrite has been put forward whichis in complete accord with all work on the decomposition of this com-pound; 201 the unstable HNO molecule is postulated as an intermediate.it has been shown that 75% of theheavy liquid which is formed consists of a cyclic trimer of CH3*N:CH2, andthat both the radicals CH2*NH* and *CH,*NH, are formed either in the primaryprocess or in a secondary reaction.Booth and Norrish 203 have demonstratedthat the photolysis of aliphatic primary and secondary amines gives productsarising mainly from a primary process involving rupture of a N-H bondto give free radicals. The same authors have studied the photolysis ofamides and conclude that two main types of primary process occur which aremolecular, rather than free-radical, in nature.A novel light-induced reaction of diazomethane with carbon tetrachlorideto give C(CH,Cl), has been reported.204 A free-radical mechanism is pro-posed.Analogous reactions were observed with chloroform and bromo-trichloromethane, the halogens in each case being replaced by a (CH,Hal)group.In the photolysis of methylaminel g l G. G. Palmer and E. 0. Wiig, J . Amer. Chew. SOC., 1952, 74, 2785.132 S. Miyazalii, J . Chern. SOC. Japan, 1951, 73, 459, 641.Ig3 H. C. Brown and G. A. Russell, J . Amer. Chem. SOC., 1952, '74, 3995.lg4 M. S. Kharascli, W. Zimmt, and W. Nudenberg, J . Chem. Phys., 1952, 20, 1659.Ig5 F.Runge, 2. EEektrochem., 1952, 56, 779. lg6 F. Povenz, ibid., p. 746.Ig7 R. R. Williams and W. H. Hamill, J . Amer. Chem. SOC., 1950, 72, 1857.Ig8 T. Riggand J. Weiss, J., 1952,4198. IgS Idem, J. Chem. Phys., 1952, 20, 1194.Zol J . A. Gray and D. W. G. Style, Trans. Faraday Soc., 1952, 48, 1137.zo2 J. S. Watson and B. de €3. Darwent, J . Chem. Phys., 1952, 20, 1041.203 G. H. Booth and R. G. W. Norrish, J . , 1952, 188.204 W. H. Urry and J. R. Eiszner, J . Amer. Chem. SOC., 1952, 74, 5822.J. P. Hunt and H. Taube, J . Amer. Chern. Soc., 1952, '74, 5999BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 57The action of light on diazoaminobenzene in on mesoazanaphth-acene and its angular benzogues,206 on phosphotungstic acid in the pre-sence of isopropyl alcohol,m7 and on aqueous solutions of sodium meta-periodate,206 has also been studied.Some work on the photolysis of solid systems has also been reported.Jacobs and Tompkins 209 have shown that the photolysis of potassium azideinvolves the reaction of pairs of trapped excited azide ions (excitons) oflife-time approximately 2 x see.; and Linschitz and Rennert 210have investigated the reversible photobleaching of chlorophyll in glassysolvents at low temperature.Much recent work is summarised in a symposium on Photochemistry andPhotography held in Germany.211Photosensitised Reactions.-The merc~ry(~P~)-sensitised reaction ofethylene has been reinvestigated 212 and the results are compatible with thesuggestion that a significant fraction of the quenching collisions of ethyleneleads to the formation of metastable (3P0) atoms.Such atoms have beendetected directly not only for ethylene but also when nitrogen, hydrogen,or ethane is the quenching gas.212aThe cadmium(3Pl)-sensitised decomposition of propane at 300" has beenstudied.212b The mercury-sensitised decomposition of nitric oxide has beenshown to be caused by (6 lP,) atoms (1849-A resonance radiation). It issuggested that Noyes's observation of photosensitised decomposition by lightof wave-length 2537 A was due to " stepwise absorption," i.e., absorption of4047 A by (6 3P,) atoms or of 4359 A by (6 3P,) atoms to give (7 3S1) atomswhich then transfer their energy to the nitric oxide mole~ules.~1~The products of the mercury-photosensitised reaction of tetrafluoroethyl-ene at 30" are reported to be mainly hexafluorocyclopropane and a linearpolymer.The kinetics appear to fit a mechanism involving the rupture ofthe ethylenic bond to give two difluoromethylene r a d i ~ a l s . ~ l ~The kinetics of reaction of various dimes, furfurylamine, and thioureawith oxygen, photosensitised by fluorescent pigments, have been de-scribed.215 Uri 216 has found it possible to sensitise the polymerisation ofmethyl methacrylate, using chlorophyll and red light. The rate is enor-mously increased by certain organic reducing agents such as ascorbic acid,and quantum yields with respect to monomer of the order of 100 may beachieved.Fluorescence and Phosphorescence.-The fluorescence emitted by formicacid, carbonyl chloride, and methylene iodide has been described 217 and206 H.C. Freeman and R. J. W. Le Fkvre, J., 1952, 2932.208 A. gtienne and A. Staehelin, Compt. rend., 1952, 234, 1453.207 L. Chalkley, J . Phys. Chem., 1952, 56, 1084.208 F. S. H. Head and H. A. Standing, J., 1952, 1457.209 P. W. M. Jacobs and F. C. Tompkins, Proc. Roy. Soc., 1952, A , 215, 254.210 H. Linschitz and J. Rennert, Nature, 1952, 160, 193.211 Idem, 2. Elektrochem., 1952, 56. 705.512 B. de B. Darwent, J . Chem. Phys., 1952, 20, 1673.21z0 B. de B. Darwent and F. G. Hurtubise, ibid., p. 1684.212h P. Agius and B. de B. Darwent, J . Chem. Phys., 1952, 20, 1679.213 J. D. McGilvery and C. A. Winkler, Canad. J . Chem., 1952, 30, 194.214 B.Atkinson, J.. 1952, 2684.215 G. 0. Schenk and K. Kinkel, Naturwiss., 1951, 38, 355.216 N. Uri, J . Amer. Chem. SOC., 1952, 74, 5808.2 1 7 P. J. Dyneand D. W. G. Style, J . , 1952, 212258 GENERAL AND PHYSICAL CHEMISTRY.discussed.21s In the case of formic acid, the emitter is the radical H.CO.0..In the case of methylene iodide no evidence has been obtained for the emis-sion of the methylene radical in the region 2400-5000 A.The quenching of the fluorescence of p-naphthylamine by carbon tetra-chloride in the gas phase has been studied2I9 and the phosphorescenceemission of benzophenone in light petroleum has been examined and re-corded.2m Two types of emission have been found, the proportion of eachdepending on the concentration of benzophenone.Polymerisation and depolymerisation.Nomenclature.-The Inter-national Union of Pure and Applied Chemistry have issued a report 221 onnomenclature in the field of macromolecules. One of the recommendations isthat the term " intrinsic viscosity " be replaced by " limiting viscositynumber,'' and that the units in which it is expressed be changed fromdecilitres/g. to ml./g.The term " depropagation reaction ' I has been introduced to denote theexact opposite of the normal propagation reaction in addition polymerisa-Condensation Polymerisation.-In some condensation-polymerisationreactions, condensation is preceded by the addition of one reagent to theother, e.g., urea and formaldehyde. References to work on the kinetics ofsuch preliminary reactions are given in another section (p.51). Work onthe kinetics of polycondensation of phenolic alcohols 225 has been publishedand it is shown that the kinetic treatment of condensation developed byFlory in polyesterification reactions is also applicable to the polyetheri-fication of phenolic alcohols.Free-radical Polymerisation.-(a) Some aspects of the kinetics ofradical polymerisation are summarised in the Tilden lo3 and Liversidge 226lectures of the Chemical Society.The first-order velocity constant forthe decomposition of ad-azodiisobutyronitrile (I) at 82" has been found to beNC.CMe,-N : N*CMe,.CN (I)practically independent of the solvent.227 By using this initiator for thepolymerisation of methyl methacrylate it has been conclusively shown thatonly about 50% of the radicals produced are effective in initiating poly-merisation and that the termination process must be by combination oftwo radicals.It is inferred that the RN2* radical is capable of initiating thepolymerisation of methyl methacrylate but that the R* radical is not?However this cannot be true for the polymerisation of styrene by (I), sincethe rate of evolution of nitrogen, as calculated from Breitenbach and Schind-ler's results,228 is actually slightly greater than that in the solvents used bytion.222-224(b) Initiators and initiation rates.218 D. W. G. Style and J. C. Ward, J., 1952, 2125.219 H. G. Curme and G. K. Rollefson, J. Amer. Cherr,. SOC., 1952, 74, 28.220 J . Ferguson and H. J . Tinson, J., 1952, 3083.221 J .Polymer Sci., 1952, 8, 257.222 F. S. Dainton and K. J. Ivin, Proc. Roy. SOC., 1952, A , 213, 207.223 W. G. Barb, ibid., p. 66.224 P. R. E. J . Cowley and H. W. Melville, ibid., A , 210, 461.325 H. Kammerer, Makromol. Chem., 1952, 8, 72, 85.226 H. W. Melville, J., 1952, 1547.227 L. M. Arnett, J. Amer. Chem. SOC., 1952, 74, 2027.228 1. W. Breitenbach and A. Schindler, Monatsh., 1952, 83, 724RETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 59Arnett.227 The initiator efficiency in various systems has been shown byradioactive tracer 229 and other methods 228, 230 to be generally between 0-5and 1.0.The rates of decomposition of the following initiators have also beenmeasured : aa-azobis-( ay-dimethylvaleronitrile) in ~ y l e n e , ~ ~ ~ 1 : 1'-azobis-cyclohexanecarbonitrile in ~ y l e n e , ~ ~ ~ benzoyl peroxide, cumenyl hydro-peroxide, and tert.-butyl hydroperoxide in methyl methacrylate and styrenerespectively,230 benzoyl peroxide in ally1 ethers,231 and para-substitutedtert.-butyl perbenzoates in diphenyl ether.232 The effect of structure ofdiacyl peroxides on the rates of initiation of polymerisation of styrene, andon their radical-induced decomposition has been in~estigated.~33 Tipper 234has studied the effect of water on the decomposition of benzoyl peroxide infour solvents. A comparative study has been made 235 of persulphates andbenzoyl peroxide as initiators in solution polymerisation.For some time it has been generally assumed that in the direct photo-chemical polymerisation of a vinyl monomer, the initial act of absorptionwould produce a diradical which would then grow in both directions bythe addition of monomer.However there is now clear evidence230>236that, in the cases of styrene and methyl methacrylate, photopoly-merisation proceeds via chains growing in one direction only. There isinsufficient evidence to say whether purely thermal polymerisation proceedsby diradicals, and Zimm and Bragg 237 have even suggested that, if there is notransfer process, self-termination of the biradical by cyclisation wouldprevent the formation of long-chain polymer. However it is possible thatthe polymerisation of styrene photosensitised by dyes such as trypaflavin,Illuminol RII, and Illuminol U proceeds via diradicals.238(c) Polymerisation of single monomers.Vaughan 239 has investigatedthe kinetics of the bulk polymerisation of styrene up to 100% conversion andsuggests that the termination and propagation reactions in turn becomediff usion-controlled. It has been shown that growing polystyrene chainsare terminated mainly by combination.236 The chain-transfer constants ofpolystyrene radicals with various halides have been determined.2403 241Iodides are more active than bromides which are more active than chlorides.Acid halides are exceptionally active.240 A preliminary account has beengiven of a method for the determination of the extent of self-branching inpolystyrene and other polymers.242 14C-Styrene is polymerised in thepresence of inactive polymers of high molecular weight (500,000). Transferwith the dead polymer occurs and the inactive polymer radical so formedproceeds to add active monomer.The polymerisation is performed under229 L. M. Arnett and J. H. Peterson, J . Amer. Chem. SOC., 1952, 74, 2031.230 B. Baysal and A. V. Tobolsky, J . Polymer Sci., 1952, 8, 529.231 N. G. Gaylord and F. R. Eirich, J . Amer. Chem. SOC., 1952, 74, 334.232 A. T. Blomquist and I. A. Berstein, ibid., 1951, '93, 5546233 W. Cooper, J., 1951, 3106; 1952, 2408.235 R. Sengupta and S. R. Palit, J., 1951, 3278.236 D. €3. Johnson and A. V. Tobolsky, J . Amer. Chem. SOC., 1952, 74, 938.237 B. H. Zimm and J. K. Bragg, J . Polymer Sci., 1952, 9, 476.238 M. Koizumi, 2. Kuroda, and A. Watanabe, J .Inst. Polytech. Osaka City Univ.,239 M. F. Vaughan, J . Appl. Chem., 1952, 2, 422; TtTans. Faraday Soc., 1952, 48, 576.240 J . A. Gannon, E. M. Feites, and A. V. Tobolsky, J . Amer. Chem. Soc., 1952, 74, 1854 .241 J . W. Breitenbach, Makromol. Chem., 1952, 8, 147.442 J . C. Bevington, G. M. Guzman, and TI. W. Melville, Nature, 1952, 170, 1026.234 C. F. H. Tipper, J., 1952, 2966.Ser. C., 1951, 2, 1; Chem. Abs., 1952, 46, 491560 GENERAL AND PHYSICAL CHEMISTRE*.conditions such that the polymer produced directly from monomer has arelatively low molecular weight (50,000), and the polymer originallyadded may then be isolated at the end of the experiment and itscontent of active monomer units determined. The transfer constant withdead polymer is found to be similar in magnitude to that of other transferreactions. Preliminary results are also given for vinyl acetate.A detailed branching mechanism has been proposed for the polymerisationof vinyl acetate, and a simplified kinetic analysis gives an expression for thedegree of branching in terms of six ratios.243 Four of these ratios have beenevaluated from experimental results.It appears that part of the branchingoccurs through ester linkages and that on hydrolysis of the polymer suchlinkages are broken.244 No such linkages are present in the polymer initiallyformed. The kinetics of the bulk and suspension polymerisation,Ms and theinhibited and retarded polymerisation of vinyl acetate have also beenstudied.246The chain-transfer reaction has been investigated in the catalysed poly-merisation of methyl metha~rylate,~~' and Matsumoto 248 has discussed thederivation of the mechanism of the termination process in the bulk poly-merisation, from the molecular-weight distribution in the polymer.The rate of the persulphate-catalysed polymerisation of methacrylicacid has been shown by Pinner 249 to decrease with decreasing acidity, andthis result is interpreted in terms of copolymerisation of the undissociatedacid with its less reactive anion.The polymerisation of vinyl chloride has been studied in solution bybenzoyl peroxide initiation,250 and in the gas phase 251 by means ofphotochemical initiation.In the polymerisation of allyl esters, termination takes place mainly bydegradative chain transfer with the monomer, a hydrogen atom being ab-stracted from the or-methylene group.It has been shown that abstraction ofhydrogen atoms from the acid-derived portion of the ester may also occurto a small extent.252 isoPropeny1 acetate behaves as an allyl compound,252whereas methyl isopropenyl ketone, containing a conjugated carbonylgroup, behaves like methyl m e t h a ~ r y l a t e . ~ ~ ~The rate of oxygen uptake in the inhibited polymerisation of acrylo-nitrile has been measured in four different systems.254 The products ofreaction in aqueous solution were quantitatively analysed and a highlyunstable peroxide isolated from non-aqueous systems.The photo-polymerisation of acetylene has been shown to yield small243 0. L. Wheeler, E.Lavin, and R. N. Crozier, J . Polymer Sci., 1952, 9, 157.244 R. Inoue and I. Sakurada, Chem. High Polymers, Japan, 1950,7, 211 ; Chem. Abs.,245 K. Noma and K. Irnai, ibid., 1951, 8, 44; Chem. Abs., 1952, 46, 11762.246 P. D. Bartlett and H. Kwart, J . Amer. Chem. Soc., 1952, 74, 3969.247 S. Basu, J. N. Sen, and S. R. Palit, Proc. Boy. Soc., 1952, A , 214, 247.248 M. Matsumoto, J . Polymer Sci., 1952, 8, 657.249 S. 13. Pinner, ibid., p. 282.250 G. V. Tkachenko, P. M. Khomikovskii, and S. S. Medvedev, Zhur. Fiz. Kkim.,251 M. Koizumi and K. Nakatsuka, J . Chem. Soc., J-n, Pure Chem. Sect., 1951, 78,162 N. G. Gaylord and F. R. Eirich, J . Amer. Chenz. SUG., 1952, 74, 337.253 G. Smets and L. Oosterbosch, Bdl. SOC. chim. Belg., 1952, 61, 139.264 K.C. Smeltz and E. Dyer, J . Amer. Chem. SOC., 1952, 74, 623.1952, 46, 4843.1951, 25, 823; Chem. Abs., 1952, 46, 3379.431; Chem. Abs., 1952, 46, 4916BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 61amounts of cycl~octatetraene.~~~ A review of the polymerisation of form-aldehyde has been The kinetics of polymerisation of methylacrylate have been 1 : 2-Dichloroethylene has been polymerisedby the application of high pre~sure.~~8 The inability of methyl a-tert.-butylacrylate to polymerise under a variety of conditions has been ascribedto potential steric hindrance in the polymer.a59Some aspects of the kinetics of polymerisation in systems in which polymeris precipitated have been discussed.260(d) Copolymerisation. Studies of the composition of copolymers as afunction of the composition of the monomer mixture have continued to giveinformation about the relative reactivity of monomers with polymer radi-cals.261-26* One of the most interesting reactions investigated was thecopolymerisation of ethylene with carbon monoxide at high pressure.2esCarbon monoxide behaves like maleic anhydride and the copolymer nevercontains more than 50% of carbon monoxide.The kinetics of copolymerisation of four further monomer pairs have been:investigated : methyl methacrylate and $-methoxystyrene, styrene andm-hydroxy~tyrene,~~~ but-l-ene and sulphur di~xide,~~O and styrene andsulphur dioxide.271 In the first system it has been shown that d,[=kt, 12/(kt, ll;kt, 22)0'5], which is a measure of the " cross-termination "process, varies from 12 to 27 as the concentration of P-methoxystyrene isincreased, whereas in the second system a value 4 < 1 fits the results quitewell. In both copolymerisations involving sulphur dioxide it has beenfound necessary to assume that one of the effective monomers is a 1 : 1complex, the presence of which has been demonstrated in each case bylight-absorption measurements. The ceiling temperature effect in thesulphur dioxide-olefin systems has been shown to be caused by the onset ofthe depropagation reaction, and the kinetics permit evaluation of theequilibrium constant, and hence of the heat and entropy changes, of thepropagation-depropagation reaction.Gee 272 has subjected to detailed analysis existing data concerning thephysical properties of liquid sulphur and has shown that the sudden increasein viscosity at 159" is due to the onset of polymerisation of (principally)S, molecules. The heat and entropy changes, unlike the values in normal255 2.Kuri and S. Shida, Bull. Chem. SOC., Japan, 1952, 25, 116.256 R. Sauterey, Ann. Chzm., 1952, 7, 5.2 5 7 P. S. Shantarovich, lzvest. Akad. Nauk, S.S.S.R. Otdel. Khiiiz. NauJz, 1952, 243;259 J. W. C. Crawford and S. D. Swift, J . , 1952, 1220.f60 C. H. Bamford, W. G. Barb, and A. D. Jenkins, Nutuve, 1952, 169, 1044.261 H. C. Haas and M. S. Simon, J . Polymer Sci., 1952, 9, 309.262 C. C. Price and R. D. Gilbert, ibid., p. 577.263 W. S. Port, E. F. Jordan, J . E. Hansen, and D. Swern, ibid., p.493.264 S. P. Mitzengendler and V. A. Chekhovskaya, Zkzw. Przklad. Khim., 1951, 24,Z65 S. N. Usliakov, S. P. Mitzengendler, and B. M. Polyatskina, ibid., p. 289; Chcnz.2 6 6 J . W. Vanderhoff, Macrofilm Abs., 1951, 11, 541; C h e w Abs., 1952, 46, 772.2 6 7 M. Yoshida and I. Sakurada, Chenz. High Polymers, Japan, 1950, 7, 334; Chem.268 D. D. Coffman, P. S. Pinkney, F. T. Wall, W. H. Wood, and H. S. Young,J . Amer. Chem. Soc., 1952, 74, 3391.269 E. P. Bonsall, L. Valentine, and H. W. Melville, Trans. Furaduy Soc., 1952, 48, 763.270 F . S. Dainton and K. J. Ivin, Pvoc. Roy. SOC., 1952, A , $319, 96, 207.2 7 1 W. G. Barb, ibid., pp. 6G, 177. 272 G. Gee, Tvans. Faraday Soc., 1962, 48, 515,Chem. Abs., 1952, 46, 9384. 258 K. E. Weale, J., 1952, 2223.485; Chem.Abs., 1952, 46, 9885.Abs., 1952, 46, 774.14bs., 1952, 46, 484462 GENERAL AND PHYSICAL CHEMISTRY.polymerisations, are both positive and a '' floor temperature " rather thana ceiling temperature is therefore found with sulphur.A general account of the degradation of polymershas been given by Burgess; 273 and Simha 274 and Madorsky 275 have sum-marised the behaviour of different polymers in terms of the percentagemonomer in the volatile products and the rate of change of molecular weightof the residue. Polymethyl methacrylate is one of the few polymers inwhich clean reversal to monomer occurs. In this case it has been shown thatthe depolymerisation can be induced photochemically above 130" andinvolves initiation, depropagation, and, in most circumstances, mutualtermination of chains.276 Using intermittent light to determine the lifeof the kinetic chains, and a retarder method to determine the initiation rate,Cowley and Melville 276 were able to deduce, for the first time, an experimentalvalue for a depropagation velocity constant.The value of this is in reason-able agreement with theoretical predictions and leads to an acceptable valuefor the change of entropy during polymerisation. On the other hand kt isabnormally small compared with radical-termination reactions in dilutesolution and this is attributed to the fact that the reaction is occurring ina highly viscous polymer. Simha 277 has discussed these results in terms ofhis theoretical treatment.278 Jellinek 279 has also derived theoreticalkinetic equations for the degradation of polymers, and has published apreliminary account of some experiments on the degradation of poly-styrene.280 The products of degradation of polystyrene 281 and polyvinylacetate 2g2 have been investigated.In the latter case acetic acid is evolvedby a chain reaction proceeding without the agency of free radicals, and aresidue of polyacetylene is left. Smets and Tasset 283 have reported data onthe degradation of four polymers in the presence of benzoyl peroxide.Ionic Polymerisation.-(a) Cationic polymerisation. When Friedel-Crafts catalysts (A) are employed as initiators, it appears that the presenceof a trace of a co-catalyst (BC), e.g., water, is generally required for thecatalyst to be effective.The catalyst and co-catalyst interact by a reactionsuch as A + BC ,--+ AB- + C+ to give a cation C+ which initiates polymeris-ation. A " system " will therefore be defined by monomer-catalyst-co-catalyst-solvent, It is extremely difficult to remove the last traces of waterfrom any system and where there is a possibility of a trace being presentthis is indicated below by H20(?).In the system isobutene-TiC14-CC1,*C02H-hexane, it has been shown 284by infra-red analysis that, in agreement with earlier work, the predominantend group is the methylene group. Trisubstituted double bonds andtrichloroacetate groups were also found. This suggests that termination(e) Depolymerisation.273 A. R. Burgess. J . Afifil. Chem., 1952, 78.274 R.Simha, Trans. N.Y. Acad. Sci., 1952, 14, 151.s y b S. L. Madorsky, J . Polymer Sci., 1952, 9, 133.276 P. R. E. J . Cowley and H. W. Melville, Proc. Roy. Soc., 1952, A , 210, 461; A ,278 R. Simha and L. A. Wall, J . Phys. Chem., 1952, 56, 707.279 H. H. G. Jellinek, J . Polymer Sci., 1952, 9, 369.280 H. H. G. Jellinek and L. B. Spencer, ibid., 1952, 8, 573.B. G. Achhammer, M. J. Reiney, L. A. Wall, and F. W. Reinhart, ibid., p. 555.282 N. Grassie, Trans. Faraday Soc., 1952, 48, 379.288 G. Smets and G. Tasset, Chim. Peintures, 1952,15,281; Chem. Abs., 1952,46,11762.384 M. St. C. Flett and I?. H. Plesch, J . , 2952, 3355.211, 320. 277 R. Simha. J . Polymer Sci., 1952, 9, 465BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 63occurs by loss of a proton from two possible positions a t the end of thegrowing cation, and by interaction with the trichloroacetate anion.Although Jordan and Mathieson 285 have reported the consumption ofcatalyst in the systems M-AlC1,-H20(?)-CCl, where M is styrene or M-methylstyrene, there is no evidence that the catalyst fragment is incor-porated in the polymer molecule.On the contrary, there is clear evidence 288that the catalyst is not incorporated in the polymer in the systems : styrene-SbC1,-H20 -nitrobenzene and styrene- SbC1, - H20( ?) - cyclohexane. Noradioactivity was detectable in the polymer when radioactive SbC1, wasused as catalyst. Williams and Bardsley 289 have studied the systemstyrene-SnCl,-HCl-CCl, a t low concentrations of styrene where the mainproduct is l-phenylethyl chloride.However, although the kinetics areconsistent with a carbonium ion mechanism, it is not possible to say whetherinitiation is by interaction of the catalyst with hydrogen chloride or withstyrene.Jordan and Mathieson have discussed their results on styrene286 andhave made a quantitative comparison with the results on a-methylstyrene.285They have also concluded 287 from molecular-weight distribution data 2mthat in the latter case termination is by monomer deactivation and solventtransfer.Norrish and Russell 291 have reported kinetic and molecular-weightmeasurements in the system isobutene-SnC14-H20-C2H,C1. Water wasshown to be essential for reaction. It was concluded that further work wasrequired with very highly purified materials before the mechanism could kefully elucidated.Further work has been published on the iodine-catalysed polymerisationof vinyl ethers.292 The effect of a number of side groups has been examinedwith results which accord with expectation.Wooding and Higginson 293 have made thefirst detailed kinetic study of anionic polymerisation.The results forpolymerisation of styrene in liquid ammonia, catalysed by potassamide, arein accord with a mechanism involving addition of the amide ion NH2- to themonomer, propagation, and termination by reaction of the growing chainwith the solvent leading to re-formation of the amide ion. A qualitativesurvey has been made of the reactivity of various anion bases, and theobserved correlation between base strength and reactivity is in accord withthe anionic mechanism of polymerisation.The interesting suggestion has been made that the formation ofrhodizonic acid when carbon monoxide reacts with liquid ammonia in thepresence of sodium, occurs through an anionic polymerisation in which sixcarbon monoxide molecules are added to an amide ion.294The relative ease of addition of two mono-mers to a growing polymeric entity may be expected to vary according to(b) Anionic polymerisation.(c) Ionic copolymerisation.286 D.0. Jordan and A. R. Mathieson, J., 1952, 611, 2354.28E Idem, ibid., p. 621. 287 Idem, ibid., pp. 2358, 2363.288 R. 0. Colclough, J . Polymer Sci., 1952, 8, 467.289 G. Williams and H. Bardsley, J., 1952, 1707.290 A.B. Hersberger, J. C. Reid, and R. G. Heiligmann, I n d . Eng. Chem., 1945, 37, 1073.291 R. G. W. Norrish and K. E. Russell, Trans. Faraday Soc., 1952, 48, 91.292 D. D. Eleyand J. Saunders, J., 1952, 4167.293 N. S. Wooding and W. C. E. Higginson, J., 1952, 760, 774, 1178.294 F. Leonard and P. Fram, Science, 1952, 118, 22864 GENERAL AND PHYSICAL CHEMISTRY.whether such an entity is an anion, a free radical, or a cation, and thishas been verified experimentally.295 The anionic copolymerisation ofbutyl vinyl sulphone with acrylonitrile 296 and the effect of reaction con-ditions on the monomer reactivity ratios for the system styrene+-chloro-styrene-SnC1, have been investigated.297 Other systems have also beenstudied 298b 299 and it has been found that for the cationic copolymerisation ofa given monomer with a series of substituted styrenes, the reactivity ratio is afunction of Hammett’s G value.298It is clear from the report 3oo of a conference held at Stoke that interestingdevelopments are to be expected in this field.Eliltulsion PoZynze~isatiolz.-This does not strictly come into thecategory of homogeneous reactions but it should be noted that it has beenpossible to derive from the kinetics,301 on the basis of Smith and Ewart’stheory,302 values for propagation velocity constants which are similar tothose obtained by the more usual methods.Radiation Chemistry.-(a) Primary Processes.-Most of the experimentaldata available on primary products has been obtained by the use of the massspectrometer.Therefore, strictly speaking, such data apply only to thecase of low-energy electron bombardment. Investigations of this kindinclude the measurement of appearance potentials of ions formed from~yclopropane,~~ cyanogen and methyl cyanide,304 and hydrogen peroxide.305Norton5O6 has studied the ionisation produced in water vapour in the pres-ence of an excess of hydrogen. An unusually sharp maximum is obtainedin the positive current at mass 19. This is due to the ion H,O+ formed in thefollowing process :H,O + H20t + H 4 OH (”+) 7 OH(27r)OH(21;+)H30Electron3 3 3 0 impact H3O+ + eThere is still no experimental information on the nature of the primaryproducts of high-energy bombardment processes. Until such results areavailable it will not be clear to what extent the different radiation chemicaleffects of, say, cr-particles and electrons are due to the different spatial dis-tribution of the entities formed or to differences in the entities themselves.There has also been very little direct experimental investigation of theprocesses immediately subsequent to the primary act.In the gas phase theprobability of electron exchange in hydrogen has been measured.307 The296 F. R. Mayo and C. Walling, Chem. Reviews, 1950, 46, 277.296 F. C. Foster, J . Aluter. Chem. SOC., 1952, 74, 2299.297 C. G. Overberger, L. H. Arond, and J. J. Taylor, J . Anzer. Chenz. Suc., 1952, ’73,298 C. G. Overberger, L. W. Arond, D. Tanner, J. J. Taylor, and T. Alfrey, ibid.,2g9 Y.Landler, J . Polymer Sci., 1952, 8, 63.300 P. H. Plesch, Nature, 1952, 169, 828.301 M. Morton, P. P. Salatiello, and H. Landfield, J . Polymer Sci., 1952, 8,111,215, 279.302 W. V. Smith and R. H. Ewart, J . Chem. Phys., 1948, 18, 592.3m F. H. Field, J . Chew. Ph sics, 1952, 20, 1734.304 C. A. McDowell and J. J W a r r e n , Trans. Faraday Soc., 1952, 48, 1084.305 A. J. B. Robertson, ibid., p. 228.306 F. J. Norton, Phys. Review, 1952, 85, 154.397 E. E. Muschlitz and J. H. Simons, J . Phys. Chem., 1952, 56, 837.5541.p. 4848BETTS et aE. : THE KINETICS OF HOMOGENEOUS REACTIONS. 65ions H,+ and Hf do not exchange appreciably with the H, molecule but theion H,+ does so readily. In hydrocarbon gases all the ions H,", H2+, and H+exchange readily, the explanation probably being that the large moleculescan absorb considerable amounts of energy as vibrational energy.It hasbeen found that the formation of the H,+ ion in hydrogen occurs by theprocess, H,+ + H, -+= H3+ + H, the H,+ ion being dissociated.308Hasted 309 has studied the charge-exchange cross-sections of severalprocesses, including that of Of ions in water, and cross-sections for processesof the type A- + B -+ A + B + C have also been measured. Suchcross-sections are expected to be negligible unless very energetic ions andatoms are presentJ31* but for 0-, Cl-, and F- in various gases unexpectedlylarge cross-sections were found. This is interpreted as due to the presence ofexcited states of these ions having low electron affinities.It has been sug-gested that electron-capture processes in polyatomic molecules generallyfall into two classes : 311AB + e -+A + B- . . . . . . . - (1)AB+e--jA++B-+C . . . . . . (2)Examples of type (1) are cyanogen and methyl cyanide, whilst type (2) isexemplified by carbon tetrachloride. Processes of type (1) are resonanceprocesses necessitating a suitable crossing in the potential-energy curves ofthe relevant electronic states of the molecule AB and the ion AB-. Studiesof the type of electron capture occurring in given cases may thus yieldinformation about the potential-energy curves of polyatomic molecules.The fact that processes of type (1) are resonance processes is significant in thatit opens up the possibility of investigating the ultimate fate of the ion B-in solution.312 A review of the reactions of gaseous ions has been presentedby Ma~sey.~lOI n a series of papers Magee and Burton have discussed certain initialprocesses in radiation chemistry.Semiquantitative treatments of simplecases followed by qualitative extension to more complex systems have led tothe following general conclusions, and the relevance of each of these toradiation chemistry, is discussed. (i) Thermal electron capture by a com-plex molecule positive ion should lead in most cases to immediate dissoci-ation into two particles, one of which is excited. The particles are morelikely to be radicals than molecules.313 (ii) Under suitable conditions low-energy electrons tend to form negative ions via capture by neutral molecules,rather than to neutralise positive i0ns.~1~ (iii) Charge transfers occurringby a resonance process, e.g.,may have large cross-sections ; non-resonant processes of the typenecessitate the crossing of two potential-energy curves of the system (A + B)+A' + A + A + A+A++B-+AfB+308 R.L. Murray, J. Appl. Phys., 1952, 23, 6.309 J. B. Hasted, Proc. Boy. Suc., 1952, A , 213, 235.310 H. S. W. Massey, Discuss. Faraday SOC., 1952, la, 24.311 J. D. Craggs, C. A. McDowell, and J . W. Warren, Trans. Faraday SOC., 1952, 48,312 F. S. Dainton, Discuss. Faraday SOL, 1952, 12, 10.313 J. L. Magee and M. Burton, J. Anzer. Chem. Soc., 1950, 73, 1965.314 Idem, ibid., 1951, ?3, 523.1093.REP.-VOL. XLIX. 66 GENERAL AND PHYSICAL CHEMISTRY.and are accompanied by vibrational excitation or dissociation ; 316 in general,complex formation is involved, lifetimes may be of the order of seconds, andother processes may therefore compete before the charge transfer is com-~ l e t e .~ ~ ~ (iv) Simple changes of the typeA+ + B- --+ C + Dare not expected to occur since charge transfer takes place a t a rather largedistance. Highly excited states of A + B are expected and the end pro-ducts should commonly be radicals.317Considerable interest was recently aroused by the work of Dee andRichards.318, 319 These authors claimed to have shown that an ultra-violetlight emission is produced by the a-particle bombardment of liquids. Thelight is strongly absorbed by the irradiated material and the wave-lengthinvolved probably lies between 1500 and 1700 A.The emission of this lightand its subsequent absorption were suggested as a mechanism for the for-mation of chemically active radicals. Miller and Brown 320 have attemptedto confirm these results, without success. They conclude that no appreciableemission of light of wave-length greater than 1800 A takes place when wateris bombarded with =-particles and that appreciable emission of light ofshorter wave-lengths is unlikely. Other workers have also been unable toobtain results consistent with those of Dee and Richards.321, 322 It isinteresting that although the ultra-violet light emitted from water exposed toy- or p-radiation is purely due to the Cerenkov effect 3z33 324 and that noultra-violet emission is found when high-intensity 50 kvp X-rays areice a t a temperature of -100" to -170" does emit ultra-violet light underthe latter type of irradiation and the emission is not of Cerenkov origin.325The light intensity is linear with dose rate over a large energy range and has amaximum energy at 3400 A.In support of these observations tritium-iceis found to be self-l~minescent.~~~~ 326A new conception of the processes occurring in liquids upon irradiationhas been suggested.327 Chemical activity is considered to be due to twotypes of excited species, M* and Mf. The M* species is produced in primaryprocesses occurring either in the main particle track or in its " spurs "(&ray tracks). It has a much smaller energy than MS and is persistent.The M* species is considered to result from ion neutralisation.It decomposesnear its production site into uncharged radicals. Most of the M* speciesare in the lowest excited state but can participate in reactions by excitonor photon transfer if energy traps are present in the solution.s15 J. L. Magee, J . Phys. Chem., 1952, 56, 555.316 M. Burton and J. L. Magee, ibid., p. 842.317 J. L. Magee, Discuss. Faraday SOC., 1952, 12, 33.318 P. I. Dee and E. W. T. Richards, Nature, 1951, 168, 736.319 E. W. T. Richards, Discuss. Faraday SOC., 1952, 12, 45.320 See N. Miller, Discuss. Faraday SOC., 1952, 12, 46.a21 See M. Magat, ibid., p. 48.322 31. A. Greenfield, A. Norman, and P. M. Kratz, U.S. Atomic En. Cornmiss.323 M.A. Greenfield, A. Norman, A. H. Dowdy, and P. M. Kratz, US. Atomic324 F. S. Dainton, Discuss. Faraday SOC., 1952, 12, 44.325 L. I. Grossweiner and M. S. Matheson, J . Chem. Phys., 1952, 20, 1654.326 W. M. Jones, ibid., p, 1974.327 M. Burton, J. L. Magee, and A. H. Samuel, ibid., p. 760.Report, 1952, UCLA-218.En. Commiss. Report, 1952, UCLA-211BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 67(b) A ctinometry. Owing to their comparative straightforwardness andease of handling, chemical methods of dosimetry are tending to be almostuniversally adopted. Of the numerous systems proposed for such measure-ments the ferrous sulphate system appears to be the most generally satis-factory and has been the subject of the most detailed calibration as yet.328A useful review and assessment of the various systems which have beenproposed for chemical dosimetry has been given.329 It is suggested that theterm “ chemical dosimetry ” should be replaced by “ actinometry,” followingthe nomenclature of photochemistry.It is unfortunate that a lack ofagreement exists between different workers as to the value of the oxidationyield of ferrous ion in aerated solutions which are conventionally 0 - 8 ~ insulphuric acid. Most authors agree that for X- and y-radiation, at doserates of up to 1000 r,/min., the yield for ferrous oxidation is of the order of20 molecules oxidised per 100 ev energy absorbed (G = Z O ) , and Miller andWilkinson have rechecked this result under varying conditions. However,using W o y-radiation, Hochanadel 330 obtained a value of G = 15.5 & 0.3,the method of calibration employed being a calorimetric one.As Hocha-nadel’s range of dose rates (1500--15,000 r./min.) was larger than that of theother authors, and since there is general agreement that the yield ultimatelyfalls on increasing the dose rate, it was thought that this may be an ex-planation of the discrepancy. However, Hardwick 331 found the yieldunchanged up to a dose rate of at least 4200 r./min. with 2000 kvp X-raysand Rigg, Stein, and Weiss,s2 using a dose rate of -3000 r./min., foundG = 19.9. Allen,333 moreover, found a constant yield over a dose-raterange of 100--10,000 r./min. with 2 Mv X-rays. It seems clear thereforethat this discrepancy is only to be settled by further experiment.Anothereffect observed in this system, which is confirmed by two investigator^,^^^ 335is that the yield falls when low-energy p-radiation is used. For high-energyp-radiation the yield remains the same as for X-radiation,336 and the fallingyield for low-energy p-radiation has been explained in terms of the differenceof ion density between the two types of r a d i a t i ~ n . ~ ~ This explanationreceives support from the fact that the yield for a-radiation in aeratedsolution is even lower, viz., G = 6-7-59 337 (depending on the exact value ofW for argon). A very marked fall in yield has been observed on increasingthe dose rate with 0.92-Mv electrons from lo3 to lo6 r./min.338 It has beenclaimed that ferrous sulphate actinometry is suitable for a-radiati~n,~~’ pileradiati0n,~3~, 340 and 24 Mevp X-raysM1 Evidence has been quoted to showthat a-radiation and lithium recoil particles do not behave additively to theferrous system.342 Though a reason for this has been suggested343 the32* N.Miller, J . Chem. Phys., 1950, 18, 79.32* N. Miller and J. Wilkinson, Discuss. Furuduy Soc., 1952, 12, 50.330 C. J. Hochanadel, J . Phys. Chem., 1952, 56, 587.331 T. J. Hardwick, Discuss. Faraday SOC., 1952, 12, 112.332 T. Rigg, G. Stein, and J. Weiss, Proc. Roy. SOL, 1952, A , 211, 375.333 A. 0. Allen, Discuss. Furuduy SOC., 1952, 12, 114.334 T. J. Hardwick, ibid., p. 203.335 E. J . Hart, U.S. Atomic En. Commiss. Report, AECU-1534.336 T. J. Hardwick, Cunad. J .Chem., 1952, 30, 39.337 N. Miller, Discuss. Furaday Soc., 1952, 12,110.3sD E. Saeland and L. Ehrenberg, Acta Chew. Scund., 1952, 6, 1133.340 J. Wright, Discuss. Faraday SOC., 1952, 12, 60.341 R. W. Hummel and J. W. T. Spinks, J . Chem. Physics, 1952, 20, 1056.342 J. Wright, Discuss. Furaday SOC., 1952, 12, 116.338 C. B. Amphlett, ibid., p. 272.843 M. Burton, ibid., p. 11768 GENERAL AND PHYSICAL CHEMISTRY,proposal is hardly borne out by the fact that a-radiation and 50 kvp X-radiation appear to be additive in their effects.337Another actinometer which has been investigated in some detail is theceric sulphate system.w When X - or y-radiation or high-energy p-radia-tion 336 was used this reaction was found to have a lower yield than the ferrous-ion actinometer.However the yield is independent of dose rate up to atleast 45,000 r./min. for 2000 kvp X-rays or 140,000 r./min. for 50 kvp X-rays,independently of the presence or absence of oxygen and independently of theceric-ion concentration down to the lowest limits which can be studied.It suffers the disadvantages of being more sensitive to impurities, and ofexhibiting an increasing yield with decreasing electron energy.334Compared with these two systems the benzene-water system 345 hasseveral disadvantages. Thus the concentration independence of yield isless well fulfilled than for the ferrous system, the yield is much lower, theanalysis is clumsy, and the reaction may exhibit a post-irradiation effect.346On the other hand this actinometer may prove useful at higher dose-rates.Other possible systems which have been proposed for actinometry arethe formic acid system,347 the diphenylpicrylhydrazyl systemYw8 a phosphateester s y ~ t e m , ~ 9 and the use of polyvinyl chloride Many systemshave been investigated for possibilities as chemical a~tinometers.~~~ Kan-wisher s62 has developed an ingenious method of measuring dose rates withthe chloroform-water system.In order to obtain reasonable standardisation of dose measurementsand expressions of yield it has been proposed that : 353 (i) Yields should beexpressed as molecules converted per 100 ev energy absorbed.This shouldbe designated by G where the actual energy input is measured. (ii) Theyield should be written as G’ if energy inputs are obtained from chemicalactinometry; in this case full details of conversion factors should be given.(iii) The yield should be written as Gm if ferrous sulphate actinometry isemployed, the value of G(Fe2+ ,--+ Fe3+) being provisionally taken as 20.(iv) The change to which G refers should be indicated, e.g., G(H20,).It isgenerally felt that the ferrous sulphate system would be the best for universaladoption in the X - and y-ray dose-rate range from 0 to at least103 r./min.3as 355Since the suggestion byEyring, Hirschfelder, and Taylor 356 it has. been commonly assumed thatboth ionisation and excitation processes play a part in radiation chemicalreactions, and the investigations by Essex and his co-workers 3g7-360 supportthis view.Nevertheless the polymerisation of acetylene by or-particles(c) Non-aqueous vapour and liquid systems.344 T. J. Hardwick, Canad. J . Chem., 1952, 30, 23.345 M. J. Day and G. Stein, Nature, 1949, 164, 671.346 J. Wright, Discws. Faraday Soc., 1952; 12, 114.34* A. Chapiro, ibid., p. 115.350 E. J. Henley and A. Miller, Nucleonics, 1951, 9, No. 6, 62.351 Illinois Univ. Progress Report No. 2, 1951 ; Nuclear Sci. Abs., 1952, 6, No. 4004.352 J. W. Kanwisher, Nucleonics, 1952, 10, No. 5, 62.353 M. Burton, Discuss. Faraduy SOC., 1952, 12, 317.354 F. S. Dainton, ibid., p. 10.356 H. Eyring, J. 0. Hirschfelder, and H. S. Taylor, J . Chem. Phys., 1936, 4, 479.357 C. Smith and H. Essex, ibid., 1938, 6, 188.3 5 * A. D. Kolumban and H.Essex, ibid., 1940, 8, 450.359 N. T. Williams and H. Essex, ibid., 1948, 16, 1153.360 Idem, ibid., 1949, 17, 995.347 E. J. Hart, ibid., p. 111.*49 B. E. Conway, ibid., p. 250.865 N. Miller, ibid., p. 318BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 69seems to provide an exception to this generalisation inasmuch as the wholeeffect can be accounted for on the basis of i ~ n i s a t i o n . ~ ~ ~A striking contrast between the chemical effects produced by irradiationin the liquid and the gaseous state is provided by a study of the a-particleirradiation of n-hexane, cyclohexane, and benzene.362 In the gaseous phasethe yields for each substance differ by a maximum factor of three, a com-pletely different result from the effect of electrons on the liquids.363In contrast to earlier findings for the effect of =-particle irradiation onethylene, an investigation of the y-irradiation of this gas showed no sub-stantial yield of hydrogen gas or of saturated hydrocarbons.364 The mainreaction is a chain polymerisation having an ionic yield of about 30.365The synthesis of ammonia by y-irradiation of nitrogen-hydrogen mixtureshas also been In this reaction the glass surface area is an im-portant factor.Three methods have now been used to obtain information concerningthe chemically active species produced in organic liquids under the influenceof ionising radiations.The first method comprises the use of iodine having :Ihigh specific activity of 1311.367 Radicals formed during radiolysis combinewith iodine to give iodides in small yield. To this product appropriateinactive alkyl iodide carriers are added and fractional distillation , followedby radioactivity measurement, permits an estimation of relative free-radicalyields.This method has been applied to the radiolysis of alkanes and alkyliodides in both the liquid and the gaseous p h a ~ e . ~ ~ 8 Almost all the radicalsformed are considered to react by the process R + I, -+RI + I. Ahigh yield of the parent substance in the case of the vapourised iodidesindicates that the C-I bond is that most frequently broken, whilst in theliquid state there is a greater ratio of C-C to C-I bond rupture. Very littlehydrogen iodide is formed, indicating only a small probability of C-Hbond rupture.With alkanes the radical corresponding to the parent sub-stance is no longer predominant except for methane. The results hereobtained are complementary to mass-spectral data.369 For example, themost important peak in the mass-spectrum of neopentane is C,H,+, whilst onradiolysis a large yield of CH, radical is found. Hence an important primarystep appears to beC(CH3)4 -f C(CH3)3+ 4- CH3 + eDose rate variation had no effect on the decomposition patterns but in thecase of ethyl iodide there were differences in the ratios of products for 2 MvX-radiation, y-radiation, and 50 kvp X-radiation. In experiments of thiskind an increase of yield at high iodine concentrations can be explained onthe basis of higher energy absorption by the heavy iodine atoms.370361 S.C. Lind, J . Phys. Chem., 1952, 56, 920.362 V. P. Henri, C. R. Maxwell, W. C. White, and D. C. Peterson, ibid., p. 153.363 M. Burton, ibid., 1948, 52, 564.364 Yale Univ. Progr. Report, No. 3, 1952, NYO-3309.365 Yale Univ. Progr. Report, No. 2, 1952, NYO-3310.3 6 6 mi. A. Selke, C. Kardys, E. V. Sherry, and R. C. Jagel, U.S. Atomic En. Commiss.367 R. R. Williams and W. H. Hamill, J . Amer. Chem. SOC., 1950, 73, 1857.368 L. Gevantman and R. R. Williams, J . Phys. Chem., 1952, 56, 569.369 A. Langer, ibid., 1950, 54, 618.370 C. C. Schubert and R. H. Schuler, J . Chem. Phys., 1952, 20, 518.Report, 1952, NYO-332770 GENERAL AND PHYSICAL CHEMISTRY.The other two methods so far used in following radical production are thetrapping of radicals by (a) the initiation of polymerisation, and (b) the re-action with diphenylpicrylhydrazyl (DPPH) radicals.Both of thesemethods have recently been employed for the determination of the numberof free radicals produced in a series of organic liquids by given doses ofy - r a d i a t i ~ n . ~ ~ ~ , 3729 373 Under the conditions of experiment the radical-trapping reaction is considered to be much more probable than radical-recombination reactions and energy yields for radical formation have beenevaluated on this basis. Results obtained by the two methods agreereasonably well in most cases, though it has been pointed out that owingto possible breakdown of the hydrazyl radical itself one would not reallyexpect to be able to count the radicals formed with accuracy greater than afactor of 2.374Manion and Burton have studied the radiolysis of mixtures of hydro-carbons in the liquid state.375 The results are consistent with a mechanismin which both ionisation transfer and excitation transfer play significantroles.Owing to this effect, radiolysis of mixtures yields products which arenot predictable on a simple law of averages. In a mixture of two com-ponents, whichever component is first ionised, there is known to follow a rapidtransfer of ionisation to the species of lower ionisation potential. Manion andBurton’s results indicate that excitation transfer usually behaves similarly,this effect being most readily appreciated in the case of radiolysis ofcyclohexane-benzene mixtures in which the two effects appear to act inopposition.Fundamental differences in mechanism are shown to existbetween radiolyses in the gaseous and the liquid state for cyclohexane-benzene mixtures.*A mass-spectrometric examination of benzene and deuterobenzeneindicated that the ratio of ions C,H,+/C,D,+ was constant for different valuesof m and n, whilst the ratio C6H,+/C6D,+ tended to increase as n decreased.376A different mechanism of formation of the two types of ion was thus in-dicated. Radiolysis of the two substances by 1.5 Mv electrons gave theresult G(H,)> G(C,H,) for benzene, and G(D,) < G(C,D,) for deutero-benzene, again indicating that at least two mechanisms are involved in theradiolysis of benzene and that these do not contribute to the same extent forC6H6 and C6D6.The results have been explained in terms of bond ruptureand rearrangement of the parent ion, and the difference in zero-point energybetween C-D and C-H bonds. It is also shown that the molecules C,H, andCGD6 exhibit mutual protection in a mixture and the implications of this arediscussed.The rate of polymerisation of styrene by y-radiation, in the dose-rate range2400-5500 r./min., has been found to be proportional to the dose rate.381This is contrary to earlier rep0rts.38~~ 371 Minder and Heydrich 383 haveinvestigated the radiolysis of halogenated hydrocarbons in alcohol andacetone solution. Halogen acids are formed in amount depending on the371 A. Chapiro, J . Chzm. phys., 1950, 47, 747.372 Idem, Compt. rend., 1951, 233, 792.373 A.Prevot-Bernas, A. Chapiro, C. Cousin, Y . Landler, and M. Magat, Discuss.374 W. Wild, ibid., p. 127.375 J. P. Manion and M. Burton, J . Phys. Chem., 1952, 56, 560.376 S. Gordon and M. Burton, Discuss. Furuday Soc., 1962, 18, 88.Faraday Soc., 1952, 12, 98.* Cf. ref. 362BETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 71concentration, the number of halogen atoms in the compound, and the typeof binding. It is claimed that, in order to effect decomposition of chloroformby y-radiation alone or in solution, oxygen must be present.377, 378 Goodyields of salicylic acid are produced on irradiation of benzyl alcohol in ethylalcohol with l-Mev electrons.379 A bibliography on the effect of a-, p-, y-,and X-rays on organic compounds has been compiled.3mA widespread interest continues tocentre upon radiation effects induced in aqueous systems, consequently noapology is made for devoting most attention to their discussion.Althoughit has been accepted for some time that the ultimate formation of H atomsand OH radicals seems to offer the most convenient explanation of the be-haviour of irradiated water, nevertheless as more experimental data becomeavailable there is an increasing feeling that our conceptions regarding thenature of the primary reacting entities, and for that matter the particularform of the substrate with which they react, are too rudimentary. Despitethe fact that almost every possible radical or ion has now been invoked toexplain this or that aspect of radiatian chemical effects in water, togetherwith almost every possible permutation of kheir formation and breakdown,results continue to appear which meet with no explanation on existingconcepts, or which seem incompatible with those of other workers.Justhow far the sensitivity of some of the systems to very small changesin experimental conditions is responsible for the discrepancies it wouldbe hard to say at present, but the recent Faraday Society Discussion384indicated that several anomalies may in fact be due to this cause.It has several times been pointed out that the majority of radiationchemical reactions in aqueous solutions are 386 and the usualvalue of the equivalent reduction potential (e.r.p.) of irradiated water, asjudged from published experimental results, indicates that the oxidisingpower of irradiated water cannot be due to a mixture of H atoms and OHradicals alone in equal proportions. It has been shown387s 388 that anyargument based on a difference of distribution of H atoms and OH radicalscannot explain this effect, but the existence of the ions Hz+ 389 and HO+ 387(or 0 atoms) may help to give the observed result.It has also been suggestedthat all cases of radiation reduction so far observed can be explained by theaction of OH radicals or hydrogen peroxide.3w This indicates that H atomsappear to be very unreactive, and in fact raises the suspicion that they maynever have independent existence. From this point of view it has been(d) Water and aqueous solutions.377 J.F. Suttle and J. W. Schulte, Discuss. Furaday SOC., 1952, 12, 317.378 J. W. Schulte, J. F. Suttle, and R. Wilhelm, US. Atomic En. Commiss. Report,379 B.P., 1952, 665,263.380 F. Sachs, Literature Search for Carbide Chemicals Co., 1952, Co(Y-12).381 B. Manowitz, R. V. Horrigan, and R. H. Bretton, U.S. Atomic En. Commiss.382 A. Chapiro, Corn@. rend., 1949, 228, 1490.383 W. Minder and H. Heydrich, Discuss. Furaday Soc., 1952, 12, 305.384385 M. Haissinsky and M. Lefort, Compt. rend., 1949, 228, 314.388 M. Haissinsky. Discuss. Faraday SOC., 1952, 12, 133.387 F. S. Dainton and E. Collinson, Ann. Rev. Phys. Cham., 1951, 2, 99.388 E. Collinson and F. S. Dainton, Discuss. Furaduy Soc., 1962, 12, 251.38D J.Weiss, Nature, 1950, 165, 728.390 M. Haissinsky and M. Lefort, Compt. rend., 1950, 230, 1166.1952, LA-1438.Report, 1951, BNL-141.Radiation Chemistry,” Discuss. Furaduy Soc., 1952, 1272 GENERAL AND PHYSICAL CHEMISTRY.suggested that instead of the H,O- ion breaking down in the usually acceptedmanner :the breakdown occurs by one of the following processes :H,O-+HO-+H . . . . . . (3)H,O- -0- + H, . . . . . . . (4) 391followed by O-+H,O+HO-+OH . . . . . * (4a)followed by H- + H,O+OH- + 13, . . . . . * (5a)H,O-+H-+OH . . . . . . - ( 5 ) orSupporting arguments for reactions (5) and (5a) have recently beenadvanced 393 but (5) seems a less likely process energetically than either (3)or (4). It has been argued that process (4) is energetically to be preferred toprocess (3),392 but it has also been pointed out that if (4) is energeticallyfavoured with respect to (3) then it cannot be followed by (4a).394 It hasbeen claimed that process (4) offers an alternative explanation to the " hotspot '' hypothesis (see next section) for the production of hydrogen gas innearly constant initial yield and that it also indicates a decreased reducingpower of irradiated solutions.Against such a hypothesis the followingarguments may be advanced : (a) The difficulty of finding a suitable processto follow (4). ( b ) The fact that there is some direct evidence of the partici-pation of D atoms in polymerisations induced in deuterium oxide solution.395(c) The fact that hydrogen peroxide has been found in greater initial yieldthan hydrogen in the ferrous sulphate system.396 (d) The fact that it isdifficult to explain the reduction of certain organic dyes on this basis.It iscertainly not true to assume that reduction occurs by H atoms formed in theprocessas is shown by the enhanced yield produced by the addition of sodiumbenzoate to such systems.397, 398The theory of Burton, Magee, and Samuel327 suggests a mechanismsomewhat different from that usually accepted for H atom and OH radicalformation and it seems likely that the present position may be summarisedby the overall expressionH,O ---+ H,O* + H + OH + other species as yet ill-defined.The excited species H20* may be able to oxidise or reduce or play no chemicalpart, depending on the substrate concerned, and this may be an explanationof the differences in .G (solute) and G (free radical) values found frominvestigations on different solutes.(i) MoZecuZar and radical yield.The postulate, first advanced by Allen,399that the primary effect of ionising radiation on water could be regarded asconsisting of two processes :. . . . . OH+H,+H+H,O - (6). . . . . H20--+3H,0, +&H, - ( F )H,O I _ f OH + H + (R) . . . . . . .391 M. Haissinsky and M. Magat, Compt. rend., 1951, 233, 954.392 M. Magat, Discuss. Faraday SOC., 1952, 12, 244.393 G. W. R. Bartindale, ibid., p. 246.395 E. Collinson and F. S. Dainton, ibid., p. 212.396 F. S. Dainton and H. C. Sutton, ibid., p. 121.398 G. Stein, ibid., p. 243.3D4 F. S. Dainton, ibid., p.245.3*7 M. J. Day, ibzd., p. 280.A. 0. Allen, J . Phys. Chem., 1948, 62, 479BETTS et aZ. : THE KIXETICS OF HOMOGENEOUS REACTIOSS. 73has received considerable direct support from measurement of initial hydro-gen peroxide 401s 402, m3 and indirect support from the factthat certain results are explicable on mechanisms involving this postu-late.404im5* 406 On the other hand there have been some dissensions onexperimental grounds,407$ hydrogen yields having been found to vary.It is not clear whether or not the yields in these last cases are initial yields.Several attempts have been made to measure the yield for each of theprocesses ( F ) and (R). H o ~ h a n a d e l , ~ ~ ~ using y-radiation from a %o source,has examined the rate of production of hydrogen peroxide in acid de-aerated potassium bromide solutions and in water containing hydrogen andoxygen.Johnson and AllenN3 found a constant initial yield of hydrogenduring the irradiation of several solutions with 2 Mev X-rays, and used theirresults to evaluate the yield due to ( F ) . In 0-8~-sulphuric acid lower yieldsof hydrogen were found, probably owing to direct energy absorption by theacid. Johnsonm9 has estimated the percentages of radicals used in theprocesses ( F ) and (R). Hart 406 has made similar estimates from the resultsof oxidation of formic acid in aerated solution by 6oCo y-irradiation andby irradiation with tritium p-rays. This worker also employed the oxidationof ferrous sulphate, in aerated and in air-free solutions, to obtain relativeyields of (R) and ( F ) 410 forOther workers have made estimates of the radical-pair yield alone.Dainton and Rowbottom 411 achieved this by comparison of radiation andphotochemical yields for the decomposition of hydrogen peroxide in aqueoussolution.Rigg, Stein, and Weiss332 made an estimate from work on they- and tritium @-radiation.ferrous sulphaie system. The data obtained frompresented in the table below.Reference Radiation330 goco y406 6OCo y406 TB4 10 6OCo y410 TP330 Y + n411 "CO y332 200 kv X403 2 Mev X412 2 Mev eleztrons413 30 kv XGP GR G H ~ O0.46 2.74 3.660.35 2-78 3-483-351.18 1.57 3.9313.40.395 *12.3these investigations areev perRadicals (yo) radicalR F pair75 25 2779 21 30.570 30 20.862 3853 4740 60 25.57.619.4* Assuming G(Fe2 + Fe3 +) = 20.80 208-1400 A.0. Allen, Discuss. Faraday SOC., 1952, 12, 79.401 P. Bonet-Maury, ibid., p. 72.402 A. 0. Allen, C. J. Hochanadel, J. A. Ghormley, and T. W. Davies, J . Phys.403 E. R. Johnson and A. 0. Allen, J . Amer. Chem. Soc., 1952, 74, 4147.404 E. J. Hart, ibid., p. 4174.405 E. R. Johnson, U.S. Atomic En. Commiss. Report, 1952, BNL-1209.406 E. J. Hart, J . Phys. Chem., 1952, 56, 594.*07 M. Haissinsky, Discuss. Faraday Soc., 1952, 12, 123.OoD E. R. Johnson, U.S. Atomic En. Commiss. Report, 1952, BNL-1209.E. J. Hart, J . Anzer. Chem. SOC., 1951, 73, 1891.F. S. Dainton and J . Rowbottom, Nature, 1952, 169, 370.*12 E. R. Johnson, J .Chem. Phys., 1951, 19, 1204.*13 M. Haissinsky and M. Lefort, J . Chim. phys., 1951, 48, 368.Chem., 1952, 68, 575.408 T. Rigg, ibid., p. 11974 GENERAL AND PHYSICAL CHEMISTRY.All such values can only represent lower limits to the free-radical yield,owing to the possibility of recombination of some of the radicals to form water.This would account for the different values obtained for different systems,even when the work has been carried out by the same investigator. Fromthis point of view the highest value obtained for the free-radical yield, ifsubsequently confirmed, bids fair to be the most likely value. Anotherpossible source of variation is the effect of the excited water molecule H20*,as discussed earlier.It has been suggested that the products hydrogen and hydrogen peroxidefrom ( F ) are formed in regions of high density of energy release (hotspots) .400-402 Bonet-Maury 401 regards each radiation as having some of theproperty of X-radiation and some of the property of a-radiation, the transi-tion from predominantly a-behaviour to predominantly X-behaviour occurr-ing at a mean ion density of 200 ion pairs per micron.Such considerationslead to the expectation that an increase in ionisation density of the radiationemployed will increase the molecular yield (GF) and decrease the free-.radical yield (GR), and that the steady state level of decomposition in purewater will rise.399 These expectations have been fulfilled experimentally.The steady state level of decomposition of water rises as we pass fromX-radiation through proton and deuteron radiation to x-radiation," thisbeing the order of increasing ionisation density.The changing ratios ofradicals produced by (R) and ( F ) for different radiations as given in the Tableare also in agreement with this hypothesis, and Hardwick 334 has shown thaton these considerations a correlation between the apparently anomalousresults of various workers on the ferrous-ferric and cerous-ceric systems canbe achieved.In view of the importance of this systemfrom the point of view of chemical dosimetry it is natural to find that con-tinued attention is paid to it. The effect of several variables on yield in theoxidation of ferrous sulphate produced by X-irradiation has been studied byRigg, Stein, and Weiss 332 who conclude that the effect of increasing pH inreducing the oxidation yield, in air-free solution, can be accounted for bythe mechanism :(ii) The ferrous-ferric system..Fe2* + OH+Fe3+ +OH- .. . . . . ( 7 ). . . . . . . . H + H+ H,+ ( 8 )(9)H + Fe3++Fe2+ + H* - (10). . . . . . Fez+ + H2++Fe3f + H,. . . . .The limiting yield in acid solutions is considered to be due to completeremoval of OH radicals and also the complete removal of H atoms, asH2+acl., in oxidation of ferrous ions. At high pH the competing backreaction (10) causes non-linearity of yield. In aerated solutions all hydrogenatoms function as HO, radicals and the kinetic scheme proposed consists ofprocess (7) together with the following steps :.. . . . . . H + 0, -+ HO, - (11)HO, + Fe2+-jFeJt- + H0,- - (12)H,O, + 2Fe2++2Fe3+ + 20H- * (13)Fe3+ + 0,-+Fe2+ + 0, (14). . . .. . . .. . . . .* Ref. 401, p. 75, Table IBETTS et al. : THE KINETICS OF HOMOGENEOUS REACTIONS. 75The fall in yield found on increase of pH is attributed to the back-reaction(14), a reaction established by independent w0rk.4~~ The proposed schemeswill account for the effect of changing the ferrous-ion concentration in bothaerated and deaerated solution and also explains the authors’ finding thatthe limiting yield in aerated acid solutions is about double that in deaeratedacid solutions. This experimental result is not in agreement with thefindings of several other workers, a value of about 2.8 being more commonlyaccepted.410 The reduction of yield caused by addition of hydrogen indeaerated solutions is explained on the basis of the back-reaction (6), asuggestion supported by the fact that hydrogen increases the rate ofreduction of ferric ions in deaerated solution.Though the above mechanism suffices to explain these authors’ results,it fails to account for results found by other investigators.Thus Daintonand Sutton396 have found that hydrogen peroxide is formed during theX-irradiation of solutions of ferrous ion at concentrations less than 1 0 - 5 ~ .This tends to support the reaction ( F ) whereas no possible mechanism forthe formation of hydrogen peroxide arises from the above postulates.Amphlett 415 has examined the effect of pH on the initial yield of the oxidationof ferrous ions in aerated solutions by X - and y-irradiation.He finds evidenceof a back-reaction as the pH is increased and of an ultimate steady state.The data are not in agreement with those of earlier workers.416 It is shownthat pH effects can only arise from some effect on the HO, radical, and theprocesswhich is equivalent to process (14), is suggested as the pH-dependent step.On the other hand it is found that the pH-dependence of the yield is notfully explained on this basis, and the suggestion is made that possibly theratio (R) : ( F ) changes with pH. Other results still requiring a satisfactoryexplanation are the steady states at high pH and the fact that the yield offerric ion produced does not begin to fall immediately after the start of thereaction.So far the suggested kinetics have failed to fit the results com-pletely and it is suggested that there may be a fundamental inadequacy ofthe proposals. Baxendale 417 has suggested that some of the discrepanciesmay be cleared up by assuming a non-uniform distribution of radicals.It should be noted here that Collinson and Dainton 395 have also found itnecessary to postulate a non-uniform distribution of radicals in order toexplain results on the polymerisation of acrylonitrile in aqueous solution byX- and y-radiations. However, the ferrous oxidation problem is complicatedby the fact that Dewhurst 418 was unable to find stationary states and couldnot obtain reduction of ferric ions, though confirming the effect of pH onboth aerated and deaerated solutions.He also found, contrary to Amphlett,that low concentrations of chloride ion had no effect on the reaction, thishaving been checked on samples of solution from other laboratories. Otherwork which has appeared on the irradiation of the ferrous-ferric system(apart from that discussed in the section on actinometry) concerns irradiation414 W. G. Barb, H. J. Baxendale, P. George, and K. R. Hargrave, Trans. FaradaySOC., 1951, 48, 462.416 H. Fricke and E. J. Hart, J . Chem. Phys., 1935, 3, 60.417 J. H. Baxendale, Discuss. Faraday Soc., 1962, 12, 253, 256.*18 H. A. Dewhurst, ibid., p. 255.Fe3+ + HO,+Fe,+ + H+ + 0, . . . . . (15)415 C. B. Amphlett, Discuss. Farada-y SOC., 1952, 12, 14476 GENERAL AND PHYSICAL CHEMISTRY.in the presence of other substances.Dewhurst 419 has studied the effect ofalcohols on the ferrous oxidation initiated by y-radiation, Hart 420 hasexamined the mechanism of the y-ray-induced oxidation of ferrous ion in thepresence of formic acid and oxygen, and Cottin, Haissinsky, and Ver-meilP219 422 have investigated the effect of hydrocarbons on the yields offerric ion produced in aerated aqueous solutions by y-rays and 24 kv X-rays.The last authors have also examined the effect of alcohols on the X-ray-induced oxidation. In each case the yields of oxidation in aerated solutionsare appreciably higher than the yields without the added material. In thecase of the addition of formic acid the kinetics can be explained on the basisof a chain mechanism including the radical HCO-0.Both alcohols andhydrocarbons appear to give rise to radicals capable of reaction with oxygento form peroxides. These then oxidise the ferrous ions by chain mechanisms,which in the case of alcohols can be inhibited by the addition of chlorideion.419 The increase in rate of oxidation due to the presence of primaryalcohols is greater the longer the alcohol chain.Garrison and Rollefson 423 examined the effect of high-energy a-particleson aqueous solutions of ferrous ions and carbon dioxide containing 14C0,.The aim of this work was to attempt a removal of all the OH radicals byFe2+ ions and hence to study the effect of H atoms on carbon dioxide, thesetwo being assumed to be the active species.The principle products wereferric ions and hydrogen, but a small fraction of the H atoms were used informing reduction products of carbon dioxide, mainly formic acid, with someformaldehyde and oxalate. A mechanism is given which fits the data overthe whole range of observations, and an estimate of the effective concen-tration of H atoms gives this as N ~ O - ~ M .The formation and destruction -of hydrogenperoxide has been the subject of several investigations.401* 4113 424-428Hart and Matheson 424 find the rate of decomposition by ‘j0Co y-radiation tobe unmistakably proportional to [H20&* and (dose rate)*. A mechanismwhich satisfies the results is proposed which, however, contains an unusualthird-order termination step :The special efficiency of hydrogen peroxide as a third body in this reaction,rather than water which is present in much greater amounts, is attributed toa hypothetical ring-complex intermediate between HO, and H202 for whichit would seem there is some indirect supporting evidence.429 Propagationand termination rate constants have been measured in intermittent radiationexperiments.Dainton and Rowbottom411,430 point out that a rate pro-portional to [H202]+ is contrary to their own findings and to the results of(iii) Other aqueous systems.2H0, + H20,+2H,0, + 0, . . . . . (16)419 H. A. Dewhurst, Trans. Faraday SOC., 1952, 48, 905.420 E. J. Hart, J . Amer. Chem. SOC., 1952, 74, 4174.421 M. Cottin, M. Haissinsky, and C. Vermeil, Compt. rend., 1952, 235, 642.422 C.Vermeil, M. Cottin, and M. Haissinsky, J . Chim. phys., 1952, 49, 437.423 W. M. Garrison and G. K. Rollefson, Discuss. Faraday SOC., 1952, 12, 155.424 E. J. Hart and M. S. Matheson, ibid., p. 169.425 M. Ebert and J. W. Boag, ibid., p. 189.426 M. Haissinsky and J. Pucheault, J . Chim. phys., 1952, 49, 294.427 J. Pucheault, M. Lefort, and M. Haissinsky, ibid., p. 286.428 &I. Carmo Anta and M. Haissinsky, Compt. rend., 1952, 235, 170.429 N. M. Luft, Discuss. Farada-y SOC., 1952, 12, 266.430 F. S. Dainton and J . Rowbottom, ibid., p. 264BETTS et d. : THE KINETICS OF HOMOGENEOUS REACTIONS. 77most of the work which has been done on the photolysis of hydrogen peroxide.They find that the rate of decomposition is proportional to [H,O2Ip0 x (doserate)05 for 1-22~-solutions. This is a major discrepancy only to beresolved by further experimentation. Ebert and Boag 485 have investigatedthe formation and decomposition of hydrogen peroxide in aqueous solutionsby the action of 1 Mev electrons, and 1.2 Mev and 200 kv X-radiation.Inaerated solutions a higher initial yield of hydrogen peroxide was found withelectrons than had previously been found by Lefort 431 with 30 kv X-irradi-ation. Experiments with 200 kv and 1-2 Mev X-radiation confirmed that adifference existed between the effect of X-rays and of 1 Mev electrons. Asubsequent investigation by a group of workers 432 confirmed these findingsand showed that for 1 Mev electrons the initial yield of hydrogen peroxidewas Go = 1.10, whilst for 30 kv and 220 kv X-radiation Go = 2.28.More-over a limiting value was attained for the hydrogen peroxide concentrationproduced by 1 Mev electrons whereas no limit to the yield was reached forthe X-irradiations. The results meet with an explanation on the differenceof ion density arising from the two types of radiation and it seems possiblethat the different effects found may arise from a difference in decompositionrate. The effect of pH on the formation and decomposition of hydrogenperoxide in aerated solutions indicates that the effective back-reaction is :0,- + H,O,+OH + OH- + 0, . . . . . (17)The yields of hydrogen peroxide produced in boric acid solutions by pileirradiation are lower than those produced by or-particle irradiation withradon.426 The effects of adding various electrolytes in these experimentshave also been s t ~ d i e d .4 ~ ~ An investigation of the formation and decom-position of hydrogen peroxide in water by irradiation with a-rays of poloniumshowed that the results varied according to the acid In the pre-sence of @8~-sulphuric or -perchloric acid a limiting concentration of hydro-gen peroxide, which depends on the polonium concentration, is reached.In @8~-nitric acid, no hydrogen peroxide is formed. The effect of poloniumand radon in similar experiments is very different, but it is not clear whetherthis is due to a difference in the radiation emitted or to some effect of thepolonium, which was dissolved in the solutions in these experiments. In aninteresting extension of earlier work 4B3 it has been shown that the yield ofhydrogen peroxide produced by the a-radiation from radon is the same fromboth water and a 0.1% solution of carb~xypeptidase.~~~ This confirms theview previously suggested that hydrogen peroxide production occurs in thecore of an a-track and that the small inactivation of carboxypeptidase bya-irradiation is entirely due to &rays arising from the main cc-track. Weisshas discussed possible results which may arise from the photolysis andradiolysis of hydrogen peroxide with particular reference to reaction in andbetween tracksu5The exchange reaction between oxygen and water initiated by y-radiationhas been studied by using oxygen enriched in the isotope 180.436 The rate431 M. Lefort, J . Chim. plays., 1950, 47, 624.492 T. Alper, M. Ebert, L. H. Gray, M. Lefort, H. C. Sutton. and F. S. Dainton,433 TV. M. Dale, L. H. Gray, and W. J. Meredith, Phil. Trans. 1949, A , 242, 33.434 W. M. Dale, J - V. Davies, C. W. Gilbert, J. P. Keene, and L. H. Gray, Biochem. J . ,436 E. J . Hart, S. Gordon, and D. A. Hutchison, J . Amev Chem. SOC., 19 52, 74,5548.Discuss. Faraday SOC., 1952, 12, 266.1952, 51, 268. 435 J. Weiss, Discuss. Faraday SOC., 1952, 12, 16178 GENERAL AND PHYSICAL CHEMISTRY.of exchange was found to increase with pH and concentration of 16, l80 2and was inhibited by hydrogen peroxide. The exchange proceeds by achain mechanism, as many as 40 oxygen molecules being exchanged per freeradical pair formed at pH >9. The chain is terminated by hydrogenperoxide. An equilibrium is proposed : HO 6 0- + H+, exchange beingthen effected by reaction of 0- ions with oxygen molecules and OH- ions.H0,- and 0,- ions act as chain terminators.Hardwick437 has studied the reduction of ceric sulphate in varyingconcentrations of sulphuric acid, using y-rays from and radium, and2000 kv X-rays. The yield of cerous ion (G = 3.2) remained constant overa wide range of dose rates, ceric ion concentration, and pH, and was indepen-dent of the presence or absence of oxygen. The addition of hydrogen gasto air-free solutions increased the yield of cerous ion to G = 6.2. Theseresults, which can be explained on the basis of reduction by H atoms onlyor by H atoms and hydrogen peroxide, differ markedly from the results ofother workers.438 However the radiation used by Haissinsky et aLU8 was14 kv X-radiation and an attempt has been made to account for theseapparent anomalies, and to correlate other results obtained for this systemand the ferrous-ferric system, on the basis of the difference in energy of theionising electrons arising from the different radiations employed.334 Suchan explanation necessitates the assumption that a greater proportion of thereduction of ceric ions proceeds by hydrogen peroxide in the case of the low-energy X-rays than in the case of y-radiation. It has been pointed out,however, that no such corresponding effects arise in the irradiation of purewater.439 The effect of radiations ranging from y-rays to infra-red rays onmethylene-blue in water or glycerol is claimed to be different in the twosolvents.u6 Spectrophotometric evidence is given to show that bleaching ofthe dye takes place via the leuco-dye in glycerol; in aqueous solution noleuco-dye is formed, bleaching is much slower and is never complete.In view of other work which has recently been done on this system 3973 440s 441it seems certain that the effects in aqueous solution were in fact due toincomplete deaeration.A study has been made of the exchange between deuterium gas and liquidwater under the action of 60Co y-rays,a, but the full results are not yetavailable. Experiments have also been started u2 on the mode of formationof hydrogen peroxide in the y-ray-induced water-oxygen reaction, with theisotope l80 as a tracer. The X-irradiation of linoleic acid in aqueoussolution leads to a chain reaction.a3 Decrease of dose rate or increase ofconcentration of the substrate both tend to increase the ionic yield. Thisis a further demonstration that radiation chemical chain reactions showgreater sensitivity to changing conditions than do single molecular changes.*It is suggested that similar reactions may account for the large effectsproduced by small doses of irradiation in animals. Experiments on the437 T. J. Hardwick, Cavtad. J . Chew., 1952, 30, 23.438 M. Haissinsky, M. Lefort, and M. Le Bail, J . Chim. phys., 1951, 48, 209.439 M. Lefort, Discuss. Faraday Soc., 1952, 12, 273.440 M. J. Day and G. Stein, Nature, 1950, 166, 146.441 E. Collinson, Discuss. Faradav SOC., 1952, 12, 285.442 S. Gordon, E. J . Hart, and P. D. Walsh, U.S. Atomic En. Commiss Report,* Cf. ref. 395.1951, AECU-1742. 443 J . F. Mead, Science, 1952, 115, 470BETTS et nl. : THE KINETICS OF HOMOGENEOUS REACTIONS. 79change in viscosity produced in solutions of polymethacrylic acid under theaction of X-radiation and " nitrogen mustard " indicate that the mechanismis different in the two cases.& The change is brought about by coiling ofthe chains in the case of " nitrogen mustard " and by degradation of thechains with X-rays in aerated solution. The fact that there is no appreciablechain breakdown during X-irradiation of deaerated solutions seems toindicate that the effective chain-breaking radical may be the HO, radical.It is suggested that effective biological protective agents function by ab-stracting an oxygen atom from HO, since the same agents protect thepolymethacrylic acid degradation.445The X-irradiation of potassium iodate showed an interesting variationin the ratio of the products formed (iodine and hydrogen peroxide) and inthe after-effect observed according to whether the solutions were aerated ordeaerated.u6Other aqueous systems which have been studied are the decolorisation ofchlorophenol-red by X-radiation,M' the X-irradiation of ammonia solu-tions,u* perchloric acid,449 mercuric and i n d ~ l e , ~ ~ l the y-irradi-ation of cysteine 452 and benzene:453 the electron-irradiation of tryptophan,tyrosine, phenylalanine, and c y ~ t i n e , ~ ~ and of fats,455$ 456 the pile-irradiationof ~ y s t i n e , ~ ~ ~ and the a-irradiation of formicvarious aspects of the radiation chemistry of aqueous solutions have appearedduring the past year.459-462Alder and Eyring 463 have presented a kinetic analysis of irradiations insolution. Their treatment is not essentially different from that given earlierby Dainton464 but they have been able to use the resulting expression forionic yield in terms of solute concentration to fit the curves of, experimentalresults. This means that certain parameters in the expression can beevaluated and the yield of water molecules decomposed per 100 ev ofenergy absorbed can be estimated for each set of experiments. The highestvalue of G(H,O) so obtained is 5.9. This is derived from results on the X -irradiation of carb~xypeptidase.~~ Formation of hydrogen and hydrogenperoxide is neglected in the treatment. A treatment which is claimed toOther reviews of.444 P. Alexander and M. Fox, Nature, 1952, 164, 572.445 Idem, ibid., 1952, 170, 1022.446 N. Todd and S. L. Whitcher, J . %hem. Phys., 1952, 20, 1172.447 E. N. Weber and R. H. Schuler, J . .4mer. Chenz. SOC., 1952, 74, 4415.448 T. Rigg, G. Scholes, and J . Weiss, J., 1952, 3034.44Q B. Milling, G. Stein, and J. Weiss, Natzire, 1952, 1'70, 710.450 G. Stein, R. Watt, and J . Weiss, Trans. Favaday Soc., 1952, 48, 1030.461 C. B. Allsopp and J. Wilson, Discuss. Faraday Soc., 1952, 12, 299.452 A. J . Swallow, J . , 1952, 1334.453 T. J. Sworski, J . Chem. Phys., 1952, 20, 1817.454 B. E. Proctor and D. S. Bhatia, Biochem. J . , 1952, 51, 535.455 R. S. Hannan and J. W. Boag, Nature, 1952. 169, 152.458 R. S. Hannan and H. J. Shepherd, ibid., 1952, 170, 1021.457 M. Lipp and H. Weigel, Naturwiss., 1952, 39, 189.4 5 * W. M. Garrison, D. C. Morrison, H. R. Haymond, and J. G. Hamilton. J . Amer.45g G. Stein, Discuss. Faraday SOC., 1952, 12, 227.460 L. H. Gray, J . Cellular Comp. Physiol., 1952, 39, Suppl. l., 57.461 W. M. Dale, ;bid*, p. 39.462 A. 0. Allen, Ann. Reviews Phys. Chem., 1952, 3, 57.463 M. G. Alder and H. Eyring, Nucleonzcs, 1952, 10, KO. 4, p. 54.464 F. S. Dainton, A n n . Reports, 1948, 45, 5.Chem. Soc., 1952, 74, 421680 GENERAL AND PHYSICAL CHEMISTRY.be simpler 465 and is based on Dee and Richards’s theory 318 yields the sameexpression for the ionic yield as does that of Alder and Eyring. The muchlower radical yields deduced for a-irradiations by this method are explainedas being due to local quenching of primary photons by molecules directlydamaged by the radiation.R. H. B.E. C.F. S. D.K. J. I.R. H. BETTS.E. COLLINSON.F. S. DAIKTON.C. W. DAVIES.D. D. ELEY.K. J. IVIN.J. W. LINKETT.C. B. MONK.4135 J. B. Binks, J . Chem. Phys., 1952, 20, 1655

ISSN:0365-6217    

DOI:10.1039/AR9524900007

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.CONSIDERABLE interest has been sustained in the study of chelate and othercomplex compounds formed between metal cations and a variety of ligands.The growing interest in this branch of the subject has in part no doubt beenstimulated by the increasing importance of these complex compounds inseveral industrial processes, and great advances have been made in theirstudy in recent years. Although a complete specificity, such that a givenchelating agent would form a compound with only one type of ion, may yetbe out of reach, the different stabilities of many of these chelates providea valuable tool for the separation and purification of elements by solvent-extraction, ion-exchange, and other fractional techniques. For example,the use of ion-exchange techniques for the separation and purification ofthe lanthanons is now well established, several different eluants having beenused by individual groups of workers.A quantitative comparison has nowbeen made of the relative value as eluants in this connection, of seven carb-oxylic acids, viz., acetic, malic, tartaric, citric, aminoacetic, nitrilotriacetic,and e t h ylenediamine-NNN' N'-tetr a-acet ic, and the stability const ants havebeen determined for the last-named with several lanthanons.2The effects of the nature of the chelating agent and of the electronicstructure of the metal ion on the stability of the complex have been thesubjects of numerous investigations. Thus, the effect of a relatively minorchange in the structure of the chelating agent is shown by a comparison ofthe stabilities of the chelates of the anions of iminodiacetic acid and imino-dipropionic acid with copper(II), nickel(II), cobalt(II), zinc, and cadmiumions: replacement of the acetate groups by p-propionate groups in theligand results in a considerable decrease in the stability of the he late.^A study of the chelates of 2-hydroxyethylaminoacetic acid with a numberof bivalent cations'4 has shown, on the other hand, that the stabilities of thechelates of iminodiacetic acid are greatly increased when an amino-hydrogenatom is replaced by the hydroxyl group, though the stability constants arestill about 100-fold smaller than those of the corresponding nitrilotriaceticacid.The effect on chelate stability, of the structure of the chelating agent hasalso been investigated with the use of 8-hydroxyquinoline and analogousreagents.g The steric effect of 8-hydroxyquinaldine, believed to be re-sponsible for the non-reaction of this reagent with aluminium(III), has alsobeen encountered in the case of nickel(x1).In the course of this work it wasshown that there is an increase of chelate stability in a series of 8-hydroxy-quinoline chelates with bivalent ions of transition elements, as the transitionelectron shell becomes more completely filled.Evidence of the effect of steric considerations in a chelate compound onR. C. Vickery, J., 1952, 4357.S. Chaberek, Jr., and A. E. Martell, J . Amer. Chem. SOC., 1952, 74, 5062.S. Chaberek, Jr., R. C. Courtney, and A.E. Martell, ibid., p. 5057.G. Schwarzenbach, H. Ackermann, and P. Ruckstuhl, Helu. Chzm. Ada, 1949, 33,W. D. Johnston and H. Freiser, J. Amer. Chem. Suc., 1962, 74, 5239.2 Idem, J., 1952, 1895.1175; G. Schwarzenbach and E. Freitag, ibid., 1951, 34, 149282 INORGANIC CHEMISTRY.the reactivity of the central metal atom is also given by the radio-isotopicexchange of zinc between zinc acetate and a number of zinc chelate cokm-pound^.^ There is little or no exchange of the zinc in zinc phthalocyanine-a " fused-ring " type of chelate compound-whereas with others of the" non-fused-ring " type, exchange is rapid.A further study of the effect of steric hindrance has been made with thechelates of copper(x1) and nickel(xx) with a series of N-alkyldiamines,R*NHCH,CH,*NH, (R = H, Me, Et, Pr", Bun, and Pri).8 Except for then-butyl derivative, there is a general decrease in stability of the straight-chainalkyl complexes as the length of the chain increases, and the complexeswith the isopropyl derivative are less stable than those containing thestraight-chain alkyl groups.A rather different steric effect of the organic groupings attached to acentral metal atom is shown by the physicochemical properties of thealkyloxides of titanium and zirconium.It was established in the firstplace that the volatility of the amyloxides of these elements depended onthe structure of the particular amyl group in question, the branched-chaincompounds being in general much more volatile than the straight-chainamyloxides.This effect, it is believed, may be due to the screening by thebranched groups inhibiting intermolecular bonding between the centralmetal atom and oxygen. A number of new tetra-tert.-alkoxides of theseelements have been prepared. lo Ebullioscopic measurements show that theyall monomeric.Differences in the stabilities of complex compounds formed by opticallyactive organic stereoisomers with some complex inorganic compounds offera method of resolution of the racemates. For example, when a racemicmixture of an organic acid reacts with an equimolecular amount of a complexsuch as Zmo-carbonatobispropylenediaminecobalt ( XIX) two isomers areformed, one containing the dextro- and the other the Zmm-form of the acid.As these prove to have different stabilities, a partial resolution of the acidbecomes possible, and experimental results have been.presented for thepartial resolution in this way of tartaric, chloropropionic and lactic acid. l1A considerable interest has been shown recently in directive influences inthe reactions of inorganic co-ordination complexes. In this connection ,mention may be made of a review of the extensive experimental work andtheoretical considerations relating to the so-called tvans-effect, especially inrelation to the platinum complexes.12 The trans-effect stipulates that thebond holding a group trans to an electronegative or other labilising group isweakened thereby, so that the trans-group is the first to be removed in asubstitution reaction.A recent example of this effect is seen in the behaviour of dichlorodi-ethyleneplatinum(xx), (C,H,),PtCl,.In all except the olefin series of plati-num(I1) complexes, a t least one geometric isomer of the simple non-ioniccompound L,PtCl, (L = ligand) is known, and is usually more stable thanthe corresponding ionic complexes (LPtC1,)- and (L,Pt) + 2. The olefinD. C. Atkine, Jr., and C . S. Garner, J . Awzer. Chem. SOC., 1952, 74, 3627.F. Bas010 and R. K. Murmann, ibid., p. 5243.D. C. Bradley, R. C . Mehrotra, and Mi. Wardlaw, J . , 1952, 2027.lo Idem, J., 1952, 4204.l1 A. D. Gott and J . C. Bailar, Jr., J . Amer. Chem. SOC., 1952, 74, 4820.1* J. V. Quagliano and L. Schubert, Chem. Reviews, 1952, 60, 201FAIRBROTHER. 83complexes, however, were found to be an exception, and until recentlyall attempts to prepare (C2H4),PtCl2 had failed, although K(C,H,PtCl,) hasbeen recognised since 1830.14 (C2Hp)2PtC12, which may be obtained as aprecipitate by passing ethylene into dichlorodiethylene-vv'-dichlorodi-platinum(i1) in acetone a t -70°, dissociates a t room temperature with thereversal of the reaction and evolution of ethylene.The instability of thisnew diethylene compound is explained by supposing it to have a trans-configuration, the instability being due to the combined effects of the ratherweak co-ordinating affinity of ethylene and the strong trans-influence, orlabilising effect, of an ethylene molecule on the group in the transpositionto itself.15Further study has been made of the nature of the co-ordinate link incomplex platinum compounds by an examination of the equilibrium betweencis- and trans-bis(triethylphosphine)dichloroplatinum(II) through the meas-urement of the dielectric polarisation of their solutions as a function oftemperature.16 The highly polar cis-isomer is more stable than the trans-by about 10 kcal./mol., as are also the cis-(AsEt,),PtCl, and cis-(SbEt,),PtCl,than their corresponding trans-isomers.l7The influence of the configuration of an ion on its retention by an exchangeresin has been made use of for the separation of the cis- and trans-isomericdinitrotetramminocobalt (111) ions.18An ion-exchange technique has also been used to demonstrate theformation of some anionic complexes of cadmium and copper.lg Forexample, if an anion-exchange resin is pretreated with sodium perchlorate,then cadmium perchlorate is not retained by it and can easily be washed outby water ; on the other hand, if the resin is treated with sodium iodide thencadmium iodide is very strongly held, as would be expected from the well-known stability of the cadmium iodide complexes.In many metal-anion complex ion systems in aqueous solution a numberof different complexes exist simultaneously, the separation or identificationof which is often very difficult, especially if the equilibria are establishedrapidly. On the other hand, if the equilibria are established sufficientlyslowly and the different species have different ionic charges, then ion-exchange methods offer a convenient method of separation.This has nowbeen carried out in the chromic thiocyanate system from which the speciesCr(H,O),+++, Cr( H20) ,(SCN) ++, and Cr (H,O),(SCN),+ have been separated.2oThe prosthetic groups in cation-exchange resins have usually been sul-phonic, carboxylic, or phenolic groups or a combination of these. Resinshave now been developed in which the exchange groups are phosphonousand phosphonic. One interesting feature of these new resins is that theyappear to show a selectivity for sodium over potassium.21Clathrate compounds of oxygen and of nitric oxide in quinol have beenprepared in which some 40--50% of the available spaces are filled.22 Meas-l3 J. Chatt and R. G. Wilkins, Nature, 1950, 165, 859.l4 Zeise, Mag.Pharm., 1830, 35, 105.l6 Idem, J . , 1952, 273.l8 E. L. King and R. R. Walters, J . Amer. Chenz. Soc., 1952, 74, 4471.2o E. L. King and E. B. Dismukes, J . Amer. Chem. Soc., 1952, 74, 1674.21 J. I . Bregman and Y . Murata, ibid., p. 1868.z2 D. F. Evans and R. E. Richards, J . , 1952, 3295.1 5 T. Chatt and R. G. Wilkins, J., 1952,2622.Tdem, J . , 1952, 4300.I. Lenden, Svensk Kem. Tidskr., 1952, 64, 145; Chew Abs., 1952, 46, 856384 INORGANIC CHEMISTRY.urement of the magnetic susceptibility suggests that the paramagnetismof a gas is but little affected by its inclusion in the cage-like structure. It hasbeen pointed out that, in the case of nitric oxide, the clathrate compoundoffers a method of studying its properties a t low temperatures without thecomplications either of change of state or of dimerisation into diamagneticdinitrogen dioxide which occurs on liquefaction at 121" K.A remarkable and unique new iron compound, dicyclopentadienyliron,the first compound to be prepared which contains only carbon, hydrogen,and iron, has been described almost simultaneously by two groups ofworkers.23 I t is a stable orange diamagnetic compound, m.p. 1726-173",which vapourises above 100" without decomposition into a monomeric,undissociated vapour which obeys the perfect-gas laws evena t 400".24 A number of its chemical and physicochemicalproperties have been studied. On the one hand, it is readilyoxidised to a blue cation Fe(C,H,),+ 25 and, on the other, itundergoes reactions like those of aromatic hydrocarbons.26Both chemical evidence 25 and direct X-ray examination 27 ofsingle crystals indicate that it possesses a pentagonal anti-prismatic structure (Fig.l), there being no evidence ofrotation of the cyclopentadienyl groups.The corresponding ruthenium compound, (C5H5)2R~, hasFIG. 1. also been prepared.27u The names ferrocene and ruthenocenehave been suggested for these compounds in view of theirbehaviour as aromatic systems and " ferricinium " and " ruthenicinium "for their unipositive ions, the methods of preparation and properties ofthese compounds and their salts suggesting that in the neutral compound themetal is in the +2 oxidation state, and in the unipositive ion in the +3 state.In a similar manner, the reaction of cobaltic acetylacetonate with cyclo-pentadienylmagnesium bromide gives the unipositive ion [ (C,H5)&o]+ ofwhich several salts have been prepared.This ion, however, cannot bereduced to a neutral c~baltocene.~~~The discovery of these compounds opens up a new field in the borderlandhetween inorganic and organic chemistry.Group 1.-One of the major difficulties encountered in the laboratorypreparation of lithium aluminium hydride by the usual method has beenthe necessity for the troublesome pulverisation of the lithium hydride. Itis reported, however, that by using aluminium bromide instead of thechloride, coarsely powdered lithium hydride can be used.28What is stated to be the first example of a coloured double hydride,namely, AgAlH,, is obtained as a yellow-gold precipitate when etherealsolutions of lithium aluminium hydride and silver perchlorate are shakentogether at -80" : the compound decomposes a t -50".29,23 T.J. Kealy and P. L. Pauson, Nature, 1951, 168, 1039; S. A. Miller, J. A. Teb-z4 L. Ka lan, W. L. Kester, and J. J. Katz, J . Amer. Chem. SOC., 1952, 74, 5531.25 G. Wiykinson, M. Rosenblum, M. C. Whiting, and R. B. Woodward, ibid., p. 2125.26 R. B. Woodward, M. Rosenblum, and M. C. Whiting, ibid., p. 3459.z7 P. F. Eiland and R. Pepinsky, ibid., p. 4971.27a G. Wilkinson, ibid., p. 6146. 27b I d e m , ibid., p. 6148.28 E. Wiberg and M. Schmidt, 2. Naturforsch., 1952, 7, b, 59.29 E. Wiberg and W. Henle, ibid., p. 250.both, and J. F. Tremaine, J., 1952, 632FAIRBROTHEK.85A new method of preparation of lithium hydroperoxide monohydrate hasbeen described : dehydration of this compound over phosphoric oxide in adesiccator at 20 mm. gives almost pure lithium peroxide. X-Ray diffractionstudies indicate that neither the anhydrous hydroperoxide Li0,H nor theperoxycarbonate Li,CO, exists at room temperatures3*An experimental study of the ternary system NaBr-Nac1-6.6~-NaOHhas shown that, contrary to some theoretical predictions, these two halidesdo in fact form a continuous series of solid soIutions.31 It has also beenshown, by X-ray examination, that when RbCl and KBr, or RbBr and KC1,are melted together in any proportion, a single solid solution is obtainedwhich contains all the ions in the original mixture.32 Continuous series ofsolid solutions have also been shown to be formed in the systems (NH,),SO,-Cs,SO,-H,O, (NH,),SO,-K,SO,-H,O, and (NH,),S04-Rb,S0,.33 On theother hand, an examination of the system NH,F-NaF-H,O at 25" hasshown that the system is a simple one, with ammonium fluoride and sodiumfluoride as solid phases.34The various and widely used sodium metaphosphate polymers havecommonly been prepared by thermal dehydration of sodium dihydrogenorthophosphate.It has now been found that the hydration of a-phos-phorus(v) oxide a t a temperature of 15" or below produces chiefly tetrameta-phosphoric acid (H,P,O,,), which offers an alternative method of preparationof the sodium salt of this acid.35Czsium hexasulphide has been prepared by disproportionation ofCs,S,,H,O in aqueous ethyl alcohol into this and one or more lower poly-sulphide ions.The crystal structures of Cs,S, and of the dehydrated Cs,S,prove to be very similar, the polysulphide ions being in the form of non-branched, non-planar, sulphur chains.36A new method of preparation of copper hydride, CuH, has been de-scribed.37 When lithium aluminium hydride in pyridine-ether solution isadded to a solution of copper(1) iodide in pyridine, the following reactiontakes place : 4CuI + LiAlH, = LiI + AlH, + 4CuH, and a blood-red solu-tion is obtained from which the solid may be precipitated as bright red-brown needles on addition of more ether. The dry hydride is stable up toabout 60°, above which it decomposes (rapidly at 100"); in water it givesCuOH and hydrogen a t a somewhat lower temperature.The existence of the chlorocuprate ion CuC1,' in aqueous solution is wellknown, but until recently evidence of its existence in the solid state has beenlacking.X-Ray examination of the yellowish-orange Cs,CuCl, has nowdemonstrated the presence of this ion in the solid.38 In contrast, however,to the more usual planar configuration of quadricovalent copper(I1) ions,the chlorine atoms appear to be arranged about the copper in the form of aflattened tetrahedron : the absorption spectrum of the solid is also markedly30 A. J. Cohen, J . Amer. Chem. SOC., 1952, 74, 3762.31 E. L. Simons, C. A. Orlick, and P. A. Vaughan, ibid., p. 5264.32 L. J. Wood and L. J. Breithaupt, Jr., ibid., p.727.33 C. Calvo and E. L. Simons, ibid., p. 1202.34 H. M. Haendler and A. Clow, ibid., p. 1843.35 R. N. Bell, L. F. Audrieth, and 0. F. Hill, Ind. Eng. Chenz., 1952, 44, 568.36 S. C. Abrahams, E. Grison, and J . Kalnajs, J . Anzer. Chem. SOC., 1952, 74, 3701.37 E. Wiberg and W. Henle, 2. Natwrforsch., 1952, 7, b, 250.38 L. Helmholz and R. F. Kruh, J . Amer. C h e m SOC., 1952, 74, 117686 IKORGANIC CHEMISTRY.different from that of the aqueous solution. It would appear therefore thatthe structure of the aqueous chlorocuprate ion is different from that of theion in the crystalline state.Some new copper( I) complexes of methyldiphenylarsine have beenprepared. Four types, containing respectively 1, 2, 3, and 4 molecules ofthe tertiary arsine to each molecule of the copper(1) halide, have beenisolated : example of the last two have not been reported previously.Thosecomplexes with an empirical formula CuX,3AsMePh2 are non-electrolytesand contain quadricovalent copper. Those with an empirical formulaCuX,4AsMePh2 (X = I, CIO,, or NO,) are salts of the univalent anion X.3yA number of complex compounds of silver( I) with polydentate chelatingagents have been studied which indicate that the co-ordination number ofsilver is four in these complexes. When aqueous or alcoholic solutions ofsilver nitrate are allowed to react with triethylenetetramine (trien), severalcomplexes are formed : [Ag trien]+ and [Ag, trien]++ are present in bothaqueous and alcoholic solutions, and [Ag trien]NO, has been isolated fromthe latter.4*It has been shown that the compound of empirical formula (C7H7!,SAuBr,probably contains the gold in both univalent and tervalent states : it cannotbe formulated as a dimer, as a salt, or as a compound of bivalent gold.41An X-ray investigation of the corresponding chloride, obtained by theinteraction of solutions of " auric chloride " and benzyl sulphide, has shownthat the crystal consists of separate molecules of benzyl sulphide-mono-chlorogold(1) , (C,H,),S -+ AuCl, and benzyl sulphide-trichlorogold(m),(C,H,),S -+ AuCl,, so arranged that a highly disordered structure results.A study has been made of the preparation and properties of a number ofgold imides, of the type MTIAuX(imido),] (X = halogen) from succinimideand of the type M1[AuX,(imido),] from o-benzoicsulphonimide (saccharin)and ~hthalimide.~ZGroup 11.-It has been known for some time that the volatility of anumber of oxides at high temperatures is greatly increased by the presenceof water vapour, a result believed to be due to some reaction between theoxide and water or between the oxide and a decomposition product of water.A study of this increase in the case of beryllium oxide at 1200-1600" hasshown that it is due to the reaction BeO,,) + H,O,, -+ Be(OH),cgl.43The dialkyl derivatives of beryllium present some interesting structuraland valency problems arising from the fact that they are strongly electron-deficient compounds.A detailed study in this connection has been made ofdimethylberyllium and a number of its co-ordination compounds.In thevapour state it appears to polymerise to some extent to the dimer and tri-rner,& and it forms co-ordination compounds with trimethylamine, trimethyl-phosphine, and dimethyl and diethyl ether, but not with trimethylarsine ordimethyl sulphide.45 The properties of these compounds indicate that theR. S. Nyholm, J., 1952, 1257.40 H. B. Jonassen and P. C . Yates, J . Amer. Ckem. SOC., 1952, 74, 3388.41 F. H. Brain, (the late).C. S. Gibson, J. A. J. Jarvis, R. F. Phillips, H. M. Powell,4a A. M. Tyabji and (the late) C. S. Gibson, J., 1952, 450.43 L. Grossweiner and R. L. Seifert, J . Amer. Chem. SOC., 1952, 74, 2701.44 G. E. Coates and N. D. Huck, J., 1952, 4496.4 5 Idem, J ., 1952, 4501.and A. Tyabji, J . , -1952, 3686FAIRBROTHER. 87order of stability is N > I? > 0. I t also reacts with methylamine, di-methylamine, dimethylphosphine, methanol, methanethiol, or hydrogenchloride, but in these cases the products are methane and di-, tri-, or poly-meric products. Dimethylamine gives a trimeric compound (MeBe,NMe,),to which a cyclic structure has been assigned.46It is reported that pure magnesium cyanide can be prepared by thepassage of hydrogen cyanide over a specially prepared magnesium oxide at730" : the latter is obtained by ignition of magnesium oxalate at 600°,samples of magnesium oxide prepared by other reactions giving only impureproducts.47As part of a systematic investigation of isomorphous replacement inhydrated salts, the systems CdC1,-MClz-H,O (M = Mg, Mn, FeII, CuII,and Ca) have now been examined.The existence has been established of thedouble salts 2CdC1,,MgC12, 12H,O; CdC1,,2MgC12, 12H,O; 4CdC1,,MnCL2, 10H,O;CdC1,,CuCl2,4H,O ; and of a number of solid solutions.48Solubility isotherms are reported for the quaternary system Ba(ClO,),-BaBr2-Ba(NO,),-H,O at 10" and for the ternary systems Ba(C10,),-BaBr,-H,O at 10" and 25", Ba(ClO,),-Ba(NO,),-H,O a t lo", 2 5 O , and 45", andBaBr,-Ba(NO,),-H,O a t 10" and 25" : also for a number of other aqueousternary systems involving barium chlorate, bromate, and iodate.49The solubility of metallic cadmium in fused mixtures of cadmium chloridewith some other chlorides has been studied.50 As a result of this and previouswork it emerges that : (1) the solubility of Group I1 metals in their fusedchlorides increases as the cation radius increases, (2) the solubility (for Cdin CdCl,) is decreased by the addition of the chloride of an electropositiveelement, and (3) the solubility increases as the ratio of the number of anionsto cations increases.The last result, e.g., the effect of CeC1, as comparedwith KCI, has been interpreted as due to the process of dissolution consistingin the entry of the metal atoms into the octahedral holes of an almost close-packed fused chloride structure, these holes being clearly relatively moreabundant when less of them are already occupied by the metal cations.A re-investigation of the X-ray diffraction patterns of the compoundsformed in the reactions between mercurous chloride and ammonia hasdisproved the formation of several mercury(1) compounds which have beensuggested by previous workers and has shown that only the well-knownmercury(I1) compounds Hg(NH,),Cl,, HgNH,Cl, and Hg,NCl,H,O areformed in addition to mer~ury.~lGroup 111.-A study of the method of preparation of diborane by thereaction of lithium aluminium hydride with boron trifluoride in etherealsolution has shown that the reaction takes place by a t least two successivestages, involving the intermediate formation of lithium borohydride :(a) LiAlH, + BF, = LiBH, + AlF,; (b) SLiBH, + BF3 = 2B,H, + 3LiF.52Diborane can also be prepared by reaction of lithium hydride withthe boron trifluoride-ethyl ether complex.An investigation of this reaction4 6 G. E. Coates, F. Glockling, and N. D. Huck, J., 1952, 4512.4 7 H. Hartmann and H. Narten, 2. anovg. Chem., 1952, 267, 37.I s H. Bassett and R. N. C. Strain, J., 1952, 1795.49 J . E. Ricci and A. J . Freedman, J . Aunev. Chem. SOC., 1952, 74, 1765, 1769.6o D. Cubicciotti, ibid., p. 1198.51 L. Nijssen and W. N. Lipscomb, ibid., p. 2113.52 I. Shapiro, H. G. Weiss, M. Schmich, S. Skolnik, and G. B. L. Smith, ibid., p. 90188 INORGANIC CHEMISTRY.under various conditions has shown that it can proceed by two differentcourses : (a) 6LiH + 8BF3 = B,H, +. GLiBF, in the absence of promoters,and (b) 6LiH + 2BF3 = B,H, + 6L1F if small amounts of the ether-soluble active-hydrogen-containing promoters lithium borohydride andlithium trimethoxyborohydride are present.This offers an explanation ofthe experimental observation that higher yields of diborane by this reactionare obtained in the presence of methyl ortho-borate.53The preparation of a new type of substituted borohydride containinga quaternary ammonium cation has been described. Tetramethyl-,tetraethyl-, and benzyltrimethyl-ammonium borohydrides have beenprepared by metathetical reactions in aqueous solution between sodium orlithium borohydride and the respective quaternary salts or hydroxides.A number of deuterated boron compounds have been prepared andcharacterised, including deuterated diborane, borine carbonyl, and dimethyl-aminodiborane. 55A cryoscopic study of mixtures of boron trifluoride and 100 yo nitricacid has revealed the existence of the solid compound HN03,2BF3, m.p.53'. If boron trifluoride is passed into 100% nitric acid considerable heatis evolved and a water-clear viscous liquid is formed from which largeprismatic crystals separate if the boron trifluoride content is sufficientlyhigh: if the composition of the mixture approaches that of the doublecompound, the whole mass eventually solidifies56When boron trichloride is passed into 1 : 4-dioxan at 20°, in an otherwiseevacuated apparatus, a stable, crystalline, 1 : l-addition compoundC4H,02,BC1, is formed. It is noteworthy that such co-ordination with oneof the oxygen atoms of dioxan apparently inhibits the other oxygen fromacting in like manner, since excess of boron trichloride does not give the2 : l-compound 2BC1,,C,H,02 either with dioxan itself or with the 1 : 1-complex.57Methyl orthoborate forms 1 : l-addition products with mono-, di-, andtri-methylamine, B(OMe),,NH,Me,,. 58A further confirmation of the analogy between benzene and borazole(B3N3H,) is given by the X-ray examination of single crystals of p-trichloro-borazole which have been shown to possess a molecular configuration closelyresembling that of 1 : 3 : 5-trichloroben~ene.~~The sodium salt of a new boron base, Na,HBMe,, has been prepared bythe action of sodium in liquid ammonia a t -78" on tetramethyldiboraneB,H2Me, which is split equally into Me,BH,NH3 and this new sodiumsalt. 6oAn additional contribution to the chemistry of covalent boron-nitrogencompounds has been made by the study of the chemical and physical pro-perties of the monomeric and dimeric dimethylaminoboron dichloride 6153 J.R. Elliott, E. M. Boldebuck, and G. F. Roedel, J . Arne.,. Chem. Soc., 1953, 74,5047.65 A. B. Burg, ibid., p. 1340.5 6 €3. Gerding, P. M. Heertjes, L. J. Revallier, and J. W. M. Steeman, Rec. Trav. chim.,67 A. K. Holliday and J. Sowler, J . , 1952, 11.~5r1 D. L. Coursen and J. L. Hoard, J . Amer. Chem. Soc., 1952, 74, 1742.61 C. A. Brown and R. C. Osthoff, ibid., p. 2340.64 M. D. Banus, R. W. Bragdon, and T. R. P. Gibb, Jr., ibid., p. 2346.1952, 71, 501.J. Goubeau and R. Link, 2. anorg. Chem., 1952, 267, 27.A. B. Burg and G. W. Campbell, Jr., ibid., p.3744FAIRB ROTHE R. 89and of diethylaminoboron dichloride which, in contrast to the dimethylMe,N-BCl, compound, does not dimerise. 62 When dimethylaminoborondichloride is kept at room temperature for several days, it isC1zB-NMe2 converted into the crystalline dimer [Me,NBCl,],, the smalldipole moment of which confirms the cyclic structure (inset) suggested byprevious workers.Improved methods of preparation of dimethylaminoboron dichloride andof the new difluoride (which also dimerises on storage) have been described :good yields of the dichloride are obtained by the dehydrogenation of thedimethylamine-boron trichloride complex by triethylamine in benzenesolution. The difluoride is prepared by refluxing the dimethylamine-borontrifluoride complex at 240-290", whereby both the dimer of dimethyl-amine-boron difluoride and the disproportionation products, trimethylamine-boron trifluoride and tetramethylammonium fluaroborate, are obtained.63The structures of dimethylaminodiborane Me,NB,H5 and aminodiboraneH,NB,H5 have been studied by electron diffraction and give furtherevidence for the bridged structure of the parent diborane.The results ofthis investigation are in accord with symmetrical structures which have4-fold co-ordination about the nitrogen atom and may be regarded asderived from diborane by the replacement of one of the bridge hydrogensby NMe, and NH, re~pectively.~~It is reported that when an electrodeless discharge is passed throughaluminium tri-iodide vapour at low pressures, in a vessel kept a t 50°, thetri-iodide undergoes decomposition with formation of a buff-colouredrn~noiodide.~~ It has also been claimed that potentiometric titration ofliquid-ammonia solutions of aluminium tri-iodide with solutions of potassiumin the same solvent gives evidence of the existence of Al++ and Al'ions.66It had been recorded 67 that when aluminium and other members of thisgroup are anodically oxidised in an electrolyte of ammonium or sodiumacetate in anhydrous acetic acid the mean oxidation state of the cationsformed was always appreciably lower than 3.In contrast to this observationit has now been shown that when the electrolytic oxidation is carried out inliquid ammonia, in a variety of electrolytes, initial valency numbers lowerthan 3 are only observed when the solution contains nitrate ions8It has long been known that hydrochloric acid will dissolve more alumin-ium than corresponds to the equation : 2A1 + 6HC1 = Al,Cl, + 3H,.When a large excess of aluminium is boiled with dilute hydrochloric acid,almost 6 equivalents of aluminium are dissolved to give a clear solutionfrom which the 5/6 basic chloride Al,(OH),Cl can be precipitated by additionof sodium or calcium chloride.69A clarification of the various solid phases formed in equilibrium with anaqueous or sulphuric acid solution of aluminium sulphate has been carried+ +62 R.C. Osthoff and C. A. Brown, J . Amer. Chem. SOC., 1952, 74, 2378.63 J. F. Brown, Jr., ibid., p. 1219.64 K.Hedberg and A. J. Stosick, ibid., p. 954.6 5 W. C. Schumb and H. H. Rogers, ibid., 1951, 73, 5806.6 6 G. W. Watt, J. L. Hall, and G. R. Choppin, ibid., 1952, 74, 5920.6 7 A. W. Dsvidson and F. Jirik, ibid., 1950, 73, 1700.6M W. E. Bennett, A. W. Davidson, and J. Kleinberg, ibid., 1952, 74, 732.6B G. Denk and L. Bauer, 2. anorg. Chew., 1952, 267, 8990 INORGANIC CHEMISTRY.out by a re-examination, at temperatures from 25" to 60°, of the systemAluminium hypophosphite, Al(H,PO,),, has been obtained as an anhydrouscrystalline precipitate by heating aluminium hydroxide, or a solution of analuminium salt, with 50% hypophosphorous acid at 80-90" for one hour,the precipitation being rather s ~ o w . ~ ~At -80" anhydrous aluminium chloride neither reacts with toluene nordissolves appreciably in it.On the addition of excess of anhydrous hydrogenchloride, however, it dissolves reversibly to give a clear, brilliantly greensolution in which one mole of hydrogen chloride is apparently taken upper mole of AlC13 which goes into solution. At -45.4" the amount ofhydrogen chloride taken up corresponds to one mole per mole of Al,Cl,.The reaction is believed to involve the formation of a carbonium cation[CH3*C,H6]+ and AlC14- or Al,C17- anions7,An X-ray and electron-diffraction study has been made of the poly-morphism of Ga203 and of the structure of gallia gels.73An examination of the In-In$, system by thermal metallographic andX-ray analysis has given evidence of the existence of four definite compounds,In2S,, (In3!&), (In&,), and 'Ins : the parentheses indicate some uncertaintywith regard to composition. No evidence was found for the existence ofthe sulphide of univalent indium In,S.74Insoluble bistripyridylindium chloride, bromide, and thiocyanate areformed by treating the corresponding indium salts with 2 : 2' : 2"-tripyridyl[2 : 6-di-(2-pyridyl)pyridine] in dilute aqueous ethanol solution.In asimilar manner, 5-nitro-1 : 10-phenanthroline gives the complexes tri-(5-nitro-1 : 10-phenanthro1ino)indium chloride, bromide, iodide, and thio-cyanate-all relatively insoluble. 75Thallium(Ir1) ions react with alkali alkyl xanthates to form the yellowxanthates (RO*CS,),Tl, which are insoluble in water but soluble in ethanoland other organic solvents.Aqueous or dilute ethanol solutions of 1 : 10-phenanthroline and 2 : 2'-dipyridyl react with thallium (111) ions to form the in-soluble chlorides, bromides, and thiocyanates, Tl(phenan)X, and Tl(dipy)X,,respectively. Thallium(m) iodide, on the other hand, co-ordinates with twomolecules of the chelating agent to form Tl(phenan),I, and Tl(dipy),I,. Itis reported that the latter compounds are so insoluble that they permit thedetection of thallium(II1) ions in a dilution of 1 in lo6 in the presence ofiron. 76A new and convenient method of preparation of thallium(II1) iodide hasbeen described which consists in the dissolution of thallous iodide in a solutionof iodine in concentrated hydriodic acid followed by evaporation to constantweight a t room temperature in vacuo over silica gel.It may be noted thatthe solution yields TlI, and not the anhydrous hypothetical acid HTlI,.The only intermediate phase in the thermal decomposition of TlI, to TI1and I, is Tl,I,.77A study has been made of a number of aqueous ternary and quaternary70 D. Taylor and H. Bassett, J., 1952, 4431. 71 D. A. Everest, J., 1952, 2945.72 H. C. Brown and H. W. Pearsall, J . Amer. Chem. Soc., 1952, 74, 191.73 R. Roy, V. G. Hill, and E. F. Osborn, ibid., p. 719.74 M. F. Stubbs, J. A. Schufle, A. J. Thompson, and J. M. Duncan, ibid., p. 1441.7 5 G. J. Sutton, AustraE. J . Sci. Res., 1951, 4, A , 651.76 Idem, zbid., p. 654.Al,(SO4),-H,SO~-H,O. 70.77 A. G. Sharpe, J., 1952, 2165FAIRBROTHER. 91systems involving thallous, ammonium, potassium, and cupric sulphatesat 25" in order to compare the behaviour of thallous salts with those of thecorresponding silver and alkali-metal salts.Despite certain well-knownsimilarities between argentous and thallous salts, it is found that Tl,SO,forms a continuous series of solid solutions a t room temperature with(NH,),SO, and K2S04, whereas Ag,SO, does not form solid solutions witheither of these salts. Thallous sulphate also forms the double saltT1,S0,,CuS04,6H,0, which is isomorphous with the corresponding doublesalts (NH,),S04,CuS04,6H,0 and K,S04,CuS04,6H,0. On the other hand,thallous sulphate does not form a solid solution with sodium sulphate at 25"or 46", whereas argentous salts form solid solutions with a variety of corre-sponding sodium salts, including the sulphate.78It is reported 79 that thallous sulphide Tl,S, free from the oxidationproducts which usually accompany it when it is precipitated in aqueoussolution, may be obtained by the action of dry hydrogen sulphide on analcoholic solution of thallous ethoxide.The well-known fact that metals usually exhibit theirhighest oxidation states as fluorides has suggested that higher oxidationstates of praseodymium and neodymium might be obtained by the use ofchlorine trifluoride or bromine trifluoride as fluorinating agents. WithClF, both Pr,O,, and Pro,, as well as the trioxides Pr,O, and Nd2O3, how-ever, yielded only the trifluorides : BrF, proved to be relatively inactivetowards the freshly ignited oxides.*OThe occurrence of the lanthanon elements as uranium-fission productshas stimulated interest in the properties of the pure metals themselves.Kilogram quantities of lanthanum and cerium, and somewhat less of praseo-dymium and neodymium, have been prepared by the reduction of theanhydrous chlorides by calcium in refractory-oxide lined crucibles, thereaction being initiated by the exothermic reaction between the calciumand a trace of added iodine.81 A technique for the preparation of smallerquantities (40 g.) of the highly pure metals has also been developed whichalso consists in the reduction of the anhydrous chlorides by calcium, thereaction being carried out, however, in tantalum crucibles and the resultingmetal vacuum-cast in tantalum containers.Pure lanthanum, cerium,praseodymium, neodymium, and gadolinium have been prepared by thismethod. It is noteworthy that samarium, europium, and ytterbium, thoselanthanons which exhibit stable bivalent oxidation states, are only reducedto the bivalent chlorides by this reaction, which can therefore be used fortheir rernoval.g2A good yield (85%) of the mixed anhydrous lanthanon chlorides has beenobtained by the direct chlorination of a mixture of monazite sand andcarbon a t 900". At this temperature the majority of impurities form volatileproducts, and the mixed chlorides can be drained away from the reactionmixture.83Lanthanons.'Is J. E. Ricci and J. Fischer, J . Amer. Chem. SOC., 1952, 74, 1443, 1607.'@ B. Reuter and A. Goebel, 2. anorg. Chem.., 1952, 268, 101.A. I. Popov and G. Glockler, J . Amer. Chem. SOC., 1952, 74, 1357.F. H. Spedding, H. A. Wilhelm, W. H. Keller, D. H. Ahmann, A. H. Daane,C. C. Hach, and R. P. Ericson, Ind. Eng. Chem., 1952, 44, 553.B* F. H. Spedding and A. H. Daane, J . Amer. Chem. SOC., 1952, 74, 2783.88 F. R. Hartley, J . Appl. Chem., 1952, 2, 2492 INORGANIC CHEMISTRY.The preparations of cerous ammonium acetylacetonate, m. p. 143-144"(decomp.), and of praseodymium ammonium acetylacetonate, m. p. 145",have been described. These compounds are only very slightly soluble(-1 mg. /ml.) in carbon tetrachloride, acetone, and benzene, and are insolublein light petroleum, hexane, and isooctane.84Group 1V.-The preparation and crystal structures of a further numberof disilicides of the lanthanon elements have been reported, namely, LaSi,,CeSi,, PrSi,, NdSi,, SmSi,, and of YSi,.85The reactions between carbon, silicon, and germanium tetrafluoridesand Al,Cl,, A1,Br6, A1216, MgCl,, CaCl,, and BaC1, have been investigated.86At high temperatures the reaction between SiF, and Al,Cl, goes to com-pletion, but a t lower temperatures a mixture of SiCl,, SiFCl,, SiF,Cl,, andSiF,C1 is obtained: similar results are obtained when Na,SiF, is sub-stituted for SiF,, and it is possible to prepare SiCl,, SiBr,, and SiI, by thereaction of SiF, or Na,SiF, and aluminium in the presence of the appropriatehalogen.Interest has revived, largely in connection with its technical applications,in the chemistry of the so-called silicon oxyhydride, the solid, highly cross-linked, polymeric hydrolysis product, with an empirical formula SiHO,,which is obtained as a precipitate when a benzene solution of SiHCl, ispoured into cold water or when the trichlorosilane vapour is hydrolysed at450" with steam.As might be inferred from its formula, it has very strongreducing properties, and when heated it gives hydrogen and silicon sesqui-oxide Si203 : ZSiHOa = Si,O, + H,.B7Evidence has been presented 88 to show that the hydrated sodiumsilicates, commonly formulated as Na,SiO,,S, 6, and 5H30, andNa,Si,O,,llH,O are in fact acid salts of orthosilicic acid and their hydrates,viz., N+[H,SiO,], 8, 5, and 4H,O ; Na3[HSi0,],5H,0.Convenient methods have been described for the preparation, as a con-tinuous process, of monosilane by the reduction of silicon tetrachloride withlithium aluminium hydride and the subsequent alkylation and alkoxylationof the silane by reaction of the monosilane with the appropriate organo-lithium compound : tetraphenyl-, tetraethyl-, triethyl-, diethyl-, triiso-propyl-, tetra-Z-naphthyl-, and tri-l-naphthyl-silane have been prepared inthis manner.Phenylsodium reacts with silane to give tetraphenylsilane andsodium hydride. Silane has been found to react with various alcohols inthe presence of alkoxide ions to give tetra-alkoxysilanes, (RO),Si, andhydrogen. 89A number of new alkylgermanium and alkylsilicon compounds havebeen prepared and their reactions studied,g0 and further work has beencarried out on the synthesis of dialkylamino-germanes and -~ilanes.~lTrichlorodimethylaminosilane and chlorobisdimethylaminosilane havebeen prepared from dimethylamine and silicon tetrachloride.Both com-a* J . R. Seehof, J. Amer. Chem. SOC., 1952, 74, 3960, 3961.8 5 G. Brauer and H. Haag, 2. anorg. Chem., 1952, 267, 198.8 6 M. Schmeisser and H. Jenker, 2. Naturforsch., 1952, 7, b, 191; W. C. Schumb87 G. H. Wagner and A. N. Pines, Ind. Eng. Chem., 1952, 44, 321.8 6 E. Thilo and W. Miedreich, 2. anorg. Chem., 1952, 267, 76.90 H. H. Anderson, J . Amer. Chem. SOC., 1951, 73, 5798, 5800, 5802, 5804.O1 Idem, ibid., 1952, 74, 1421..and D. W. Breck, J. Amer. Chem. SOC., 1952, 74, 1754.J. S. Peake, W. H.Nebergall, and Y. T. Chen, J. Amer. Chem. SOC., 1952, 74, 1526FAIKBROTHER. 93pounds give silane instead of the expected dimethylaminosilane on reductionwith lithium aluminium hydride. They are sufficiently basic to form severalhydrochlorides but do not form quaternary salts with methyl iodide.92Several methods have been described for the preparation of the newcompounds TiCl,,CH,CO,Et ; TiC13*OEt,CH,*C0,Et ; andTiC1,*OPri,CH,*C02Et ; these can be distilled under reduced pressurewithout change in composition, which suggests the possibility of a quinque-covalent titanium. A new series of titanium trichloride monoalkoxidesTiC1,mOR (R = Me, Et, Pri, and Bun) has also been obtained by the rapidradical-interchange reaction between titanium tetrachloride and the appro-priate tetra-alk~xide.~,The preparation of a number of new alkoxides of zirconium and hafniumand the effect of molecular complexity on their properties has already beenmentioned.loWhen a solution of zirconyl chloride, ZrOC1,,6H20, in alcoholic hydrogenchloride is treated with pyridine, a quantitative yield of pyridinium chloro-zirconate (C,H,N),ZrCI, is obtained. This compound forrns a very con-venient starting material for the preparation of the zirconium alkoxidesZr(OR), (where R = Et, Pri, Bus, and Bun), which have been obtained in apure state by passing ammonia into a suspension of (C5H,N),ZrC1, in amixture of benzene and the appropriate alcohol.94A study of the thermal decomposition of ammonium heptafluorozirconatehas shown that the decomposition takes place in three distinct stages, viz.,(NH4),ZrF, 4 (NH,),ZrF, -+ NH,ZrF6 -+ ZrF,.The decompositiontemperatures for the three successive decompositions are a function of thepressure : at 760 mm. they are 297", 357", and 410°, respecti~ely.~~Details have been given of a method of purification of zirconium fromcommon impurities, and especially iron, by the alternate precipitation ofZr(S0,),,4H20 by the addition of concentrated sulphuric acid to an aqueouszirconium sulphate solution in the presence of hydrochloric acid (essentialfor the removal of iron) and the dissolution of the precipitate in wateragain .96The complexes formed by zirconium( ~ v ) with 2-nitroso-l-naphthol havebeen investigated in aqueous ethanol and aqueous dioxan solutions, in theabsence and in the presence of HC10,.In the absence of HC10, a 1 : 1complex is formed, whereas if the solution is 3~ or stronger with respect toHClO, and 3 x ~O-,M in Zr(Iv), a 1 : 4 complex is formed.g7A detailed investigation has been carried out on the chemistry of zir-conium in nitric, hydrochloric, perchloric, and sulphuric acid solutions by acombination of ion-exchange, radiochemical, and other techniques. Theresults indicate the presence at lower acid concentrations' of a variety ofpolynuclear hydrolysis products, and at higher acidities of such complexes(in nitric acid) as [Zr(NO,),H,O),]++, [Zr(OH),(NO,) (H20),]+,[Zr(OH) ,(NO,) 2(H,O) 2]++, and [zr( OH) ,(NO,) 41 * -989a R. Cass and G.E. hates, J., 1952, 2347.O3 D. C. Bradley, D. C. Hancock, and W. Wardlaw, J., 1952, 2773.94 D. C. Bradley, F. M. Abd-el-Halim, E. A. Sadek, and W. Wardlaw, J., 1952, 2032.96 H. M. Haendler, C. M. Wheeler, Jr., and D. W. Robinson, J . Anzer. Chem. SOC.,97 H. B. Jonassen and W. R. de Monsabert, ibid., p. 5298.1952, 74, 2352. 9 6 W. S. Clabaugh and R. Gilchrist, ibid., p. 2104.B. A. J. Lister and (Miss) L. A. McDonald, J . , 1952, 431594 INORGANIC CHEMISTRY.A process has been developed for the concentration of hafnium from amixture of zirconium and hafnium in which it occurs only to the extentof 2% by weight up to about 90% in two cycles. Each cycle consists of theadsorption of the mixed zirconium and hafnium chlorides in methanolsolution on activated silica gel, followed by extraction with 1.W-anhydroushydrogen chloride in methanol (which preferentially removes the zirconium),followed by 7~-sulphuric acid which removes the remaining ad~orbate.~gThis follows the earlier experiments reported lo0 that silica gel adsorbshafnium in strong preference to zirconium from a methanol solution of thetetrachlorides.It has long been known l01 that zirconium and hafnium tetrachloridesform addition products with phosphorus pentachloride and phosphorusoxychloride which, since they can be distilled, are of interest in connectionwith the separation of the metals. From this point of view a wider studyhas now been made of the reactions of these tetrahalides with phosphorusoxychloride and the oxyfluorides POFCl,, POF,CI, and POF, ; lo2 withPOC1, and POFC1, the tetrahalides give addition products with the com-position 2POX3,MC14, which decompose when heated under reduced pressure(< 0-1 mm.) to give the 1 : 1 addition products POX,,MCl,. With POF,Cland POF,, however, the metal tetrahalides give only POX,,MCl, at roomtemperature.The introduction of fluorine not only decreases the thermalstability of the addition products but also introduces -the possibility ofhalogen exchange. If the tetrahalides are kept sufficiently long in contactwith excess of POFCl, or POF,Cl, complete halogen exchange takes placewithin the phosphoryl molecule and 2POC13,MC14 crystallises from solution,whilst i f the 1 : 1 addition products with POF,Cl or POF, are heated, somefluorination of the metal halide takes place.Whilst an f electron in thorium is not essential to the general actinidehypothesis, the existence of a tervalent fluoride isostructural with uranium(Ir1)fluoride might be expected on the basis of an electron in the 5f orbitalparalleling cerium(zI1) fluoride with an electron in the 4f orbital.In con-trast, however, to the preparation of the other lower halides lo3 by reductionof the tetrahalides, especially the iodide, by the metal, a number of attempts,by a variety of methods, to reduce ThF? by the metal a t temperatures upto 1600" have failed. There was some indication, however, that thoriumdissolves slightly in its tetrafluoride a t high temperatures as do a number ofother metals in their molten halides.lMThermal, metallographic, X-ray, and chemical analysis have demon-strated the existence of four definite phases in the binary Th-Se system,viz., ThSe, Th,Se,, Th,Se,,, and ThSe2.lo5Distribution measurements of thorium ion between aqueous solutionsand a solution of thenoyltrifluoroacetone in benzene have confirmed thatG.H. Beyer, A. Jacobs, and R. D. Masteller, J . Amer. Chem. SOC., 1952, 74, 825.loo R. S. Hansen, K. Gunnar, A. Jacobs, and C . R. Simmons, ibid., 1950, 72, 5043;Ann. Reports, 1950, 47, 108, ref. 91.lol A. E. Van Arkel and J. H. de Boer, 2. anorg. Chem., 1924, 141, 289.loe E. M. Larsen, J. Howatson, A. M. Gammill, and L. Wittenberg, J . Amer. Chem.SOC., 1952, 74, 3489.lo3 J. S. Anderson and R. W. M. D'Eye, J., 1949, S244; E.Hayek and Th. Rehner,Experientia, 1949, 5, 114; E. Hayek, Th. Rehner, and A. Frank, Monalsh., 1951,83, 575.106 R. W. M. D'Eye, P.G. Sellman, and (Miss) J. R. Murray, J., 1952, 2555.104 J. C . Warf, J . Amer Chem. SOC., 1952, 74, 1864FAIRBROTHER. 95thorium(1v) is present a s a simple, hydrated, tetrapositive ion in perchloratesolutions of an acidity greater than about 0 . 0 8 ~ . The same technique hasbeen used to measure the association constants of some complexes formedbetween thorium ion and fluoride, chloride, nitrate, sulphate, and phosphateions, severally.lo6Some investigations have been reported in connection with bivalentgermanium. Freshly prepared hydrous germanous oxide, obtained byprecipitation with alkali in the cold, is yellow and retains its colour if storedunder water at room temperature.It is, however, thermodynamicallyunstable and on boiling or treatment with aqueous hydrochloric acid changesto dark brown. Potential measurements give GeO(y,llow) = GeO(broq, AGO =-7.2 kcal./mole and GeO, + 2Hf + 2e- = GeO(brown), E" = -0.118 If 0.010volt at 250.1°7 Measurements have also been made of the heat of oxidationof GeI, to germanic acid lo* and of the equilibrium Ge(s) + GeO,(s) =2GeO(g).lo9Several additional new complex compounds of bivalent germaniumhave been prepared : GeI2,2NH,Me ; Ge(H,PO,),,GeCl, ; 3Ge(H2P0,),,GeBr,.These resemble the corresponding compounds of bivalent tin. If ger-manium dioxide is heated alone with hypophosphorous acid it goes intosolution and is reduced to bivalent germanium.This is in contrast tothe behaviour of stannic hydroxide which, although soluble in hypo-phosphorous acid, is not reduced in the absence of hydrochloric acid.l1°It is well known that ordinary tin is converted into the low-temperaturegrey (a) modification at temperatures around 0" if a few particles of pre-viously prepared grey tin are also present. The difficulty usually met withis to obtain some of the latter to initiate the transition. It has now beenshown that if a small cylinder of pure white tin is surrounded by solid carbondioxide, and cold-worked a t this temperature (e.g., submitted to a pressureof several tons), and then kept at -78", it is almost completely transformedinto the grey variety in 24 hours.lllAn examination of the reaction between stannic chloride and hydrazinemono- or di-hydrochloride in varying amounts, has shown that mono-hydrazinium chlorostannate, N2H4,H,SnC1,, or N,H,SnCl,, although re-ported in the literature, does not appear to exist.The only product isolatedfrom these reactions is dihydrazinium chlorostannate, (N,H,),SnC16. 112Group V.-If hydrazine is added to an aqueous solution of a metal ion,such as Zn++ or Ni++, one usually obtains a precipitate in which the pro-Dortion of hvdrazine to metal ion is half that to be exDected from the usual I J co-ordinationH,N NH, I .'-.S,"' Inumber of the metal, e g . , Zn(N,HJ,X,, Ni(N,H,),X,,Ni(N,H,),X,. This has led to the supposition that in thesecompounds both nitrogen atoms of a given hydrazine moleculeare involved with the same metal ion in the formation of aH2N" NH2 three-membered chelate ring (inset).Evidence has now beenobtained which suggests that these metal hydrazine complexes may be inI *OLv'~~,.llo6 E. L. Zebroski, H. W. Alter, and F. K. Heumann, J. Amer. Chem. Soc., 1951,lo' W. L. Jolley and W. M. Latimer, ibid., 1952, 74, 5751.lo8 I d e m , ibid., p. 5752. 109 I d e m , ibid., p. 5754.110 D. A. Everest, J., 1952, 1670.ll1 E. S. Hedges and J . Y. Higgs, Nature, 1952, 160, 622.73, 5646.W. Pugh and A. M. Stephen, J . , 1952, 413896 INORGANIC CHEMISTRY,fact not chelate compounds, but endless networks in which each hydrazinemolecules i s bound to two metal cations :H N H N H4Nz H4N2 H N H N ,A a++ P .,,a++ ,' '.++ ,' ',,* ,A,:++ ,e4*8; .;M:' ;M' ';Ma' ;Ml ,m,' '\:2" H N 'HN 'HN H< H N 4 a 4 2 4 2 4 a 4 2 4 2In two cases no precipitate is obtained-those of the perchlorates and of thefluoroborates. The former are too explosive for investigation, but it hasbeen shown that in the fluoroborates, where the system remains homogeneous,Ni++ ion co-ordinates six molecules of hydrazine, and Zn++ four, the hydrazinefunctioning therefore as a monodentate group.l13Further progress has been made in the study of the liquid dinitrogentetroxide solvent system. The properties of a solution of diethylnitrosamine,which behaves as a " base " in this solvent, indicate that the double com-pound N,O,,SEt,N*NO, which is formed between solvent and solute, under-goes electrolytic dissociation according to the scheme :N204 + 2Et2N*N0 + N2O4,2Et2N-NO + (Et,N.NO),NO+ + NO,-Metallic zinc has been found to react rapidly with solutions of " bases " inliquid dinitrogen tetroxide.With a solution of diethylnitrosamine, nitricoxide is evolved and a red liquid is formed which is immiscible with thedinitrogen tetroxide. This red liquid is indistinguishable from the productobtained by dissolving the compound Zn(N0,),,2N20, in diethylnitrosamineor by adding dinitrogen tetroxide to a solution of anhydrous zinc nitrate indiethylnitrosamine. The reactions which take place are analogous to thereactions of metallic zinc and of zinc hydroxide with aqueous solutions ofalkali : 115Zn + 4N20, + 4Et,N*NO + [(Et2N-NO),NO+],[Zn(N0,),] + 2N0Zn(NO,), + 2N20,, + 4EtaN*N0 + [(Et2N~NO)2NO+]2[Zn(N0,),]Dinitrogen tetroxide also forms addition compounds with ethers, ofwhich a number have been prepared ; 116 with diethyl ether N,O4,2(C,H,),O,m.p. -74.8"; with tetrahydrofuran N,O,,C,H,O, m. p. -20.5", andN20,,2C4H,O (incongruent melting) ; with tetrahydropyran N20,,2C,Hlo0,m. p. -56.8"; and with dioxan N,O,,O[C,H,],O, m. p. 45.2". The struc-tures of these compounds have been studied by spectroscopic and magneticmethods. It is of interest that a suggested explanation of the relativelyhigh melting point of the dioxan compound is the use of both oxygens ofthe dioxan molecule to make possible the formation of an indefinitelyextended aggregation. It may be recalled 67 that co-ordination of dioxanwith one molecule of boron trichloride inhibits the donor character of theother oxygen atom.In connection with the study of liquid dinitrogen tetroxide systems,evidence has been obtained for the existence of a new series of nitrogenoxyacid compounds of the general formula Na,N,O,(x = 3-6).Il7 Thefirst member of this series Na,N,O,, the familiar sodium hyponitrite, is113 G.Schwarzenbach and A. Zobrist, Helv. Chim. A d a , 1952, 35, 1291.11* C. C. Addison and C. P. Conduit, J . , 1952, 1390.116 Idem, J., 1952, 1399.116 B. Rubin, H. H. Sisler, and H. Shechter, J. Amer. Chew. Soc., 1952, 74, 877.117 C. C. Addison, G. A, Gamlen, and R. Thornson, J., 1952, 338, 346FAIR3ROTHER. 97rapidly oxidised by liquid dinitrogen tetroxide to sodium P-oxyhyponitrite(p-Na,N,O,) which differs in chemical properties from the a-compound, ofthe same empirical formula, prepared from hydroxylamine and ethyl nitrate.The latter, sodium a-oxyhyponitrite, also undergoes rapid oxidation to thecompound Na,N,O, which again is a different compound from sodiumnitrite.N%N,04 undergoes a further slow oxidation in liquid dinitrogentetroxide to a compound of empirical formula NaNO, which may be thedimer Na,N,O,, and a silver salt believed to have the formula Ag,N20,has been prepared. Sodium p-oxyhyponitrite undergoes slow oxidation inliquid dinitrogen tetroxide to the compound Na,N,O, which is also formedrapidly by the action of nitrogen dioxide gas a t 100" on sodium hyponitrite,and is further oxidised slowly under these conditions to the NaNO, (orN+N,O,) stage.Ultra-violet absorption spectra of aqueous solutions ofthe hydrolysis products of these compounds have been examined and anattempt has been made to formulate structures for them.Hydrogen peroxide has been shown to react with nitrous acid, nitricoxide, and nitrogen dioxide with the formation of pernitrous acid, HNO,.From the behaviour of the products of these reactions in initiating the poly-merisation of methyl methacrylate and in hydroxylating and nitratingbenzene, it has been suggested that pernitrous acid undergoes homolyticfission to give OH radicals and nitrogen dioxide.' l8Further studies have been made of nitrosyl chloride as an acid-baseionising solvent and of the behaviour in solution of several nitrosyl doublecompounds : NOFeCl,, NOAlCl,, NOBF,, (NO),SnCl,.Nitrosyl com-pounds react in nitrosyl chloride solution with the slightly soluble (CH,),NC!in the sense of the acid-base neutralisation NO+ + C1-c NOCl as demon-strated by a conductometric titration of NOFeC1, by (CH,),NCl and by thepartial neutralisation equilibria of NOBF,, NOClO,, and (NO),S,O,, eachwith (CH,),NCl. The idea that NO+ represents " acid I' and C1- " base "is further justified by the electrolysis of NOFeC1, in NOC1, which gives NOat the cathode and C1, at the anode.llsSome work has been carried out on the constitution and reactions ofnitryl chloride, N0,Cl. On hydrolysis and alcoholysis this behaves as anitrosyl hypochlorite. 120 By the reaction of nitryl chloride with antimonypentachloride in liquid chlorine, one can obtain a compound NO,Cl,SbCl,which behaves as nitrosyl chloroantimonate [No,]+[sbc~,]- : it dissolves inliquid sulphur dioxide to give a conducting solution and undergoes ionicreactions with tetramethylammonium perchlorate and fluoroborate to givenitryl perchlorate and fluoroborate respectively : 121[NO,][SbCl,] + [NMe,]ClO, = [NO,]CIO, + [NMeJSbCl,[NO,][SbCI,] + [NMeJBF, = [N0,]BF4 + [NMe,]SbCI,An investigation of the behaviour of nitryl chloride towards ammoniaand a number of Lewis acids suggests that the nitrogen-chlorine bond isnot so strongly polarised as to act as a source of negative chlorine, excepttowards exceedingly strong electron acceptors such as sulphur trioxide,with which it forms N0,C1,2S03, presumably nitronium chlorodisulphate118 E.Halfpenny and P. L. Robinson, J., 1952, 928.ll9 A. B. Burg and D. E. McKenzie, J . Amer. Chem. SOC., 1952, 74, 3143.lZo F. Seel and J. N6grAdi, 2. anorg. Chew., 1952, 269, 188.leL I?. Seel, J. N6gr&di, and R. Posse, ibid., p. 197.REP.-VOL. XLIX. 98 INORGANIC CHEMISTRY.N0,(ClS206). Thus, on reaction with ammonia it yields chloroamine andammonium nitrite, rather than nitramide and ammonium chloride, and itdoes not react with SnCl, or BF,, which might be expected to co-ordinatea negative chlorine. It has been suggested that the addition of the secondoxygen atom in going from nitrosyl chloride to nitryl chloride either greatlyreduces the polarity of the N-C1 bond or actually reverses its direction, sothat the chlorine becomes positive.122Dinitrogen tetrasulphide, N,S,, which has been known for a long time,123has received renewed attention.This compound, which is prepared bythe action of sulphur in N,S, (e.g., in CS, solution in an autoclave a t 100-120"), is a dark red, fairly unstable solid, m. p. 23". It is soluble in manyorganic solvents and is diamagnetic. The latter excludes a dissociation intoNS, molecules, which would be paramagnetic, whilst its chemical behaviourtowards a variety of reagents suggests that its structural formula is quitedifferent from that of its oxygen analogue dinitrogen tetroxide.124The two new double compounds Li,AlP, and Li,AIAs, have been pre-~ared.1,~ In their chemical reactions these compounds behave more likeLi,P and Li,As than as A1P or A1S respectively.It is reported that compounds of the type PX,,IY, where X and Y aredifferent halogens, can be synthesised directly, either by fusion together ofthe components PX, and IY, or by dissolving these in CCI,. PBr,ICl hasbeen prepared by the latter method and forms cherry-red needle-shapedcrystals, m.p. 112.8". It is formulated by the authors as [PBr,+][BrICI-].PC1,IBr forms yellow crystals, m. p. 140" (decomp.).12,A spectrophometric study of phosphorus hexachloroiodide and hexa-bromoiodide has shown that these compounds dissociate in carbon tetra-chloride solution into their component molecules, PCl,I 2 PCl, + ICI;PBr,I -+ PBr, + IBr + Br,, whereas in polar solvents such as aceto-nitrile the dissociation is ionic : PCI,I -+ PC1,' + Ic12- and PBr,I 4PBr,+ + IBr2-.127Solubility measurements of antimonous oxide in water and in dilutesolutions of hydrochloric acid and of sodium hydroxide show that in bothacid and alkaline solutions the antimony is present as a univalent ion, SbO+and Sb02-, respectively.lZ8Antimony pentafluoride , a compound with some remarkable physicalproperties,l29 appears to possess a power of compound formation which ismuch greater than that of arsenic pentafluoride.Some unusual chemicalcompounds which include antimony pentafluoride have been reported. Itdissolves sulphur, selenium] and tellurium to give blue, yellow, and redsolutions, respectively, from which the stable crystalline compounds(SbF,),S, (SbF,),Se, and (SbF,),Te can be isolated.Sulphur dioxide formsSbF,SO,, and NO, forms SbF,N0,.13*122 H. H. Batey and H. H. Sisler, J . Amer. Chem. SOC., 1952, 74, 3408.134 M. Goehring, H. Herb, and H. Wissemeir, 2. anorg. Chem., 1952, 267, 238.lZ6 R. Juza and W. Schulz, ibid., 1952, 269, 1.126 I. D. Muzyka and Ya. A. Fialkov, Doklady Akad. Nauk. S.S.S.R., 1952, 83, 415;127 A. I. Popov and E. H. Schmorr, J . Amer. Chem. Soc., 1952, 74, 4672.128 K. H. Gayer and A. B. Garrett, ibid., p. 2353.lee A. A. Woolf and N. N. Greenwood, J., 1950, 2200.l30 E. E. Aynsley, R. D. Peacock, and P. L. Robinson, Chem. and I s d . , 1951, 1117.F. L. Usher, J., 1925, 730.Chem.Abs., 1952, 46, 6983FAIRBROTHER. 99It is reported131 that almost pure vanadium monoxide (99.68%) hasbeen prepared by heating a compressed intimate mixture of V203 andfinely divided vanadium in a vacuum a t 1750". The product is describedas having a speeific gravity of 5.55, a hardness of 8-9 on Mohs' scale, andto dissolve in acids to give the blue or violet solutions characteristic ofhypovanadous salts.The monoboride VB and the mononitride VN have also been examined,the former being prepared 132 as the product of the simultaneous reductionof V205 and B203 with carbon in a graphite crucible at 1650" in an atmosphereof hydrogen, and VN in a crystalline form by the action of nitrogen andhydrogen on the vapour of vanadium tetrachloride in the presence of aheated filament.The latter technique has also been used to prepare niobiummononitride NbN, though in the form of smaller crystals than the vanadiumnitride.133A preliminary report has been made of a new solvent extraction methodfor the separation of niobium and tantalum. It has been found, by usinga tracer technique, that niobium can be extracted almost quantitativelyfrom concentrated hydrochloric acid solution by a solution of methyldioctyl-amine in xylene : under these conditions the extraction of tantalum appearsto be almost negligible. The niobium can then be extracted from theorganic phase with nitric, sulphuric, or dilute hydrochloric a ~ i d . 1 ~ ~An inorganic chromatographic separation of these two elements fromone another and from other elements present in complex minerals, andsuitable for their quantitative determination, has been developed.Thismethod is based on the adsorption of the metals as fluorides on a cellulosecolumn in a Polythene tube, and selective extraction by ethyl methylketone containing hydrofiuoric acid. 135The elution by 7.0~-hydrochloric acid of carrier-free 95Nb, adsorbed froma 10.0M-hydrochloric acid solution on a Dowex 2 anion-exchange resin,instead of giving the usual symmetrical curve of activity of eluant versusvolume of eluant, gives a curve which shows several peaks. As these can beidentified by the characteristic disintegration rate of 95Nb, the presence ofany other species, or of isotopic separation, may be excluded.This resulthas been attributed to the slow establishment of equilibrium among thevarious ionic species present, which would not necessarily have differentcharges as in the case of the thiocyanate complexes of chromium, whichhave been separated by this kind of technique,20 but may contain differentnumbers of chloro-, oxy-, and hydroxy-groups. Elution with 6.0~-hydro-chloric acid gives the usual symmetrical elution curve.136It has been shown that niobium pentachloride and tantalum penta-chloride form a continuous series of mixed ~rysta1s.l~~When niobium pentachloride is heated at 350-400" with niobium metal,in a molar ratio greater than 4 : 1, niobium tetrachloride may be obtained131 M. Frandsen, J . Amer. Chem. Soc., 1952, 74, 5046.132 H.Blumenthal, ibid., p. 2942.133 F. H. Pollard and G. W. A. Fowles, J., 1952, 2444.la4 G. W. Leddicotte and F. L. Moore, J . Amer. Chem. Soc., 1952, 74, 1618.lS6 F. H. Burstall, P. Swain, A. F. Williams, and G. A. Wood, J., 1952, 1497;136 E. H. Huffman and G. M. Iddings, J . Amer. Ckem. Soc., 1952, 74, 4714.137 H. Schafer and C. Pietruck, 2. anorg. Chem., 1952, 267, 174.A. F. Williams, J., 1952, 3155; R. A. Mercer and A. F. Williams, J . , 1952, 3399100 INORGANIC CHEMISTRY.as large needles. With a greater proportion of metal, the trichloride isobtained, or some lower chloride which disproportionates near 600" into themetal and the trichloride.138Niobium tetrachloride also disproportionates on heating, and the equili-brium pressure of the decomposition 2NbC1, = NbCl, + NbC1, has beenmeasured.139Although quinquevalent tantalum is much less easily. reduced thanquinquevalent niobium, TaCl, being unaffected by hydrogen a t temperaturesup to 400°, there is evidence that at temperatures over 500" some reductionof TaCl, does occur. Similarly, if hydrogen chloride or hydrogen bromideis passed over the metal a t about 400' only the pentahalide is formed. Athigher temperatures (between 600" and SOO"), however, lower halides areformed which may undergo some disproportionation with the deposition offilms of metallic tantalum on the walls of the apparatus.140The reduction of niobium and tantalum pentoxides, and mixtures of 'thetwo, to the quadrivalent dioxides by moist hydrogen a t 900°, has beeninvestigated.141Group VI.-A comprehensive review has been published 142 of themethods used for the production and determination of abundance of isotopicoxygen and of its applications. Details have also been given 143 of theconstruction and operation of a number of fractionating columns for theenrichment of l 8 0 in water. One of these is reported as being capable ofproducing per day, 200 C.C. of 0.6% H,180, or 50 C.C. of 1.7% H2180 or20 C.C. of 3.2% H,I80 : another, operating as a second stage, gives 10 C.C.of 12% H,180 per week.The isotope l80 has been used as a tracer in the study of the mechanismof oxidation of hydrogen peroxide.lU The oxygen liberated when H,O,is oxidised in aqueous solution by Ce(Iv), Mn04-, Cl,, HC10, and Cr20,.p isderived wholly from the hydrogen peroxide and not from the water.Simi-larly, the oxygen liberafed in the catalytic decomposition of H,O, by Fe(m),I-, I,, Br-, Br,, MnO,, and Pt is derived only from the H,O,.A series of higher sulphur chlorides with the composition S&1, (where xcan have values up to about 100, depending upon the temperature of re-action), and consisting of long sulphur chains terminated a t the ends bythe two chlorine atoms, has been prepared by a " hot-cold '' tube methodfrom S,Cl, and h ~ d r 0 g e n . l ~ ~Some new trifluoromethyl derivatives of sulphur have been prepared.Trifluoroiodomethane, CFJ, reacts with sulphur to give bistrifluorornethyldisulphide (CF3),S,, carbon disulphide, thiocarbonyl fluoride, and poly-sulphides.Bistrifluoromethyl disulphide undergoes an unusual type ofhydrolysis in aqueous alkali, the first stage of which consists in the hydrolyticfission of the S-S bond to give trifluoromethanethiol and trifluoromethane-138 H. Schafer, C. Goser, and L. Bayer, 2. anorg. Chem., 1951, 265, 258; C. H.139 H. Schafer, L. Bayer, and H. Lehmann, 2. anovg. Chem., 1952, 268, 268.140 R. C. Young and C. H. Brubaker, Jr., J . Amer. Chem. SOC., 1952, 74, 4967.1 4 1 H. Schafer and B. Breil, 2. anorg. Chem., 1952, 267, 265.142 M. Dole, Chem. Reviews, 1952, 51, 263.143 I. Dostrovsky, D. R. Llewellyn, and B. H. Vromen, J . , 1952, 3509 : I. Dostrov-sky, J. Gillis, D. R. Llewellyn, and B. H. Vromen, J., 1952, 3517.144 A. E. Cahill and H. Taube, J .Amer. Chem. SOC., 1952, 74, 2312.145 F. FCher and M. Baudler, 2. an0p.g. Chem., 1952, 267, 293.Brubaker, Jr., and R. C. Young, J . Avner. Chem. SOC., 1952, 74, 3690FAIRBROTHEH. 101sulphenic acid which subsequently break up to give fluoride, carbonate; andsulphide ions :NaOHCF,*S*S*CF, -> CF,-SH + CF,*S*OHF-, CO,', S" f- F2C:S + HF F-,CO,', S"J. J.On irradiation in the presence of mercury, the disulphide yields bis(trifluor0-methy1thio)mercury (CF3S),Hg : in the absence of mercury it gives bistri-fluoromethyl sulphide which, in contrast to the disulphide, is quite stableto aqueous alkali. 146It is reported that the chloride of trichlorophosphazosulphuric acid,ClSO,N:PCl,, has been prepared by the reaction a t 100" between sulphamicacid and phosphorus pentachIoride.147New methods have been described for the preparation of seleniumoxyfluoride and selenium tetrafluoride. The latter is prepared by theaction of dilute fluorine on selenium a t 0". It is a liquid, m.p. -9-5', b. p.106", with some remarkable solvent properties. It dissolves the fluoridesof sodium, potassium, rubidium, and caesium to form complexes with acomposition approaching MSeF, which is different from that of any of theother complex selenium halides, viz., M,SeX,. 148Selenium, diselenium, and triselenium di(benzenesu1phinate) and di-(toluenesulphinate), Se(SO,R),, Se,(SO,R),, and Se,(SO,R),, have beenprepared, and represent a new class of selenium compounds of which thesulphur analogues have been known for a long time.In their reactionsthey behave as derivatives of Se++, Se2++, and Se,++, re~pectively.1~~ Selen-ium and tellurium di(benzenethiosu1phonate) and di(to1uene-p-thiosulphate)have also been prepared. 15*Conductivity measurements have shown that tellurium tetrachloridebehaves as an " acid " in arsenic trichloride solution and may be titratedconductimetrically in this solvent with (CH3),NC1. Compounds can beisolated from the resulting solution which are probably the " acid " and" normal " salts respectively, (NMe,) (AsCl,) (TeC1,) and (NMe4),TeC1,.151The system chromium(II1) oxide-water has been studied in the temper-ature range 145-560" by the hydrothermal method. A definite blue-greycompound, CrO(OH), d = 4-12, is formed below 419424'. This decom-poses sharply and endothermically a t about 430".Rhombohedra1 Cr,O,is the stable phase above 450°.152The products obtained when chromium(v1) trioxide is heated in a vacuumhave been investigated by X-ray and chemical ana1y~is.l~~ Evidence hasbeen obtained of the existence of three definite compounds intermediatebetween CrO, and C1-203, vix., Cr,O,, Cr,O,, and CrO,.Pure chromyl fluoride, CrO,F,, has been prepared for the first time, bythe reaction between CrO, and anhydrous hydrogen fluoride in an apparatusbuilt out of copper, silica-free glass, and Kel-F tubing. It forms violet-red1413 G. A. R. Brandt, H. J. Emelkus, and R. N. Haszeldine, J., 1952, 2198.14' A. V. Kirsanov, Zhur. Obshckei Khim., 1962, 22, 88; Chem. Abs., 1952, 46, 6984.148 E.E. Aynsley, R. D. Peacock, and P. L. Robinson, J., 1952, 1231.149 0. Foss, Acta Claem. Scand., 1952, 6, 508.150 Idem, ibid., p. 521.161 V. Gutmann, Monatsh., 1952, 83, 159.152 A.158 R. S . Schwartz, I. Fankuchen, and R. Ward, ibid., p. 1676.Laubengayer and H. W. McCune, J . Apner. Chem. SOC., 1952, 74, 2362102 INORGANIC CHEMISTRY.crystals which have a v. p. of 760 mm. at 29.6" and melt to an orange-redliquid at 31.6" under a pressure of 885 rnrn.15,An examination of the spectra of chromic acid and chromic acid-phos-phoric acid systems has indicated the formation of two chromate-phosphatecomplex ions, HCrPO," and H,CrPO,-. 155The alkali-metal compounds of chromium of the type MCr3.0, have beenprepared and examined.156 The oxidation states of chromium in thesecompounds, which are obtained by heating mixtures of the compositionM,Cr,O, + XrO, at 350" in air for two hours and extracting the excess ofthe dichromate with water, appear somewhat problematical. The blackmetallic appearance of, for example, the potassium compound suggests thatit is not a compound containing chromium in its two usual and independentstates of oxidation 3 and 6, K,Cr,(CrO,), or K2(CrO)2(Cr207)2, but that thereis some interaction between the chromium ions so that the effective overalloxidation state is +5.A compound of univalent chromium (dipy3Cr1)(C10,) (dipy = 2 : 2'-dipyridyl) is reported to be formed by reduction of the bivalent compound(dipy,Crrl) (ClO,), by magnesium in the presence of ammonium perchlorate,and with exclusion of air.157On treating chromium hexacarbonyl with alcoholic potassium hydroxide,a brilliantly yellow derivative is obtained, which on acidification yields awhite, volatile, unstable, crystalline substance, the properties of whichsuggest that it is C T ( C O ) ~ H , .~ ~ ~The term " tungsten bronze " is used to describe the non-stoicheiometriccompounds of general formula M,WO, (where M is an alkali metal and x isless than unity) obtained on reduction of the alkali tungstates. Thesehave been considered (a) as solutions of tungsten(v1) oxide in a hypotheticaltungsten(v) compound MWO,, and also ( b ) , on account of their high electricalconductivity, low magnetic moment, and general metallic appearance, assolid solutions of alkali metal in WO,.The essential difference betweenthese two models is that in (a) the electron from the alkali metal is con-sidered to be strongly associated with the tungsten(v) ion, which wouldtherefore be paramagnetic, whereas in (b) the electron from the alkalimetal is part of the electron gas that is associated with the whole lattice.To distinguish between these two models, the magnetic susceptibilities of avery wide series of lithium tungsten bronzes have been measured.159 Thevalues of the susceptibilities are very low and actually become diamagneticas the concentration of lithium is decreased. The results are in agreementwith those calculated for an electron-gas model.Studies have been made of the alkali-metal molybdate systems, K,MoO,-MOO,, Rb,MoO,-MoO,, and CS,MOO~-MOO,,~~~ and of the alkali fluoridernolybdenum(v) systems, LiF-MOO,, NaF-MOO,, KF-MOO,, RbF-Moo,,and CsMoO,.lG11 5 4 A.Engelbrecht and A. V. Grosse, J . Amer. Chem. Soc. 1952, 74, 5262.155 F. Holloway, ibid., p. 224.1 5 6 L. Suchow, I. Fankuchen, and R. Ward, ibid., p. 1678.1 5 7 Fr. Hein and S. Herzog, 2. anorg. Chem., 1952, 26'4, 337.1 5 8 M. G. Rhomberg and B. B. Owen, J . Amer. Chem. Soc., 1951, 73, 5904.1 5 9 L. E. Conroy and M. J. Sienko, ibid., 1952, 74, 3520.160 V. I. Spitsyn and I. M. Kuleshov, J . Gen. Chem. U.S.S.R., 1951, 1493; Chem.161 0. Schmitz-Dumont and I. Heckmann, 2. amrg. Chem., 1952, 26'4, 277..Abs., 1952, 46, 9006FAIRBROTHER. 103Uranium and the trans-uranic elements.Further investigation has beenmade of the sodium uranates. Chemical, X-ray diffraction, pH, and con-ductivity data indicate that when sufficient sodium hydroxide is added touranyl nitrate solutions, two compounds Na,U702, and Na6U,O2, (ormixtures of these) are precipitated. In the first place, when just insufficientsodium hydroxide to produce precipitation is added (which requires 1 mol.or more of NaOH per mol. of U02++), basic uranyl ions UO,UO,++ and(U03),U02++ are formed. Further addition of NaOH to a mole ratioNaOH/U of 2.29, causes the quantitahe precipitation of the uranium asNa,U,O,,. This in turn may react with excess of alkali to give Na6U7Oz4.l6,The diuranates of the alkaline-earth metals have been prepared by theignition of the corresponding metal uranyl acetates, a method of preparationwhich has been found to give a product free from an excess of either thealkaline-earth metal or uranium oxide.The thermal stabilities in vacuumand in oxygen up to 1100" have been investigated and the results have shownthat the metal diuranate-oxygen systems are reversible below thistemperature. 163The magnetic susceptibilities of UF4-ThF, solid solutions reportedearlier,164 which seemed to indicate the presence of two 5f electrons in UF,,have been corrected by the author. The amended values 165 show that,within experimental error, both the susceptibility at room temperature andthe moment extrapolated to infinite dilution agree with the values predictedfor two unpaired spins with the orbital contribution to the moment com-pletely quenched.These results therefore fall into line with those obtainedfor the U02-Th0, solid solutions 166 and imply a configuration of 6d2 forthe U4+ ion.The magnetic susceptibilities of plutonium dioxide and tetrafluoridehave also been measured, over the temperature range 90-450" K. Measure-ments made on the solid solutions of PuF, in the isomorphous ThF, lead toan extrapolated susceptibility at infinite dilution in agreement with a 5f4configuration. The dioxide has approximately the same susceptibility atinfinite dilution, but the behaviour with increasing concentration is morecomplex and some of the evidence may indicate that 6d levels are occupied.167The sexavalent plutonium ion should have two unpaired electrons, and inorder to determine whether these are in the 5f or the 6d level, the magneticsusceptibility of sodium plutonyl acetate has been measured over the tem-perature range 90-300" K.The results agree with the theoretical value forspin-only for two electrons, which therefore may be taken as evidence thatthe ground state of the plutonyl ion has a 6d2 configuration.168 + H(aq)+. = + 2.4 v, and Pqaq)++ + +H,,,) = Pr,,,,3+ + H(aql+ = + 2.9 v have been estim-ated from thermodynamical data and .measurements of the heats of reactionof the oxides with nitric acid and fluoroboric acid in a micro-calorimeter.169The potentials of the couples + +H,,, =162 C. A. Wamser, J . Belle, E. Bernsohn, and B. Williamson, J.Amer. Chem. SOL,H. R. Hoekstra and J . J . Katz, ibid., p. 1683.164 J. K. Dawson, J., 1951, 2889; Ann. Reports, 1951, 48, 102, ref. 146.166 I d e m , J., 1952, 1185.166 W. Trzebiatowski and P. W. Selwood, J. Amer. Chem. SOL, 1950, 72, 4504;Ann. Reports, 1950, 4'7, 116, ref. 164.1 6 7 J . K. Dawson, J., 1952, 1882.16s L. Eyring, H. R. Lohr, and B. B. Cunningham, J . Amel.. Chem. SOC., 1952,74,1186.1952, 74, 1020.lB8 Idem, J . , 1952, 2705104 IXOKGANIC CHEMISTRY.An interesting feature of this work was that the primary objective was theevaluation of the Am4+-Ama+ potential and that the chemically similar butmore abundant praseodyrninium was used-as the authors express it-as a" stand-in " for the perfection of the technique.A further study has been made of the chemistry of sexavalent americium,which has been shown to resemble that of U(VI), Np(vr), and Pu(v1).170A search has been made in aqueous solution for oxidation states ofcurium higher than Cm3+ by using macro-amounts (up to 238 pg.per experi-ment) of the element, and using 'americium(m), which does exhibit thehigher oxidation states +5 and +6 in solution, as an internal check. Noevidence was found for the existence of Cm4+, Cm5 I , or Cm6+ in the oxidationof Cm3+-Am3+ mixtures in either acid or alkaline solutions, under con-ditions where the Am3+ was oxidised quantitatively to Am5+ or Am6+.171Group VI1.-The conditions and products of reaction of elementaryfluorine with zinc, zinc oxide, zinc bromide, zinc sulphide, nickel, nickel(I1)oxide, nickel(m) oxide, and nickel(r1) sulphate have been investigated.There was no evidence of the production of a higher fluoride of nickel bythe fluorination of the so-called nickel(II1) oxide, Ni20, : in all cases thebivalent fluorides were the only non-volatile products observed.172Silver tetrafluoroborate can be simply prepared by the action of brominetrifluoride on dry silver borate, and undergoes rapid decomposition at 200"into silver fluoride and boron trifluoride.These reactions form a convenientmethod of preparation of small quantities of anhydrous silver fluoride, andcan be carried out in quartz apparatus.173The magnetic susceptibilities of a number of simple and complex fluoridesof transition metals have been measured, vzz., K2TiF, ; K,TiF,,H,O ;VF, ; K,VF, ; K,CrF5,H,0 ; KCrOF, ; K,MnF5,H20 ; Li,FeF, ; Na,FeF, ;K,FeF, ; CsFeF, ; CuF,,2H20 ; TaF, ; RhF, ; Na,RhF, ; PdF, ; PtF, ;K,PtF, ; AuF, ; AgAuF,.Compounds of the first transition series, exceptwhen magnetically concentrated, show the number of unpaired electronswhich would be expected for ionic binding. For the second and third tran-sition series, however, when the number of electrons in the metal ion iseven, the compounds are diamagnetic, and paramagnetic when the number isodd, but with a moment which corresponds to only one unpaired electron,which shows that for these two series, minimum multiplicity is the rule evenfor f l ~ 0 r i d e s . l ~ ~The commercial availability of chlorine trifluoride, and the ease withwhich it can be used, offer the possibility of its substitution for elementaryfluorine as a fluorinating agent in a number of reactions, and a number ofmetal fluorides have been prepared from the metals by its use.Detailshave now been given of the preparation of cobalt(m), nickel(II), and silver(I1)fluorides from chlorine trifluoride and cobalt(rI), nickel(n), and silver(1)chlorides, re~pective1y.l'~The existence of bromine monochloride in carbon tetrachloride solution170 L. B. Asprey, S. E. Stephanou, and R. A. Penneman, J . Amer. Chem. SOC.,171 S. E. Stephanou and R. A. Penneman, ibid., 1952, 14, 3701.172 H. M. Haendler, W. L. Patterson, Jr., and W. J . Bernard, ibid., p. 3167.173 A. G. Sharpe, J., 1952, 4538.174 R.S. Nyholm and A. G. Sharpe, J . , 1952, 3579.175 E. G. Rochow and I. Kukin, J . Amer. Chem. Soc., 1952, 74, 1615.1951, 73, 5715FAIRBHOTHE R. 105was clearly proved nearly 25 years ag0,1'~ and described as probably highlydissociated. The extent of this dissociation has now been re-investigatedspectrophotometrically and found to amount to 43.2&1% at 25". Theequilibrium constant for the reaction 2BrCl + Br, + C1, in carbon tetra-chloride has been calculated to be 0-145 & 0-006.177Alkali hypobromites are familiar in aqueous solution, but no solid hypo-bromites appear to have been isolated.178 It is reported, however, that at-5" it is possible to isolate the crystalline alkali hypobromites NaBrO,SH,Oand 7H20, and KBr0,3H20 from the products of the action of bromine onsolutions of the respective hydroxides at this temperat~re.~'~that molecular iodine formedbrown solutions, and was polarised, in electron-donor or " basic " solvents,which included aromatic and olefinic hydrocarbons.It was subsequentlydemonstrated that iodine formed 1 : 1 addition compounds with severalaromatic hydrocarbons. Ultra-violet absorption measurements havenow shown that iodine forms 1 : 1 addition compounds also with olefins atlow temperatures. 82The system MnS0,-H2S04-H,O has been investigated at O", 20", 25",45", 65", and 95.7", and the following solid phases identified : MnS0,,5H20,MnSO,,H,O, MnS0,,H2S0,,H,0, MnSO,,H,SO,, and MnS04,3H,S04.183The separation of technetium from uranium-fission product wastes hasmade this element available in weighable amounts and therefore madepossible the investigation of its chemistry by ordinary analytical methodsinstead of only by tracer techniques. Approximately 0.6 g.of the spectro-graphically pure metal has been prepared by the hydrogen reduction ofammonium pertechnetate lS4 and it has been established that the lightyellow crystalline oxide (m. p. 119.5" 0.1') obtained when technetium isheated in dry oxygen at 400-600" is Tc,O,. The pertechnetate ion possessesan intense ultra-violet absorption (molar extinction at 2470 = 4000)which can be used for its spectrophotometric detennination-as little asg. of technetium can be detected in this way.lS5 Technetium hepta-sulphide, previously assumed to be Tc2S7 on the basis of analogy with Re$,,has also been examined and its formula confirmed by chemical analysis.186The existence of rhenium in aqueous solution in the -1 oxidation stateis now accepted on the basis of the stoicheiometry of its reduction.A solidrhenide, however, has recently been reported for the first time. Whenpotassium perrhenate is reduced by potassium in ethylenediamine, a whitesolid is deposited which is stated to contain rhenium in the -1 oxidationstate, together with some potassium hydroxide.la7It was pointed out several years ago17& A. E. Gillam and R. A. Morton, Proc. Roy. Soc., 1929, A, 124, 604.177 A. I. Popov and 3. J. Mannion, J . Amer. Chem. Soc., 1952, 74, 222.1'9 R. Scholder and K. Krauss, 2. anarg. Chem., 1952, 288, 279.180 F.Fairbrother, J., 1948, 1051.181 H. A. Benesi and J. H. Hildebrand, J . Amer. Cham. Soc., 1949, 71, 2703.1*2 S. Freed and K. M. Sancier, ibid., 1952, 74, 1273.183 D. Taylor, J., 1952, 2370.184 J. W. Cobble, C. M. Nelson, G. W. Parker, W. T. Smith, Jr., and G. E. Boyd.J . Amer. Chem. SOC., 1952, 74, 1852.185 G. E. Boyd, J . W. Cobble, C. M. Nelson, and W. T. Smith, Jr., ibid., p. 556,186 C. L. Rulfs and W. W. Meinke, ibid., p. 235.187 E. Griswold, J . Kleinberg, and J. B. Bravo, Science, 1962, 115, 375.N. V. Sidgwick, " The Chemical Elements and Their Compounds," Oxford,1950, p. 1221106 INORGANIC CHEMISTRY.Group VII1.-The bicentenary of the discovery of nickel in 1751 byCronstedt has been marked by a symposium on recent developments in thechemistry and applications of nickel and its compounds.188A detailed X-ray examination of the compound Ni(CN),,NH,,C,H,,which is obtained as a precipitate when benzene is added to a solution ofnickel cyanide in ammonia, has shown that the benzene-which exhibits no'detectable vapour pressure a t room temperature-is not linked to thenickel complex by chemical bonds, but that the benzene molecules are heldin cavities formed by the solid structure of the complex.189A study of the reaction between nickel tetracarbonyl and o-phenylene-bisdimethylarsine has shown that two of the carbonyl groups are readilyreplaced by the chelate group to yield a stable, crystalline, diamagneticcompound of the formula Ni(CO),(diarsine) : attempts to replace all fourcarbonyl groups, however, were unsuccessful. Oxidation of this complexwith iodine liberates carbon monoxide, giving the compound NiI,(diarsine) ,the first of a previously unknown class of cis-planar bivalent nickel complexes.The corresponding chloride and bromide are much less stable.By oxidationof the bromide with excess of bromine, a tervalent nickel complex bromideof the formula NiBr,(diarsine) has been prepared.lgODetails have been given of a convenient laboratory method of preparationof nickel and cobalt carbonyls and of a number of their derivatives, which isbased on the reaction between carbon monoxide, at atmospheric pressure,and aqueous ammoniacal solutions of nickel and cobalt salts in the presenceof sodium dithionite.lglSeveral new reactions of sodium in liquid ammonia with the carbonylsof cobalt and iron have been reported.lg2Cobalt(I1) chloride is well known to form a mono-, a di-, and a hexa-hydrate, but there is less definite evidence of the existence of a tetrahydrate.An investigation of the system CoC1,-H,O-acetone has now shown that thetetrahydrate and a hitherto unreported trihydrate also exist over narrowranges of water a c t i ~ i t y .1 ~ ~A spectrophotometric study of the deep blue solution obtained when acobalt(I1) salt is dissolved in strongly alkaline solution has shown that thecolour is due to a trihydroxycobalt(I1) ion, C O ( O H ) ~ - . ~ ~ ~The products of the reduction of cobalt(I1) nitrate with two equivalentsof potassium in liquid ammonia are (i) insoluble cobalt(I1) amide and (ii) amixture of soluble nitrate and nitrite.If a large excess of potassium isused, however, almost all the nitrate is reduced to nitrite, and the insolubleproduct consists principally of potassium hydroxide and elemental cobalt.The cobalt which is obtained by the reduction of cobalt(II1) bromide inliquid ammonia in this way exhibits a marked activity as a catalyst for thehydrogenation of ally1 alcohol a t room temperature.lg5Some preliminary results have been published of an investigation of theSymposium, I n d . Eng. Chem., 1952, 44, 949.J . H. Rayner and H. M. Powell, J., 1952, 319.190 R. S. Nyholm, J., 1952, 2906.191 W. Hieber, E. 0. Fischer, and E. Bockley, 2. anorg. Chem., 1952, 269, 308.192 H.Behrens, 2. Nalurforsch., 1952, 7, b, 321.lgS L. I. Katzin and J. R. Ferraro, J . Amer. Chem. Soc., 1952, 74, 275.lg4 S. Gordon and J. M. Schreyer, ibid., p. 3169.195 G. W. Watt and C . W. Keenan, ibid., p. 2048FAIRBROTHER. 107preparation and properties of the curious compound known as " cobalticacetate "-the product obtained by anodic oxidation of cobalt(I1) acetateThe elucidation of thex4c0<~~>cOx4 structure of this compound presents some difficulties, butits properties seem to indicate a possibility that it may be a binuclearcomplex containing the p-dihydroxo-bridge grouping (inset). lg6Tracer experiments with H,180 have shown that in the aquation ofcarbonat open t amminocobalt (111) ionwhich takes place rapidly in water, and still more rapidly when the solutionis acidified, the cobalt-oxygen bond remains intact, the removal of carbonatefrom the complex ion taking place by the removal of carbon dioxide, i.e.,by the breaking of the carbon-oxygen bond.lg7 The mechanism is thereforesimilar to that observed in the hydrolysis of an ester.lg8A study of the type of bonding in a number of bidentate chelate cobaltcomplexes has been made by a radio-isotope exchange technique, using 6oCo.Where the bonding is mainly ionic, a rapid exchange occurs and as the co-valent character of the bonding increases so one can expect a diminution inthe rate of exchange of the cobalt.The same technique has been used tostudy the behaviour of bis(salicylideneani1ine) cobalt (11) and cobalt (11)acetate in pyridine solution on alumina and similar surfaces and on an ion-exchange resin, The break-up of the complex on these surfaces points tothe considerable ionic nature of the binding of the cobalt atom in suchcomplexes. lg9Further sexadentate cobalt (111) compounds have been prepared by theuse as ligands of condensation products of a series of sulphur-containingaw-diamines of the general formula : NH,*[CH,]Z*S*[CH,],*S*[CH2]z*NH2,where x, y , and x are 2 or 3, with salicylaldehyde or 2-hydroxy-l-naphth-aldehyde.Most of the complex salts prepared have been resolved intooptical isomers, some with extremely high rotations.200In connection with a study of the magnetic moments of octahedralcomplexes of Cr, Mn, Ni, Co, and Fe, with the chelate agents dipyridyl,and o-phenylenebisdimethylarsine, C,H,(AsMe,),, the following newcompounds have been prepared: [Co(diarsine),] (ClOJ,, [Co(diarsine),] (C1OJ3,[Co(diarsine),( OAc) 2] (C10,) , [Co( dipy),] ( C10,),,3H20, and[Cr(dipy),Cl,]Cl,ZH,O. Also the co-ordination of tervalent chromiumwith a tertiary arsine has been reported for the first time.In compoundsof the type MIr(dipy),X2 the bonds are ionic 4s4P34d2 when MI1 = Mn orCo and covalent 3d24s4P3 when the metal is Fe or Cr. The paramagnetismof the corresponding nickel compounds indicates that the bonds are ionicrather than covalent. In the dipyridyl complexes of tervalent iron orcobalt, the bonds are covalent, as are also the bonds in the stable octahedralcomplexes of the ditertiary arsine with Ni, Co, and Fe in their bi- and ter-valent states.2otetrahydrate in glacial solution.[Co(NH,),CO,]f + 2H+ = [Co(NH3),HZO]+++ + HZC03l9* J . A. Sharp and A. G. White, J., 1952, 110.197 J. P. Hunt, A. C. Rutenberg, and H. Taube, J . Amer. Chem. SOC., 1952, 74, 268.198 M. Polanyi and A. L. Szabo, Trans. Faraduy SOC., 1934, 30, 508.lg9 B. West, J., 1952, 3115, 3123.goo F. P. Dwyer, N. S. Gill, E. C. Gyarfas, and F. Lions, J . Amer. Chem. SOC., 1952,74, 4188. 201 F. H. Burstall and R. S. Nyholm, J., 1952, 3570108 INORGANIC CHEMISTRY.Potentiometric titrations in aqueous solution show that cobalt tetra-carbonyl hydride, CO(CO)~H, is a strong acid and that iron tetracarbonyldihydride, Fe(CO),H,, is a weak dibasicA new method has been described for the preparation of nitrosylcobalttricarbonyl Co(N0) (CO), and of dinitrosyliron dicarbonyl Fe(NO),(CO), ;it consists in the acidification of solutions of the alkali salts of the respectivecarbonyl hydrides in the presence of corresponding amounts of nitrite,=, e.g.Fe(CO),HNa + 2NaN0, + 3HOAc --+ Fe(NO),(CO), + 2CO + 3NaOAc + 2H20Fe(CO), + 3NaOH -+ Fe(CO),HNa + Na2C03 + H20Iron can be removed from solutions of ferric phosphate by either cation-or anion-exchange resins.Evidence has been obtained which indicates thatthe extraction of the iron as an anion is due to the formation of a complexion containing 3 phosphate groups to each iron atom, the phosphate groupspresumably behaving as bidentate groups, forming H3[Fe(HP0,)] orH,[Fe(P0,),].204What is claimed to be the first cationic iron(x1x) complex to be obtainedin enantiomorphic forms has been prepared bv the ceric ammonium nitrate-nitric acid oxidation of (+)- and (-)-tris-2 : 2'-dipyridyliron(n) perchlorates.The resolution of the latter compounds was carried out through the iodideantimony1 tartrate : (+)- and (-)-tris-1 : 10-phenanthrolineosmium(Ix1)perchlorates have also been prepared by oxidation of the correspondingosmium(xx) compounds by chlorine.205The stabilities of some 5-substituted 1 : 10-phenanthrolineiron(1x) com-plexes have also been determined.2o6A contribution has been made to the preparation of trinuclear rutheniumcompounds by that of the basic acetate, [Ru,(OAc),(OH),] (OAc),7H20,by the reduction of ruthenium tetroxide by acetaldehyde in anhydrousacetic acid-carbon tetrachloride solution.This compound dissolves inwater to give an intensely blue solution, and rapidly in pyridine to givea solution which becomes green when warmed. Addition of chloro-platinic acid to the aqueous solution of the pyridyl derivative precipitatesSexavalent ruthenium is commonly met with as an anion in the form ofalkali-metal ruthenates M,RuO,, which are stable in alkali but immediatelydisproportionate on treatment with acid, into the +4 and +S oxidationstates; no simple salts of the ruthenyl cation RuO,++ have hitherto beenisolated. The reduction of ruthenium tetroxide by a variety of reducingagents in sulphuric acid solution has given evidence that a sexavalent stateis capable of existence, as a green solution, in this medium, but decomposesin a few hours at room temperature, probably by the above disproportion-ation. The experiments suggest, however, that even in these solutions theruthenium is present as the anionic complex [RuO,(SO,),]' rather than asthe ruthenyl ion RUO~++.~O~A study has been made by spectrophotometric methods of the solution[ RU,(OAC),py,]ClPtC16.2072*2 W. Hieber and W. Hubel, 2. Naturforsch., 1952, 7, b, 322.203 F. Seel, 2. anorg. Chem., 1952, 269, 40.204 J. E. Salmon, J . , 1952, 2316.205 F. P. Dwyer and E. C. Gyarfas, J . Amer. Chem. SOC., 1952, 74, 4699.206 W. W. Brandt and D. L. Gullstrom, ibid., p. 3532.207 F. S. Martin, J . , 1952, 2682. 208 Idem, .I., 1952, 3055FAIRB ROTH E R. 109chemistry of ruthenium in the +6, +7, and +S oxidation states. The +7state, which is known in the solid compounds NaRuO,,H,O and KRuO,,has also been identified in aqueous solution, and its properties studied.20gSpectrophotometric techniques have also been used to study the form-ation of a number of complex compounds of ruthenium. The orange-coloured complex formed by the reaction of ruthenium(1v) perchlorate withthiosemicarbazide was identified as Ru[SC(:NH)*NH*NH,]+~, and the brightred complex with 4-phenylthiosemicarbazide as Ru[SC( :NPh)*NH*NH,] +2.Both the thiosemicarbazide and the 4-phenylthiosemicarbazide behaved asweak acids, liberating a hydrogen ion for each molecule of ligand whichentered the complex.210With a number of complexing ions, both ruthenium(1v) and ruthenium(II1)form the same coloured complex, the quadrivalent ruthenium being reducedin each case by the ligand before complexing occurs; i.e., with thiocyanate,the same deep blue [Ru(CNS)lf2, with thiourea the blue-green complexes,Ru[SC(:NH)*NH2lf2 and Ru[SC(:NH)*NH,],,~~~ and with dithio-oxamide, theblue-green complexes Ru[SC(:NH)*CS*NH,]+~ and Ru[SC( :NH)*CS*NH2]3.212A new series of a nitrosopentamminoruthenium(I1I) ion [Ru(NH,),*NO]+~has been prepared : the salts are diamagnetic.213A number of salts of tetracyanopalladic(11) acid have been studied : 214the acid, which is prepared by acidification of a solution of palladium(11)cyanide in excess of cyanide ions, forms insoluble salts with silver andcopper(I1) ions or with their ammines. It also forms normal salts withbenzidine, naphthaquinoline, and oxine, and the salts of nitron. Palladium(I1)cyanide itself also forms co-ordination compounds with a large number ofnitrogen-containing organic compounds.A number of fluoro-complexes of palladium and gold of the type M,{PdF,]and M[AuF,] (M = alkali metal) have been prepared, viz., Cs,PdF,, Rb,PdF,,K2PdF6, and KAuF,, by the fluorination of the corresponding chlorine com-pounds. All these compounds are bright orange to yellow and, in contrastto the corresponding chlorine or bromine compounds, are immediatelyhydrolysed by water. During the fluorination of the alkali-metal chloro-aurates red intermediate products-possibly mixed fluorochloroaurates-were obtained : these were more stable towards ~ a t e r . ~ l ~The reactions of NN-diethylglycine and N-ethyl-N-methylglycine withcobalt (111) and platinum(I1) have been studied, and dinitro-(N-ethyl-N-methylglycine)platinate(II) has been prepared ; this has been shown tocontain an asymmetric nitrogen atom through its resolution by fractionationwith (-)-quinine and treatment with optically active quartz powder.216F. FAIRBROTHER.20s R. E. Connick and C. R. Hurley, J . Amev. Chem. SOC., 1952, 74, 5012.210 R. P. Yaffe and A. F. Voigt, zbid., p. 5043.2 1 1 Idem, ibid., pp. 2500, 2503.212 Idem, ibid., p. 3163.213 K. Gleu and I. Buddecker, 2. anorg. Chem., 1952, 268, 202.214 F. Feigl and G. B. Heisig, J . Amev. Chem. Soc., 1951, 73, 5630.215 R. Hoppe and W. Klemm, 2. anorg. Chew,., 1952, $368, 364.216 J. R. Kuebler and J. C. Bailar, Jr., J . Amer. Chew Soc., 1952, 74, 3535

ISSN:0365-6217    

DOI:10.1039/AR9524900081

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

ORGANIC CHEMISTRY.1. INTRODUCTION.THE following report on organic chemistry covers work published duringthe year except for the theoretical topics which are better reviewed at longerintervals than one year, so that the work discussed can be considered critic-ally in relation to contemporary views. The section on theoretical organicchemistry, therefore, deals with the more salient features of the chemistryof free radicals in solution, since that rapidly advancing field has not beenreviewed since 1948. The mechanism of the ozonisation of aromatic com-pounds, which was last reported in 1947, now merits special attention inview of the wider application of recent theories to other contemporary studiesof the reactivity of polynuclear aromatic systems.Perhaps the most novel discoveries of the year are the recognition ofiron dicyclopentadienyl as a new type of symmetrical structure showingtypical aromatic behaviour, and the use of clathrate compounds for opticalresolutions.In synthetic organic chemistry the year has been notable fora stereospecific total synthesis of cortisone, a synthesis of flavin-adenine-dinucleotide, a synthesis of morphine, and a synthesis of all-trans-methyl-bixin; each of these considerable achievements exemplifies in some way orother the high degree of specificity of modern techniques in organic chemistry,to which has been added a welcome catalytic hydrogenation method forreducing triple bonds to double bonds. The structure of lanosterol has nowbeen established and the stereochemistry of the p-amyrin and lupeolgroups of triterpenes has been elucidated, while appreciation of the richvariety of types of substance found to occur naturally is increased by theisolation of an antibiotic incorporating every known type of carbon-carbonunsaturation.The increasing use of enzymic methods for the study of organic chemicalproblems is seen in recent work on nucleotides and macromolecules, whileexpanding facilities for infra-red spectroscopy are reflected in the increasinguse being made of this tool in structural problems.J.W.W. A. W.2. THEORETICAL ORGANIC CHEMISTRY.Bromonium Cations.-Though iodonium salts have long been known,stable bromine and chlorine analogues (I) and (11) have been prepared byR. B. Sandin and A.S. Hay only in the year under review.sponding iodonium salts were made by L. Mascarelli in 1907.2The corre-Previously,1 J . Amer. Chew. SOC., 1952, 74, 274.2 AttiR. Accad. Lincei, 1907, 16,11, 562; 1908, 17,'11, 580; 1912, 21, 11, 617; Gazzetta,1908, 38, 624WATERS : THEORETICAL ORGANIC CHEMISTRY. 111cyclic bromonium catihs (111) had been postulated by I. Roberts andG. E. Kimball3 in order to explain trans-addition to olefins. Their theoryhad received strong support from the work of S. Winstein and H. J. Lucas *and other American investigators of the stereochemistry of the reactions ofolefins, 1 : 2-glycolsJ and their derivative^.^ M. J. S. Dewar has advocatedthe x-bond formula (IV) but there now seems to be no special need for it,since it depends on the assumption that a halogen atom can only form asingle covalent bond.6 Related studies of neighbouring group displacementreactions have led D. J. Cram to postulate the transient existence of aphenonium ion ” (V), but a detailed report of this subject is deferred untilnext year.RZC--C / R f f Rf\c=C /Rf Rf\c-C/RffR/ \G~/ \Rf I f R/ J. \,,ff R/ / \,fffBr + ?+\ I: ;I(111) (IV) \*/ (V)Ozonisation. The Action of Double-bond Reagents.-Continuation ofthe detailed studies of ozonisation by J. P. Wibaut and his school in Amster-dam 8 has in the past two years led to results of major theoretical significance.Kinetic measurements of the velocities of ozonisation of several benzene,pyridine, quinoline, and isoquinoline derivatives have been made.+l4 Thevelocity of addition of ozone to benzene is proportional to the concentrationof the ozone as well as to that of the benzene.11-13 Apparently benzenetriozonide is formed in successive stages, the velocity of the first being muchless than that of the subsequent ones.Alkyl substituents increase thereaction vel~city,~, lo whilst halogens have the opposite effect, as the followingC,H,Me2 > C,H5Me; C,H5Me >C6H,*CH2C1 > C,H5*CHC12 CI,H,*CC1,. Anisole is attacked exceedinglyrapidly whilst pyndine derivatives do not react as fast as their benzeneanalogues.14 This has led J. P. Wibaut and F. L. J. Sixma to concludethat the first stage in the ozonisation of an aromatic compound is an electro-philic reaction in which the central, electropositively polarised, oxygen atomof the ozone molecule (VI) becomes attached to the activated aromaticsystem, giving the primary transition state (VII).In this, only four electronsremain distributed over the five carbon centres, 2-6, of the benzene ring,which is thus positively charged, whilst the two terminal oxygen atoms ofthe ozone residue are negatively charged. Consequently, stabilisation of(VII) occurs very rapidly, to give the structures (VIII) and (IX) which, inthe case of benzene alone, will be identical and correspond to H. Staudinger’ssequences show 1oy14 C6H6 < C6H5Me < CGHSEt; P-C6H4Me2 > m(o)-C,H6 > C,H,F > C6H5C1 N C6H5Br;J . Amer. Chem. Soc., 1937, 59, 947.See E. R. Alexander, ‘‘ Ionic Organic Reactions,” J .Wiley & Sons, New York,J. Anzer. Chem. Soc., 1949, 71, 3863, 3871, 3883; 1952, 74, 2129, 2137, 2149,J . van Dijk, Rec. Trav. chim., 1948, 67, 945.lo J. P. Wibaut, F. L. J . Sixma, L. W. F. Kampschmidt, and H. Boer, ibid., 1950,11 H. Boer, F. L. J . Sixma, and J . P. Wibaut, ibid., 1951, 70, 509, 1006.l2 H. Boer and F. L. J . Sixma, ibid., p. 997.lo F. L. J . Sixma, ibid., p. 1124.16 J. P. Wibaut and F. L. J. Sixma, Proc. K. Ned. Akad. Wet., 1948, 51, 776.Ibid., 1939, 61, 1576.1950, pp. 100-102.2152, 2159.69, 1355.See Ann. Reports, 1950, 47, 133; 1951, 48, 118.* Ann. Reports, 1947, 44, 127.J . P. Wibaut and F. L. J. Sixma, ibid., 1952, 71, 761112 ORGANIC CHEMISTRY.“ molozonides.” l6 The conversion of these initial molozonides of olefins(X) into the stable structures (XI), which have been established by the workof A.Rieche with simple olefins l7 and of B. Witkop and J. B. Patrick 18in the indole series, has been explained by R. Criegee as an intramolecular~hange.1~ This completes the fission of the carbon-carbon double bond;opening up of the ozonide finally occurs by an acid-base-catalysed hydro-lysis 2.0 which has a mechanism similar to that involved in the acid-catalyseddecompositions of hydroperoxides.21The electrophilic nature of the attack of ozone on aromatic compounds(VI --+ VII) has been substantiated by showing that the reaction canbe catalysed by the ‘‘ Lewis acids ’’ aluminium chloride, ferric chloride, andboron fluoride. These electron-deficient molecules enhance the electrophiliccharacter of the ozone :+ -O=O-0 + AICl, O=6--O-~lC13The view that the initial stage in the ozonisation of an aromatic compoundresembles nitration, or the Friedel-Crafts reaction, has been challenged byG.M. Badger 22 who maintains that ozone, osmium tetroxide, and diazo-acetic ester differ from cations such as NO2+ in that they attack the n-elec-trons of double bonds and not localised electrons a t the site of individua!carbon atoms.23 It is characteristic of these “ double-bond reagents ” thatthey can often attack polycycfic aromatic systems a t bonds of high electrondensity which sometimes do not correspond to the carbon centres attackedby typical electrophilic substituting agents. Pyrene exemplifies this ;ozonisation occurs a t the “ K ” bonds 1-2 and 6-7 whereas nitration occursalmost exclusively at atoms 3 or 5.Though they concede that the fonn-ation of a “x-complex” 24 may possibly precede the formation of thetransition structure, Sixma and Wibaut 25 counter Badger’s argument bypointing out that the reversible formation of the transition structure (VII)is followed in ozonisation by a process different from that which occurs inCf. RCl + AlCI, R+[AlCI,]-16 Ber., 1925, 58, 1088. l7 Ibid., 1932, 65,.1274; Annalen, 1942, 553, 187.18 J . Amer. Chem. Soc., 1952, 74, 3855.19 Annalen, 1948, 560, 127; cf. J. E. Lefler, Chem. Reviews, 1949, 45, 38520 B. Witkop and J. B. Patrick, J . Amer. Chem. Soc., 1952, ‘74, 3801. :: gVef:l29. 22 Rec.Trav. chim., 1952, 71,468. 23 Quart.Reviews, 1951, 6,147.S . Dewar, “ Electronic Theory of Organic Chemistry,” Oxford Univ. Press,1949,pp. 17,169. 26 Rec. Trav. chim., 1952, 71, 473.Cf. thls vol., p. 123WATERS THEORETICAL ORGANIC CHEMISTRY. 113bromination or nitration. Ozonisation involves ring closure by stabilisationof vicinal electrostatic charges of opposite sign (VII+VIII, IX), whereasbromination involves stabilisation by extrusion of a proton, (XII), and there-formation of the aromatic sextet. The Dutch workers calculate that ifthe stabilising effects of vicinal charges are taken into account then thetransition structure (XIII) has a slightly lower energy content than (XIV),though in pyrene itself the electron density is higher at atom 3 than atatom 1, since the localisation of the nuclear positive charge in (XIII) givesan activated phenanthrene structure with an energy level below that of theactivated naphthalene arrangement in (XIV).Ring closure of (XIII) thus-0 0-0- \;/&b/ + I H\ /-H.i;G,&t,fi)A)+ 1 /v\1\r-. II p \A&(XW ( X W CYY A/ 'V\/ (XIV) (XV)B y ? )H"C;r! Lgives a more stable product than that which could be derived from (XIV),and consequently ozonisation of pyrene is to be expected at bond 1-2.Sixma and Wibaut 25 suggest that the whole conception of mechanisticallydistinct " double-bond reagents " is untenable.Ethyl diazoacetate has been considered to be another reagent of thistype26 since it adds to the 1 : 2-positions of anthracene.However, thereaction products, e.g., (XV), which have locaked double bonds since theyeasily add on bromine, are much less reactive towards ethyl diazoacetatethan are the aromatic molecules from which they have been formed : hereagain " double-bond character " cannot be a satisfactory explanation of thechemical reactivity. It is evident to the Reviewer that ethyl diazoacetateis typically a reagent which attacks 9oZarisabZe bonds and that the final ringclosure would favour reaction via a particular transition state ; osmiumtetroxide is a reagent with similar characteristics. All these reagents thusexemplify the theoretical dangers inherent in attempts to assess the energylevels of the transition states of organic reactions by calculations whichtake into account the detailed electronic structure of only one of the par-t icipat ing molecules.Free radicals and their reactions.Triphenylmethyl and Related Compounds.-Of the methods availablefor determining the degree of dissociation of compounds of the hexaphenyl-ethane series, most reliance has, in recent years, been placed on magneticsusceptibility measurements.G. W. Wheland27 and P. W. Selwood andR. M. Dobres28 have pointed out that this method has a serious inherenterror : molecular diamagnetic susceptibility is compounded of both atomicand resonance terms, and the latter, which may be large for stable mesomericradicals, is incalculable and has hitherto been neglected. Consequently ifthe paramagnetism, Xp, due to an unpaired electron is estimated as X, =X cu~c.it gives results which may be much too found -l- x diumag.,26 G. M. Badger, J. W. Cook, and A. R. M. Gibb, J., 1951, 3456.2 7 " Advanced Organic Chemistry," J. Wiley & Sons, New York, 1949, p. 696.28 J . Amer. Chern. soc., 1950, 72, 3860114 ORGANIC CHEMISTRY.low. The discrepancy is noticeable when observations are made over arange of temperatures. This difficulty may however be overcome bymeasuring the paramagnetic resonance ab~orption.~~ Colorimetric measure-ments, on absorption bands characteristic of the free radicals themselves,show the expected temperature dependence and are considered to be trust-worthy.28 Magnetic-susceptibility methods however are still valuable formeasuring reaction velocities 30 and for the qualitative detection of freeradicals.New radicals which have been examined in this way includepentaphenylpyrrolium perchlorate (XVI) 31 and the uncharged reductionproduct of the tetrazolium salt (XVII).32 Somewhat similar in reactions arethe free radicals obtained by reducing triphenylmethane dyes with zinc dustin pyridine solution.33Stepwise polarographic reduction of triphenylmethane and acridine dyeshas been studied by R. C. Kaye and H. I. Stonehil134 who consider that thefree-radical stage is of biological significance. They point out that thechemotherapeutically active dyes give radicals which are stable over a con-siderable pH range, and they suggest that these radicals may act by stoppingreaction chains essential for bacterial metab0lism.~5 Polarographic reduc-tion of coenzymes has also been examined from this viewpoint.36 Chemicalone-electron reduction of pyridinium salts has also been disc~ssed.~'K. Ziegler and W.Deparade 38 have shown that many compounds suchas 2 : 3-dimethyl-2 : 3-diphenylbutane slowly evaporate at temperatures wellbelow their normal boiling points owing to dissociation and disproportion-ation :Barton and Holness in a brilliant exposition g2 of the problem havediscussed the relative configurations in rings c, D, and E of p-amyrin andconcluded that the junction D-E is cis, and that the C,lo)-hydrogen atomand the C(,,)-methyl group are both trans to the C,,,)-methyl group(cf. LXXIV and LXXV). The junction B-c is in the more stablearrangement .92p 93Making the probable assumption that the Ct5)- and the C,,)-methylgroup are cis, Barton concluded that there are only two structures (LXXIVand LXXV) for P-amyrin which will accommodate the facts describedabove.Now, (LXXIV) and (LXXV) have terminal ring E units which areenantiomeric. Klyne 67 has distinguished between these two structures8 8 Cf. D. H. R. Barton, Quart. Reviews, 1949, 3, 36; 0. Jeger, l r Fortschritte derL Y dF. A. Alves, Exfierientia, 1952, 8, 10.D. H. R. Barton, Experientia, 1950, 6, 316.T. G. Halsall, E. R. H. Jones, and G. D. Meakins, J., 1952, 2862.n1 Cf. A. Lardon and T. Reichstein, Helv. China. Acta, 1949, 33, 2003.Q1c J. A. Mills, J., 1952, 4982.92 D. H. R. Barton and N. J. Holness, J., 1952, 78.s3 R.Budziarek, W. Manson, and F. S. Spring, J., 1951, 3336.Chemie organischer Naturstoff e," Springer-Verlag, 1950, VoI. VII188 ORGANIC CHEMISTRY.by showing that the terminal ring E of p-amyrin is of the same enantiomerictype as that in (LXXIV), which therefore is the correct formulation ofp-am yrin .(LXXIV) (LXXV)The configurations of C(Q C(5)r C(e>, C,), C(lo), C(14))t and C(1,) of lupeol(cf. LXXVI) are the same as in p - a m ~ r i n . ~ ~ Lupeol has also been convertedinto germanicol (LXXVII) in which the hydrogen atom at and-1 IMe Me(LXXVI) (LXXVII)the methyl group at are cis.95 Finally it has been proved that thejunction D-E is trans, and that the isopropenyl group and the C(l,l-methylgroup are trans.90 Lupeol is therefore (LXXVI).(LXXIX)Asiatic acid, the aglycone of asiaticoside, has been shown to beThis structure is supported by proof of the presence of94 T.R. Ames, T. G. Halsall, and E. R. H. Jones, J., 1951, 450.9 5 D. H. R. Barton and C. J. W. Brooks, J., 1951, 257.913 (Mme.) Judith Polonsky, Bull. SOC. chirn., 1952, 649, 1015; Compt. vend., 1949,228, 1450; 1950, 280, 485, 1784; 1951, 5338, 1878; 1951, 233, 93, 671.(LXXVIII).gHALSALL ALICYCLIC COMPOUNDS. 189an a-glycol group, the formation of a lactone involving the carboxyl groupand the double bond, and the conversion of (LXXVIII) into 23-nor-a-amyrene (LXXIX) as shown.Zeorin, a pentacyclic secondary-tertiary diol, has been fully character-i ~ e d . ~ ' It forms a monoacetate, dehydration of which with phosphorusoxychloride in pyridine gives isozeorinin acetate.This contains the group-ing (>C=CH,). The secondary hydroxyl group is not at the typical tri-terpene 2-position.New triterpenes isolated include gratiogenin (as its glycoside gratioside)which may be 21-keto-olean-12-ene-2 : 19 : 29-tri01,~~ and psidiolic acid,C3,H,,0,.99 S-Amyrin, hitherto not found in Nature, has been isolatedfrom Spanish broorn.100 The so-called crataegolic acid lol is a mixture ofknown triterpenes. 102p-Triketones.-Considerable progress has recently been made in thechemistry of the group of naturally occurring alkali-soluble substances whichowe their acidity to the presence of a p-triketone system. Birch lo3 hasconsidered the evidence concerning angustione, dehydroangustione, andcalythrone, and concluded that they are best represented by structuresMeCO <ge g&CO*CH2CHMe2Me Me 0II0II0If0(LXXX) (LXXXI) (LXXXII)Me Me Me Me Me0 \,i\/ocHzoy Pri-CO o\@o =CH- O\& CO*Pri pri.COIA 1- CO-Pri \/II I10II0II0 0(LXXXIII) (LXXXIV)(LXXX), (LXXXI), and (LXXXII) .Flavaspidic acid, which was formul-ated by Boehm lo4 as (LXXXIII) with a cydobutane ring, is now believedto be (LXXXIV),103 the quinonoid nature of which would account for theyellow colour of the acid.Protokosin, isolated from the anthelmintic drug kousso, was originallyformulated as C,,H,,O, and also thought to have a cyclobutane ring. Theformula has now been modified to C,5H,0,, and structure (LXXXV) hasbeen proposed.lo5 (LXXXVI) and (LXXXVII) follow for a- and 8-kosinwhich result from the action of zinc and alkali on protokosin.The hop constituents lupulone and humulone have been synthesised : 106O7 D.H. R. BartonandT. Bruun, J., 1952, 1683.98 R. Tschesche and A. Heesch, Chem. Ber., 1952, 85, 1067.99 G. Soliman and M. K. Farid, J., 1952,134; H. R. Arthur and W. €3. Hui, Chem.loo 0. C . Musgrave, J. Stark, and F. S . Spring, J., 1952, 4393.lo1 R. Tschesche and R. Fugmann, Chenz. Ber., 1951, 84, 810.lo2 T. Bersin and A. Miiller, HaZv. Chim. Acta, 1952, 85, 1891.lo3 A. J. Birch, J., 1951, 3026.lo5 A. J. Birch and A. a. Todd, J., 1952, 3102.lo6 W. Riedl, Chsm. Bey., 1952, 85, 692.and Ind., 1952, 693.lo* R. Boehm, Awnden, 1903, 329, 310190 ORGANIC CHEMISTRY.lupulone by trialkylation of 2 : 4 : 6-trihydroxyisovalerophenone withl-bromo-3-methylbut-2-ene, and humulone by similar dialkylation of thesame trihydroxyisovalerophenone followed by oxidation of the product withMe MeOH0(LXXXV) (LXXXVI)0 0 I1 II(LXXXVIII) o ; Q y H 2 - f e 2 QyH2*CHMe2 (LXXXIX)0R R R OHR = -CH,*CH:CMe,.oxygen.in the presence of lead acetate in methanol. These syntheses areconsistent with, but do not prove, structures (LXXXVIII) and (LXXXIX)which have been proposed for lupulone lo'* lo8 and humulone.lo61 l0*lloThese structures, however, are said not to provide a satisfactory explanationof all the properties of these substan~es.1~~~ 1 1 1 9 112T. G. H.7. STEROIDS.Total Syntheses.-The year's outstanding achievement in syntheticchemistry is a stereospecific total synthesis of cortisone by Sarettand his associates " Stereo-specific " is defined by the authors to mean that in each reaction producinga fixed asymmetric centre the ratio, to all other isomers, of the isomer havingthe configuration of the end product is greater than unity; they add thatin the present synthesis there is no such ratio less than 8 : 1.An account of earlier stages in the synthesis, leading to the hydroxy-diketone monoketal (I) is still in the press.This ketone was alkylated, firstwith methyl iodide and then with 2-methylallyl iodide. The product (11)after oxidation to the diketone was condensed with ethoxyethynylmagnesiumbromide ; rearrangement of the acetylenic ether (111) gave the unsaturatedat the Merck Laboratories in New Jersey.lo7 M.Verzele and F. Govaert, Bull. SOC. chim. Belg., 1950, 68.l o * J. F. Carson, J . Amer. Chem. SOC., 1951, 73, 4652.lo* G. Harris, G. A. Howard, and J. R. A. Pollock, J., 1952, 1906.l10 A. H. Cook and G. Harris, J., 1950, 1873.ll1 Cf. G. A. Howard and J. R. A. Pollock, J , , 1952, 1902.lla Cf. S. David and C. Imer, Bull. SOC. chim., 1951, 634.1 L. H. Sarett, R. M. Lukes, R. E. Beyler, G. I. Poos, W. F. Johns, and J. M. Con-stantin, J . Amer. Chem. SOC., 1952, 74, 4974CORNFORTH : STEROIDS. 191ester (IV). This was hydrolysed to the acid and reduced stepwise by threeselective reagents : first, sodium borohydride (carbonyl group), then potas-sium and isopropanol in liquid ammonia (conjugated double bond), andfinally lithium aluminium hydride (carboxyl group).The resulting diol(V ; R = H) formed a monotoluene-9-sulphonyl derivative (V ; R =C,H,Me*SO,) which was then oxidized stepwise by three selective reagents :chromium trioxide-pyridine (>CH*OH __+ >CO), osmium tetroxideCMeXH,IYMeXH,(11)Oxidn. ;EtOCpMg BrCMe:CH2(i) Hydrol.(ii) NaBH,(iii) K-NH,-PriOH(iv) LiAlH,YMeXH,(VW[ > CXH, ---+ > C( OH) *CH,*OH] , and periodic acid [ > C (OH) *CH,*OH --+>CO + CH,O]. Cyclization with sodium methoxide of the toluene-p-sulphonyloxy-ketone (VI) and isomerization with alkali of the initiallyformed 17a-stereoisomer gave the 3-ethylene ketal (VII ; R = H) of (&)-ll-ketoprogesterone.Resolution was achieved by way of the strychnine sal192 ORGANIC CHEMISTRY.of the 21-oxalyl acid (VII; R = CO*CO,H) : the (+)-acid, on removal ofthe oxalyl group and hydrolysis of the ketal, gave 1 l-ketoprogesterone.Synthesis of cortisone from the (+)-oxalyl acid (VII ; R = CO*CO,H) wascompleted by idination and acetoxylation to the 21-iodo-compound (VII ;R = I) and 21-acetate (VII ; R = OAc) ; the remaining stages followedestablished procedures. Comparison of the synthetic compounds withmaterial derived from natural sources was made at several of the intermediatestages as well as with the final product.Earlier stages of this synthesis may be discerned in two papers 2l deal-ing with the condensation of benzoquinone with 3-ethoxypenta-1 : 3-diene.The diene was obtained by pyrolysis of 1 : 3 : 3-triethoxypentane,CH3*CH2*C(OEt),*CH2-CH2*OEt --+ CH,*CH:C(OEt)CH:CH,, as a mixtureof geometrical isomers. The major constituent reacted easily with benzo-quinone. The adduct (VIII) was stereochemically unstable, contact withalkaline alumina giving two trans-decalin isomers ; however, neutral Raneynickel in benzene reduced the double bond of the enedione system withoutcausing isomerization. Further reduction by lithium aluminium hydrideand hydrolysis with acid then gave the diol (IX). The configuration ofMe 0!I(IX) b Hthis substance was carefully studied and the structure shown was assignedon various grounds (e.g., steric hindrance of one hydroxyl group ; formationof lactol ethers between the carbonyl group and both hydroxyl groups).Other papers of the same series*, 5 describe the preparation of somecyclohexene-2 : 5-diones (e.g., X) and their condensation with ethoxy-pentadiene.In a different approach, still involving the Diels-Alder re-action, Robins and Walker found that l-vinylcyclohex-l-ene condensedreadily with benzoquinone, affording the decahydrophenanthrenedione (XI ;R = H). When this procedure was applied to a mixture of methylvinyl-(XI) (XII) (XIII)cyclohexenes prepared from 2-methyl-l-vinylcycZohexanol, the product(XI; R = Me) was shown to arise from 3-methyl-2-vinylcycZohexene, themore important l-methyl isomer failing to react. Catalytic reduction ofL. H. Sarett, R. M. Lukes, G. I. Poos, J.M. Robinson, R. E. Beyler, J. M. Vande-grift, and G. E. Arth, J . Amer. Chem. SOC., 1952, 74, 1393.R. E. Beyler and L. H. Sarett. ibid., p. 1406.P. A. Robins m d J. Walker,,a Idem, ibid., p. 1397.ti R. M. Lukes, G. I. Poos, and L. H. Sarekt, Qbid., p. 1401. ., 1952, 642, 1610; see also N. C. Deno and J. D.Johnston, J. Org. Chem., 1062, 17, l 468CORNFORTH : STEROIDS. 193(XI; R = H and Me) was studied : it is interesting that of the two keto-groups that a t C(41 was reduced preferentially.A partial synthesis of the " Windaus acid " (XIII ; derived from, andreconvertible into, cholestenone) from the -ketone (XII) is reported.' Itwas necessary to block the methylene group at position 6 (steroid numbering)with a methylanilinomethylene group in order to induce reaction with acrylo-nitrile at position 10.Direct angular methylation of a methoxyhexalone (XIV --+ XV) canbe effected with potassamide and methyl iodide in liquid ammonia.Theproduct is a potentially useful intermediate in further syntheses.Hydrolytic procedures then gave the acid (XIII).MeA novel method of building a steroid ring D is indicated 8a by the conver-sion of dimethyl marrianolate methyl ether (XVa) into 16-keto-a-oestradiol3-methyl ether in 60% yield with sodium in liquid ammonia. The methodwas also successfully applied to the recyclization of ring c from an 11 : 12-seco-dioic ester.OHDetailed accounts have been given of work reported in earlier years :the Harvard steroid synthesi~,~ the preparation of some androsteronestereoisomerides,1° and a total synthesis of oestrone.llProduction of Cortisone.-The problem of producing cortisone economic-ally in large quantity from naturally occurring steroids continues to attractmuch attention, most of the papers being concerned with introducing anll-oxygen atom into molecules unsubstituted in ring c.Chemical methodsof achieving this continue to be centred on the 7 : 9(11)-dienes. Contri-butions from several laboratories have notably simplified the transformationof these dienes into lla-hydroxy- and ll-keto-steroids. ' The primaryproduct of epoxidation of a 7 : 9(11)-diene in the 5-allo-series appears tobe a 7-ene-9a : lla-epoxide (XVI) ; when this is treated with dilute sulphuricacid the products, under progressively less gentle conditions, are the 8(9)-ene-7E : lla-diol (XVII), the 9(11)-en-7-one (XVIII), and the 8-en-7-one7 A.R. Pinder and Sir Robert Robinson, J., 1952, 1224. * A. J. Birch, J. A. K. Quartey, and H. Smith, ibid., p. 1768.*a J. C. Sheehan, R. C. Coderre, L. A. Cohen, and R. C. O'Neill, J . Amer. Chem. Sot.,9 R. B. Woodward, F. Sondheimer, D. Taub, K. Heusler, and W. M. McLamore,lo J. R. Billeter and K. Miescher, Helv. Chim. Acta, 1951, 34, 2053.11 W. S. Johnson, D. K. Bannerjee, W. P. Schneider, C . D. Gutsche, W. E. Shelberg,1952, 74, 6155.J . Amer. Chem. Sot., 1962, 74, 4223.and L. J. Chin, J . Amer. Chem. Sot., 1952, 74, 2833.REP.-VOL. XLIX. 1 94 ORGANIC CHEMISTRY.(XIX).12y 133 1 4 9 l5 When, however, the epoxide is treated with the borontrifluoride-ether complex,l2* 13 or with ferric chloride,14 in benzene, theHO, /(XXII) (XX) (XXI)product is the 8-en-ll-one (XX) and this can be reduced to the saturatedketone of natural ” configuration (XXI) by lithium in liquid ammonia ; 1 5 9 16when ethanol is present, reduction proceeds as far as the lla-01 (XXII).[It is interesting that reduction of an 1 l-keto-group (ergostane series) withsodium and rt-propanol l7 also gives the lla-01, in contrast to the stereo-chemical course of catalytic or metal-hydride reduction.] Thus a way ofintroducing the ll-oxygen atom has been found which does not involveelimination of a 7-keto-groupJ and this has been carried out in the ergostaneand the allospirostane series.Catalytic reduction l6 of the unsaturatedketone (XX ; allospirostane series) gives a stereoisomeric 1 l-ketone thoughtto have the “ unnatural ” configuration at Ctsl and C(91.On the other hand, epoxidation of 7 : 9(11)-dienes in the 5-normal (bileacid) series seems to occur preferentially at the 7 : 8-double bond.This isindicated both by molecular-rotation differences between the diene and itsepoxide and by the formation of an 8-en-7-one from the epoxide with borontrifluoride.l2S l4Improvements and elucidations of methods for making 1 l-oxygenatedsteroids from 7 : 9(11)-dienes via 7 : ll-dioxygenated derivatives have beenp~blished,l*-~~ but space to review them is lacking. A method which doesnot start from the usual diene involves oxidation of ergosta-7 : 22-dienylacetate (XXIII) with tert.-butyl chromate; the 8 : 9-epoxy-7-one (XXIV) is1% H.Heusser, K. Eichenberger, P. Kurath, H. R. Dallenbach, and 0. Jeger, Helv.Chim. Acta, 1951, 34, 2106.18 H. Heusser, K. Heasler, K. Eichenberger, C. G. Honegger, and 0. Jeger, ibid.,1952, 35, 295.14 H. Heusser, R. Anliker, K. Eichenberger, and 0. Jeger, ibid., p. 936.15 E. Schoenewaldt, L. Turnbull, E. M. Chamberlin, D. Reinhold, A. E. Erickson,W. V. Ruyle, J . M. Chemerda, and M. Tishler, J . Amer. Chem. SOL, 1952, 14, 2696.16 F. Sondheimer, R. Yashin, G. Rosenkranz, and C. Djerassi, ibid., p. 2696.17 H. Heusser, R. Anliker, and 0. Jeger, Helv. Chim. A d a , 1952, 35, 1537.16 C. Djerassi, E. Batres, M. Velasco, and G. Rosenkranz, J . Amer.Chern. SOC.,20 R. Budziarek, G. T. Newbold, R. Stevenson, and F. S. Spring, J . , 1952, 2892.21 R, C. Anderson, R. Stevenson, and F. S. Spring, ibid., p. 2901.22 R. Budziarek, F. Johnson, and F. S. Spring, ibid., p. 3410.23 R. Budziarek and F. S. Spring, Chem. and Ind., 1952, 1102.1952, 14, 1712. l@ J. Romo, G. Stork, G. Rosenkranz, and C. Djerassi, ibid., p. 2918CORNFORTH : STEROIDS. 195formed (along with the 8 : 14epoxy-7-one in comparable amount) and thisis reduced to the 8-en-7-one (XXV) by zinc and acetic acid.24 A methodalready exists 25 for the conversion of 8-en-7-ones into ll-ones.(XXIII) (XXIV) (XXV) (XXVI)Some important work has appeared on the biosynthetic hydroxylationof ring c. A detailed study has been made of optimum conditions forhydroxylation, by adrenal homogenates, of deoxycorticosterone and its17a-hydroxy-analogue to corticosterone and 17a-hydroxycorticosterone(hydrocortisone) respectively.26 A similar hydroxylation in the 11 p-positionwas effected by the mould Stre$tomyces fradiae, 17a-hydroxy-1 l-deoxy-corticosterone being converted in small yield into hydrocortis~ne.~~ Certainmoulds of the order Mucurales, on the other hand, are capable of hydroxyl-ation in the lla-position : thus when progesterone was introduced into agrowing culture of Rhizupzcs arrhtiz.us, 11 a-hydroxyprogesterone (XXVI)could later be isolated in 10% yield.28 An unidentified strain of Rhizupushas been found to effect the same oxidation in 45% yieId.29 This micro-biological hydroxylation is of great potential importance, for progesterone isreadily available from diosgenin, and 11 a-hydroxyprogesterone (XXVI) hasspecial advantages as an intermediate for cortisone synthesis.Hydrogen-ation of the double bond in A4-3-ketones having an 11/3-hydroxy-S* or ll-keto-COMe COMesubstituent 31 affords largely the 5-dlU(A/B trans)-configuration, but with11 a-hydroxyprogesterone the product is the 5-normal(~/~ cis)-compoundand on oxidation affords pregnane-3 : 11 : 20-trione (XXVII),29 and a later24 H. Heusser, G. Saucy, R. Anliker, and 0. Jeger, Helu. Chim. Acta, 1952, 35, 2090.25 C. Djerassi, 0. Mancera, G. Stork, and G. Rosenkranz, J . Amer. Chem. Suc.,1951, 73, 4496; idem and M. Velasco, ibid., 1952, 74, 3321.28 F. W. Kahnt and A.Wettstein, Helu. Chim. Acta, 1951, 34, 1790.27 D. R. Collingsworth, M. P. Brunner, and W. J , Haines, J . Amer. Chem. SOC.,1952, 74, 2381. 28 D. H. Peterson and H. C. Murray, ibid., p. 1871.2s 0. Mancera, A. Zaffaroni, B. A. Rubin, F. Sondheimer, G. Rosenkranz, and C.Djerassi, ibid., p. 3711.ZsoD. H. Peterson, H. C. Murray, S. H. Eppstein, L. M. Reinecke, A. Weintraub,P. D. Meister, and H. M. Leigh, ibid., p. 5933.30 J. Pataki, G. Rosenkranz, and C. Djerassi, J . Bid. Chem., 1952, 195, 751.31 J. M. Chemerda, E. M. Chamberlin, E. H. Wilson, and M. Tishler, J . Amer. Cham.SOL, 1951, 73, 4052; E. Wilson and M. Tishler, ibid., 1952, 74, 1609; E. P. Oliveto,C. Gerold, and E. B. Hershberg, t v d . , p. 2248. A trace of alkali favours formation ofthe (AIB cis)-isomer : cf.Julian, Recent Progress in Hormone Research,” AcademicPress, New York, 1951, Vol. VI, pp. 207, 212106 ORGANIC CHEMISTRY.paper 29a reports 85-95% yields with Rhixopzts nigricans. Preferentialreduction of the 3-keto-group is possible with sodium borohydride in pyr-idine; 29 the resulting 3a-01 (XXVIII) can be converted into cortisone(see below).The biologically important 17-hydroxycorticosterone (hydrocortisone)has been synthesized 32 by modifying a known cortisone synthesis : in theintermediate (XXIX) the 3-keto-group is protected (dimethyl ketal orsemicarbazone) so that the ll-keto-group may be reduced (lithium or sodiumborohydride) to the 11p-01. The protecting group is removed and thesynthesis then proceeds by known paths to hydrocortisone (XXX).The 11 ct-epimer of hydrocortisone has also been ~ynthesised.~~Further progress is reported with methods for elaborating the cortisoneside chain.From 3a-hydroxypregnane-11 : 20-dione (XXVIII) with aceticanhydride-toluene-fi-sulphonic acid a dienol triacetate (XXXI ; or theA11(12)-isomer) is obtainable which can be epoxidized with perbenzoic acidCMeCN COCH,.OHCMe. OAc COMeIH d H (XXXII)selectively at the 17(20)-double bond. Alkaline hydrolysis then gives3a : 17a-hydroxypregnane-11 : 20-dione (XXXII), into which the 21-hydroxyl group can easily be introd~ced.~~ This method has also beenapplied 35 for preparation of the 3p : 5a-stereoisomer of (XXXII). Fulldetails have been given 36 of another method involving formation andepoxidation of a 16 : 17-double bond.The tertiary 17ct-hydroxyl group in (XXXII) has been acetylated (aceticanhydride-toluene-fxulphonic acid) ; the 17-acetoxy- is comparable with a21-acetoxy-group in ease of h y d r ~ l y s i s .~ ~ ~ ~ * The CH,*OH group in thecortisone side chain has been oxidized 39 to CHO : pyridine and toluene-fi-sulphonyl chloride , followed by p-nitrosodimethylaniline gave the nitrone,-CH=N(+O)C,H,*NMe, ; this was hydrolysed by dilute acid to the aldehyde,32 N. L. Wendler, R. B. Graber, R. E. Jones, and M. Tishler, J . Amer. Chem. SOC.,1952, 74, 3630.33 J. Romo, A. Zaffaroni, J. Hendrichs, G. Rosenkranz, C. Djerassi, and F. Sond-heimer, Chem. and Ind., 1952, 783.34 T. H. Kritchevsky, D. L.Garmaise, and T. F. Gallagher, J . Amer. Chem. SOC.,1952, 74, 483.36 F. B. Colton, W. R. Nes, D. A. van Dorp, H. L. Mason, and E. C. Kendall, J.Biol. Chem., 1952, 194, 235; F. B. Colton and E. C . Kendall, ibid., p. 247.37 Huang-Minlon, E. Wilson, N. L. Wendler, and M. Tishler, J . Amer. Chem. SOC.,1952, 74, 5394.30 E. F. Rogers, J. B. Conbere, K. Pfister, and W. J. Leanza, ibid., p. 2946.s5 J. Pataki, G. Rosenkranz, and C. Djerassi, ibid., p. 5615.38 R. B. Turner, ibid., p. 4220CORNFORTH : STEROIDS. 197which proved approximately as effective as cortisone in the rat-liver glycogentest.A radioactive cortisone labelled with tritium has been prepared 40 in aninteresting manner. 3a-Acetoxypregnane-l l : 20-dione with a platinumcatalyst and tritium-enriched water gave a product " permanently " labelledin the 16-position, and this was converted into cortisone as already described.Modification of Individual Groups.-Protection of steroid hydroxylgroups as tetrahydropyranyl ethers (XXXIII) by reaction with dihydropyranhas been examined.41~ 42 The carbethoxylation (" cathylation ") of steroidhydroxyl groups by ethyl chloroformate is shown to be a selective process,esters (R*O*CO,Et) being formed preferentially from " equatorial " hydroxylgroups.Thus of the three hydroxyl groups in methyl cholate only one (theequatorial 3cc) reacts even when excess of reagent is available.43 Experiencewith the formation of thioketals (XXXIV or XXXV) from cyclic steroidketones and ethanethiol (EtSH) or ethanedithiol (HS*CH,*CH,*SH) may besummarized thus: 44 the ketones which reacted with both thiols had thecarbonyl group in ring A or D ; ketones with a carbonyl group in ring B or creacted with ethanedithiol only, except the ll-keto-group which was inert toboth thiols.M~(oAc):CHz ?b 'ICMe* OAcEtS\ / CH,-S\ /C/-I(XXXVII)()OR EtS/\ CH,-S/ \ /(XXXIII) (XXXIV) (XXXV) (XXXVI)Some interesting data on the formation of enol acetates are now available.20-Ketones are well known to give A17(20)-enol acetates (XXXVI) withacetic anhydride-toluene-9-sulphonic a ~ i d , 4 ~ but with isopropenyl acetatethe isomeric A20-enol acetates (XXXVII) are f ~ r m e d .~ ~ ~ 47 An 11-keto-groupgives an enol acetate with the former reagent 34 but not with the latter.46With a 12-keto-group, both reagents are reported to fail."? 48 These curiousresults seem consistent with the idea that the isopropenyl acetate reagent ismore susceptible to steric hindrance than is acetic anhydride, and thatformation of an enol acetate is inhibited if the removal of the cc-hydrogenatom is sterically hindered.The inertia of the 12-keto-group may beutilized to eliminate the 7-substituent in 3a-hydroxy-7 : 12-diketocholanicacid by catalytic hydrogenolysis of the 7-monoenol acetate which it forms.48Shoppee and Summers 49 have devised a route to the efiicholesterylhalides. 3p-Hydroxycholestan-6-one (XXXVIII) with phosphorus penta-chloride or pentabromide gave the 3cc-halides (XXXIX) which were reducedwith lithium aluminium hydride to the 6p-01s; these were dehydrated to thedesired halides (XL).The normal (3p) cholesteryl halides were obtainable40 D. K. Fukushima, T. H. Kritchevsky, M. L. Eidinoff, and T. F. Gallagher, J .Amer. Chem. SOC., 1952, '44, 487.44 A. C. Ott, M. F. Murray, and R. L. Pederson, ibid., p. 1239.43 L. F. Fieser, J. E. Herz, M. W. Klohs, M. A. Romero, and T. Utne, ibid., p. 3309.44 H. Hauptmann and M. Moura Campos, ibid., p. 3179.45 T. F. Gallagher and T. H. Kritchevsky, J . Bid. Chem., 1949, 1'79, 507.4 6 R. B. Moffett and D. I. Weisblat, J . Amer. Chew Soc., 1952, 74, 2183.4 7 H. Vanderhaeghe, E. R. Katzenellenbogen, K. Dobriner, and T. F. Gallagher,48 R. Hirschmann, M. Brown, and N. L. Wendler, ibid., 1951, '43, 5373. ** C. W.Shoppee and G. H. R. Summers, J., 1952, 1786, 1790.41 W. G. Dauben and H. L. Bradlow, ibid., p. 559.ibid., p. 2810198 ORGANIC CHEMISTRY.by a modification of the same process : 3 : 5-cycZocholestan-6-one (XLI)[from the toluene-fi-sulphonyl derivatives of (XXXVIII) and potassiumhydroxide] with hydrogen halides gave 3P-halogenocholestan-6-ones (XLII)which were reduced and dehydrated.X(XXXVIII) (XXXIX)A discovery 50 which may prove generally useful is that steroid 3-ketonesundergo " reductive methylation " on catalytic hydrogenation in methanolcontaining hydrogen bromide, the product being a methyl ether : >CO -+> CH-OMe. 3p-Methoxy-compounds were produced from both cholestanone(do-series) and methyl 3-keto-A9(11)-cholenate (normal series).In a studyof non-catalytic reduction of cholestanone, Nace and O'Connor 51 showedthat whereas with lithium aluminium hydride the ratio of 3p-01 to 3a-01 inthe product was 7-3 : 1, with aluminium alkoxides Al(OR), more of the 3a-01was formed. This effect could be exaggerated by increasing the bulk of theR group : with di-tert.-butylcarbinol Me,C*CH(OH)*CMe, and its aluminiumalkoxide the reduction product contained 55% of 3a-01. The results areattributed to steric hindrance in formation of an intermediate complex. -Some Reactions involving Double Bonds.-The diacetate of androst-7-enediol (XLIII) was found 52 to be rearranged by hydrogenation catalystsin the known manner to the AKl4)-isomeride (XLIV), but further isomeriz-ation by hydrogen chloride to the A14-isomeride (XLV) did not occur.Thisfailure to isomerize, in contrast to the results obtained with cholesterol andergosterol analogues, has also been observed with A8(14)-aZZ~pregnen~lone andwith dehydro t igogenin. 53Me?*' M e yM e C b p!fP/": J AcO H -+ /c"" M e P 5/HVAcOPh /\/HVAcO(XLIII) (XLIV) (XLV)Two methods of obtaining A5: '-steroids from A4-3-ketones (XLVI) havebeen elaborated. By bromination and dehydrobromination the 4 : 6-dien-%one can be made, the enol acetate (XLVII) of which with sodium boro-50 J. C. Babcock and L. F. Fieser, J. Amer. Chem. SOC., 1952, 74, 5472.61 H. R. Nace and G. L. O'Connor, ibid., 1951, 73, 6824.52 R. Antonucci, S. Bernstein, D. Giancola, and K. J. Sax, J.Org.Chem., 1961,16,1891.63 0.Mancera, D. H. R. Barton, G. Rosenkranz, and C. Djerassi, J., 1952, 1021CORNFORTH : STEROIDS. 199hydride affords the 5 : 7-dien-3p-01 (XLVIII). This has been done in thecholestane and 22-iso-allospirostane 55 series. Alternatively one canobtain the A5-ketal (XLIX) from the unsaturated ketone (XLVI ; cholest-enone, progesterone, 21-acetoxyprogesterone) and ethylene glycol ; 56bromination and dehydrobromination then give an unusually high yield ofthe 5 : 7-diene (L)563 57___,0 AcO HO(XLVI) (XLVII) (XLVIII)3 : 5-cycloSteroids.-A hydrocarbon obtained from ergosterol withtoluene-$-sulphonyl chloride and pyridine, and formerly thought to be anergostatetraene, is now shown 58 to be 3 : 5-cycloergosta-6 : 8(14) : 22-triene(LI).By working at -lo", ergosterol and 7-dehydrocholesterol can beconverted into toluene-9-sulphonyl derivatives (LII) and these with lithiumaluminium hydride give 3 : 5-cyclo-7-enes (LIII) .59(LIII)Wagner, Wolff, and Wallis report 60 that both epimers of 3 : 5-cyclo-cholestan-6-01 (LIV) are rearranged under acidic conditions to give the same(3P) cholesterol derivatives, and have advanced arguments that the 3 : 5-64 W. G. Dauben, J. F. Eastham, and R. A, Micheli, J . Amer. Chem. SOG., 1951,73,4496.6 5 H. J. Ringold, G. Rosenkranz, and C. Djerassi, ibid., 1952, 74, 3441.6 6 R. Antonucci, S. Bernstein, R. Littell, K. J. Sax, and J. H. Williams, J . 9%.cf. E. Fernholz and H. E. Stavely, Abstr. 102nd meeting,57 R. Antonucci, S. Bernstein, R. Lenhard, K.J. Sax, and J. H. Williams, J . OYg.s8 M. Fieser, W. E. Rosen, and L. F. Fieser, J . Amer. Chem. SOL, 1952, 74, 5397-69 P. Karrer and H. Asmis, Hek. Chim. A d a , 1952, 35, 1926.6o A. F. Wagner, N. E. Wolff, and E. S. Wallis, J . Org. Chem., 1952, 17, 529; N- E.Chewz., 1952, 17, 1341;Amer. Chem. Soc., Sept. 1941, M39.Chem., 1952, 17, 1369.WoIff and E. S . Wallis, ibid., p. 1361200 ORGANIC CHEMISTRY.cycEo-6-01s (the iso-steroids) prepared by rearrangement of 3P-hydroxy-A5-steroids have the 6ceconfiguration. However, isocholesterol can be hydro-genated61 to cholestan-6p-01 (its epimer gives cholestan-6a-01) and shouldtherefore be 3 : 5-cycZocholestan-6~-01. The mechanisms of isocholesterolrearrangements have been discussed.60*The structure of the unsaturated hydrocarbon obtained 62 by acid treat-ment of 3 : 5-cycZocholestane has been established as (LV) by an unequivocalsynthesis.63Naturally Occurring Steroids.-There have been several advances inthe chemistry of steroid saponins.Infra-red absorption measurementsindicate 64 that the spiroketal side chain present in the sapogenins, and the12-keto-group present in some of these, occur also in the original saponinsand are not artefacts of hydrolysis, as has been suggested.65 A method hasbeen given 66 for detecting steroidal sapogenins in hydrolysates of planttissue by means of the characteristic infra-red absorption of the seiroketalside chain. The effect of several catalysts on the opening of the 6-memberedheterocyclic ring in sapogenins by acetic anhydride has been studied.67Reductive fission of this ring (to give a primary alcohol) can be effected withlithium aluminium hydride and ether saturated with hydrogen chloride.Without the acid no cleavage occurs.68Manogenin (2a ? : 3~-dihydroxy-22-isoaZZospirostan-12-one 69) has beenconverted into hecogenin (3~-hydroxy-22-isoaZZospirostan-12-one) via theA3-analogue and its epoxide.70The 3-(hydrogen succinate) 12-methanesulphonate (LVI ; R =HO,C*CH,*CH,*CO) of rockogenin suffers rearrangement of the carbonskeleton under remarkably mild conditions (boiling methanol). The struc-ture (LVII ; R = HO,CCH,*CO) is indicated for the product ; the exocyclicmethylene group was demonstrated by two-stage oxidation to formaldehyde.CH2 M2 -4- (q,;+A>-MeM e * s 0 2 0 7 M e M ~ ~ ~ M eRo d&ho (LVI) RO -" (LVII)The corresponding 1%-derivative was unchanged under similar con-d i t i o n ~ .~ ~ A carbon skeleton identical with that of (LVII) has been postul-ated for the alkaloid jer~ine.~,61 C. W. Shoppee and G. H. R. Summers, J., 1952, 3361.62 H. Schmid and K. Kagi, Helv. Chim. Acta, 1950, 33, 1582; cf. F. S. Prout and63 C. W. Shoppee and G. H. R. Summers, J . , 1952, 2528.64 E. S. Rothman, M. E. Wall, and C. R. Eddy, J . Amer. Chem. SOC., 1952, 74, 4013.66 R. E. Marker and J. Lopez, ibid., 1947, 69, 2390.66 M. E. Wall, C. R. Eddy, M. L. McClennan, and M. E. Klumpp, Analyt. Chem.,6 7 D. H. Gould, H. Staeudle, and E. B. Hershberg, J . Amer. Chem. Soc., 1952, 74,For some evidence of configuration see J.Pataki, G. Rosenkranz, and C. Djerassi,71 R. Hirschmann, C. S. Snoddy, and N. L. Wendler, ibid., p. 2694.73 J- Fried, 0. Wintersteiner, M. Moore, B. M. Iselin, and A. Klingsberg, ibid., 1951,B. Riegel, J . Amer. Chem. SOC., 1952, 74, 3190.1952, 24, 1337.3685.&id., p. 5375.73, 2970.H. M. Doukas and T. D. Fontaine, ibid., 1951, 73, 5918.70 N. L. Wendler, H. L. Slates, and M . Tishler, ibid., 1952, 74, 4894CORNFORTH : STEROIDS. 201Reichstein and his collaborators have published numerous papers add-ing to the systematic knowledge of naturally occurring cardiac glycosides.Two glycosides from Gomphocarpzls fruticosus, gofruside and frugoside, wererespectively hydrolysed 73 to the aglycones corotoxigenin and corogluaci-genin previously obtained by Stoll, Pereira, and Renz '4 from Coronkllaglauca.Corotoxigenin has been identified as a 5-deoxystrophanthidin(LVIII ; R = CHO), and coroglaucigenin as the corresponding strophanthidol(LVIII; R = CH,*OH), by degradation to an ester (LIX) obtainable alsofrom strophanthidin.The cholesterol isomer, cholest-7-en-3p-01, has been isolated from the skinof albino rats.75Biogenesis of Steroids.-Langdon and Bloch 76 have shown that 14C-labelled squalene, obtained from the tissues of rats fed with l*C-label€edacetic acid, when fed to other rats is converted into cholesterol more effici-ently than any previously known precursor. This observation, indicatinga close relation between steroid and terpenoid biogenesis, lends additionalinterest to the recent elucidation of the structure of lanosterol. Evidenceon the point of attachment of the side-chain has been obtained by chemical 77and by X-ray crystallographic 78 methods, and lanosterol may now beregarded as 4 : 4 : 14-trimethylzymosterol (LX), a steroid with some terpenoidfeatures.Me IMe I CH.CH,.CH,*CH:CMe,Me,Physical Properties of Steroids.-Several papers on the infra-red spectraof steroids have appeared, and features of the spectra have been correlatedwith the configuration of 3-hydroxyl groups,79 with methyl and methylenegroups,8o and with the A5-3p-hydroxy-system.81 Several methods for paper73 A.Hunger and T. Reichstein, Helv. Chim Acta, 1952, 35, 1073.74 A. StolI, A.Pereira, and J. Renz, ibid., 1949, 32, 293.7 6 D. R. Idler and C. A. Baumann, J . Biol. Chem., 1952, 195, 623.76 R. G. Langdon and K. Bloch, J . Amer. Chem. SOC., 1952, 74, 1869.7 7 W. Voser, M. V. Mijovic, H. Heusser, 0. Jeger, and L. Ruzicka, Hclv. Chim. Ada,7 8 R. G. Curtis, J. Fridrichsons, and A. McL. Mathieson, Natuve, 1952, 170, 321.70 A. R. H. Cole, B. N. Jones, and K. Dobriner, J. Amer. Chem. Soc., 1952, 74, 5571.R. N. Jones and A. R. H. Cole, ibid., p. 5648; idem and B. N o h , ibid., p. 506281 H. Hirschmann, ibid., p. 5357.1952, 35, 2414202 ORGANIC CHEMISTRY.chromatography of steroids have been reported.82 A fractionation of oxbile by counter-current distribution showed, among other things, that nounconjugated bile acids are present in fresh bile.=Stereochemistry of Steroids.-Chemical evidence for the assignmentof configurations to the two 7-hydroxycholesterols has been provided byHeymann and Fieser; the seco-3 : 4-dioic acid (LXI) obtained by hydro-genation and oxidation of the more dextrorotatory epimer forms a y-lactone,which is only possible with a 7p-hydroxyl group.Klyne B5 has published a paper correlating the stereochemistry of thetriterpenoids with that of the steroids on the basis of molecular-rotationcontributions.J. W.C.8. HETEROCYCLIC COMPOUNDS.Further volumes in the series edited by R. C. Elderfield and byA. Weissberger have appeared, and a comprehensive tabular survey ofthiazoles has been published.Three- and Four-membered Ring Systems.-Studies on the fission of theoxiran ring by a variety of reagents * continue to be reported.o-, m-, and$-Nitrostyrene oxides react with the phenoxide ion to give predominantly thesecondary alcohols,5 while, under suitable conditions in the presence ofexcess of phenol as solvent, styrene oxide can give the primary alcohol almostexclusively.6 The secondary alcohol is the major product from styreneoxide and benzylamine, and p-nitrostyrene oxide and diethyl sodiomalonategive the lactone (I),8 indicating- steric factors to be then a controlling in-fluence.9 The reaction between Grignard reagents and the oxiran ring havebeen reviewed.10 The stereochemistry of the opening and closure of thering in 2 : 3-dimethylethyleneimine,ll 2 : 3-epoxybutane,12 and cyclo-hexeneimine (2 : 3-cyclohexanoaziridine) l3 has been studied, both re-82 R.B. Davis, J. M. McMahon, and G. Kalnitsky, J . Amer. Chem. Soc., 1952, 74,4483; R. Neher and A. Wettstein,Helv. Chim. A d a , 1952, 35, 276; I. E. Bush, Biochem. J., 1952, 50, 370.83 E. H. Ahrens and L. C. Craig, J . Biol. Chem., 1952, 195, 763.8 1 H. Heymann and L. F. Fieser, Helv. Chim. Acta, 1952, 35, 631.86 W. Klyne, J., 1952, 2916; cf. W. M. Stokes and W. Bergmann, J . Org. Chem.,1951, 16, 1817.1 “ Heterocyclic Compounds. Vol. I11 : Polycyclic Derivatives of Pyrrole ; Poly-cyclic Systems with One Nitrogen Common to Both Rings; Pyrindene and RelatedCompounds. Vol. IV : Quinoline, Isoquinoline, and Their Benzo Derivatives.” J .Wiley and Sons, Inc., New York, 1952.2 “ Thiophene and its Derivatives,” by H.D. Hartough. ’ ‘ Five-membered Hetero-cyclic Compounds with Nitrogen, Sulphur and Oxygen (except Thiazole),” by L. L.Bambas.9 Kartothek der Thiazolverbindungen (in 4 vols.), by B. Prijs. S. Karger, Basel,1951.6 C. 0. Guss, J . Org. Chem., 1952, 17, 678.6 C. 0. Guss and H. R. Williams, ibid., 1951, 16, 1809.7 C. L. Browne and R. E. Lutz, ibid., 1952, 17, 1187.8 S. J. Cristol and R. I;. Helmreich, J . Amer. Chem. Soc., 1952, 74, 4083.9 Cf. also R. Rothstein and J. Ficini, Compt. rend., 1952, 234, 1293, 1694.l o N. G. Gaylord and E. I. Becker, Chem. Reviews, 1951, 49, 413.l1 F. H. Dickey, W. Fickett, and H. J. Lucas, J . Amer. Chem. Soc., 1952, 74, 944.l2 G. K. Helmkamp and H. J. Lucas, ibid., p.961.l3 0. E. Paris and P. E. Fanta, ibid., p. 3007.D. Kritchevsky and M. R. Kirk, ibid., p. 4484;Intersci. Publ., New York, 1952.4 Cf. Ann. Reports, 1950, 47, 220WALKER : HETEROCYCLIC COMPOUNDS. 203actions being accompanied , as would be expected, by Walden inversion.Alkaline hydrolysis of either the 0- or the S-acetyl derivative of Z-mercapto-ethanol gives ethylene sulphide and polymeric material, and cyclohexenesulphide is similarly 0btainab1e.l~ Glycidol (11) is obtained in high yieldfrom glycerol and ethylene carbonate, or phenyl carbonate, a cross-linkedpoly(glycero1 carbonate) being presumably an intermediate.14uR*CH:C-CHR I I 0-coNO,C,H,*CHCH *CH*CO,Et CH,--CHCH,*OH0- I ' i co '0'In analogy with the formation of coumaranone in the decomposition ofo-ani~oyldiazomethane,1~ I-oxas$iro[3 : 51nonan-3-one (111) has been ob-tained by the decomposition of l-acetoxycyclohexane-l-carbonyldiazo-me thane.l6Further examples of the condensation of indoles with P-propiolactone havebeen described, and pyrrole gave p-2-pyrrolylpropionic acid. l7 Confirmatoryevidence has been produced to show that monosubstituted keten dimers areP-lactones (IV) containing a semicyclic double bond. l8Five- and Six-membered Ring Systems.-A detailed analysis has beenmade of the stereochemical factors governing the synthesis of cyclic acetals ofpolyhydric alcohols, and a theoretical basis has been provided l9 for certainempirical rules 2O developed to enable the pattern of condensation between agiven carbonyl compound and a given polyhydric alcohol to be predicted.y-Valerolactone has been used in the Friedel-Crafts reaction with theisomeric xylenes for the synthesis of various polymethylnaphthalenes.21Perfluorobutyrolactone, the main product of the degradation of silverhexafluoroglutarate with excess of iodine, is a highly reactive compound andreacts with water, ethanol, ammonia, hydriodic acid, and ethanethiol to givederivatives of perfluorosuccinic acid.22The stereochemical course of the temperature-dependent re-action 23 between furan and maleinimide is similar to that between furan andmaleic anhydride,24 the endo-adduct (V) being formed at 25" and the exo-com-pound (VI) a t higher temperatures ; both adducts are relatively unstable,having endo-bridges ,25 but hydrogenation to the hexahydro-3 : 6-endo-oxophthalimides permitted further investigation.% Electrolytic methodshave been described for the alkoxylation of furan and substituted furans withFuran.l4 L.W. C. Miles and L. N. Owen, J., 1952, 817.140 H. A. Bruson and T. W. Riener, J. Amer. Chem. SOC., 1952, 74, 2100.l6 E. R. Marshall, J . A. Kuck, and R. C. Elderfield, J. Org. Chem., 1942, 7 , 444;A. K. Bose and P. Yates. J. Amer. Chem. SOC., 1952, 74, 4703.J . R. Marshall and J . Walker, J., 1952, 467.J . Harley-Mason, J., 1952, 2433.l 8 C. M. Hill, M. E. Hill, H. I. Schofield, and L. Haynes, J. Amer. Chew%. Soc., 1952,S. A. Barker, E. J. Bourne, and D. H. Whiffen, J., 1952, 3865.2o S. A. Barker and E. J . Bourne, ibid., p, 905.21 W.L. Mosby, J. Amer. Chem. Soc., 1952, 74, 2564.22 M. Hauptschein, C. S. Stokes, and A. V. Grosse, ibid., p. 1974.23 H. Kwart and I. Burchuk, ibid., p. 3094.24 R. B. Woodward and H. Baer, ibid., 1948, 70, 1161.25 Cf. Ann. Reports, 1950, 47, 179; M. Kloetzel, Organic Reactions, 1948, 4, 9.74, 166. 204 ORGANIC CHEMISTRY.the production of 2 : 5-dialkoxy-2 : 5-dihydrofurans ; 26 with methanol,maleinaldehyde tetramethylacetal is a by-product. Acyloxylation of furansis effected with lead tetra-acyloxylates 27 and pyrolysis of 2 : 5-diacetoxy-2 : 5-dihydrofuran gives 2-acetoxyf~ran,~S while conversion of thedialkoxydihydrofurans into l-arylpyrroles proceeds in good yield.%The Willgerodt reaction is applicable in the furan series if lower temper-atures are used than is customary.30 Formation of a 1 : 2-adduct (VII) offurfuraldehyde and batadiene has been reported,31 and appears to be theonly known example of furfuraldehyde acting as a dienophile in a dienereaction. Another product is formed in the reaction and appears, fromvarious degradations, to be (VIII).32 The reaction of diazonium salts withfurylacrylic acid 33 leads mainly to 5-aryl-2-styrylfurans, 2-styrylfurans andp-(5-aryl-2-furyl)acrylic acids being formed as by-products.The methylenedihydrofuran, obtained together with 2-methylfuran byapplying the Wolff-Kishner reaction to furfuraldehyde, has been shown by 4y l-&cohH <?/\ /\/ CH* \p+OHco’ \p0,/ d! (Ao/..CO-NH CHO(V) t VI 1 ( V W (VIII)ultra-violet absorption to be the conjugated 2 : 5-dihydro-2-methylene-f ~ r a n .~ ~ The reaction between the two stereoisomeric forms of tetrahydro-5-hydroxy-3-methyl-2-propenylfuran and aniline is said to give selectively thetwo forms of the corresponding anilino t e trahydrof urans.Further experience has been obtained of the use of dihydropyranfor the protection of secondary alcohol groups in steroids.36 Other novelreactions in this series include the reaction of 2-alkoxy-3 : 4-dihydropyrans 37with ammonia over alumina a t 400°, which gives pyridine, and thermalcleavage over an alumina-silica catalyst to isomeric 5-alko~ypent-4-enals.~~Addition of alcohols, carboxylic acids, phenol, and hydrogen cyanide yieldsthe appropriate 6-alkoxy-, 6-acyloxy-, 6-phenoxy-, and 6-cyano-derivativesof 2-alkoxy t e trahydropyran .3 Hydrogenation of 2-alkoxydih ydropyransover Raney nickel gave 2-alkoxytetrahydropyrans and hydrolysis followedby hydrogenation gave the corresponding pentane-1 : 5-di0ls.~~ The latterPyran.26 N.Clauson-Kaas et al., Acta Chem. Scand., 1952, 8, 531, 545, 551, 556, 569;27 N. Elming and N. Clauson-Kaas, ibid., p. 535; N. Elming, ibid., p. 578.28 N. Clauson-Kaas and N. Elming, ibid., p. 560.29 N. Elming and N. Clauson-Kaas, ibid., p. 867; N. Clauson-Kaas and 2. Tyle,30 J. A. Blanchette and E. V. Brown, J . Amer. Chem. Sac., 1952, 74, 2098.31 J . C. Hillyer, S. Swadesh, M. L. Leslie, and A. P. Dunlop, I n d . Eng. Chem., 1948,33 W. Freund, J., 1952, 3068; cf. D. M. Brown and G.A. R. Kon, J . , 1948, 2150.34 H. L. Rice, J . Amer. Chem. SOC., 1952, 74, 3193.3 5 C. Glacet, Compt. rend., 1952, 234, 2371,36 A. C. Ott, M. F. Murray, and R. L. Pederson, J . Amer. Chem. SOC., 1952, 74, 1239;37 Ann. Reports, 1950, 47, 226; 1951, 48, 211.38 C. W. Smith, D. G. Norton, and S. A. Ballard, J . Amer. Chem. SOC., 1952, 74, 2018.39 R. I. Longley, W. S. Emerson, and T. C. Shafer, ibid., p. 2012.N. Elming, ibid., p. 572.ibid., p. 667.40, 2216. 12 J. C. Hillyer and J. T. Edmonds, J . Org. Chern., 1952, 17, 600.E . Elisberg, H. Vanderhaeghe, and T. F. Gallagher, ibid., p, 2814WALKER : HETEROCYCLIC COMPOUNDS. 205are also obtained directly by hydrogenation over copper chromite in thepresence of water,39 the saturated S-lactone being a by-product in the caseMe Meof dihydro-2-methoxy-4-methylpyran. Dihydrodeoxypatulinic acid (IX)has been synthesised from A3-dihydropyran and formaldehyde by way ofthe methylene ether (X) or the diacetate (XI)J41 and tetrahydro-3 : 4-dihydroxypyran is accessible from erythrol (but-l-ene-3 : 4-diol) and form-aldehyde.42Dieckmann ring-closure of ethyl y-carbethoxymethylthiobutyrate givesethyl tetrahydro-3-ketothiapyran-2-carboxylate (XII), converted by aseries of stages into A2-dihydrothiopyran 1 : l-dioxide (XIII) ; the latterreadily passes irreversibly into the A3-sulphone (XIV) 43 in contrast with thesituation arising with isoprene sulphone (XV) .Vapour-phase reaction oftetrahydropyran with primary aromatic amines gives l-arylpiperidines inhigh yield,&Deuterated y-pyrones have been prepared by exchange and synthesis,and exchange, rather surprisingly, takes place only at the cc-p0sition.4~Pyrrole.The molecular structures of pyrrole and some of its simplederivatives have been studied by electric dipole-moment measurements 46and fit into a general pattern with indole derivatives.4' Pyrroles react withisocyanates with C-substitution at previously unsubstituted positions in thenucleus. The imino-group is unreactive and no reaction takes place withH H1-methylpyrrole in accordance with the rule that N-substitution deactivatesthe pyrrole nucleus generally.48 Similarly, diketen reacts with pyrroles togive C-acetoacetylpyrroles (e.g. , XVI), hydrolysed by alkali to C-acetyl-40 Cf.L. P. Kyrides and F. B. Zienty, J . Amer. Chem. SOL, 1946, 68, 1385.41 S. Olsen, Acta Chem. Scand., 1951, 5, 1326.43 E. Fehnel, J . Amer. Chem. SOL, 1952, 74, 1569.44 A. N. Bourns, H. W. Embleton, and M. K. Hansuld, Canad. J . Chem., 1952, 30, I .4 5 R. C. Lord and W. D. Phillips, J . Amer. Chem. Soc., 1952, 74, 2429.4 6 H. Kofod, L. E. Sutton, and J. Jackson, J . , 1952, 1467.4 7 E. F. J , Janetzk andM. C . Lebret, Rcc. Trav. chzim., 1944, 63, 123.48 A. Treibs and d Ott, Annabn, 1952, 577, 119.42 Idem, ibid., p. 1339206 ORGANIC CHEMISTRY.pyrr~les.*~ Hydroxymethylpyrroles containing only alkyl groups as othersubstituents are unknown and are not even accessible by lithium aluminiumhydride reduction of suitable precursors ; the reaction either fails completelywith recovery of starting material, even with excess of reagent in boilingtetrahydrofuran, or reaction occurs with subsequent destruction of thelabile product.Analogous secondary alcohols are also not accessible by thismeans, 3-acetyl-2 : 4-dimethylpyrrole, for example, yielding cryptopyrrole(3-ethyl-2 : 4-dimethylpyrrole) . 50 When the reducible functional groupsare not directly attached to the pyrrole nucleus reduction with lithiumaluminium hydride proceeds normally. 51Substituted pyrrolidines are prepared by the addition of aliphatic nitro-compounds to acrylic ester, followed by reduction of the y-nitro-esters, ringclosure, and further reduction of the resulting pyrrolidones with lithiumaluminium hydride. 52 Similar reduction of alkylsuccinimides proceedsnormally.53 The relative ease of formation of the pyrrolidine ring is shownby the ready cyclisation, under the conditions of amidine formation, of3-chloro-l-phenyl-, 3-chloro-1 : l-diphenyl-,= and 3-dimethylamino-1 : 1-diphenyl-propyl cyanide 55 to iminopyrrolidines, ring closure in the lastinstance being accompanied by loss of a methyl group.Evidence has beenNHII /C-NMe + Ph,C I Ph,C PN\CH,*CH,.NMe, \CH,-CH,obtained to suggest that the biosynthesis of proline follows the path:glutamic acid --+ glutamic acid y-semialdehyde -+ Al-pyrroline-5-carboxy-lic acid --+ pr0line,~6 and it has been shown that natural hydroxy-L-prolinecan be converted into the other three stereoisomeric modifications by selectiveinversions.57Pyridine. The Tschitschibabin synthesis of pyridines has been improvedby carrying out the reaction in acetic acid-ammonium acetate,58 and certain2 : 3 : 5-trisubstituted pyridines are conveniently prepared by disproportion-ation of 2 : 3 : 5-trisubstituted l-benzyl-1 : 2-dihydropyridines obtained bycondensation of aldehydes with N-ben~ylaldimines.~~ A kinetic study hasbeen carried out on the reaction between butadiene and cyanogen, by which2-cyanopyridine is formed.60 Although N-bromosuccinimide would beexpected to introduce bromine atoms into the methyl groups, 2-hydroxy-,2-amino-, and 2-acetamido-4 : 6-dimethylpyridine undergo nuclear bromin-ation even in presence of benzoyl peroxide.61 2-Vinylpyridine, being a49 A.Treibs and K. H. Michl, Annalen, 1952, 577, 129.50 A. Treibs and H. Scherer, ibid., p. 139.51 0. Klamerth and W. Kutscher, Chem. Ber., 1952, 85, 444; W. Kutscher and0. Klamerth, 2. physiol. Chem., 1952, 289, 229.52 R. B. Moffett and J. L. White, J . Org. Chem., 1952, 17, 407.53 D. E. Ames and R. E. Bowman, J.. 1952, 1057.54 F. E. King, K. G. Latham, and M. W. Partridge, ibid., p. 4268.5 5 W. Wilson, J . , 1950, 2173; 1952, 3524; J. Cymerman and W. S. Gilbert, ibid.,5 7 D. S. Robinson and J . P. Greenstein, J . Biol. Chem., 1952, 195, 383.5 8 M. Weiss, J . Amer. Chem. SOC., 1952, 74, 200.58 T. M. Patrick, ibid., p. 2984.61 R. P. Mariella and E. P. Belcher, ibid., p. 1916.p. 3529. 56 H. J. Vogel and B. D. Davis, J . Amer. Chem. SOL, 1952, 74, 109.6o P.J. Hawkins and G. J. Janz, ibid., p. 1790WALKER HETEROCYCLIC COMPOUNDS. 207vinylogue of acrylonitrile, takes part in Michael addition reactions to giveappropriate pyridylethyl derivatives.62 Ultra-violet absorption charac-teristics have shown the existence of restricted rotation in 4-aryl-3 : 5-di-carbethoxy-2 : 6-1~tidines.~~A synthesis of pyridoxine based on biogenetic considerations has beendescribed,6* and pyridoxal5-phosphate (codecarboxylase) (XVII) , which maybe purified as the acridine salt ,65 has 'been obtained from 00-isopropylidene-pyridoxine (XVIII) by reaction with phosphoric oxide in phosphoric acid,and subsequent oxidation of pyridoxine 5-phosphate. 66 Anhydrous phos-phoric acid also converts pyridoxamine into the crystalline 5-pho~phate.~'(-)-Pipecolinic acid has been recognised as a natural amino-acid of relativelywide occurrence.68CHOHO/~H~.O-PO,H,(XVII) Me!! N' '-H27 YH2(XIX) Me& h'Me,,HClph\/CN+ Q + NMe,(XX) Me,HC1Convenient syntheses of alkylpiperidines, 53 piperidin-4-01,~~ 3 : 3-di-substituted 2 : 6-diketopiperidine~,~* substituted 3-piperidones 71 and 1-alkyl-3-hydroxypiperidines 72 have been described, while a novel ring-closure of a=-bis-2-dimethylaminoet hyl- =-phenylacet onitrile hydrochloride(XIX) proceeds with loss of trimethylamine and formation of 4-cyano-1-methyl-4-phenylpiperidine hydrochloride (XX) in 78 yo yield.73Monocyclic compounds with more than one hetero-atom. PreliminarylfX1, 'Y'(XXII)EtO(XXIV)/s(XXVI)i!s>OAc/N=CHC2BH3808)C\ I C28H3808}C0 f NH3 $- [HS'CH2'CH01S-CH,Uscharin Uscharidinstudies of the series (XXI) and (XXII) have been reported where X = S,Y = 0, and X = Y = S.Monothioglycol(2-mercaptoethanol) and chloro-62 R. Levine and M. H. Wilt, J . Amer. Chem. SOC., 1952, 74, 342.64 A. Cohen, J. W. Haworth, and E. G. Hughes, J.. 1952, 4374.66 M. Viscontini and P. Karrer, Helv. Chim. Acta, 1952, 35, 1924.66 J . Baddiley and A. P. Mathias, J., 1952, 2583.97 E. A. Peterson, H. A. Sober, and A. Meister, J . Amer. Chem. Soc., 1952, 74, 570.68 R. M. Zacharius, J. F. Thompson, and F. C. Steward, ibid., p. 2949; G. Harris6s K. Bowden and P. N. Green, J., 1952, 1164.7O E. Tagmann, E. Sury, and K. Hoffmann, Helv. Chim. Acta, 1952, 35, 1235.7l F.F. Blicke and J. Krapcho, J . Amer. Chem. Soc., 1952, 74, 4001.73 J . H. Biel, H. L. Friedman, H. A. Leiser, and E. P. Sprengeler, ibid., p. 1485.73 F. F. Blicke, J. A. Faust, J . Krapcho, and E. Tsao, ibid., p. 1844.A. P. Phillips and P. L. Graham, ibid., p. 1552.and J. R. A. Pollock, Chem. and Ind., 1952, 931808 ORGANIC CHEMISTRY.acetaldehyde dimethyl acetal gave 2-methoxy-1 : 4-oxathian (XXIII), con-verted by catalytic decomposition over phosphoric oxide into 1 : 4-oxathien(XXI; X = S, Y = O).74 2-Mercaptoacetal, HS*CH,*CH(OEt),, passesslowly into 2 : 5-diethoxy-1 : 4-dithian (XXIV). The latter is hydrolysed tomercaptoacetaldehyde, which dimerises to give the two stereoisomericforms of 2 : 5-dihydroxy-1 : 4-dithian (XXV), and the derived acetatespass when heated into the same acetoxy-1 : 4-dithien (XXVI).75 Theheterocyclic fragment of the African arrow poison uscharin consists appar-ently of a thiazoline ring since hydrolysis gives uscharidin, ammonia, anddimeric mercaptoacetaldehyde (XXV).76Applications of intermediate oxazoline formationin stereochemical problems have already been reviewed. 77 Analogousstudies based on the intermediate formation of the tetrahydro-1 : 3-oxazinering have clarified the stereochemistry of tropine and pseudotropine. 78 Anovel application of N-acyl + O-acyl migration via the oxazoline is in thedegradation (XXVII) of silk fibroin at serine residue^,'^ and an account hasbeen given of cyclisation, ring-fission, and acyl-migration reactions involvingthiazolines.80 Preservation of spatial configuration during various pro-cedures for closing the hetero-ring in hexahydrobenzoxazolones (XXVIII ;X = 0) and related compounds (XXVIII; X = S, or NH) has beendemonstrated, and both cis- and trans-series are obtainable. 81Oxaxoline ; thiazolirze.R(XXVII) (XXVIII) (XXIX)Further studies of the ultra-violet light absorption ofpyrimidine derivatives have been reported,S2 and an empirical rule has beenfound for calculating the wave-length of absorption maxima of polysub-stituted compounds containing not more than one potentially tautomericgrouping. 83 Infra-red absorption characteristics of a wide range of deriv-atives have been published,8* and a novel technique in this field, with possiblewide application^,^^ uses the substance embedded in a plate of potassiumbromide formed under high pressure.86 The infra-red absorption data aremore in accord with amino- than with imino-dihydro-structures for potentialaminopyrimidines, in line with conclusions reached on similar evidence foraminopyridines.87Pyrimidim.74 W. €3. Parham, I. Gordon, and J. D. Swalen, J . Amer. Chem. SOC., 1952, 74, 1824.75 G. Hesse and I. Jorder, Chem. Ber., 1952, 85, 924.7 8 G. Hesse and H. W. Garnpp, ibid., p. 933.7 7 Ann. Reports, 1951, 48. 217; cf. G. Fodor and K. Koczka, J., 1952, 860.713 G. Fodor and K. NAdor, Nature, 1952, 169, 462; A. Nickon and L. F. Fieser,J. C. Crawhall and D. F. Elliott, J., 1952, 3094.81 M. Mousseron, F.Winternitz, and M. Mousseron-Canet, Compt. rend., 1952,235,373.82 D. Shugar and J. J. Fox, Biochim. Biophys. Acta, 1952, 9, 199; M. P. V. Boarland84 L. N. Short and H. W. Thompson, ibid., p. 168.85 Cf. U. Schiedt and H. Reinwein, 2. Naturforsch., 1952, 7b, 270.86 M. M. Stimson and M. J . O’Donnell, J . Amer. Chem. Soc., 1952, 74, 1805.C. L. Angyal and R. L. Werner, J., 1952, 2911; J. D. S. Goulden, ibid., p. 2939;J . Amer. Chem. Soc., 1952, 74, 5566. 79 D. F. Elliott, Biochem. J., 1952, 50, 542.and J. F. W. McOmie, J., 1952, 3716. *3 Idem, ibid., p. 3722.cf. also S. J. Angyal and C. L. Angyal, ibid., p. 1461WALKER : HETEROCYCLIC COMPOUNDS. 209Although 5-aminopyrimidine itself fails to undergo diazotisation,88 thepresence of other suitable substituents allows normal diazonium salt form-ation to occur, and in the presence of a 4(6)-mercapto-, -hydroxy-, orprimary-amino-group, ring closure to pyrimidino-thiadiazoles (XXIX ;X = S), Loxadiazoles (XXIX; X = 01, and -triazoles (XXIX; X = NH)occurs; 89 ring closure even takes place with a 4(6)-alkyl group, giving1 : 2 : 4 : 6-tetra-azaindenes (XXIX; X = CH,), isomeric with purines.A new reaction of acetylene with nitriles, e g ., propionitrile, results in theformation of 2 : 4-diethylpyrimidine and the isomeric aminopyridine ;a carbanion mechanism is suggested for the reaction.90Insight into the mechanism of formation of s-triazines fromnitriles has been obtained since all nitriles which form triazines readily giveprimary products containing two molecules of nitrile to one of hydrogenhalide, their properties being compatible with ionic ~ t r u c t u r e s .~ ~ Besides theuse of strong acids, nitriles may also be trimerised in the presence of methanolor weak bases at high pressures (7000-8500 atm.) ; besides the triazine, theisomeric 4-amino-2 : 6-dimethylpyrimidine is also obtained from acet~nitrile.~~The novel formation of aminotriazines has been observed in the reactionbetween a-cyano-carbonyl compounds and g ~ a n i d i n e . ~ ~a-li$oic (thioctic) acid. A new growth factor has been isolated anddescribed under several names : protogen A,% thioctic acid,g4 and ol-lipoicacid.95 Degradation 94-96 and synthesis 97, 98 of a-lipoic acid (from y-tetrahydro-2-furylbutyric acid) and of some of its isomersg9 have shownit to be “ 5 : 8-dithio-octanoic acid ” (3-3’-carboxypropyl-l : 2-dithian)(XXX).Another growth factor, protogen B, is possibly a closely relatedTriazine.~-~H.[CH2] ,*CO,HH,C NH ‘c6 (XXXI)sulphoxide.lO0 (95) The amide of cc-lipoic acid with thiamine pyrophosphateappears to be a coenzyme in the oxidative decarboxylation of a-keto-acids,lo1and it may also be concerned in photosynthesis.lo28 8 M. P. V. Boarland and J. F. W. McOmie, J., 1951, 1218.89 F. L. Rose, J . , 1952, 3448.T. L. Cairns, J. C. Sauer, and W. K. Wilkinson, J . Amer. Chem. Soc., 1952, 74, 3989.y1 C. Grundmann, G. Weisse, and S. Seide, Annalen, 1952, 577, 77.92 T. L. Cairns, A. W. Larchar, and B. C. McCusick, J . Amer. Chem. Soc., 1952, 74, 5633.93 P.B. Russell, G. H. Hitchings, B. H. Chase, and J . Walker, ibid., p. 5403.g4 J. A. Brockman, E. L. R. Stokstad, E. L. Patterson, J. V. Pierce, M. Macchi, and95 L. J. Reed, B. G. DeBusk, I. C. Gunsalus, and G. H. F. Schnakenberg, ibid.,96 L. J. Reed, Q. F. Soper, G. H. F. Schnakenberg, S. F. Kern, H. Boaz, and I. C.9 7 M. W. Bullock, J . A. Brockman, E. L. Patterson, J . V. Pierce, and E. L. R. Stok-98 C. S. Hornberger, R. F. Heitmiller, I. C. Gunsalus, G. H. F. Schnakenberg, and9g M. W. Bullock, J . A. Brockman, E. L. Patterson, J . V. Pierce, and E. L. R.loo E. L. Patterson, J. A. Brockman, F. P. Day, J. V. Pierce, M. E. Macchi, C. E.lol L. J. Reed and B. G. DeBusk, ibid., 1952, ‘94, 3457, 3964, 4727; J . Biol. Chern.,lo2 hl.Calvin and J. A. Barltrop, ibid., p. 6153.F. P. Day, ibid., p. 1868.1951, 73, 5920.Gunsalus, ibid., 1952, 74, 2383.stad, ibid., p. 1868.L. J. Reed, ibid., p. 2382.Stokstad, ibid., p. 3455.Hoffman, C. T. 0. Fong, E. L. R. Stokstad, and T. H. Jukes, ibid., 1951, 73, 5919.1952, 199, 881210 ORGANIC CHEMISTRY.Actithiazic acid. Two other groupslo3 have independently isolated a novelantibiotic, CsHl,O,NS, from Strefitomyces spp. Treatment with mercuricchloride lo* or alkali lo5 removed the nitrogen, the sulphur, and two carbonatoms to give the semialdehyde of pimelic acid; the substance was therefore(-)-2-5~-carboxypentylthiazolid-4-one (XXXI), and the (&)-form wassynthesised by condensation of this aldehyde with thioglycollamide w lo6and resolved with brucine.104Dihydroquinoline is obtainablefrom quinoline by reduction with lithium aluminium hydride, a reagent whichgenerally converts heterocyclic compounds into dihydro-derivatives whichare often difficult of access and ~ n s t a b l e .1 ~ ~ Several instances of lability ofhalogen substituents in the Bx-ring of quinoline have been reported : thebromine atoms in S-amino-5 : 7-dibromoquinoline are replaced by chlorineduring diazotisation and deamination in hydrochloric acid ; lo8 S-amino-5-bromo-6-methoxyquinoline is converted into the 7-bromo-isomer byboiling hydrobromic acid ; los 5-chloro-8-hydroxy-7-iodoquinoline is saidto undergo disproportionation in boiling dioxan to give 8-hydroxy-5 : 7-di-iodo- and 5 : 7-dichloro-S-hydroxy-quinoline.110 Reactive halogen atomsin the heterocyclic rings of 2-chloro- and 4 : 7-dichloro-quinoline, and of2-chlorobenzothiazole, undergo the Friedel-Crafts reaction with resorcinol togive the corresponding dihydroxyphenyl derivatives.lllThe base-catalysed condensation of quinolinium methiodide with sub-stances containing a reactive methylene group is now well-established, theproducts being derivatives (XXXII) of 1 : 4-dihydro-l-methyl-4-methylene-quinoline.1l2 y-Aminotropolone (XXXIII) undergoes the Gould- JacobsCondensed Ring Systems.--QuinoZine.(XXXII) (XXXIII) (XXXIV) (XXXV)modification c f the Conrad-Limpach reaction,l13 the Doebner-Miller re-action,l13 and +he Skraup reaction 114 to give the apEjropriate pyridino-tropolones (XXXIV).Three of five antibiotics produced by Pseudomonas aeruginosa have beenlo3 W.E. Grundy, A. L. Whitman, E. G. Rdzok, E. J. Rdzok, M. E. Hanes, andJ. C. Sylvester, Antibiotics and Chemotherapy, 1952, 2, 399; B. A. Sobin, J . Amev. Chem.SOC., 1952, 74, 2947.lo4 W. M. McLamore, W. D. Celmer, V. V. Bogert, F. C. Pennington, and I. A.Solomons, ibid., p. 2946.lo5 J. R. Schenck and A. F. De Rose, Arch. Biochem. Biophys., 1952, 40, 263.lo@ R. K. Clark and J . R. Schenck, ibid., p. 270.lo7 F. Bohlmann, Chem. Ber., 1952, 85, 390.lo8 R. C. Elderfield and E. F. Claflin, J . Anzer. Chem. SOC., 1952, 74,2953.log W. M. Lauer, C . J. Claus, R. W. Von Korff, and S. A. Sundet, zbzd., p. 2080.110 T. N6grAdi. Chem. Ber., 1952, 85, 104.ll1 G. Illuminati and H.Gilman, J . Amer. Chem. SOC., 1952, 74, 2896.11* N. J. Leonard, H. A. DeWalt, and G. W. Leubner, J . Amer. Chem. Soc., 1951,73, 3325; N. J. Leonard and R. L. Foster, ibid., 1952, 74, 2110, 3671.113 R. Slack and C. F. Attridge, Chem. and Ind., 1952, 471.114 J. W. Cook, J. D. Loudon, and D. K. V. Steel, ibid., p. 562WALKER : HETEROCYCLIC COMPOUNDS. 211shown by degradation 115 and synthesis to be 2-heptyl-, 2-nonyl-, and2-non-l'-enyl-quinolin-4-01. 1 : 2-Dihydro-2-keto-l-azapyrene (XXXV) hasbeen isolated from the pitch fraction, b. p. 470°, of coal tar.l17The infra-red absorption spec-tra of 4-hydroxy-, 2 : 4-dihydroxy-, and 4-mercapto-quinazolines supportthe tautomeric carbonyl and thiocarbonyl structures.118Relatively high pH values have been found to favour the formation ofmonoacyl derivatives of tetrahydroquin~xaline,~~~ which is convenientlyprepared from o-amino-N-2-hydroxyethylaniline.120Elegant methods for the removal of terminal protecting N-chloroacetylgroups or terminal amino-acid residues from peptides have been described.Reaction of the chloroacetyl derivatives with o-phenylenediamine affords1 : 2 : 3 : 4-tetrahydro-2-ketoquinoxaline (XXXVI) and the free 'peptidedirectly.121 The reaction is not conveniently applied by reduction ofdinitrophenyl peptides prepared by the standard method,122 but condens-ation of a peptide with methyl 4-fluoro-3-nitrobenzoate affords the appropriatesubstituted phenylpeptide (XXXVII), passing on reduction into the tetra-hydroket oquinoxaline (XXXVI I I), characteristic of the terminal amino-acidresidue, and the lower peptide (XXXIX) .123s 124 Terminal o-nitrophenoxy-Quinazoline ; quinoxaline ; benzoxazine.1 fjNH2 + CI-CH,*CO*NH-CHRCO. .. -+ [alNHz ~\NH,CH,CO-NH-CHR.CO . , ,\/"HZybNH'yHR + NH,CHR'.CO.. . ~\NH-CHRCO.KH.CHR~.CO . . .MeO,Ci)! NO, --+ Me0,C' \\/\NH/CO '1(XXXVII) ( XXXVI I I) (XXXIX)acetyl groups are similarly eliminated from peptides, reduction affording the1acta.m (XL; R = H) of o-aminophenoxyacetic acid and theOHHO Me(XL) (XLI) (XLII)123 The ready formation of the ring system (XL) wasfree pep-also seenin the formation of 2 : 3-dihydro-3-keto-4-methylbenz-1 : 4-oxazine (XL ;R = Me) when the normal conditions for the StolI6 oxindole synthesis wereapplied to N-cc-halogenoacetyl-N-methyl-o-anisidine, though rearrangement116 I.C. Wells, W. H. Elliott, S. A. Thayer, and E. A. Doisy, J . Biol. Chem., 1952,11' 0. Kruber and R. Oberkobusch, Chem. Ber., 1952, 85, 433.118 H. Culbertson, J. C. Decius, and B. E. Christensen, J . Amer. Chem. Sot., 1952,G. R. Ramage and G. Trappe, ibid., p. 4406.lZ1 R. W. Holley and A. D. Holley, J . Amer. Chem. SOL, 1952, 74, 3069.lZ2 F. Sanger, Biochem. J., 1945, 39, 507.lZ3 R. W. Holley and A. D. Holley, Zoc. cit., p. 1110.12'. Idem, ibid., p. 5445.190, 321.74, 4834.116 I. C. Wells, ibid., p. 331.ll9 J. S. Morley, J . , 1952, 4004212 ORGANIC CHEMISTRY.to the isomeric oxindoles (XLI) and, surprisingly, (XLII) took place at highertemperatures.125Miscellaneous sulphur-containing compounds.The properties of aninteresting compound, C,H,,S, from Middle East oil distillates recall adaman-tane in some respects and, as desu-lphurisation gave bicycZo[l : 3 : Slnonane,it is formulated as thia-adamantane (XLIII).126 Raney nickel desulphuris-CH2-CH- I I(XLIII) (XLIV) (XLV)ation of 1 : 2-dihydro-l-keto-2-thianaphthalenes (e.g. , XLIV) gave indanones(e.g., XLV).127Full details have now been given of the isolation 128 of biocytin fromyeast and its recognition by degradation 129 and synthesis 130 as c-N-biotinyl-L-lysine.Ring systems with a nitrogen atom common to two rings. The reductivecyclisation of nitro oo'-dicarboxylic esters, previously used for pyrroliz-idines,131 has been extended. The addition of methyl y-nitrobutyrate tomethyl sorbate gave the ester (XLVI), which passed on hydrogenation overcopper chromite into 2-methyl-7-azabicycZo[5 : 3 : Oldecane (XLVII) .132The method has been extended to the synthesis of tricyclic systems (XLIX)Me cs"I PI-J \/\\ ('y qH I/CHMe.CH( 7 3 2 - p\P(LI) (L)/CHz LIJ CH NO, \" C0,Me C0,Me(XLVI) (XLVII).""; "YCz2], \" -j [CH,], /"?y/cY lCH21,\ /g\ /HF: YHCCH2Iz \ /c\ /HC: YH H,C-[CH2], (XLIX) (XLVIII) H,C---[CH,],from the oximes of keto-dicarboxylic esters (XLVIII) under similar con-d i t i o n ~ .~ ~ ~ The hexahydrojulolidine obtained in this way (where x = y = z= 2) was identical with one of the stereoisomers obtained on catalytic re-duction of julolidine,l3* and gave evidence of resolution 133 over a column125 J.W. Cook, J. D. L'oudon, and P. McCloskey, J., 1952, 3904.lZ6 S. F. Birch, T. V. Cullum, R. A. Dean, and R. L. Denyer, Nature, 1952, 170, 629.lZ7 D. J. Dijksman and G. T. Newbold, J . , 1952, 13; J. J. Brown and G. T. Newbold,L. D. Wright, E. L. Cresson, H. R. Skeggs, T. R. Wood, R. L. Peck, D. E. Wolf,ibid., p. 4397.and K. Folkers, J . Amer. Chem. SOC., 1952, 74, 1996.129 R. L. Peck, D. E. Wolf, and K. Folkers, ibid., p. 1999.13* D. E. Wolf, J. Valiant, R. L. Peck, and K, Folkers, ibid., p. 2002.131 N. J. Leonard and D. L. Felley, ibid., 1950, 72, 2537.133 N. J. Leonard and W. J. Middleton, ibid.. p. 5114.134 M. Protiva and V. Prelog, Helv. Chim. Acta, 1949, 32, 621.N. J. Leonard, D. L.Felley, and E. D. Nicolaides, ibid., 1952, 74, 1700WALKER : HETEROCYCLIC COMPOUNDS. 213of D-lactose, indicating the cis : trans-structure (L), the cis : cis- andtrans : trans-stereoisomers being meso-forms.(-)-Octahydropyrrocoline (LI) has been correlated with (+)-coniine andD( +)-pipecolinic acid and therefore belongs to the ~ - s e r i e s . l ~ ~The electrolytic reduction of a-amino-ketones 136 has now been appliedto bicyclic representatives in a new synthesis of medium-sized nitrogen-containing rings, octahydro-l-ketopyridocoline (LII) giving 5-hydroxyaza-cyclodecane (LIII) .13’Et Me 0 4x2\Hi/R MeII Me/\/PA I I I I + t I\/ Y/ i Y 5 + P5Me\/N\/ \/&/(LII) (LIII) (LIV) (LV)The “ ethiodide ” of 1 : 5 : 8-trimethyl-2 : 3-benzopyrrocoline (LIV;R = Me) and the “ methiodide ” of l-ethyl-5 : 8-dimethyl-2 : 3-benzo-pyrrocoline (LIV; R = Et) are identical, indicating alkylation at the p-carbon atom of the indole ring system and the salt is therefore the pyridiniumcompound (LV) .l3 *Indole. The mechanism of the Fischer indole synthesis is still the subjectof discussion 139 though the general correctness of the Robinson mechanismis not disputed, and an analog9 is seen between the Fischer indole synthesisand the conversion of 1-phenylthiosemicarbazide (LVI) into Z-aminobenzo-thiazole (LVII) . 141 The conversion of 2 : 6-dichlorophenylhydrazanes(LVIII) into 7-chloroindoles (LIX) in presence of stannous chloride and 5 : 7-dichloroindoles (LX) with zinc chloride has been discussed.142 Polyphos-phoric acid is also usefully emp10yed.l~~(LVI) (LVII) (LXI)C f h &ZnC1,FH2RSnCh /\ci E*R’ -+ A1 lmIz/ +- 1 11, ,,N \cp$ \d M NC(y(LIX) (LVIII) (LX)Indole-3-aldehyde has been obtained by improved methods ; these arethe reaction of potassium indole with carbon monoxide at high temperaturesand pressures,l4 a modification of the N-methylformanilide process,145136 Ann. Reports, 1951, 48, 223.l37 N. J. Leonard, S. Swann, and J. Figueras, J . Amsv. Chew. SOC., 1952, 74, 4620.138 Sir R. Robinson and J. E. Saxton, J., 1952, 976.139 R. B. Carlin, J . Amer. CEtem. SOC., 1952, 74, 1077.14* G. M. Robinson and R. Robinson, J., 1924, 125, 827.141 K. Clusius and H. R. Weisser, Helv. Chim. Acta, 1952, 35, 400.14, R.B. Carlin, J. G. Wallace, and E. E. Fisher, J . Amev. Chew. Soc., 1952, 74, 990.143 H. M. Kissman, D. W. Farnsworth, and B. Witkop, ibid., p. 3948.144 F. T. Tyson and 3 . T. Shaw, ibid., p. 2273.14s A. C. Shabica, E. E. Howe, J. B. Ziegler, and M. Tishler, ibid., 1946, 68, 1156.N. J. Leonard and W. J. Middleton, loc. cit., p. 5776214 ORGANIC CHEMISTRY.and the reaction between hexamethylenetetramine and gramine (LXI) inaqueous acetic or propionic a~id.1~6 The red pigment (urorosein) obtainedby the action of acids on indole-3-aldehydes has been shown to be the methene(LXII), recalling pterorhodin formation amongst pterins, and the carbonatom which is lost is eliminated as formic acid.lP7 ad-Di-indolyl-methaneand -methene have also been described.148Although “ gramine methiodide ” has frequently been used, its recordedproperties have varied and no significant analytical data have hitherto beenrecorded.It has now been shown that “gramine methiodide,” as usuallyobtained, is really a mixture of 3 : 3‘-bis(indolylmethyl)dimethylammoniumiodide, [ (RCH,),N+Me,]I- (R = 3-indolyl) and tetramethylammoniumiodide ; 149 the authentic methiodide has, however, now been prepared.149(LXII)The oxidation of indoles has been further extensively studied and re-viewed with special reference to the biological oxidation of tryptophan.lMHydrogen peroxide in the presence of ammonium molybdate affords deriv-atives of anthranilic acid in the case of indoles unsubstituted in the 3-position,and the appropriate ketones from 3-substituted derivatives.151 Treatmentwith osmium tetroxide followed by hydrolysis of the resulting esters gave2 : 3-dihydro-2 : 3-dihydro~yindoles,l~~ and further study of the autoxidationof tetrahydrocarbazoles to give derivatives of cycZopentanes#iro-2-+indoxylis r e ~ 0 r t e d .l ~ ~ The reactions of the stable ozonide (LXIII) formed by2-phenylskatole have been interpreted in terms of an equilibrium betweenthis structure (LXIII) and the tautomeric hydroperoxide form (LXIV),while numerous reductive transformations have been carried out linking theozonide with the hvdroperoxide (LXV) derived from the same parent com-pound, and acid- a i dbeen examined.lUMeI I( o,To ‘’a Ph(LXIII)base-catalysed rearrangements of the ozonide have alsoA novel synthetic route to the eserine (physostigmine) ring system hasemerged ; lM S-methyl- or -hydroxy-indolenines with an alanine side-chainundergo an internal condensation at pH < 6 to give eseroline derivatives and146 H.R. Snyder, S. Swaminathan, and H. J. Sims, J . Amer. Chew. Soc., 1952,74,5110.14’ J. Harley-Mason and J. D. Bu’Lock, Biochem. J., 1952, 51, 430.14* H. Dobeneck and G. Maresch, 2. physiol. Chem., 1952, 289, 271.149 T. A. Geissman and A. Armen, J . Amer. Chem. So;., 1952, 74, 3916.150 A. Ek, H. Kissman, J. B. Patrick, and B. Witkop, Experiential 1952, 8, 36.151 C. Mentzer and Y . Berguer, Compt.rend., 1952,234,627 ; Bull. Soc. chim., 1952,218.152 D. W. Ockenden and K. Schofield, Nature, 1951, 168, 603.153 R.J. S. Beer, T. Broadhurst, A. Robertson, and L. McGrath, J., 1952, 4351;154 B. Witkop, J. B. Patrick, and H. M. Kissman, Chem. Ber., 1952, 85, 949; B.R. J. S. Beer, T. Broadhurst, and A. Robertson, ibid.,’p. 4946.Witkop and J. B. Patrick, J . Amer. Chem. Sac., 1952, 74, 3855, 3861WALKER : HETEROCYCLIC COMPOUNDS. 215it is impossible to synthesise P-methyl-$-tryptophan by the Fischer indolesynthesis from (LXVI), as (LXVII) results instead.(LXVI) (LXVI I )Evidence is now available to show that the molecule of the toxic cyclicpeptide phalloidin, obtained from Amanita phalloides, may consist not ofsix but of seven amino-acid residues,155 and that, as already suggested,156 theformation of oxindolylalanine (2-hydroxytryptophan) (LXVIII) on hydrolysisis an artefact.Treatment of phalloidin with Raney nickel and subsequenthydrolysis have afforded t r y p t ~ p h a n , l ~ ~ indicating the presence of the frag-ment (LXIX) in phalloidin, and, as the ratio, after hydrolysis, of oxindolyl-alanine to cysteine appears to be 2 : 1, it may be that the hydroxyl group ofthreonine or that of allohydroxyproline may participate in an analogousstructure, while the amino-acid residue next to the cysteine may be ala-nine.15' A simple new synthesis of oxindolylalanine has been described.15sYH ...CH,*CH-CO . . .I @\-~H*CH,*CH(NH,)CO,H II f > d\/\gCO ~/'~'\s-cH,.FH.co.. .(LXVIII) (LXIX) N H . . .Convenient syntheses of 5- and 7-hydroxyindole have been recorded 159and bufotenine (LXX), the pressor amine from the skin of the toad, hasbeen obtained from 2 : 5-dimethoxybenzyl cyanide by way of the nitrile(LXXI) and the derived phenylethylamine.160 The biological effects ofserotonin (5-hydroxytryptamine)161 are reversed by 2 : 3-dialkyl-&amino-indoles.162M~o//\-cH(cN).cH,.cH,.N~~, (ii) H B ~ . HOfh,CH2*CH,*NMe,(i) H,-Ni;\/\a' (LXX)I IIOMe -jzjT&$ v (LXXI)3-Indolylacetonitrile has been recognised as a naturally occurring plant-growth hormone163 and the related aldehyde has been synthesised andstudied for such activity. lG4156 T. Wieland and G. Schmidt, Annalen, 1952, 577, 215.156 J. W. Cornforth, C. E. Dalgliesh, and A. Neuberger, Biochem. J . , 1951, 48, 598.157 F. Sorm and B. Keil, Coll. Czech. Chem. Comm., 1951, 16, 366.158 H.Behringer and H. Weissauer, Chem. Ber., 1952, 85, 743; this vol., p. 163.15n R. I. T. Cromartie and J. Harley-Mason, J., 1952, 2525; J. Harley-Mason, Chem.lb0 J. Harley-Mason and A, H. Jackson, Chem. and Znd., 1952, 954.161 New synthesis: B. Asero, V. Colb, V. Erspamer, and A. Vercellone, Annalen,lBz D. W. Woolley and E. Shaw, J . Amev. Chem. Soc., 1952, 74, 2949; cf., however,lbS E. R. H. Jones, H. B. Henbest, G. F. Smith, and J . A. Bentley, Nutwe, 1952,and Ind., 1952, 173.1952, 576, 69.T. D. Spies, and R. E. Stone, J . Amer. Med. Assoc., 1952, 150, 1599.169, 485. 164 J. B. Brown, H. B. Henbest, and E. R. H. Jones, J., 1952, 3172216 ORGANIC CHEMISTRY.Pteridirte. The pteridines have recently been reviewed 165 and progresshas been made in the study of some of the simpler representatives.All fourmonohydroxypteridines are now known and 6-hydroxypteridine (LXXII)shows on titration a hysteresis loop ascribed to slow tautomerism.166 6- and7-Hydroxypteridine (LXXIII) were obtained simultaneously by con-densation of ethyl glyoxylate hemiacetal with 4 : 5-diaminopyrirnidine, thelatter predominating in condensations carried out a t low pH values.166Similarly, xanthopterin (LXXIV) is obtained from 2 : 4 : 5-triamino-6-hydroxypyrimidine and diacetoxyacetic acid in concentrated sulphuric acidat 90” ; 167 xanthopterin is also conveniently obtained from leucopterin(2-amino-4 : 6 : 7-trihydroxypteridine) via dihydroxanthopterin.1“8 ‘ ‘ p-Di-hydroxanthopterin ’ ’ has now been identified as 2 : 6-diamino-5‘-hydroxy-1’ : 4‘-oxazino(2’ : 3’-4 : 5)pyrimidine (LXXV),169 and attempts to preparepteridines by reduction and cyclisation of 4 : 2’-chloroethylamino-5-nitro-pyrimidines gave instead the tetrahydroglyoxalinopyrimidines (LXXVI) .170(LXXII) (LXXIII) (LXXIV) .(LXXV) (LXXVI)The action of alkylamines on 4-amino-2-mercapto- and 4-hydroxy-2-mercapto-pteridines gives either 2-alkylamino-4-amino- or 2 : 4-bisalkyl-amino-pteridines,171 and evidence has been obtained supporting the viewthat these replacements occur with ring cleavage to a thioureidopyrazineintermediate (LXXVII) and subsequent ring-closure ; a similar mechan-ism is advanced for the formation of 2 : 4-bisalkylamino- from 2 : 4-diamino-pteridines and alkylamines.178Pterorhodin formation from pterins, linking two pteridine ring-systemsthrough the 7-position by a methine bridge, is possible if there is present amolecule capable of providing the methine bridge under oxidative con-ditions,l7* and a novel formula (LXXVIII) 175 for erythropterin is believedto account for the notable stability of this ene-diol compound.lS6 A. Albert, Quart. Reviews, 1952, 6, 197.le6 A. Albert, D. J . Brown, and G. Cheesman, J., 1952, 1620.167 F. Korte, Chcm. Ber., 1952, 85, 1017; F. Korte and E. G. Fuchs, ibid., 1953, 86,lBS A. Albert and H. C. S. Wood, J. Appl. Chem., 1952, 2, 591.lsg G. B. Elion and G. H. Hitchings, 3. Amer. Chem. SOC., 1952, 74, 3877.170 G. R. Ramage and G. Trappe, J., 1952, 4410.171 E. C.Taylor and C. K. Cain, J. Amer. Chem. SOC., 1951, 73,4384; 1952,74, 1644.174 R. Tschesche and F. Korte, Chew. Ber., 1952, 85, 139.175 Due to H. G. Khorana; cf. R. Tschesche and F. Korte, Zoc. cit.114.E. C. Taylor, ibid., p. 1651. Idem, ibid., p. 1648WALKER : HETEROCYCLIC COMPOUNDS. 217Further descriptions of the chemistry 176 and the synthesis 177 of leuco-vorin (LXXIX) have been published. In the preparation of leucovorinfrom pteroyl-L-glutamic acid by formylation, reduction and rearrangement,a new asymmetric centre is created at C(61 (marked *), and partial separationof the resulting diastereoisomerides has been eff e ~ t e d . ~ ~ ~ The 7-isomer ofpteroylglutamic acid has also been synthesised.HNucleotides and related compoumis. Physical and physico-chemicalaspects of pyrimidines, purines, and nucleic acids have been reviewed,together with such other studies as bear on structure.lm Spectrophoto-metric patterns have been presented enabling distinction to be made betweenribofuranosides and their deoxyribofuranoside analogues ; similarly, differ-ences are reported between pyrimidine glycopyranosides and glycofurano-sides.181 Riboflavin-5’ phosphate is simply obtained by warming ribo-flavin with metaphosphoric acid,lg2 and diphosphopyridine nucleotide(cozymase) has been obtained in the form of a crystalline quinine salt.ls3Substantial progress has been made during the year in the synthesis ofnycleotides.Condensation of 5’-trityl adenosine with dibenzyl chloro-phosphonate (phosphorochloridate) and removal of protecting groups gavetwo adenylic acids, identical with adenylic acids a and b from ribonucleicacids ; these are formulated as adenosine-2’ phosphate and -3’ phosphate(not necessarily respectively), and ready phosphoryl migration under acidconditions enables interconversion to take place by way of the cyclic 2’ : 3’-phosphate.ls4 Cyclic 2’ : 3’-phosphates of adenosine, cytidine, and uridinehave been synthesised.The cytidine and uridine derivatives have beenidentified as products of incomplete ribonuclease digestion of ribonucleicacids lS6 but they are converted respectively into cytidylic acid b anduridylic acid b by further action of the enzyme, and cytidylic acid b isdeaminated by alkali to uridylic acid b, so that in these two substancesthe phosphoryl group occupies the same position.lS6 It has been suggestedon physico-chemical grounds that cytidylic acid b is cytidine-3‘ phosphate.lS7176 D. B. Cosulich, B. Roth, J. M. Smith, M. E. Hultquist, and R. P. Parker, J .Amev. Chem. SOC., 1952, 74, 3252.177 B. Roth, M. E. Hultquist, M. J. Fahrenbach, D. B, Cosulich, H. P. Broquist,J. A. Brockman, J. M. Smith, R. P. Parker, E. L. R. Stokstad, and T. H. Jukes, ibid.,p. 3247.178 D. B. Cosulich, J . M. Smith, and H. P. Broquist, ibid., p. 4215.170 C . W. Waller, M. J. Fahrenbach, J. H. Boothe, R. B. Angier, B. L. Hutchings,J. H. Mowat, 3 . F. Poletto, and J. Semb, ibid., p. 5405; cf. J. H. Boothe, J. H. Mowat,C. W. Waller, R. B. Angier, J. Semb, and A.L. Gazzola, ibid., p. 5407.18* D. 0. Jordan, Ann. Rev. Biochem., 1952, 21, 209.lal J. J. Fox and D. Shugar, Biochem. Biophys. A d a , 1952, 9, 369.lS3 K. Wallenfels and W. Christian, Angew. Chem., 1952, 64, 419.185 D. M. Brown, D. I. Magrath, and A. R. Todd, ibid., p. 2708.lS6 D. M. Brown, C. A. Dekker, and A. R. Todd, ibid., p. 2715.187 L. F. Cavalieri, J . Amer. Chem. Soc., 1952, 74, 5804.M. Viscontini, C. Ebnother, and P. Karrer, Helv. Chim. Acta, 1952, 35, 457.D. M. Brown and A. R. Todd, J., 1952, 44218 ORGANIC CHEMISTRY.Uridine-5' pyrophosphate has been synthesised 188, 189 and found to beidentical with " uridine diphosphate " from the naturally occurring coenzyme" uridine-diphosphate-glucose, " lgo and uridine-5' pyrophosphate linkedto an amino-sugar through the reducing group has been isolated from peni-cillin-treated Staphylococcus aureus cells.lgl Adenosine-5' uridine-5' phos-phate has been synthesised from a suitably protected silver adenosine4phosphate and 2' : 3'4sopropylidene 5'-deoxy-5'-iodouridine lg2 but this typeof method has limitations. A new method for the preparation of mixedsecondary phosphites (LXXX) lS3 and the fact that these could be chlorinatedwith N-chloro-amides, rather than with more vigorous reagents, to the chloro-phosphonates (LXXXI) 189 paved the way for the synthesis of unsymmetricaldiribonucleoside pyrophosphates, culminating in an outstanding achieve-ment : 194 the synthesis of flavin-adenine-dinucleotide ( PI-riboflavin-5'P,-adenosine-5' dihydrogen pyrophosphate, FAD) (LXXXII) , identicalwith the naturally occurring coenzyme, by condensation of 2' : 3'-isopro-pylidene adenosine-5' benzyl chlorophosphonate with the monosilver saltof riboflavin-5' phosphate and subsequent removal of protecting groups.RO'\p//OCH,Ph/ \ c l (LXXXI)r----o------ IyH,*[CH( OH)],*CH,*O.PO( OH)*O*PO( OH).O*CH,CH*[CH( OH)] 2*qHVitamin B,,.In this field the situation has been complicated by theappearance of Pseudovitamin B,,,1955 lg6 which contains adenine instead of5 : 6-dimethylbenziminazole in the nucleotide portion of the r n o l e ~ u l e . ~ ~ ~Fresh spectroscopic evidence has been produced, however, to show that thebenziminazole chromophore is present in intact vitamin B,, itself,l97 and thespectroscopic examination of authentic synthetic benziminazolo-cobaltousand -cobaltic co-ordination compounds has proved the validity of criteriapreviously employed in establishing the presence of the related complex inthe vitamin.Ig8 Details have been published of the degradation of vitaminB,, to 5 : 6-dimethyl-l-a-~-ribofuranosylbenziminazole (cr-ribazole) lg9 andof the syntheses of the four l-D-ribosides of 5 : 6-dimethylbenziminaz0le.~~~N.Anand, V. M. Clark, R. H. Hall, and A. R. Todd, J., 1952, 3665.189 G. W. Kenner, A. R. Todd, and F. J. Weymouth, ibid., p. 3675.lg0 A. C. Paladini and L. F. Leloir, Biochem. J., 1952, 51, 426.191 J. T. Park, J . Biol. Chem., 1952, 194, 885.lg2 D. T. Elmore and A. R. Todd, J., 1952, 3681.lg3 N. S. Corby, G. W.Kenner, and A. R. Todd, ibid., p. 3669.19* S. M. H. Christie, G. W. Kenner, and A. R. Todd, Nature, 1952, 170, 924.lS5 H. W. Dion, D. G. Calkins, and J. J. Pfiffner, J . Amer. Chem. Soc., 1952, 74,1108.lg6 U. J. Lewis, D. V. Tappan, and C. A. Elvehjem, J . BioE. Chem., 1952, 194, 539;lS7 G. H. Beaven and E. R. Holiday, J . Pharm. Pharmacol., 1952, 4, 344.198 M. T. Davies, P. Mamalis, V. Petrow, B. Sturgeon, G. H. Beaven, E. R. Holiday,lS9 N. G. Brink and K. Folkers, J . Amer. Chem. Soc., 1952, 74, 2856.m0 F. W. Holly, C. H. Shunk, E. W. Peel, J. J. Cahill, J. B. Lavigne, and K. Folkers,1952, 199, 517.and E. A. Johnson, ibid., p. 448.ibid., p. 4521BAILEY : ALKALOIDS. 219A crystalline 2’- or 3’-phosphate of a-ribazole has now been obtained both bydegradation of vitamin B,, and by synthesis.%lMacrocyclic Compounds.-A report on this field must be deferred becauseof limitations of space, but it may be noted that the subject of chlorophyllhas been reviewed exhaustively for the period 1938-1951.202J.W.9. ALKALOIDS.has appeared.This covers the chemistry of the morphine, colchicine, acridine, indole,erythrina, strychnos, and amaryllidaceae groups of alkaloids up to 1951.The biogenesis of alkaloids has been reviewed 3 and has been investigated bymeans of radioactive ~ a r b o n . ~Simple Bases.-Cornforth and Henry have isolated ( -)-stachydrine fromthe fruit of Capparis tomentosa Lam. and from the fruit of Courbonia virgataA. Brongn. ; both cis- and trans-3-hydroxystachydrine (I) have been i~olated.~Both compounds were dehydrated to the same optically inactive anhydro-compound which was reduced to (-J-)-stachydrine and oxidised to P-dimethyl-aminopropionic acid.Since the last Report,l volume 2 of ‘‘ The Alkaloids ’’CH,-CH-CH,I I I SJMey-o\COCH,--CH-CH-C/II(1) (11) CMe,Simple syntheses of mezcaline and trichocereine (NN-dimethyl-mezcaline) 67 7 and of arecoline 8 have been described.Mezcaline containing14C has been pre~ared.~Tropane Group.-The stereochemistry of the tropane alkaloids has beendiscussed.10 Lithium aluminium hydride reduction of tropinone givesentirely $-tropine.ll The Robinson synthesis has been used for the pre-paration of 6-hydroxytropinone 12, l3 and 6 : 7-dihydroxytropinone,13 theintermediate aldehydes being obtained from furan.Pinder has isolated201 E. A. Kaczka, D. Heyl, W. H. Jones, and K. Folkers, J . Amer. Chem. SOC., 1952,2oa A. Stoll and E. Wiedemann, Fortschr. chem. Forsch., 1952, 2, 538.74, 5549.Ann. Reports, 1951, 48, 228.Ed., R. H. F. Manske and H. L. Holmes; Academic Press, New York, 1952.(Sir) R. Robinson, Bull. World Hlth. Org., 1952, 6, 211.K. Bowden and L. Marion, Canad. J . Chem., 1951, 29, 1037, 1043; E. Leete,S. Kirkwood, and L. Marion, ibid., 1952, 30, 749; S. A. Brown and R. U Byerrum,J . A6 J. W. Cornforth and A. J. Henry, J., 1952, 597, 601.K. Banholzer, T. W. Campbell, and H. Schmid, Helv. Chim. Acta, 1952, 35, 1577.L. Reti and J. A. Castrill6n, J . Amer. Chem. SOC., 1951, 73, 1767.A.Dobrowsky, Monatsh., 1952, 83, 443.W. Block and K. Block, C h e w Ber., 1952, 85, 1009.mey. Chem. SOC., 1952, 74, 1523.lo G. Fodor, Nature, 1952, 170, 278; G. Fodor, 0. KOV~CS, and L. Mkszdros, Research,1952, 5, 534; B. L. Zenitz, C. M. Martini, M. Priznar, and F. C. Nachod, J . Amer. Chem.Soc., 1952, 74, 5564; A. Nickon and L. F. Fieser, ibid., p. 5566.l1 R. Mirza, Nature, 1952, 170, 630.la A. Stoll, B. Becker, and E. Jucker, Helv. Ckim. Ada, 1952, 35, 1263.l3 J. C. Sheehan and B. M. Bloom, J . Amer. Chem. SOC., 1952, 74, 3826220 ORGANIC CHEMISTRY.an alkaloid, probably dioscorine, from Dioscorea hzispida Dennst. ; l4 thealkaloid does not appear to have the structure (11) suggested by Gorter l5since it gave no acetone on ozonolysis. It is an ap-unsaturated lactone (atleast a six-membered ring) containing a C-methyl group.Lupinane Group.-Rhombifoline has been shown to possess structure(111 ; R = CH2*CH2*CH:CH2).When heated with hydrogen iodide it gavecytisine (I11 ; R = H) ; and the latter re-formed rhombifoline on alkylationwith but-3-enyl bromide.16 Deoxytetrahydrocytisine (V) has been syn-thesised from 1 : 3-dicarbethoxy-4-quinolizone (IV) and resolved via thetartrate.17C0,EtCH, I’\/ ‘CH, NR I /\’\ H,-Pt *CH-~,yjl,)-COzEt * II 1\(N\ \ II, CH,-CH-CH, II(111) 0 0 (IV)CH,*OH CH- CH,b&\ \ I CH,-CH-CH,(V)isoQuinoline Group.-Manske has deduced formula (VI) for corpaverine ;oxidation gave p-anisic acid, and ethylation followed by Hofmann degradationand oxidation led to 3-ethoxy-4 : 5-dimethoxyphthalic acid.18H,-Pt(VIIIEmetine (VII ; R = Et).19 Openshaw and Wood have shown 2o thatrubremetinium chloride (VIII) is reduced to two dihydrorubremetines (IX) ,both substances giving identical colour reactions and differing in stereo-chemistry at C*.These authors’ observations on the oxidation productsof emetine differ from those reported by HazIett and M~Ewen.~1 A prelimi-nary account of the synthesis of (&)-“ c-noremetine ” (VII; R = H) hasl4 A. R. Pinder, J., 1952, 2286.l6 W. F. Cockburn and L. Marion, Cmad. J . Chem., 1952, 30, 92.l7 F. Galinovsky, 0. Vogl, and W. Moroz, Monatsh., 1952, 83, 242.lS Cf. Ann. Beports, 1949, 46, 202.2o H. T. Openshaw and H, C. S. Wood, J., 1952, 391.21 R.N. Hazlett and W. E. McEwen, J . Amer. Chem. SOL, 1951, 73, 2578.16 K. Garter;Rec. Trav. chim., 1911, 30, 161.R. H. F. Manske, J . Auzer. Chem. SOC., 1952, 14, 2864BAILEY : ALKALOIDS. 221appeared.22 Oxidation of laudanosoline (X) yields dehydrolaudanosoline(XI ; R = H) which is methylated to (XI ; R = Me).23* A new alkaloid,C,H2404NI , related to dehydrolaudanosoline, has been isolated 25 from thebark of Cryptocarya bowiei (Hook), Druce, of Northern Queensland. Thesubstance contains three methoxyl groups and yields a monomethyl ether.The latter, on treatment with alkali, gave an optically active methine (A) ;Hofmann degradation of A led to an optically inactive methine (B) identicalwith the compound from (XI; R = Me).23924 Pyrolysis of the O-methylalkaloid chloride gave the known 23 indole (XII).Bark from SouthernQueensland contained an alkaloid, C,gH,,O,NI, probably of this type, butcontaining one methylenedioxy-group and one methoxyl group.been announced.26 (&)-p-was resolved, the (+)-formMorfihine. The synthesis of morphine hasA6-Dihydrodeoxycodehe methyl ether (XIII) 27being identical with the substance obtained from natural sources: ' Hydr-ation of (XIII) with dilute sulphuric acid gave p-dihydrothebainol methylether (XIV; R Me) ; alkaline demethylation then yielded 8-dihydro-thebainol (XIV ; R = H) which was oxidized to p-dihydrothebainone (XV),Bromination (2 mols.) of this, followed by treatment with 2 : 4-dinitro-phenylhydrazine, gave a 2 : 4-dinitrophenylhydrazone (XVI) , identicalwith the product obtained from thebainone (XVII) or p-thebainone (XVII ;C(,,,-epimer) by treatment with 2 : 4-dinitrophenylhydrazine followed bybromination.This reaction involves epimerisation at C(14) of the p-series(trans --+ cis) , leading to the natural configuration at C(14) (B-c cis). Cleavageof (XVI) with acetone produced l-bromothebainone which was then reducedto dihydrothebainone (XVIII). Bromination (3 mols.) of (XVIII) , followedby treatment with 2 : 4-dinitrophenylhydrazine, gave a small yield ofl-bromocodeinone 2 : 4-dinitrophenylhydrazone (XIX) which was cleavedby acetone to l-bromocodeinone; the latter was reduced to codeine (XX;R = Me) which had previously been demethylated to morphine (XX;R = H) .28 The biogenesis 29 and the absolute stereochemical configuration 30of morphine have been discussed.Evidence has been obtained that theethanamine chain and the C(,]-hydroxyl group are trans in codeine.31 Anaccount of the reactions of phenyldihydrothebaine has been published.3222 M. Pailer and H. Strohmayer, Monatsk., 1951, 82, 1125; 1952, 83, 1198; cf. M.Pailer, K. Schneglberger, and W. Reifschneider, ibid., 1952, 83, 513.23 R. Robinson and S. Sugasawa, J., 1932, 789.24 C. Schopf and K. Thierfelder, Annalen, 1932, 497, 22.25 J. Ewing, G. K. Hughes! E. Ritchie, and W. C. Taylor, Nature, 1952, 169, 618.26 M. Gates and G. Tschudi, J . Amer. Chern. Soc., 1952, 74, 1109.2 7 Idem, ibid., 1950, 72, 4839.28 H. Rapoport, C. H. Lovell, and B. M. Tolbert, ibid., 1951, 73, 5900.29 C.Schopf, Naturwiss., 1952, 39, 241. 30 I. R. C . Bick, Nature, 1952, 160, 755.31 H. Rapoport and G. B. Payne, J . Amer. Chern. SOL, 1952, 74, 2630.32 K. W. Bentley and (Sir)- R. Robinson, J., 1952, 947; cf,., ref. 2 and L. F: FieserReiahold Publ. Corp., and M. Fieser, I' Natural Products Related to Phenanthrene,New York, 1949, p. 19222 ORGANIC CHEMISTRY.Reduction of thebaine by sodium in liquid ammonia gives dihydrothebaine-4(XXI) (phenolic dihydrothebaine) ; 33 this structure is preferred to (XXII) asa result of a study of ultra-violet and infra-red spectra 34 and because it does/\Meoll IHo\//\,Meal AII/ivy I l J 4 I----CH*(XXI) Meo\/I(XXII)H O f YMeo\/ (XXIV)not add dienophile~.~~ Formula (XXII) is that of the p-dihydrothebaineprepared by Karrer and S~hmid.~5 The isomerism of the thebainones has83 K.W. Bentley, (Sir) R. Robinson, and A. E. Wain, J., 1952, 958.34 G. Stiork, J . Amer. Chem. SOC., 1952, 74, 768.35 P. Karrer and H. Schmid, Helv. Chim. Acta, 1950, 33, 863BAILEY : ALKALOIDS. 223been studied, their nomenclature revised, and structures allotted on thebasis of their ultra-violet and infra-red spectra. A fourth thebainone,thebainone-B (XXIII), has been obtained by hydrolysis of dihydro-thebainone-4 (XXI) .36Aporphine Group.-The structure suggested for artabotrine 37 is in-correct, the substance is identical with isocorydine (XXIV) .38Indole Group.-Alstonine (ref. 1, p. 233) has now been isolated fromvarious species of Rauwolja; 39 structure (XXV) is preferred to (XXVI) onthe basis of the infra-red spectrum.Serpentine (ref. 1, p. 233) has beenfound to contain a C-methyl group and is now formulated as (XXVII), adihydro-derivative of alstonine (XXV) .40 Two new quaternary salts,melinonine A, C,,H,,O,N,Cl, and B, C,H,g.ON,Cl, have been isolated fromStrychnos melinonzana Baillon.41 Melinonine A lost methyl chloride onbeing heated, giving a tertiary base, normelinonine A (identical with tetra-hydroalstonine, XXVIII) ; the latter re-formed the alkaloid on methylation.The ultra-violet spectrum of melinonine B suggests it is an ctp-substitutedindole. It is suggested that S-yohimbine and mayumbine are stereoisomersof tetrahydroalstonine (XXVIII) .42 Hydrogenation of sempervirine (XXIX)/ L A /\AI A II B I1 c I+ I II II I f\/‘?+@\ \/‘?’\,P\MeO,C’(XXV) (XXVI) (XXVII)IJ,MeI D 1\/OMe0,C v<hMe \/O M~o,c\/O MMe(XXVIII) (XXIX) (XXX)gave (&)-alloyohimbane (XXX) which was resolved via the tartrate 43 andfound to be identical with the product obtained by Wolff-Kishner reductionof aUoyohimbone (corynanthidone) .44 Corynantheine (XXXI) appearsalways to be admixed with dihydrocorynantheine (XXXII) ,45 and thisexplains the results obtained by various workers : 46 (XXXI) gives form-aldehyde on ozonolysis, and (XXXII) gives acetic acid on Kuhn-Rothoxidation.Lithium aluminium hydride reduction of dihydrocorynantheine36 K. W. Bentley and A. E. Wain, J., 1952, 967.37 G. Barger and L. J . Sargent, J., 1939, 991.3B E.Schlittler and H. U. Huber, Helv. Chim. Acta, 1952, 35, 111.39 E. Schlittler, H. Schwarz, and F. Bader, ibid., p. 271.40 F. Bader and H. Schwarz, ibid., p. 1594.41 E. Schlittler and J. Hohl, ibid., p. 29.42 R. Goutarel and A. Le Hir, Bull. SOC. chim., 1951, 18, 909; M. M. Janot, R.A. Le Hir, R. Goutarel, and M. M. Janot, ibid., 1952, 235, 63; Bull. SOC. chim.,Goutarel, and J. Massonneau, Compt. rend., 1952, 234, 850.1952, 19. 1091. 44 A. Le Hir, Compt. rend., 1952, 234, 2613.45 P. Karrer, R. Schwyzer, and A. Flam, Helv. Chim. Acta, 1952, 35, 851.46 Ref. 1, p. 232; cf. M. M. Janot and R. Goutarel, Compt. rend., 1952, 234, 1562224 ORGANIC CHEMISTRY.followed by catalytic hydrogenation gave tetrahydrodemethoxycoryn-antheine alcohol (XXXIII).Dehydrogenation of the last with seleniumgave alstyrine (XXXIV; R = H) and a small quantity of methylalstyrine(XXXIV ; R = Me) ; however, palladium dehydrogenation afforded flavo-corynanthyrine (XXXV) .457 47 Similarly, yohimbyl alcohol (XXXVI)with selenium gives a little yobyrine (XXXVII; R = H) and mainlymethylyobyrine (XXXVII; R = Me), but use of palladium leads only toyobyrine (XXXVII ; R = H).48MeO,C.C:CH.OMe MeO,C*kCH*OMe HO*CH,kHMe(XXXI) (XXXII) (XXXIII)(XXXIV) (XXXV) (XXXVI) (XXXVII)5-Methoxy-1 : 9-dimethyl-p-carboline (XXXVIII) has been synthesised 49and shown to be identical with a degradation product of mitragynine.50Three new alkaloids, (A) canthin-6-one, C,,H,ON, (XXXIX; R = H),(B) 5-methoxycanthin-6-one, C,,H,,0,N2 (XXXIX ; R = OMe), and(C) C1,Hl0OSN2 have been isolated from Pentaceras australis Hook.f.The bases A and B were oxidised by permanganate to p-carboline-l-carb-oxylic acid, and were hydrolysed to acids which readily re-formed the alkaloids ;the acid from A was isomerised by alkali to an acid which did not re-formthe lactam ring; both isomers gave the same dihydro-derivative on reduc-tion. The position of the methoxyl group in B was established by the reactionof the demethylated substance (XXXIX; R = OH) with o-phenylene-diamine.52 This ring system has not been previously observed in Nature.OMe / L AI I1 ll 1 L/\ ‘\/“/\dN\/‘i&\&N \g I I1 II 1 0:I I(XXXVIII) (XXXIX)Gelsemine. Application of the Hofmann degradation to gelsemine (ref.1,p. 234) is complicated by the fact that >NMe(b) alkylates CO*NH(a),+4 7 R. Schwyzer, Helv. Chim. A d a , 1952, 35, 867.4 * P. Karrer, R. Schwyzer, A. Flam, and R. Saemann, ibid., p. 865.49 J. W. Cook, J. D. Loudon, and P. McCloskey, J., 1952, 3904.50 H. R. Ing and C. G. Raison, J., 1939, 936.51 H. F. Haynes, E. R. Nelson, and J. R. Price, Austral. J. Sci. Res., 1952, 5 , A , 387.52 E. R. Nelson and J. R. Price, ibid., p. 563BAILEY : ALKALOIDS. 225giving CO-NMe(a) ; for example, the substance described as N-demethyl-gelsemine 53 is actually N(a)-methylgelsemine. It is reduced by lithiumaluminium hydride to deoxydihydro-N(a)-methylgelsemine. The latter isalso obtained from deoxydihydrogelsemine by formylation, followed bylithium aluminium hydride reduction.54 Heating gelsemine with tetra-methylammonium hydroxide yields N(a)-methylgelsemine.55None of the structures suggested for p-erythroidine(ref. 1, p. 230) has been accepted by Boekelheide and his colleagues.56 Theseworkers find that a@-p-erythroidine, C,,H,,O,N, is readily dehydrogenatedto dehydroapo-P-erythroidine, C,,H,,O,N ; the latter is a lactone, giving anindole colour reaction (Ehrlich) . Alkaline permanganate oxidises dehydro-ape-p-erythroidine to 2-aminoisophthalic acid, isatin-7-carboxylic acid (XL) ,and 4-hydroxyquinoline-3 : 8-dicarboxylic acid (XLI), the last not giving2-aminoisophthalic acid on oxidation. Similar oxidation of a@- p-erythroidineafforded (XL) and (XLI). These observations indicate that a@-p-erythro-p-Erythroidine.(XL) (XLI) (XLII)idine contains a structure of type (XLII).Contrary to earlier claims, apo-p-erythroidine does not appear to contain a :CH,.group, and oxidativedegradation of p-erythroidine derivatives gave phthalic acid and not 3-meth-oxyphthalic acid. Hofmann degradation of apo- p-erythroidine 57 shows thepresence of (*CH,*CH,*) ,N-. Dc-N-met hyldihydro- p-eryt hroidinol (XLI I I ;R = OH) on two-stage Hofmann degradation gave a substance C15H1802,and reduction of this, followed by permanganate oxidation, gave o-ethyl-benzoic acid. Hydrogenolysis of (XLIII; R = OH) yielded (XLIII;R = H); Hofmann degradation of the latter with reduction at each stageshowed the presence of (*CH,*CH,:),N*, and ozonolysis of the end productgave ethyl methyl ketone.A consideration of these results lead to structure(XLIV) for p-erythroidine, and (XLV) for ape-p-erythroidine.f% ,/\CH,.CH,.NMe \\/\N( \/”<MeOZ c, C,H2 I ,CH,H+’ ‘Y-CH, H 2 y Q ~ . ~ ~HO-H,C*H,C CH2R OCwCH, OC,(yCH,I \ , ~ ~ : F - C H , C H , II I(XLIII) (XLIV) (XLV)Strychnos Alkaloids.-The long suspected relation between a-colubrine(XLXVI ; R = H, R’ = OMe), p-colubrine (XLVI ; R = OMe, R’ = H), andstrychnine (XLVI; R = R’ = H) has been e~tablished.~~ Lithium alu-m R. Goutarel, M. M. Janot, V. Prelog, and R. P. A. Sneeden, Helv. Chirn. Acfa, 1951,64 T. Habgood, L. Marion, and H. Schwarz, ibid., 1952, 35, 638.66 V. Prelog, J. B. Patrick, and B. Witkop, ibid., p. 640.56 M. F. Grundon and V.Boekelheide, J . Awzer. Chem. SOC., 1952, 74, 2637.67 V. Boekelheide, M. F. Grundon, and J. Weinstock, ibid., p. 1866.34, 1962.S. P. Findlay, ibid., 1951, 13, 3008.REP.-VOL. XLIX. 226 ORGANIC CHEMISTRY.minium hydride reduction of the colubrines gave the corresponding colu-bridines which were then oxidised to 2 : 3-diketonucidine, the oxidation pro-duct of stry~hnidine.~~ A new alkaloid, novacine (N-methyl-sec.-pseudo-brucine), has been isolated from Strychnos utux-vomica seeds.60 Boit hascontinued his degradative studies on pseadobrucine. 61 Phenols have beenfound to form solid complexes with certain strychnine derivatives.62 TheCH,-OH(XLVI) (XLVII)Wieland-Gumlich aldehyde (XLVII) has been condensed with malonic acid,forming isostrychnic acid (XLVIII ; inversion at C* relative to strychnine).63isoStrychnic acid had previously been converted into isostrychnine-1(XLIX),64 and hence into strychnine (XLVI; R = R' = H).G5 Theoxidation of strychnine with osmium tetroxide,66 and that of strychnine andbrucine N-oxides with permanganate has been described.67I A I I B I c \fir?dG I A I I B I C \/y$,qAH 7" o:"' '6.CH,*OHH0,C O-CH,(XLVIII) (XLIX)Quinazolone Group.68-Koepfli, Brockman, and Moff at 69 considerfebrifugine and isofebrifugine, Cl6HIgO3N,, to be isomers of (L), the semi-ketal of (LII), differing in stereochemistry at C*. This explains the ready(L) (LI)interconversion of the two alkaloids. Both are oxidised by periodate to thesame optically inactive substance, C16H1703N3, which yields the pyrazole(LI) on treatment with semicarbazide.However, the alkaloids are reducedto different dihydro-derivatives, and febrifugine forms carbonyl derivatives6D H. Leuchs and H. S. Overberg, Ber., 1931, 64, 1009.80 W. F. Martin, H. R. Bentley, J. A. Henry, and F. S. Spring, J . , 1952, 3603.61 H. G. Boit, Chem. Ber., 1952, 85, 19, 106.62 J. T. Edward and (Sir) R. Robinson, J., 1952, 1080.63 (Sir) R. Robinson and J. E. Saxton, J., 1952, 982.64 H. G. Boit, Ber., 1951, 84, 16.6 5 V. Prelog, J. Battegay, and W. I. Taylor, Helv. Chim. Acta, 1948, 31, 2244.6 7 K. Hirayama, ibid., p. 45.1 3 ~ J. B. Koepfli, J. A. Brockman, and J. Moffat, J . Amev. Chem. SOC., 1950, 73, 3323.A. Kogure and M. Kotake, J . Inst. Polytech.Osaka City Univ., 1951, sec. C2, 39Cf. Ann. Reports, 1949, 46. 210.(Chem. A h . , 1952, 46, 6131)BAILEY : ALKALOIDS. 227whilst isofebrifugine does Febrifugine has also been isolated fromhydrangea leaves71 Pennanganate oxidation gave 3-carboxymethyl-4-quinazolone (LII; R = CO,H), zinc dust distillation afforded the ketone(LII; R = Ac), and the alkaloid contained a carbonyl group, a hydroxylgroup, and a sec.-amino-group, indicating a structure of type (LIII).72The racemic form of the alkaloid (LV) has been synthesised by treating ethyl2-3'-bromoacetonyl-3-methoxypiperidine- 1 -carboxylate (LIV) with quin-azol-4-one and then removing the protecting groups. 73QC,H,*OH n 0II/V\N.CH,COCH,.CHI II I \,2H2\/"/ (LIII) H( L W C0,Et (LV)Steroid Alkaloids.-A 3p-dimethylaminopregn-5-ene structure (LVI ;R = Me) has been suggested for conessine.'* This is in agreement with theoptical rotation, ultra-violet, and infra-red spectral data.Degradation ofconessine by von Braun's method affords isoconessimine (LVI; R = H).75Hofmann degradation of the N-acetyl derivative (LVI; R = Ac), followedby Emde reduction, gave (LVII; R = Ac) identical with the substanceprepared by reaction of 3~-toluene-~-sulphonyloxypregna-5 : 20-diene withmethylamine followed by acetylation of the resulting amine (LVII ; R = H).The presence of a sec.-amino-group in solasodine (LVIII) has been con-firmed ; molecular-rotation differences indicate that solasodine has the samestereochemical configuration as cholesterol ; N-nitrososolasodine has beenconverted in small yield into diosgenin (LIX), confirming structure (LVIII).76A new alkaloid, solamargine, has been isolated 77 from Solanunz marginaturn ;complete hydrolysis gave rhamnose, glucose, and solasodine (LVIII) ;partial hydrolysis yielded solasodine p-glucoside.Tomatidine yields a diacetyl derivative (m.p. 194') containing >NAc,7O J. B. Koepfli, J. F. Mead, and J. A. Brockman, J . Ameu. Chem. SOC., 1949, 71, 1048.7 l F. Ablondi, S. Gordon, J . Morton, and J. H. Williams, J . Org. Chem., 1952, 17, 14.7a B. L. Hutchings, S. Gordon, F. Ablondi, C. F. Wolf, and J. H. Williams, abid.,73 B. R. Baker, R. E. Schaub, F. J. McEvoy, and J. H. Williams, ibid., p. 133.74 R. D. Haworth, J. McKenna, R. G. Powell, and H.G. Whitfield, Chem. and Ind.,7 5 S. Siddiqui, Proc. Indian Acad. Sci., 1936, 3, A , 249, 257.7 f ~ L. H. Briggs and T. O'Shea, J . , 1952, 1654.7 7 L. H. Briggs, E. G. Brooker, W. E. Harvey, and A'. D. Odell, ibid., p. 3587.p. 19.1952, 215228 ORGANIC CHEMISTRY.which is isomerised by light to a compound (m. p. 92”) containing -NHAc.The former product is oxidised by chromic acid to 3-acetyltigogenin lactoneMeIHO AN (LVIII)(LX); 78 the lower-melting isomer is oxidised to a mixture of (LX) and3~-acetoxyaZZopregn-16-en-20-one (LXI),78, 79 suggesting that tomatidinemay be (LXII), the nitrogen analogue of tigogenin.’8MeM$All.o Me 1 /----\-Me/q+,>NH-/ Mqd9AH AT%-(LXII) NH, (LXIII)HO h/.J HSolanocapsine , C,,H4602N2,H20, contains no double bonds, two or threeC-methyl groups, three active hydrogen atoms, one amino-, and one secondarycyclic imino-group.Treatment with nitrous acid gives an unsaturatednitroso-compound and nitrogen ; one oxygen atom is present as a tertiary orhindered secondary hydroxyl group, and the other as an ether linkage.80Selenium dehydrogenation yielded Diels’ hydrocarbon and 2-ethyl-5-methyl-pyridine, observations differing from those of earlier workers.81 These re-actions lead to a formula of type (LXIII ; stereochemistry unknown). Infra-red spectral studies indicate that salt formation by this type of structureinvolves opening of the ether ring.Careful hydrolysis of cevadine gives cevagenine and angelic acid ; simi-larly veratridine gives veratric acid and cevagenine.82 Further action of78 R. Kuhn and I. Low, Chem. Ber., 1952, 85, 416.79 Y . Sato, A. Katz, and E. Mosettig, J . Amer. Chem. SOC., 1952, 74, 538.81 G. Barger and H. L. Fraenkel-Conral, J., 1936, 1537.82 A. Stoll and E. Seebeck, Helv. Chim. Acfa, 1952, 35, 1270, 1942; cf. N. Elming,E. Schlittler and H. Uehlinger, HeEv. Cham. Acta, 1952, 35, 2034, 2608.C. Vogel, 0. Jeger, and V. Prelog, ibid., p. 2541BAILEY : ALKALOIDS. 229alkali isomerises cevagenine to the known cevine. Hence cevagenine is thetrue alkamine; its infra-red spectrum is similar to that of the alkaloids andshows the presence of a carbonyl group. This group is absent in cevine.Reduction of cevadine produces two dihydrocevadines ; both these yieldcevagenine on hydrolysis, but one gives (+)-a-methylbutyric acid and theother the (-)-isomer.Cevagenine contains a keto-group and seven hydroxylgroups ; a consideration of its reactions lead to a formula of type (LXFV).The skeleton of isorubijervine (LXV; R = OH) has been established bythe oxidation of dihydroisorubij ervine to the corresponding aldehyde and0Me OH IIMe(LXV)MeHO’ d g G Q M e H (LXVI) HO N ereduction of the latter to solanidan-3p-01 (LXVI),s3 and also by reaction ofthe toluene-$-sulphonic ester of isorubijervine with potassium iodide to give(LXV ; R = I). Reduction of this iodide gave solanidine (LXV ; R = H). 84Further evidence for the presence of an aromatic ring in veratramine(LXVII) has been obtained by the nitration of triacetyldihydroveratramineMe Me1 I AcMe MeAcO (LXX)Me Mep2Me MeMe0Ac,O-AcOAcO -.v (LXXI)(LXVIII) ; the resulting nitro-compound was reduced to a diazotisableamine.N-Acetylveratramine has been oxidised to an +-unsaturated83 D. Burn and W. Rigby, Chem. and Ind., 1952, 668.04 S. W. Pelletier and W. A. Jacobs, J . Amer. Chem. Soc., 1952, ’44, 4218230 ORGANIC CHEMISTRY.ketone, indicating that ring B is not aromatic. 85 Triacetyldihydroveratr-amine (LXVIII) has been oxidised by chromic acid to a ketone (LXIX)whose chemical and spectral properties indicate a carbonyl group atON-Diacetyljervine (LXX) is converted on acetolysis into a triacetatehaving an indanone structure (LXXI).S6 This has now been reduced to(LXIX), identical with the product from veratramine, establishing therelation between veratramine and j ervine.87A. S. B.10. NATURALLY-OCCURRING OXYGEN RING COMPOUNDS.Furans and Benzofurans-The chemistry of usnic acid has been re-viewed.l Details of the work leading to the determination of the structureof griseofulvin3 have now been given. Contributions to the chemistry ofcournaranones include work on the synthesis of the naturally occurringleptosidin (2-benzylidene-6 : 3’ : 4’-trihydroxy-7-methoxycoumaranone) andits 6-glycoside, leptosin ; the rearrangement of 2-benzylidenecoumaranonesunder weakly alkaline conditions to flavones, a change that may prove usefulin flavone synthesis ; and the formation of 2-arylidenecoumaranones in theattempted conversion of some arylidenephloracetophenone derivatives intoflavonols by treatment with alkaline hydrogen peroxide.’The structure of ipomeamarone (I),8 a furan produced in sweet potato byinfection with Ceratostomella~fimbriata Elliot, has been elucidated by JapaneseH,C-----CH, H,C-CH, H,C--CH,H\l I I t >L,o,CMeCH,R I‘O/CMe*CH2R H0,CC CMeCH,R OC II I1 \O/\n/H,C-CH,H\I 1MeO,CCH,CH,*CMe:CHR CH2XH-C\ /CMe.CH,R(IV) 0 .,(R = - CO*CH,*CHMe,) (V)chemists.9 Preliminary work indicated the presence of a carbonyl group,two double bonds, and two oxide rings. Ozonolysis gave as chief productsipomic lactone (11) and ipomeanic acid (111). The lactone gave isovalericacid and lzevulic acid on oxidation, and ozonolysis of the semicarbazone of8 5 C. Tamm and 0.Wintersteiner, J . Amer. Chem. SOG., 1952, 74, 3842. ** J. Fried, 0. Wintersteiner, A. Klingsberg, M. Moore, and B. M. Iselin, ibid.,1 F. M. Dean, Sci. Progr., 1952, 40, 635.8 J. F. Grove, J. MacMillan, T. P. C. Mulholland, and M. A. T. Rogers, J., 1952,3949; J. F. Grove, D. Ismay, J. MacMillan, T. P. C. Mulholland, and M. A. T. Rogers,ibid., p. 3958; J. F. Grove, J. MacMillan, T. P. C. Mulholland, and J. Zealley, ibid.,p. 3967; J. F. Grove, J. MacMillan, T. P. C. Mulholland, and M. A. T. Rogers, ibid.,p. 3977; T. P. C. Mulholland, ibid., p. 3987, 3994.1951, 73, 2970. 87 0. Wintersteiner and N. Hosansky, ibid., 1952, 74, 4474.Ann. Reports, 1951, 48, 210,,T. A. Geissman and C. D. Heaton, ibid., 1943, 65, 677.D. M. Fitzgerald, E.M. Philbin, and T. S. Wheeler, Chem. and Ind., 1952, 130.* T. A. Geissman and W. Mole, J . Amer. Chem. Soc., 1951, 73, 5765.7 H. Ozawa and M. Kawanishi, J . Pharm. SOG. Japan, 1951, 71, 1186.8 I. Oze and M. Hiura, Ann, Rep. Jup. Veget. Path., 1939, 9, 123.9 T. Kubota and T. Matsuura, Proc. Japan Acad., 1952, 8, 44, 83, 198KING : NATURALLY-OCCURRING OXYGEN RING COMPOUNDS. 231the compound (IV) obtained by dehydration of the methyl ester formedon ring-opening of the lactone gave chiefly methyl lzvulate and isobutyl-glyoxal semicarbazone. The structure (IV) of the keto-acid, thus deduced,was confirmed by synthesis, and the point of attachment of the carboxylgroup in (111) was proved by degradation to the lactone (11). The furanstructure of the remaining C(*) moiety was shown by colour tests, the form-ation of Diels-Alder adducts, and by a degradation lo typical of acc'-un-substituted furans, in which the adduct with acetylenedicarboxylic ester waspartially reduced and heated, giving furan-3 : 4-dicarboxylic ester and anolefin (V).The olefin, on oxidative decomposition of its ozonide, gaveformic acid, ipomeanic acid, and ipomic lactone. Further work l1 is de-scribed which independently confirmed the position of the carbonyl groupin the side chain of ipomeamarone.Flavones-Several useful papers have appeared on the separation andidentification of flavone derivatives by paper partition chromatography.Gage, Douglas, and Wender l2 give the RF values of 38 flavone derivativesin 11 solvent systems and also the colours produced on paper by each com-pound with 8 sprays in both visible and ultra-violet light.Paris13 givesR F values in various solvents of 41 flavone derivatives. In two papers l4the R M [log (1/RF - l)] values of many natural and synthetic flavones(including 13 new compounds) are reported, and the interactions ofsubstituent groups, in particular hydrogen bonding, are discussed in thelight of the results. Partition chromatography has also been applied to theidentification 15 of flavanones in extracts of various Pinus species. Theultra-violet absorption spectra of flavones have been studied in relation totheir structure by Briggs and Locker l6 who also discuss the effects of struc-ture on the acidity and basicity of flavones.The determination of theultra-violet absorption spectra of substances, including flavones, iso-flavones, and coumarins, present as spots on paper after chromatographyhas been investigated 1' as an analytical method.The literature concerning colour reactions of flavones is notoriouslyconfused and many conclusions about the specificity of certain reactionshave been reached on insufficient evidence. One aspect of this field hasbeen clarified l8 by an investigation of the colours given by 57 flavonederivatives with two reagents (magnesium-hydrochloric acid and zinc-hydrochloric acid 19). Whereas the first reagent appears to give stableanthocyanidin-like colours with all flavone derivatives, the second givesstable colours only with flavonols substituted in the 3-position ; fadingcolours are produced with flavones and 3-hydroxyflavanones.A furthercolour test,20 reported as specific for flavanones, depends on the formation10 K. Alder and H. F. Rickert, Ber., 1937, 70, 1354.l1 T. Kubota and T. Matsuura, J . Chem. SOC. Japan, 1952, 73, 530.l2 T. B. Gage, C. D. Douglass, and S. H. Wender, AnaZyt. Chem., 1951, 23, 1582.13 R. Paris, Bull. SOC. Chim. biol., 1952, 34, 767.14 T. H. Simpson and (in part) L. Garden, J., 1952, 4638; B. L. Shaw and T. H.16 G. Lindstedt and H. Misiorny, Acta Chem. Scand., 1952, 6, 744.16 L. H. Briggs and R. H. Locker, J., 1951, 3136.l7 A. E. Bradfield and A. E. Flood, J., 1952, 4740.l8 M. Shimizu, J. Pharm. SOC. Japan, 1951, 71, 1329; 1952, 72, 338.Is J .C. Pew, J . Amer. Chem. SOC., 1948, 70, 3031.a. S. Shibata and A. Kasahara, J. Pharm. SOC. Japan, 1952, 72, 1386.Simpson, ibid., p. 5027232 ORGANIC CHEMISTRY.of a blue fluorescent spot (ultra-violet light) when the compound, on paper,is sprayed with magnesium acetate.Experiments on the isolation, identification, and synthesis of flavonescontinue. New flavone derivatives isolated include ayanin 21 from thetimber of Distemonanthus Benthamianus, shown by degradation and synthesisto be 3 : 7 : 4’-trimethylquercetin ; 3-O-rhamnoglucosidylk~mpferol22 fromthe leaves of Hyptis capitata and Dryopteris oligophlebia ; rhoifolin (7-0-rhamnoglucosidylapigenin) from both the Japanese wax tree 23 (Rhussuccedenia) and the peel of the ripe fruit of Japanese varieties of Citrusauyantium 24 where it is accompanied by naringin (the peel of Europeanvarieties of this plant contains only hesperidin 25) ; a new glycoside ofgenkwanin from the bark of the Japanese cherry; 26 and astilbin (a rhamnos-ide of 3 : 5 : 6 : 3’ : 4’-pentahydroxyflavanone) from Astilbe Thwbergii 27which also contains quercetin and the isocoumarin, bergenin.The substancearomadendrin, long known to occur in the kinos of many Eucalyptus species,has been identified 28 as dihydrokzempferol which is also identical withk a t ~ r a n i n . ~ ~ In the light of new evidence the structure of meliternatin hasbeen m0dified.3~Several known flavones have been isolated from new sources, includingquercetin and its 3-glucoside (by the use of ion-exchange resins) fromgrapes 31 and black currants,32 and from a variety of Rosa polyantha; 33rutin from date-palm pollen 34 and the leaves of GreviElea robusta; 35 andnaringenin from the timber of Ferreirea ~pectabilis.~~Synthetic investigations in the field include the synthesis of 5 : 4’-di-methoxyfurano(3” : 2”-6 : 7)flavone and 7 : 4’-dimethoxyfurano(2” : 3”-5 : 6)flavone,37 possibly isomeric with, but shown not to be identical with, ging-keti11.3~ During experiments on the solubilising of flavones with boricacid 39 an observation has been made which may prove useful in the synthesisof partially methylated compounds.In the presence of borate, diazo-methane fails to methylate not only the 5-hydroxyl, but also vicinal hydroxyl,groups; rutin can thus be methylated to the 7-methyl ether, and quercetinto the 3 : 7-dimethyl ether.Addition of boric acid also improves the reduc-tion 40 of flavonols to hydroxyflavanones by dithionite.19isoF1avones.-A new isoflavone, muningin (6 : 4’-dihydroxy-5 : 7-di-21 F. E. King, T. J. King, and K. Sellars, J . , 1952, 92.22 K. Kobayashi, J . Pharm. SOC. Japan, 1952, 72,l; K. Kob.ayashi and K. Hayashi,24 S. Hattori, M. Shimokoriyama, and M. Kanao, J . Amer. Chem. Soc., 1952, 74, 3614.26 F. Kolle and K. E. Gloppe, Pharm. Zentralh., 1936, 77, 421.2 6 T. Ohta, J . Pharm. SOC. Japan, 1952, 73, 456.2 7 H. Shimada, T. Sawada, and S. Fukuda, ibid., p. 578.28 W. E. Hillis, Austral. J . Sci. Res., 1952, 5, 379.29 H. Voda, B. Fukushima, and T.Kond6, J . Agric. SOC. Japan, 1943, 19, 467.30 L. H. Briggs and R. H. Locker, J., 1951, 3131.31 B. L. Williams and S. H. Wender, J . Amer. Chem. SOC., 1952, 74, 4372.32 R. L. Williams, C. H. Ice, and S. H. Wender, ibid., p. 4566.33 T. Ohta and T. Myazaki, J . Pharm. SOC. Japan, 1951, 71, 1281.34 M. S. El Ridi, L. A. Strait, and M. H. Aboul Wafa, Arch. Biochem., 1952, 39, 317.35 K. Kobsyashi, J . Pharm. SOC. Japan, 1951, ‘21, 1493.38 F. E. King, M. F. Grundon, and K. G. Neill, J . , 1952, 4580.37 A. Kogure, J . Chem. SOC. Japan, 1952, 73, 271, 308.3 8 W. Baker and W. H. C. Simmonds, J., 1940, 1370.3g M. Shimizu et al., J . Pharm. SOC. Japan, 1951, 71, 875 st seq.40 M. Shimizu and T. Yoshikawa, ibid., 1952, 72, 331.ibid., p. 3. 23 S.Hattori and H. Matsuda, Arch. Biochem., 1952, 37, 85KING : NATURALLY-OCCURRING OXYGEN RING COMPOUNDS. 233rnethoxyisaflavone) has been isolated 41 from the heartwood of Pterocarpusangalemis which also contains a small amount of p r ~ n e t i n . ~ ~ Formo-nonetin and genistein have been isolated from subterranean clover,43 andgenistein has been shown to be estrogenic. Two independent groups ofworkers have isolated simple dihydroisoflavones, previously known in Natureonly as complex derivatives, from natural sources. Indian workers on theconstituents of Prunus +uddum, known to contain prunetin as well asgenkwanin and sakuranetin,u have isolated two new substance^,^^ theglycoside padmakastin and its aglycone padmakastein. The latter wasidentified as dihydroprunetin (2 : 3-dihydro-5 : 4’-dihydroxy-7-methoxyiso-flavone) by synthesis and by dehydrogenation to prunetin derivatives (bythe action of selenium dioxide on the acetate).British workers36 isolatedfrom Ferreirea spectabikis, in addition to biochanin-A (4-methylgenistein) andnaringenin, two compounds ferreirin and homoferreirin. Dehydrogenation(palladised charcoal), oxidation, and synthesis of the fully methylatedderivatives established both compounds as derivatives of 5 : 7 : 2’ : 4’-tetra-hydroxyisoflavanone ; investigation of the ethyl ethers established thestructures 46 of the natural compounds as, respectively, 5 : 7 : 2’-trihydroxy-4‘-methoxy- and 5 : 7-dihydroxy-2’ : 4’-dimethoxy-isoflavanone.‘A new synthetic route to isoflavones has been developed 47 which isparticularly useful for the direct preparation of hydroxylated derivatives.The appropriate deoxybenzoin is treated, in pyridine, with ethoxalyl chloride,giving the 2-carbethoxyisoflavone, readily hydrolysed and decarboxylatedunder mild conditions.By this method biochanin-A, genistein, $-bapti-genin, and 5 : 7 : 2‘-trihydroxyisoflavone 48 have been made. The lastwas not identical with an aglycone from a soya-bean glycoside whichhad been allotted this structure.49 The synthesis 42 from biochanin-A of7 : 4‘-dihydroxy-5-methoxyisoflavone, the so-called prunusetin 44 fromPrunus fiuddum, does not give the substance described as occurring naturally,which was probably impure prunetin. The method of nuclear oxidationwith persulphate, well known in the flavone field, has been successfullyapplied to several isoflavone~.~~Miscellaneous Benzopyrones and Coumarins.-The first natural naphtho-pyrone, eleutherinol, has been found 51 in Eleuthera bulbosa; 52 only 500 mg.were obtained but the structure has been unambiguously established as (VI).Analysis, colour tests, the formation of a piperonylidene derivative of thedimethyl ether, and alkaline degradation [which gave acetone, acetic acid,a trihydroxy-ketone (VII; R = Ac, R’ = H), and a small amount of atrihydroxy-compound (1711; R = R‘ = H)] indicated that the substance4 1 F.E. King, T. J. King, and A. J. Warwick, J., 1952, 96.42 F. E. King and L. Jurd, J., 1952, 3211.43 R. B. Bradbury and D. E. White, J., 1951, 3447.44 D.Chakravarti and C. Bhar, J . Indian Chem. Soc., 1945, 22, 301.46 N. Narasimhachari and T. R. Seshadri, Proc. Indian Acad. Sci., 1952, 35, A, 202.46 F. E. King and K. G. Neill, J., 1952, 4752.47 W. Baker and W. D, Ollis, Nature, 1952, 169, 706.48 W. Baker, J. H. Harborne, and W. D. Ollis, Cham. and Ind., 1952, 1058.49 K. Oliano and I. Beppu, J . Agric. Chem. SOC. Japan, 1939, 16, 645.50 N. Narasimhachari, L. R. Row, and T. R. Seshadri, Proc. Indian Acad. Sci., 1952,5 1 A. Ebnother, Th. M. Meijer, and H. Schmid, Helv. Chim. A d a , 1952, 35, 910.62 Cf. Ann. Reports, 1950, 47, 226.35, A , 46234 ORGANIC CHEMISTRY.was a dihydroxy-2-methylchromone with one further methyl group (Kuhn-Roth) . Alkaline degradation of dimethyleleutherinol gave the correspondingderivatives (VII; R = Ac, R’ = Me, and R = H, R = Me) ; oxidationof the former gave 3 : 5-dimethoxyphthalic anhydride, and of the latter(VI) (VII) (VIII) (IX)(lead tetra-acetate) gave a mixture of a 2-hydroxy-dimethoxy-methyl-1 : 4-naphthaquinone and the corresponding dimethoxy-methyl-1 : 2-naphtha-quinone. The data thus obtained did not distinguish between the twostructures (VIII) and (IX) for the 1 : 4-quinone, but an unambiguoussynthesis 53 of both quinones identified the degradation product as (VIII),and the structure (VI) for eleutherinol followed.Some analogous naphtho-pyrones have been synthesised by standard methods.54Several papers concerning the chemistry of khellin and its analogueshave appeared ; visnagin has been converted into the more physiologicallyactive khellin by a process which makes use of nuclear oxidation withpersulphate ; 55 khellol 66 and a visnagin isomer [5-methoxy-Z-methyl-furano(2’ : 3’-7 : 8)(2 : 3-benzopyrone)] 57 have been prepared by standardmethods.Work on natural coumarins has been largely confined to the analyticalfield. Paper chromatographic studies of coumarins have been published bytwo school^.^*^^^ Spectral studies are represented by a paper 6o on thevariation of fluorescence spectrum with pH of 59 coumarin derivatives, anda variety of coumarins and furanocoumarins have been investigated polaro-graphically.61Lactones and Lacto1s.-A series of closely argued paperss2 on thestructure of picrotoxin has appeared but the investigations described arenot yet sufficiently complete to allow final conclusions to be reached.Further details 63 have now appeared concerning the synthesis of picrotoxa-diene and its production from picrot~xinin.~~ The lignan arctigenin (a-3 : 4-dimethoxybenzyl-a-4-hydroxy-3-methoxybenzylbutyrolactone) 65 has beensynthesised.6653 H. Schmid and M. Burger, Helv. Chim. Acta, 1952, 35, 928.54 H. Schmid and H. Seiler, ibid., p. 1990.5 5 S. K. Mukherjee and T. R. Seshadri, Proc. Indian Acad. Sci., 1952, 35, A , 323.56 T. A. Geissman and J. W. Bolger, J . Amer. Chem. SOC., 1951, 73, 5875.5 7 G. H. Phillips, A. Robertson, and W. B. Whalley, J., 1952, 4951.58 K. Riedl and N. Neugebauer, Monatsh,, 1952, 83, 1083.69 A. B. Svendsen, Pharm.Acta Helv., 1952, 27, 44.60 R. H. Goodwin and F. Kavanagh, Arch. Biochem., 1952, 36, 442.61 R. Patzak and L. Neugebauer, Sitzungber. Akad. Wiss. Wien, 1952, 161, 776.62 J . C. Benstead, H. V. Brewerton, J. R. Fletcher, M. Martin-Smith, S . N. Slater,and A. T. Wilson, J., 1952, 1042; S. N. Slater and A. T. Wilson, ibid., p. 1597; J. C.Benstead, R. Gee, R. B. Johns, M. Martin-Smith, and S. N. Slater, ibid., p. 2292.63 H. Conroy, J . Amer. Chem. SOL, 1952, 74, 491, 3047.64 Cf. Ann. Reports, 1951, 48, 211.$6 R. D. Haworth and W. Kelly, J., 1936, 998.e6 T. Ozawa, J. Pharm. SOC. Japan, 1952, 73, 285, 551BOURNE : MACROMOLECULES. 235Gladiolic acid, a metabolic product of Penicillium gladioli, has beenshown 67 to have the tautomeric structure (X; R = CHO).The presenceof a formyl group was proved by the formation of carbonyl derivatives andMe0 CO Me0by the existence of reducing properties which(XI)disameared on mild oxidationduring which a new carboxyl group appeared. TLL 0, product so obtainedhad two carboxyl groups and one methoxy-group, and showed both carbonyland hydroxyl properties, which are best explained by assuming a tautomericsystem as shown. Rearrangement under alkaline conditions t o give acarboxy-lactone (XI; R = C0,H) was best explained by an ortho-arrange-ment of formyl and lactol grouping, and vigorous oxidation gave 4-methoxy-benzene-1 : 2 : 3 : 5-tetracarboxylic acid (structure by synthesis). The finalorientation of the substituents followed from detailed arguments for whichthe original paper should be consulted; they depend chiefly on the inter-pretation of infra-red spectra and the isolation 68 from the phthalide (XI;R = Me), obtained by Clemmensen reduction of gladiolic acid, of 2 : 4 : 5-trimethylphenol.T.J, K.11. MACROMOLECULES.During 1952, workers engaged in the study of macromolecules mournedthe deaths of C. S. Hudson and K. H. Meyer, whose researches laid thefoundations of so much of the work reported below.Poly saccharides.It is the turn of polysaccharides to receive the main emphasis in a yearwhich, in addition to furnishing its full quota of studies on new and rarepolysaccharides, has seen some readjustments in widely accepted conceptsof the structures of certain " simple " and well-known polysaccharides, suchas starch, glycogen, and dextran.Structural studies have been facilitatedby the continued use of chromatographic techniques for the fractionation ofmixtures of oligosaccharides on filter paper, on charcoal col~mns,l-~ and, astheir acetates, on columns of " Silene EF." 4 It has been shown that caremust be exercised in interpreting paper dhromatograms of sugar solutionscontaining ammonium salts, or other nitrogenous compounds, becauseglycosylamines formed, in certain circumstances, on the paper itselfmay produce extra spots.5 Studies of filter-paper ionophoresis of sugars inborate buffers have demonstrated that this new method is potentially very6 7 J. F. Grove, Biochem. J., 1952, 50, 648.6 s H. Raistrick and D.J. Ross, ibid., p. 635.* S. A. Barker, E. J. Bourne, G. T. Bruce, and M. Stacey, Chem. and Ind., 1952,1156.4 M. L. Wolfrom and J. C. Dacons, J . Amer. Chem. Sot., 1952, 74, 6331.R. L. Whistler and Chen-Chuan Tu, J . Amer. Cham. Sot., 1952, 74, 3609.S. Peat, W. J. Whelan, and G. J. Thomas, J., 1952, 4546.R. J. Bayly, E. J. Bourne, and M. Stacey, Nature, 1952, 169, 876236 ORGANIC CHEMISTRY.valuable for characterisations; there is no doubt that it will shortly bewidely used to unravel the complexities of polysaccharide structures, as alsowill electrokinetic ultra-filtration analysis. Infra-red absorption, havingyielded valuable results with dextran and hyaluronic acid,g likewise willprobably find extensive application in the polysaccharide field.A usefulmethod of structural analysis, involving periodate oxidation of a poly-saccharide, reduction of the newly formed aldehyde groups, and acidichydrolysis of the product to give readily identifiable fragments, has beenreported. loStarch and Glycogen.-Maple-sapwood starch has been shown, bypotentiometric titration with iodine, to contain ca. 19% of amylose.11Hydrolysis of the trimethyl ether gave 2 : 3 : 4 : 6-tetramethyl and 2 : 3 : 6-trimethyl glucose (3.3-3.4 and 92-93y0, respectively), together withdimethyl glucoses (4-5y0), a result which indicated that the principal gluco-sidic linkages involved positions 1 and 4, and that the average chain lengthof the amylopectin fraction was 26 glucose units. A somewhat lowerfigure (22 units) was derived from a determination of the formic acid liberatedduring oxidation of the starch with periodate.The presence of xylose in thestarch was attributed to an associated xylan.lf Nuclear-substituted tri-carbanilates of maize starch, amylose, and amylopectin have been preparedby treatment of the polysaccharides, in pyridine, with derivatives of phenylisocyanate.12 The greatly differing optical rotations and melting points ofthe ortho-substituted products, as compared with the meta- and para-isomers,were consistent with their different intramolecular bondings. Alkaline ferri-cyanide, in the presence of cyanide, has been used for measurement ofmolecular weights of amylodextrins and other substances of the starch type.13Determinations of the molecular weight of an amylopectin acetate, byosmotic and light-scattering methods, have given approximate values of6 x lo6 and 400 x lo6, respectively, the former being a number-averageand the latter a weight-average.14 The swelling of starch granules, causedby the sorption of water vapour,l5 and the effect of temperature and aggre-gation on the absorption spectrum of the amylose-iodine complex,16 havebeen studied.Important advances have been made concerning the finer structures ofthe starch components.A detailed account has been given of the propertiesof Z-enzyme, which occurs in impure samples of soya-bean p-arnyla~e.~'Whereas the purified soya-bean p-amylase, like the crystalline p-amylasefrom sweet potatoes, effects only a 70% conversion of potato amylose intomaltose (and not ca.lOOyo, as was believed previously), in the presence ofA. B. Foster, Chern. and Ind., 1952, 828; R. Consden and W. M. Stanier, Nature,S. F. D. Orr, R. J. C. Harris, and B. SylvCn, Nature, 1952, 169, 544.1952, 169, 783. D. L. Mould and R. L. M. Synge, Biocham. J., 1951, 50, xi. * S. C. Burket and E. H. Melvin, Science, 1952, 115, 516.lo M. Abdel-Akher, J. K. Hamilton, R. Montgomery, and F. Smith, J . Amev. Chem.11 C. E. Ballou andE. G. V. Percival, J., 1952, 1054.l2 I. A. Wolff, P. R. Watson, and C. E. Rist, J . Amer. Chew. Soc., 1952, '44,3061,3064.Is S. Nussenbaum and W. 2. Hassid, Analyt. Chem., 1952, 24, 501.l4 B. H. Zimm and C. D. Thurmond, J . Auner. Chem. Soc., 1952, 14, 1111.l6 N.N. Hellman, T. F. Boesch, and E. T. Melvin, ibid., p. 348.l6 J.. F. Foster and E. F. Paschall, ;bid., p. 2105.l7 S. Peat, S. J. Pic, and W. J. Whelan, J., 1952, 705, 714; S. Peat, G. J. Thomas,Soc., 1952, 74, 4970.and W. J. Whelan, zbad., p. 722BOURNE MACROMOLECULES. 237Z-enzyme an almost complete conversion into the disaccharide results. Theamyloses of sago, tapioca, and maize behave simi1arly.l' It was concluded(a) that some degree of branching occurs in amyloses, and that the branches,which serve as obstructions to pure p-amylase (and also to phosphorylase),are removed by Z-enzyme, (b) that Z-enzyme is a p-glucosidase, and (c) thatthe branches consist of single p-glucose units attached to the main chain.17If the Z-enzyme-sensitive links are, in fact, at branch points, it seems thatthe enzyme responsible for their synthesis still remains to be found.Alter-natively, the anomalous links may not be branches, but may occur at thenon-reducing ends of 30% of the amylose molecules, and may resultfrom imperfections in the synthesis by phosphorylase. Branching in amylosehas been postulated also on the basis of the rates of sugar production withamylo-glucosidase and with p-amylase ; l8 it appears that potato amylosehas 1-2, and tapioca amylose 2-3, branches per molecule.Evidence that amylopectin and glycogen have structures similar to that(I) suggested by Meyer, rather than the simpler " laminated " formula (11)due to Haworth, or the " comb-like " structure (111) proposed by Freuden-berg, has been obtained by two methods 2$ l9 (cf.ref. 20). In the first, thepolysaccharides were treated with salivary or-amylase and then with R-enzyme (which hydrolyses the 1 : 6-=-branch linkages), and the resultingmixtures of linear saccharides were analysed on charcoal columns. Fromthe analytical figures, it was deduced that multiple branching occurred inthe polysaccharide ~ t r u c t u r e s . ~ ~ ~ 21 The second method entailed a similar0 boPossible structural formule f o r anzylopectin.0 0-Rb(1) (11)o = Non-reducing chain end, = a-1 : 6-Link,(WR = Free reducing chain end.analysis of the amylosaccharides formed when the P-limit dextrin fromamylopectin was treated with R-enzyme.2A new procedure for the determination of polysaccharide structureshas been illustrated by its application to amylopectin.1° Periodate-oxidisedamylopectin (IV) was hydrogenated and hydrolysed, and the resultingmixture was analysed for glycerol and erythritol.Since the former- arisesonly from the non-reducing terminal units, and the latter from the remainingunits, the molar ratio glycerol : erythritol is related to the chain length ofthe polysaccharide. In addition, about 0.5% of the sugar units resistedperiodate, and gave glucose on hydrolysis, from which it was concluded 10that some 1 : 3-linkages occur in amylopectin. Glycogen (1%), amylosel8 R. W. Kerr and F. C. Cleveland, J . Amer. Chem. SOC., 1952, 74, 4036.1 9 W. J. Whelan and P. J. P. Roberts, Nature, 1952, 170, 748.20 G. T.Cori and J. Larner, J . Biol. Chem., 1951, 188, 17.21 P. J. P. Roberts and W. J . Whelan, Biochem. J., 1952, 51, xviii238 ORGANIC CHEMISTRY.(0.2-0.5%) , and cellulose ( 0 - 1 4 - 2 ~ 0 ) likewise contain periodate-resistantunits. loH,-OH ,Other studies have been devoted to the determination and purificationof amylases. An improved method has been developed for the preparationof hog pancreatic amylase.22 Adsorption indicators have been used for thedetermination of p-amylase a~tivity.~3 Earlier reports that indole deriv-atives, and other plant hormones, inhibit human a-amylase have been dis-proved.24 Crystalline malt P-amylase is a very soluble albumin, which canbe stored in the cold for long periods without loss of activity; it is totallyand irreversibly destroyed by the salts of heavy metals, but is relativelystable to low pH; its isoelectric point is at pH 6.1, and it displays itsoptimum activity at pH 5.2.25 An interesting observation is that cell-freehomogenates of Tetrahymena pyriformis contain, in addition to phosphorylase,an enzyme capable of hydrolysing starch, glycogen, and maltose to glucme.26Enzymic syntheses of the starch components have continued to receiveattention.Potato phosphorylase has been prepared in a highly purifiedform, following a new method of purification; 27 the enzyme, which had anactivity nine times greater than that of any sample described previously,was free from phosphatase, amylases, and Q-enzyme. It is believed thata two-fold increase in purity remains to be achieved,27 so that the crystallis-ation of the enzyme at last seems to be imminent.A detailed study hasbeen made of the equilibrium ratio [orthophosphate] : [glucose-1 phosphate]established by potato phosphorylase, and the effect of Mg++ ions on thisratio has been explained in equations relating it to the concentration ofMg++ ion, and to the dissociation constants of magnesium complexes withorthophosphoric and glucose-1 phosphoric acids2* Magnesium ions arebelieved to have little effect on the ratio under physiological conditions.The second dissociation constant of glucose-1 phosphoric acid has beenredetermined as 3.09 x at 30°.28 The free-energy change, at 30°, ofthe reaction glucose-1 phosphate -> acid orthophosphate + polysaccharideis -1460 ca1.28 Additional support for the current theory that potato22 M.L. Caldwell, M. Adams, J. T. Kung, and G. C. Toralballa, J . Amer. Chenz. SOG.,24 E. H. Fischer and J. Fellig, ibid., 1952, 115, 684.26 A. Piguet and E. H. Fischer, HeEv. Chim. Acta, 1952, 35, 257.26 J. F. Ryley, Biochem. J., 1952, 52, 483.27 G. A. Gilbert and A. D. Patrick, ibid., 1952, 51, 186.z8 W. E. Trevelyan, P. F. E. Mann, and J. S. Harrison, Arch. Biochem., 1952, 39,1952, 74, 4033. 23 B. Carroll and J. W. Van Dyk, Scieme, 1952, 116, 168.419, 440BOURNE : MACROMOLECULES. 239phosphorylase functions by lengthening the chains of all primer moleculessimultaneously, and not by converting one primer molecule into amyloesbefore attacking another, has resulted from measurements of the spectra ofthe iodine stains of the products formed when different proportions ofglucose-1 phosphate and primer molecules are employed, and also fromelectrokinetic ultra-filtration analysis of the products.29 Chromatographicanalysis of the non-protein fraction of crystalline muscle phosphorylase hasrevealed uridylic acid, cystine, and (probably) 2-methyl-1 : 4-naphtha-quinone; 30 the cystine was isolated in sufficient quantity to suggest thatcysteine may constitute an end group of the protein molecule, and serve as aconnecting link with the prosthetic The crystalline enzyme isinhibited significantly by D-glucose, and by a-methyl- and a-phenyl-D-gluco-pyranoside, but not by a variety of other sugars, including p-methylglucosideand p-D-glucose-1 p h ~ s p h a t e .~ ~Details have been given of the preparation and properties of crystallinepotato Q-en~yme.~Z ( Q-enzyme converts the slightly branched amylosecomponent of starch into the highly branched amylopectin structure.) Likeearlier, less pure, samples of the enzyme, the crystalline enzyme is rapidlyinactivated in solution at 30"; it is more stable in the presence of starch.32In support of the hypothesis that Q-enzyme is a transglucosylase, it has beenshown by two independent groups of workers 339 34 that the potato enzymecannot utilise amylose-type molecules as substrates unless they containmore than ca. 42 glucose units. For the synthesis of starch from acetate,Polytomella coeca utilises inter alia a phosphorylase and a Q-enzyme, thesebeing very similar in their actions to the potato enzymes.35 Productsformed from amylose by the protozoal Q-enzyme have been shown, bychemical and enzymic methods, to be members of the amylopectin-glycogenclass ; they were readily distinguishable from amylose-fatty acid c0mplexes.~6This amylase+ amylopectin conversion is more rapid in the presence ofamylosaccharides having a small average chain length, presumably becausesuch molecules serve as receptors of the transferred chains.Confirmatory evidence has been obtained3' of the presence in E.coli ofamylomaltase, which catalyses the reaction : n maltose -e (glucose), + nglucose. The extra-cellular saccharides, formed when washed cells of theorganism were incubated with maltose in the presence of iodoacetate, werefractionated on a charcoal column into glucose, unchanged maltose, and thelower members of the homologous series of 1 : 4-c~-glucosans.~~ Improvedconditions for the production of Schardinger dextrinogenase by B. macerans 38have facilitated the preparation of an enzyme sample which behaves asessentially one component in solubility tests, in electrophoretic analysis, andin the ~ltra-centrifuge.~~20 J.M. Bailey and W. J . Whelan, Biochem. J., 1952, 51, xxxiii.30 M. V. Buell, Fed. Proc., 1952, 11, 192.81 P. N. Campbell, N. H. Creasey, and C. W. Pam, Biochem. J., 1952, 52, 448.3 I G. A. Gilbert and A. D. Patrick, ibid., 1952, 51, 181.33 S. Nussenbaum and W. Z. Hassid, J . Biol. Cheun., 1952, 196, 785.34 J.M. Bailey, S. Peat, and W. J. Whelan, Biochem. J., 1952, 51, xxxiv.56 A. Bebbington, E. J. Bourne, M. Stacey, and I. A. Wilkinson, J., 1952, 240.36 A. Bebbington, E. J. Bourne, and I. A. Wilkinson, ibid., p. 246.37 S. A. Barker and E. J. Bourne, ibid., p. 209.ae S. Schwimmer and J . A. Garibaldi, Cereal Cheun., 1952, 29, 108.S. Schwimmer, Fed. Proc., 1962, 11, 283240 ORGANIC CHEMISTRY.Interest has been focussed on glycogen in papers additional to thosementioned above. A polysaccharide synthesised by Tetrahymena pyriforrnishas been proved to be a glycogen, having a molecular weight of 9.8 x lo6(light-scattering method) and an average chain length of 13 glucose residuesMThe molecular weights of other glycogens have been determined41 by alight-scattering method as 3-15 x lo6 (cf. ref.14). Maltulose has beenfound in the saccharides resulting from the action of salivary a-amylase ona glycogen obtained from the livers of .pregnant rabbits.42 This importantobservation raises the question of the possible occurrence of fructose in otherglycogens, and perhaps in starches. By periodate oxidation, and deter-mination of the liberated formic acid, chain lengths of 13 units were foundfor cat-liver and fetal-Sheep-liver glycogens, while three samples of glycogenfrom Mytilus edulis had chain lengths of 5, 12, and 17.43 The structuresof these and other glycogens were discussed in the light of their behaviourduring P-amyl~lysis.*~gThe liver “ branching factor,” freed from cc-amylase, has been shown toconvert amylopectin into a polysaccharide giving a reddish-brown, ratherthan a purple, iodine stain ; it was believed that the reaction entailed branch-ing of the outer chains of amyl~pectin.~~ As confirmation of this, a syntheticpolysaccharide, prepared from glycogen by lengthening the outer chains bymeans of phosphorylase and [14C] glucose-1 phosphate, was treated withthe “ branching factor,” and the product was proved by an enzymic methodto possess radioactivity at the new branch points. The liver enzyme, whichfunctions in the absence of added phosphate, probably detaches a short chainof glucose residues by scission of a 1 : 4-link and attaches the chain, as abranch, through a 1 : 6-link; 45 this mechanism is similar to that establishedfor Q-enzyme.The syntheses of glycogen and other carbohydrates duringfermentation of glucose by baker’s yeast have been studied and discussed interms of the enzymic processes of fermentati~n.~~Cellulose.-A polysaccharide from Posidonia australis, previously thesubject of conflicting reports, is now known to be a cellulose; when methyl-ated and hydrolysed, it gives 2 : 3 : 6-trimethyl glucose almost excl~sively.~~An important recent contribution to cellulose chemistry is the isolation ofcellodextrins containing 2-7 glucose residues ; this notable achievementwas accomplished by fractionating, on a column of ‘‘ Silene EF,” the dextrinacetates produced by acetolysis of cellulose, and then deacetylating them.It seems certain that studies of these cellodextrins will lead to a betterunderstanding of the properties of cellulose.It has been demonstrated thata certain amount of re-esterification occurs during the hydrolysis of celluloseacetate with aqueous acetic acid,48 and that the heterogeneous hydrolysis ofhighly methylated cotton cellulose causes scission in the non-crystallineregions, followed by more rapid destruction of the smaller fragrnent~.~~4O D. J. Manners and J. F. Ryley, Biochem. J., 1952, 52, 480.41 B. S. Harrap and D. J. Manners, Nature, 1952, 170, 419.42 S. Peat, P. J. P. Roberts, and W. J. Whelan, Biochem. J., 1952, 51, xvii.43 D. J. Bell and D. J. Manners, J., 1952, 3641.44 D. J. Manners, Biockem. J., 1952, 51, xxx.4 5 J. Larner and G. T. Cori, Fed. PYOC., 1952, 11, 245.46 W.E. Trevelyan, J. N. Gammon, E. H. Wiggins, and J. S. Harrison, Biochem. J.,48 C. J. Malm, L. J. Tanghe, B. C. Laird, and G. D. Smith, J . Amer. CAem. SOL,1952, 50, 303.1952, 74, 4105.4 7 D. J. Bell, J . , 1952, 3649.49 R. E. Reeves, B. J. Barrett, and L. W. Mazzeno, ibid., p. 4491BOURNE MACROMOLECULES. 241Other papers have dealt with the molecular dimensions of cellulose tri-butyrate and trio~tanoate,~O the alcoholysis of cellulose and its derivativeswith 2-methoxyethan01,~l and the oxidation of hydrocellulose withhypoiodite. 52Limnoria Zignorum, a marine wood-boring isopod, has been found tosecrete a cellulase which converts cellulose into reducing substances ; 53earlier work had failed to detect this enzyme.The cellulase of Myrotheciumverrucaria is stimulated by proteins.= An investigation of the relationbetween the action of brown rot fungi, cellulose degradation, and lignincomposition in bagasse has been made.55 An observation which may be offundamental importance with regard to the enzymic synthesis of cellulose isthat an enzyme from Neisseria meningitidis catalyses the reversible reaction :maltose + phosphate p-D-glucose-1 phosphate + glucose.56 This tran-sition from the a- to the @-series may well be the key to the synthesis ofp-glucose polymers.Dextran.-The common tacit assumption that the branches of all dextransinvolve positions 1 and 4 has been proved to be invalid by several inde-pendent groups of workers. Periodate oxidations of the dextrans fromLeuconostoc mesenteroides NRRL B-742 and NRRL B-512 have shown thepresence of periodate-resist ant units, which yield glucose on hydrolysis.l0y 57It was suggested that these units carried branches at position 3, or positions2 and 4.Similar observations have since been made on other dextransss Insuch cases there are anomalous optical rotations and infra-red spectra.** 57* 58A full structural analysis of a Betacoccus arabinosaceous dextran (used inBritain for the production of a blood plasma substitute) has revealed thatthe branches are attached at position 3 almost excl~sively.~ Methylationand end-group assay gave 2 : 3 : 4 : 6-tetramethyl, 2 : 3 : 4-trimethyl, and2 : 4-dimethyl glucose, in proportions corresponding to an average chainlength of ca. 6 glucose residues.Partial acidic hydrolysis of the dextran andfractionation of the resulting oligosaccharides on a charcoal column yielded,inter alia, isomaltose and 3-glucosyl glucose ; there were periodate-resistantunits giving glucose on hydr~lysis.~ An added complication is that somedextrans can be separated, by graded precipitation with ethanol, into frac-tions with no 1 : 3-branches and with an increased proportion of suchbranches.57. 58 In the thermal degradation of dextran, there is a iotableabsence of reducing oligosaccharides when oxygen is excluded.59 Thetoxicity and blood anticoagulant properties of dextran sulphates have beenexamined over a range of molecular weights and sulphate contents.60The optimum conditions for the production of dextran sucrase byLeuconostoc mesenteroides NRRL B-512 have been ascertained ; from50 L.Mandelkern and P. J . Flory, J . Amer. Chem. Soc., 1952, 74, 2517.51 M. G. Blair, ibid., p. 3411.52 M. G. Blair and R. E. Reeves, ibid., p. 2622.53 D. L. Ray and J. R. Julian, Nature, 1952, 169, 32.54 D. R. Whitaker, Scie~zce, 1952, 116, 90.5 5 G. de Stevens and F. F. Nord, J . Amsr. Chem. Soc., 1952, 74, 3326.5 G C . Fitting and M. Doudoroff, J . Biol. Chem., 1952, 199, 153.67 R. Lohmar, J . Anzsr. Chem. Soc., 1952, '94, 4974.5 8 A. Jeanes and C. A. Wilham, ibid., p. 5339.5D M. Stacey and F. G. Pautard, Chem. and Ind., 1962, 1058.6O C. R. Ricketts, Biochem. J., 1952, 51, 129.61 H. J. Koepsell and H. M. Tsuchiya, J .Bact., 1952, 63, 293242 ORGANIC CHEMISTRY.sucrose the culture filtrates produce small amounts of levan, in addition todextran. High sucrose levels in the culture medium lead to viscous cultures,from which the separation of the cells is dificult.sl It has been claimed 62that a new disaccharide, leucrose [5-~-(glucopyranosyl)-~-fructopyranose]," plays a role in the polymerisation process " ; this hypothesis is at variancewith the accepted mechanism of dextran synthesis, and, if substantiated,would cast doubt on current concepts of the formation of other polysacchar-ides from sucrose. Perhaps the disaccharide arises in a side reaction in-volving the transfer of a glucose residue to fructopyranose, instead of toa growing dextran molecule.Cell-free culture filtrates of certain bacteriafrom the human intestine,63 and of an Aspergillus strain isolated fromdisplay dextranase activity, inasmuch as they decrease the average mole-cular weights of dextrans (to ca. 75,000 in the latter case) without liberatingsignificant quantities of reducing sugar.1 : $Linked G1ucosans.-It appears that 1 : 3-linked glucosans occurmore widely in Nature than has been believed hitherto; studies of three ofthem have been reported this year. Confirmation that laminarin is com-posed of p-glucopyranose units, mutually linked through positions 1 and 3,was obtained when it was proved that the disaccharide (laminaribiose), towhich it gives rise when partially hydrolysed with acid, is identical with asynthetic specimen of 3-p-~-glucopyranosyl-~-glucopyranose.65 The syn-thesis was accomplished by condensing 2 : 3 : 4 : 6-tetra-acetyl glucosylbromide with 1 : 2-5 : 6-diisopropylidene glucofuranose, and then removingthe protecting sub~tituents.~~ The flesh of the bracket fungus, PolyporusbetuZinus, when methylated and hydrolysed, has given 2 : 3 : 4 : 6-tetra-methyl, 2 : 4 : 6-trimethyl, 4 : 6-dimethyl, and a monomethyl glucose, in themolar ratio 1 : 13 : 4 : 1, and would thus seem to contain a highly branched1 : 3-gl~cosan.~~ An interesting polysaccharide (" mycodextran ") separateswhen hot-water extracts of AspergiZlus niger 152, grown on a sucrose medium,are cooled ; 67 it has [a]= +283" in alkali, an unusually high figure.68 Chemi-cal analyses of the products of partial hydrolysis of the polysaccharide, andof the methyl glucoses formed by hydrolysis of its trimethyl ether, haveshown " mycodextran " to be a glucosan containing 1 : 3-a- and 1 : 4-a-linkages in approximately equal amount.68Garactans and Ga1actomannans.-Methylation of the galactan of beeflung has indicated that a main chain of 1 : 6-~-galactopyranose units carriesa single D-galactopyranose residue, as a branch, at position 3 of every alternateunit ; in addition, there is one titratable acid function, probably carboxyl,per 3 5 4 0 sugar residues. 69A structure has been proposed for guaran on the basis of enzymicand acidic hydrolyses; 71 the former gave Gal la-6 Man (0.5%) andMan 1 p-4 Man l p 4 Man (7-5%), and the latter, Gal la-6 Man 1 p 4 Man(3%) (where Gal and Man are galactopyranose and mannopyranose residues,62 F.H. Stodola, H. J . Koepsell, and E. S. Sharpe, J. Amer. Chem. SOL, 1952, 74,3202.64 V. Whiteside-Carlson and W. W. Carlson, Science, 1952, 115, 43.65 P. Bachli and E. G. V. Percival, J., 1952, 1243.6 6 R. B. Duff, ibid., p. 2592.68 S. A. Barker, E. J . Bourne, and M. Stacsy, ibid., p. 756.69 M. L. Wolfrom, G. Sutherland, and M. Schlamowitz, J. Amer. Chem. Soc., 1952,'1 R. L. Whistler and D. F. Durso, ibid., p. 5140.a3 E. J. Hehre and T. W. Sery, J . Bact., 1952, 63, 424.6 7 J . L. Yuill, Chem. and I n d . , 1952, 755.74, 4883. 70 R. L. Whistler and C. G. Smith, ibid., p. 3795BOURNE : MACROMOLECULES. 243respectively). It was concluded that guaran consists of a chain of 1 : 4-linked p-D-mannopyranose units, with an a-D-galactopyranosyl group a tposition 6 of every other (average) mannose residue of the chain.Thegalactomannans of lucerne and clover seed resemble guaran in that they arehighly branched, and contain D-galactopyranose end-groups united tochains of 1 : 4(or 1 : 6)-linked D-mannose residues (probably in the pyranose~OX-I-II).~~ A similar structure has been assigned to the galactomannan offenugreek seed, but in this case the galactose : mannose ratio is appreciablyhigher (5 : 6), as also is the degree of branching.73 2-Cyanoethyl ethers havebeen prepared from guaran with acrylonitrile, and have been hydrolysedwith alkali to the corresponding 2-carboxyethyl ethers. 74Fructosans.-A polysaccharide from elecampane has been proved to beof the inulin class by hydrolysis of its methyl ether to 1 : 3 : 4 : 6-tetramethyl,3 : 4 : 6-trimethyl, and a dimethyl fructose (molar ratio, 1 : 32.7 : 1 ~ 5 ) .~ ~Polysaccharides from leaf cocksfoot and I talian rye grass have been classifiedas levans, because their methyl ethers yield 1 : 3 : 4 : 6-tetramethyl, 1 : 3 : 4-trimethyl, and a dimethyl fructose (molar ratios, 1 : 12 : 2 and 1 : 11 : 1,re~pectively).~~ It is interesting, in view of the enzymic studies reportedbelow, that each of these three polysaccharides contained ca. 3% of glucoseresidues. However, the glucose did not appear to be present as non-reducingend-groups (as it is in the inulin of dahlia tubers),76 because it was isolatedduring the end-group assays principally as trimethyl glucose.75Studies of transfructosidases have extended the work of Bacon andEdelman,77 and Blanchard and Albon; 78 they provide possible routes tothe synthesis of inulin and levan." Difco " invertase solution catalyses theconversion of sucrose into a reducing disaccharide, two trisaccharides, and atetrasaccharide, all containing fructose unit(s) linked to a single glucoseresidue. 79 p-Methylfructofuranoside has been prepared from sucrose and25% methanol with yeast invertase.80 With an enzyme from Aspergillusoryzae, sucrose has been converted into a trisaccharide containing oneglucose and two fructose units, and a tetrasaccharide composed of oneglucose and three fructose residues.81 All of these reactions conform withthe equation :Sucrose + HOR Fructosyl-O-R + Glucosewhere ROH is sucrose, glucose, methanol, or a growing oligosaccharide chainwith a non-reducing terminal fructofuranose group, A related phenomenonappears to be responsible for the occurrence, in barley leaves and stems, ofglucose, fructose, sucrose, and at least four higher oligosaccharides withdecreasing glucose : fructose ratioss2Xy1an.-A valuable contribution to the chemistry of xylan has been72 P.Andrews, L. Hough, and J. K. N. Jones, J . Anzev. Chem. Soc., 1952, 74, 4029.73 Idem, J . , 1952, 2744.74 0. A. Moe, S. E. Miller, and M. I. Buckley, J . Amer. Chem. Soc., 1952, 74, 1325.7 5 D. J. Bell and A. Palmer, J., 1952, 3763.76 E. L. Hirst, D.I. McGilvray, and E. G. V. Percival, J., 1950, 1297.7 7 J. S. D. Bacon and J. Edelman, Arch. Biochem., 1950, 28, 467.7 8 P. H. Blanchard and N. Albon, ibid., 1950, 29, 220.79 L. M. White and G. E. Secor, ibid., 1952, 36, 490.81 J. H. Pazur, Fed. Proc., 1952, 11, 267; J , Biol. Chem., 1952, 199, 217.82 H. K. Porter and J. Edelman, Biochem. J . , 1952, 50, xxxiii.J. S . D. Bacon, Biochem. J., 1952, 50, xviii244 ORGANIC CHEMISTRY.made by Whistler and his colleagues, who separated, on charcoal columns,the oligosaccharides resulting from partial acidic hydrolysis of the poly-saccharide.% 83 They isolated a series of five oligosaccharides, all crystalline,extending from the dimer to the hexamer, and obtained evidence that allwere composed of unbranched chains of 1 : 4-linked p-D-xylopyranose units;each of them gave a crystalline p-acetate.Hemicel1uloses.-European beech hemicellulose A gives xylose and auronic acid (not glucuronic acid) when hydrolysed ; the pentosan and uronicacid anhydride contents are 81.4 and 10.4%, respectively.a Hydrolysis ofextractive-free aspen sawdust yields L-rhamnose, L-arabinose, D-xylose,D-galactose, xylobiose, xylotriose, 4-methyl D-glucuronic acid, D-galacturonicacid, ~-a-(4-methy~-~-g~ucuronosy~)-a-D-xy~ose, and several unidentifiedacidic fractions of higher molecular weight.85 The uronic acid anhydrideand pentosan contents of hemicellulose fractions of hays and straws havebeen compared for different plant families and for members of the samefamilies.86Pectic Substances, Gums, and Mucilages.-Chromatographic methods areassisting the elucidation of enzyme actions on pectic substan~es.~~-8~ Withtheir aid crystalline mono-, di-, and tri-galacturonic acids have been isolatedfrom the products of polygalacturonase action on pectic a ~ i d . 8 ~ ~ 8* Bysso-chlamys fulva has been shown to produce a pectin esterase and a poly-galacturonase.% This year has revealed that the problems to be faced instudies of the enzymic degradation of pectic materials are even more complexthan had been realised previously, as the following four examples show.First, a pectin depolymerase of Neurospora crassa differs from others reportedearlier in that it yields lower polyuronides, rather than galacturonic acid, asend products, and also in that it degrades pectin without preliminary de-rnethylati~n.~~ Secondly, Aspergillus foetidus utilises at least two enzymesto effect the conversion of pectic acid into galacturonic acid; one producesdi- and tri-uronides, which serve as substrates for the other.89 Thirdly, apolymethylgalacturonase from commercial " hydralase,' which attackspectin more rapidly than pectic acid, cannot hydrolyse more than 26% ofthe available uronide bonds of the pectin.92 Fourthly, Schubert 93 claimsto have shown with certainty the presence of at least four different poly-galacturonases in extracts of a single culture of Aspergillus niger.The monomethyl aldobiuronic acid which, together with 4-methylD-glucuronic acid, results from controlled hydrolysis of mesquite gum,%is now known to be 6-p-(4-methyl D-glucuronosyl) ~-galactopyranose.~~Acidic hydrolysis of Khaya grandifolia gum gives galactose and a degraded83 R.L. Whistler, J. Bachrach, and Chen-Chuan Tu, J . Amer. Chem. Soc., 1952, 74,3059 ; R. L. Whistler and Chen-Chuan Tu, ibid., p. 4334.84 I. R. C. McDonald, J . , 1952, 3183.s 5 J. K. N. Jones and L. E. Wise, ibid., pp. 2750, 3389.8 6 C. A. Flanders, Arch. Biochem., 1952, 36, 421, 425.87 H. J. Phaff and B. S. Luh, ibid., p. 231.8 8 H. Altermatt and H. Deuel, Helv. Cham. Acta, 1952, 55, 1422.8s A. Ayres, J. Dingle, A. Phipps, W. W. Reid, and G. L. Solomons, Nature, 1952,~41 E. Roboz, R. W. Barratt, and E. L. Tatum, J . Biol. Chem., 1952, 195, 459.93 E. Schubert, Nature, 1952, 169, 931.y* F.Smith, J., 1951, 2646.95 M. Abdel-Akher, F. Smith, and D. Spriestersbach, J., 1952, 3637.170, 834. W. W. Reid, Biochenz. J., 1952, 50, 289.C. G. Seegmiller and E. F. Jansen, ibid., p. 327BOURNE : MACROMOLECULES. 245polysaccharide containing galactose, rhamnose, and galacturonic acid units ;Anogeissus schiwperi gum yields arabinose, galactose , and a degraded poly-saccharide containing arabinose , galactose, and glucuronic acid residuesg6A polysaccharide of Lapinus termis seeds consists of D-galactose, L-arabinose,and galacturonic acid residuesg7Hyaluronic Acid.-Methods for the isolation of hyaluronic acid withtrichloroacetic acid,98 and for the determination of hyaluronidase activity 99have been reported.The polysaccharide has been obtained from the callustissue of healing rabbit fractures.lW Attempts have been made to find thebest method for the isolation, without degradation, of the protein-hyaluronicacid complex of ox sinovial fluid.lo1 About 93% of the complex wasaccounted for in terms of N-acetylglucosamine, glucuronic acid, protein, andash; its particle weight is ca. lo7. Methylation and methanolysis of hyal-uronic acid have been studied.lo2 The crystalline disaccharide, preparedpreviously from hyaluronic acid,lo3 has been shown to be 3-p-D-glUCO-pyruronosyl-D-glucosamine by its conversion into 2-p-~-glucopyranosyl-D-arabinose, which has been obtained also from laminaribio~e.1~~ Infra-redspectroscopy has confirmed the presence in hyaluronic acid of free carboxylgroups and monosubstituted amides ; none of the hydroxyl groups is acetyl-ated.g Purified testicular hyaluronidase converts the polysaccharide intoa mixture of oligosaccharides, but the crude testicular extract givesglucuronic acid and N-acetylglucosamine.1°5 A trisaccharide constituent ofthe oligosaccharide mixture, when treated with glucosaminidase, affordsN - ace t y lglucosamine and a glucuronosy1-N- ace t y lglucosamine .lo Tracerexperiments suggest that the glucosamine moiety of the polysaccharide arisesfrom glucose during biosynthesis.lo6Other Po1ysacchandes.-Alginates have been examined with respect toviscosity 107 and electrolyte absorption.108 It has been confirmed that theirmain structural feature is a chain of 1 : 4-linked p-D-mannuronic acidresidues.lo9 A useful method developed for fractionation of the cell carbo-hydrates of yeast is applicable to as little as 10 mg.of material.ll* Theoccurrence of L-fucose, rhamnose, and methylated carbohydrates in soil hasbeen reported.111 It is interesting that, whereas L-arabinose had been foundpreviously in polysaccharides only in the furanose form, independentresearches have now revealed the presence of the pyranose form in larchE-galactan, 112 and in sapote gum. 113 An electrophoretically pure non-s6 R. J. McIlroy, J., 1952, 1918.s8 W. E. Jancsik and E. Kaiser, Nature, 1952, 169, 114.8s R. L. Greif, J . Biol. Chem., 1952, 194, 619; J. G. Bachtold and L. P. Gebhardt,100 P. H. Maurer and S. S. Hudack, Arch.Biochem., 1952, 38, 49.Iol A. G. Ogston and J. E. Stanier, Biochem. J., 1952, 52, 149.lo2 R. W. Jeanloz, J . Biol. Chem., 1952, 19'9, 141; Helv. Chim. Acta, 1952, 35, 262.lo3 M. M. Rapport, B. Weissmann, F. Linker, and K. Meyer, Nature. 1951, 168, 996.lo4 B. Weissmann and K. Meyer, J . Amer. Chem. SOC., 1952, 74, 4729.1°5 A. Linker and K. Meyer, Fed. Prac., 1952, 11, 249.Io6 S. Roseman et al., ibid., p. 276.lo' M. L. R. Harkness and A. Wassermann, J., 1952, 497.lo8 I. L. Mongar and A. Wassermann, ibid., pp. 492, 500, 510.lo9 S. K. Chanda, E. L. Hirst, E. G. V. Percival, and A. G. Ross, ibid., p. 1833.110 W. E. Trevelyan and J. S. Harrison, Biochem. J., 1952, 50, 298.D7 W. Tadros and M. Kamel, ibid., p. 4532.ibid., p. 635.R. B. Duff, Chem.and Ind., 1952, 1104;J. K. N. Jones, Chem. and Ifid., 1952, 954!E. V. White, J. Amer. Chem.-Soc., 1952, 74, 3966.. Sci. Food Agric., 1952, 3, 140246 ORGANIC CHEMISTRY.reducing oligosaccharide from the cell wall of Corynebacterium diphtheriaeappears to contain two D-galactose residues, one of D-mannose, and three ofD-arabinose, but the molecular weight of such a molecule is only ca. 75% ofthat actually f0und.11~ Polysaccharides isolated from three fresh-wateralgz, NiteZZa, Oscillatoria, and Nostoc, were, respectively, a cellulose-likepolyglucosan, a polyglucosan of the amylopectin class, and a mucilaginousacidic polysaccharide containing at least six different monosaccharideunits. 115 Chondrosine, the component disaccharide of chondroitin sulphuricacid, has been characterised as 4-~(?)-[~-amino-2-deoxy-~-ga~actopyranosy~]D-glucuronic acid ; 116 in the heteropolymer, which is very probably linear,one sulphate acid ester group and the glycosidic attachment of the adjacentD-glucuronic acid unit are yet to be assigned between positions 3, 4, and 6of each chondrosamine residue.l16Nucleic acids.This year has been an important one in the development of nucleic acidchemistry, mainly as a result of contributions by Brown and Todd, and byMarkham and Smith.The former workers 117 showed that phosphorylationof 5’-trityl adenosine with dibenzyl chlorophosphonate (phosphorochloridate),followed by removal of the protecting groups, yielded two adenylic acids,seemingly identical with the isomeric adenylic acids a and b derived fromribonucleic acids ; evidence was presented for their formulation as adenosine-2’ and adenosine-3’ phosphate, although not necessarily respectively.Theirix$erconversion under acidic conditions into an equilibrium mixture of thetwo was explained by ready phosphoryl migration via an intermediate cyclicortho-structure ; there was no rearrangement under alkaline conditions.In these respects, there is a close parallel with the behaviour of glycerolmonopho~phates.~~7 On the other hand, it was recalled that glycerol a-(methylhydrogen phosphate) and triesters of phosphoric acid are unstable to alkali ;in the former case, the reaction probably proceeds via the neutral cyclictriester (V), which is hydrolysed immediately to methanol and the cyclicCH,*O\ yoFH-O/ \OH (VI)I P‘I ICH,.OH CH,*OHphosphate (VI), and this, in turn, gives glycerol a- and p-phosphate.l17Dialkyl phosphates, devoid of a hydroxyl function in proximity to thephosphoryl group, are stable to alkali.For these and other reasons, a simplestraight-chain polynucleotide sequence was represented as (VII), in whichthe individual nucleoside residues are shown briefly as C~F~--C~r~-Cp~ ;alkaline degradation was regarded as proceeding through an intermediate(VIII), followed by ready fission of the triester groups exchsively at theP-O-C,,, linkage, to give eventually a mixture of nucleoside-2’ and -3’phosphates.117 In addition to structure (VII) , in which -the polymericlinkage is shown joining the 3’- and 5’-positions, other structures withE.S. Holdsworth, Biochim. Siophys. Acta, 1952, 8, 110; 1952, 9, 19; T. J.Bowen, ibid., p. 29. 115 L. Hough, J. K. N. Jones, and W. H. Wadman, J . , 1952,3393.l l s M. L. Wolfrom, R. K. Madison, and M. J. Cron, J . Amer. Chew. Soc., 1952, 74,1491. 117 D M. Brown and A. R. Todd, J., 1952, 44, 52BOURNE MACROMOLECULES. 247C(,.)-C(,) or C,)-C,,.) links, or mixed C,)-C,, and C(r)-C(y) units insequence would all show alkali lability. A C(5')-C(5' linkage, however,cannot occur anywhere in the molecule as this would be stable to alkali andwould lead to the appearance of dinucleotides in ribonucleic acid hydro-1 y ~ a t e s . l ~ ~ Reasons were given for believing that CC5,) is involved in themain internucleotide linkage of both ribonucleic and deoxyribonucleic acids,thus restricting the choice of linkage to C,,)-C,,) and C(r)-C,,).Sincedeoxyribonucleic acids cannot be of the former type, it was regarded asadvantageous, at the moment, to represent the " backbone " of ribonucleicacids as (VII). Deoxyribonucleic acids are not degraded to small moleculesby mild treatment with alkali because the essential formation of a cyclicstructure is prec1uded.l'Brown and Todd 1 1 7 pointed out that, although deoxyribonucleic acidsappear to be largely straight-chain polynucleotides, ribonucleic acids probablyhave a branched-chain structure. They considered the known productionof large amounts of pyrimidine nucleotides during ribonuclease treatment ofribonucleic acids to suggest that these nucleotides are derived from short sidechains, which occur at frequent intervals and probably for the most partcontain only one nucleoside residue.Accordingly, they envisaged a possiblegeneral structure for ribonucleic acid as (IX), an extension of (VII).(IX) a and b are pyrimidine nucleoside residues; P represents a phosphate group.Further experimental support for the above concepts of the architectureof the ribonucleic acid molecule was obtained subsequently. The cyclic2' : 3'-phosphates of adenosine, cytidine, and uridine were prepared 118 fromthe corresponding 2'- and 3'-phosphates, by the widely applicable esteri-D. M. Brown, D. I. Magrath, and A. R. Todd, J., 1952, 2708248 ORGANIC CHEMISTRY.fication process promoted by trifluoroacetic anhydride.l19 With acid oralkali, the cyclic esters gave mixtures of the a and b nucleotides.ll* Ribo-nuclease converted cytidine-2’ : 3’-phosphate into cytidylic acid b, anduridine-2’ : 3’ phosphate into uridylic acid b, but it hadno action on adenosine-2’ : 3’ phosphate; 120 these observations accord well with the fact that thereis little or no purine nucleotide in the mononucleotide fraction of ribonucleasedigests of ribonucleic acids.120p 121 The conversion of cytidylic acid b intouridylic acid b, by alkaline deamination, indicated that the phosphorylgroup in each of these two compounds occupies the same position in theribofuranose residue.12*Markham and Smith, who had already observed 122 that a new class ofnucleotide appears during the digestion of ribonucleic acid with ribonuclease,have extended their studies 123 and have provided excellent confirmation ofpart of the theory of Brown and Todd.l17 They have shown 123 that thenew class of nucleotide is, in fact, composed of nucleoside-2‘ : 3’ phosphates,which are formed also by mild alkaline hydrolysis of ribonucleic acid, andhave confirmed that the cyclic phosphates of pyrimidine, but not of purine,nucleosides are substrates for ribonuclease.In a more detailed analysis,based on chromatography and paper electrophoresis, methods were givenfor the isolation of fifteen of the smaller products formed from ribonucleicacid by ribon~clease.12~ The general structure of the dinucleotides was toy i-I’P voYr ‘1-1Py ’ O y‘1-1 Peither (X) or (XI) (Py = pyrimidine ; X = pyrimidine or purine) ; the3‘-phosphate groups shown may in fact have been 2’-phosphate groups.Thedinucleotides with a cyclic phosphate group were the first liberated, andwere then slowly transformed into the 3’(or 2’)-phosphates. The trinucleo-tides all contained at least one pyrimidine nucleotide residue. 123 Adenosine-2’ : 3’ phosphate, guanosine-2’ : 3’ phosphate, and adenylic, guanylic,cytidylic, and uridylic acids were all identified as end-groups in the ribo-nucleic acids of yeast and turnip yellow mosaicAC:U:C:U:C:C:AGAGC:U:C:C:AAGU:U:GU:U:C:C:GC:C:U:AGC:A(=I)In spite of such a large measure of agreement, Markham and Smith werenot able to accept the branched structure (IX) advanced by Brown and Toddfor ribonucleic acid. They believed the acid to be composed of a mixture110 E.J. Bourne, M. Stacey, J. C. Tatlow, and J. M. Tedder, J., 1949, 2976.l a o D. M. Brown, C. A. Dekker, and A. R. Todd, J . , 1952, 2715.I a r R. Markham and J. D. Smith, Nature, 1951, 168, 406.lee Idem, Research, 1951, 4, 344. lfS Idem, Bioclzem. J., 1952, 52, 552, 558, 585BOURNE : MACROMOLECULES. 249of many kinds of comparatively short chains, with the general features of(XII) in which A, G, C, and U represent adenylic, guanylic, cytidylic, anduridylic acid residues, respectively, each nucleoside being joined at position-2‘ (or -3‘) through a phosphate ester link to the adjacent residue on theright-hand side, and at position-5’ through a similar link to its neighbouron the left ; the bonds which are broken by ribonuclease are shown as colons.A purine nucleoside-2’ : 3‘ phosphate can be liberated only if it is situated atone end of the chain.la3 The ribonuclease-resistant “ core ” appears to bea mixture of polynucleotides about three to five residues in length, eachpolynucleotide consisting of a chain of purine nucleotides terminated by apyrimidine nucleotide residue, with the terminal phosphoryl group on C(z?or C,).The failure of this “ core ” to dialyse through Cellophane is dueapparently largely to its charge, rather than to its molecular size 123 (see alsoref. 127). Methylation evidence has been claimed to demonstrate that yeastribonucleic acid possesses internucleotide linkages between ribose andphosphoryl residues, and also that there is a high degree of branching, dueto triply phosphorylated ribose units.12* Several dinucleotides have beenisolated in an analytically pure state from acid-ireated yeast ribonucleicacid.la5 Studies have been made of the splitting of purine ribosides by botha hydrolytic and a phosphorolytic system found in autolysates of driedbaker’s yeast.126 A promising method for the degradation of ribonucleicacid, catalysed by methoxide ion, has been announced.126aDeoxyribonucleic acids have continued to receive considerable attention.Samples derived from animal, plant, and bacterial sources have been analysedcarefully,127* 128 as also have the enzyme-resistant “ cores ” produced there-from by deoxyribonuclease ; 127 a new pyrimidine base, 5-hydroxymethyl-cytosine, is present in bacteriophage nucleic acids. 128 The deoxypentose-nucleic acids from three different strains of E. coli possess unusual purine andpyrimidine ~ 0 n t e n t s . l ~ ~ Light-scattering techniques have revealed that themethod for the isolation of calf-thymus deoxyribonucleic acid developed bySchwander and Signer 130 is reproducible, and that the product has a highermolecular weight (6-7-8.0 x lo6) than have samples prepared in otherways 13’ (see also ref. 144) ; the shape of the molecule is greatly dependenton pH.I3l The irreversible decrease in the viscosity of deoxyribonucleicacid solutions, caused by phenol or urea, is attributed to the breakage ofhydrogen bonds.132 Ultrasonic waves have a similar effect, but in additionthere is some scission of the polynucleotide ~hain.l3~ Dilute acid and alkaliincrease the intensity of colour given by Schiff’s reagent ; this might possiblybe due to the rupture of labile C(r)-phosphate l i n k ~ . l ~ ~ Under mild acidic124 A. S. Anderson, G. R. Barker, J. M. Gulland, and M. V. Lock, J., 1952, 369.1z6 L. A. Heppel and R. J. Hilmoe, ibid., 1952, 198, 683.1260 D. Lipkin and J. S. Dixon, Science, 1952, 116, 525.lZ7 S. G. Laland, W. G. Overend, and M. Webb, J., 1952, 3224.lz8 G. R. Wyatt and S. S. Cohen, Nature, 1952, 170, 846, 1072.lz9 B. Gandelman, S. Zamenhof, and E. Chargaff, Biochim. Biophys. Acta, 1952, 9,399.130 H. Schwander and R. Signer, Helv. Chim. Acta, 1950, 33, 1521.131 M. E. Reichmann, R. Varin, and P. Doty, J . Amar. Chern. Soc., 1952, 74, 3203;132 B. E. Conway and J. A. V. Butler, J . , 1952, 3075.133 S. G. Laland, W. G. Overend, and M. Stacey, ibid., p. 303.134 W. A. Lee and A. R. Peacocke, ibid., p. 130.R. B. Merrifield and D. W. Woolley, J . Biol. Chem., 1952, 197, 521.I?. Doty and B. H. Bunce, ibid., p. 5029250 ORGANIC CHEMISTRY.conditions purines can be removed quantitatively from calf-thymus deoxy-ribonucleic acid, without completely destroying the original highly poly-merised structure and without changing the distribution of the pyrimidinenucleo t ides. 135The nucleotides and dinucleotides resulting from deoxyribonucleaseaction on the deoxyribonucleic acids of calf thymus,136 wheat embryo, 137and herring sperm 137* 138 have been examined; in one case 5'-deoxycytidylicacid was identified in the digest. 139 An ion-exchange chromatographicprocedure, suitable for use on a large scale, has been described for theseparation of deoxyrib~nucleosides.~~~ Earlier assumptions that sodiumarsenate, sodium citrate, and sodium borate (known inhibitors of pancreaticdeoxyribonuclease) inhibit intra-cellular deoxypentosenucleases of mam-malian tissues have been shown to be invalid.140It has been demonstrated, by indirect methods, that enzyme preparationsfrom Lactobacillus helveticus, Lactobacillus delbrueckii, and Thermobacteriumacidoplzilus R. 26 catalyse the transfer of the deoxyribose residue from onepurine or pyrimidine to another.141 These enzyme(s) are trans-N-glycos-idases ; they are unable to utilise either deoxyribose or deoxyribose-1ph0~phate.l~~ Among other topics studied are (a) the binding of sodiumchloride 142 and mercuric chloride 143 with calf-thymus deoxypentosenucleate,and (b) the spectrophotometry of this nucleic acid,144 and of natural andsynthetic pyrimidine ribo- and deo~yribo-nucleosides,1*~ as a function of pH.Proteins.Since the chemistry of proteins was covered very fully in the AnnualReports for 1951, only brief reference to the subject will be made this year.The formidable task of condensing such a vast field into so small a space canbest be accomplished by drawing attention to useful reviews of currentresearches; five such reviews, published during 1952, give a fairly compre-hensive picture of the present position. Writing from the viewpoint of theorganic chemist, Khorana 146 has surveyed structural investigations, andchemical methods of synthesis of polypeptides and proteins. Edsall 147has provided a concise account of a Royal Society Discussion, in which themain emphasis was on the contributions of X-ray and infra-red techniquesto the problem of the structural pattern of the polypeptide chains in proteins.Particular attention was paid to synthetic poly-y-methyl L-glutamate fibres,and it was concluded 147 that, although further work is certainly needed, thebalance of evidence on these synthetic polypeptides seems to be in favour ofthe a-helix. In a survey of recent developments in the separations of pro-teins and enzymes by paper chromatography, Boman 148 laid stress on theR. L. Sinsheimer and J . F. Koerner, J. Amer. Chem. SOG., 1952, 74, 283.J . D. Smith and R. Markham, Nature, 1952, 170, 120; Biochim. Biophys. Acta,139 J . L. Potter, K. D. Brown, and M. Laskowski, Biochim. Biophys. Acta, 1952,141 W. S. Macnutt, Biochem. J., 1952, 50, 384.142 J. Shack, R. J. Jenkins, and J. M. Thompsett, J . Biol. Chem., 1952, 198, 85.143 S. Katz, J. Amer. Chem. SOG., 1952, 74, 2238.144 J. Shack and J. M. Thompsett, J . Biol. Chem., 1952, 197, 17; G. Frick, Biochim.14* H. G. Khorana, Quart. Reviews, 1952, 6, 340.147 J. T. Edsall, Nature, 1952, 170, 53.135 C: Tamm, M. E. Hodes, and E. Chargaff, J. Biol. Chem., 1952, 195, 49.1952, 8, 350.9, 150.138 W. Andersen, C. A. Dekker, and A. R. Todd, J., 1952, 2721.140 M. Webb, Nature, 1952, 169, 417.Biophys. Ada, 1952, 8, 625. 145 D. Shugar and J. J . Fox, ibid., 1952, 9, 199, 369.148 H. G. Boman, ibid., p. 703BOURNE MACROMOLECULES. 251phenomenon of ‘‘ double-fronting.” An interesting discussion u9 of thephysical chemistry of proteins ranged over such topics as the globular-fibrous protein transformation, zone electrophoresis in filter-paper, mechan-isms of muscular action, the conversion of fibrinogen into fibrin, muco-proteins, nucleopro teins , ant igen-an t ibod y reactions, and protein inter-actions with heavy metals, alkaline earths, heparin, and other organicmolecules. The biogenesis of proteins was the subject of a symposium inParis. 150E. J. B.A. S. BAILEY.E. J. BOURNE.J. W. CORNFORTH.T. G. HALSALL.T. J. KING.J. F. W. MCOMIE.R. A. RAPHAEL.J. WALKER.W. A. WATERS.B. C. L. WEEDON.149 The Physical Chemistry of Proteins, Discuss. Faraday Soc., 1952.lLo Symposium on the Biogenesis of Proteins, 2nd Internat. Congr. Biochem., Paris,1952

ISSN:0365-6217    

DOI:10.1039/AR9524900110

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

BIOCHEMISTRYI. INTRODUCTION.THE present report forms the third of the series since the commencementof the new attempt to report on " larger fields of biochemistry." The SecondInternational Congress of Biochemistry, held in Paris in July, 1952, wasconsidered to be a great success.E. B.2. BACTERIA& NUTRITION.Micro-organisms, because of their widely differing nutritional require-ments, have proved valuable tools in the elucidation of biosynthetical path-ways and the metabolic functions of B-group vitamins. This Report hasbeen written from this point of view, though it is obviously limited, since adiscussion of bacterial nutrition in its widest sense would include all sub-stances and environmental conditions influencing bacterial growth. Somerecently published reviews and books dealing with aspects of the field aregiven in ref.1.Methods of approach to problems of biosynthesis and metabolic functionhave been discussed by Woods,2 who stresses the importance of nutritionalinvestigations ; these may guide the planning of further experiments (eg.,with cell suspensions and enzyme preparations) likely to provide more directinformation. Induced biochemical mutant strains of bacteria are nowwidely used to investigate mechanisms of biosynthesis. The penicillintechnique 3 for the isolation of such strains has contributed greatly to thedevelopment of this field; it has been improved recently by Adelberg andMyers4Nature and Function of the Vitamin B Group Comp1ex.-It may now beaccepted as a working hypothesis that B-group vitamins function catalyticallyin cell metabolism as components of coenzymes.An outstanding recentadvance in this field has been in the clarification of the nature and functionof the protogen-lipoic acid group of factors, which can now be included inthe vitamin-B complex.Protogen, Zifioic acid, and fiyruvate-oxidation factors. Early work onthese factors developed independently along three lines. Substances werefound in yeast extract which (a) replaced acetate for growth of some lacto-bacilli (" acetate-replacing factor " ) , 5 (b) promoted pyruvate oxidation bycell suspensions of Streptococcus faecalis 10 C1 grown in a semi-syntheticI H. C. Lichstein, Ann. Rev. Microbial., 1952, 6, 1 ; J. L. Stokes, ibid., p. 29; E.C.Barton-Wright, " The Microbiological Assay of the Vitamin B Complex and Amino-acids," Pitman and Sons Ltd., London, 1952 ; F. A. Robinson, " The Vitamin €3 Com-plex," Chapman and Ha11 Ltd., London, 1951; C . H. Werkman and P. MJ. TVjlson(editors), " Bacterial Physiology," Academic Press, New York, 1951 ; D. W. WooIIey," A Study of Antimetabolites," Chapman and Hall Ltd., London, 1952.2 D. D. Woods, Bull. World Hlth. Org., 1952, 6, 35.3 R. D. Davis, Experientia, 1950, 6, 41.4 E. A. -4delbergand J. W. Myers, Fed. Proc., 1952, 11, 179.6 B. M. Guirard, E. E. Snell, and R. J. Williams, Arch. Biochem., 1946, 9, 381LASCELLES BACTERIAL NUTRITION. 253medium (" pyruvate-oxidation factor "),6 and (c) were growth factors forTetrahymena geleii and an unidentified Corynebacterium sp.( I ' protogen ' ').Snell and Broquist 8 found preparations of these factors to be interchangeablein the different test systems and suggested that they were closely related;subsequent work has confirmed this view. There is now strong evidencethat Butyribacterium rettgeri factor also belongs to this group.These substances have all been found to exist in natural materials inseveral biologically active but chromatographically distinct f~rrns.~-~~ Oneof the acetate-replacing factors from liver has been obtained crystalline(a-lipoic acid) 12 and simultaneously, protogen-B was isolated from the samesource as the cryst d i n e benzylthiuronium salt .I3 Highly purified concen-trates of a-lipoic acid and of protogen-B each contained another activeprinciple, named p-lipoic acid and protogen-A, respectively.I& l5 Aspurification proceeded these were transformed into the factors finally isolated.The chemical properties of or-lipoic acid and protogen-B suggest that both arederived from a dimercapto-n-octanoic acid.1*-16 The Lederle workers l7find (&)-5 : 8-dimercapto-octanoic acid (" thioctic acid ") and (-J-)-6 : 8-dimercapto-octanoic acid (" 6-thioctic acid ") to have the biological activityof protogen-B in a number of test systems (acetate replacement, pyruvateoxidation, and growth-promoting activity for Cmynebacterium sp.and T.geleii) ; 6-thioctic acid is 1OO-lOOO times more active than 5-thioctic acid.A synthetic greparation with properties similar to those of a-lipoic acid hasalso been obtained; it is suggested, on the basis of experiments with thesynthetic substance and a-lipoic acid, that the latter is one of the opticalisomers of the cyclic disulphide derived from 5 : 8-dimercapto-octanoic acid. l8The present chemical data are insufficient to permit assignment of definitestructures to a-lipoic acid and protogen-B.The relationship of these eom-pounds to the other biologically active, natural substances is also not yetclear.Factors of this group act a t very low concentration in promoting bacterial'I E. L. R. Stokstad, C. E. H o h a n n , M. A. Regan, D. Fordham, and T. H. Jukes,Arch. Biochem.. 1949, 20, 75; E. L. R. Stokstad, C. E. Hoffmann, and M. Belt, Pvoc.SOL Ex$. Biol.N.Y., 1950, 74, 571.E. E. Snell and H. I?. Rroquist, Arch. Biochern., 1949, 23, 326.L. Kline and H. A. Barker, J . Rnci., 1950, 60, 349; L. KIine, L. Pine, I. C. Gun-salus, and H. A. Barker, ibid., 1952, 64, 467.lo L. J. Reed, R. G. De Busk, P. M. Johnston, and M. E. Getzendaner, J . Biol.Chem., 1951, 192, 851 ; L. J. Reed, M. E. Getzendaner, B. G. De Busk, and I?. M.Johnston, ibid., p. 859.l1 I. C. Gunsalus, L. Struglia, and D. J. O'Kane, ibid., 1952, 194, 859.l2 L. J. Reed, €3. G. De Busk, I. C. Gunsalus, and C. S. Hornberger, Jnr., Science,1951, 114, 93.l3 E. L. Patterson, J. A. Brockman, Jnr., F. P. Day, J. V. Pierce, M. E. Macchi,C. E. Hoffmann, C. T. 0. Fong, E. L. R. Stokstad, and T. H. Jukes, J . Amer. Chem. SOC.,1951, 7'3, 5919.l4 L.J. Reed, B. G. De Busk, I. C. Gunsalus, and G. H. F. Schnakenberg, ibid., p.5920.lS J. A. Brockman, Jnr., E. L. R. Stolcstad, E. L. Patterson, J. V. IYieree,hl. Macchi,and F. P. Day, ibid., 1952, 7'4, 1868.I6 L. J. Reed, Q, F. Soper, G. H. F. Schnakenberg, S. F. Kern, H. Boaz, and I. C.Gunsalus, ibid., p, 2383.M. W. Bullock, J. A. Brockman, Jnr., E. L. Patterson, J. V. Pierce, and E. L. R.Stokstad, ibid., p. 1868, 3455.C. S. Hornberger, Jnr., R. F. Heitmiller, I. C. Gunsalus, G. H. F. Schnakenberg,and L. J. Reed, ibid., p. 2382.D. J. O'Kane and I. C. Gunsalus, J . Bact., 1948, 58, 499254 BIOCHEMISTRY.growth. Other compounds besides acetate have been found to replace themfor different organisms. These include malate, succinate, hydrogen carbon-ate (a strain of Strep.faecalis) l9 and sorbitan mono-oleate (Streptococcuscremoris).20 A mutant strain of Bacterium coli normally requiring a higherform of a-lipoic acid (see below) grows in its absence provided that acetate,citrate, and succinate are all present in the medium.21 It appears, therefore,that acetate and di- and tri-carboxylic acids are direct or indirect products ofreactions requiring factors of this group as coenzymes. Experiments withdeficient cell suspensions and enzyme preparations promise to provideinformation about the mechanisms of these reactions. Using these methodsof approach, Reed and De Busk21 find that a-lipoic acid functions in theoxidative decarboxylation of pyruvate and a-ketoglutarate in the form of alipoic acid-thiamine pyrophosphate coenzyme.A mutant strain of Bact.coli was isolated which requires for growth " lipothiamide " (prepared by heat-ing a-lipoic acid and thiamine together in vacuo) ; a-lipoic acid is not utilised.Lipothiamide is also essential for the oxidation of pyruvate and a-keto-'glutarate by deficient cell suspensions of this organism ; with cell-free ex-tracts, lipothiamide pyrophosphate is needed. Lipothiamide and itsphosphorylated derivatives appear to be identical with bound forms of a-lipoic acid present in extracts of natural materials.Many organisms utilise pantoic acid or p-alanine forgrowth in place of pantothenic acid, suggesting that these compounds areintermediates in the formation of the vitamin. Synthesis of the vitaminfrom p-alanine and pantoic acid has also been observed in cell extracts ofBact.c 0 2 i . ~ ~ Preparations from a mutant strain of this organism, whichrequires pantothenic acid only when grown a t >30", also form this substancefrom its precursors, but the enzyme system is much more heat-labile thanthat from the parent ~train.~3The synthesis of coenzyme A (the coenzyme form of pantothenic acid)from pantothenic acid may occur through the intermediate formation ofpantetheine (a-pantothenoylaminoethanethiol) (I) or its correspondingHOCH2~CMe,*CH(OH)*CO~NH-[CH2],*C0.NH~[CH2],*SH (I)disulphide, ~antethine.~4 Pantethine has the same activity as highly purifiedconcentrates of Lactobacillus bulgaricus factor for growth of that and relatedorganisms.Pantothenic acid also promotes growth of these organisms butis active at high concentrations 26 The several chromatographicallydistinct forms of Lb. bulgaricus factor found in extracts of natural materialsare probably mixed disulphides formed between pantetheine and othert h i o l ~ . ~ ' ~ ~ ~Pantotkenic acid.18 V. 1,. Lytle, S. M. Zulick, and D. J. O'Kane, J . Riol. CAem., 1951, 189, 551.20 V. L. Lytle and D. J. O'Kane, J . Bact., 1951,61, 240.21 L. J. Reed and B. G. de Busk, J . Amer. Chem. SOL, 1952, 14, 3457, 3964, 4727;Idem, J . BioE. Chem., 1952,199, 873, 881. 22 W. K. Maas, J . Biol. Chem., 1952,198,23.23 W. K. Maas and B. D. Davis, Proc. Nat. Acad. Sci. Wash., 1952, 38, 785.24 E. E. Snell, G. M. Brown, V. J. Peters, J.A. Craig, E. L. Wittle, J. A. >!Toore,V. M. McGlohan, and 0. D. Bird, J . Amer. Chem. SOC., 1950, 72, 5349.25 G. M. Brown, J. A. Craig, and E. E. Snell, Arch. Riochem., 1950, 21, 473 ; R. A.McRorie, P. M. Masley, and W. L. Williams, ibid., p. 471; R. A. McRorie and W. L.Williams, J . Bact., 1951, 61, 737.27 G. M. Brown and E. E. Snell, J . Bzol. Chem., 1952,198, 375.Arch. Btochew., 1951, 34, 409.26 J . A. Craig and E. E. Snell, ibid., p. 283.J..C. Vitucci, N. Bohonos, 0. P. Wieland, D. V. Lefemine, and B. L. HutchingsLASCELLES : BACTERIAL KUTRITIOK. 255The importance of coenzyme A in reactions involving transfer of acetylgroups and also in other systems had been fully reviewed by Lipmann,Ochoa, and other^.^^^^^Snell 31 has discussed someof the recent work concerning the function and mechanism of action of thesefactors in the amino-acid metabolism of micro-organisms.Vitamin B, isconcerned in the synthesis of many amino-acids. Thus, in the presence ofvitamin B,, Lactobacillus arabinosus no longer requires lysine, serine, alanine,histidine, threonine, or cystine for growth; 32333 with both vitamin B, andcarbon dioxide present it can also dispense with phenylalanine , tyrosine,arginine, and aspartic acid.32 The stage a t which vitamin B, acts in thesynthesis of these amino-acids was not shown by these experiments. InLeuconosfoc mesenteroides, however, it is involved in the conversion of glycineinto serine; it is essential for growth when high concentrations of glycinereplace serine.34 Pyridoxal is also needed for serine synthesis from glycineand fonnate by cell suspensions of Sfrep.f a e ~ a l i s . ~ ~ Vitamin B, is requiredfor growth of Lb. arabinosus and Strep. faecalis when cc-keto-acid analoguesare substituted for the corresponding amino-acid~.~~ These experimentsindicate that transamination reactions (requiring pyridoxal phosphate asco-factor) are responsible for the formation of amino-acids from the cc-keto-acids. The latter may not, however, be normal intermediates in the synthesisof all the amino-acids in whose formation vitamin B, is implicated, and thefactor may well play a part at some stage other than transamination.Pyridoxal phosphate is, for instance, a coenzyme for the system which con-denses indole and serine to give tryptophan in enzyme preparations fromN e u ~ o s p o r a .~ ~D-Alanine becomes essential for growth of Strep. faecalis and Lactobacilluscasei in media devoid of vitamin B,; suggesting that the latter is needed forthe synthesis of the ~-amino-acid.~’ Subsequent work with enzyme pre-parations has confirmed this; L-alanine is converted into the D-form by aracemase requiring pyridoxal phosphate for a c t i v a t i ~ n . ~ ~ Many D-amino-acids are utilised for growth of Lb. arbbinosus in place of the L-isomers,provided that vitamin B, is present in the medium.39@ It appears that theco-racemase function of the factor also accounts for these observations.This compound occurs, mainly in bound forms, in many naturalproducts.41 Recently the isolation, identification, and chemical synthesis of29 “ Symposium sur le Cycle Tricarboxylique,” Second Int.Congr. Riochem. , Paris,1952.30 S. Ochoa and J. R. Stern, Ann. Rev. Biochem., 1952, 21, 547; A. D. Welch andC. A. Nichol, ibid., 9; 633.31 E. Em. Snell, Symposium sur le RfPltabolisme Microbien,” p. 47, Second Tnt.Congr. Riochem., Paris, 1952.32 C. M. Lyman, 0. Moseley, S. Wood, B. Butler, and F. Hale, J . Biol. Chem., 1947,167, 177.34’ J. Lascelles and D. D. Woods, Nature, 1950, 166, 649.35 J. T. Holden, R. B. Wildman, and E. E. Snell, J . Biol. Chem., 1951, 191, 559.36 MT. W. Umbreit, W. A. Wood, and I. C. Gunsalus, ibid., 1946, 165, 731; C.37 J. T. Holden, C. Furman, and E. E. Snell, ibid., 1949, 178, 789; J.T. Holden and38 W. A. Wood and I. C. Gunsalus, ibid., 1951, 190, 403.39 C. M. Lyman and K. A. Kuiken, Fed. Pvoc., 1948, 7, 170.40 M. N. Camien and M. S. Dunn, J . Biol. Chem., 1950, 182, 119.Pyridoxine and derivatives (vitamin-B, group).Biotin.33 J. L. Stokes and M. Gunness, Science, 1945, 101, 43.Yanofsky, ibid., 1952, 194, 279.E. E. Snell, ibid., p. 799.R. C. Thompson, R. E. Eakin, and R. J. Williams, Science, 1941, 94, 589256 BIOCHEMISTRY.one of these complexes, biocytin, has been described; 42343 it was obtainedfrom yeast and identified as E-N-biotyl-lysine (11). The synthetic compoundhas the same biological activity as the crystalline natural material. Biocytinis not attacked by proteolytic enzymes, such as papain and trypsin, ariaHN-CO-NH I I (11) "-7" H,C---S-CH*[CH,] 4*CO*NH.[CH,] ,CH( NH,)CO,Hstrong acids or alkalis are needed to liberate biotin.It is, however, as activeas biotin itself for growth of many organisms (e.g., Lb. casei), but is inactivefor L b. arabinosus, Ln. mesenteroides, and Penicillium chrysogenum. Likebiotin, it overcomes competitively inhibition of growth of Lb. casei byhomobiotin. Biocytin also behaves similarly to biotin in reactivating aspar-tic acid deaminase in " aged " cells suspensions of Prateus vulgaris, but doesnot appear to be identical with Lichstein's " biotin coenzyme " since it doesnot replace preparations of this substance in the aspartic acid deaminasesystem of Bacterium cadaveris.@Pimelic acid replaces biotin for growth of Corynebacterium diehtheriae 45and is presumably a precursor in this organism.Evidence that it is also aprecursor in BaciZZus tenuis and other organisms has come from work withgrowth-inhibitory analogues of pimelic acid ; inhibition by these compoundsis overcome competitively by pimelic acid whereas, in the presence of biotin,growth is insensitive to the analogues.46The function of biotin in cell metabolism is not clear; Lichstein 47 hasreviewed some aspects of this probIem. Research with bacteria has pointedto its possible role in carboxylation reactions and in the synthesis of oleicacid. Thus, growth of Lb. nrabinoszas (and other lactobacilli) occurs in theabsence of biotin provided that aspartic acid and oleic acid (together withTween-40 or -80 to detoxify the fatty acid) are present in the ~ n e d i u r n .~ * ~ ~ Growth under these conditions is stimulated by carbon dioxide, but in thepresence of biotin either aspartic acid or carbon dioxide is stimulatory.Biotin does not however appear to be involved in aspartic acid formation inClostridium bzttyricum and Lactobacillus fermenti ; oleic acid alone promotesgrowth in the absence of the vitamin, and under these conditions the organ-isms synthesise aspartic a ~ i d . 4 ~ Blanchard d aLm have suggested that biotinis concerned in the formation of enzymes required in carboxylation reactionsrather than as a co-factor in these systems; this conclusion was based onexperiments with the " mafic enzyme " system from Lb. arabinosas, which42 L.D. Wright, E. L. Cresson, H. R. Skeggs, T. R. Wood, R. L. Peck, D. E. Wolf, andK. Folkers, J . Amer. Chern. SOL., 1950, 72, 1048.43 Idem, ibid., 1952, 74, 1996; R. I,. Peck, D. E. Wolf, and K. Folkers, ibid., p.1999; D. E. Wolf, J. Valiant, R. L. Peck, and K. Folkers, wid., p. 2002; L. D. Wright,E. L. Cresson, K. V. Liebert, and H. R. Skeggs, ibid., p. 2004.44 H. C. Lichstein, J. F. Christman, and W. L. Boyd, J . Bact., 1950, 59, 113; H. C.Lichstein, ibid., 1950, 60, 485.46 J. H. Mueller, J . Biol. Chem., 1937, 119, 121; V. Du Vigneaud, K. Dittmer, E.Hague, and B. Long, Science, 1942, 96, 186.40 D. W. Woolley, J . Biol. Chem., 1950, 183, 495.4 7 H. C. Lichstein, Vitamiws and Hormones, 1951, 9, 27.4 8 R. L. Potter and C. A. Elvehjem, J .BioE. Chem., 1948, 172, 531.49 H. P. Broquist and E. E. Snell, zbid., 1951, 188, 431.50 M. L. Blanchard, S. Korkes, A. del Campillo, and S. Ochoa, ibad., 1950, 187, 875LASCELLES : BACTERIAL NUTRITION. 257catalyses the reversible decarboxylation of malic acid to pymvic acid andcarbon dioxide.It may be significant that traces of biotin have been found in cells of Lb.arabinosus, CI. b~tyricum,4~ Lb. casei,51 and Clostridium perfringens 52 grownin the complete absence of the factor.This group includes 9-aminobenzoic acid,pteroylglutamic acid, and Leuconostoc citrovorzcm factor. Aspects of thesubject have been reviewed recently by Woods,2* 53 Welch and Nich01,~Oand Shive.54Investigations of the requirement of different organisms for factors of thefolic acid group have shown that 9-aminobenzoic acid is converted into ahigher form closely related to, though not necessarily identical with Ln.citrovorum factor ; there is strong evidence that sulphonamides inhibitbacterial growth by preventing competitively the utilisation of $-amino-benzoic acid in this way.55 Some organisms (e.g., Lb.casei and Strep. faecalis)are unable to grow on 9-aminobenzoic acid but respond to either pteroyl-glutamic acid or Ln. citrovoruw factor, while Ln. citrovorum utilises the lattersubstance only. The status of pteroylglutamic acid as a normal intermediatein the conversion of p-aminobenzoic acid into higher forms is, however, verydoubtful .The outstanding recent advance in this field has been the identificationof Ln.citrovorum factor as a formyltetrahydropteroylglutamic acid ; syntheticLn. citrovorum factor (leucovorin 56 or folinic acid-SF 67) is 5formyl-5 : 6 : 7 : 8-tetrahydropteroylglutamic acid. (cf. Ann. R@orts, 1951, 48, 227),and full details of its synthesis have now been published.58 Leucovorin hasonly one half the activity of the natural factor (isolated as the crystallinebarium salt from liver) for growth of Ln. c i t r o v o r ~ m . ~ ~ It is also less activethan pteroylglutamic acid as a growth factor for Lb. casei and Strep. faecaliswhereas the natural substance has the same The fact thatthe synthetic compound is a mixture of the (+):L- and the (-):L-isomerprobably accounts for these differences. The calcium salts of the isomershave been separated, and the (-)L-form shown to have the same activity asnatural citrovorum factor and to be twice as active as the (+):L-isomer.62That Ln.citrovorum factor is more closely related than pteroylglutamicacid t o the coenzyme form of folic acid is suggested also by the greater activityFactors of the foZic acid groz@.51. E. A. Andrews and V. R. Williams, I. Boil, Chem., 1951, 193, 11.5z E. Rosenwasse:,and M. J. Boyd, Fed. Proc., 1952, 11, 277.53 D. D. Woods, Symposium sur le MCtabolisme Microbien,” p. 86, Second Int.Congr. Riochem., Paris, 1952.54 W. Shive, Vitamins a n d Hormones, 1951, 9, 75 ; Ann. Rev. Microbiol., 1952, 6, 437.65 R. H. Nimmo-Smith, J . Lascelles, and D. D. Woods, Brit. J . Exp. Path., 1948,29, 264 : J .Lascelles and D. D. Woods, ibid., 1952, 33, 288.56 J . Brockman, Jnr., B. Roth, H. P. Broquist, M. E. Hultquist, J. M. Smith, Jnr.,M. J. Fahrenbach, D. B. Cosulich, R. 1’. Parker, E. L. R. Stokstad, and T. H. Jukes,J . Anaer. Chem. SOC., 1950, 72, 4325.5 7 E. H. Flynn, T. J. Bond, T. J. Rardos, and W. Shive, ibid., 1951, 73, 1979; A.Pohland, E. H. Flynn, R. G. Jones, and W. Shive, ibid., p . 3247.5* B. Roth, M. E. Hultquist, M. J. Fahrenbach, D. B. Cosulich, H. P. Broquist,J. A. Brockman, Jnr., J. M. Smith, Jnr., R. P. Parker, E. L. R. Stokstad, and T. €3.Jukes, ibid., 1952, 74,3247. 59 J . C. Keresztesy and M. Silverman, ibid., 1951, 73,5510,6o H. E. Sauberlich, J . Biol. Chem., 1952, 195, 337.61 0. P. Wieland, B. L. Hutchjngs, and J. H. TVillams, Arch.Riochem., 1952, 40, 205.D. B. Cosulich, J. M. Smith, Jnr., and H. P. Broquist, J . Amev. Chetn. SOC., 1952,74, 4216.REP.-VOL. XLIX. 258 BIOCHEMISTRY.of leucovorin and the natural factor in overcoming inhibition of growth ofStrep. faecalis by 4-aminopteroylglutamic acid (aminopterin) 63 Likepteroylglutamic acid, leucovorin is a competitive antagonist of the analogue.With one exception, leucovorin has so far been found inactive in replacingP-aminobenzoic acid for growth of organisms requiring that compound.Ln. mesenteroides, however, utilises it in place of 9-aminobenzoic acid, whereaspteroylglutamic acid is inactive.64 Possibly, Ln. citrovorum factor may beconverted into a still more complex form before it functions in cell metabolism.Recently, strains of Strep. faecalis and Ln.citrovorum have been described,whose growth is insensitive to inhibition by 4-amino- and 4-amino-10-methyl-pteroylglutamic acid (amethopterin).65 The resistant strain of Strep. faecalisutilises the analogues in place of pteroylglutamic acid, but the variant strainof Ln. citrovorum does not respond to the analogues instead of leucovorin.Factors of the folic acid group may be concerned as cofactors in reactionsinvolving transfer of a one-carbon unit. They are involved in the synthesisof methionine, serine, histidine, and possibly other amino-acids, as well asin the formation of purines and thymine.2v30f 53, 54 The initial informationconcerning the function of these factors was provided by investigations ofthe substances able to replace them for growth of micro-organisms.Forinstance, the importance of Ln. citrovorum factor in the conversion of glycineinto serine is shown by the requirement of Ln. mesenteroides for leucovorinwhen high concentrations of glycine replace serine for growth; under theseconditions, 9-aminobenzoic acid is utilised instead of leucovorin only if incu-bation is in an atmosphere enriched with carbon dioxide.34S6* In Torulacremoris inhibition of growth by aminopterin is overcome competitively byconcentrates of Ln. citrovorum factor ; in the absence of the latter inhibitionis overcome non-competitively by a mixture of methionine, purines, andhistidine.66 The requirement of mutant strains of Saccharomyces cerevisiczfor 9-aminobenzoic acid is abolished by similar mixtures.67,The precise stage in the various syntheses at which folic acid acts has notalways been clearly shown by growth experiments.For methionine and serine,more direct evidence has come from work with deficient cell suspensions. Thus,p-aminobenzoic acid is needed for the conversion of homocysteine into meth-ionine by cell suspensions of Bact. coli deficient in that factor ; the p-carbonatom of serine may serve as a source of the one-carbon residue needed in thisreaction.6g Deficient cell suspensions of Strep. faecalis form serine from glycineand formate provided that pteroylglutamic acid or leucovorin is present.34It is probable that folic acid is concerned in the formation of the amidinecarbon in the glyoxaline ring of histidine; this has been found by isotopictechniques to arise from formate in yeast.'O In purine synthesis factors ofthe folic acid group are very probably needed for the formation of the 2-and the 8-carbon atom of the nucleus.54 The factors are involved in theutilisation of 4-aminoglyoxaline-5-carboxyamide, a possible precursor of63 H.P. Broquist, E. L. R. Stokstad, and T. H. Julres, Fed. Proc., 1951, 10, 167.64 J. Lascelles, M. J. Cross, and D. D. Woods, Biochenz. J., 1951, 49, lxvi.8 5 J. H. Burchenal. G. B. Waring, and D. J. Hutchison, Proc. SOC. Exp. Biol. N.Y.,1951, 78, 311 ; D. J. Hutchison and J. H. Burchenal, ibid., 1952, 80, 516.6 6 H . P. Rroqujst, Fed. PYOC., 1952, 11, 191.6 7 N. S. Cutts and C.Rainbow, J. Gen. Microbiol., 1950, 4, 150.6 8 S. Pomper, J . Bact., 1952, 64, 353.F. Gibwn and D. D. Woods, Biochem. J., 1952, 51, v.70 L. Levy and M. J. Coon, J. Biol. Chew., 1951, 192, 807LASCELLES BACTERIAL NUTRITION. 259purines, since the amine accumulates in cultures of Bact. coli when the effectiveconcentration of fi-aminobenzoic acid is limited by sulphonamides; 71 it isalso found in cultures of mutant strains of Bact. coli requiring fi-aminobenzoicacid, when that compound is supplied in suboptimal concentration. 72The chemistry and function of this vitamin have beenreviewed recently by Jukes and Stokstad; 73 little is known about its bio-synthesis. Vitamin B,, contains a 5 : 6-dimethylbenziminazole moietywhereas pseudovitamin B,, contains adenine instead.74 Nevertheless, bothfactors are equally active in promoting growth of mutant strains of Bact. coliand both exert the same sparing effect on the requirement of other mutantstrains for fi-aminobenzoic acid.75 Thus, the suggestion that the lattercompound is a precursor of the benziminazole portion of vitamin B,, seemsuntenable. 76 There is evidence that 4 : 5-dimethylphenylene-1 : 2-diaminemay serve as a precursor of this residue in some organisms. This isbased mainly upon the action of 4 : 5-dimethylphenylene-1 : 2-diamine inovercoming competitively growth inhibition by 4 : 5-dichlorophenylene-1 : 2-diamine. 77 The dichloro-analogue inhibits growth only of those organismswhich do not require vitamin B,,; addition of that factor does not howeverovercome the inhibition.In Lactobacillus . lactis Dorner, which requiresvitamin B,, for growth, 5 : 6-dimethylbenziminazole and 4 : &dimethyl-phenylene-1 : 2-diamine are inhibitory. 78Nutritional investigations with bacteria have suggested that vitaminB,, is concerned in the conversion of homocysteine into methionine. Mutantstrains of Bact. coli, needing vitamin B,, for growth, respond also to methio-nine but not to homo~ysteine.~~ Dubnoff has claimed, however, that suchmutants do respond to homocysteine (but not homocystine) when grownanaerobically, and suggests that one of the functions of vitamin B,, inmethionine synthesis is to keep homocysteine in the reduced state. Thesuggestions from growth experiments of the role of vitamin B,, in methionineformation have been followed by more direct experiments with deficient cellsuspensions of R,,-requiring strains of Bact. coli ; the factor is essential forthe formation of the amino-acid from homocysteine (cf.p. 258).69Vitamin B,., also appears to be concerned in the formation of nucleosides.,Purine deoxyribosides or thymidine abolish the requirement of many lacto-bacilli (e.g., Lb. Zeichmannii) for vitamin B,,; in its presence the organismscan utilise free purines, suggesting that vitamin B,, is needed for theirconversion into deoxyribosides.81 Cell extracts of some of these lactobacillicontain enzymes catalysing the transfer of the deoxyribosyl group fromnucleosides to free purines or pyrimidines. 82 Such reactions probablyaccount for the equal ability of different deoxyribosides to abolish the needfor vitamin B,,..J.Amer. Chem. Soc., 1947, 69,725.Vitamin B,,.'l W. Shive, W. W. Ackermann, M. Gordon, M. E. Getzendaner, and R. E. Eakin,73 T. H. Jukes and E. L. R. Stokstad, Vitamins and Hormones, 1951, 9, 1 .74 H. W. Dion, D. G. Calkins, and J. J. Pfiffner, J . Amer. Chenz. SOC., 1952, 74, -1108.7 6 B. D. Davis, J . Bact., 1952, 64, 432.7 8 Idem, ibid., 1951, 62, 221.79 B. D. Davis and E. S. Mingioli, ibid., 1950, 60, 17.72 J. S. Gots and E. C . Chu, J . Ract., 1952, 64,537.7 7 D. W. Woolley, J . Exp. Med., 1951, 93, 13.D. Hendlin and M. H. Soars, .I. Bact., 1951, 62, 633.J. W: Dubnoff, Arch. Biochem., 1952, 37, 37.E. Kitay, W. S. McNutt, and E.E. Snell, J . Bact., 1950, 59, 727; E. Kitay andE. E. Snell, ibid., 1950, 60 ,49. W. S. McNutt, Biochem. J., 1952, 50, 384260 BIOCHEMISTRY.Higher forms of B-group vitamins. Some organisms fail at a stage in theconversion of a free B-group vitamin into its coenzyme form and consequentlyrequire the latter or a precursor (more complex than the free vitamin) forgrowth. Such observationsmay provide clues to the intermediates in the synthesis of coenzyme formsfrom the free vitamins. With most organisms so far studied, however, theOrganisms repiring higher forms of B-group vitamins.Examples of these are shown in the Table.Free factor Higher formNicotinic acid . . . Di- or tri-phosphopyridineThiamine ...... , .. Thiamine pyrophosphatePantothenic acid PantethinenucleotideVitamin B, , .. . . . Pyridoxal or pyridoxaminephosphatesa-Lipoic acid . , . Lipothiamide pyrophosphateOrganisms requiring ReferenceHaemophilus para- aHaem. pisciurn bNeisseria gonorrhoeci? cLb. bulgaricus and 26Lb. lactis Dorner dLb. helveticus and re- ehigher forminfluenzrerelated organismslated organismsLn. mesenteroides fBact. coli (mutant) 21( a ) A. Lwoff and M. Lwoff, Proc. Roy. Soc., 1937, 8, 122, 352. ( b ) P. J. Griffin,Avch. Biochem., 1951, 30, 100. (c) C. E. Lankford and P. K. Skaggs, ibid., 1946, 9,265. ( d ) D. Hendlin, M. C. Caswell, V. J. Peters, and T. R. Wood, J . Biol. Chem.,1950, 186, 647. ( e ) W. S. McNutt and E. E. Snell, ibtd.., 1950, 182, 557. (f) V. H.Cheldelin, A.P. Nygaard, H. A. Kornberg, and R. J. Williams, J. Bact., 1951, 62, 134.more complex forms of these compounds are less active or are inactive inpromoting growth in place of the free factors. For example, coenzyme Adoes not replace pantothenic acid for growth of many yeasts and lactobacilli,and it has only slight activity for one strain of Lb. acidophilzcs which respondsto pantothine; the latter compound is less active than pantothenic acid asa growth factor for some lactobacilli and inactive in strains of yeast.26Coenzyme A , however, promotes more rapid growth of A cetobacter suboxydansthan pantothenic acid.83 Satisfactory explanations are yet to be found toaccount for the differences among bacteria with respect to their ability torespond to higher forms of the vitamins.Amino-acids and Peptides-Nutritional research with micro-organisms,particularly with induced mutant strains, has thrown light upon the inter-mediates in the synthesis of many amino-acids.Aromatic amino-acids.Davis 85 has provided strong evidence thatshikimic acid (V) is an intermediate in the synthesis of the aromatic meta-bolites , tryptophan , tyrosine , phenylalanine, 9-aminobenzoic acid, andp-hydroxybenzoic acid. Quintuple mutant strains of Bact. coli were iso-lated which respond to a mixture of those compounds or to shikimic acidalone. Other strains, unable to utilise shikimic acid, accumulate it in theculture fluid. Further work along these lines has shown that Ei-dehydro-quinic acid (111) and 5-dehydroshikimic acid (IV) may be precursors of shiki-mic acid.84 The suggested intermediates still contain the ring structurewhich may arise directly from glucose ; labelled shikimic acid is formed by a83 G.D. Novelli, R. M. Flynn, and F. Lipmann, J . Riol. Chem., 1949, 177, 493.84 B. D. Davis, “ Symposium siir le Mktabolisme Microbien,” I>. 32, Second Int.C o w . Biochem., Paris, 1962; J. Bact., 1962, 64, 729, 749.85 Idem, J . Biol. Chenz., 1951, 191, 315LASCELLES : BACTERIAL NUTRITION. 261quintuple mutant strain of Bact. coli grown with [1-14C]gl~~ose.86topically labelled acetate, formate, or carbon dioxide are not incorporated.Iso-CO,H II IiCO,H II II I(111) (IV) (V)HO CO,HH,C CH,/C,,CH*OH I 1 --+ HC,cGCH.OH --3A H/C\CH,\ /HC CH, AHo-HC\&cH*oHOH0 CH 0OH OHThe aromatic amino-acids may also arise from a common precursor in Lb.arabinosus.87 Strains which grow in the absence of tyrosine give rise tovariants which have also lost their requirement for phenylalanink.Suchvariants readily become independent of tryptophan, whereas cultures of theparent organism (requiring all three amino-acids) do not show this tendency.Studies with mutant strains of Bact. coli have suggested thataa'-diaminopimelic acid is an intermediate in lysine synthesis.88 Somelysineless-mutants accumulate diaminopimelic acid, which replaces lysinefor growth of other strains. Cell suspensions of mutants, which utilise thiscompound for growth, contain diaminopimelic acid decarboxylase and canthus convert the precursor into lysine (in turn degraded by lysine decarboxy-lase to cadaverine and carbon dioxide). Wild type strains of Bact.coli alsocontain this enzyme. On the other hand, cell suspensions of mutant strains,unable to utilise diaminopimelic acid for growth, are also unable to decarb-oxylate it ; this suggests that their failure to synthesise lysine is due to theabsence or inactivity of the decarboxylase. In Newospora, a-aminoadipicacid is probably an intermediate in lysine synthesis.89 This compound isnot utilised by lysineless-mutants of Bact. coli, nor is diaminopimelic acidutilised by Neurospora mutants. This suggests that the pathways of lysinesynthesis in Bact. coli and Neurospora may differ.Sulphur-containing amino-acids.The synthesis of methionine withintermediate formation of cysteine, cystathionine (formed by condensationof homoserine and cysteine), and homocysteine has been well established bynutritional studies with mutant strains of Neurospora,m Bact. C O Z ~ , ~ ~ andBacillus s ~ b t i l i s . ~ ~ Similarly, methionine formation by the pathogens,Salmonella typhim.uri~rn,~~ Brucella suis,04 and Pastewella p e ~ t i s , ~ ~ appearsto involve the same intermediates. The last-named organism normallyneeds both cysteine (replaced by thiosulphate, sulphite, or sulphide) andmethionine for growth ; cystathionine or homocystine replaces methionine.Lysine.8 6 H. Shigeura and D. B. Sprinson, Fed. PYOC., 1952, 11, 286.D. E. Atkinson and S.W. Fox, Avch. Biochem., 1951, 31, 212.88 D. L. Dewey and E. Work, Nature, 1952, 169, 533; €3. D. Davis, ibid., p. 634.89 H. K. Mitchell and M. €3. Houlahan, J . B i d . Chem., 1948, 174, 883.H. J. Teas, N. H. Horowitz, and M. Fling, ibid., 1948, 172, 651.91 J. 0. Lampen, R. R. Roepke, and M. J. Jones, Arch. Biochem., 1947, 13, 55.92 H. J. Teas, .I. Bact., 1950, 59, 93.93 H. H. Plough, H. Y . Miller, and M. B. Berry, Puoc. Nut. Acad. Sci., 1951, 37, 640.94 L. J Rode, C. E. Lankford, and V. T. Schuhardt, J . Bact., 1951, 63, 571 : C. E.Lankford, L. J. Rode, and V. T. Schuhardt, PYOC. SOC. Exp. Biol. N.Y., 1952, 80, 727.B6 E. .Englesberg, J . Bact., 1952, 63, 675262 BIOCHEMISTRY.A mutant strain is able, however, to utilise cysteine, though not methionine,as sole Source of sulphur.These results and similar findings with mutantstrains of Bact. coli 96 and S. typhimurium 93 suggest that the reactions lead-ing to methionine synthesis from cysteine are not all reversible. Mostcysteineless-mutants which have been described also utilise methionine (orcystathionine or homocysteine) as sole source of sulphur. Whether or notcysteine is formed from methionine with intermediates differing from thosein the transformation of cysteine to methionine must await further work.In BY. suis 94 homocystine (or homocysteine) promotes growth in a sulphur-free medium only in the presence of trace amounts of methionine, aloneinsufficient to give measurable growth. Some commercial samples ofhomocystine contain sufficient methionine to give this effect, the cause ofwhich is unknown.isoLeucine and valine.The properties of mutant strains of Neurospora,Bact. coli, B. szcbtilis, and S. typhimurium have indicated that ap-dihydroxy-p-methylvaleric acid and ap-dihydroxy-p-methylbutyric acid, as well as thecorresponding a-keto-acids, are precursors of isoleucine and valine, respec-t i ~ e l y . ~ ~ The dihydroxy-acids accumulate in cultures of a strain of Neuuro-spora needing both amino-acids for They are utilised by somestrains of Bact. coli responding to isoleucine and valine, as are the correspond-ing a-keto-acids, whereas with other strains only the keto-acids replace theamino-acids for g r o ~ t h . ~ ~ ~ ~ ~ Another strain of Bact. coli which has anabsolute requirement for isoleucine and a partial one for valine (evident onlyunder semi-aerobic conditions) accumulates the keto-acid analogues of bothisoleucine and ~ a l i n e .~ ~ The results suggest that isoleucine and valine areformed as follows :Precursors -+ dihydroxy-acid analogues -+ keto-acid analogues --+ isoleucine, valine.The immediate precursors of the carbon chains of these amino-acids are notknown, though work with mutants has suggested that D-threonine anda-amino- and a-keto-butyric acids may 99 Experiments with iso-topically labelled acetate have shown that this compound is a precursor inNeurospora.lm The inhibitory inter-relationships of isoleucine and valineare discussed elsewhere.Proline. Vogel and Davis,lol working with mutant strains of Bact.colirequiring proline, have shown that the amino-acid may be formed fromglutamic acid with intermediate formation of glutamic acid y-semialdehyde.This compound is accumulated by one such mutant and is utilised by anotherstrain, which also responds to either proline or glutamic acid. Glutamicacid is also a precursor of proline in PenicilZium.102Ornithine, citrulline, and arginine. The synthesis of arginine from glut-amic acid with intermediate formation of ornithine and citrulline has beenO 6 S. Simmonds, J. Biol. Chem., 1948, 174, 717.O 7 E. A. Adelberg, J. Bact., 1961, 81, 365; H. E. Umbarger and E. A. Adelberg, J.Biol. Chem., 1951, 192, 883.98 E. A. Adelberg and E. L. Tatum, Arch. Biochm., 1950, 89, 235; E. A.Adelberg,D. M. Bonner, and E. L. Tatum, J . Biol. Chem., 1951, 190, 837.sg H. E, Umbarger and J. H. Mueller, ibid., 1951, 180, 277; H. E. Umbarger andB. Magasanik, ibid., p. 287.loo E. L. Tatum and E. A. Adelberg, J . Biol. Chem., 1951, 190, 843.101 H. J. Vogel and B. D. Davis, J . Amer. Chem. SOL, 1952, 74, 109.101 D. Bonner, Cold Spring Harbor Symp. Quant. Biol., 1946, 11, 14LASCELLES : BACTERIAL NUTRITION. 263established by work with mutant strains of Neurospora lo3 and PePzicilZium.102Evidence for a similar mechanism in Lb. arabinosus has been obtained byHood and Lyman.lo* This organism grows in the absence of arginine ifincubated in an atmosphere enriched with carbon dioxide. Under theseconditions the requirement for glutamic acid is increased beyond thatneeded for growth with arginine present.In a medium containing methion-ine sulphoxide (which prevents conversion of glutamic acid into glutamine lo5)growth is promoted by glutamine, or more effectively by either arginine orcitrulline, but not by ornithine or carbamyl-L-glutamic acid. It was concludedthat glutamine is concerned in citrulline synthesis as a donor of ammonia.It is well known that many organisms grow more rapidly onmedia containing partial hydrolysates of proteins than on free amino-acids.Woolley has shown that peptides are largely responsible for the activity of" strepogenin " concentrates (prepared from partially hydrolyzed proteins)in stimulating growth of Lb. casei and other organisms.lo6 In most casesstudied synthetic di- and tri-peptides are less active than the free amino-acids in promoting growth, and their activity seems to be due to hydrolysisto their component amino-acids.107 Marshall and Woods log have found,however, that L-tyrosyl-L-tryptophan and L-tryptophanyl-L-phenylalanineare more active than tryptophan in overcoming inhibition of growth of Strep.faecalis and StaphyZococcus aureus by 4-methyltryptophan. In the presenceof the dipeptides, growth is insensitive to the inhibitor, whereas tryptophanacts competitively in overcoming the inhibition.Tyrosine and phenyl-alanine are also competitive antagonists though less active than tryptophan.In the absence of the inhibitor the peptides have the same growth-promotingactivity as the free amino-acids.One interpretation of these results is thatphenylalanine and tyrosine are concerned in the utilisation of tryptophan ;these reactions are inhibited by $-methyltryptophan which competes withtryptophan. Growth inhibition by P-2-thienylalanine is also overcomecompetitively by tyrosine, phenylalanine, or tryptophan (though less active),suggesting that this analogue inhibits similar reactions. Tyrosine peptides aremore active than free tyrosine in promoting growth of Strep. faecalis in mediacontaining vitamin B,.lo9 Without this factor (the medium containedD-alanine and all the necessary amino-acids except tyrosine) L-1eucyl-L-tyrosine has the same activity as tyrosine. The experimental evidenceindicates that tyrosine decarboxylase, active only in cells grown with vitaminB,, decomposes free tyrosine, but does not attack tyrosine produced byhydrolysis of the peptides.Glutamine plays an important role in bac-terial metabolism (reviewed by Waelsch 110) and is essential for growth ofhaemolytic streptococci.lll It is a non-competitive antagonist of manyPeptides.Glutamine and asparaghe.103 A.M. Srb and N. H. Horowitz, J . Biol. Chem., 1944, 164, 129.lo' D. W. Hood and C. M. Lyman, ibid., 1950, 185, 39.lo6 H. Waelsch, P. Owades, H. K. Miller, and E. Borek, ibid., 1946, 166, 273.lo6 H. Sprince and D. W. Woolley, J . Amer. CAem. SOC., 1945, 67, 1734; D. W.lo7 J. S. Fruton and S. Simmonds, Cold Spring Harbor Sym?. Quad. Biol., 1949. 14, 55.lo8 J. H. Marshall and D. D. Woods, Biochem.J . , 1952, 51, ii.loS H. Kihara, 0. A. Klatt, and E. E. Snell, J . Biol. Chem., 1952, 197, 801.110 H. Waelsch, Adv. Enzymology, 1952, 13, 237.ll1 H. McIlwain, P. Fildes, G. P. Gladstone, and B. C. J. G. Knight, Biochem. J.,Woolley, J . Biol. Chenz., 1948, 172, 71.1939, 33, 223264 BIOCHEMISTRY.inhibitory analogues of glutamic acid.lo5, 112 Its function is unknownthough it may play a part in citrulline synthesis.lO4 In Lb. arabinosusglutamine is more active than glutamic acid in the early stages of growth;the dipeptides glutaminylglycine and glycylglutamic acid, have the sameactivity as g1~tamine.l~~ On the other hand, asparagine is much less activethan aspartic acid for this organism (grown in the absence of carbon dioxide)and for Ln.mesenteroides, but the glycine dipeptides of asparagine haveactivity almost equal to that of aspartic acid. The peptides are morereadily deaminated by cell suspensions than the free amide, suggesting thatthey may give rise to aspartic acid by deamination followed by hydrolysis.114Nucleic Acid Derivatives.-Research with micro-organisms has also pro-vided information on the mechanism of synthesis of purines and pyrimidinesand their utilisation (see review by Christman l15).Purines. The observation that 4-aminoglyoxaline-5-carboxyamide ac-cumulates in bacterial cultures when the availability of P-aminobenzoic acidis limited (see p. 258 ; refs. 71 and 72) .first indicated that it might be a pre-cursor of purines. It also accumulates in cultures of a purineless-strain ofBact.coli, and replaces purines (though it is less active) for growth of anothermutant strain.1l6 Glycine stimulates production of the a~l?ine.~lr 72 Thisamino-acid, formate, and carbon dioxide have been found by isotopic tech-niques to be precursors of purines in yeastJ117 and Bact. coli 11* and Bacteriumprodigiosum,llg as in animals.lmPyrimidines. That orotic acid (4-carboxyuracil) is closely related to anintermediate in pyrimidine synthesis is suggested by its activity in replacinguracil for growth of mutant strains of Neurospora.121$122 It is also accumu-lated by other .pyrimidineless-mutants of this organism, but there is evidencethat it is not a normal intermediate in Neurospora.122 Orotic acid is essentialfor growth of a strain of Lb.bulgaricus; lZ3 ureidosuccinic acid replaces it(though at a higher concentration), and may be a precursor.124 Uracil isnot utilised for growth of this organism ; nevertheless isotopically labelledorotic acid and ureidosuccinic acid are both incorporated into the uracil ofthe cell nucleic acids.125 Clarification of the role of orotic acid in pyrimidinemetabolism must await more detailed knowledge of the mechanism of incor-poration of the free bases into nucleic acids, if indeed the free bases areintermediates.Some micro-organisms are unable to utilisefree purine or pyrimidine bases and require nucleosides or nucleotides forNucleosides and nucleotides.l12 P. Ayengar and E. Roberts, Proc. SOC. Exp. Biol. N.Y., 1952, 79, 476.113 H.K. ,91iller and H. WaeZsch, Arch. Biochem., 1952, 35, 184.114 Idem, Nature, 1952, 169, 30.116 J. Gots, Arch. Biochmz., 1950, 29, 222.117 M. Edmonds, A. M. Delluva, and D. \%'. Wilson, J . Biol. Chem., 1952, 197, 251.Il8 A. L. Koch, F. W. Putnam, and E. A. Evans, Jnr., ibid., p. 105.119 D. J. McLean and E. F. Purdie, ibid., p. 539.120 G. R. Greenberg, ibid., 1951, 190, 611.121 H. S. Loring and J. G. Pierce, ibid., 1944, 153, 61.lZ2 H. K. Mitchell, M. R. Houlahan, and J. F. Nyc, ibid., 1948, 172, 525.123 L. D. Wright, J. W. Huff, H. R. Skeggs, K. A. Valentik, and D. K. Bosshardt,1. Amer. Chem. SOC., 1950, 72, 2312; 0. P. Wieland, J. Avener, E. M. Boggiano, N.Bohonos, R. L. Hutchings, and J . H. Williams, J . Biol. Chem., 1950, 186, 737.D. S.Spicer, K. V. Liebert, L. D. Wright, and J. W. Huff, PPOC. SOC. Exp. Riol.N.Y., 1952, 79, 587.lZb L. D. Wright, C. S. Miller, H. R. Skeggs, J. W. Huff, L. L. Weed, and D. W.Wilson, J , Amer. Chem. SOC., 1951, 73; 1898.111 A. A. Christman, Physiol. Rev., 1952, 32, 303LASCELLES : BACTERIAL NUTRITION. 265growth, suggesting that these are intermediates in the synthesis of nucleicacids (see also p. 259 ; ref. 81). Lb. gayonii, for instance, requires adenylic,guanylic, uridylic, or cytidylic acid ; guanosine (the only nucleoside tested)is inactive.126 Recently, a strain of Strep. faecalis has been describedwhich needs a pyrimidine nucleoside or nucleotide for rapid growth;uridine is the most active of the compounds tested, whereas purine nucleo-sides and nucleotides are inactive.lZ7 Uridine is also more active thanuracil in promoting growth of a mutant strain of Neurospora.121 Merrifieldand Woolley 128 have evidence that Lb.helveticus may incorporate uracildirectly into a dinucleotide without intermediate formation of a mono-nucleoside or nucleotide. Certain dinucleotides (isolated from acid-hydrolys-ates of yeast nucleic acid) and their dephosphorylated derivatives replaceuracil for growth of this organism, whereas pyrimidine and purine mono-nucleotides and 'nucleosides are inactive. The smallest unit common tothe active compounds is cytidine-5' phosphate diesterified at the 3'(or 2')-position of another nucleoside ; similar derivatives of uridylic acid were nottested.Inhibitory Interrelationships of Growth Factors.-Many examples areknown of antagonism between essential metabolites, particularly betweenamino-acids of similar structure where competition for an enzyme mayoccur.129 Another type of inhibition, observed frequently in research withbiochemical mutants, may occur when an intermediate in the synthesis ofone essential metabolite may prevent the utilisation of a precursor of an-other metabolite. An inhibition of this type has been shown to account forthe requirement of a mutant strain of Bact. coli for both isoleucine and~ a l i n e . ~ ~ This strain cannot form isoleucine from its a-keto-acid analogue,a-keto-P-methylvaleric acid ; this compound accumulates and inhibits theconversion of the corresponding analogue of valine (a-keto-p-methylbutyricacid) into valine.In mutants of Neurospora with the same double require-ment for isoleucine and valine, the dihydroxy-acid analogue of isoleucineaccumulates (not the keto-acid analogue as postulated by Bonner I3O) andinhibits utilisation of the corresponding analogue of ~ a l i n e . ~ ' An interestingexample of antagonism has been described by Kihara et They foundthat alanylpeptides are responsible for the activity of enzymic digests ofcasein in replacing vitamin B, for growth of Lb. casei ; a number of syntheticL-alanylpeptides have the same effect as the digests. For replacement, D-alanine has also to be added to the medium, and this compound inhibitsutilisation of L-alanine, but not that of the L-alanylpeptides.The peptidesappear, therefore, to be required for growth in the absence of vitamin B,because utilisation of free L-alanine is prevented by D-alanine, present inexcess under the experimental conditions.Another example of antagonism has been shown by Rabinowitz andSnell 132 with Saccharomyces carlsbergensis. This organism grows in thelas B. L. Hutchings, N. H. Sloane, and E. Boggiano, J . Biol. Chem., 1946, 162, 737.lZ7 H. A. Hoffmann and P. L. Paveck, J . Amer. Chem. SOC., 1952, 74, 344.12* R. B. Merrifield and D. W. Woolley, J . Baol. Chern., 1952, 197, 521.129 E. L. Tatum, Fed. Proc., 1949, 8, 511.130 D. Bonner, .J. BioZ. Chem., 1946, 166, 545.H. Kihara, W. G. McCullough, and E. E. Snell, ibid., 1952, 197, 783; 13.Kiharaf . C. Rabinowitz and E. E. Snell, Arch. Rzochm~, 1951, 33, 472.and E. E. Snell, ibid., p. 791266 BIOCHEMISTRY.absence of both vitamin B, and thiamine ; in a medium containing thiamine,however, pyridoxine (or derivatives) becomes essential for growth. Thereason for this is not known.General.-Substances which do not come under the above headings, butwhich have been found to be growth factors for some micro-organisms includeP-hydroxybenzoic acid, putrescine, and " coprogen." p-Hydroxybenzoicacid is a component of a mixture of aromatic compounds needed for growthof mutant strains of Bact. ~ o l i . ~ ~ ~ ~ Its effect on growth is most marked inmedia containing aspartic acid. It also overcomes inhibition of growth ofBact. coli by high concentrations of 9-aminobenzoic acid.133 Replacementexperiments have suggested that P-hydroxybenzoic acid is concerned a t astage in the conversion of cysteine into methionine and in lysine synthesks4Putrescine is essential for growth of Haemophilus Parainjuenza? ; its functionis unknown.lN A crystalline compound (" coprogen ") isolated from dung,is needed for growth of P i l o b o h spp. High concentrations of haeminreplace this substance, which contains iron and may possibly be a precursorof iron porphyrins.135 A similar compound, active for Pilobolus, has beenobtained from the cells of a rust fungus when grown under conditions whichresult in a high production of cytochrome c.136J. L.3. VITAMINS.Nomenclature.-The Commission for the Reform of Nomenclature inBiological Chemistry of the International Union of Pure and Applied Chemis-try has adopted the following names :Present nameVitamin D, or calciferol ....................................Vitamin D3 ......................................................Vitamins E ......................................................Vitamin B,, aneurin, or thiamineVitamin B,, or riboflavin ....................................Vitamin PP, niacinamide, or nicotinamideVitamins possessed of B,, activity ........................Vitamin B,, ...................................................Vitamin B,,, .......................................................................................Vitamin B12e ...................................................Vitamin C or ascorbic acid .................................Name adoptedErgocalciferolCholecalcif erola-, /3-, and y-TocopherolThiamineRiboflavinNicotinamideCobalamin (collective name)CyanocobalaminH ydroxocobalaminNitrosocobalamin *Ascorbic acid* This name will probably need altering to Nitritocobalamin ; cf.Lester-Smith,Biochem. J., 1952, 50, xxxvi.-ED.The names panthothenic acid, biotin, 9-aminobenzoic acid, and cholineNames of other vitamins are under discussion.Fat-soluble Vitamins.-Because of limitations of space, attention islimited to the fat-soluble vitamins, with the exception of vitamin A, whichhas recently been reported on.l*A new international standard hasremain unchanged.Vitamins D.-Standards and assay.135 B.D. Davis, J . Exp. Med., 1951, 94, 243.134 E. J. Herbst and E. E. Sndl, J . Biol. Chem., 1949, 181, 47.135 C. W. Hesseltine, C. Pidacks, A. R. Whitehill, N. Bohonos, B. L. Hutchings. andJ. H. Williams, J . Amer. Chem. SOC., 1952, 74, 1362. 136 J . B. Neilands, ibid., p. 4846.la R. A. Morton, Ann. Reports, 1949, 66, 244.Biochem. J . , 1952, 52, 1 ; J., 1951, 3526DATTA : VITAMINS. 267been adopted, in which the international unit is 0.025 pg. of crystallinecholecalciferol.2 This has the advantage over the League of Nations stan-dard based on ergocalciferol that cholecalciferol is identical with the naturalvitamin and is equipotent in mammals and birds.An enormous effort has been made to improve methods of assay, and todate the most useful methods remain biological rather than chemical.Ratgrowth on Steenbock and Black’s rachitogenic diet can be improved by theaddition of 0.5% of l y ~ i n e . ~ The A.O.A.C. basal rachitogenic diet for chicksdoes not appear to be susceptible to much impr~vement.~ The use of thechick toe-ash rather than the tibia-ash has been advocated as an assay~riterion.~ The B.S.I. curative test has been compared with, and foundsuperior to, the A.O.A.C. preventive test.6 New bioassays suggested includethe uptake of injected 32P by the paws of rats,7 and the level of chick-plasmaalkaline phosphatase. * A microbiological assay for pure ergocalciferol andcholecalciferol has been de~cribed.~Among the physicochemical methods investigated are the colorationswith antimony trichloride,lO- l1 dichlorohydrin,12, l3 and iodine trichloride, l4 ’a modified Pettenkofer’s reaction,15 and the “ carbenium salts.” l6 Theabsorption spectra of the vitamins D have been investigated as a method ofassay.11, l7 In order to remove interfering substances chemical separation l3and chromatographic fractionation 1 1 9 1 4 3 18 have been used.Chemistry. Syntheses of 7-dehydrocholesterol, l 9 and the preparationand separation of a complex of cholecalciferol and cholesterol which isreputed 20 more stable during processing have been described ; biologicallyactive alkyl ethers of the vitamins D have been prepared from metallicvitamin derivatives.21 Pro-ergocalciferol22 has been isolated as a dinitro-2 “ Expert Committee on Biological Standardization.Rept. Sub-committee on9 P. S. Francis, J . Assoc. Off. Agric. Chem., 1947, 30, 364.4 C. I. Bliss, ibid., 1946, 29, 396; B. B. Migicovslcy and A. R. G. Emslie, Avch.5 C. I. Bliss, Poultry Sci., 1945, 24, 534; C. I. Bliss and G. H. Kennedy, J . Assoc.6 J. A. Campbell and A. R. G. Emslie, Poultry Sci., 1947, 26, 255.7 R. H. Synder, H. J. Eisnerj and H. Steenbock, J . Nutrzt., 1951, 45, 305.8 I. Motzok, Biochem. J . , 1950, 47, 196.10 F. W. Lamb, A. Mueller, and G. W. Beach, Ind. Eng. Chem. Anal., 1946, 18, 187;A. Mueller, ibid., p. 214.11 D. T. Ewing, M. J. Powell, R. A. Brown, and A. D. Emmett, Analyt. Chenz., 1948,20, 317; J . B. de Witt and M. X. Sullivan, Ind. Eng. Chern. Anal., 1946, 18, 117; I.N.Garkina and V. N. Bukin, Biokhim., 1951, 16, 176.l2 A. E. Sobel, A. M. Mayer, and B. Kramer, Ind. Eng. Chem. Anal., 1945, 17, 160;J. A. Campbell, Analyt. Chem., 1948, 20, 766.l3 E. V. Rouir and G. Pirlot, Bull. SOC. Chim. biol., 1947, 29, 1005.l4 J. Green, Biochem. J., 1951, 49, 36, 45, 54; 1952, 51, 144.l6 V. Villar Palasf, Nature, 1947, 160, 88.l6 H . Schaltegger, Helv. Chkm. Ada, 1946, 29, 285.1’ W. Huber, G. W. Ewing, and J. Kriger, J . Amer. Chem. SOC., 1945, 67, 609; G.Pirlot, Analyt. Chem. Acta, 1948, 2, 744.l8 A. Fujita and M. Aoyama, J . Biochem., Japan, 1950, 37, 113; H. E, Cox, Analyst1950, 75, 521.l9 J. A. K. Buisman, W. Stevens, and J . v. d. Wet, Rec. Trav. chim., 1947, 66, 8 3 ;A. E. Bide, H. B. Henbest, E. R. H. Jones, R.W. Peevers, and P. A. Wilkinson, J., 1948,1783; J. Redel and B. Gauthier, Bull. SOC. chim., 1948, 607.2o J. Waddelland W. W. Waessner, U.S.P. 2,410,25411946.f 2 L. Veliuz and G. Amiard, Compt. rend., 1949, 228, 692, 853, 1037.Fat-soluble vitamins,” W.H.O. Tech. Rept. Ser. No. 3, 1950, Geneva.Biochem., 1947, 13, 175, 185.Off. Agric. Chem., 1950, 33, 860.E. Kodicek, ibid., 1950, 46, xiv.N. A. Milas, U.S.P. 2,410,893/1946268 BIOCHEMISTRY.benzoate which differs from that of ergocalciferol in its crystalline form,optical rotation, and extinction at 265 mp; it is unstable to heat and isconverted into ergocalciferol at temperatures such as are reached whensolutions of irradiated ergosterol are concentrated. Ergocalciferol is, how-ever, the predominating isomer at equilibrium.A new provitamin D,norcholesta-5 : 7-dien-3p-01,~~ has been described ; unlike other such sub-stances it possesses a saturated unbranched side-chain. X-Ray analysis =of ergocalciferol indicates that C(5), C(s), C(,), and c(8) lie in a straight chain.Infra-red spectra 26 indicate a trans-configuration of the C(22)-C(23) doublebond in ergocalciferol, ergosterol, ergosteryl acetate, stigmasterol, andst igmasteryl acetate.Very little progress has been made in determining the exactmode of action of the vitamins D. That vitamin D increases the absorptionof calcium and phosphorus from the gut has been shown by a number ofworkers; in man by balance experiments 26 an increased absorption of allkinds of phosphorus with a concomitant increased retention of calcium isfound on administration of vitamin D.The absorption of calcium fromisolated loops of intestine during 24 hours is greater in rats given vitamin Dthan in controls, and absorption appears more rapid in the upper part of thesmall intestine than in the lower part.27 The vitamins D appear to enhancethe absorption of phosphorus from the gut when the latter is present asphytin,26* 287 29 though it had no effect on the phytase activity of the gut 28and could not increase the absorption of phytate phosphorus as much asthat of the inorganic element.29 It is concluded that the best method ofcombating a high level of phytate in the diet is by administration of calciumas well as vitamin D.29 The use of *5Ca and 32P a s tracers has also failed toyield mnch information about the mode of action of vitamins D.There areconsiderable difficulties with these techniques in that these elements appearto exchange very rapidly with the bone salt which makes interpretation ofresults hazardous. Vitamin D increases the absorption and skeletal deposi-tion of 45Ca and s9Sr 30 in rats weaned on to a rachitogenic diet for 15-20days. The rate of turnover of 45Ca in bone is increased by vitamin D as isthe absorption from the small intestine,31 absorption being demonstratedfrom both proximal and distal parts. In chicks more *%a was incorporatedin bone with vitamin D when the element was fed but no difference was foundwhen it was injected.32In vitamin D deficiency, the crystal structure of bone is reported to bedisoriented as shown by X-ray studies ; 33 on the other hand the mechanicaland structural properties of bone in rats on rachitogenic diets are reported toPhysiology.23 C.G. Alberti, B. Camerino, L. Mamoli, Helu. Chim. Acta, 1949, 32, 2038; 1950, 33,z 5 J. H. Turnbull, D. H. Whiffen, and W. Wilson, Chem. and Iutd., 1950, 53, 626.26 K. Wang, S. H. Liu, H. I. Chu, T. F. Yii, H. C. Chao, and H. C. Hsu, Chinese Med.27 R. Nicolaysen, Acta fdzysiol. Scand., 1951, 22, 260.28 R. R. Spitzer, G. Maruyama, L. Michaud, and P. H. Phillips, J . Nutrit., 1948,Sir E. Mellanby, J . Physiol., 1949, 109, 488.30 D. M. Greenberg, J . Biol. Chem., 1945, 157, 99.31 H. E. Harrison and H. C. Harrison, J . Bid. Chem., 1951, 188, 83; 1950, 185, 857.32 R.B. Migicovsky and A. R. G. Emslie, Arch. Biochem., 1949, $0, 325; 1950, $38, 324.33 C. 1. Reed and B. P. Reed, Amer. J . PhysioE., 1945, 143, 413.229. 24 D. Crowfoot and J. D. Dunitz, Nature, 1948, 162, 608.J . Wash., 1944, 62, 1.35, 185DATTA : VXTAMINS. 269be normal except that the strength is low.= The local effect of ergocalciferolon bone has been investigated by implantation of pellets of the vitamin onpieces of parietal bone grafted intracerebrally in mice. After 14 days thereis diffuse re-absorption of bone. Ergosterol, cholesterol, and cestradiol wereinactive.35 Vitamin D is reported to improve healing of experimentalfractures.3QA possible site of conversion of cholesterol into procholecalciferol is thegut.It is reported that in the lining of the small intestine of the guineapig, the rat, and the ox there is a sterol having an ultra-violet absorptionspectrum characteristic of the pro-cholecalciferols. In the guinea pig it isconcentrated in the mucosa and lamina propria of the duodenum. It per-sisted after 24 hours’ fasting and 2 weeks on a diet of low sterol content. Onadministration of cholesterol, spectroscopically free from pro-cholecalciferol,the amount of the provitamin in the gut wall a t first increased, later returningto normal while the amount in the liver increased. It is concluded that7-dehydrocholesterol may be formed in the gut by dehydrogenation ofcholesterol.Rickets. There was no evidence of an increase in rickets in Great Britainduring the last war.The incidence of rickets was reduced with longerbreast-feeding. The percentage of children with radiological rickets who hada t some time received cod-liver oil was however high.38 The occurrence ofrickets in more than half of a group of 118 premature infants leads to thesuggestion that human milk cannot satisfy the phosphorus req~irement,~~rickets not being prevented by vitamins D alone. The use of the serumalkaline phosphatase level as a diagnostic criterion for rickets is suggested.MThe prophylaxis of rickets requires more vitamin D than had been thought.Study of the prevention of radiological rickets in infants suggests an intakeof 1500-3000 i.u. per day; 41 from data on the maximal absorption of calciumand phosphorus from the gut an intake of 250-300 i.u.per day42 appears.to be adequate. It is also suggested that ergocalciferol is only half as potentin infants as cholecalciferol, in terms of international units.43 Massivedosage of vitamin D has been used successfully in prophylaxis of rickets ; 423 44the preferred dose is 600,000 i.u. (15 mg.), the protection lasting for 4-6months.The use of vitamin D in massive doses in the treatment of cutaneoustuberculosis has been popular in recent years,45 but doubt has beenNo toxic effects were noted.84 G. H. Bell, J. W. Chambers, and I. M. Dawson, J . Physiol., 1947, 106, 286.35 N. A. Barnicot, J . Anat., 1951, 85, 120.36 D. H. Copp and D. M. Greenberg, J . Nutrit., 1945, 29, 261; M. Mourgue, J .Physiol.path. gen., 1939-1940, 37, 1269.37 M. Scott, J . Glover, and R. A. Morton, Nature, 1949, 163, 530; M. Glover, J.Glover, and R. A. Morton, Biochenz. J., 1952, 51, 1.3* Brit. Pediatric Assoc. “ The Incidence of Rickets in War-Time,” Min. of HealthRep. Pub. Hlth. and Med. Subjects, No. 92, 1944, H.M.S.O., London.39 G. V. Sydow, Acta Pczdiat., €946, 33, Suppl. 2, p. 1; 1948, 35, Suppl. 1, p. 169.40 J. D. Barnes, R. Munlrs, and M. Kaucher, J . Pediat., 1944, 24, 159; Y . Raoul andA. Vinet, Bull. SOC. Cham. biol., 1941, 23, 205.I1 D. Krestin, Arch. Dis. Childhood, 1945, 20, 28.42 R. Houet, Ann. Pediat., 1946, 167, 225.I4 D. Krestin, Lancet, 1945, I, 781 ; T. Johnsson, Acta Pediat., 1944-1945, 32, 473 ;J. Charpy, Brit. J . Derm. Syfih., 1948, 60, 121; S.Lanholt, ibid., p. 132.; G. B.43 Idem, ibid., 1949, 172, 28.G. Klackenberg, ibid., p. 508.Dowling, S. Gauvain, and D. E. Macrae, Brit. Med. J., 1948, I , 430270 BIOCHEMISTRY.expressed as to its superiority over ultra-violet light treatment.46 The useof such massive dosages has led to reports of many cases of vitamin Dinto~ication.~'Vitamins E.-A fourth tocopherol, 6-tocopherol, has been described ;it is more resistant to oxidation than the other tocopherols, but biologicallyit has only 1/100th of the activity (+)-a-tocopherol. The coumarin analogueof a-tocopherol has been synthesised; it has only 1/20th of the biopotencyof a-toc~pherol.~~ A reversible-oxidation product of a-tocopherol, contain-ing one more oxygen atom and which is probably an epoxide, has beenisolated." The dependence of biological activity on structure has beenstressed ; almost all compounds showing vitamin-E activity in the rat-sterility test being chroman derivatives, the requisite substituents are (a)one or more alkyl groups on the carbocyclic ring, (b) a free or esterifiedhydroxyl a t C,,), and (c) a short and a long side-chain at C(2J.51 Analyticalmethods have been improved; 52 a scheme for the analysis of individualtocopherols in mixtures of the four forms has been devised.53While we do not yet know how the tocopherols function inthe body the idea that there is a dual role in vivo, a specific vitamin-likefunction and a secondary antioxidant action,% is still useful.A third phar-macological role may be of importance when large doses are given.The roleof tocopherols in the nutrition of farm animals has been reviewed.54aThe commercial use of tocopherols in the stabilisa-tion of fats has been ~umrnarised.~5 The protective action of tocopherolsagainst the hzemolysis of erythrocytes by alloxan or dialuric acid 56 can beconsidered as an antioxidant effect. The protective action of a-tocopherolagainst X-ray mortality is attributed to the inhibition of peroxide formationin fats5' From histochemical studies it is suggested that the yellow-brownpigment occurring in granules in the fat cells of rats deficient in vitamin Erepresents, at least partly, the oxidation of highly unsaturated fatty acidsbeyond the peroxide stage.5* The increased liver storage of vitamin Acaused by feeding tocopherols to chicks on a diet containing cod-liver oilcould also be obtained by feeding methylene blue.59Relation to enzyme systems.The enzymic oxidation of linoleic acid by48 J . T. Ingram and S. T. Anning, Brit. J . Derm. Syph., 1948, 60, 159; J. Dawson,ibid., p . 164.47 T. S. Danowski, A. M. Winkler, and J . P. Peters, Ann. Intern. Med., 1945, 23, 22;G. W. Covey and H. H. Whitlock, ibid., 1946, 25, 508; J . M. Bauer and R. H. Freyberg,J . Amer. Med. Assoc., 1946, 130, 1208; H. Bell, Brit. Med. J . , 1949, I , 139.M. H. Stern, C . D. Robeson, L. Weisler, and J. G. Baxter, J . Amsr. Chem. Soc.,1947, 69, 869.P. D. Boyer, M. Rabinovitz, and E. Liebe Ann. N . Y . Acad. Sci., 1949-1950, 52,188.61 Idem, J . B i d . Chem., 1951, 192, 95.62 €3. W. Rawlings, N. H. Kuhrt, and J. G. Baxter, J . Amer. Oil Chem. SOC., 1948,25, 24; R. W. Swick and C. A. Baumann, AnaZyt. Chem., 1952, 24, 758; M. L. Quaifeand P. L. Harris, ibid., 1948, 20, 1221.M. L. Quaife, J . Biol. Chem., 1948, 175, 605; F. Brown, Biochem. J . , 1952, 51, 237. '' K. C. D. Hickman and P. L. Harris, Adv. Enzymology, 1946, 6, 469.6b K. L. Blaxted and F. Brown, Nutrit. Abs. Reviews, 1952, 22, 1.66 W. 0. Lundberg, '' A Survey of the Present Knowledge, Researches and Practicesin the US. Concerning the Stabilization of Fats," No. 20 (The Hormel Institute of theUniv. of Minnesota, Minneapolis, Minn. , 1947).6 6 C . S. Rose and P. Gyorgy, J . Nt4trit., 1949, 39, 529; Amer. J .Pltysial., 1952, 168,414. 67 A. Herve and Z. M . Bacq, Compt. rend. SOC. Biol., 1949, 143, 1158." H. Granados and H. Dam, Acta Path. Microbiol. Scand., 1950, 27, 591. '@ H. Dam, I. Prange, and E. Smdergaard, Experientia, 1951, 7 , 184.Physiology.Antioxidant activity.4Q L. I . Smith and G. A . Boyack, ibid., 1948, 70, 2690DATTA : VITAMINS. 27 1crystalline lipoxidase is inhibited by tocopherols,60 this is a selective in-hibition in that the desired oxidation is permitted but the undesired autoxid-ation of linoleic peroxides is prevented.61 Plasma lipase and cholinesteraseare reduced in tocopherol deficiency, 62 as is muscle adenosinetriphosphataseactivity in some species.63 Tocopheryl phosphates have been shown toinhibit a number of enzyme systems in vitro, diphosphopyridine nucleo-tidase,6P succinic o x i d a ~ e , ~ ~ and muscle acid phosphatase.63 The possibilitythat these actions of tocopheryl phosphates are due to some non-specificdetergent action must be remembered.66No difference is found in the blood tocopherol level in normal,pregnant, or aborting or in normal and sterile men 71 though thisis disputed.74 Lesions of the reproductive system in male rabbits are shownin tocopherol deficiency,68 while increased work intensifies the degenerationof the testes in deficient male rats 69 though there is no decrease in androgenprod~ction.~~ Reports at a conference on human infertility were contra-dictory concerning the value of tocopherol therapy. 72 Tocopherols arenecessary for successful implantation of the fertilised ovum in rats, thoughless is required than for gestation to proceed toa-Tocopherol protects rats on a low-protein dietagainst carbon tetrachloride poisoning ; this effect is duplicated by increasingthe protein intake or .by giving methionine.75 Massive liver necrosis in ratson a diet low in low sulphur-containing amino-acid is prevented by toco-pher01.~~ A similar effect is found in rats fed a semisynthetic diet containinga British baker’s yeast as the sole source of protein.77 The protective effectof methionine on sodium selenate liver damage is only evident when tocopherolis present.78 From a study of the protective action of tocopherol andmethionine on liver necrosis in rats caused by feeding raw soyabean meal asthe sole source of protein it was concluded that methionine gave better pro-tection than tocopherol, the action of the former being specific while the latteracts non-specifically.79Fertility.Liver degeneration.6o S. Bergstrom and R. T. Holman, Nature, 1948, 161, 55.6 1 K. C. D. Hickman, Arch. Biochem., 1948, 17, 360; H. 0. Kunkel, ibid., 1951,63 J . P. Hummel, J . Bid. Chem., 1948, 172, 421: M. M. Corey and D. D. Dziewiat-64 W. M. Govier and N. S. Jetter, Science, 1948, 107, 146.6 5 S. R. Ames and H. A. Risley, Ann. N . Y . Acad. Sci., 1949-1950, 52, 149.6 7 K. Faaborg-Andersen, Nord. Med., 1946, 32, 2401.30, 306, 317.kowski, ibid., 1949, 179, 119.W. Hess and G. Viollier, Helv. Chim. Acta, 1948, 31, 381.M. Rabinowitz and P.D. Boyer, J . Biol. Chem., 1950, 183, 111.M. L. Chevrel and M. Cormier, Compt. rend., 1948, 226, 2013.E. Kokas, B. Gorka, and A. Hesz. 2. Vitamin-, Hormon- u. Fermentforsch., 1947-70 J . R. Valle and L. C. U. Junqueira, Endrocrinol., 1947, 40, 316.7 1 E. C. Jungck, W. 0. Maddock, J . T. Van Bruggen, and C. G. Heller Fed. Proc.,72 Family Planning Assoc. Conf. on Infertility, Lancet, 1948, 11, 542.73 H. Kaunitz, C. A. Slanetz, and R. E. Johnson, J . Nutrit., 1948, 36, 331; R. J .74 G. Athanassiu, Med. Monatsschr., 1948, 2, 186.7 6 E. L. Hove, Arch. Biochem., 1948, 17, 467; M. V. R. Rao, Nature, 1948, 161, 446;7 6 0. Lindan and H. P. Himsworth, Brit. J . Exp. Path., 1950, 31, 651; M. Goettsch,7 7 P. Gyorgy, C. S. Rose, R. M. Tomarelli, and H.Goldblatt, Qbid., 1950, 41, 265.78 E. A. Sellers, R. W. You, and C. C. Lucas, Proc. Soc. Exp. Biol. N . Y . , 1950,75,11879 A. Matet, J . Matet, and 0. Friedenson, Compt. vend. SOC. Biol., 1949, 148. 235.1948, 1, 466.1947, 6, 139.Blandau,’H. Kaunitz, and C. A. Slanetz, ibid., 1949, 38, 97.A. Neuberger and T. A. Webster, Biochem. J . , 1947, 41, 449.J . Nutrit., 1951, 44, 443272 BIOCHEMISTRY.The relative potencies of various tocopherols in protecting rats againstmassive hepatic necrosis have been studied; a-tocopherol is active while y-and &tocopherols are inactive, p-tocopherol was not s t ~ d i e d . 7 ~ ~Muscdar dystyophy. A detailed study of the muscles of rabbits on adiet deficient in vitamin E has been reported. The optical behaviour offibres which have not yet grossly degenerated resembles that of normalfibres from which actomyosin has been removed ; there is a loss of bi-refrin-gent material,79b and the appearance of the actin G under the electron micro-scope is altered.79c The amount of both actomyosin and myosin which canbe extracted from dystrophic muscles is reduced, the myosin even dis-appearing.9dMedicine. Tocopherols in massive doses have been used in the treatmentof a large number of morbid conditions with claims of success ; these includeanginal pain and cardiac failure,SO acute nephritis,81 Dupuytren's contrac-ture,s2 Peyronie's disease, 83 disease characterised by collagen degeneration,obliterative vascular disease,s5 and diabetess6 Time alone. will show howmany of these claims are justified and how many are on a par with the rashassertions with which the history of the vitamins in ther-apeutics is full.Menadione (2-methyl-1 : 4-naphtha-quinone) is unstable in dilute solution on exposure to radiation at 366 mp;it may be protected, however, by small amounts of chloride or bromide ions.s7Methods of conversion of common carbohydrates into menadione and theincorporation of isotopic carbon at various positions are described.s8 Thefate of such labelled menadione in dogs has been investigated ; 87a most ofthe administered dose was excreted in the urine, only traces being found inthe blood, liver, and lungs. Vafious compounds related to rnenadione havebeen made including 4-amino-2-methyl-1-naphthol hydrochloride, " K,," 891 : 4-diamino-2-methylnaphthalene dihydrochloride, I ' K,," 9o 4-amino-3-methyl-l-naphthol hydrochloride, ' K,." 91 Colorimetric estimations ofvitamin K with 2 : 4-dinitrophenylhydra~ine,~~ polarographic estimation ofmenadi~ne,~~ and a spectrophotometric estimation of mefiadione by usingthe absorption at 430 rnp 94 have been described.A simple diet deficient in79p G. Selzer, R. G. F. Parker, D. McKenzie, and G. C. Linder, Byit. J . Exp. Path.,1951, 32, 493.79b M. Aloisi, A. Ascenzi, and E. Bonetti, J . Path. Bact., 1952, 64, 321.79c Idem, Experientia, 1952, 0, 266.82 C. L. Steinberg, N.Y. State J . Med., 1947, 47, 1679.84 J . F. Burgess, Lancet, 19&3, 11, 215.8 5 E. V. Shute, Ann. N.Y. Acad. Sci., 1949-1950, 52, 358; A.M. Boyd, A. HallRatcliffe, G. W. H. James, and R. P. Jepson, Lancet, 1949, 11, 132.8 6 A. Vogelsang, Ann. N.Y. Acad. Sci., 1949-1950, 52, 406.8 7 R. H. Davis, A. L, Mathis, D. R. Howton, H. Schneiderman, and J . F. Mead. J .Biol. Chem., 1949, 179, 383.870 P. F. Solvonuk, L. B. Jaques, J. E. Leddy, L. W. Trevoy, and J. W:T. Spinks,Proc. SOC. E x p . Bzol. N . Y,, 1952, 7@, 597." P. P. T. Sah, 2. Vitamin-, Hormon- u. Fermentforsch., 1949-1950, 3, 40.s: F. N:-H. Chang, J. F. Oneto, and P. P. T. Sah, ibid., p. 61 ; P. P. T. Sah and T. C .Daniels, zbzd., p. 81.P. P. T. Sah, ibid., p. 324.O2 D. V. S. Reddy and V. Srinivasan, Current Sci., 1948, 17, 22; E. E. v. Koestveld,Rec. Tvav. chim., 1930, 89, 1217.94 Pereira Forjaa, Anais Azevedos, 1950, 2, 278.Vitamin K.-Chemistry and assay.79d Idem, ibid., p.69.A. B. Vogelsang, E. V. Shute, and W. E. Shute, Med. Record, 1947, 160, 21, 91,81 W. E. Shute, Urol. Cutaneous Reviews, 1946, 50, 679.W. W. Scott and P. L. Scardino, Southern Med. J . , 1948, 41, 173.163, 230, 279.8D P. P. T. Sah, G. Subbaraju, and T. C . Daniels, ibid., p. 87.93 H. Onrust and B. Wostmann, zbid., p. 1297.DATTA : VITAMINS. 273vitamin K which regularly produces marked hypoprothrombinamia in chickshas been devised.95 The determination of vitamin K by the curative methodin chicks has been simplified ; a single dose of the test substance is given andthe effect on the prothrombin time 20-22 hours later is determined.96Vitamin K and menadione both counteract thehypoprothrombinamic action of dicoumarin and are equipotent in thisrespect ; 95 the equipotency is, however, disputed.lM The exact mechanismof the anti-vitamin K action of dicoumarin and other substances has beenstudied by several investigators.Dam 97 has pointed out that, in the plasmaof dicoumarol-poisoned chicks and chicks deficient in vitamin K, in additionto a lack of prothrombin there are two other common factors : (a) the 8-factorJS8 which is absent from vitamin K-deficient plasma but present indicoumarol-poisoned plasma which, when added to the former, stimulatedcoagulation ; and ( b ) the factor,^^ which is absent in dicoumerol-poisonedplasma but present in vitamin K-deficient plasma which, when added to theformer, also stimulates coagulation.The 6- and the K-factor may beinactivated by two entities partially separable from normal blood.lm Fromvarious considerations it is supposed that vitamin K is not part of the pro-thrombin molecule but is concerned in the mechanism of prothrombin pro-duction. It is suggested that vitamin K serves as the prosthetic group whichcomplements the apo enzyme AE, to form the active synthesising enzyme,AEK.lol I t is claimed that dicoumerol decreases both prothrombin andaccelerator globulin, vitamin K being able to restore the former, but not thelatter.lo2 The structural requirement for anti-vitamin K activity is a 3-hydroxy-1 : 4-naphthaquinone substituted at C(2), the nature of the sub-stituent being important, one condition being that it contains a hydrocarbonchain of at least six carbon atoms.lo3The hypoprothrombincemia occurring in hypervitaminosis A can be pre-vented by giving vitamin K, but the other effects are in no way affected.lo5Hypoprothrombinzemia from liver injury such as that caused by injection ofpyramidone is relieved by vitamin K lo6 but this effect is not obtained incancer of the liver.lo7 Vitamin K is still considered of value in preventionof haemorrhagic manifestations in new-born infants.lo8 The value of ad-ministering 10 mg.of synthetic vitamin K (tetrasodium 2-methyl-1 : 4-naphthaquinone diphosphate) before labour is established in a trial with20,000 mothers (half this number being controls), the incidence of malznaand hzematemesis in the offspring being much reduced.loSMiscellaneous Fat-soluble Factors.-Essential fatty acids.The necessity95 A. J . Quick and M. Stefanini, J. B i d . CJaem., 1948, 175, 945.O 6 H. Dam, I. Kruse, and E. Ssndergaard, Acta Physiol. Scand., 1951, 22, 238.O 7 H. Dam and E. Sendergaard, Biochem. et Biophys. Acta, 1948, 2, 409.0. Serbye, I. Kruse, and H. Dam, Acta Chem. Scand., 1950, 4, 831.Idem, ibid., p. 549.lol A. J . Quick and G. E. Collentine, Amev. J , Physiol., 1951, 164, 716.loa K. Felix, I . Pendl, P. Pin, and L. Roka, 2. physiol. Chem., 1949, 284, 185.lo3 C. Mentzer, Bull SOC. Chim. biol., 1948, 30, 872; C. C. Smith, Proc. SOC. Exp.lo' K. Miller, W. P. Harvey, and C. A. Finch, New Engl. J. Med., 1950, 242, 211.loK S. E. Walker, R. Eylenburg, and T.Moore, Biochem. J . , 1947, 41, 575.lo8 J . E. Galimard, Bull. Soc. Chinz. biol., 1947, as, 641.lo7 W. Begtrup, Acta Med. Scand., 1947-1948, 129, 33.lo8 H. N. Sanford, M. Kostalik, and B. Blackmore, Amer. J. Dis. Children, 1949, 78,Blood Coagulation.loo Idem, ibid., 1951, 5, 487.l3iol. N . Y . , 1950, 73, 562.886. log H. Dyggve, Trans. 5th Intern. Congr. Pediat., New York, 1947274 BIOCHEMISTRY.for linoleic and linolenic acid in the diet of various species has been investi-gated. Linoleic acid is necessary for the emergence and development of themoth Ephestia, but some moths can synthesise this nutrient.l1° Rats onfat-deficient diets do not grow more rapidly when given pituitary-growthhormone. Hormone with linoleate gave better growth than linoleatealone; ll1 male rats require 50 mg.of linoleic acid daily, females 10-20 mg.Linolenic acid at the same level was poor in growth-promotion but when fedwith linoleate in sub-optimum amounts it was much more efficient.l12Chicks on fat-free diets fail to grow a t the same rate as chicks receivingsupplementary linoleic acid; 113 they can convert dienoic acids into tetra-enoic and pentaenoic acids, and trienoic acids into hexaenoic and other poly-enoic acids.llq The laying hen can probably synthesise small amounts oflinoleic acid, and it is interesting that egg production and hatchabilityremain normal with hens fed on the fat-free diet.l16 The follicular hyper-keratosis in man, normally associated with vitamin-A deficiency, can becured by fats containing polyunsaturated fatty acids.llsThe distribution of unsaturated fatty acids has been studied in horse,beef and mutton,ll* rats,l17 guinea pigs,l19 dogs,lm and milk.lma The fattyacid requirements of bacteria have been studied.121Linoleic acid has been synthesised by the partial hydrogenation of thecorresponding p-diacetylenic acid which is, however, difficult to obtain ingood yield.122Guinea-pig anti-stiflness factor.This crystalline factor, isolated from cane-sugar juice,123 continues to receive considerable attention. Many sterolshave been tested,l= but only ergostanyl acetate is active. Deficiency isthought to lead to a disturbance in the phosphate distribution in muscle; 125deafness and disorganisation of the ear are associated phenomena.12s Theresults, and particularly the lack of a good method of assay have beenc r i t i c i ~ e d .~ ~ ~Anti-gizzard-ulcer factor. This factor, which was reported as occurring110 G. Fraenkel and M. Blewett, Biochem. J., 1947, 41, 475.H. Deuel, Jr., S. M. Greenberg, C . E. Calbert, E. E. Savage, and T. Fukui, J .112 S. M. Greenberg, C . E. Calbert, E. E. Savage, and H. J. Deuel, Jr., ibid., 1950,113 R. Iieiser. ibid., 1950, 42, 319.114 Idem, ibid., p. 325. 115 Idem, ibid., 1951, 44, 159.P. S. Menon, P. G. Tulpule, and V. N. Patwardhan, Indian J . Med. Hes., 1950,117 C. Widmer, Jr., and R. T. Holman, Avch. Biochem., 1950, e5. 1.lL8 F. B. Shorland, Nature, 1950, 165, 766.119 A. Chevallier, C. Burg, M. Lagoutibre, and R.Schneider, Compl. rend. SOC. Biol.,120 H. F. Wiese, R. T. Holman, and A. E. Hansen, Fed. PYOC., 1950, 9, 374.l2O0 P. S . Schaffer and G. E. Holm, J . Dairy Sci., 1950, 33, 865.121 M. R. Pollock, G. A. Howard, and B. W. Boughton, Biocham. J., 1949, 45, 417 ;122 R. A. Raphael and I?. Sondheimer, Nature, 1950, 165, 235.123 W. J . van Wagtendonk and R. Wulzen, J . Biol. Chem., 1946, 164, 597.12' J. J. Oleson, E. C. van Donk, S. Bernstein, L. Dorfman, and Y . Subarrow, ibid.,125 W. J. van Wagtendonk, ibid., 1947, 167, 219; W. J. van Wagtendonk and A. M.126 H. Krueger, R. Wulzen, and P. Leveque, Abs. Comm. 18th Intern. Physiol. Congv.,lZ7 W. Dasler, Chicago Med. Sch. Quart., 1950, 11, 70; W. Dasler and C. D. Bauer,Nutril., 1950, 40, 351.41, 473.38, 173.1949, 143, 1380.J .B. Hassinen, G. T. Durbin, and I?. W. Bernhart, Arch. Biochem., 1950, 25, 91.1947, 171, 1.Freed, ibid., p. 225.1950, p. 316.Proc. SOC. Exp. Biol. N . Y . , 1949, 70, 134NEEDHAM : PHOSPHATE METABOLISM. 275in the saponifiable sterol fraction of fats and designated vitamin U,128 hasbeen the cause of considerable confusion, Highly unsaturated fatty acids ofhog-liver fat exert a marked effect against gizzard ulcers,129 as does arachi-donic a~id.1~0 That the factor may not be fat-soluble is shown by the factsthat cyanocobalamin partially prevents chick-gizzard ulcers,131 and bothether-extracts of calves brain and water-extracts of the ether-extracted brainare active.132 Both extracts together exert a greater effect than eitherseparately, and cyanocobalamin can replace the aqueous extract.Thus, thisgizzard ulcer is probably caused by an interplay of deficiencies of severalfactors, some of which are fat soluble. There is a corresponding problemwith stomach ulcers in r a t ~ . 1 ~ ~S. P. D.4. PHOSPHATE METABOLISM.Abbreviations used are : ATP = adenosine triphosphate : ADP = adenosinediphosphate; AMP = adenylic acid; CoI, CoII, CoA = Coenzyme I, Coenzyme 11,Coenzyme A; diNP = dinitrophenol.In this Report, since it is impossible to cover all aspects of the subject,first place has been given to the part played by phosphate in the storage andtransfer of energy. It is interesting that, though the energy-rich phosphatebond still keeps its place as providing the most important known mechanismfor storage of readily available energy, the metabolic importance of an energy-rich bond not involving phosphate, the acylmercaptide bond, has recentlycome to light.The transfer of a component of the acylmercaptide compound,together with energy, can take place without the intervention of phosphate,although phosphate may act as an acceptor. In this connection also thediscussion by Woolley is of great interest, on the free energy to be derivedfrom the reduction of quaternary ammonium and sulphonium ions, and thepossible biological rble of such ions.Oxidative Phosphory1ation.-The phosPhorus : oxygen ratio. In 1948,Green, Loomis, and Auerbach la started the series of studies on cyclophorase,which showed that this preparation of washed tissue particles can catalyseall the oxidations of the tricarboxylic acid cycle, as well as oxidise manyamino- and fatty acids2 Cross, Taggart, Covo, and Green3 studied phos-phate esterification with this preparation, and found that usually more thantwo atoms of phosphorus were esterified for every atom of oxygen absorbed,thus confirming the earlier values with cruder preparations, where a largeallowance had been necessary for phosphatase activity (see, e.g., Ochoa 4).By 1948 the work of Hogeboom, Schneider, and Pallade had made possiblethe isolation, by differential centrifugation of tissue homogenates in hyper-lZ8 G.Chesney, Arch. Intern. Med., 1942, 70, 532.lzg H. Dam, Acta Physiol. Scand., 1946, 12, 189.lS0 H.Dam and H. L. Segal, ibid., 1945, 10, 295.lS1 C. W. Mushett and W. H. Ott, Poultry Sci., 1949, 28, 850.132 H. Dam, B. Noer, and E. Ssndergaard, Acta Physiol. Scand., 1950, 21, 315.lS3 E. L. Hove and P. L. Harris, J. Nutrit., 1950, 40, 177; G. Chesney, J . Amer.Is D. E. Green, W. F. Loomis, and V. H. Auerbach, J. Biol. Chern., 1948, 172, 389.D. E. Green, Biol. Reviews, 1951, 28, 410.R. J. Cross, J.V. Taggart, G. A. Covo, and D. E. Green, J. Biol. Chem., 1948,177,655. * S . Ochoa, ibid., 1941, 138, 751; 1943, 151, 493; 1944, 155, 87.G. H. Hoogeboom, W. C. Schneider, and G. E. Pallade, ibid., 1948, 172, 619.Dietet. ASSOC., 1950, 26, 668. D. W. Woolley, Nature, 1953, 171, 323276 BIOCHEMISTRY.tonic sucrose solution, of the large cell granules or mitochondria, in a mor-phological state apparently identical with that in vivo.It was soon foundthat this mitochondria1 fraction was the main site of cell oxidations andshowed a higher phosphorus : oxygen ratio than other cell constituents.6Harman and co-workers showed that the activity of cyclophorase dependedon the number and integrity .of the mitochondria.With the use of these intact, isolated mitochondria, many interestingrelationships have come to light. Thus, Kielley and Kielley * have shownthat ageing of the preparations by maintaining them for some time undervarious conditions without substrate before the experiment, causes a tenfoldincrease in adenosine triphosphatase activity on addition of ATP. At thesame time the content in ATP and ADP falls and inorganic phosphorus islost into the medium.This rise in adenosine triphosphatase activity mustbe an important factor in causing the low phosphorus : oxygen ratios so oftenencountered with mitochrondria preparations, but probably there are moresubtle aspects also. Thus, it is suggested that a certain level of internalADP (to act as phosphate acceptor) is necessary for initiating the phos-phorylation process ; and that continual resynthesis of essential co-factorsmay go on, so that any period during which internal ATP is absent and duringwhich degradation products of such factors might leak away, would haveirreversible deleterious results. Hunter and Hixon’s work had earliershown the importance of experimentation a t a low temperature (15’) to obtainhigh phosphorus : oxygen ratios.The influence of phosphorus acceptors on oxidation rate is very clearlyseen with the intact mitochondria.6*10 Lardy and Wellman lo found verylow oxygen uptake with rat-liver mitochondria, prepared in isotonic sucrosesolution and fortified with ATP, magnesium, and phosphate; the rates weregreatly enhanced by addition of phosphorus acceptors.Some complicated questions of permeability of the intact mitochondria,and of the accessibility of their enzyme systems, have been discussed byLehninger.llFromenergy considerations and from analogy with glyceraldehyde dehydrogen-ation during glycolysis, we should expect only one phosphorus atom to beesterified for every pair of hydrogen atoms removed from the substrate;whereas-an average of three is found for the passage of pyruvate through thetricarboxylic acid cycle to carbon dioxide and water.3* This means that thelater stages of hydrogen transport (or at any rate some of them), throughflavin and cytochrome C to oxygen, must be involved.The latest assess-ments l2 of the free energy of the encrgy-rich phosphate bond give valuesbetween about 12,000 cal. per mole for the pyrophosphate bond in ATP, andabout 15,000 cal. per mole for the phospho-enolic bond in phosphopyruvate.The free energy likely to be available at the different stages may be gaugedA. L. Lehninger and E. P. Kennedy, J . Biol. Chem., 1949, 179,957; V. R. Potter,G. G. Lyle, and W. C. Schneider, ibid., 1950, 190, 293.7 J.W. Harman, Exp. Cell. Hes., 1950, 1, 382, 394; J . W. Harman and M. Feigelson,ibid., 1952, 3, 47, 509.8 W. W. Kielley and R. K. Kielley, J . Biol. Chem., 1951, 191, 485.@ F. E. Hunter and W. S. Hixon, ibid., 1949, 181, 73.lo H. A. Lardy and H. p l l r n a n , ibid., 1952, 195, 215.A. L. Lehninger, inThe evidence for phosphorylation accompanying hydrogen transport.Phosphorus Metabolism,” Johns Hopkins Press, Baltimore,1951, p. 344. 12 P. Oesper, ibid., p. 523SEEDHAM : PHOSPHATE METABOLIShl. 277from the charts given by Dixon; l3 the values per two hydrogen atoms atpH 7.0 are approximately 12,000 cals. between the CoI stage and the flavo-protein stage; 14,000 between the latter and the cytochrome C system;and 24,000 between this last system and oxygen at one atmosphere. cf.13aOnly two steps in the tricarboxylic acid cycle have been studied in-dividually. The oxidation of a-ketoglutarate to succinate and carbondioxide was found by Hunter and Hixon to give a phosphorus : oxygen ratioof 3 or more (probably 4) in conditions where about 75% of the succinatecould be recovered after the oxidation. The same workers also examinedthe oxidation of succinate to fumarate practically as a single step (undertheir conditions, fumarate was being oxidised at only one-fifth of the ratefor the succinate). Here, as well as in experiments of Cross et aL3 and ofLehninger and Smith,14 experimental phosphorus : oxygen values of 1.4-1.7, indicated a true ratio of 2. The oxidation of succinate does not passthrough CoI or CoII, and the low phosphorus : oxygen ratios are probably to beexplained by the availability of only the stages from cytochrome C onwards.With regard to the remaining oxidations in the tricarboxylic acid cycle,the case of pyruvate is considered below.The oxidation of isocitrate tooxalosuccinate, and of malate to oxaloacetate has not been investigated asisolated steps, and it is not possible to say definitely whether phosphorylationis connected with these substrate stages. From the probable position oftheir equilbria on the rH scale,15 this seems unlikely.We may now consider the direct evidence for esterification at variousstages of the hydrogen-transport chain. In experiments with washed liver-particles, Lehninger 16 showed that the anaerobic oxidation-reductionbetween P-hydroxybutyrate and oxaloacetate is not accompanied by phos-phate esterification, as indeed is to be expected from the position of itsequilibrium on the electrode-potential scale.However, when conditionswere aerobic, incorporation of 32P into ATP was found to be coupled with theoxidation, and Lehninger and Smith, using high concentrations of ADP orAMP as acceptor, found phosphorus : oxygen ratios higher than 2. Sinceacetoacetate was not further oxidised and since the substrate stage alone didnot lead to phosphate uptake, this esterification must be coupled with the laterstages of electron transfer. Lehninger 17waslatersuccessfulin showing that theoxidation of high concentrations of reduced CoI could give a ratio of nearly 2.The question of phosphorus esterification associated with transport ofhydrogen between reduced CoI and cytochrome C has been studied byFriedkin and Lehninger,l* using large amounts of cytochrome C as hydrogenacceptor, but without success ; Slater,ls using a-ketoglutarate oxidation byheart mitochondria, compared phosphorus : oxygen ratios with either cyto-chrome C in high concentration or oxygen as the final hydrogen acceptor,and found no difference.Too much weight must not be laid on such nega-tive results, since they probably mean that experimental difficulties (such asl3 M. Dixon, " Multi-enzyme Systems," University Press, Cambridge, 1948, pp. 65,13a A. W. D. Avison and J . D. Hawkins, Quart. Reviews, 1951, 5 , 171 ; S.Ochoa andA. L. Lehninger and S. W. Smith, J. Biol. Chem., 1949, 181, 4?5.M. Dixon, " Multi-enzyme Systems," University Press, Cambridge, 1948, p. 28.l 7 Idem, ibid., 1951, 190, 345M. Friedkin and A. L. Lehninger, ibid., 1949, 178, 611.E. C. Slater, Nature, 1950, 166, 982.73, 87.J . H. Stern, Ann. Rev. Biochem., 1952, 21, 547.l6 A. L. Lehninger, J. Biol. Chem.. 1949, 178, 625278 BIOCHEMISTRl'.the lability of the individual esterification mechanisms or limitations due topermeability barriers in the mitochondria) have not yet been overcome.Judah seems to have had some success in showing esterification associatedwith the oxidation of reduced cytochrome C, by using a liver-mitochondria1system in which ascorbic acid provided continual reduction of cytochromeC.Control experiments showed that the dehydroascorbic acid was notfurther oxidised.A good deal of information has recentlybeen gained on the mechanism of phosphate uptake a t the substrate stage inthe tricarboxylic acid cycle.Lipmann 21 had shown that the primary product of oxidation of pyruvateby extracts of B. Delbruckii was acetyl phosphate. However, efforts to bringabout synthesis of citrate in animal tissues by means of acetyl phosphateand oxaloacetate failed, although synthesis was obtained either duringoxidation of pyruvate or fatty acids or in the presence of acetate and ATP.22Light was first thrown on the nature of " active acetate " a s acetyl-coenzymeA by the work of Stadtman and his collaborators.Stadtman23 preparedfrom extracts of CZ. Kluyveri an enzyme, phosphotransacetylase, which couldmake available the acetyl group of acetyl phosphate for condensations, e.g.,citrate formation in presence of the condensing enzyme from liver. Phos-photransacetylase is CoA dependent, and further work 24 indicated that thereaction catalysed is :acetyl phosphate + CoA =+ acetyl-CoA + phosphateLynen, Reichert, and Rueff 25 had meanwhile isolated acetyl-CoA, and thiswas shown by Stern, Shapiro, Stadtman, and Ochoa 26 to react, in presenceof the crystalline condensing enzyme, to give citrate. Stadtman 27 alsoisolated the acetyl-CoA formed by phosphotransacetylase action.Lipmann and his colleagues 28 have recently studied the mechanism of thereaction whereby acetyl-CoA is formed in yeast and pigeon-liver preparations,in presence of ATP, CoA, and acetate, although acetyl phosphate is unavail-ing. Lynen, Reichert, and Rueff 25 had suggested that CoA is phosphoryl-ated by ATP, with formation of an energy-rich bond, and that the phosphatecan then exchange for acetyl, acetyl-CoA resulting :Mechanism of Phosphate uptake.ATP + CoA -+ CoA-phosphate + ADPCoA + acetate + acetyl-CoA + phosphateHowever, Lipmann's investigation showed that the final form of the ATPis AMP + pyrophosphate; and further that, while pyrophosphate can dis-place acetyl from acetyl-CoA, inorganic phosphate cannot do so.It wasconcluded that the reactions were :ATP + CoA + AMP + &A-pyrophosphateCoA-pyrophosphate + acetate acetyl-CoA + pyrophosphate~ ~ ~ ~~ ~~~~ ~ ~~~~ ~~~~~ ~lo J .D. Judah, Biochem. J . , 1951,49,27.B p J. R. Stern and S. Ochoa, ibid., 1949, 179, 491.2 1 F . Lipmann, J . B i o l . Chem., 1944,155,55.E. R. Stadtman, Fed. PYOC., 1950, 9, 233.E. R. Stadtman, G. D. Novelli, and F. Lipmann, J . Biol. Chem., 1951, 191, 365;l6 F. Lynen, R. Reichert, and L. Rueff, A m . Chem., 1951, 574, 1.26 J . R. Stern, B. Shapiro, E. R. Stadtman, and S. Ochoa, J . Biol. Chem., 1951,193,703.27 E. R. Stadtman, ibid., 1952, 195, 536.1.9 F. Lipmann, M. E. Jones, and S. Black, " Symposium sur le Cycle Tricarboxy-E. R. Stadtman, ibid., 1952, 196, 527.lique," Second Int. Congr. Biochem, Paris, 1962, p. 66NEEDHAM : PHOSPHATE METABOLISM. 279The same reactions are catalysed by a soluble enzyme from pig’sheart .29Partially purified, soluble systems have been isolated 30 from E.coli andfrom heart, which catalysed the oxidation of pyruvate in presence of bothCoI and CoA. With catalytic amounts of CoA, the reaction only proceededif an acetyl acceptor was present , together with the appropriate acetylatingenzyme. The supply of CoI could be kept up by coupling reaction with lacticdehydrogenase :Pyruvate + CoI + CoA + acetyl-CoA + CO, + CoI-H,Schweet, Fuld, Cheslock, and PaulJ31 using a soluble preparation from pigeon-breast muscle , came to similar conclusions. Littlefield and Sanadi,32 usinglarge amounts of CoA, have recently been able to show stoicheiometricrelations between the disappearance of pyruvate and CoA-SH groups (seebelow) and the appearance of active acetate (by the hydroxamic reaction)and reduced CoI.These findings explain how the free energy of pyruvateoxidation is used in the tricarboxylic acid cycle for the synthesis of citratefrom pyruvate and oxaloacetate. No examination of phosphate uptakeassociated with pyruvate oxidation has been described, but it seems likelythat the acetyl-CoA might , under some conditions, undergo pyrophosphoro-lysis or phosphorolysis.The esterification of phosphate accompanying the oxidation of a-keto-glutarate to succinate and carbon dioxide has been studied by K a ~ f m a n , ~ ~by using a soluble enzyme preparation from heart. This catalyses the dis-mutation of a-ketoglutarate to glutamate and succinate, in the presence ofammonium ions.If phosphate acceptors are added, phosphate is esterified.The following formulation seems to fit the facts :a-ketoglutarate + CoI + CoA succinyl-CoA + CO, + CoI-H,a-ketoglutarate + NH, + CoI-H, + glutamate + CoIsuccinyl-CoA + H,O =+ succinate + CoAsuccinyl-CoA + ADP + H,PO, + succinate + ATP + CoAAlthough this is not actually suggested by Kaufman, it seems likely that thelast reaction is :succinyl-Coh + H,PO, =+ succinate + CoA-phosphateCoA-phosphate + ADP ATP + CoAIt is significant that, in contrast to the system with acetate studied byLipmann et al. ,2* this could catalyse the liberation of inorganic phosphatefrom ATP in presence of succinate and CoA. Acetyl-CoA could not reactwith ADP and phosphoric acid in this system.Succinyl-CoA has been iso-lated by Sanadi and Littlefield.34 Ochoa35 has reported that, by furtherammonium sulphate fractionation of Kaufman’s heart preparation, twoprotein fractions were obtained, one of which catalysed oxidation of a-keto-*@ Quoted by D. E. Green, Science, 1952, 115, 661.S. Korkes, A. del Campillo, I. C. Gunsalus, and S. Ochoa, J. Biol. Chem., 1951, 193,721 ; S. Korkes, A. del Campillo, and S. Ochoa, ibid., 1932, 195,.54:.31 R. S. Schweet, M. Fuld, K. Cheslock, and M. H. Paul, in Phosphorus Meta-bolism,” Johns Hopkins Press, Baltimore, 1951, p. 246.32 J. W. Littlefield and D. R. Sanadi, J . B i d Chem., 1952, 199, 65.33 S. Kaufman, in “ Phosphorus Metabolism,” Johns Hopkins Press, Baltimore,1951, p.370.ss S. Ochoa, “ Symposium sur le Cycle Tricarboxylique,” Second Int. Congr. Bio-chem., Paris, 1962, p. 73.34 D. R. Sanadi and J . W. Littlefield, Science, 1952, 116, 327280 Bf OCHEhlISTIiY.glutaric acid without coupled phosphorylation. Addition of the secondfraction (completely inactive in absence of the first) caused phosphorylation.Recent work 36 points to the formula :CH,.CMe,*CH( OH)*CO*NH*[CH,1 ,-CO-NH*[CH,] ,.SHCo-enzyme A.I P0IHO*P:O HO*P:O I I0 ICH,-CH-CH-CH (OH).CH*AdenineI---O---.-lPLynen, Reichert, and Rueff 25 showed that reaction of acyl groups with CoAtakes place through the thiol group of the pantothenic acid :During the previous discussion. it has been assumed that the acylthio-bondis energy-rich, since the acetylations and the pyrophosphorylation which itis known to implement, as well as the phosphorylations which seem to dependupon it, are reactions requiring energy provision.The free energy of itsrupture has been assessed by Stern, Ochoa, and L ~ n e n . ~ ' They measuredthe equilibrium constant of the reaction :CoA-SAC + malate + CoI + H,O =+ Co.%-SH + citrate + CoI-H,and from this, together with that of the reaction catalysed by malic dehydro-genase a t the same pH, calculated that the free energy of the acylthio-bondis of the order of 12,000 cals./mole.The reversibility which is such a marked feature of theseries of reactions participating in hydrogen transfer and phosphorus uptakemeans that any accumulation of intermediates will hold up the whole course.This is probably the reason for the stimulating effect upon oxygen uptake ofthe presence of phosphate acceptors, and, as we shall see, of uncouplingagents.The need for inorganic phosphate, which is often observed in oxid-ation systems, may arise from the need for regeneration of intermediates :e.g., of CoA by phosphorolysis of acyl-CoA, followed by transfer of the phos-phate group from the CoA-phosphate to an adenylic acceptor. This mustremain at present a matter of speculation, since so far CoA-phosphate hasnot been isolated, and the enzymes concerned in the suggested transfershave not been identified. The need for some mechanism to bring aboutrapid splitting of acyl-CoA compounds is shown by the work of Gergely,Hele, and Ramakri~hnan.~g Using purified a-ketoglutarate oxidase, theyshowed that the oxidation only proceeds in presence of catalytic amounts ofCoA if another enzyme, succinyl-CoA deacylase, is provided. This enzymebrings about the reactionCOA-SH + AcR -+ COA-SAC + R HReversibility.Succinyl-CoA + H,O --+ succinate + CoA36 J.Baddiley and E. M. Thain, J., 1951, 2253; J . D. Gregory, G. I). Novelli, ands7 J. R. Stern, S. Ochoa, and F. Lynen, Fed. Proc., 1952, 11, 293.sE J. Gergeley, M. P. Hele, and C. V. Ramakrishnan, J. Bzol. Chcm., 1062, lS8, 323.F. Lipmann, J . Amar. Chenz. Soc., 1952, 74, 854SEEDHAM : PHOSPHATE METABOLISM. 28 1and evidence was obtained for a similar enzyme acting upon acetyl-CoA.The activity of such enzymes could, of course, speed up oxidations, butwould involve dissipation of the energy of the acylthio-bond.Esterification of Phosphate during Oxidation of Glyceraldehyde Phos-phate.-It will be noticed that in the conceptions of phosphate uptakedescribed above, no phosphorylation of the substrate is postulated, as it wasin Warburg and Christian’s theory with regard to the esterification accom-panying the oxidation of glyceraldehyde phosphate during glycolysis.It isof great interest, therefore, to find that a new view of the action of glyceralde-hyde phosphate dehydrogenase has emerged, in which phosphate uptake is apost-oxidation stage.Krimsky and Racker 3D have recently obtained evidence that crystallineglyceraldehyde phosphate dehydrogenase contains glutathione as a firmlybound prosthetic group.Racker and Krimsky then showed that oxidationof aldehydes proceeds in two stages : first the aldehyde reacts with the thiolgroup of the enzyme and is oxidised to a thiol ester ; and only later does phos-phorolysis take place with removal of the acyl group to phosphate. Theevidence for the first step may be summarised as follows : (1) formation of athiol ester when the reaction was camed out in the presence of glutathioneand the absence of phosphate; (2) the power of the reaction to provide acylgroups for acylation of, e g . , sulphanilamide in presence of the appropriateadditional enzyme system; and (3) release of acyl groups from the washeddenatured enzyme into solution with hydroxylamine. The evidence for thesecond step depends on a study of the back reaction : in the presence ofarsenate the enzyme liberated inorganic phosphate from diphosphoglycerate,even though there was no hydrogen donor present and no CoI reduction;and even though iodoacetate was present to inhibit any oxidation or reduction.It will be seen that this arsenolysis is incompatible with the old formulationof the reaction series :glyceraldehyde + phosphate =+Racker and Krimsky suggestRc: 011II-+ 7-S HIR1IH-C-OHI S I enzyme enzymeglyceraldehyde diphosphate diphosphoglycericacidB c: 0Rc:oIIIphosphate O*PO,H, - - co Ii-SH Ienzyme enzymeA similar conclusion was reached by Holzer and Hol~er,~l who found thatcrystalline triosc phosphate dehydrogenase can be protected from iodoacetateinhibition by previous addition of its substrate.They showed the dissoci-ation constants of the enzyme-substrate complex to be in the ratio, 500 : 1,for glyceraldehyde and glyceraldehyde phosphate ; and the amounts of thetwo substrates which had to be added to obtain protection bore roughly thissame relation-300 : 1. They concluded that the aldehydes combine with39 I . Krimsky and E. Racker, J. Baol. Chem., 1952, 198. 721.40 E. Racker and I. Krimsky, ibid., p. 731.4 1 H. Holzer and E. Holzer, 2. Phpzol. Chem., 1952, 2@l, 87282 BIOCHEMISTRY.the enzyme by means of the same group as the iodoacetate, i e . , through thethiol group.Uncoupling of Oxidation and Phosphory1ation.-Many reagents can beused to dissociate phosphorylation from oxidation and an intensive study hasbeen made recently of some, e.g., dinitrophenol (diNP).It has long beenknown that this substance, while stimulating metabolism, can prevent manysorts of anabolic process-growth, differentiation, nitrogen and phosphateassimilation, etc. Ronzoni and Ehrenfe~t,~, using intact frog muscle, seemto have been the first to show that the increased metabolism was associatednot, as might be expected, with increased phosphocreatine synthesis, butwith a very marked breakdown. Then Loomis and Li~mann,*~ using washedkidney particles, found that the increased oxygen-uptake in presence of diNPwas accompanied by inhibition of phosphate esterification, and that the rateof oxidation became independent of added phosphate.The most likelyexplanation is that in its presence a small amount of residual inorganic phos-phate in the homogenate can be used over and over again, presumably onaccount of very rapid release of inorganic phosphate from phosphorylatedintermediates. Indeed, Judah 2o has shown, by exhaustive washing of livermitochondria (which did not damage their powers of oxidative phosphoryl-ation under appropriate conditions) that with less than about ~/1000-phosphate, little or no stimulating effect of diNP on oxidation is seen.This uncoupling effect seems to have no connection with phosphorylationat the substrate level, but only with that accompanying the later hydrogen-transport stages. Thus, both HunterM and Judah20 have observed thatdiNP has little effect on the phosphorus : oxygen ratio of the anaerobicdismutation of or-ketoglutarate in presence of mitochondria ; and Grevilleand Rowsell45 found no effect on phosphate uptake during the oxidation-reduction between glyceraldehyde phosphate and pyruvate, by extract ofmuscle acetone powder.DiNP reduces the phosphorus esterification con-nected with or-ketoghtarate oxidation to one quarter ; while with p-hydroxy-butyrate oxidation (where no phosphate uptake is associated with the sub-strate level) diNP abolishes the whole phosphate uptake. As we knownothing of the nature of the phosphorylated intermediates during the passageof hydrogen from CoI-H, to oxygen, any suggestion as to the mechanism ofthe diNP effect must be speculation. The scheme here is based on one givenby Hunter :These facts are suggestive but not conclusive.H,PO, + a-ketoglutarateI -H..&-Cb,H,PO, + hydrogen transport fromCOI to 0,I +Y-PO,X - PO,(CoA-phosphate ? )E. Ronzoni and E. Ehrenfest, J . Biol. Chem., 1936, 115, 749.43 W. F. Loomis and,?. Lipmann, ibid., 1948, 173, 807.44 F. E. Hunter, in‘5 G. D. Greville and E. V. Rowsell, unpublished results.Phosphorus Metabolism,” Johns Hopkins Press, Baltimore,1951, p. 297NEEDHAM : PHOSPHATE METABOLISM. 283Hunter points out that, since the energy of the phosphate link in the hypo-thetical Y-PO, compound is probably of the same order as that of the pyro-phosphate link in ATP, one would expect the reaction between the twocompounds to be reversible.If this is the case, ATP from any source wouldrun a risk of dephosphorylation by means of the diNP leak. Whether or notthis dephosphorylation happene 3. would depend on the relative rate of phos-phate transfer to acceptors othfr than the compound Y, and on the rate ofY-PO, dephosphorylation. From all the considerations which have beenput forward above, we should expect that only the oxidised form of thecompound Y would be capable of accepting phosphate in high-energy bonding,and the energy, of course, would be dissipated on dephosphorylation. Thescheme given might thus explain the greatly increased dephosphorylation ofATP in presence of diNP by mitochondria and by minced muscle 46 aslong as oxygen were available; this dephosphorylation is in contrast to thelack of effect of diNP on partly purified potato apyrase and the compar-atively small effect on myosin.46a It might also account for Ronzoni andEhrenfest’s observations 42 of the uncoupling of phosphorylation with intactfrog muscle even under anaerobic conditions with greatly accelerated lacticacid formation, since here oxygen may not have been completely excluded.It would not explain the finding by Hunter that diNP exerts its effect ofincreasing the apparent adenosine triphosphatase activity of mitochondriaeven in strict anaerobiosis.Lynen and Koenigsberger 47 have found withyeast suspensions that , in aerobic conditions, disappearance of inorganicphosphate is prevented by diNP, while anaerobically phosphorylation con-tinues unchanged. Aerobic fermentation becomes marked in presence ofdiNP and these workers regard this as strong support for their conceptionthat lack of inorganic phosphate (which would reduce the activity of triosephosphate dehydrogenase) is the cause of the diminished carbohydrateutilisation seen in the Pasteur effect.They bring forward some furtherinteresting anomalies in diNP effects-the facts that although the energy-providing phosphorylation in fermentation is not interrupted, yet anaerobicsynthesis of glycogen and also of enzyme proteins during adaptation seemto be prevented.Besides diNP and other substituted phenols, a number of uncouplingagents are known, e.g., amongst antibiotics, aureomycin, gramicidin ; azide ;atebrin ; various dyes.It is interesting that Loomis 48 found no uncoupling effect with penicillin,chloromycetin, and sulphadiazine.The concentration of aureomycin(200 pg. /ml.) needed with mitochondria for 80% uncoupling, correspondsclosely to that (150 mg./kg.) giving 80% mortality in mice. Doses only one-hundredth of this are needed with bacteria to bring about other toxic effects(inhibition of protein synthesis 48a) so that it seems likely that the uncouplingeffect is related, not to the chemotherapeutic action but to the toxicity tothe host.Loomis and L i ~ m a n n , ~ ~ using kidney homogenates, report that azide4 6 H. A. Lardy, unpublished results, mentioned in H. A. Lardy and C. A. Elvejhem,4 7 F.Lynen and R. Koenigsberger, Ann. Chsm., 1951, 573, 60.4 3 W. F. Loomis, Science, 1950, 111, 474.E. F. Gale and J. P. Folkes, Biochem. J , , 1953, 63, 493.Ann. Rev. Biochem., 1945, 14, 1. 46a H. L. Webster, personal communication.W. F. Loomis and F. Lipmann, J. Biol. Ckem., 1949, 179, 403284 BIOCHEMISTRY.cannot " replace " phosphate but can partially " replace " adenylic acid.They suggest that azide acts upon the stage of phosphorus transfer fromprimarily formed phosphate (Y-PO, above ?) to adenylic compounds.Spiegelman, Kamen, and Sussman found dissociation of phosphorylationfrom oxidation-reduction in anaerobic fermentation with yeast suspensions ;and from the azide effects in presence of other inhibitors, they suggest thatthe azide, under the influence of phosphoglycerate phosphokinase, can acceptphosphate from diphosphoglycerate, with formation of an unstable compoundwhich releases inorganic phosphate.It is not clear why, with such a system,azide should not show some phosphate " replacement." Spiegelman et al.found no uncoupling effect in Lebedew yeast extracts, nor could Judah 20find any effect with anaerobic dismutation of a-ketoglutarate.Judah and Williams-Ashman 51 list a number of dyes, notably pheno-safranine, Janus green, Brilliant cresyl blue, which increase the oxygen uptakein absence of added phosphate and greatly decrease the phosphorus : oxygenratio. The dyes may act as supplementary electron carriers, and in so doingmay by-pass reactions connected with phosphorylation.Hormonal Effects.-Thyroxine.The stimulation of metabolic rate bythyroxine suggests comparison with the increased metabolism found withsuch drugs as diNP, and many workers have wondered whether uncouplingplayed a part in thyroxine effects. The position at present is rather con-fused, as the results from different laboratories have been conflicting, butpossible reasons for the disagreements begin to emerge. Lardy and Feldott 52found that thyroxine added in vitro had no effect on phosphorus : oxygenratios of fresh mitochondria by using the Krebs cycle ; however, it and itsbiologically active analogues did inhibit the one-step oxidation of glutamateto succinate and the associated phosphorus : oxygen ratio was affected morethan proportionately.Liver tissue of hyperthyroid rats (fed on thyroid forat least two weeks) had lower phosphorus : oxygen ratios; neverthelessowing to the greatly stimulated metabolism, the actual amount of phosphateesterification was greater. Lipmann 53 reported no difference in phos-phorus : oxygen ratios between tissues of thyroxine-injected and normal rats.There was, however, an interesting effect of the thyroxine. There hadbeen found 54 with mitochondria1 preparations from liver of normal animalsa greatly enhanced oxygen-uptake as the result of addition of phosphateacceptors ; in similar preparations from thyroxine-injected animals, theoxygen uptake was already high, and there was no phosphate-acceptor effect.Since the phosphorus : oxygen ratio was not changed, this seems to indicatethat under certain conditions, thyroxine can cause more effective trans-phosphorylat ion.Martius and Hess 55 found depression of phosphate-uptake in vitro, butonly if the mitochondria were treated with thyroxine (3 x 10-6-5 x 10-6~)for 30 minutes at 0" before measurements; very small thyroxine concen-trations had the opposite effect, stimulating phosphate uptake.They found50 S. Spiegelrnan, M. D. Kamen, and M. Sussman, Arch. Bzochem., 1948, 18, 409.51 J. D. Judah and H. G. Williams-Ashman, Biochem. J., 1951, 48, 33.52 H. A. Lardy and G. Feldott, Ann. N . Y . Acad. Sci., 1951, 54, 531.53 C. H. Dutoit, F. L. Hoch, E. Wright, and F. Lipmann, Abstracts, Second Int.64 H. Niemeyer, R. K. Crane, E. P. Kennedy, and F.Lipmann, Fed. Proc., 1951, 10,Congr. Biochem., Paris, 1952, p. 50.229. 55 C. Martius and B. Has, Arch. Biochem. Biwhys., 1951, 88, 486NEEDHAM : PHOSPHATE METABOLISM. 285lower phosphate uptake than normal if animals were previously injectedwith thyroxine (4-12 mg. over 2 A 7 2 hours), but here there was a markedseasonal variation.Thyroxine also affects some phosphokinases. Askonas 56 found creatinephosphokinase to be 80% inhibited in viko by M-thyroxine ; with a singlelarge injection there was 25% inhibition when the crude muscle extract wastested some hours later. Crude muscle extracts from thyroid-injected ratsshow much enhanced hexokinase activity. 57An effect of insulin has also been recorded which seems to be on oxidativephosphorylation.5* In liver homogenates carrying on oxidation of ct-keto-glutarate with phosphorylation under sub-optimal conditions (e.g., with highadenosine triphosphatase content of the system) insulin had a significanteffect in increasing phosphorylation without increasing oxidation. Thiseffect cannot be through an inhibition of adenosine triphosphatase activity. 59Foa et aZ.,60 using a suspension of washed liver particles from normal andalloxan-diabetic rats, with glutamate as substrate for oxidation, found thatinsulin addition brings about an increase in the degree of phosphorylation ofthiamine in the diabetic preparations, but not in the normal. Goranson andErulkar,61 with heart and brain homogenates, found the aerobic phosphoryl-ation of creatine during succinate and malate oxidation was significantlyless than normal in preparations from alloxan-diabetic rats, although theoxygen uptake was unchanged.Injection of insulin restored the phospho-creatine synthesis to normal without affecting the oxygen uptake. Insulinadded in vitro could also increase synthesis.A similar action of insulin in increasing ATP-provision could, of course,explain its well-known effect of increasing glucose uptake in vitro by dia-phragm. Krah162 has summarised the evidence that there is rather aneffect here directly upon glucokinase. He emphasises that the value for theeasily hydrolysable phosphorus of ATP is the same (about 18 mg.-%) fordiabetic and normal diaphragms in aerobic conditions; and Walaas andWalaas 63 found that even under strictly anaerobic conditions, when this valuehad fallen to 2-3 mg.-%, insulin caused a significant increase in glucoseuptake.It would seem therefore that ATP provision is not a limiting factor.The main identified effect of adrenaline injection seems to be accelerationof formation of active from inactive pho~phorylase.~~ But it is well knownalso to have an inhibitory effect on glucose utilisation, and the work ofCohen and Needham 65 with crude muscle extracts from injected animals,suggests that some interference with ATP resynthesis is concerned here.They found no diminution in hexokinase activity.Utilisation of Phosphate Bond Energy.-We will consider first some casesof synthesis where we have at least a little insight into the mechanism of thereactions.5 6 B.A. Askonas, Nature, 1951, 167, 933.5 7 R. H. Smith and H. G. Williams-Ashman, Acta Biochim. Siophys., 1951, 7, 295.5 8 B. D. Polis, E. Polis, M. Kerrigan, and L. Jedeikin, Arch. Biochem., 1949, 23, 505.59 R. H. Broh-Kahn, P. Foldes, and I. A. Mirsky, ibid., 1950, 26, 460.6o P. P. Foa, H. R. Weinstein, J. A. Smith, and M. Greenberg, ibid., 1952, 40, 523.6L E. S. Goranson and S. D. Erulkar, ibid., 1949, a4, 40.63 E. Walaas and 0. Walaas, J . Biol. Chem., 1952, 195, 367.64 E. W. SutherIand, Ann. N.Y. Acad. Sci., 1951, 54, 693.66 J. A. &hen and D. M. Needham, A d a Biochenz. Biophys., 1960-1961, 6, 141.M. Krahl, Ann. N.Y. Acad. Sci., 1951, 64, 649286 BIOCHEMISTRY.In the case of the formation of the *CO*NH* bond in the synthesis of hip-puric acid, from benzoate and glycine, CoA as well a s ATP is needed.Cohenand McGilvery 66 showed that N-phosphoglycine cannot replace glycine,and Chantrenne 67 that benzoyl phosphate cannot replace benzoate. Thereis no detailed evidence, but it seems likely that CoA-phosphate is first formedand then benzoyl-CoA; in fact, that this synthesis involves a reversal of thesort of process suggested for ATP formation during oxidation of a-keto-glutarate. A rather similar train of events is indicated by the considerationsput forward by Green 68 on the well-known sparking phenomenon pre-liminary to the oxidation of fatty acids by mitochondria. He and his col-laborators have studied fatty acid oxidation in soluble extracts of pig heartand the steps seem to be :ATP + CoA -+ CoA-phosphate (or -pyrophosphate) + ADPCoA-phosphate + fatty acid -+ (fatty) acyl-CoA(fatty) acyl-CoA + 8-ketoacyl-CoAAnother mechanism for synthesis of the *CO*NH* bond has been studiedindependently by Speck e9 and by Elliott 70 in the formation of glutaminefrom glutamate and ammonia.Partially purified, soluble preparations fromacetone-dried liver and brain were mainly used, and the dependence of thesynthesis upon stoicheiometric dephosphorylation of ATP was shown. Ithas not so far been possible to isolate any phosphorylated intermediate com-pound, or to show that more than one enzyme is concerned. The synthesisof glutathione has been studied by Bloch 71 and his collaborators by usingextracts of acetone-dried pigeon liver and glycine and glutamic acids withlabelled carbon or nitrogen atoms, At least two enzymes are concerned, onein the formation of glutamylcysteine, the other in the reaction of this com-pound with glycine; ATP is essential in both cases.The enzyme systemconcerned in the latter reaction has been considerably purified, and it hasbeen shown that stoicheiometric amounts of phosphate are set free fromATP during the synthesis.There are now strong indications that phosphorylation plays an essentialpart at three stages in the ornithine cycle of urea formation. Grisolia andCohen 72 have shown that the reaction :proceeds in three steps :fl-ketoacyl-CoA f acyl-CoA (with 2 carbon atoms less) + acetyl-CoAATP M&+ornithine + CO, + NH, --> citrullineATP glutamate + CO, + NH, -> carbamoylglutarnate .. (1)carbamoylglutamate + CO, + NH, -> intermediate . . (2a)intermediate + ornithine --+ citrulline + carbamoylglutarnate . (2b)ATPThe last two enzyme systems have been partially separated, and can bestudied separately, since (2b) only comes into play if ornithine is added. In6* D. E. Green, Science, 1952, 115, 661.6 6 P. P. Cohen and R. W. McGilvery, J . Bid. Chem., 1947, 171, 121.6 7 H. Chantrenne, ibid., 1951, 189, 227.6a J. F. Speck, J . Bid. Cham., 1949, 179, 1405.7* .W. H. Elliott, Biochem. J., 1951, 49, 106.71 K. Bloch, J . Bid. Chem., 1949, 179, 1245; R. B. Johnston and K. Bloch, ibid.,1951, 188, 221; J. E. Snoke and K.Bloch, ibid., 1952, 199, 407; K. Bloch, J. Snoke,and S. Yanari, ‘‘ Symposium sur la Biog6nGse des Prot6ines,” Second Int. Congr. Bio-chem., Paris, 1952, p. 32.72 S . Grisolia and P. P. Cohen, J . B i d . Chem., 1961, 191, 189; 1952, 198, 561NEEDHAM : PHOSPHATE METABOLISM. 287absence of ornithine, the accumulation in (2a) of an activated compound canbe demonstrated, which can be estimated by its power to react with ornithine.The incorporation of carbon dioxide and ammonia in (Za) is proportional tothe carbamoylglutamate added ; and with all constituents present, the in-organic phosphate set free is proportional to the citrulline formed. There issome evidence that the intermediate formed in (Za) is a phosphorylated com-pound. Under certain conditions, inorganic phosphorus is not set free in(2a) ; then (a) this mixture can be deproteinised, and by addition of system(2b) + ornithine, liberation of inorganic phosphorus as well as citrullineformation is obtained; (b) if the incubation mixture (Za) is heated, there isan increase in inorganic phosphate, and it can be shown that the increaseruns parallel to a decrease in the power of the system to react with ornithine.The formation of arginine from citrulline has been shown by Ratner and hercollaborators 73 to involve at least three enzymes, which have been partiallypurified by alcoholic fractionation of extract of acetone liver powder.The steps studied are :citrulline + aspartate + ATP -+ intermedate + ADP + phosphateintermediate + H,O --+ arginine + malateThere is evidence that the first reaction involves two enzymes : upon frac-tionation of the system, a fraction was obtained which had little activityunless supplemented with a protein fraction from yeast (itself having nocondensing activity).It seems likely that there is phosphorylation of thecitrulline before the condensation, but no phosphorylated intermediate hasyet been detected. Possibly the equilibrium conditions are such that sig-nificant amounts cannot accumulate, and the dephosphorylation of the ATPonly goes on at a perceptible rate when dephosphorylation of the intermediateoccurs on condensation. The ratio of 1.4-1.8 moles of ATP dephosphoryl-ated per mole of citrulline used suggests that phosphorylation outstripscondensation and that some breakdown of the phosphorylated intermediatecan go on by phosphatase activity.A case of synthesis in which until recently it was believed that phos-phorus bond energy was used, is trans-methylation to nicotinamide orguanidinoacetic acid with methionine as the donor.74 This transfer tookplace in a soluble enzyme system but only in the presence of ATP, andmethionine addition increased inorganic phosphorus formation from ATP.The formation of an intermediate labile phosphorylated compound had notbeen shown, but an active “ methionine,” free from phosphorus, accumulatedon incubation of methionine with partially purified enzyme preparations.This substance could methylate nicotinamide, in absence of high-energyphosphate, when a preparation containing methylkinase (not yet purified)was added.Cantoni 74a has now shown that active methionine is probably :H.CH,dMe*CH,CH,.CH (NH,)*CO,- 773 S. Ratncr and A. Pappas, J . Biol. Chem., 1949, 179, 1183, 1199; S. Ratner and B.Petrack, ibid., 1951, 191, 093; S. Ratner, in “ Phosphorus Metabolism,” Johns HopkinsPress, Baltimore, 1951, p. 601.74 G. L. Cantoni, ibid., p. 641; J. Biol. Chem., 1951, 188, 203, 745.74a G. L. Cantoni, J . Amev. Chem. SOC., 1952, 74, 2942288 BIOCHEMISTRY.and can be considered as a product of methionine and the adenosineportion of ATP. The sulphur of the methionine acquires an additionalcovalent bond ; and it seems likely (see also Woolley l) that-the reductionof this sulphonium compound, when the methyl group is removed and thevalency falls to 2, provides the free energy for the methylation of theaccept or.From the work of Vogt 75 on the isolated perfused adrenal gland, it seemsthat secretion of the adrenal cortical hormones must depend on a continuoussynthetic process, since stores of active hormone in the gland are very small.Her finding that the amounts secreted can be temporarily increased by addi-tion of ATP or phosphocreatine to the perfusing fluid shows that thesecompounds can supply readily available energy.We may turn now to more complicated physiological processes wherethere is evidence of participation of phosphate in the energy-providingmetabolism.Little will be said of muscle contraction, since three reviews 76have appeared on this subject during 1952.It may be mentioned thatfurther interesting studies of the adenosine triphosphatase activity of myosinand actomyosin have been made.7’- 78 The increase in adenosine triphos-phatase activity obtained by pre-treatment of the myosin with calciumions, mentioned by Mommaert~,~~ may prove important, though the increasein activity found in these preliminary experiments does not seem greatenough to suggest that here is the entire explanation of the discrepancybetween rate of adenosine triphosphatase activity in vitro and the rate tobe presumed in vivo if all the energy of contraction is supplied throughATP breakdown. Other cases where movement seems to depend on ATPprovision have been described. Thus Mann found with spermatozoa thatdecrease in ATP content, whether the conditions are aerobic or anaerobic,coincides with loss of motility; and Goldacre and Lorch *l found that in-jection of 1% of the sodium salt into amcebz led to a several-fold increase inspeed of streaming.McElroy a2 has reviewed our knowledge of the mechanism of biolumines-cence in the firefly. In the presence of the purified enzyme, luciferase,there are needed for the emission of light the oxidisable substrate luciferin,oxygen, magnesium, cobalt, or manganese ions, and ATP.The emission oflight quickly fails and it is clear that ATP has become the limiting factor,since only by addition of this constituent can renewed output be obtained.Nevertheless the greater part of the.ATP originally added can be shown stillto be present, for example, by reaction with glucose in presence of hexokinase.I t seems that it undergoes some complexing reaction with the luciferase-7 6 M. Vogt, J . Physiol., 1951, 113, 129.7 6 H. H. Weber and H. Portzehl, Adv. Protein Chem., 1952, 7 , 162; hi. Dubuisson,Ann. Rev. Biochem., 1952, 21, 387; D. M. Needham, Adv. Enzymology, 1952, 13, 161.See also A. Szent-Gyorgyi, “ Chemistry of Muscular Contraction,” Acad. Press, Inc., 2ndedn., New York, 1951 ; and W. I;. H. M. Mommaerts, in “ Phosphorus Metabolism,”Johns Hopkins Press, Baltimore, 1951, p. 551.7 7 W Hasselbach, 2. Naturforsch., 1952, 7 , B, 163, 338.L. Ouellet, K. J . Laidler, and M. 1;. Morales, Arch. Biochem. Biophys., 1952, 39, 37.79 W.H. F. M. Mommaerts, in “ Phosphorus Metabolism,” Johns Hopkins Press,T. Mann, Biochem. J . , 1945, 39, 451.81 K. J. Goldacre and I. J . Lorch, Nature, 1950, 166, 497.W. D. McElroy, in “ Phosphorus Metabolism,” Johns Hopkins Press, Baltimore,Baltimore, 1951, p. 518.1951, p. 585NEEDHAM : PHOSPHATE METABOLISM. 289luciferin-oxygen system, after which it becomes unavailable for the light-producing process. The light-emitting system may be an intermediate inthis complexing reaction. It is interesting that pyrophosphate and tri-phosphate, quite inactive if replacing ATP in the original system, causelight-emission if added after the ATP has become inaccessible. This isinterpretated as due to displacement of the ATP from the complex. Re-cently, Strehler and Totter have succeeded in maintaining luminescencewith little decay for several minutes, by using arsenate or phosphate buffersa t concentrations of 0 .0 2 ~ or more. These substances thus seem to preventthe disappearance of ATP by complexing, although their addition will notstimulate light emission once it has fallen off.Dixon 13 has outlined a general mechanism whereby chemical energycould be utilised in the passage of substances into cells against an osmoticgradient. This depends upon the substance in question undergoing a chemi-cal reaction on the inner side of the cell membrane; and further (in orderthat the absorption may proceed practically to completion) upon the re-action being one with the equilibrium far to one side, i.e., proceeding withliberation of free energy.With regard to absorption of sugars from theintestine, Hele 8Q has recently shown a close correlation between the relativerates of absorption in vivo of different hexoses and the rates of phosphoryl-ation in vitro by hexokinase preparations from the intestinal mucosa. Dratzand Handler, 85 however, using injection of =P-labelled phosphate, could notfind in renal tubules any indication that either glucose-1 phosphate or -6 phos-phate mediated the absorption of sugar. From in vitro studies on erythro-cytes with 32P-labelled phosphate, Gourley 86 has brought forward evidenceconsistent with the view that inorganic phosphate is incorporated into ATPa t the cell membrane before entering the cell. I t is possible that some alsoenters by diffusion.Sacks a7 came to rather similar conclusions on examin-ing the acid-soluble phosphate fractions of liver after injection of =P-labelledphosphate ; but here the impossibility of assessing the true intracellularinorganic phosphate causes difficulties of interpretation. Presumably inthese cases the irreversible reaction would be the subsequent dephosphoryl-ation of the ATP. Gourley has shown with red blood cells that glucose isnecessary for phosphate uptake, and he, as well as Kamen and Spiegelman 88with fermenting yeast and Hotchkiss 89 with respiring staphylococci, foundthat poisons preventing phosphate esterification also prevented phosphorusabsorption. There is evidence, depending on the use of uncoupling agents,that interference with oxidative phosphorylation prevents absorption of suchsubstances as phenol-red, aminohippuric acid, etc,, in kidney tubules;and also prevents the active transport of water, which, it is suggested, isresponsible for the maintenance of normal volume and intracellular hyper-tonicity of kidney slices.g1 In such cases the mechanism of utilisation of83 B.La. Strehler and J. R. Totter, Arch. Biochem. Biophys., 1952, 40. 28.84 M. P. Hele, Nature, 1950, 166, 786, 1018.8 5 A. 1;. Dratz and P. Handler, J . B i d . Chem., 1952, 197, 419.86 D. R. H. Gourley, Arch. Biochenz. Siophys., 1952, 40, 1, 13.J . Sacks, Arch. Biochem., 1951, 30, 423.M. D. Kamen and S. Spiegelman, Sywip. Quanf. Biol., 1948, 13, 151.K. D. Hotchkiss, Fed.Proc., 1947, 6, 263.@O R. P-. Forster and J. V. Taggart, J, Cell. Cowzp. Physiol., 1950, 36, 251.91 J . R. Robinson, Nature, 1960, 166, 989.REP.-VOL. XLIX. 290 BIOCHEMISTRY.phosphorus bond energy remains obscure. Davies and Krebsg2 have out-lined a tentative hypothesis directed towards explaining this utilisation inthe secretion of hydrochloric acid by the oxyntic cells of the stomach; andin maintaining the concentration of potassium ions against a gradient innervous tissue.Phosphate Transfer catalysed by Alkaline and Acid Phosphatases.-Meyerhof and Greeng3 have extended the work on phosphate transfer bymeans of phosphatase activity. Using alkaline intestinal phosphatase, inconditions of high inorganic phosphate concentration where synthetic actionof the enzyme could go on, they showed that this synthetic action was greatlyincreased if phosphate donors were also added.Morton 94 has recentlypurified alkaline phosphatase from intestine and from milk, obtaining themessentially homogeneous electrophoretically. It has thus been possible toshow definitely for the first time that the phosphate transfer is carried out bythe hydrolytic enzyme. In Morton’s experiments the initial rates of phos-phatase and of phosphate-transferring activity were measured ; he found thepercentage transfer to be constant for a given donor, under varying conditions,e.g., of pH and donor concentration; it increased up to a maximum withincreasing acceptor concentration. The percentage transfer was unrelatedto the energy content of the phosphate bond of the donor.This view is alsoexpressed by Green and Meyerh0f,~5 though their earlier results had led themto think that energy relations played an important r81e. The physiologicalsignificance of this met hod of phosphate transfer is still uncertain especiallyas the concentration of acceptor needed, at any rate to show measurableeffects in vitro, is very high, viz., 1-2 M. Ross et aLg6 have shown that theoptimum pH falls with falling substrate concentration, and this has beenconfirmed by Morton. I t seems possible that conditions might arise in thecell under which phosphorylation by this mechanism might spare energy, forexample phosphorylation of glucose by hexose diphosphate. Danielli 97 hassuggested that the alkaline phosphatases may have their main function inproviding energy by phosphate transfer for changes in shape of contractileprotein systems and that in vivo their phosphatase activity may be negligible :he instances the cytological distribution of the enzyme in support of thisview.Morton’s results suggest, however, a fundamental difference betweenthe phosphatases and the phosphokinases, in that with the former water isactivated and acts as an acceptor competing with the organic acceptors.Pentose Metabolism and the Alternative Path of Glucose Oxidation.-Work on the CoII specific oxidation of glucose-6 phosphate has continuedactively, with animal tissues 98 and bacteria and y e a ~ t . ~ ~ J ~ Using purifiedphosphogluconate dehydrogenase, Horecker and Smyrniotis loo have shownO 2 R.E. Davies and H. A. Krebs, Biochem. SOC. S-ymp., 1952, 8, 77.O3 0. Meyerhof and H. Green, ibid., 1950, 183, 377.O4 R. A. Morton, Nature, 1950, 166, 1092; Abstracts, Second Int. Congr. Biochem.,O5 H. Green and 0. Meyerhof, J . Biol. Chem., 1952, 197, 347.O 6 M. H. Ross, J. 0. Ely, and J . G. Archer, ibid., 1951, 192, 561.O 7 J. F. Danielli, Nature, 1951, 166, 464.O 8 F. Dickens and C. E. Glock, Biochem. J . , 1951, 50, 81 ; G. E. Glock, ibid., 1952,D. M. B. Scott and S. S. Cohen, ibid., 1951, 188, 509; J . Comp. Cell. Physiol., 1951,loo B. L. Horecker and P. 2. Smymiotis, J. Biol. Chem., 1961, 198, 371; B. L.Paris, 1952, p. 262.52, 575; J . E. Seegmiller and B. L. Horecker, J .Bid. Chem., 1952, 194, 261.38, Suppl. I, 173.Horecker, P. 2. Smyrniotis, and J . E. Seegmiller, ibid., p. 383MACLAGAN AND WILKINSON : THE THYROID HORMONE. 291that ribulose phosphate is an intermediate in the formation of ribose phos-phate. Scott and Cohen 99 describe the formation of an unknown ester,suspected to be an enediol pentose phosphate, during pentose formation bythis pathway in yeast. G l o ~ k , ~ ~ using liver preparations, has carried furtherthe examination of the fate of the ribose-5 phosphate. Anaerobically, 75%of the ribose carbon appears as glucose-6 phosphate; it seems likely thatthere is a split to triose phosphate and glycollaldehyde (by an aldolase distinctfrom muscle aldolase) followed by condensation to hexose monophosphate ;more carbon than that contained in the triose phosphate appears in thehexose.No free glycollaldehyde was formed. Aerobically the course ofevents seems to be similar, followed by oxidation of the glucose-6 phosphate.These findings have interesting similarities with those of Dische lol onthe fate of ribose-5 phosphate in human red blood cells. Here 75% of theribose disappearing was found as hexose-6 phosphate and fructose diphos-phate. Hough and Joneslo2 have discussed the metabolism of pentoses.They obtained xylulose phosphate from glycollaldehyde and triose phosphatein presence of pea-seed aldolase. Horecker and Smyrniotis Io3 describe thesynthesis of sedoheptulose from pentose phosphate with crystalline musclealdolase, together with pentose-splitting enzyme from rat liver.Oxidation of glucose-6 phosphate by this path proceeds in the absence ofinorganic phosphate, and there is no evidence so far that the free energy ofthe oxidations (of glucose-6 phosphate to phosphogluconate, and of the latterto ribulose phosphate possibly through 2-keto-6-phosphogluconate) is con-served or utilised.Its biological significance seems most likely to be in theprovision of essential ribose phosphate. This question has been consideredby Cohen.lo4D. M. N.5 . THE THYROID HORMONE.Since the last report by F. G. Young in 1944, others have dealt adequatelywith the general physiology of the gland,lY2 the biosynthesis of the hor-m ~ n e , l ? ~ the metabolism of i ~ d i n e , ~ ~ ~ antithyroid substance^,^ the mode ofaction of thyroid hormone,6 and the experimental 49 and clinical * use oflo1 2.Dische, in “ Phosphorus Metabolism,” Johns Hopkins Press, Baltimore, 1951,p. 171.lo2 L. Hough and J. K. N. Jones, Nature, 1951, 167, 180; J., 1952, 4047.lo3 B. L. Horecker and P. 2. Smyrniotis, J . Amer. Chem. Soc., 1952, 74, 2123.lo* S. S. Cohen, J . Biol. Chem., 1951, 189, 617; in “ Phosphorus Metabolism,”Johns Hopkins Press, Baltimore, 1951, p. 148.A. Albert, Ann. Rev. Physiol., 1952, 14, 481.J. Kuhnau, W. Grab, C. Martius, and B. Hess, Arch. exp. Path. Pharmak., 1952,216, 1 ; Sir C. R. Harington, Endocrinol., 19?1, 49, 401 ; J. Roche and R. Michel, Adv.Protein Chem., 1951, 6, 253; W. T. Salter, The Hormones : Physiology, Chemistryand Applications,” Eds.G. Pincus and K. V. Thimann, Academic Press, Inc., New York,1950, p. 181; C. Niemann, Fortschr. Chem. org. Naturstoffe, 1950, 7, 167; “ Transactionsof the American Goiter Association,” C. C. Thomas, Springfield, Ill., U.S.A.R. Michel, “ Symposium sur les Hormones ProtCiques,” Second Int. Congr. Bio-chem., Paris, 1952, p. 75. C. P. Leblond, J . Amer. Pharm. Assoc., 1951, 40, 595.R. Pitt-Rivers, Physiol. Rev., 1950, 30, 194; A. Lawson and C. Rimington, Ann.Reports, 1947, 44, 247. S. B. Barker, Physiol. Rev., 1951, 31, 205.N. B. Myant, ibid., p. 141; E. J. Wayne, A. G. MacGregor, and G. W. Blomfield,ibid., p. 148; R. Paterson, H. C. Warrington, and C . W. Gilbert, ibid., p. 154; E. E.Pochin, Lancet, 1960, 11, 41, 84.7 J . Gross and R.Pitt-Rivers, Brit. Med. Bull., 1952, 8, 136B 2 BIOCHEMISTRY.1311. This Report will therefore be restricted to recent work concerning thenature of the thyroid hormone, a new synthesis of thyroxine, and the studyof thyroxine antagonists.Nature of the Hormone.-It is in this field that the most striking develop-ments have occurred. Despite the impressive evidence that the circulatinghormone consists essentially of free thyroxine in loose association with pro-tein,@ difficulties have been experienced by various workers in expressing themetabolic activity of thyroid preparations in terns of thyroxine content.10The probable explanation of these discrepancies is provided by recent dis-coveries made possible by the development of paper and column chromato-graphy and paper electrophoresis in conjunction with autoradiography,1311 being used as a labelling agent.It has been established that, although thyroxine and di-iodotyrosinemake up the major part of the organic iodine in the thyroid gland, monoiodo-tyrosine is also present.11-15 Several workers have also reported thepresence of small amounts of a number of other unidentified iodine com-pounds.l21 l4 In the plasma the main iodine-containing constituents de-monstrated were thyroxine and iodide with small amounts of unidentifiedmaterial, but earlier reports l6 of the presence of di-iodotyrosine have notbeen ~ubstantiated.~~ l5 Roche, Michel, Michel, and Lissitzky l3 introduceda fresh approach by showing that mono- and di-iodotyrosine were deiodinatedby a specific enzyme3 whose presence they demonstrated in thyroid slicesand, in smaller amount, in slices of liver, kidney, and intestine.Thyroxinewas found to be resistant to this deiodination, an observation which appearsto explain its preponderance in the The association of circulatingthyroxine with a human-serum constituent having an electrophoretic mobilitya t pH 8.5 simiIar to that of a,-globulin was demonstrated by Gordon, Gross,O’Connor, and Pitt-Rivers.17announced the identification as3 : 5 : 3‘-tri-iodo-~-thyronine of their “ unknown I ” component,lg previouslyisolated from the plasma of patients under treatment with therapeutic dosesof 1311. This implies that the substance in thyroid-gland extracts knownas “ compound I” l4 must also have been tri-iodothyronine.’ Almostsimultaneously, Roche, Lissitzky, and Michel 2o described the preparation of9 C.R. Harington, Proc. Boy. Soc., 1944, B, 152, 223; A. Taurog and I. L. Chaikoff,J . Biol. Chem., 1948, 176, 639; J. C. Laidlaw, Nature, 1949, 164, 927; C. P. Leblond andJ. Gross, J . Clin. Endocrinol., 1949, 9, 171; A. Taurog, I. L. Chaikoff, and W. Tong, J .Biol. Chem., 1950, 184, 99; L. N. Rosenberg, J . Clin. Invest., 1951, 30, 1 ; A. Lachazeand 0. Thibault, Bull. SOC. Chim. biol., 1951, 33, 1458.10 C. R. Harington, “The Thyroid Gland,” Oxford Univ. Press, London, 1933;J . H. Means, J. Lerman, and W. T. Salter, J . Clin. Invest., 1933, 12, 683; A. E. Meyerand A. Wertz, Endocrinol., 1939, 24, 683; E.Frieden and R. J. Winzler, ibid., 1948, 43, 40.11 K. Fink and R. M. Fink, Science, 1948, 108, 358; A. Taurog, W. Tong, and I. L.Chaikoff, J . Biol. Chevn., 1950, 184, 83; J. Roche, G. H. Deltour, S. Lissitzky, and R.Michel, Compt. rend. SOC. Biol., 1950, 144, 1321 ; J. Gross, C. P. Leblond, A. E. Franklin,and 3 . H. Quastel, Science, 1950, 111, 605.12 G. H. Tishkoff, R. Bennett, V. Bennett, and L. L. Miller, ibid., 1949, 110, 452.I 3 J. Roche, R. Michel, 0. Michel, and S. Lissitzky, Cmnpt. rend. Soc. Biol., 1951, 145,288. l4 J. Gross and C. P. Leblond, Proc. SOC. Exp. Biol. N.Y., 1951, 76, 686.l5 Idem, Endocrinol., 1951, 48, 714.16 V. Treverrow, J . Biol. Chem., 1939, 187, 737.1 7 A. H. Gordon, J. Gross, D. O’Connor, and R. Pitt-Rivers, Nature, 1952, 169, 19.lo Idem, ibid., 1951, 11, 766.ao J. Roche, S.Lissitzky, and R. Michel, Compt. rend., 1952, 284, 997.Subsequently Gross and Pitt-RiversJ. Gross and R. Pitt-Rivers, Lancet, 1952, I, 439MACLAGAN AND WILKINSON : THE THYROID HORMONE. 293tri-iodothyronine by the iodination of the di-iodo-derivative, followed bychromatographic separation from thyroxine. Later tri-iodothyronine wasshown by Gross and Pitt-Rivers to be several times more active than thyrox-ine, both by the goitre-prevention method in rats 21 and by the dose requiredto relieve myxcedematous manifestations in two hypothyroid patients.22It was suggested that tri-iodothyronine is the active form of the thyroidhormone and that thyroxine requires conversion into the tri-iodo-compoundbefore becoming physiologically active.21 Some confirmation of the physio-logical role of tri-iodothyronine has also been obtained from the study ofanti-thyroxine compounds,23 which apparently act by inhibiting deiodinationprocesses (see below).The fact that thyroxine is antagonised by thesecompounds, while tri-iodothyronine is not, fits in well with this newhypothesis.Gross and Pitt-Rivers appear to have made a noteworthy advance bydrawing attention to the importance of tri-iodothyronine. A t present thesite and mode of its production are uncertain. It might arise by the com-bination of mono- and di-iodotyrosine in the thyroid by a process analogousto that suggested by Harington and Barger 24 for the production of thyroxine.Alternatively, it could be produced by the deiodination of thyroxine, aprocess well known to occur from older work 25 and from the newer and morespecific methods employing 1311-labelled rnaterial.l*~ 15, 26i 27 The con-version of thyroxine into tri-iodothyronine has not been unequivocallydemonstrated, although Gross and Leblond’s experiments l4* l5 have beensubsequently interpreted by Gross and Pitt-Rivers 21 as a probable indicationof this process. In this study l4 tri-iodothyronine was found in the plasmaand excreta of both intact and thyroidectomised rats treated with radio-active thyroxine. If tri-iodothyronine is indeed the active form of thehormone then extrathyroidal sites of production must be a t least as importantin deiodination as the thyroid, since thyroidectomised animals respond tothyroxine and to anti-thyroxine compounds.It is therefore still possiblethat thyroxine is the main secretion of the thyroid, and is converted intotri-iodothyronine in other tissues. This hypothesis is consistent with mostof the facts now known, but awaits more detailed investigation.Anti-thyroxine Compounds.-Following Woolley’s pioneer work 28 onthe inhibitory effects of certain ethers of N-acetyldi-iodotyrosine on tadpolemetamorphosis, attempts have been made to produce compounds effectivein antagonising the peripheral actions of thyroxine. Harington 29 discussedthe question and showed that the thio-ether analogue of thyroxine had21 J. Gross and R. Pitt-Rivers, Lancet, 1952, I, 593.22 Idem, ibid., 1952, I, 1044.23 N.F. Maclagan, W. E. Sprott, and J . H. Wilkinson, ibid., 1952, 11, 915.24 C. R. Harington and G. Barger, Biochem. J., 1927, 21, 169.e 5 A. W. Elmer, “ Iodine Metabolism and Thyroid Function,” Oxford Univ. Press,London, 1938.26 F. Joliot, R. Courrier, A. Horeau, and P. Sue, Compt. rend. 1944, 218, 769; Compt.rend. SOC. Biol., 1944, 138, 325; A. Horeau and P. Sue, Bull. SOC. Chim. biol., 1945, 27,483. F. Joliot, Proc. Roy. Soc., 1945, A , 184, 1 ; N. B. Myant and E. E. Pochin, Clin.Sci., 1950, 9, 421; J. Gross and S. Schwartz, Cancer Res., 1951, 11, 614.27 J. C. Clayton, A. A. Free, J. E. Page, G. F. Sorners, and E. A. Woollett, Biochern.J . , 1950, 46, 598.28 D. W. Woolley, J . Biol. Chem., 1946, 164, 11.29 Sir C.R. Harington, Biochem. J., 1948, 43, 434294 BIOCHEMISTRY.thyroxine-like properties and was not inhibitory. Tetrabromothyroninewas administered to patients with thyrotoxicosis, but the results wereindefinite.a The range of compounds active in the tadpole test was consider-ably extended by Frieden and W i n ~ l e r . ~ ~ ? ~ ~ One of their most effectivecompounds, 4-benzyloxy-3 : 5-di-iodo benzoic acid,32 was shown by Maclagan,Sheahan, and Wilkinson 33 to be active in depressing the metabolism of intactthyroxine-treated mice, by using a simplified method of measuring oxygencons~mption.~~ Later, a number of alkyl 35 and hydroxyalkyl 36 esters of4-hydroxy-3 : 5-di-iodobenzoic acid, several ethers of this acid and theiresters,37 and some derivatives of 4-hydroxy-3 : 5-di-iodobenzaldehyde 38were shown to be active.The most active inhibitors observed during thisstudy were n-butyl (BHDB),35 2-hydroxyethyl and 2- and 3-hydroxy-propyl 36 4-hydroxy-3 : 5-di-iodobenzoates. Evidence, based upon a studyof the physicochemical properties of a series of these esters, has been pre-sented in support of the view that the inhibiting reaction is the same for allthese compounds and that differences in potency are caused by variations indistribution and cell ~ e n e t r a t i o n . ~ ~Barker and his co-workers found that BHDB was active in thyroidectom-ised rats maintained on thyroxine.m The same group reported that certainiodophenoxyacetic acids 41 exhibited anti-thyroxine effects : the 2 : 4-di-iodo-derivative was the most effective, but the 2-, 3-, and 4-iodo-compoundswere also active.A somewhat different approach was that of C ~ r t e l l , ~ ~who found that 2’ : 6’-di-iodothyronine 43 exerted some anti-thyroxine effectwhen tested by the goitre-prevention method. This compound, however,proved almost inactive by the mouse oxygen-consumption method.44The nature of the biological effects produced by this class of compoundhas not been completely elucidated, but in addition to those mentionedabove, BHDB has been shown to inhibit the uptake of 1311 by the thyroidgland in rats45 and mice,46 an effect which appears unlikely to be due toliberation of iodide. Some workers have found it to increase the growth rateof thyroxine-treated rats47 but others reported either no effect 45 or areduction of growth rate.48 The raised metabolism following administration30 J .Lerman and Sir C. R. Harington, J . Clin. Endocrinol., 1949, 9, 1099.5 1 E. Frieden and R. J . Winzler, J . Biol. Chem., 1948, 176, 155.3e I d e m , ibid., 1949, 179, 423.33 N. F. Maclagan, hi. M. Sheahan, and J . H. Wilkinson, hTature, 1949, 164, 699.34 N. F. Maclagan and M. M. Sheahan, J . Endocrinol., 1950, 6, 456.35 M. M. Sheahan, J. H. Wilkinson, and N. F. Maclagan, Biochem. J . , 1951, 48, 188.36 J. H. Wilkinson, W. E. Sprott, and N. F. Maclagan, ibid., 1953, in the press.37 J . H. Wilkinson, M. M. Sheahan, and N. F. Maclagan, ibid., 1951, 49, 710.38 I d e m , ibid., p. 714.J . H. Wilkinson and N. F. Maclagan, Abstracts, Second Int.Congr. Biochem.,Paris, 1952, p. 69; J . H. Wilkinson, Biochenz. J., 1953, in the press.do S. B. Barker, H. B. Dirks, Jr., W. R. Garlick, and H. M. Klitgaard, Proc. SOC.Exp. Biol., N . Y . 1951, 78, 840.4 1 S. B. Barker, C . E. Kiely, Jr., H. B. Dirks, Jr., H. M. Klitgaard, S. C . Wang, andS . Wawzonek, J . PharmacoZ., 1950, 99, 202; Endocrinol., 1951, 48, 70. ‘* R. E. Cortell, J . Clin. Endocrinol., 1949, 9, 955.43 C. Niemann and G. E. McCasland, J . A m e r . Chem. SOC., 1944, 66, 1870; J. H.Barnes, R. C. Cookson, G. T. Dickson, J. Elks, and V. D. Poole, J . , 1953, in the press.4 4 N. F. Maclagan and M. M. Sheahan, unpublished.4 5 M. Lawson and C. E. Searle, J . Endocrinol., 1952, 8. 32.I6 M. K. Brayne and N. F. Maclagan, ibid., in the press.4 7 H.M. Sharp and W. F. J . Cuthbertson, ibid., 1961, 7, xxxviii.4 B N. F. Maclagan and W. E. Sprott, unpublishedMACLAGAN AND WILKINSON : THE THYROID HORMONE. 295of dinitro-o-cresol was inhibited.49 It did not antagonise the anti-goitrogeniceffects of thyroxine and was not itself goitr~genic,~~ thus differing profoundlyfrom antithyroid drugs of the thiouracil type. A clinical trial in thyrotoxi-cosis has so far proved disappointing. Fraser and Maclagan 50 used BHDBin doses up to 3 g. per diem in ten cases and, although some improvement insymptoms was noted, the effects were indecisive. They may have been dueto liberation of inorganic iodide, which is difficult to demonstrate in the urinein these circ~mstances.~~ It appeared that this compound was too toxic tobe used in doses large enough to produce genuine anti-thyroxine effects.Of the several hundred compounds tested, those which exhibited anti-thyroxine activity, with few exceptions, contained 2 : 6-di-iodophenoxy- or4 : 6-di-iodophenoxy-groups in their molecule^.^^ 35 It has been postulatedthat these groups enable the inhibitor to displace thyroxine from an enzymebut the fact that certain monoiodo-compounds are also active 239 40suggests that even simpler structures may be capable of similar interference.This view has been extended by the observation that BHDB actuallyenhanced the metabolic effects of tri-i~dothyronine,~~ the exact opposite ofthe results obtained with thyroxine. A similar increase was obtained withn-butyl 4-hydroxy-3-iodobenzoate. These results, in conjunction with thework on tri-iodothyronine reviewed above, strongly suggest that theseinhibitory compounds act by interfering with deiodination, leading toantagonism in the case of thyroxine and to diminished destruction in the caseof tri-iodothyronine. If this explanation is correct, the term anti-thyrox-ine compound ” is still appropriate, since interference occurs with thepreliminary deiodination of thyroxine which is probably essential for itsphysiological action.New Synthesis of Thyroxine.-An important new route to thyroxine, thefirst alternative to that of Harington and Barger,24 has been described byHems et aZ.52-58 The original synthesis depended upon the reaction of3 : 4 : 5-tri-iodonitrobenzene with $-methoxyphenol to give the diphenylether (I), from the aromatic nitro-group of which the L-alanine side-chain hadto be built up by a somewhat laborious process. This difficulty has beenovercome by the new process, which is based on two new methods of prepar-ing 2 : 6-dinitrodiphenyl ethers.53The first of these involves the conversion, by means of phosphoryl chlorideand a tertiary base,59 e g . , diethylaniline or pyridine, of a suitably substituted2 : 6-dinitrophenol into the corresponding chloronitrobenzene. The pyri-dinium quaternary salt (11) of this reacts with a variety of substitutedphenols in pyridine to give high yields of the corresponding diphenyl ethers.The latter may also be obtained easily from the benzene- or toluene-$-49 N. F. Maclagan, W. E. Sprott, and J. H. Wilkinson, Abstracts, Second Int. Congr.60 T. Russell Fraser and N. F. Maclagan, J . Endocrin., in the press.51 N. F. Maclagan and J. H. Wilkinson, Nature, 1951, 168, 251.52 E. T. Borrows, J. C. Clayton, and B. A. Hems, J., 1949, S185.53 E. T. Borrows, J. C. Clayton, B. A. Hems, and A. G. Long, J., 1949, S190.64 E. T. Borrows, J. C. Clayton, and B. A. Hems, J . , 1949, S199.5 5 E. T. Borrows, B. A. Hems, and J. E. Page, J., 1949, S204.6 6 J . R. Chalmers, G. T. Dickson, J. Elks, and B. A. Hems, J . , 1940, 3424.5 7 J. C. Clayton and B. A. Hems, J., 1950, 860.5* J . H. Barnes, E. T. Borrows, J. Elks, B. A. Hems, and A. G. Long, J . , 1950, 2824.69 J . Raddiley and A . Topham, J . , 1944, 678.Biochem., Paris, 1952, p. 58296 BIOCHEMISTRY,sulphonate 53 of the 2 : 6-dinitrophenol by treating the pyridinium quater-nary salt 6o with a phenol.TNO.,NH NH(a) Catalytic 'k NO, reductionHOH-NOfl-kH,*CH-CO - HOy-\Oy-kH,*CH-CO \=/ \-/ I I ( b ) Tetrazotisation \=/ \=/ I INH NH K1 NH NHI1-Hydrolysis i (VIJI IHOfl-'\\OH--\CH,*CH( NH,)*C02H -A> Thyroxine. \-J \=/(VII) IIn the thyroxine synthesis the C(,pubstituent of the 2 : 6-dinitrophenolmay be one of several groups capable of easy transformation into the alanineside-chain, e.g., forrnyl, the oxazolone derived from alanine (in 111), or thecorresponding hydantoin (IV) . Catalytic hydrogenation of the dinitro-diphenyl ether (V), followed by tetrazotisation with nitrosylsulphuric acidunder anhydrous conditions 529 54 and reaction with iodide, gave the di-iodo-compound (VI). Alkaline hydrolysis. converted this into 3 : 5-di-iodo-thyronine (VII) which, on treatment with iodine in ammoniacal solution,24gave DL-thyroxine. The explosion hazard which results from the presenceof nitrogen iodide during the final stage has been obviated by the replacementof the ammonia by an organic base,57 e.g., aqueous ethylamine.Chalmers et L z Z . , ~ ~ in applying this route to the synthesis of L-thyroxinefrom L-tyrosine, found that appreciable racemisation occurred when thealanine side-chain was protected by conversion into the hydantoin ring, Thedesired product, however, was obtained in an overall yield of 26%, withoutloss of optical activity, when the amino- and carboxy-groups were protectedby acetylation and esterification, respectively.A similar process was used by Elks and Waller 61 for the synthesis of D-thyroxine from 3 : 5-dinitro-~-tyrosine. The D-isomer had previously beenprepared in small amounts by Harington,62 who iodinated the 3 : B-di-iodo-6o W. Borsche and E. Feske, Ber., 1927, 60, 157.62 C. R. Harington, Biochem. J., 1928, 22, 1429.J. Elks and G. J. Waller, J., 1952, 2366MACLAGAN AND WILKINSON : THE THYROID HORMONE. 297D-thyronine obtained by resolution of the synthetic racemic compound, andby Pitt-Rivers and L e ~ m a n , ~ ~ by the inversion of L-tyrosine, followed byiodination and mild oxidation of the resulting 3 : 5-di-iodo-D-tyrosine withhydrogen peroxide.was obtained by the reaction of the L-isomer with nitrosyl bromide to giveL-ol-bromo- p- (4-hydroxy-3 : 5-dinitrophenyl) propionic acid which underwentinversion on subsequent treatment with ammonia.The 3 : 5-dinitro-D-tyrosine used in the new processN. F. M.J. H. W.E. BOYLAND.S. P. DATTA.J. LASCELLES.N. F. MACLAGAN.D. M. NEEDHAM.J. H. WILKINSON.63 R. Pitt-Rivers and J. Lerman, J . Endocrinol., 1948, 5, 223

ISSN:0365-6217    

DOI:10.1039/AR9524900252

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.I. INTRODUCTION.ANALYSIS is " the separation, the identification or the determinationof the concentration of part or all of the constituents or components ofa sample." This dispassionate statement, one of the definitions recentlyrecommended by the Committee on Nomenclature, Division of AnalyticalChemistry of the American Chemical Society,l is one to which no onecould take serious exception. It is bald, but in a definition there is noroom for imagination. An article of faith, as distinct from a definition,has also, however, recently been forthcoming.2 " Analysis, qualitative andquantitative, is the basis of the technique of chemical operations. Nosynthesis can be accounted complete until the synthesised product has beenanalysed, its component parts established and determined.In fact,chemistry is founded, is based, on analysis. The theories of the thinkers areproved or disproved by analysis ; the guesses of the inspired can only becomecertainties through the manipulation of the analyst." Up to this point thedefinitive essence parallels precisely enough with the previous quotation , andthe addenda are the logical consequences of serious thinking about the placeand scope of this branch of chemistry.It would not, however, be right to end the quotation a t this point, sincethe sequel contains more than the germ of a truth. It continues: " Butanalysis is not a separate discipline, although from the importance it hasattained . . . it might be assumed it were an end in itself.Although analysisis but an aspect of chemical technique, the analyst himself has almostbecome such a specialist that he may be divorced from the genuine trend ofchemical development and become immersed in the study of the break-downof compounds or of the determination of ' pointers ' to the composition ofnatural or of manufactured compounds. And so it is that one of the dan-gers. . . is that workers lose their love of chemistry, and, instead, take tothemselves analysis. 'This divorce from the genuine trend of chemical development, a veryreal danger in any branch of chemistry, is perhaps particularly so in analyticalchemistry, and is always to be seen in any close survey of the literature.Specific aspects of it will appear later in this Report.On the general issue,however, it behoves anyone presenting advances in analytical chemistry toconsider how best his work can serve the general body of chemistry. Thesubject may range over the vast field from the most specialised of appliedanalyses to fundamental problems whose spheres of influence are obviouslylarge though their boundaries may not be clearly discernible. The ad hocwork of the industrial analyst may be of no interest to the vast mass ofanalytical chemists, much less to the body of chemists in general. On theother hand it might well have within it an idea which, more widely knownL. T. Hallett e t aZ., AnaZyt. Cham., 1952, 24, 1348.L. H. Lampitt, Analyst, 1952, 77, 564WILSON : INTRODUCTION. 299and applied, could revolutionise some branch of chemistry.One must, then,take note of those apparently minor papers which “ analytical intuition ”or one’s own interest suggests might be of interest to one’s chemical colleagues.One must do this, moreover, always unpleasantly aware of the unreliabilityof intuition’s aid. Who would have been inspired by a paper describingphysicochemical studies on chlorophyll in 1906 or one on the manipulationof small precipitates in 1909 4 to forecast that these were seeds which wouldproduce, in 1923 and in 1952, Nobel prizes awarded for distinction in thefield of analytical chemistry ?At the same time the Reporter must select from the extensive series ofpapers dealing specifically with analytical chemistry-certainly more than4000 per annum-those which will present a starting point for any analystwishing to follow up any particular section. His selection must in additionrepresent fairly the distribution of work throughout the past year.In thisway chemists whose main interests are other than analytical may be able tonote activities and to judge trends.His selection, however, must always be personal, and it can never behighly critical. It is possible to refute or to support a theory. But analyticalchemistry is in excelsis that branch of the science where the proof lies at thebench. A method may sound promising, or novel, but until one has triedit one can rarely say more than this about it.There is still that“ trend of chemicd development ” and the action and reaction between it andthe field of analytical chemistry.Just as the chemist benefits from thework of the analyst in all fields, the analyst must benefit from the work ofthe chemist in all fields. The necessity for fundamental research in analyticalchemistry was stressed in this Report last year. The fundamental work may,however, be of two kinds-that done by analytical chemists within their ownfield, usually easy to recognise; and that done by other workers, who haveno knowledge that they are increasing (and perhaps, indeed, no desire toincrease) the resources of the analyst. Assessment of such work mustagain, of necessity, be largely by intuition and personal interest, but nowadditionally hampered by the fact that one is working outside one’s specialistfield.Themost obvious fundamental development in which the analytical chemistmust interest himself at the present time is that dealing with the structuresof organometallic compounds.Both within and without the analyticalfield this branch has been increasingly active during the past few years anda valuable survey of this field is now a~ailable.~“ In the long term the majorpart of the work must fit together to form a pattern. At the present time,since little assembly and less pattern can be said to exist, it can only be hopedthat a few of the more critical pieces near the centre can be indicated.None of these major aims of the Reporter will be satisfactorily achieved ;but the Report may, in spite of this, attain a final form which will please someof the people some of the time.With all this the Reporter’s work is not finished.Indeed, the selection on this last basis must almost be random.M.Tswett, B e y . deut. bot. Ges., 1906, 24, 316.F. Emich and J. Donau, Monatsh., 1909, 30, 746.A. E. Martell and M. Calvin, “ Chemistry of the Metal Chelate Compounds,” NewYork, 1952300 ANALYTICAL CHEMISTRY.In Great Britain, in 1952, much interest was centred in the InternationalCongress held in Oxford in September, and now fully documented,5 and inthe smaller, but still quite important Symposium in Birmingham whichfollowed the Congress, and which is, as yet, only reported in abstract form.sFrom the former of these we have freely and gratefully used one of theCongress lectures to illustrate our opening remarks.Individual papers willbe reported in their appropriate places.The remaining two Congress lectures may be mentioned here as expressingclearly two topical aspects of analytical chemistry. R. H. Muller,’ indealing with research in analytical instrumentation, was mainly concernedwith future trends. He maintained that analytical chemists have not yetmade anything like full use of the resources of the science of instrumentation,although he claimed that the use of instruments is widespread and alreadydominates many types of analysis.” The use of the term “ dominates ” is,one would hope, ill-founded, and is, perhaps, a slip, since the speaker wenton to point out that the analyst could, and more and more should, relegatehis instrumental problems to the specialist, but that only the analyst coulddetermine the problems.The other Congress speaker, C.J. van Nieuwenburg8 was concernedwith the place of “ classical ” methods in analytical chemistry. The growthof instrumental methods has given rise in some quarters to the belief thatclassical methods are a dying species. This he regards a9 completely un-founded. That the two opposite types of solution to analytical problems arenot opposed types, but are capable of being employed together, was hisprincipal theme. The variety of weapons available has been increasedrather than altered. His conclusions are strikingly similar to those ofMiiller when one considers the different terms of reference. He holds thatinstrumentation and organisation “ will not be any use unless there areleading men who understand the whole job.Maybe the old classical methodswill disappear some day, although I do not think that day is very near. Butthe old classical knowledge of analytical chemistry will remain. In thelong run brains will count.”The practice of analytical chemistry has been discussed on other occasions.It is significant that similar conclusions regarding the need for integrationof instrumental and classical methods, rather than a complete replacementof classical by instrumental methods, is explicitly emphasised from thepedagogic point of view 9 as well as implicitly from that of the professionalpractitioner.10 In the latter case we are reminded that the practisinganalytical chemist is called upon to apply “ a knowledge not only of hisbackground in the field of analytical chemistry, but the broadest backgroundof chemical subjects that he can command, and to strive for a solution bythe application of known methods, principles and procedures in flew patterns.”Much of the research in analytical chemistry today is concerned, not with theprovision of new principles and methods, but with the summation of know-ledge in a new way..Analyst, 1952, 77, 557 ff.Ind.Chem. Chem. Manuf., 1952, 28, 487.Analyst, 1952, 77, 557.Ibid., p. 573.9 P. W. West, J . Chem. Educ., 1952, 29, 222.l o S. E. Q. Ashley, Analyt. Chem., 1952, 24, 1690WILSON GENERAL. 3012. GENERAL.In the Progress Report of the Committee on Nomenclature alreadyreferred to,1 specific definitions are put forward as recommendations, but theReport is not regarded as final.A number of the definitions are not novel,but it is useful to have them in compact form. The term ‘‘ volumetric,”it is recommended, should refer to measurement by volume, and is not to beregarded as synonymous with “ titrimetric,” which is measurement bytitration. This is a view that will be welcomed by many analysts, althoughit will require constant caution to prevent falling into the older usage.Definitions are proposed, based on sample size, for the prefixes macro-,semimicro-, micro-, and ultramicro-, and this is more likely to be a subjectfor future debate.It is somewhat unexpected, in view of the distinction that some workershave stressed in the past between “ iodimetry ” and “ iodometry,” to findthat “iodometry” is defined as the measurement of concentration bytitration with a standard solution of iodine ; but measurement of concentra-tion by titration with a standard solution of thiosulphate is denoted by theterm “ thiosulphatimetry.” There seems to be no reason for the divergenttreatment of the two terms, and one wonders on what basis the Committeewill discriminate between the various forms that have been proposedfrom time to time for the performance of titrations by measurement ofconductance.The definitions so far proposed are limited in number, and many termshave yet to be considered.A more detailed Report on proposed terms and definitions in appliedspectroscopy has also been published.ll In the Report, in addition toproposals, a group of general principles of nomenclature-standardisation isstated, and there is also included a list of terms about which no decision hasyet been reached.The preparation of sodium chloride suitable for use as a primary analyficalstandard has been described.12 Acetylsalicylic acid l3 and sulphamic acid 14have been proposed as primary standards in alkalimetry.The former hasthe advantage that its purity can be checked, after titration, by hydrolysiswith excess alkali to salicylic acid, and back titration, which should indicatethe consumption of a further equivalent of alkali. The latter reagent isknown to hydrolyse slowly, a slight but appreciable test for sulphate beingobtained after six days storage of the solution.The hydrolysis is to bi-sulphate, however, and the replaceable hydrogen of the sulphamic acidought merely to be substituted by the replaceable hydrogen of the bi-sulphate. In consequence there should be no alteration in the normalitytowards alkali; no appreciabIe change in normality was found, on test, after213 days. The advantages claimed for the reagent are its ready solubilityin water; the fact that it is an acid only slightly weaker than the mineralacids so that it can be titrated readily by using indicators whose workingrange is pH 4 - 9 ; and the ease of obtaining and maintaining it in a highl1 H. K. Hughes et al., Analyt. Ckenz., 1952, 84, 1349.l2 L. Meites, J . Chem. Educ., 1952, 29, 74.lS F.Barriel, F. Pino, and M. D. Vinuesa, Afinidad, 1950, 87. 337.l4 W. F. Wagner, W. F. Wuelher, and C. E. Feiler, Amlyt. Chem., 1952, 24, 1491302 ANALYTICAL CHEMISTRY.state of purity. In addition, since practically all its salts are soluble, thereis little danger of interference with the titration through formation ofprecipitates.Calcium acid malate hexahydrate has been recommended l5 as a standardfor alkalimetry and for the calibration of pH meters. In addition it provesuseful as a standard for calcium titrations-a field which has extendedconsiderably in recent years (p. 305). With a very high equivalent weight of207, it possesses all other desirable qualifications of such a standard exceptthat it cannot be dried a t 100".However, it is non-hygroscopic, and anytrace of adsorbed moisture, which is not a likely feature, can be removed byaspiration of dry air over the solid. The same solid may be used indirectlyas a standard for acidimetry by ignition to the oxide, solution of this in excessof acid, and back titration with alkali.Statistical aspects of analytical chemistry have been discussed by anumber of authors.16 Methods for approximating to the standard deviationhave been proposed and applied to practical examples.1' The reconciliationof scientific and statistical hypotheses, in the special case of radiochemistry,has been considered.18H. Ballczo l9 has pointed out some of the ways in which errors in titri-metric analysis, particularly with dilute solutions, may be reduced byattention to calibration of apparatus and to temperature corrections.Thespecial case of the double titration has been included in this treatment. Thepossible sources of error inherent in weighing techniques have been discussedby M. J. Marteret.20 The titrimetric error arising from adsorption of silverions on glass has been studied by a radioactive indicator method.21The importance of training students of chemistry to appreciate sourcesof error has been pointed out,22 and a suitable course outlined which includessuch procedures as the determination of uncertainty in analytical results.It has also been stressed 23 that in addition to operational error there may,in such conditions, also be instructional error, which may exist even ifstudents obtain the correct result.The consequences of this, methods ofappreciating its existence, and methods of reducing it have been outlined.Tables have been issued for use in the calibration of graduated glass-ware24 and specifications have been drawn up for one-mark graduatedflasks 25 and automatic microchemical burettes.26The field of inorganic microchemistry has been reviewed,27 and semi-micro-techniques for titrimetric analysis, employing sealed vessels of thepharmaceutical-serum type, and hypodermic syringes, with measurementscarried out by weighing rather than by volume, have been described.28Its only notable drawback is its low molecular weight.l6 A. C. Shead, Analyt. Chem., 1952, 24, 1451.l6 R. J. Hader and W. J.Youden, ibid., p. 120; W. J. Youden, Analyst, 1952, 77,874; G. E. P. Box, ibid., p. 879; E. G. Gracheva, J . Anal. Chem., U.S.S.R., 1952, 7 , 48;J. M. Pertierra, Inform. Qudm. analit., 1952, 6, 117.17 B. Woolf, Nature, 1952,170, 631 ; H. de Miranda, Chenz. Weekblad, 1951, 47, 1046.18 L. Martin, Analyst, 1952, 77, 892.lo 2. anal. Chem., 1952, 134, 321.z1 H. M. Hershenson and L. B. Rogers, Analyt. Chem., 1952, 24, 219.2z W. R. Carmody, J . Chem. Educ., 1952, 29, 349.a* W. J. Blaedel, J. H. Jefferson, and H. T. Knight, ibid., p. 480. *' B.S.I. Specif., 1952, No. 1797.26 Ibid., No. 1428, Pt. D1.31 D. M. Smith, J. Mitchell, and A. M. Billmeyer, ibid., p. 1847.2o Chim. analyt., 1952, 34, 149.Ibid., No. 1792.P. W. West, Analyt. Chem., 1952, 24, 76WILSON : GENERAL.303A general review of ultramicro-quantitative analytical methods has beengiven,29 and micro-manipulators 3c, 31 and other apparatus 31s 32 designed forwork on the microgram scale have been described.Reagents.-In the field of reagents there has been much work of directuse to the analytical chemist, and probably even more that is likely to beof future importance to him. A. E. Martell 33 has discussed some of the waysin which aqueous metal ions are affected by complex formation, with par-ticular reference to the formation of chelate compounds. Such propertiesas solubility, electrical conductance, interaction with hydrogen ions, ab-sorption spectra, oxidation potentials and, above all, stabilities as measuredby the equilibrium constants of the formation reactions, are all fundamentalproperties which are of value in the investigation of the formation of com-plexes.Such study must lead to the development of new and valuableapplications of complex fonnation. New analytical reagents utilisingunusual oxidation states have been reviewed.34Many investigations of the structures of complexes have been reported,both by analytical chemists and by those outside the field of analyticalchemistry, and it is difficult to determine which of these will, in the longterm, have most significance. In this connection earlier comments regardingthe tendency of the analytical chemist to fall behind the general stream ofdevelopment have considerable force. It is unfortunate that in many of thestudies which have been made on organometallic compounds, and, indeed inthe general literature of analytical chemistry, there is a tendency to clingto conceptions which are, as far as the general theory of chemistry is con-cerned, out-of-date and by now almost meaningless.Thus the classificationof such complexes which was current some time ago, and which was neveranything more than an ad hoc classification, into groups such as “ pene-tration,” and “ inner-complex ” compounds, still persists in many of thepublications, although modern ideas on the structures and binding forces ofmolecules, atoms, and ions permit us at least to discard this for somethingmore in keeping with the times. Ina t least one recent publication valencies were referred to as “ principal ”and “ auxiliary,” which might almost be said to smack of the phlogistonera.If analytical chemists are to make satisfactory contributions to thetheoretical side of this topic, they must familiarise themselves with modemideas on bond structure, and they can, with profit, read some of the public-ations referred to in this section. Many of these, which have no direct orimmediate bearing on practical problems of analytical chemistry, seem tocontribute significantly to the theory of complex-formation, and thus to havean ultimate value for the man a t the bench.It is, perhaps, going to the other extreme to refer, as some authors do, tocompounds such as calcium oxalate and calcium acetate under the classific-ation of complexes.While it is true that an extreme current view is to regardany anion derived from more than one atom as a complex ion, the term‘ I complex ” loses much of its significance, in the analytical sense a t least,and probably also in a wider field, if some sort of division is not indicatedSuch terms still appear too frequently.a9 A. E. Sobel and A. Hanok, Mikrochem. Mikrochim. Acta, 1952, 39, 51.ao T. Brindleand C. L. Wilson, ibid., p. 310.33 A. Lazarow, J . Lab. Clin. Med., 1951, 38, 660.34 M. Kapel, Ind. Chem. Chem. Manuf., 1952, 28, 466.31 M. C. AlvarezQuerol,ibid., p. 117.33 J . Chem. Educ., 1952, 20, 27304 ANALYTICAL CHEMISTRY.between these structures and the more complicated ones which are normallyclassed as complexes. It may be that the distinction will be supplied by theincreasing use of the term " chelates."There is now available an excellent account 4a of methods of study inthis field, and of the results which these methods have so far given.Anorder of stability for metal complexes has been reported, and generallyspeaking, this seems to agree among the various groups of complexes be-tween the metallic ions and a variety of organic compounds.35 The studiesalso support the greater stability of five- than of six-membered chelates.It is found that zinc, nickel, and cobalt(I1) co-ordinate with three moleculesof tropolone to form singly charged ions, while the corresponding copper(n),beryllium, and lead complexes contain only two organic molecules and areneutral.The co-ordination chemistry of the transition metals has been studied,36and magnetic data for many of these compounds have been related tovalency, structure, and bond type, with particular reference to the ionic orcovalent nature of the linking.From a more strictly analytical point ofview H. M. Irving and R. J. P. Williams 37 have considered a number of thefactors controlling the action of organic reagents. The stabilities of thecomplexes have been considered in relation to their solubilities, the nature ofthe metallic ion, the nature and the acid dissociation constant of the reagent,and the pH a t which the complex exists. Particular attention is paid to thespecificity of reagents.H. Freiser 38 discusses stability in relation to analytical use for a widerange of metal-chelate compounds, and brings home clearly the enormousextent of the field which has to be examined before any comprehensivetheory can be advanced, and the complexity of the factors involved, suchas steric hindrance and solubility.In this paper particular examples usedfor illustrative purposes are 2-o-hydroxyphenylbenzoxazole as a reagent forcadmium, 2-o-hydroxyphenylbenzothiazole for copper or cadmium, and2-0-hydroxyphenylbenziminazole for mercuric mercury.Probably the reagent which has received most analytical attentionthroughout the past year is ethylenediaminetetra-acetic acid. Uses for thisreagent were reviewed in last year's Report,39 but many extensions ofexisting uses and many new uses have since been developed.The uses of thisreagent and of the related nitrilotriacetic acid have been reviewed from apractical point of view 40 and theoretical aspects of its application have beendiscussed.41claims that in order to overcome the instability of theindicator Eriochrome Black T [or sodium 1-( 1-hydroxy-2-naphthy1azo)-5-nitr0-2-naphthol-4-sulphonic acid] it may be made up in diethanolamine ortriethanolamine solution, which will remain stable for at least seven months.It should be stored in such a way that the solution is protected from atmo-E. M. Diskanta6 B. E. Bryant, W. C. Fernelius, and B. E. Douglas, Nature, 1952, 170, 247.36 F. H. Burstall and R. S. "yholm, J., 1952, 2906, 3570; R. S. Nyholm and A. G.Sharpe, ibid., p. 3579. 37 Analyst, 1952, 77, 813.38 Ibid., p.830. 39 Ann. Reports, 1951, 48, 311.40 M. 0. Lawson, IRd. Chem. Chem. Manwf.., 1952, 28, 512, 559; G. C. Krijn, Chem.Weekblad, 1952, 48, 165; H. Flaschka, Mikvochem. Mikvochh. Acta, 1952, 30, 38.4l G. Schwarzenbach, Analyt. Claim. Ada, 1952, '7, 141.42 AnaZyt. Chem., 1952, 24, 1856WILSON GENERAL. 305spheric moisture, but need not be protected from light or from alterations ofatmospheric temperature. Several variants of methods for determination ofcalcium- and total-hardness of water have been proposed,43 and in one casecopper and iron are first removed by addition of cyanide and passage throughan anion-exchange resin column.& The reagent has been widely applied tothe determination of calcium 45 and magnesium 46 in biological fluids, and ofthese elements in other materials such as lirne~tones.~~ The effect of varyingthe concentration of potassium chloride in the calcium determination hasbeen examined.4s Direct or indirect titration methods for a number of otherelements have been proposed.Phosphate is determined by precipitation asmagnesium ammonium phosphate and subsequent determination of themagnesium.49 Barium and zinc 51 may be titrated directly. Sodium maybe estimated through zinc after precipitation as sodium zinc uranyl acetate.62Nickel, first precipitated by dimethylglyoxime, may be titrated directly.53When a solution of a silver salt is allowed to react with ammoniacal nickelcyanide solution, an equivalent amount of nickel ion is set free which may betitrated, thus giving a measure of the silver.54.55 This, in turn, may be usedt o determine halide after precipitation as silver halide. This determinationmay be used in coloured or cloudy solutions where the classical methods forhalide are unsatisfactory. Thallium may be titrated directly with a solutionof the magnesium complex.56 Lead may be titrated directly, either alone 57or in the presence of which latter may be masked by cyanide andthen subsequently estimated by a total titration in absence of cyanide.Apart from its uses as a titrimetric reagent, ethylenediaminetetra-aceticacid has been used to prevent interference in the estimation of ~ u l p h a t e , ~ ~nitrate,60 beryllium,61s 62 and ir0n.6~ It has been recommended for the43 J.E. Houlihan, Analyst, 1952, 77, 158; R. Sijderius, Chern. Weekblad, 1952, 48,44 J. W. McCoy, Analyt. Chim. Acta, 1952, 6, 259.46 A. C. Mason, Analyst, 1952, 77, 529; H. Lempfrid and J. Stiirmer, Klin. Woch-enschr., 1952, 30, 227; H. Neilsen, Nord. Med., 1952, 48, 1059; H. Flaschka and A.Holasek, 2. Physiol. Chem., 1951, 288, 244.IS A. Holasek and H. Flaschka, ibid., 1952, 290, 57; E. S. Buckley, J. C. Gibson, andT. R. Bortolotti, J . Lab. Clin. Med., 1951, 38, 751; A. H. Holtz, Chern. Weekblad, 1951,47, 907; A. E. Sobel and A. Hanok, Proc. SOC. Exp. Biol., N.Y., 1951, 77, 737; KuangLu Cheng and R. H. Bray, Soil Sci., 1951, 72, 449.4 7 J. J. Banewicz and C. T. Kenner, Analyt. Chem., 1952, 24, 1186; Kuang Lu Cheng,T. Kurtz, and R. H. Bray, ibid., p.1640; J . Banks, Analyst, 1952, 77, 484; L. E. Smith,Pulp and Paper, 1952, 26, No. 5, 86, 88; K: E. Langford, Electroplating, 1952, 5, No. 2,41.4 8 F. F. Carini and A. E. Martell, J . Amer. Chem. Soc., 1952, 74, 5744.O9 H. Flaschka and A. Holasek, Mikrochem. Mikrochirn. A d a , 1952, 39, 101; F.Huditz, H. Flaschka, and I. Petzold, 2. anal. Chem., 1952, 135, 333.51 E. W. Debney, Nature, 1952, 169, 1104.5* H. Flaschka, Mikrochem. Mikrochim. Acta, 1952, 39, 391.53 W. F. Harris and T. R. Sweet, Analyt. Chenz., 1952, 24, 1062.64 H. Flaschka, Mikrochem. Mikrochim. A d a , 1952, 40, 21.5 5 H. Flaschka and F. Huditz, 2. anal. Chem., 1952, 137, 104.66 H. Flaschka, Mikrochem. Mikrochirn. Acta, 1952, 40, 42.5 8 H. Flaschka and F. Huditz, 2. anal.Chew., 1952, 137, 172.5D D. Gibbons, I n d . Chem. Chem. Manuf., 1952, 28, 487.8o F. L. Hahn, Analyt. Chim. Acta, 1952, 7, 68.81 J . Hur6, M. Kremer, and F. le Berquier, ibid., p. 37; R. G. Smith, A. J . Boyle,P. I. Brewer, Analyst, 1952,J. A. Adam, E. Booth, and J . D. H. Strickland, Analyt. Chim. A d a , 1952, 6, 462.378; W. Fivian and M. Moser, Sugar I n d . Abstr., 1951, 13, 131.T. J . Manns, M. U. Reschovsky, and A. J. Certa, Analyt. Chem., 1952, 24, 908.5 7 Idem, ibid., 39, 315.W. G. Fredrick, and B. Zak, Analyt. Chem., 1952, 24, 406;77, i 3 9 .63 R. L. Morris, Analyyt. Chem., 1952, 24, 1374306 ANALYTICAL CHEMISTRY.colorimetric determination of cobalt .64 The complexes with europium 65and with thorium and uranyl ions 66 have been examined. R.C. Vickery 6 7 9 68has investigated the stability constants of metallic ions with this reagent,with particular reference to their use in ion-exchange methods for separatingthe lanthanons. He has shown that the elution series for complexes ofbivalent metals is affected by the presence or absence of tervalent metalcomplexes. He has also achieved a good separation of praseodymium fromneodymium by addition of manganese to act as a separating element. Forthe most efficient separation, low concentration of the reagent together witha low flow rate, a high pH value, and an exchange resin in the ammoniumform are recommended. Finally, H. Flaschka 69 has investigated the effectof the presence of ethylenediaminetetra-acetic acid on the behaviour ofthioacetamide as an alternative precipitant to hydrogen sulphide, and hasdescribed the behaviour of a wide range of cations in acid, neutral, andalkaline solution towards the combined reagents.While discussing this reagent it is perhaps pertinent to introduce amore general note.In the literature the range of synonyms for ethylene-diaminetetra-acetic acid is bewildering-EDTA, ED, enta, Complexone(together with its derivative Complexometric titration), Versene, Versenate,and Trilon B all have considerable currency. For an internal report suchnames may have their advantage, but it is doubtful if the space saved in aprinted paper is sufficient to offset the confusion which must exist. Nodoubt the tendency to apply shortened names to organic reagents becamepopular with " oxine," though this has little advantage over 8-hydroxy-quirioline or 8-quinolinol, either of which is unequivocal.It was not alto-gether to be expected by those who incautiously lent " oxine " currencythat we should ultimately be assailed by ferroin, cuproin, neo-cuproin,tiron, magneson-I, and magneson-11, to choose only a few of those whichspring immediately to mind. None of these names gives any clue to thenature of the reagent, and they are not altogether to be trusted as a guide touse. It is true that the nomenclature of organic reagents must cause dismayto those analytical chemists who make use of these reagents, and an easysolution of the problem is not to be expected. But strenuous efforts arebeing made to standardise the nomenclature in other branches of chemistry,and theconclusion has regretfully been reached that many of the trivial namesof the nineteenth century must be retained though they are misleading inthe light of systematic nomenclature.It seems a pity, therefore, that thefield of analytical chemistry bids fair to provide a further problem for com-mittees on nomenclature by the lavish use of trivial names which may ormay not have gained general acceptance.In a comprehensive study of the complexes of copper with 1 : 10-phenan-throline and its methyl derivatives 70 the range of pH which permits of theirformation, and their stabilities have been examined. The structures havebeen related to such properties as absorption spectra, and use has been madeof this in predictions for some of the methyl derivatives.Similar studies** M. Jean, Analyt. Chim. Acla, 1952, 6, 278.8 6 M. J. Cabell, Analyst, 1952, 77, 859.70 W. H. McCurdy and G. F. Smith, AnaZysf, 1062, 77, 346.E. I . Onstott, J . Amer. Chem. Soc., 1952, 74, 3773.Nature, 1952, 170, 665.2. anal. Chem., 1952, 187, 107.6 8 J . , 1952, 4357WILSON : GENERAL. 307have been made for the 1 : 10-phenanthroline complexes with iron(^^),^^iron(111),~~ and zinc.73 Investigations on various oximes and dioximes havebeen rep0rted.7~ Measurements of the stabilities of complexes of 8-hydroxy-quinoline and related compounds 75 confirm the greater stability of 5-membered chelate rings mentioned above, and also indicate an order ofstability for the bivalent metals Cu > Ni > Co > Zn > Pb > Cd > Mn >Mg which is in general agreement with other investigations.It has beenshown that 8-hydroxyquinaldine may be quantitatively brominated, 76 anda number of quantitative precipitations with this reagent, notably of indium,uranyl, scandium, lead, and thorium, have been described.On the assumption that an indophenol of 8-hydroxyquinoline shouldpossess both the redox-indicating properties of indophenols and a pre-cipitating power related to the parent compound, a number of indophenolsof this compound and its derivatives have been prepared.77 Most of theseproducts were unstable. However, 2-methylindo-8-hydroxyquinoline, pre-pared by the action of hydroxylamine in an alkaline oxidising medium on8-hydroxy-Z-rnethylquinoline, gives precipitates a t pH 5 with certain cations,and at pH 12 with a wider range of ions.Work on the stabilities of metal chelates of iminodiacetic acid andiminodipropionic acid and their derivatives 78 suggests an order corre-sponding to that quoted above, but with lead and cobalt interchanged, andagain supports the greater stability of 5-membered chelates.The analyticalbehaviour as precipitants of thiourea and of 4- and 5-phenyl-substituted1 : 2-dimercapto-3-thiones 80 has been reported. Ammonium thiocarb-amate has been recommended 81 as an alternative to hydrogen sulphide forthe precipitation of sulphides. An extensive investigation of disubstituteddithiocarbamates s2 has shown that many metallic ions may be precipitatedas stable crystalline compounds which frequently have characteristic colours,generally brighter than those of the corresponding sulphides.The extract-ability of these metal dithiocarbamates has been investigated.The separation from bivalent cations of iron, aluminium, and man-ganese as hydroxides may be carried out 83 by aminomercuric chloride,NH2=HgCl, prepared in situ through successive additions of mercuric chloride,ammonium chloride, and ammonia. Consideration of the " weighting "effect as applied to benzidine, its homologues, and related compoundsindicate that 4 : 4'-diaminotolane is likely to form a sulphate of lowsolubility.84 This compound has been examined, and found to have theAluminium is not precipitated.'1 W.W. Brandt and D. K. Gullstrom, J. Amev. Chem. SOC., 1952, 74, 3532.72 A. E. Harvey and D. L. Manning, ibid., p. 4744.73 J . M. Kruse and W. W. Brandt, Analyt. Chem., 1952, 24, 1306.74 C. V. Banks and A. B. Carlson, Analyt. Chim. A d a , 1952, 7 , 291; R. Pallaud,7 6 W. D. Johnston and H. Freiser, J. Amer. Chem. SOC., 1952, 74, 5239.7 @ J . P. PhilIips, J . F. Emery, and H. P. Price, AnaZyyf. Chem., 1952, 24, 1033.7 7 J . P. Phillips, J . F. Emery, and Q. Fernando, J. Amer. Chem. SOC., 1952, 74, 5542.78 S. Chaberek and A. E. Martell, ibid., p. 5052; S . Chaberek, R. C. Courtney, and7a K. B. Yatsimirsky and A. A. Astasheva, J. Anal. Chem., U.S.S.R., 1952, 7 , 43.8a H. Malissa and F. F. Miller, Mikrochem. Mikrochim. Acla, 1952.40, 63.83 S. K. Susic and N. V. Njegovan, Analyt. Chim. Acla, 1952, 7 , 304.84 M. Kapel, Ind. Chem. Chem. Manuf., 1952, 28, 490.Chim. analyt., 1951, 33, 239, 343.A. E. Martell, ibid., p. 5057.M. G. Voronkov and F. P. Tsiper, ibid., 1951, 6, 331.E. Wiberg and R. Bauer, Angew. Chem., 1952, 64, 27D308 ANALYTICAL CHEMISTRY.lowest solubility recorded for an amine sulphate. The stabilities of a rangeof alkaline-earth compounds have been discussed theoretically.85General methods for the estimation of magnesium in calcium metal 86and of zinc in zinc-cadmium mixtures 87 have been critically examined.D. C. Atkins and C. S. Garner 88 have divided chelate compounds of zincinto two classes, I‘ fused-ring ” compounds where isotopic exchange withradioactive zinc takes place very slowly if at all, and “ non-fused-ring ”complexes where this exchange is very rapid.The structures and propertiesof salicylideneamine 89 and N-alkylethylenediamine complexes of copperand nickel have been described. An order of stability for amino-acidcomplexes of copper has been related to the structures of the amino-acid~.~lSilver has been shown to form several types of complex ion with triethylene-tetramine,92 The complexes formed by chromium and gallium with iodinehave been studied,93 and the bearing of these on other halide complexes andon general bond-type theory is indicated.In a general article B. J. Lerner, C. S. Grove and R. S. Casey 94 point outthat much of the knowledge required for a complete explanation of the“ complex ” chemistry of iron-knowledge of all forces operating at molecularlevel and a valid all-inclusive theory of valency-is still not available. Suchfactors as solvation, magnetic susceptibility, electron transfer, the effect ofpH, and the relation of colour to structure are discussed. Complexes ofcobalt with salicylaldehyde, its derivatives and related compounds 95 andwith the unusual sexadentate sulphur-containing aw-diamines 96 have beendescribed.Organometallic compounds of cobalt,97 nickel,97* 98 chromium,99uranium,lW and zirconium Io1 have been investigated. Formulae have beenproposed for a number of the ions formed by zirconium in mineral acidsolutions.1O2 The reactions of some thiosemicarbazides with ruthenium havebeen examined. lo33.INORGANIC QUALITATIVE ANALYSIS.In a scheme for the separation and recognition of the more familiarcations, J. Galmes lo* recommends removal of the alkaline-earth metalstogether with the usual chloride group by following the addition of hydro-chloric acid with ethanol and sodium sulphate. After removal of the acid-insoluble sulphides, the cations normally precipitated as hydroxides and as86 R. J . P. Williams, J . , 1952, 3770.8 6 S. Abbey, Chem. Canad., 1951, 3, No. 10. 53.87 W. Scheller and W. D. Treadwell, Helv. Chirn. Acta, 1952, 35, 754.8 8 J . Amer. Chem. SOC., 1952, 74, 3527.8Q A. P. Terentev and E. G. Rukhadze, J . Anal. Chem., U.S.S.R., 1951, 6, 303;91 N. C . Li and E. Doody, ibid., p. 4184.O2 H. B. Jonassen and P.C. Yates, ibid., p. 3388.93 A. S. Wilson and H. Taube, ibid., p. 3509.n4 J . Chem. Educ., 1952, 29, 438. O6 B. West, J . , 1952, 3115, 3123.s6 F. P. Dwyer, N. S . Gill, E. C . Gyarfas, and F. Lions, J . Amer. Chem. Soc., 1952,97 C. F. Callis, N. C . Neilsen, and J. C. Bailar, ibid., p. 3461.O 8 L. Sacconi, ibid., p. 4503. OD W. K. King and C . S. Garner, ibid., p. 5534.loo J. T. Barr and C. A. Horton, ibid., p. 4430.lol H. B. Jonassen and W. R. de Monsabert, ibid., p. 5298.lo2 B. A. J . Lister and L. A. McDonald, J . , 1952, 4315.lo3 R. P. Yaffe and A. F. Voigt, J . Amer. Chem. SOC., 1952, 74, 5043.lo4 Afinidad, 1951, 28, 154.A. P. Terentev, E. G. Rukhadze, and 2. A. Fadeeva, ibid., 1952, 7, 120.F. Basolo and R. K. Murmann, J .Amer. Chern. Soc., 1952, 74, 5243.74, 4188WILSON : INORGANIC QUALITATIVE ANALYSIS. 309sulphides in alkaline solution are precipitated by solid sodium carbonate.The unsatisfactory separation of the alkali-insoluble sulphides from thehydroxides may be overcome, it is claimed,105 by the application of selectivespot tests without reliance on separation methods. An alternative scheme Io6removes the chlorides in the usual manner, followed by tin and antimony,which are separated by evaporation with nitric acid. The insoluble sul-phates and the insoluble hydroxides constitute the two major succeedinggroups. Potassium xanthate is recommended lo' as a satisfactory alternativeto hydrogen sulphide, being used to precipitate a large group of elements,including a number of the less familiar ones, after removal of the insolublechlorides and sulphates.The xanthate group is then subdivided by treat-ment with alkali hydroxide, which produces a group of soluble and a groupof insoluble sulphides.A method has been described lo8 for the preparation of the titaniumreagent recommended for the removal of phosphate in the orthodox schematicMethod of analysis. Alternative procedures have been proposed for thetreatment of the sulphides of the copper group log and the nickel group,l1°and of the alkali-metal group.111J. Gillis 112 has discussed a number of aspects of theoretical and practicalimportance regarding the " sensitivity " of a reaction. The general fieldof spot reactions has been reviewedJ113 particularly with reference tospecificity.Among tests for the identification of individual ions a method has beenoutlined for the removal of interferences before detecting chloride by silvernitrate.ll* A bismuth mercaptoglyoxaline gives a red complex with iodidewhich is specific for this Nitrate may be removed and identified asvolatile methyl nitrite.l16 Sulphur in any form is reduced to hydrogensulphide which gives a red colour with a molybdate-thiocyanate s01ution.l~~Thiocyanate is extracted and identified by a ferric chloride-aluminiumchloride reagent .l18 Azo-dyes based on pyrocatechol and haematoxylinare sensitive colour reagents for boric a~id.11~ A range of specific reagentsfor germanium has been critically examined, and their behaviours de-scribed.120 R.J. Winterton 121 has investigated claims for sodium cobalti-thiosulphate, sodium calcium ferrocyanide, and sodium uranyl chromate asl06 A. Okac and M. Bezdek, Publ. Fac. Sci. Univ. Masaryk, 1950, No. 3, 9.lo6 F. Bianchi, Monit. Farm. Terap., 1952, 58, 139.lo' L. R. Chaves Lavin, Inform. Quint. anal., 1951, 5 , 62.lo8 A. J. Nutten and W. I. Stephen, Analyt. Chim. Acta, 1952, 7, 31.log M. S. Jovanovic and B. M. Jovanovic, Bull. SOC. chim. Belgrade, 1951, 16, 167.110 E. G. Maleeva, J . Anal. Chem., U.S.S.R., 1951, 6, 383.111 A. Casini, Ann. Chim. Roma, 1952, 42, 317.112 Mikrochenz. Mikrochim. Acta, 1951, 38, 381 ; J , Chem. Educ., 1952, e9, 170; Ind.113 F. Feigl, Mikrochem. Mikvochim. Acfa, 1952, 39, 368; P. W. West, Analyst,114 C.Mahr and W. Bromer, 2. anal. Chew.., 1952, 135, 107.116 R. A. McAllister, Nature, 1952, 169, 708.116 C. Franzke and K. Romminger, 2. anal. Chem., 1952, 136, 1.117 L. P. Pepkowitz and E. L. Shirley, Nuclear Sci. Absfv.. 1952 6. 15.L. Mennucci, Rev. Fac. Cienc. quim., La Plata, 1947, 22, 7.119 I. M. Korenman and F. R. Sheyanova, J . Anal. Chem., U.S.S.R., 1952, 7, 128.lao P. Bevillard, Mikrochem. Mikvochim. Acta, 1952, 89, 209;Chem. Chem. Manuf., 1952, 28, 488.1952, 77, 611.A. Tchakirian andP. Bevillard, Compt. vend., 1951, 233, 256, 1033.Ind. Chem. Chem. Manzcf., 1952, 28, 482310 ANALYTICAL CHEMISTRY.precipitants for potassium. None of these has proved as sensitive as sodiumcobaltinitrite, although the first may be used to detect rubidium in theabsence of potassium, and the first and last may prove useful as tests forpotassium in the presence of ammonium, as no precipitate is given by thelatter ion.A spot procedure for the detection of zinc using potassium ferrocyanide,122and methods for the recognition of cadmium after precipitation as an am-monium iodide complex 123 and of mercury as red cuprous mercuric iodide 124have been described.Alizarin-blue, which contains the active groups ofboth alizarin and 8-hydroxyquinoline, may be used for the detection of tracesof copper,125 although the general behaviour of the individual reagents haslargely been lost by combining the two structures. Aluminium, bismuth,iron, and titanium are precipitated by diphenyl phosphate.126 Manganesegives a green colour with triethanolamine in the presence of alkali hydr-0xide,1~~ and is satisfactorily detected in field tests on minerals by 8-hydroxy-quinoline.128 The zinc 1 : 10-phenanthroline complex mentioned earlier 73may be used to provide a sensitive test for ferricyanide in the presence offerrocyanide.F. Buscarbns and J. Artigas 129 recommend 2-mercapto-acetamido-4-nitrophenol as a reagent for cobalt. Gossypol forms a redcomplex with rn01ybdenum.l~~ It is claimed I 3 l that the interference offluorides in the detection of molybdenum by orthodox reagents is not somarked as has previously been reported, and that detection is still possiblein the presence of 100 times its concentration of fluoride as sodium fluoride.A photochemical reaction of tungsten in the presence of hydrochloric acidand ethanol is stated 132 to be suitable for the detection of a few pg.of thiselement. Tungsten may also be detected in ores by 8-hydroxyquin01ine.l~~The test for antimony with rhodamine-B may be made specific for thiselement, and will enable 0-2 pg. to be detected.134On the assumption that the mandelic acid group, *CH(OH)*CO,H, shouldbe generally sensitive for zirconium, R. E. Oesper, R. A. Dunleavy, andJ. J. Klingenberg 135 prepared m-2-hydroxynaphthylazomandelic acid so asto introduce a coloured centre into the reagent. As expected, this forms acoloured precipitate with zirconium, but the precipitate has the same colouras the reagent. It may be used, however, semi-quantitatively by theconfined spot-test technique.Colour reactions between finely divided solids have been discussed 136as a basis for qualitative analysis, and a number of highly sensitive testshave been described which may be applied directly to minerals.122 A.Lewandowski, Roczn. Chem., 1952, 26, 8.12s A. A. Komarovskaya, J. Gen. Chem., U.S.S.R., 1949, 19, 1459.124 E. Van Dalen and B. Van't Riet, Analyt. Chtm. Acta, 1952, 6, 101.1 2 ~ F. Feigl, Ind. Chem. Chem. Manu.., 1952, 28, 487.126 F. Knotz, Anal. veal SOC. esp. Fis. Quim., 1952, 48, B, 564.12' E. Jaffe, Ann. Chim. Roma, 1951, 41, 397.A. de Sousa, Analyt. Chim. Acta, 1952, 7, 393.120 Anal. real SOL. esp. Fis. Quim., 1952, 48, B, 140.A. Vioque-Pizarro, Analyt. Chim. Acta, 1952, 6. 105.lS1 F.Bermejo Martinez, A. Prieto Bouza, and J . Flores de Ligondes, Anal. real SOC.lS2 A. de Sousa, Analyt. Chzm. Acta, 1952, 7 , 24.lSs Idem, Mikrochem. Mikrochim. Acta, 1952, 40, 104.lS4 P. W. West and W. C. Hamilton, Analyt. Chem., 1952, 24, 1025.lS6 Ibid., p. 1492.esp. Fis. Quim., 1951, 47, B, 523.136 P. M. Isalrov, J. Anal. Chem., U.S.S.R., 1951, 6, 281WILSON : INORGANIC GRAVIMETRIC ANALYSIS. 31 14. INORGANIC GRAVIMETRIC ANALYSISFive types of weighing vessel have been specified for microchemicalana1y~is.l~~ W. H. Rromund and A. A. Benedetti-Pichler 138 have de-scribed the use of an assay balance for the gravimetric analysis of milligramsamples with use of microchemical equipment. A quartz microbalance forthe determination of magnetic susceptibility on milligram samples has beendescribed 139 and its performance investigated.The ageing of crystalline precipitates has been considered from thetheoretical standpoint by I.M. Kolthoff,lm and factors influencing bothphysical and chemical ageing have been discussed. It has been suggestedthat some form of numerical indications of the analytical characteristics of aprecipitate such as “ coefficient of filtration,” “ rate of sedimentation,” lQ1and “ nucleation potential ” 142 should be available. Such values would be avaluable guide to the analytical behaviour of precipitates. They might permita more fundamental approach to precipitation problems, and they wouldhelp in the development of new or the improvement of existing methods.Precipitation in Homogeneous Solution.-The method by which theprecipitating agent is produced slowly throughout the body of the solution,so that uniform precipitating conditions are achieved, continues to beextended.Calcium maybe determined in the presence of magnesium by using the hydolysis ofmethyl oxalate.lU Barium has been precipitated by the hydrolysis ofsulphamic a ~ i d . 1 ~ ~ Praseodymium has been separated from lanthanum bythe fractional precipitation of the carbonates from trichloroacetic acidsolution. 146 Thorium is gradually precipitated by ammonium picrate orby 2 : 4-dinitrophen01,l~~ and lead is satisfactorily precipitated as phosphatein a solution whose pH is altered gradually by the hydrolysis of urea.148Recent gravimetric methods of analysis have beenre~iewed.14~ C.Duval 150 has collated earlier work, using the thermobalance.From a study of the thermolysis curves, nitron, cinchonamine, and di-l-methylnaphthylamine are recommended 151 as gravimetric reagents fornitrate; no reagent tested was found to be suitable for the determination ofnitrite, hyponitrite, or azide. R. C. Brasted 152 has described an indirectgravimetric determination of nitrite through the loss in weight from gasevolution with sulphamic acid. Optimum conditions have been proposed 153for the determination of phosphorus as ammonium phosphomolybdate,A review of existing methods has been made.143Methods OJ analysis.n7 B.S.I. Specif., 1952, No. 1428, Pt. H1.lS8 Mikvochem. Mikrochim. Acta, 1951, 38, 505.18s F.Blaha, ibid., 1952, 39, 339.A. V. Nikolaev and M. P. Elentukh, J . Anal. Chem., U.S.S.R., 1952, 7, 21.142 R. A. Johnson, I n d . Chem. Chem. Manuf., 1952, 28, 489.I43 L. Gordon, Analyf. Chem., 1952, 24, 459.L. Gordon and A. F. Wroczynski, ibid., p. 896.145 W. F. Wagner and J . A. Wuellner, ibid., p. 1031.146 L. L. Quill and M. L. Salutsky, ibid., p. 1453.14’ C. L. Rao, M. Venkataramaniah, and B. S. V. R. Rao, J . Indian Chem. Sot., 1951,140 F. E. Beamish and W. A. E. McBryde, Analyt. Chem., 1952, 24, 95.I 5 O Chim. anal., 1952, 34, 55.151 C. Duval and N. D. Xuong, Analyt. Chim. Acta, 1952, 6, 245.lS2 Analyt. Chem., 1952, 24, 1111.lS3 -4. Bacon and H. C. Davis, Metal Abstr., 1952, 19, 734.140 Analysf, 1952, 77, 1000.28, 515.Shu-Chuan Liang and Kuo-I Lu, Analyt. Chim. Acta, 1952, 7, 451312 ANALYTICAL CHEMISTRY.either in simple phosphate solutions or in the presence of iron or chromium,and for the determination of sulphate as barium sulphate in the presence ofir0n.1~~ Following a study of five co-ordination compounds of cobalt,octa-ammino-pamino-pnitrodicobaltic nitrite has been proposed lS5 asa gravimetric reagent for sulphate. Although the precipitate is moresoluble than barium sulphate, it is little affected by foreign ion adsorption.In particular, nitrate does not interfere. Germanium may be estimated by3 : 4-dihydroxya~obenzene.~~~Critical examination of the precipitation of potassium with sodiumcobaltinitrite lS7 has confirmed the unsuitability of this reagent for thegravimetric determination of potassium, even under the most stringentempirical conditions, because of variability in the structure of the pre-cipitate and co-precipitation of reagent. If this reagent is used, some indirectmethod of determination, such as that based on a colorimetric cobalt deter-mination, must be utilised.The gravimetric determination of potassium aspotassium tetraphenylboron, K[B(C,H,),],lS8 is claimed to be rapid and freefrom error. A method has been described for the separation of rubidiumand caesium in large amounts of sodium and potassium chl0rides.15~ Theprecipitation of beryllium and its deterrnination as pyrophosphate havebeen critically examined, and suitable procedures have been selected. 160J.L. Walter and H. Freiser 161 have found 2-o-hydroxyphenylbenzox-azole, one of the reagents which they investigated from the structural pointof view,38 suitable as a gravimetric reagent for cadmium. Only nickel andcobalt interfere seriously, and copper interference can be avoided. Micro-gram amounts of mercury in the mercurous form have been determinedgravimetrically as the chloride with a coefficient of variation of _+l%.lSZInvestigations with the thermobalance have indicated some twenty gravi-metric methods which are suitable for the determination of copper, with the.conditions which are appropriate for drying the pre~ipitates.1~~ Copper maybe determined gravimetrically as cuprous thiocyanate by using ferrousammonium sulphate as reducing agent,164 or as sulphide by using theammonium or sodium salt of trithiocarbonic acid as precipitant.165 Pre-cipitation of copper with 6 : 6-benzoquinaldinic acid has been described.166Silver has been determined gravimetrically on the microgram scale as thechloride,162 and gold may be precipitated by morpholine 0xalate.1~'Aluminium can be precipitated quantitatively as the hydroxide byusing pyridine.16* Interference by iron in the precipitation with ammonium154 N.Gandolfo, R. C . 1st. sup. Sanit., 1951, 14, 654.156 R. Belcher and D. Gibbons, J . , 1952, 4216.156 A. Tchakirian and P. BCvillard, Compt. rend., 1951, 233, 1112.157 D. Bourdon, Chim. anal., 1950, 38, 273; J. W. Robinson, I ~ d . Chem. Chem.158 H. Flaschka, 2. anal. Chem., 1952, 136, 99; H.W. Spier, Biochem. Z . , 1952, 322,160 R. Airoldi, A n n . Chim. appl, Roma, 1951, 41, 478.161 Nuclear Sci. Abstr., 1952, 6, 212; Analyt. Chem., 1952, 24, 984.1's Y. Marin and C. Duval, Analyt. Chim. Acta, 1952, 6, 47.16* R. Belcher and T. S. West, ibid., p. 337.165 E. Gagliardi and W. Pilz, Monatsh., 1952, 83, 54.166 A. K. Majumdar and A. K. Mallick, J . Indian Chem. SOC., 1952, 29, 255.1e7 L. S. Malowan, Rev. SOC. venezol. Quim., 1961, 5, No. 23, 23.1 6 8 E. Peltenburg, Rev. Fac. Cienc. qrim., La Plata, 1947, 23, 175.Manzif., 1952, 28, 491.467. 159 D. Meier and W. D. Treadwell, Helv. Chim. Acta, 1951, 34, 805.H. M. El-Badry and C . L. Wilson, Analyst, 1952, 77, 596WILSON INORGANIC GRAVIMETRIC ANALYSIS. 313hydroxide may be prevented by complexing with thioglycollic acid.169The micro-determination of aluminium with 8-hydroxyquinoline has beenm0dified.1~~ Lanthanons may be precipitated by ammonium sebacate.171From themolytic examination, tetraphenylarsonium perrhenate isstated to be the most satisfactory weighing form for rhenium.17a Iron andchromium may be precipitated as the hydroxides with pyridineJ168 andcobalt as the double mercuric thiocyanate.173 Molybdenum may be separ-ated from interfering elements by a preliminary precipitation with u-benzoin oxime followed by conversion into ~u1phide.l~~ The sulphide mayalso be obtained by precipitation with sodium trithi0~arbonate.l~~ Amethod for volatilisation of tin as stannic iodide permits estimation of thiselement in br0nzes.1~~ Lead has been determined with phenylarsonicacid 177 and on the microgram scale as sulphate.162For the quantitative precipitation of zirconium, benzilic acid,178 cinnamicacid,179 and salicylic and phenoxyacetic acids 180 have all been found satis-factory.Quantitative precipitants proposed for thorium include cam-phoric,181 anisic,l82 ~uccinic,18~ adipic,l83 b e n ~ o i c , l ~ ~ ~ 184 and m-tolyloxy-acetic acids,lS5 ammonium furoate,lg6 sodium suIphani1ate,ls6 and cinnamicacid.Antimony may be precipitated as the sulphide by sodium trithio-carbonate 188 or as a cobalt complex with bisethylenediaminocobalticchloride. ls9 Vanadium may be precipitated with diantipyrylphenyl-methane and ignited to the pentoxide. The temperatures of decompositionof a number of niobium complexes have been rec0rded.1~~ Separation of thetannin complexes of niobium and tantalum may be achieved in aqueousammonium oxalate s01ution.l~~ From temperatures of decomposition,precipitation of tantalum by tartaric acid is indicated as the most satisfactoryof the current methods.lg3lG9 R.A. Hummel and E. B. Sandell, Analyt. Chim. Acta, 1952, 7, 308.170 M. C. Alvarez Querol, Mikrochem. Mikrochim. Acta, 1952, 39, 121.171 G. B. Wengert, R. C. Walker, M. F. Loucks, and V. A. Stenger, Analyt. Chem.,172 S. Tribalat and C. Duval, Analyt. Chim. Acta, 1952, 6, 138.173 F. Sierra and F. Ckrceles, Anal. real SOC. esp. Fis. Quim., 1951, 47, B, 811.174 J , Iron Steel Inst., 1952, 171, 75.175 E. Gagliardi and W. Pilz, 2.anal. Chenz., 1952, 136, 103.1 7 G J. Besson and R. Budenz, Chinz. anal., 1952, 34, 163.177 A. K. Majumdar and R. N. S. Sarma, J . Indian Chem. Soc., 1951, 28, 654.17* M. Venkataramaniah and B. S. V. R. Rao, ibid., p. 257.179 C. Venkateswarlu and B. S. V. R. Rao, ibid., p. 354.180 T. V. Sastry and B. S. V. R. Rao. ibid., p. 530.lS1 D. 9. N. Murty and B. S. V. R. Rao, ibid., p. 218.lS2 K. V. S. Krishnamurty and B. S. V. R. Rao, ibid., p. 261 ; Rec. Trav. chim.,T. V. S. Suryanarayana and B. S. V. R. Rao, J . Indian Chem. Soc., 1951, 28, 511.lS4 M. Venkataramaniah, C. L. Rao, and B. S. V. R. Rao, AnaEyst, 1952, 7'4, 103;lS6 M. Venkataramaniah, B. S. V. R. Rao, and C. L. Rao, Analyt. Chem., 1952,24,747.lS6 0. Lakshminarayana and B. S. V.R. Rao, J . Indian. Chem. SOC., 1951, 28, 551.lS7 K. V. S. Krishnamurty and C. Venkateswarlu, Rec. Trav. chim., 1952, 71, 668.lSs E. Gagliardi and W. Pilz, 2. anal. Chenz., 1952, 136, 344.l90 S . I. Gusev, li. G. Beyles, and E. V. Sokolova, J . Anal. Chem., U.S.S.R., 1951,lB2 N. H. Bailey, S. A f r . I n d . Chem., 1951, 5, 235.lg3 U. M. Doan and C. Duval, Analjlt. Clzim. Acta, 1955, 6, 135.1952, 24, 1636.1951, 70, 421.J . Sci. Ind. Res., India., 1951, 10, B, 254.D. Gibbons, I n d . Chem. Chem. Manuf., 1952, 28, 487.6, 43. lgl U. M. Doan and C. Duval, Analyt. Chinz. Acta, 1952, 6, 81314 ANALYTICAL CHEMISTRY.Precipitation of platinum by thioformamide is stated lg4 to be moresatisfactory than precipitation by hydrogen sulphide, and reduction ofprecipitated ammonium hexachloroplatinate by zinc is recommended inpreference to the more usual meth0ds.1~5 Errors in the assay of iridium lg6and of osmium lg79 lg8 have been investigated, and precipitation of osmiumby " thionalide '' followed by ignition in hydrogen to the metal is recom-mended.Palladium may be precipitated as the sulphide by thioform-amide lg9 or as a complex with 1 : 10-phenanthroline.2C@ The latter pre-cipitate or the precipitate with 8-hydroxyquinoline is recommended asweighing form on the basis of thermolysis curves.2o15. INORGANIC TITRIMETRIC ANALYSIS.Recent advances in titrimetric analysis are presented in the new editionof a standard work 202 and in a review.203 A titration bench with built-inlighting and stirring apparatus has been de~cribed.~04 Reductors andreductor methods have been reviewed205 and new or improved reductormethods have been proposed.206 A study by potentiometric methods ofsome of the reactions of bromide-bromate and iodide-iodate systems hasbeen reported.207 An extensive correspondence on the standardisation ofiodine solutions by sodium thiosulphate has stressed the inadvisability ofalkaline stabilisers for standard thiosulphate solutions, and the necessity foracid conditions in the titration.208 A comprehensive review of the titri-metric uses of cerium(1v) solutions has been made.209 L.S. Theobald andJ. P. Stern 210 have recommended methods for preparing standard solutionsof aluminium and zinc.210 The stability of aqueous potassium ferratesolutions to light, temperature, and varying conditions of alkalinity andconcentration has been examined.211 Chloramine-T has been recommendedas a more economical titrimetric reagent than iodine.212 The use of stan-dard stannous ~ h l o r i d e , ~ l ~ potassium rnetaperi~date,~~~ and manganese(II1) 215lg4 E.Gagliardi and R. Pietsch. Monatsh., 1951; 82, 656.lB6 A. P. Blackmore, M. A. Marks, R. R. Barefoot, and F. E. Beamish, Analyt.lg6 R. R. Barefoot and F. E. Beamish, ibid., p. 840.197 W. J. Allan and F. E. Beamish, ibid., p. 1608.lg8 Idem, ibid., p. 1567. lS9 E. Gagliardi and R. Pietsch, Monatsh., 1951, 82, 432.zoo D. E. Ryan, Analyst, 1952, 77, 46.201 P. Champ, P. Fauconnier, and C. Duval, Analyt. Chim. Acta, 1952, 6, 250.202 I ' Neuere massanalytische Methoden," Ed.W. Bottger, 3rd edtn., Stuttgart, 1951.203 C. S. Rodden and C. G. Goldbeck, Analyt. Chem., 1952, 24, 102.*04 W. Schoniger, Mikrochem. Mikrochirn. Acta, 1951, 38, 456.205 W. I. Stephen, Ind. Chem. Chem. Manuf., 1952, 28. 13, 55, 107.208 C. W. Sill and H. E. Peterson, U.S. Bur. Man., 1952, Rep. Invest. 4882; Analyt.Chem., 1952, 24, 1175; J. M. Thompson, ibid., 1632; E. R. Riegel and R. D. Schwartz,ibid.. p. 1803; J . A. Rahm, ibid., p. 1832; C. C. Miller and R. A. Chalmers, Analyst, 1952,77, 2 ; P. Wehber and H. Hahn, 2. anal. Chern., 1952, 136, 321, 325; M. I. Kriventsov,J . Anal. Chem., U.S.S.R., 1951, 6,384; E. GagliardiandW.Pilz, Monatsh., 1951, 82, 1012.207 H. T. S. Britton, R. E. Cockaday, and J.K. Foreman, J., 1952, 3877; H. T. S.Rritton and H. G. Britton, ibid., pp. 3879, 3887, 3892.208 R. Rands, Chem. and Ind., 1952, 1001 ; J. J. Lamond, ibid., p. 1128; A. I. Vogel,ibid., p. 1177; T . A. H. Peacocke, ibid., p. 1245.209 P. Yonng, Analyt. Chem., 1952, 24, 152.210 Analyst, 1952, 7'4, 99.211 W. F. Wagner, J. R. Gump, and E. N. Hart, Analyt. Chem., 1952, 24, 1497.212 W. Poethke and F. Wolf, 2. anorg. Chem., 1952, 268, 244.213 2. G. Szab6 and E. SugAr, Analyt. Chim. Acta., 1952, 6, 293.214 B. Singh and A. Singh, J . Indian Chem. SOC., 1952, 29, 34.215 R . Belcher and T. S. West, Analvt. Chim. Acta, 1952, 6, 322.Chem., 1952, 24, 1815WILSON INORGANIC TITRIMETRIC ANALYSIS. 315solutions as general titrimetric reagents has been described.R. H. Mullerand A. M. Voge1216 have recommended an instrument with temperature-compensation for the standardisation of titrimetric solutions by conductancemeasurements.Methods of Analysis.-From a critical examination of methods for theestimation of hypochlorite, A. Lassieur and D. Jouslin 217 recommendtitration with standard arsenious oxide solution using an internal indicator.Bromide ion may be oxidised to bromate by chlorine 218 or by hypochlorite 219before iodometric determination. Iodide may be accurately titrated bypermanganate,220 and fluoride by zirconium solution.221 Ammonia may beprecipitated by Nessler's reagent, and the precipitate reduced to mercury,which is then treated with iodate-iodide and the liberated iodine estimatedby thiosulphate.222 Treatment of hydroxylamine with excess of cerium(1v)solution enables the compound to be determined by back titration withstandard arsenic solution.223 The estimation of nitrate by the method of2.G. Szabo and L. Bartha 224 has been modified and converted to the micro-scale.225 Azide may be determined by reduction to give an ammonia-nitrogen mixture in which the ammonia is estimated.226and it is statedthat significant errors occur except when the end-point acidity is maintainedwithin the range 1.2-3.5~. Ozone may be determined iodometrically,228and peroxide by titration with ~ e r m a n g a n a t e . ~ ~ ~ Sulphite is oxidised tosulphate by hypochlorite, the excess of hypochlorite being estimated by aniodide-thiosulphate t i t r a t i ~ n .~ ~ ~ G. Denk 231 has shown that a directalkalimetric titration for alkaline-earth metals is possible, and that this mayin turn be applied to the indirect determination of sulphate. Titrimetricmethods have been described for selenium 2329 233 and 234A method for alkali carbonate and bicarbonate in the presence of each otherutilises titration with standard barium chloride and back titration, afteraddition of excess of acid, with carbonate-free sodium Cyanidemay be titrated with standard nickel solution, murexide being used asindicator.236The estimation of potassium as the tetraphenylboron compound 15* may216 AnaZyt. Chem., 1952, 24, 1590.217 A. Lassieur and D. Jouslin, Chim. anal., 1951, 33, 45.21s 2. G. Szab6 and L. Csanyi, Analyt.Chim. Acta, 1952, 6, 208.218 M. R. Block, S. Kertes, and I. Schnerts, Bull. Res. Council Israel, 1952, 1, No. 4, 82.220 S. A. Celsi and M. ,4. Copello, Monit. Farm., 1951, 57, 158.221 H. v. Zeppelin and J. Fuchs, Angew. Chem., 1952, 64, 223.222 H. Lestra and G. Roux, Compt. rend., 1951, 233, 1453.223 S. R. Cooper and J. B. Morris, Analyt. Chem., 1952, 24, 1360.224 Ann. Reports, 1951, 48, 323.225 2. G. Szabo and L. Bartha, Mikrochem. Mikrochim. A d a , 1951, 38, 413.226 L. P. Pepkowitz, Analyt. Chenz., 1952, 24, 900.227 D. J. Kew, M. D. Amos, and M. C. Greaves, Analyst, 1952, 77, 488.228 C. M. Birdsall, A. C . Jenkins, and E. Spadinger, Analyt. Chem., 1952, 24, 662.22e J. Mattner, 2. anal. Chem., 1952, 135, 415.230 B. L. Dunicz and T.Rosenquist, Analyt. Chem., 1952, 24, 404.231 2. anal. Chem., 1952, 137, 99.232 G. S. Deshmukh and B. R. Sant, AnaZyst, 1952, 77, 272.233 K. Geiersberger and A. Durst, 2. anal. Chem., 1952, 135, 11; K. Geiersberger,234 R. A. Johnson and D. R. Fredrickson, Analyt. Chem., 1952, 24, 866.235 D. Koszegi and E. Salgo, 2. anal. Chem., 1952, 137, 22.236 F. Huditz and H. Flaschka, ibid., 136, 185.The bromate titration of arsenic(II1) has beenibid., pp. 15, 18316 ANALYTICAL CHEMISTRY.be completed titrimetrically instead of gravimetricany, an argentometrictitration in acetone solution being Interference from iron,aluminium, and chromium is masked by fluoride. The direct alkalimetricestimation of alkaline-earth metals 231 is possible in hot solution, with sodiumcarbonate, thymol-blue being used as indicator.Beryllium solutions maybe titrated directly with barium hydroxide to a phenolphthalein end-point,or may be estimated by precipitating the hydroxide, treating this withpotassium fluoride, and titrating the liberated alkali with standard acid.238Cadmium and zinc may be indirectly estimated with alkali, making use ofthe fact that the hydroxides or basic carbonates, when dissolved in sodiumthiosulphate, liberate an equivalent amount of acid.2ag The salts of cadmiumwith strong acids may be titrated directly against sodium hydroxide to acresolphthalein end-poin t .mThe effect of nitric acid on the iodometric determination of copper maybe eliminated almost completely by addition of sufficient solid sulphamicacid to retain crystals in the solution throughout the t i t r a t i ~ n .~ ~ ~ L. Meitesclaims 242 that comparison shows that addition of sufficient excess of potas-sium iodide to retain cuprous iodide in solution is more satisfactory than themore usual method by which the iodide is precipitated. The increase incost is held to be offset by the greater speed and accuracy attained. Goldmay be titrated by using '' dithizone," and interference from other metalscan be o v e r ~ o m e . ~ ~ Alkaline aluminate solutions may be estimated by adouble titration with standard acid and standard potassium fluoride solu-tion.244 The iodometric determination of copper described by R. 0. Bras-ted 241 may be extended to deal simultaneously with the estimation of ironalso present in the solution.The titration of iron with perrnanganate onthe micro-scale has been found to be more satisfactory after reduction withstannous chloride than after use of the silver r e d ~ c t o r . ~ ~ ~ Conditions for theiodometric determination of iron(II1) have been established.246 Ferro-cyanide has been determined in the presence of cyanide by titration withcerium(1v),247 and ferricyanide can first be reduced by metallic mercury andthen titrated in the same way 248 since the presence of cyanide, or alternativelyof thiocyanate, enhances the reducing power of the mercury. The sameeffect can be utilised in the reduction of iron(m), and appears to have someadvantages over the use of amalgam reductors.Precipitated nickel di-methylglyoxime may be dissolved in acid, treated with excess of vanadatesolution, and back titrated with iron(I1) solution, phenylanthranilic acidbeing used as indicator.249 Nickel may also be oxidised by persulphate, andthe resulting compound estimated iodometrically.2m Chromium(m) oxid-z37 W. Rudorff and H. Zannier, 2. anal. Chem., 1952, 13'7, 1.238 V. K. Zolutukhin, J . Anal. Chem., U.S.S.R., 1951, 6, 246.239 M. M. Tillu, Analyt. Chem., 1952, 24, 1495.240 G. Denk, 2. anal. Chem., 1952, 138, 336.z41 R. 0. Brasted, Analyt. Chem., 1952, 24, 1040.243 L. Erdey and G. Rady, 2. anal. Chem., 1952, 185, 1.244 M. Beck and Z. G. Szab6, Analyt. Chim. Acta, 1952, 8, 316.245 M. C . Alvarez Querol, Miiirochenz. Mikrochim.Ada, 1952, 39, 126 ; F. de A. Bosch246 L. J. White, Coke and Gas, 1952, 14, 285.247 F. Burriel Marti, F. Lucena-Conde, and S. Bolle, Analyt. Chinz. Acta, 1952, 7, 302.248 F. Burriel Marti, Ind. Chem. Chem. Manuf., 1952, 28, 487.249 V. S. Syrokomsky and S. M. Gubelbank, J . Anal. Chem., U.S.S.R., 1951, 6, 207.*so E. S. Tomula, 0. Juutinen, and P. Tanskanen, 2. anal. Chem., 1952, 185, 265.242 Ibid., p. 1618.Arino and M. C . Alvarez Querol, Anal. veal SOC. es?. Fis. Quim., 1952, 48, B, 267WILSON INORGANIC TITRIMETRIC ANALYSIS. 317ation by mixed perchloric-sulphuric acids is more complete in the presence ofsilver nitrate,251 and the resulting chromium(v1) may then be estimatediodometrically without interference from precipitated silver iodide.The iodometric determination of tin has been reviewed, and a procedurerecommended.252 Bronzes may be dissolved in acid and reduced by antimonypowder, thus enabling the copper to be precipitated as cuprous thiocyanatebefore iodometric determination of tin(11) .253 Tin salts, when treated withsodium tartrate, liberate hydrogen ions which may then be estimated bytitration to a phenolphthalein end-point.254 Thorium may be precipitatedas molybdate 255 and the molybdate reduced and titrated, or by seleniousacid in the presence of ethanol 256 followed by an iodine-thiosulphatetitration.Thorium may also be titrated directly against standard oxalicacid, alizarin-S being used as an internal indicator.257 A direct titrationof vanadate solution using standard silver nitrate is possible, with an alcoholicgallic acid test-paper as indi~ator.~~8 Preliminary treatment and titrationconditions for the estimation of vanadium in steels,259 ferrovanadium,2m anduranium 261 have been described.Indicators and Related Topics-R.G. Bates 262 has discussed thedefinition of pH and the uncertainty in the value as measured, relating thisto the necessity for a more precise definition of the conditions of measurementthan is usually given. Methods have been described for the calculation ofthe pH of solutions.2m The desirable characteristics of an indicator havebeen discussed in terms of colour theory, and such processes as the screeningof indicators have been examined in the light of ideal behaviour.2m Colori-metric methods for the determination of pH have been described and dis-cussed. 26A method for stabilising litmus solutions over a period of a year hasbeen described.266 9-Ethoxychrysoidine adsorbed on silver iodide hasbeen recommended as an acid-base indicat0r.26~ The behaviour of arange of indicators with various compounds in chlorobenzene and othernon-aqueous solvents has been examined.268Investigation of a wide range of protective colloids for the retention ofsilver chloride in suspension, with dichlorofluorescein solution as indicator,has shown the best to be polyethylene glycol 400, a condensation productof ethylene oxide.26g The protective colloids usually recommended-dextrin251 S.Lynn and D. M. Mason, Analyt. Chem., 1952, 24, 1855.252 A. Doadrio, Inform.Quim. anal., 1952. 6, 79.253 M. L. Malaprade, Bull. SOC. chim., 1951, 18, 739.254 V. K. Zolutukhin, J . Anal. Chern., U.S.S.R., 1951, 6, 300.2 5 5 C. V. Banks, Iowa State Coll. J . Sci., 1951, 25, 145.256 G. S. Desmukh and L. K. Swamy, Analyt. Chem., 1952, 24, 218.257 P. Venkateswarlu and A. N. Ramanathan, Current Sci., 1952, 21, 45.258 M. Nivoli, Ann. Ghim., Roma, 1952, 43, 370.25n Methods of Analysis Committee, J . Iron Steel Inst., 1952, 171, 81.260 Idem, ibid., 170, 343.261 S. H. Simonsen, Analyt. Chim. Acta, 1952, 7, 33. a62 Analyst., 1952, 77, 653.263 J. Eeckhout, Analyt. Chim. A d a , 1952, 7, 203; A. J. McBay, J . Chem. Educ.,264 J . King, Analyst, 1952, 77, 742.265 T. B. Smith, C. A. White, P. Woodward, and P.A. H. Wyatt, J . , 1952, 3848;266 L. W. Cumming, J . Pharm. Pharmacol., 1952, 4, 324.267 E. Schulek and E. Pungor, Analyt. Chm. Acta, 1952, 7, 446.268 R. V. Rice, S. Zuffanti, and W. F. Luder, Analyt. C k m . , 1952, 24, 1022,26n R. B. Dean, W. C . Wiser, G. E. Martin, and D. W. Barnum, ibid., p. 1638.1952, 29, 526.R. H. &I. Simon, Analyt. Chem., 1952, 24, 1215318 ANALYTICAL CHEMISTRY.or gum arabic-may affect the end point significantly. Acid-violet 4BL 270and acid-red 6B 271 have been recommended as indicators for silver titrations.The systems iron(II1) with benzidine, tolidine, and a-dianisidine have beenfound satisfactory for the argentometric titration of bromides and iodidesa t great dilution 272 and for mercurous titration ofNaphthidinesulphonic acid 274, 275 and 3 : 3’-dimethylnaphthidinesul-phonic acid 274 have been recommended for a range of oxidation-reductiontitrations, and their oxidation potentials have been established.Rhodamine-B has been proposed as a fluorescent indicator in iodometric titrations withcoloured solutions,276 although in straightforward titrations sodium starchglycollate is to be preferred to any other indicator examined.Diphenylcarbazone screened with bromophenol-blue, which also permitsadjustment of pH,277 or with a nickel solution,278 has been recommended asan indicator in mercuric titrations of chloride. Alternatively, the chloridemay be treated with silver solution and mercuric solution, and diphenyl-carbazone is used to indicate the e n d - p ~ i n t .~ ~ ~ Conditions are describedfor the titration of zinc with ferrocyanide, diphenylthiocarbazone being usedas indicator.2@)6. CLASSICAL ORGANIC ANALYSIS.General.-General microchemical methods,281 volumetric methods inorganic analysis,282 the determination of metals in organicand the determination of organic functional groups 284 have been reviewed.The use of derivative melting points 285 and general precautions to be takenin the small-scale preparation of derivatives 286 have been discussed.Qualitative.-Methods have been proposed for the identification ofamides and nit rile^,^^^ carbonyl compounds,288 hydroxyquinones,290and steroids.291Quantitative.-H. Goldberger and M. Pohm 292 have described theweighing of hygroscopic liquid samples for combustion analysis.Stainless270 W. H. Weihe, Klin. Wochenschr., 1952, 30, 85.271 G. Mannelli and M. L. Rossi, Analyt. Chim. Acta, 1952, 6, 333.272 F. Sierra and J. HernSndez Cabavate, Anal. yea1 Soc. esp. Fis. Quim., 1952, 48,273 F. Sierra and J. A. SAnchez FernQndez, ibid., p. 339.274 R. Belcher, A. J. Nutten, and W. I. Stephen, J., 1952, 1269, 3857.276 G. W. C . Milner, Analyt. Chim. Acta, 1952, 6, 226.276 L. Deibner, Chim. anal., 1951, 33, 207.277 G. B. Smit, Analyt. Chtim. Acta, 1952, 7 , 330.278 J. S. Parsons and J . H. Yoe, ibid., 6, 217.279 J. Rodolfo Bayer, Anal. Asoc. Qulm. Argentina, 1951, 39, (193), 131.280 J. P. Mehlig and A. P. Guill, Analyt. Chem., 1951, 23, 1876.281 C. 0. Willits and C . L. Ogg, ibid., p.70.282 W. T. Smith and R. E. Buckles, ibid., p. 108.283 R. Belcher, D. Gibbons, and A. Sykes, Mikrochem. Mikrochim. Acta, 1952, 40, 76.284 A. J. Nutten, Ind. Chem. Chem. Manuf., 1952, 28, 273, 321; H. Lieb, Chimia,285 M. Brandstatter and H. Thaler, Mikrochem. Mikrochim. Acta, 1951, 38, 358.286 N. D. Cheronis and A. Vavoulis, ibid., p. 428.287 S. Soloway and A. Lipschitz, Analyt. Chem., 1952, 24, 898.288 L. Rosenthaler, Mikrochem. Mikrochim. Acta, 1952, 39, 360; C. Neuberg, A.Grauer, and B. V. Pisha, Anulyt. Chim. Acta, 1952, 7 , 238; J . J. Ritter and M. J. Lover,J . Amer. Chem. SOC., 1952. 74, 5576; G. Uttolino and M. Valente, Boll. SOC. ital. Biol.sper., 1951, 27, 446.290 J. R. Anderson, K. G. O’Brien, and F. H. Reuter, Amlyt. Chim. Acta, 1952, 7 , 226.H.Tauber, AnaZyt. Chem., 1962, 94, 1494.Ob2 Mikrochem. Mikrochim. Acta, 1962, 80, 73.B, 451, 457.1952, 6, 34.P. Clarke, Chem. and Ind., 1952, 450WILSON : CLASSICAL ORGANIC ANSLYSIS. 319steel has been proposed 293 as a material suitable for making absorption tubesfor semi-micro carbon-hydrogen determination. A. A. Sirotenko 294 reportsthat potassium persulphate should be mixed with the sample in carbon-hydrogen determinations on compounds containing alkali metals, in orderto prevent the formation of stable alkali carbonates, and magnesium oxidepellets have been used 295 to retain silicon tetrafluoride and other objection-able combustion products from fluorine-containing compounds. Standardmethods for carbon-hydrogen combustion have been modified by a numberof workers.296A furnace for use in the direct determination of oxygen has been de-scribed,297 and detailed accounts of the method have been given.298 Theimportance of proper preparation of the iodine pentoxide used for conversionof carbon monoxide into carbon dioxide in this determination has beens t r e s ~ e d .~ ~ ~ ~ 299Specifications have been drawn up for apparatus for the combustiondetermination of halogens and Modifications of the standardcombustion method for sulphur and halogens have been proposed.301 Arapid combustion method for these elements, using apparatus which followsthe general design of the rapid combustion method for carbon and hydro-gen,m2 has been de~cribed.~O~ A modified combustion method suitable forvery small amounts of sulphur has been proposed.304 The reactions resultingin the formation of silver sulphate in the sulphur determination 305 and thosetaking place in the decomposition of organic compounds with potassium 306have been examined.Decomposition with magnesium has been recom-mended for compounds containing sulphur and nitr~gen.~O' Wet oxidationmethods for sulphur compounds have been proposed, using potassiumchromate in phosphoric acid 308 or a nitric acid-hydrochloric acid mixturein the presence of sodium chloride with selenious acid as catalyst.309Specifications have been given for the apparatus for determination ofnitrogen by combustion,310 and modifications of the Dumas method have203 J. A. Kuck and M.Arnold, Mikrochem. Mikrochim. A d a , 1951, 38, 521.294 Ibid., 1952, 40, 30.296 W. H. Throckmorton and G. H. Hutton, Analyt. Chem., 1952, 24, 2003.206 S . S. Israelstam, Analyt. Chem.. 1952, 24, 1207; 0. G. Backeberg and S. S.Israelstam, ibid., p. 1209; G. De Vries and E. van Dalen, Analyt. Chim. Acta, 1952, 7,274; G. Kainz, Mikrochem. Mikrochirn. Acta, 1952, 39, 166; G. Mangeney, Bull. SOC.chim., 1951, 4, 809; V. A. Klimova and M. 0. Korshun, J . Anal. Chenz., U.S.S.R., 1951,6, 230; M. 0. Korshun, ibid., 1952, '7, 96; M. 0. Korshun and N. S. Sheveleva, ibid.,p. 104.287 A. Steyermark, M. J . McNally, W. A. Wiseman, R. Nivens, and F. P. Biava,Analyt. Chem., 1952, 24, 589.208 J. Unterzaucher, Analyst, 1952, 77, 584; I n d . Chem. Chem. Manuf., 1952, 28,492.208 E.G. Adams and N. T. Simmons, J . Appl. Chem., 1951, Suppl. 1, S 20.300 B.S.I. Specif., 1952, No. 1428, Pt. A3.301 E. D. Peters, G. C. Rounds, and E. J. Agazzi, Analyt. Chem., 1952, 24, 710;0. E. Sundberg and G. L. Royer, ibid., p. 907; G. W. Perold, S. Afr. I n d . Chem., 1951,5, 135. 302 R. Belcher and G. Ingram, Analyt. Chim. Acta, 1950, 4, 118.303 Idem, ibid., 1952, 7, 319.304 F. Grassner, 2. anal. Chem., 1952, 135, 186.306 M. 0. Korshun, J . Anal. Chem., U.S.S.R., 1952, 7, 101.306 G. Kainz and A. Resch, Mikrochem. Mikrochim. Acta, 1952, 30, 75.307 P. N. Fedoseev and N. P. Ivashova, J . Anal. Chem., U.S.S.R., 1952, 7, 112, 116.308 D. Koszegi and J. Barcsay, 2. anal. Chem., 1952, 135, 349.A. Steinbergs, J . Aust. Inst. Agvic.Sci., 1961, 17, 3, 166.alo B.S.T. Specif., 1952, No. 1425, Pt. A2320 ANALYTICAL CHEMISTRY.been proposed.311 The reactions taking place in the Dumas method havebeen discussed in some detai1312 and means of avoiding errors have beensuggested.313W. Kirsten3lP has described apparatus for the Kjeldahl method fornitrogen, and catalysts for the digestion process have been examined.315Reduction before digestion may be achieved by zinc and methano1316 orthiosalicylic acid.317 In describing a diffusion microgram method fornitrogen, B. W. Grunbaum, F. L. Schaffer, and P. L. Kirk31* point outthat, in spite of the mass of empirical information about the Kjeldahldigestion process, little fundamental information regarding it is available.Their experiments show that digestion in a sealed tube without a catalystis quite satisfactory provided that the temperature is not allowed to riseabove 450°, a t which temperature the sulphuric acid begins to oxidise theammonia with consequent loss.A diffusion method is also proposed byD. Seligson and H. S e l i g ~ o n . ~ ~ ~ M. Marzadro 320 shows how it is possible,by utilising the selective action of the Kjeldahl method together with theDumas method, to distinguish between nuclear and extra-nuclear nitrogenin heterocyclic compounds.The determination of phosphorus after decomposition in the Parr bombhas been described.321 Halogens have been determined by combustion,322by potassium by peroxide decornp~sition,~~ and by a modificationof Viebock’s method.325 Acid chlorides have been estimated by argento-metric titration in acetone s0lution,~26 aliphatic halogens on aromatic side-chains by hydrolysis with alkali in ethylene glycol solution,327 and halogencompounds have been reduced by hydrogen with a nickel catalyst in anaqueous-e t hanolic all<alisolu tion.328The reaction velocities of organic halides with mines have been claimedto have diagnostic value in the identification and determination of mono-halides and in the identification of more complex substances.329 Iodinemay be determined by reduction with zinc powder in sodium hydroxidesolution, followed by titrimetric determination of the iodide.330 The lead311 W. C. Alford, Analyt. Chern., 1952, 24, 881; H. Swift and E. S. Morton, Analyst,1952, 77: 392; H.Gysel, Helv. Chim. Acta, 1952, 35, 802; W. Schoniger, Mikrochem.Mikrochzm. Acta, 1952, 39, 229.312 Sheau-Shya Kao and W. C. Woodland, ibid., 1951, 38, 309; W. Kirsten, ibid.,1952, 39, 389.313 Idem, ibid., p. 245; H. A. Page1 and I. J. Oita, Analyt: Chem., 1952, 24, 756.314 Ibid., p. 1078.316 A. Mallol, Anal. real SOC. esp. Fis. Quinz., 1951, 47, B, 659; S. Dahl and R.Oehler, J . Amer. Leather Chern. Assoc., 1951, 46, 317 ; G. Middleton and R. E. Stuckey,J . Pharm. Pharmacol., 1951, 3, 829; G. N. Badami and J. W. Whitaker, Fuel, London,1951, 30, 211.316 V. B. Fish, Analyt. Chern., 1952, 24, 760.317 P. McCutchan and W. F. Roth, ibid., p. 369.318 Ibid., p. 1487. 31D J. Lab. Clin. Med., 1951, 38, 324.320 R.C. I s t . sup. Sanit., 1951, 14, 668; Mikrochenz. Mikrochim. Acta, 1951, 38, 372.321 W. Perkow and H. Koddesbusch, 2. anal. Chem., 1952, 136, 189.322 W. Kirsten and I. Alperowicz, Mikrochern. Mikrochim. Acta, 1952, 39, 234.323 G. Kainz and A. Resch, ibid., p. 1 .324 Idem, ibid., p. 292.326 D. Klamann, Monatsh., 1952, 83, 719.327 F. Buscaronsand P. Mir, Analyt. Chim. Ada, 1952, 7, 185.323 A. K. Ruzhentseva and V. V. Kolpakova, J . Anal. Chem., U.S.S.R., 1951, 6, 223.328 G. Salomon, Analyst, 1952, 77, 1017.330 C. W. Ballard and S. Spice, J . Pharm. Pharmacol., 1952, 4, 322.325 A. J. Nutten, ibid., p. 355WITSON : INSTRUMENTAL METHODS. 32 1chlorofluoride method for the determination of flporine has been adapted toprovide a Volhard titration finish.331Oxalic acid may be titrated with permanganate at room temperaturein the presence of ferric a l ~ m .~ 3 ~ Tartaric acid has been determined bytreatment with excess of standard sodium vanadate solution and backtitration with standard iron(I1) solution.333 A method has been describedwhich is suitable for the simultaneous determination of aldehydes, ketones,and compounds such as a ~ e t a l s , ~ ~ ~ and methods for carbonyl compoundshave been critically e~amined.33~ The necessity for close tolerances on thestandard glass joints in methoxyl apparatus has been stressed.336 A modi-fication has been proposed for the van Slyke apparatus for determiningamino-groups in which carbon dioxide is used as a sweeping gas.337 Methodsfor the determination of reactive hydrogen have been reviewed.338A method of titration referred to as “ solubilisation titration ” has beenproposed for the analysis of binary mixtures which are not readily analysedby other methods.339 This is based on phase changes in the presence ofaqueous solutions of substances such as Teepol.Thus a hexane-octan-1-01mixture is titrated with hexane-Teepol-water either to the point where aclear isotropic mixture results or where an aqueous phase just begins todeposit. These phase changes are readily detected, and provide preciseend-points.7. INSTRUMENTAL METHODS.In a new edition of their book, H. H. Willard, L. L. Merritt, and J. A.Deanm present an up-to-date account of the more important branches ofinstrumental analysis, with full working descriptions of simple apparatusfor applying the methods.The single drawback, for British users of thebook, is that commercial models of apparatus described are of Americanorigin, but this does not prevent the book from being a very valuable labora-tory adjunct. Other reviews of instrumental operations in analyticalchemistry, with special reference to automatic operations 341 and to work inthe organic field,342 have appeared.R. H. Muller illustrates possible future developments by reference to somevery recent types of apparatus and the requirements which led to theirconstruction.Electroana1ysis.-Recent developments have been reviewed.343 Anindirect method for the determination of mixed halides has been devised344which is based on precipitation of the silver h;lides, solution of these inIn the paper already referred to331 R.Belcher, E. F. Caldas, and S. J. Clark, Analyst, 1952, 77, 602.332 G. E. Mapstone and J . W. Smith, Chem. and Ind., 1952, 856.333 G. G. Rao and H. Sankegowda, Current Sci., 1952, 21, 188.334 R. H. Buchanan, Austr. J . Appl. Sci., 1951, 2, 276.335 J . J . Perret, Helv. Chim. Acta, 1951, 34, 1531.336 R. L. Huang and F. Morsingh, Analyt. Chem., 1952, 24, 1359; C. A. Redfarn andD. R. Newton, Chem. and Ind., 1952,404,857; R. G. Stuart, ibid., p. 520; W. McCorkin-dale and A. C. Syme, ibid., p. 758; G. Weston, ibid., p. 1059.337 A. S. Hussey and J . E. Maurer, Analyt. Chenz., 1952, 24, 1612.338 E. D. Olleman, ibid., p. 1425.339 E. C. Lumb and P.A. Winsor, Analyst, 1952, 77, 1012.340 “ Instrumental Methods of Analysis,” 2nd edtn., New York, 1951.341 G. D. Patterson and G. Mellon, Analyt. Chern., 1952, 24, 131.342 R. L. Peck and P. H. Gale, ibid., p. 116.343 S. E. Q. Ashley, ibid., p. 91. 344 R. Fort, Chinz. atzalyt., 1952, 34, 143.REP.-VOL. XLIX. 322 ANALYTICAL CHEMISTRY.cyanide solution, and electrochemical deposition of the silver. Electro-deposition methods have been described for the determination of copper inf e r r o t i t a n i ~ m , ~ ~ ~ and of copper and silver in alloys containing the twometalsu6 Manganese can be deposited on a mercury cathode from aqueoussolution and thus estimated.347 Plutonium can be electrodeposited onplatinum. 348Controlled potential analysis has been applied to copper-base alloys 349and to mixtures of copper, bismuth, lead, and tin.350 Internal electrolysishas been used for the determination of copper in stee1.351Coulometry and Related Methods.-In a general consideration of theapplication of polarisation curves to electrochemical processes, the use ofthese curves and other factors in deducing conditions for coulometric andpotentiometric analysis is di~cussed.~5~ P.Delahay 353 has dealt with therelation between equilibrium potentials and the irreversibility of electrodeprocessed in relation to coulometric titrations. Coulometric methods havebeen developed for cerium(1v) , dichromate, permanganate, and vana-d i u m ( ~ ) , ~ ~ ~ iron(1r) and arsenic(rII) ,355 ~ilver,~5G thallium(1),357 manganese,35*and uranium.359 Titanium(1v) chloride has been recommended as anintermediate in coulometric titrations which provides a more powerfulcouple than those hitherto reported, and hence permits the method to bemore widely applied.3m Inner electrolysis has been applied on a time basisto the titration of manganese and other element~.~~l Low concentrations ofoxygen have been measured by the capacity of a cell in which the gassurrounds a platinum electrode to form one of thePo1arography.-Probably the most significant contribution to thisbranch is the new edition of the standard work by I.M. Kolthoff and J. J.Li11gane,~63 which is approximately doubled in size. Polarography has beenreviewed,364 and in a review of the polarography of organic compoundsJ.E. Page3G5 gives an excellent introduction to general aspects of thesubject. Theoretical aspects of polarographic currents have been dis-cussed.366 The application of square-wave polarography to the detection345 L. Bonnafous, Chim. analyt., 1952, 34, 176.346 H. Diehl and J . P. Butler, Analyst, 1952, 77. 268.s47 B. McDuffie and L. S. Hazlegrove, AnaZyt. Chein., 1952, 24, 826.34* H. W. Miller and R. J. Brouns, ibid., p. 536.349 G. W. C. Milner and R. N. Whittem, Analyst, 1952, 77,.11.350 J. J. Lingane and S. L. Jones, Analyt. Chem., 1952, 24, 1798.3 5 1 D. L. Carpenter and A. D. Hoplcins, Analyst, 1952, 77, 86.352 R. Gauguin, G. Charkit, and J . Coursier, Analyl. Chim. Acta, 1952, 7, 172;R. Gauguin, G. Charlot, C.Bertin, and J . Badoz, ibid., p. 360; R. Gauguin and G.Charlot, ibid., p. 408; R. Gauguin, Ind. Chem. Chem. Manuf., 1952, 28, 487.364 L. Meites, Analyt. Chem., 1952, 24, 1057. 353 Analyt. China. Acta, 1952, 6, 542.355 W. M. MacNevin and B. B. Baker, ibid., p. 386.356 S. S. Lord, R. C. O'Neill, and L. B. Rogers, ibid., p. 209.357 R. P. Buck, P. S. Farrington, and E. H. Swift, ibid., 1195.3 5 8 W. D. Cooke, C. N. Reilley, and N. H. Furman, ibid., p. 205.359 N. H. Furman, C. E. Bricker, and R. V. Dilts, Nucleay Sci. Abstr., 1952, 6, 179.360 P. Arthur and J. F. Donahue, Analyt. Chenz., 1952, 24, 1612.361 A. Schleicher, 2. anal. Chem., 1952, 136, 330; W. Oelsen, H. Haase, and G.362 P. Hersch, I n d . :hem. Chem. Manuf., 1952, 28, 488.363 " Polarography,364 J.A. Lewis, Ind. Chem. Chem. Manuf., 1952, 28, 531.365 Quart. Reviews, 1952, 6, 262.366 P. Delahay and G. L. Stiehl, J . Anzer. Chem. SOC., 1952, 74, 3500; P. Delahay,ibid., p. 3506; P. Delahay and T. J. Adams, ibid., p. 5740; S . L. Miller, ibid., p. 4130.Graue, Angew. Chem., 1952, 64, 76.2nd edtn., New York and London, 1952WILSON : INSTRUMENTA4L METHODS. 323and determination of very low concentrations of ions, of the order of lo-'to l O W 9 ~ , has been described.367 W. Furness 365 has discussed the desir-ability of more precise measurement of the diffusion current and potential ofthe dropping-mercury electrode, and has suggested methods by which thismay be achieved. Recording apparatus suitable for polarography has beendescribed.369 J.Heyrovsky 370 has instanced advantages of using a cathode-ray oscilloscope for qualitative analysis by means of potential-time curves.A rotating mercury electrode which combines advantages of the dropping-mercury and of the rotating-platinum electrode, though with certain con-sequent disadvantages, is stated371 to be applicable to the analysis ofmaterials at very low concentrations. A method of differential polaro-graphy using a single dropping electrode has been proposed.372Individual polarographic methods have been proposed for the deter-mination of fluoride by complexing with aluminium and estimation of theexcess of aluminium,373 of sulphate by conversion into cadmium sulphideand determination of cadmium,374 of t e t r a t h i ~ n a t e , ~ ~ ~ of potassium byprecipitation with excess of dipicrylamine,376 of germanium,377 of copper-baseof copper by excess ofquinaldinic acid,381 of silver,382 of indium,383 of iron,384 of chromium,385of molybdenum,386 and of titanium.387388and polarographic methods of determination have been proposed fora ~ r a l d e h y d e , ~ ~ ~ f~rmaldehyde,~~ and glucose.391 Polarographic studieshave been made of some heterocyclic nitrogen compounds392 and somedyes.393 G.E. 0. Proske 394 has proposed the use of certain wetting agentssuch as the dialkyl sodium sulphosuccinates, which have little effect onpolarographic waves, for the solubilisation of organic compounds which areinsoluble in water, thus enabling polarographic determinations to be carried367 G.C. Barker and I. L. Jenkins, Analyst, 1952, 77, 685. 368 Ibid., pp. 246, 345.360 E. B. ThomAs and R. J . Nook, J , Chem. Educ., 1952, 29, 414; M. T. Kelley andH. H. Miller, Nuclear Sci. Abstr., 1952, 6, 148; Analyt. Chenz., 1952, 24, 1895.370 I n d . Chem. Chem. Manuf., 1952, 28, 489.371 T. S. Lee, J . Amer. Chem. SOC., 1952, 74, 5001.372 M. Ishibashi and T. Fuginaga, Bull. Chem. SOC. Japan, 1952, 25, 68.373 B. J. MacNulty, G. F. Reynolds, and E. A. Terry, Nature, 1952, 169, 888.374 A. D. Horton and P. F. Thomason, Analyt. Chem., 1951, 23, 1859.376 W. Furness and W. C. Davies, Analyst, 1952, 77, 697.376 D. Monnier and Z . Besso, Analyt. Chim. Acta, 1952, 7, 380.377 D. Cozzi and S. Vivarelli, Mikrochem. Mikrochim. Acta, 1952, 40, 1378 W.E. Allsopp and T. E. Arthur, Analvt. Chem., 1951, 23, 1883.37s F. Burriel Marti and J. F. Saiz del Rio, Anal. real SOC. esp. Fis. Quiun., 1951,380 0. I. Milner, J. R. Glass, J. P. Kirchner, and A. N. Yurick, Analyt. Chem., 1952,382 G. C. B. Cave and D. N. Hume, Analyt. Chem., 1952, 24, 588.383 G. Rienacker and E. Hoschek, 2. anorg. Chem., 1952, 268, 260.384 L. Meites, Analyt. Chern., 1952, 24, 1374.385 E. C. Mills and S. E. Hermon, Metallurgia, 1951, 44, 327.386 M. G. Johnson and R. J . Robinson, Analvt. Chem., 1952, 24, 366.387 R. P. Graham and A. Hitchen, Analyst, 1952, 77, 533.388 S. Wawzonek, Analyt. Chern., 1952, 24, 32.38s A. S. Kirillova and I. A. Korshunov, J . Anal. Chem., U.S.S.R.. 1951, 6, 257.3s0 A. S. Bogorad and S.N. Aleksandrov, ibid., p. 276.301 R. N. Adams, C. N. Reilley, and N. H. Furman, Analyt. Chewz., 1952, 24, 1200.302 R. C. Kaye and H. I. Stonehill, J., 1952, 3240.303 Idem, ibid., pp. 3231, 3244.of trace elements in lead379 and inRecent developments in organic polarography have been47, B, 803.24, 1728.P. E. Wenger, D. Monnier, and L. Epars, Helv. Chirn. Acta, 1952, 35, 561.3 ~ ~ 4 Analyt. Chem., 1952, 24, 1834324 ANALYTICAL CHEMISTRY.out. A polarographic study of certain metal salts and a number of acidchlorides in non-aqueous solution has been carried out, and the difficultiesnormally encountered in such work have been discussed.395Methodshave been proposed for the determination of fluoride through a decrease inthe diffusion current from an aluminium-organic for the deter-mination of iodine,Z98 of potassium with sodium dipi~rylaminate,~~~ and ofzinc with potassium ferr0cyanide.mPotentiometric Titrations.-The mechanism of the dead-stop end-pointhas been discussed,M1 and it has been shown that the method ought to beapplicable to any oxidation-reduction system by choosing suitable con-ditions. G.Granm2 has described a method, applicable to all types ofpotentiometric titrations, by which end-points which are not normally well-defined may be represented precisely by transforming the curves intointersecting straight lines. E. Bishopm3 has proposed the use of “ in-dicator-reference ” electrodes, thus simplifying the apparatus in potentio-metric titrations, and has extended the method to deal with non-aqueousas well as aqueous solutions.Peroxides have been determined iod~metrically.~~ Small amounts ofchloride have been estimated by making use of two half-cells which differonly in the chloride content due to the unknown 405 or by precipitating thechloride with iodide as carrier, the iodide being removed before titration.w6The errors involved in the potentiometric titration of mixtures of halideswith silver nitrate have been studied.” Methods have been proposed forthe argentometric titration of mixtures of bromides and thiocyanates,408 forthe mercurimetric titration of bromide,409 for the cerimetric titration ofhypophosphate,*1° for the estimation of phosphate by precipitation as zincphosphate and titration of the acid liberated,411 of thiocyanate using a silverthiocyanate electrode,412 of rubidium and czsium as chlorides argento-metrically,f59 of magnesium by addition of excess of fluoride and titrationof the excess with ferric chloride,413 of cadmium by applying an empiricalfactor in the bromate-bromide titration of 2-o-hydroxyphenylbenzoxa-zo1e,161, 414 of copper in the presence of oxidising anions iod~metrically,~~~ ofAmperometric Titrations.-Recent work has been r e v i e ~ e d .~ ~ 6395 P. Arthur and H. Lyons, ibid.. p. 1422.396 H. A. Laitinen, ibid., p. 46; T. D. Parks, Analyt. Chim. Acta, 1952, 6, 653.397 C. R. Castor and J. H. Saylor, Analyt. Chem., 1952, 24, 1369.398 H. P. Kramer, W. A. Moore, and D. G. Ballinger, ibid., p. 1892.399 Y . Yasumori, Bull.Chena. SOC. Japan, 1951, 24, 107.400 A. L. Woodson, B. H. Johnson, and S. R. Cooper, Analyb. Chem., 1952, 24, 1198.401 K. G. Stone and H. G. Scholten, ibid., p. 671 ; J. E. B. Randles, I n d . Chem.Chem. Manuf., 1952, 28. 490.402 AnaZyst, 1952, 77, 661.404 E. W. Abrahamson and H. Linschitz, Analyt. Chem., 1952, 24, 1355.405 W. J . Blaedel, W. B. Lewis, and J. W. Thomas, ibid., p. 509.406 G. S. Spicer and J. D. H. Strickland. Analyt. Chim. A d a , 1952, 6, 493.407 H. Chateau and J. Pouradier, Compt. rend., 1952, 234, 623.408 C. Leon, ibid., 1951, 253, 170.409 F. Sierra and 0. Carpena, Anal. real SOC. esp. Fis. Quim., 1951, 47, B, 527.410 T. Moeller and G. H. Quinty, Analyt. Chem., 1952, 24, 1354.411 R. N. Bell, A. R. Wreath, and W. T.Curless, ibid., p. 1997.412 R. N. Parida, S. Aditya, and B. Prasad, J . Indian Chem. SOC., 1952, 29, 377.‘13 W. Mannchen, Metal Abstr., 1952, 19, 795.414 J. L. Walter and H. Freiser, Analyt. Chem., 1952, 24, 1985.415 J. Bernal Nievas and L. Serrano Berges, Anal. real SOC. esp. Fis. Quim., 1951,403 Ibid.. p. 672.47, B, 601WILSON INSTRUMENTAL METHODS. 325manganese, chromium, and vanadium in steels,416 of chromium and iron inchromite ores,*17 of iron(1Ir) by titration with mercurous solution,41a oftungsten with chromous chloride,419 of uranium ~erimetrically,~~ and ofthorium as m ~ l y b d a t e . ~ ~ ~Conductance Methods.-In the last few years methods have been pro-posed for high-frequency titrations in addition to the normal methods forconductimetric titrations ; and high-frequency conductance measurementsare being used in ways other than titrimetric for analytical purposes.Asimple apparatus for conductimetric titration has been described.421 Aconductimetric titration method has been proposed for the determination offree acid in the presence of hydrolysable salts, and is applicable both tovery small aliquots of solution and to solutions of low concentration, so thatit is recommended for the titration of highly radioactive solutions.422 Thesulphate titration with barium solution has been studied, and it is pointedout 423 that the conductimetric end-point and the true equivalence-point arenot necessarily coincident, the former being affected by composition andconcentration of the solution. Such divergence should be taken into accountin precise work.Potassium perchlorate titrations are suitable for con-ductance measurements.& A method is described by which calcium andstrontium occurring together may be determined by conductance measure-ment, without titrati0n.4~~ R. P. Taylor and N. H. Furman426 havereported favourably on the possibility of using direct rather than alternatingcurrent for conductance measurements, and have devised an apparatus whichdoes not require either the specialised or inconvenient equipment necessaryfor alternating-current measurements. The accuracy and precision of thisapparatus, as applied to several different conductimetric determinations,compare favourably with those of the more normal methods.Theoretical and practical aspects of chemical analysis by high-frequencyconductance measurements have been discussed.427 P.W. West has de-scribed an apparatus suitable for both titrimetric and concentration deter-m i n a t i o n ~ , ~ ~ ~ and simple apparatus which could be set up and maintainedin the ordinary laboratory has also been de~cribed.~29 The high-frequencytitration of sulphates 430 and of calcium 431 has been reported.Colorimetry and Absorptiometry.-A new edition of a standard work hasappeared.432 General colorimetric methods have been reviewed.433 A416 F. Burriel Marti and R. Su&rez Acosta, Inform. Quirn. anal., 1951, 5 , 159; P.41' D. ZivanoviC, Bull. SOC. chim. Belgrade, 1951, 16, 151.418 R. Belcher and T.S. West, Analyl. Chinz. Acta, 1952, 7, 470.4lD S. E. S . El Wakkad and H. A. M. Rizk, Analyst, 1952, 77, 161.420 R. B. Hahn and M. T. Kelley, Nuclear Sci. Abstr., 1952, 6, 211.421 R. Weiner and L. Koller, 2. anal. Chem., 1952, 138, 241.422 L. P. Pepkowitz, W. W. Sabot, and D. Dutina, Analyt. Chent., 1952, 24, 1956.423 D. Lydersen and 0. Gjems, 2. anal. Chem., 1952, 137, 189.424 R. Weiner and L. Koller, ibid., p. 246.425 G. 0. Assarsson and A. Balder, Analyt. Chem., 1952, 24, 1679.426 Ibid., p. 1931.427 W. J . Blaedel, T. S. Burkhalter, D. G. Flom, G. Hare, and F. W. Jensen, ibid.,p 198; J . L. Hall, ibid., p. 1236; W. J . Blaedel, H. V. Malmstadt, D. L. Petitjean, andW. K. Anderson, ibid., p. 1240. 420 Ind. Chem. Chem. Manuf., 1952, 28, 492.429 J .L. Hall, Analvl. Chem., 1952, 24, 1244.430 0. 1. Milner, ibid., p. 1247. 431 S. Musha, Sci. Rep. TGhoku, 1951, A , 3, 56.432 B. Lange, " Kolorimetrische Analyse," 4th edtn., Weinheim, 1952.433 M. G. Mellon, Analyt. Chein., 1952, 24, 924; E. Geffroy, Chim. analyt., 1962, 34, 119.Enghag, J . Iron Steel Inst., 1952, 171, 443326 ANALYTICAL CHEMISTRY.capillary colorimeter for very small amounts of material 434 and a photo-electric comparator have been d e s ~ r i b e d . ~ ~ Means of improving precisionhave been suggested,436 and the fallacy of assuming that addition of a knownamount of constituent to a trace sample will improve the precision bybringing the final amount out of the region of high relative analysis errorhas been pointed Methods of dealing with two-component coloursystems 438 and with turbid solutions 439 have been discussed.Filters for themercury lines have been described,* and alkaline potassium chromate hasbeen recommended as a transmittancy standard for work in the ultra-violet .ulAbsorptiometric methods of analysis have been put forward for alloys 442and for trace metals in petroleum fraction^.^^ Individual analyticalmethods have been described for fluoride by its bleaching effect on variouslakes,P44 for hydrazine by $-dimethylarninoben~aldehyde,~~ for high nitratecontent by phenoldisulphonic acid,446 for phosphorus as molybdate 4479or as vanadate-m~lybdate,~~ for arsenic as m ~ l y b d a t e . ~ ~ , 451Oxygen in metallic tin is estimated by removing the metal with mercuryand estimating the tin in the residual oxide by phosph~molybdate,~~~ andgaseous oxygen is determined by the colour given with alkaline pyrogall01.~~~Metal sulphide sols have been examined for the estimation of sulphur, and amethod for preparing a satisfactory bismuth sulphide sol is given.454 Sulphurmay also be estimated by conversion into methylene-blue 455 or into Lauth'sviolet .456 Colorimetric procedures have been described for selenium andtellurium,233 for cyanide by reduction of sodium p i ~ r a t e , ~ ~ ~ and for boronby 1 : l-dianthraq~inoylamine,~~8 q ~ i n a l i z a r i n , ~ ~ ~ or pentamethylquer-434 G.Gorbach, Mikrochem. Mikrochim. Acta, 1952, 39, 204.435 T. I;. Stanton, Fuel, London, 1951, 30, 208.438 F.F. Pollak and J . W. Nicholas, Metallurgia, 1951, 44, 319.437 W. A. E. MacBryde, Analyt. Chem., 1952, 24, 1639.03* E. Allen and E. M. Hammaker, ibid., p. 1295; R. G. Milkey, ibid., p. 1675.439 J . Fog, Analyst, 1952, 77, 454.440 J. W. Nicholas and F. F. Pollak, Analyst, 1952, 77, 49; J . Chance, E. Guillemot,J . Lenoble, and G. Tendron, Compt. rend., 1951, 233, 35.44l G. K. Haupt, J . Opt. SOC. Amer., 1952, 42, 441.442 G. W. C. Milner and W. R. Nall, Analyt. Chim. A d a , 1952, 6, 420; M. Jean, ibid.,7, 338.443 J . H. Karchmer and E. L. Gunn, Analyt. Chant., 1952, 24, 1733.444 A. D. Horton, P. F. Thomason, and F. J . Miller, ibid., p. 548; M. J . Price and0. J . Walker, ibid., p. 1593; H. E. Bumsted and J . C. Wells, ibid., p. 1595.445 G.W. Watt and J . D. Chrisp, ibid., p. 2006.446 J. M. Komarmy, W. J. Broach, and M. K. Testerman, Analyt. Chim. Acta, 1952,7, 349.447 G. R. Nakamura, Analyt. Chem., 1952, 24, 1372.448 W. Teichert, J . Iron Steel Inst., 1952, 170, 181.449 S. Gericke and B. Kurmies, 2. anal. Chem., 1952, 137, 15.450 J . .C. Bartlet, M. Wood, and R. A. Chapman, Analyt. Chem., 1952, 24, 1821 ;C. Wadelin and M. G. Mellon, Analyst, 1952, 77, 708; Y . Kakita, Sci. Rep. Tdhokzt,1951, 3, A , 698.451 W. C. Coppins and J . W. Price, Melallurgia, 1952, 46, 52.452 L. Silverman, Nuclear Sci. Abstr., 1952, 6, 145.453 C. H. Blachly and R. R. Miller, Anal. Chem., 1952, 24, 1819.4S4 E. Treiber, H. Koren, and W. Gierlinger, Mikrochem. Mikrochim. Acta, 1952,40, 32.455 M. S.Budd and H. A. Bewick, Analyt. Chem., 1952, 24, 1536.456 D. S. C. Polson and J. D. H. Strickland, A n d y t . Chim. Acta, 1952, 6, 452.457 F. B. Fisher and J . S. Brown, Analyt. Chem., 1952, 24, 1440.468 D. A. Brewster, ibid., 1951, 23, 1809.459 D. MacDougall and D. A. Biggs, ibid., 1952, 24, 566WILSON : INSTRUMENTAL METHODS. 327~ e t i n . ~ ~ O Silicon may be determined as ~ilicomolybdate,~~~~ 462 and ger-manium with q~inalizarin.~63Methods for the determination of potassium have been reviewed,464 andmethods based on chloroplatinate 465 and silver cobaltinitrite 466 have beendescribed. Methods for the determination of sodium have been reviewed.467Colorimetric methods for calcium using m u r e ~ i d e , ~ ~ ~ chloranilic 470or the reaction of oxalate with diphenylamine to give aniline-blue 471 havebeen examined.Methods for beryllium use a l ~ m i n o n , ~ ~ ~ acetylacetone,62or r n ~ r i n . ~ ~ ~ Magnesium has been estimated by using Eriochrome-cyanine-R(Solochrome-cy anine-RS) ,474 Tit a n - y e l l ~ w , ~ ~ ~ ~ 47 3-hydroxy- 1 -$-nit rophenyl-3-~henyltriazen,~~~ 8-hydro~yquinoline,~~~ or the complex formed by8-hydroxyquinoline and iron.47s Zinc has been determined by o-[a-(2-hydroxy-5-sulphophenylazo) benzylidenehydrazino] benzoic acid.479 Forcadmium 480 and mercury 481 diphenylthiocarbazone has been used. Mercuryhas also been determined by its effect on the colour of ferric thiocyanatesolution.482Copper has been estimated as tartrate,4m by diethyldithio~arbamate,~~by rubeanic a ~ i d , 4 ~ ~ and by biscyclohexanone oxalyldihydrazone ; 486 silverby $-dimethylaminobenzylidenerhodanine ; 487 gold by diphenylamine 488 orby diphenylthiocarbazone ; 243 aluminium by Eriochrome-cyanine-R,4s9by $-hydroxyquinoline,4~~ 491 or by aluminon ; 402 manganese as per-460 M.K. Urs and K. Neelakantarn, J . Sci. I n d . Res., India, 1952, 11, B, 259.461 J . R. Boyd, Analyt. Chem., 1952, 24, 805.462 A. B. Carlson and C. V. Banks, ibid., p. 472.u3 C. K. N. Nair and J. Gupta, J . Sci. I n d . Res., India, 1951, 10, B, 300; 1952, 11,465 R. E. Eckel, J . Bzol. Chem., 1952, 195, 191.466 E. M. Chenery, Analyst, 1952, 77, 102.4 6 7 T. S. West, I n d . Chem. Chem. Manuf., 1952, 28, 225.468 H. Ostertag and E. Rinck, Compt. rend., 1951, 232, 629; Chinz. analyt., 1952, 34,4G0 F.Koroleff, Suomen Kem., 1951, 60, 56.470 R. F. U. Frost-Jones and J . T. Yardley, Analyst, 1952, 77, 468.4 7 1 J . de la Rubia Pacheco and F. Blasco L6pez-Rubio, Inform. QuCm. analit., 1952,473 T. Y. Toribara and P. S. Chen, ibid., p. 539.474 A. Bacon, Metallurgia, 1951, 44, 207.4 7 5 0. Glemser and W. Dautzenberg, 2. anal. Chem., 1952, 136, 254; A. C. Mason,4 7 0 K. N. Pochinok and V. Y. Pochinok, J . Anal. Chem., U.S.S.R., 1951, 6, 288.4 7 7 J. Davidson, Analyst, 1952, 77, 263.4 7 8 R. Bittel, Ann. nut. Inst. rech. Agron., 1951, 1, A , 144.470 J. H. Yoe and R. M. Rush, Analyt. Chim. Acta, 1952, 6, 526.480 L. Silverman and K. Trego, Anal-wt, 1952, 77, 143.481 D. J. S. Gray, ibid., p. 436. 482 R.0. Brumblay, Analyt. Chem., 1952, 24, 905.483 M. Bobtelsky and C. Heitner, Bull. SOC. chim., 1951, 18, 502.484 J. L. Hague, E. D. Brown, and H. A. Bright, J . Res. Nut. Bur. Stand., 1951, 47,485 A. Lemoine, Analyt. Chim. A d a , 1952, 6, 528; W. L. Miller, M. Acampora, and4 8 6 C. U. Wetlesen and G. Gran, Svensk Pappevstidning, 1952, 55, 212.4 8 7 G. C. B. Cave and D. N. Hume, Analyt. Chem., 1952, 24, 1503; E. B. Sandell and488 P. A. Heredia and J. C. Cuezzo, Monit. Farm., 1951, 57, 361.489 L. C. Ikenberry and A. Thomas, Analyt. Chem., 1951, 23, 1806; A. Bacon,490 W. Sprain and C. V. Banks, Analyt. Chim. Acta, 1952, 6, 363.4B1 0. A. Kenyon and H. A. Bewick, Analyt. Chem., 1952, 24, 1826.492 C. L. Luke and K. C . Braun, ibid., p. 1120; C. L.Luke, ibid., p. 1122.B, 274. 464 T. S. West, I n d . Chem. Chem. Manuf., 1952, 28, 158.108; J . Raaflaub, 2. physiol. Chem., 1951, 288, 228.6, 40. 472 C. L. Luke and M. E. Campbell, Analyt. Chem., 1952, 24, 1056.A.R.E. Malling Res. Sta., 1951, 126.380; C. A. No11 and L. D. Betz, Analyt. Chem., 1952, 24, 1894.G. Norwitz, Metal Abstr., 1952, 19, 856.J. J. Neumayer, ibid., 1951, 23, 1863.AnaZvst, 1952, 77, 90328 ANALYTICAL CHEMISTRY.rnanganateJq6l, 4933 4949 or through permanganate by the starch-iodideblue ;Iron has been estimated as acetate 497 or t h i o ~ y a n a t e , ~ ~ ~ ~ 498, 499 or byS-hydroxyquinoline,m thioglycollic acid,493 1 : 10-phenanthrolineJ38~ 490, 5014 : 7-diphenyl-1 : 10-phenanthroline,502 1 : 2-dihydroxybenzene-3 : 5-disulphonic acid ; 503 cobalt as tartrate 483 or t h i o ~ y a n a t e , ~ ~ or by nitroso-Rsalt , 505 diphenylthiocarbazone, 506 peroxide-bicarbonate treatment,m7zsonitrosomalonylguanidine,64 ethylenediaminetetra-acetic acid,64 or 4-nitro-2-mercapt oacetamidophenol ; 129 nickel as tartrate 483 or with dimethylgly-oxime; 3 8 0 9 493, chromium as dichromate 509 or with diphenylcarb-azide ; 510 molybdenum by thiocyanateJal, 515 prot~catechualdehyde,~~~ or1 : 2-dihydroxybenzene-3 : 5-disulphonic acid ; 513 tungsten by treatmentwith thiocyanate and stannous chloride ; 514 uranium by thiocyanate 516 orby resacetophenone ; 517 tin by 4-methyl-] : 2-dimercaptobenzene (toluene-dithiol) stabilised by Teepol ; 518 lead by diphenylthiocarbazone ; 519titanium as pertitanate 498 or by thym01,~~ 1 : 2-dihydroxybenzene-3 : 5-disulphonic acid,a3 or chromotropic acid ; 521 zirconium by precipitation asphosphate and conversion into phosph~molybdate,~~~ by a l i ~ a r i n - S , ~ ~ ~ orby chloranilic acid ; 470 thorium by o-arsenophenylazo-2-naphthol-3 : 6-disulphonic acid ; 524 antimony as the iodoantimonite byand rhenium as tetraphenylarsonium errh hen ate."^^or403 G.W. C. Milner and H. Groom, Metallurgia, 1951, 44, 271.494 B.S.I. Specif., 1951, No. 1121, Pt. 23.495 N. M. Silverstone and D. W. D. Showell, Metal Ind., 1952, 80, 467.496 S. Tribalat, I. Pamm, and M. L. Jungfleisch, Analyt. Chim. Acta, 1952, 6, 142.497 W. Reiss, J. F. Hazel, and W. M. McNabb, Analyt. Chem., 1952, 24, 1646.498 H.Seiser, Ber. deut. keram. Ges., 1951, 28, 699.499 W. Teichert, J . Iron Steel Inst., 1952, 170, 181.500 A. G. Hamlin, J . Text. Inst., 1952, 43, T, 234.601 A. Gottlieb, Mikrochem. Mikrochim. A d a , 1952, 39, 176.502 G. F. Smith, W. H. McCurdy, and H. Diehl, Analyst, 1952, 77, 418.503 R. H. Beaumont, Nuclear Sci. Abstr., 1952, 6, 212.504 W. A. C. Campen and H. Geerling, Chem. Weekblad, 1952, 78, 193.‘05 W. Stross and G. Stross, Metallurgia, 1952, 45, 315.606 J . Mermillod, Metal Abstr., 1951, 19, 215.507 G. Telep and D. F. Boltz, Analyt. Chem., 1952, 24, 945.508 J. Haslam, F. R. Russell, and N. T. Wilkinson, Analyst, 1952, 77, 464; V. T.Chuyko, J . Anal. Chenz., U.S.S.R., 1951, 6, 297.609 E. Asmus, 2. anal. Chem., 1952, 135, 179.510 B.S.I.Specif., 1952, No. 1121, Pt. 24; Methods of Analysis Committee, J . IronSteel Inst., 1952, 170, 268; H . J . Cahnmann and R. Bisen, Analyt. Chem., 1952, 24,1341 : B. E. Saltzman, ibid., p. 1016.511 R. B. Henrickson and E. B. Sandell, Analyt. Chim. Acta, 1952, 7, 57; P. Karstenand J. H. C . van Mourik, Rec. Trav. chim., 1952, 71, 302.512 M. Y . Shapiro, J . Anal. Chem., U.S.S.R., 1951, 6, 371.613 J. H. Yoe and F. Will, Analyt. Chim. Acta, 1952, 6, 450.514 G. Gran, Svensk Papperstidning, 1951, 54, 764.516 F. Jungblut, Chim. analyt., 1951, 33, 248.516 C. E. Crouthamel and C . E. Johnson, Analyt. Chew., 1952, 24, 1780.517 M. K. Urs and K. Neelakantam, J . Sci. I n d . Res., India, 1952, 11. B, 79.518 F. R. Williams and J. Whitehead, J . Appl.Chem., 1952, 2, 213.519 F. Neuwirth, J . Iron Steel Inst., 1952, 170, 310.520 J. V. Griel and R. J. Robinson, Analyt. Chem., 1951, 23, 1871.521 T. C . J. Ovenston, C. A. Parker, and C. G. Hatchard, Anulyt. Chim. Acta, 1952,523 E. W. Kiefer and D. F. Boltz, Analyt. Chem., 1952, 24, 542.523 G. B. Wengert, ibid., p. 1449; A. Mayer and G. Bradshaw, Analyst, 1952,524 Idem, ibid., p. 154; A. E. Taylor and R. T. Dillon, Analyt. Chem., 1952, 24, 1624;6, 7 ; R. Rosotte and E. Jaudon, ibid., p. 149.77, 476.R. Kronstadt and A. R. Eberle, Nuclear Sci. Abstr., 1952, 6, 179WILSON INSTRUMENTAL METHODS. 329met hyl-violet ,525 or by triphenylmethylarsonium iodide ; 526 bismuth byt hic urea,527 cupferron ,528 or dial1 yldit hiocarb amidoh ydrazine ; 529 vanadiumas kanadyl ion,=() by catalytic liberation of iodine,%l as the complex phos-phoiungstic acid,380 or with benzhydroxamic acid; 632 niobium as thio-cyanate 533 or as perniobic acid; 634 osmium by thiourea; 197 rutheniumby p-nitrosodimethylaniline ; 535 rhodium by the blue complex formed withhypochlorite ; 536 and palladium with p-furfuraldoxime 537 or phenyl-thiourea. 538From the large number of colorimetric methods for organic compoundsthe following may be mentioned : determination of methanol by Schiff'sreagent ; 539 of acetic acid 5~ and glycerol by reduction of dichromate ;of nitroparaffins by decomposition, and combination of the resulting nitrousacid with resorcinol; 542 of amides through the reaction of the derivedhydroxam ic acids with ferric chloride.543 The system dichromate-chromium(111) has been studied with a view to its use for the colorimetricdetermination of sulphite and of organic compounds,"l, 545 and it hasbeen found to be very sensitive, particularly if absorptiometric measure-ments are carried out in the ultra-violet region. A similar indirect methodfor organic compounds depends on treatment by standard oxidising agentsfollowed by an oxidisable dye. The amount of oxidising agent used, andhence of organic compound, is determined by colorimetry of the residualdye. 5.1~Photometric tit rations have been proposed for bromide-bromate re-action~,"~ using the absorption of the tribromide ion to indicate the end-point, and absorptiometric methods have also been used to follow the titra-tion of arsenic by cerium(~v).~~* Luminol has been proposed as a chemi-luminescent indicator to enable detection of the end-point photometricallyin acid-base titrations of highly opaque solutions; M9 for example, by usingthis method it was possible to determine the end-point of the titration of asolution containing Indian ink.525 M.Jean, Analyt. Chim. Acta, 1952, 7, 462.526 B. Figgis and N. A. Gibson, ibid., p. 313.527 B. B. Bendigo, R. K. Bell, and H. A. Bright, J . Res. Nut. BUY. Stand., 1951, 47,628 H. Bode and G. Henrich, 2. anal. Chem., 1952, 135, 98.529 J . Gupta and K. P. S. Sarma, J . I n d i a n Chem. Soc., 1951, 28. 89.530 R. Santini, J. F. Hazel, and W. M. McNabb, Analyt. Chim. A d a , 1952, 6, 368.531 T.Shiokava, Sci. Rep. TGhoku, 1950, 2, A , 613.532 A. K. Das Gupta and M. M. Singh, J . Sci. I n d . Res., India, 1952, 11, B, 268.533 H. Freund and A. E. Levitt, Analyt. Chem., 1951, 23, 1813; A. B. H. Lauw-Zecha, S. S. Lord, and D. N. Hume, ibid., 1952, 24, 1169.534 G. Telep and D. F. Boltz, ibid., p. 163.535 J . E. Currah, A. Fischel, W. A. E. McBryde, and F. E. Beamish, ibid., p. 1980.536 G. H. Ayres and F. Young, ibid., p. 166.538 G. H. Ayres and B. L. Tuffly, ibid., p. 949.539 J . F. Guymon, J . Ass. Off. Apric. Chem., 1951, 34, 310.640 E. Ciaranfi and A. Fonnesu, Biochem. J . , 1952, 50, 698.541 D. T. Englis and L. A. Wollerman, Analyt. Chem., 1952, 24, 1983.542 L. R. Jones and J. A. Riddick, ibid., p. 1533.643 I;. Bergmann, ibid., p.1367.544 S. Sussman and I. L. Portnoy, ibid., p. 1652.545 M. J . Cardone and J . Compton, ibid., p. 1903.546 H. T. Gordon, ibid., 1951, 23, 1853.547 P. B. Sweetser and C. E. Bricker, ibid., 1952, 24, 1107.548 Idem, ibid., p. 409.549 1;. Kenney and R. B. Kurtz, ibid., p. 1218.252; C. J . Hall, Analyst, 1952, 77, 318.537 E. W. Rice, ibid., p. 1995330 ANALYTICAL CHEMISTRY.Nephelometry.-Chloride has been determined in titanium sponge byprecipitation as silver chloride followed by conversion into a silver sulphideZinc may be precipitated in a form suitable for nephelometricestimation by 8-hydro~yquinoline,~51 and tin(1v) by precipitation with4-hydroxy-3-nitrobenzenearsonic acid.552 A nephelometric titration hasbeen devised from the estimation of very small amounts of halides based onthe colour change at the end-point of the sol formed with silver nitrate.553F1uorimetry.-Fluorimetric analysis has been reviewed.554 Fluorescenttests have been described for h y d r a ~ i n e , ~ ~ ~ aluminium,556 lead,557 and8-hydroxyquinoline and its derivatives.558Quantitative methods depending on fluorescence have been proposed forfluoride,559 beryllium,560 and uranium. 561Emission Spectrography .-Advances in instruments and in analyticalmethods have been reviewed.562 R. C. Hughes has described a method ofapplying powdered samples to graphite electrodes in a reproducible man-ner.563 The line-width method of quantitative analysis has been applied toplant products so as to produce reproducible results over a wide range ofconcentration^.^^^ Methods of concentrating 565 and analysing 566 traceelements have been described, and spectroscopic analysis has been appliedto small amounts of impurities in tungsten,567 of metals in cracking cata-lysts 56* and in and to the analysis of coppers and brasses,570 oflanthanon mixtures 571 and of mixtures of the platinum m e t a l ~ .~ 7 ~For individual elements spectrographic methods have been recommendedfor the determination of lithium and rubidi~m,~74 l i t h i ~ m , ~ ~ jiron,576 lead,577 and tantalum and niobium.578 A spectrographic study has650 M. Codell and J. J. Mikla, Analyt. Chem., 1952, 24, 1972.651 L. Bertiaux, Chim. analyt., 1951, 33, 59.652 P. Karsten, H. L. Kies, and J . J .Walraven, Analyt. Chim. Acta, 1952, 7 , 355.553 M. Hasselmann and G. Laustriat, Compt. rend., 1952, 234, 625.554 C. E. White, Analyt. Chem., 1952, 24, 85; C. E. White et al., ibid., p. 1965.555 F. Feigl and W. A. Mannheimer, Mikrochem. Mikrochim. Acta, 1952, 40, 50.5 5 6 F. Feigl and G. B. Heisig, J . Chem. Educ., 1952, 20, 192.5 5 7 S. Slijivic, Bull. SOL. chim. Belgrade, 1951, 16, 147.5 6 8 F. Feigl, Mikrochem. Mikrochim. Acta, 1952, 39, 404.550 H. H. Willard and C. A. Horton, Analyt. Chem., 1952, 24, 862.660 H. A. Laitinen and P. Kivalo, Nuclear Sci. Abstr., 1952, 6, 69; Analyt. Chem.,561 M. D. Yeaman, Nuclear Sci. Abstr., 1952, 6, 104; N. S. Guttag and F. S. Grimaldi,662 W. F. Meggers, Analyt. Chem., 1952, 24, 23; R. L. Mitchell, Ind. Chem.Chem.663 Analyt. Chem., 1952, 24, 1406.564 R. T. O'Connor and D. C. Heinzelman, ibid., p. 1667.565 G. Gorbach and F. Pohl, Mikrochem. Mikrochim. Acta, 1951, 38, 328.566 Idem, ibid., p. 335; S. Wilska, Acta Chem. Scand., 1951, 5 , 1368.5 6 7 C . H. R. Gentry and G. P. Mitchell, Metallurgia, 1952, 46, 47.5 6 8 J . P. Pagliassotti and F. W. Porsche, Analyt. Chem., 1952, 24, 1403.560 A. J . Ham, J. Noar, and J . G. Reynolds, Analyst, 1952, 77, 766.570 F. V. Schatz, J . Inst. Met., 1951, 80, 77.571 J . A. Norris and C. E. Pepper, Analyt. Chem., 1952, 24, 1399.672 G. H. Ayres and E. W. Berg, ibid., p. 465; H. Oberlander, Metal Abstr., 1952, 19,573 A. B. Chandler, Brit. Ceram. Abstv., 1952, 107 A.574 A. Halperin and S. Samursky, J . Opt. SOC.Amel.., 1952, 42, 475.5 i 5 G. I. Stukenbroeker, D. D. Smith, G. K. Werner, and J. R. McNally, ibid., p. 383.5 7 6 J . E. Barney and W. A. Kimball, Analyt. Chem.. 1952, 24, 1548.5 7 7 V. Brustier, P. Cornec, and H. Triche, Compt. rend., 1952, 234, 2367.578 W. J . Poehlman and R. E. Sarnowski, J . Opt. SOL. Amer., 1952, 42, 489.1952, 24, 1467.ibid., p. 145; M. Nakanishi, Bull. Chem. SOC. Japan, 1951, 24, 33, 36.Manuf., 1952, 28, 491 ; J . K. Hurwitz, J . Opt. SOC. Amer., 1952, 42, 484.403; J. E. Hawley, W. J . Wark, C . L. Lewis, and W. L. Ott, ibid., p. 856WILSON INSTRUMENTAL METHODS. 33 1been made of the co-precipitation of vanadium with the hydroxides oftervalent metals. 579Improved flame photometers have been d e s ~ r i b e d , ~ ~ ~ 581 and an im-proved method for the flame analysis of plant ash has been devi~ed.~8~Individual flame photometric methods have been proposed for the elementsboron,5= lithi~m,~M 5869 587 potas~ium,~~~9 586 rubidi~m,~88 andcalcium,586~ 589 G.C. Collins and H. Polkinhome 581 have studied the effectof anions on the flame-photometric determination of sodium and potassium.An emission spectrographic method has been proposed for the deter-mination of halogen compounds. 590 In this, the emission spectrum excitedby a high-frequency electrodeless discharge has been used. Little workseems to have been done along these lines, and with modern apparatus itwould seern to the Reporter feasible to assume that the characteristic high-frequency spectra of many organic compounds, first studied many yearsago from a theoretical point of view,591 ought to be capable of considerableanalytical application.Absorption Spectra.-Analytical applications of absorption spectrain the visible and ultra-violet regions have been re~iewed.5~~9 593 Anelectrodeless hydrogen discharge tube as a source of ultra-violet continuumhas been described.594 The absorption spectra of substances may bemeasured as reflection spectra, and this has been utilised to identify materialson an adsorption c0lumn.~9~Infra-red spectroscopy has also been 596 A differentialmethod of analysis depending on the comparison of known and unknownsamples has been discussed theoretically, and possible sources of error havebeen e~amined.5~7 A simple infra-red absorption cell has been de~cribed.5~8A.E. Martin 599 has pointed out the potential value of a comprehensivecatalogue of infra-red spectra of organic compounds, and the ease withwhich this could be obtained, in a fairly complete form, within a reasonablyshort time, if workers were to co-operate in providing data according to ascheme which he outlines. Infra-red absorption studies of aromatic hydro-67Q F. Burriel Marti, E. Fernandez Caldas, and J. Ramirez Mufios, Anal. real SOC.680 J . U. White, AnaZyt. Chem., 1952, 24, 394; C. A. Dubbs, ibid., p. 1654; L. Leyton,582 F. H. Vanstone, A.R.E. Malling Res. Sta., 1951, 122.683 C. E. Bricker, W. A. Dippel, and N. H. Furman, Nuclear Sci. Abstr., 1952, 6, 212.684 L. H. Kalenowski and S. M. Runke, U.S.Bur. Mines, 1952, Rep. Invest., 4863.686 L. 1. Obolenskaya, Soils and Fert., 1951, 14, 449.6 8 6 R. Herrmann, 2. ges. exp. Med., 1952, 118, 187.6 8 7 S. B. Knight and M. H. Peterson, Analyt. Chem., 1952, 24, 1514.5 8 8 H. E. Freytag, 2. anal. Chem., 1952, 138, 161.68Q H. J . Hubener, 2. physiol. Chem., 1952, 289, 188.690 R. E. Keller and L. Smith, Analyt. Chem., 1952, 24, 796.6Q1 A. W. Stewart and C. L. Wilson, “ Recent Advances in Physical and Inorganic6Q2 0. D. Shreve, Analyt. Chem., 1952, 24, 1693.5Q3 M. G. Mellon, ibid., p. 2 ; E. J. Rosenbaum, ibid., p. 14.6Q4 G. H. Dieke and S. P. Cunningham, J . Opt. SOC. Amer., 1952, 42, 187.5Q5 F. Pruckner, M. van der Schulenberg, and G. Schwuttke, Naturwiss., 1951, 38,45.696 R. C. Gore, Analyt.Chem., 1952, 24, 8 ; N. Sheppard, Analyst, 1952, 7 7 , 7 3 2 ;R. C. Lord, R. S. McDonald, and F. A. Miller, J . Opt. SOC. Amer., 1952, 43, 149; A. E.Martin, Indust. Chem. Chem. Manuf., 1952, 28, 243.6n7 D. 2. Robinson, Analyt. Chem., 1952, 24, 619.5Q8 K. S. Tetlow, J. Sci. Insty., 1951, 28, 322. 6Dn Nature, 1952, 170, 20.esp. Fis. Qulm., 1952, 48, B, 59.Biochem J . . 1952, 50, Proc., xl. 681 Analyst, 1952, 77, 430.Chemistry,” 7th edtn., London, 1944, p. 452332 ANALYTICAL CHEMISTRY.barbiturate derivatives,m1 alkaloids,m2 and polymer degradationproducts 603 have been reported.F. A. Miller and C. H. Wilkins6e4 have discussed the use of infra-redabsorption spectra in the identification of inorganic polyatomic ions. Point-ing out that no systematic study has, up to the present, been made of thesespectra, and that little up-to-date information is available, they present, bothgraphically and in tabular form, the spectra of about 160 inorganic compoundswhich can be used, in conjunction with other methods of analysis, to provideuseful information about the composition of inorganic materials.Theprincipal drawback to more extended use of the method is the necessity €ordetermining the spectra from samples in powder form.Chemical Microscopy.-Hot-stages for work with the microscope havebeen described 605 and a method has been outlined for the determination ofboiling points and boiling ranges using such a hot-stage.m6 The use ofmixed melting points for the construction of phase diagrams has been dis-and a method has been described by which the techniques applic-able in such studies may be used for purification.m8 Fusion methodsaccompanied by crystallographic examination have been compared with themethods used for phase studies,609 and the former have been extended to theinorganic field by an examination of the fusion behaviour of a wide range ofinorganic compounds with 8-hydroxyquinoline.610A simple method has been described for determining the optic axial angleof crystals,611 and crystallographic data have been presented for lanthanumoxalate decahydrateJ612 ethylenedinitramine,613 2 : 4 : 6 : 2’ : 4’ : 6’-hexani-t rodiphen y lamine , l4 N-ace t yl-N’-phen ylh ydrazine, 61 pht halic anhydride, 616dibenzyl ~ u c c i n a t e , ~ ~ ~ s-diphenylcarbazide,618 ~-threonine,619 pseudotro-pine,G20 ( &)-mandelic acid,621 2 : 4-dinitrophen01,~~2 and 4 : 6-dinitro-resorcinol.623Nicotine thiocyanate has been found 624 to give crystalline precipitateswhich are suitable for identification under the microscope with a number ofcations. Crystal tests have been proposed for nitrate and nitrite usingp-aminophenylmercuric and for cobalt using potassium tri-600 R. B. Williams, S. H. Hastings, and J . A. Anderson, A n a l y t . Chem., 1952, 24. 1911.601 C. J . Umberger and G. Adams, ibid., p. 1309.602 G, Papineau-Couture and R. A. Burley, ibid., p. 1918.603 B. C. Achhammer, ibid., p. 1925.605 E. G. Steward, J. Sci. I n s t r . , 1952, 29, 214; W. Kofler, Mikrochem. Mikrochim.606 J .S . Wiberley, R. K. Siegfriedt, and A. A. Benedetti-Pichler, ibid., 1951, 38, 471.60’ L. Kofler, Z . anal. Chem., 1951, 133, 27.608 R. Fischer, Mikrochem. Mikrochirn. A c t a , 1951, 38, 342.60Q W. C. McCrone, ibid., p. 476.610 P. W. West and L. Granatelli, A n a l y t . Chem., 1952, 24, 870.6 1 1 A. J. Pollard, L. I. Braddock, and M. L. Willard, Mikrochem. Mikrochim. A c t a ,613 W. C. McCrone, ibid., p. 421.615 M. B. Williams and W. P. Van Meter, ibid., p. 762.616 M. B. Williams, W. P. Van Meter, and W. C. McCrone, ibid., p. 911.1 3 ~ 7 J . Krc, ibid., p. 1070.618 M. B. Williams, W. P. Van Meter, and R. J. Robinson, ibid., p. 1220.621 H. A. Rose, ibid., p. 1680.623 W. C. McCrone and I. Corvin, ibid., p. 2008.624 S, E. Burkat, E.N. Skrynnik, and S. S. Yaroslavskaya, J. A n a l . Chem., U.S.S.R.,604 Ibid., p. 1253.Ada, 1952, 39, 84; F. Hippenmeyer, ibid., p. 409.1952, 39, 192. 612 V. Gilpin and W. C. McCrone, A n a l y t . Chem., 1952, 24, 225.614 I d e m , ibid., p. 592.R. L. Clarke and J . Krc, ibid., p. 1378. 620 I d e m , ibid., p. 1516.622 W. C. McCrone and J . Krc, ibid., p. 1863.1951, 6, 325. 625 I. M. Korenman and A. A. Belyakov, ibid., 1952, 7, 52WILSON PHYSICAL SEPARATION METHODS. 333oxalatoferrate.626 Zirconium and hafnium may be distinguished by theproper application of the crystal test using quinoline and ammonium thio-~ y a n a t e . ~ ~ ~Miscellaneous Instrumental Methods.-X-Ray methods have beenreviewed.628 X-Ray spectra have been used for the quantitative analysisof minerals,629 and powder patterns have been used for the identification ofmolybdenum and tungsten oxides. 630The application of the mass spectrometer to analytical problems has beenreviewed and a simple pen recorder has been described.632 The massspectrometer has been applied to the analysis of hydrocarbons.633 Anextension of the use of the instrument for the analysis of non-volatilematerials, by examination of pyrolysis products obtained under controlledconditions, has been recommended.634 Various modes of pyrolysis havebeen investigated, and the method may be used, either for direct identificationin the simpler cases, or for identification by comparison with known samplesin the case of more complex materials.8.PHYSICAL SEPARATION METHODS.H. H. Strain and G. W. Murphy635 have reviewed what they term“ chromatography and analogous differential migration methods,” and anumber of other reviews of these methods have also appeared.636Any survey of this field leads to the conclusion that it will be many yearsbefore any coherent overall picture of the methods and their potentialitiescan be presented. The confusion in terminology which already exists seemsto become greater with the passage of time and with the formation of newsub-divisions, some of these unfortunately with rather slight justification.Among relatively new terms which have to be fitted into the complete pictureare “ gradient elution analysis,” 637 “ ionography,” “ papyrography,” 639“ ultra-violet papyrography, ” 640 even “ ultra-micro-papyrography ” 641(achieving a double distinction in that paper is not used in the separation, whichis achieved by means of cotton thread), “ electrokinetic ultrafiltration,” 642“ electrophoresis-convection,” 643 and “ chromathermography.” 64438, 466.626 J .C. Ryan, L. K. Yanowski, and M. Cefola, Mikrochem. Mikrochim. Acla, 1951,627 C. J . van Nieuwenburg and J . W. L. van Ligten, Analyt. Chim. Acta, 1962, 7, 390.628 H. A. Liebhafsky, Analyt. Chem., 1952, 24, 16; H. S. Kaufman and I. Fankuchen,829 G. Talvenheimo and J. L. White, ibid., p. 1784; M. Tournay, Compt. rend., 1952,630 A. Magneli, G. Anderson, B. Blomberg, and L. Kihlborg, Analyl. Chem., 1952,6ss H. Sobcov, ibid., pp. 1386, 1908; I. W.Kinney and G. L. Cook, ibid., p. 1391.634 P. D. Zemany, ibid., p. 1709. 635 Ibid., p. 50.636 A. Tiselius, Ewdeavour, 1052, 11, 5 ; G. B. Marini-Bettolo, Chiplz. e Ind., 1952, 34,269; Anon., Chem. Eng. News, 1952, 30, 4244.637 R. J . P. \Villiams. Analyst, 1952, 77, 905.638 H. J . McDonald, J . Chem. Educ., 1952, 29, 428.a39 M. K. Nayar and V. K. M. Rao, J . Sci. I n d . Res., India, 1952, 11, B, 78.640 Y. Hashimoto and I. Mori, Nature, 1952, 170, 1024.641 D. S. Venkatesh and M. Sreenivasaya, Current Sci., 1951, 20, 156.642 D. L. Mould and R. L. M. Synge, Analyst, 1952, 77, 964.643 D. M. Tennent and M. Kniazuk, Analyt. Chem., 1952, 24, 1661.ibid., p. 20.234, 2527.24, 1998. 631 V. H. Dibeler and J . A. Hipple, ibid., p. 27.K. K. Jensen, W. E.Bell, and F. E. Blacet, ibid., p. 1614.A. A. Zhukhovitsky, 0. V. Zolotareva, N. A. Sokolov, and N. M. Turkeltaub,Compt. rend. Acad. Sci., U.R.S.S., 1951, 77, 435334 ANALYTICAL CHEMISTRY.This multiplication of terminology is objectionable, merely on thegrounds stated earlier (p. 306). It is additionally objectionable here on twocounts : it increases the confusion regarding the causes of such separations,and it makes more difficult the recognition of really novel techniques.“ Chromatographic analysis ” has been soberly defined 1 as the “anaIysisof a solution by the use of solid sorbents such as paper or alumina, to separatesubstances in solution by selective sorption.” This definition tallies closelyenough with the terminology of H. H. Strain and G.W. Murphy G35 to meritacceptance. However, it does not seem to be sufficiently all-embracing forthe enthusiast, who continues to present us with other definitions whichare not so readily defensible. Thus T. I. Williams and H. Wei1,645 whileadmitting that “ so many processes are now by cummun consent accepted asforms of chromatography that an unequivocal definition of the word in itspresent chemieal sense presents difficulties,” have proposed that it be definedas “ those processes which allow the resolution of mixtures by effectingseparation of some or all of their components in concentration zones or inphases different from those in which they are originally present, irrespectiveof the nature of the force or forces causing the substance to move from onephase to another.’’ They claim that this definition embraces not only thevarious forms of chromatography hitherto achieved, but also all forms whichhave been postulated as theoretical possibilities.It -does this, of course,but it surely includes also such analytical operations as precipitation andsteam-distillation ; and in any case, common consent without criticaldiscussion is no ground for attempting to make “ chromatography ” thetouchstone-term for every new device, whatever its merits and whateverits mechanism.To provide a definition that does not define is only to add further con-fusion to an already overcrowded pattern. The word “ chromatography ”has, a t the present time, become one of the magic words-in the same classas “ resonance ” in the nineteen-thirties.The illusion exists that to give aprocess a name explains the process; and this in turn may lead to mis-interpretation of the causes which are operating in any separation, and to theconclusion that new causes have been observed when in fact they do notexist.Some of the dangers in this state of affairs seem likely to arise, for example,from the increased use of impregnated papers which has been reportedrecently. Papers impregnated with alumina,646 borate,647 and various otherinorganic salts,64* glycerol and various glycols, 6469 649 silicones, 650 phenyl-cellosolve,651 toluene-$-~ulphonate,~~~ and stearatochromic chloride 653 haveall been used. It is almost impossible, in some of these cases, to determineon the published information and in view of the little that is known about thesimpler separations, the mechanism by which the separations are taking place.646 Nature, 1952, 170, 503.646 I.E. Bush, Nature, 1950, 166, 445; Biochem. J . , 1952, 50, 370.647 C. A. Wachtmeister, Acta Chem. Scand., 1951, 5, 976.648 M. Lederer, Analyt. Chim. Acta, 1952, 7, 458.649 R. J . Boscott, Biochem. J., 1951, 48, Proc. xlvii; A. Zaffaroni, R. B. Burton, and660 T. H. Kritchevsky and A. Tiselius, Science, 1951, 114, 299.661 R. Neher and A. Wettstein, Helv. Chim. Acta, 1952, 35, 276.66z R. J . Foscott, Chem. and Ind., 1952, 472.663 D. Kritchevsky and M. R. Kirk, J. Amer. Chem. SOC., 1952, 74, 4484.E. H. Keutmann, Science, 1950, 111, 6 ; J . Biol.Chem., 1951, 188, 763WILSON PHYSICAL SEPARATION METHODS. 335That considerable caution must be used is stressed by the ease withwhich artefacts may appear in separations which are apparently quitestraightforward, as has been pointed out by a number of authors.654 Evensuch simple operations as acid-washing of paper 655 may produce a radicalchange in mechanism, while insufficient attention to water-content 656will certainly do so, and can lead to the anomalous result that a column ofmaterial such as hydrated magnesium silicate is condemned because ofvariation in water content on the one hand,657 and is recommended foradsorption chromatography, using elution by ethyl acetate satwrated withwater, on the other ; 658 or that “ single-phase chromatography ” of inorganicions,65g or even “ salting-out chromatography,” 660 may be regarded asadvances on partition chromatographic methods when they are in factprobably largely the result of separative forces recognised before the intro-duction of partition methods, such as ion exchange, or even simple adsorption.Finally, resolution of substances by complex liquid mixtures such asprogressively changing mixtures of chloroform, rt-amyl alcohol, and tert.-amylalcohol,661 while probably empirically satisfactory, can nevertheless onlymake theoretical interpretation of these separations more difficult.Inview of difficulties of this nature, it is only possible here to refer to isolatedinstances of methods which appear to be practically useful, and to payinadequate attention to theoretical considerations other than those whichmake a very simple approach to small sections of the larger problem.I tmust also be stressed that the allocation to separate types which is madehere must, of necessity, be somewhat arbitrary since the mechanisms are notalways evident.Adsorption Chromatography.-A number of less usual, sparingly soluble,inorganic compounds have been investigated in respect of their adsorptionproperties,662 and it has been found that when both natural and syntheticsources are available the natural product has a higher adsorptive capacity.A range of reagents for use in the detection of colourless zones in the separ-ation of a wide range of organic compounds has been tabulated, together withuseful information about their application.663 Various other methods,many of them instrumental, have been proposed for the detection of zones orfractions.664Inorganic chromatographic separations (as distinct from partitionseparations) have been discussed theoretically, 665 and have been appliedto the separation and identification of the more familiar cations 666 and654 E. L. Smith, Nature, 1952, 169, 60; T. C. J. Ovenston, ibid., p. 924; J. D. Acland,665 S. Burrows, F. S. M. Grylls, and J. S. Harrison, ibid., p. 800.656 A. Sibatani and M. Fukuda, J . Biochem. Tokyo, 1951, 38. 181.657 M. L. Wolfrom, A. Thompson, T. T. Galkowski, and E. J . Quinn, Aizalyt. Chem.,659 B. MiliCeviC, Bull. Soc. chim. Belgrade, 1952, 16, 101.660 L. Hagdahl and A.Tiselius, Nature, 1952, 170, 799.661 L. M. Marshall, K. 0. Donaldson, and F. Friedberg, Analyt. Chem., 1952,24,328,773.662 D. J . O’Connor and F. Bryant, Nature, 1952, 170, 84.6g3 A. L. LeRosen, R . T. Moravek, and J. K. Carlton, A n a l y t . Chem.. 1952, 24, 1335.664 P. H. Monaghan, P. B. Moseley, T. S. Burkhalter, and 0. A. Nance, ibid., p. 193;R . A. Glenn, J . S. Wolfarth, and C. W. DeWalt, ibid., p. 1138; J . M. Miller and J. G.Kirchner, ibid., p. 1480 : H. Hoyer, Kolloid Z . , 1952,’ 127, 166.665 M. Tanaka and M. Shibata, Bull. Tokyo Inst. Technol., 1951, B, 1, 11.G66 H. H. Fillinger and L. A. Trafton, J . Chem. Educ., 1952, 29, 255.ibid., 170, 32; H. G. Boman, ibid., p. 703.1952, 24, 1670. 6 5 8 C. H. Ice and S. H. Wender, ibid., p.1616336 ANALYTICAL CHEMISTRY.anions 667 and to the detection or determination of strontium,668 zinc incadmium,66g and copper in zinc.670 Further work has been carried out onthe separation of metal-chelates, the separation of 8-hydroxyquinolinecomplexes having been studied,671 and separation of cobalt by 2-nitroso-1-naphthol 672 and further investigations of the separation of alkaline-earth and alkali cations by violuric acid 673 having been reported.‘ I Gas chromatography ” of volatile organic mixtures, using displacementchromatography from charcoal columns, has been recommended 674 as avaluable method, capable of high accuracy and of considerable furtherdevelopment.Ion Exchange.-The principles and the application of ion exchange toanalytical problems have been extensively reviewed,675 and it is clear thatthese extend far beyond the simple possibilities of separations by columnaror analogous means.Chromatography of amino-acids has been carried outon oxidised cellulose, and study has shown 676 that the process taking placeis probably an ion-exchange process, the movement of individual acids beingrelated to the carboxyl content of the cellulose. Ion-exchange processeshave been used to remove or concentrate ions in water,677 to separateordinary 678 or radioactive 679 halogens, to separate calcium prior to phos-phate determination,6m to separate arsenic from iron,681 to remove inter-ferences prior to sulphate determination 682 or boron toseparate aluminium, iron , and manganese as chloro-complexes, 684 to separatethorium and lanthanum,685 to separate molybdenum from rhenium 686 orfrom other heavy metals,687 and to separate vanadium from phosphoricacid solutions.688An interesting development is the increasing application of ion-exchangecolumns for the production of standard solutions, and 0 .1 ~ - 689 and 0.001~-alkali hydroxide G90 free from carbonate have been prepared in this fashionfrom alkali chloride. The exchange is stoicheiometric, and the column willY. Oka and A. Murata, Sci. Rep. TGhoku, 1951, A , 3, 82.66E H. Ballczo and H. Muthenthaller, Mikrochem. Mikrochivn. A d a , 1952, 39, 152.669 Y. Oka and A. Murata, Sci. Rep. TGhoku, 1951, A , 3, 711.870 Idem, ibid., p. 707.671 L. B. Hilliard and H. Freiser, Analyt.Clzem., 1952, 24, 752.672 R. 0. Bach and A. A. Garmendia, Anal. Asoc. Quim. Argentina, 1951, 39, 11.*‘j H. Seiler, E. Sorkin, and H. Erlenmeyer, Helv. Chim. Acta, 1952, 35, 120.675 E. R. Tompkins, ibid., p. 970; R . Kunin, Analyt. Chem., 1952, 24, 64; Anon.,676 T. Wieland and A. Berg, ibid., 1952, 64, 418.877 H. Ballczo and G. Mondl, Mikyochem. Mikrochim. Acta, 1952, 39, 247 ; s. SUSSman878 W. Riemann and S. Lindenbaum, ibid., p. 1199.679 E. Berne, Acta Chem. Scand., 1951, 5, 1260.881 Y. Yoshino, Bull. Chem. SOC. Japan, 1951, 24, 39.68* H. Frey, AnaZyt. Chim. Acta, 1952, 6, 126.884 E. Blasius and M. Negwer, Naturwiss., 1952, 39, 257.8Eb P. Radhakrishna, Analyt. Chim. Acta, 1952, 6, 351.6E6 S. A. Fisher and V. W. Meloche, Analyt. Chem., 1952, 24, 1100.w7 R.Klement, 2. a n d . Chem., 1952, 136, 17.J. E. Salmon and H. R. Tietze, J., 1952, 2324.dm J . Steinbach and H. Freiser, Analyt. Chem., 1952, 24, 1027.6so B. W. Grunbaum, W. Schoniger, and P. L. Kirk, ibid., p. 1857.J. Griffiths, D. James, and C. Phillips, Analyst, 1952, 77, 897.Nature, 1952, 170, 150; G. Dickel and E;. Titzmann, Angew. Chem., 1951, 63, 450.and I. L. Portnoy, Analyl. Chem., 1952, 24, 1644.B. H. Kindt, E. W. Balis, and H. A. Liebhafsky, Analyt. Chem., 1952, 24, 1501.J. R. Martin and J . R. Hayes, Analyt. Chew., 1952, 24, 182; G. Brunisholtz andJ. Bonnet, Helv. Chim. A d a , 1951, 34, 2074WILSON PHYSICAL SEPARATION METHODS. 337deliver accurately standardised alkali without attention over a period ofmany months.C. Calmon 691 has proposed the use of the volume-changecharacteristics of an ion-exchange resin for quantitative analysis, either on alarge scale, where the volume occupied in a column is measured, or on a smallscale, where the change in volume of a single bead of resin is measured underthe microscope. The amount of swelling or shrinkage is related to thestructure of the resin, to the cation being exchanged, and to the concentrationof the exchanging solution.692In the organic field, separations of aldehydes and ketones from acids 693and of amino-acids 694 and nitrogenous plant extracts 695 have been reported.Extraction.-Solvent-extraction methods have been reviewed,696 and aradio-tracer study has been made of the solvent extraction of the halides ofgallium, indium, and thallium 697 from which it is possible to recommend anextraction of indium as iodide for separation from other elements.Leadiodide may be extracted by methyl isopropyl ketone,698 bismuth iodide byisobutyl methyl ketone,69g and copper by organic solutions containing organicacids.700 Apparatus for countercurrent e~traction,~Ol and a simple apparatusfor continuous extraction '02 have been described. In quantitative analysis,extraction procedures have been used in the removal of iron(Ir1) by extractionwith 12-butyl phosphate prior to aluminium determinati0r-1,~~~ in the estim-ation of zinc in soils by diphenylthiocarba~one,~~~ and in the extraction byethyl methyl ketone of niobium and tantalum from uranium alloys as thefluorides, prior to determination.705Partition Chromatrography.-As in recent years, the individual publica-tions on partition chromatography probably outnumber those in any othercomparable branch of analytical chemistry.Two books have been publishedwhich deal extensively with existing literature,'06 and the methods havebeen reviewed elsewhere. 707 Several investigations of factors affectingpartition separations have been reported, 708 the most fundamental probablybeing those of H. G. C a s ~ i d y , ~ ~ ~ who has analysed the factors into threemain groups, not, of course, mutually exclusive, affecting flow, R p values,691 Analyt. Chem., 1952, 24, 1456.692 K. W. Pepper, D. Reichenberg, and D. K. Hale, J . , 1952, 3129.693 G.Gabrielson and 0. Samuelson, Acta Chem. Scand., 1952, 6, 729, 738.694 C. H. W. Hirs, S. Moore, and W. H. Stein, J . Biol. Chem., 1952, 195, 669.695 S. M. Partridge, Analyst, 1952, 77, 955.696 L. C . Craig, Analyt. Chem., 1952, 24, 66; D. Pillon, Bull. SOC. chim., 1952, 1 9 , ~ 1.697 H. M. Irving and F. J. C. Rossotti, Analyst, 1952, 77, 801.698 P. W. West and J. K. Carlton, Analyt. Chim. Acta, 1952, 6, 406.69g P. W. West, P. Senise, and J. K. Carlton, ibid., p. 488.700 P. W. West, T. G. Lyons, and J. K. Carlton, ibid., p. 400.701 F. C. Hickey, Analyt. Chern., 1952, 24, 1993; R. Spence and R. J . W. Streeton,'02 W. W. Meinke and R. E. Anderson, Analyt. Chem., 1952, 24, 708.703 M. Aven and H. Freiser, Analyt. Chim. A d a , 1952, 8, 412.$04 E.Shaw and L. A. Dean, Soil Sci., 1952, 73, 341.705 G. W. C. Milner and A. J. Wood, Atomic Energy Res. Establ., 1952, C/R 895.706 R. J. Block, R. LeStrange, and G. Zweig, " Paper Chromatography : A Labora-tory Manual," New York and London, 1952 : J. N. Balston and B. E. Talbot, " Guide toFilter Paper and Cellulose Powder Chromatography," London, 1952.707 P. von Tavel, Chimia, 1951, 5, 256; R. Signer, ibid., p. 245.' 0 8 G. N. Kowkabany and H. G. Cassidy, Analyt. Chem., 1952, 24, 643 ; A. Lacourt,G. Sommereyns, and G. Wantier, Analyst, 1953, 77, 943; C. N. Trumbore and H. E.Rogers, J . Chem. Educ., 1952, 29, 404; G. Heinrich, Naturwiss., 1952, 39, 257.709 Analyt. Chem., 1952, 24, 1415.Analyst, 1952, 77, 578338 ANALYTICAL CHEMISTRY.and zone-definition respectively, and has considered some of these factorsin more detail.Instrumental methods have been recommended for con-trolling separations, 710 and numerous devices of apparatus, application ofreagent, choice of support for the stationary phase, and detection of zoneshave been reported.711 I t has been shown that the measurement of spotareas 712 or the excision of spots and elution for quantitative analysis 713 maybe considerably simplified either by direct analysis on the cut paper 714 or bycutting out the spots and weighing d i r e ~ t l y . 7 ~ ~ In the latter case the result ismore closely related to the concentration than the actual spot area, probablybecause of compensation for errors arising from varying paper thickness.In the organic field alcohols,716 the 2 : 4-dinitrophenylhydrazones ofaldehydes and ketonesJ717 a m i n e ~ , ~ ~ ~ azo-dyes derived froma ~ y l a m i n e s , ~ ~ ~ phenols,721 sugars and related compounds 7 2 2 9 723 and amino-acids and related compounds 7237 724 are among the long list of substancesthat have been separated.Because of the considerable use of benzidine in the detection of zones,its behaviour with a wide range of materials, including inorganic salts, hasbeen The halides from halogen compounds, after sodium fusion,have been separated.726 Separations of a number of mixtures of inorganic710 D.C. Miiller, AnaZyst, 1952, 77, 933.711 P. Meredith and H. G. Sammons, ibid., p. 416; L. A. Boggs, Analyt. Chem., 1952,24, 1673; L. A. Boggs, L.S. Cuendet, M. Dubois, and F. Smith, ibid., p. 1148; D. F.Meigh, Nature, 1952, 169, 706; U. S. von Euler, ibid., 170, 664; A. Grieg, ibid., p. 845;G. Zimmermann and K. Nehring, Angew. Chenz., 1951, 63, 556; J . G. Marchal and T.Mittwer, Proc. K. Ned. Akad. Wet., 1951, 54, c 4, 391; S. Berlingozzi and G. Serchi,Sper. Sez. Chim. biol., 1952, 3, 1.?la J. A. Brown and M. M. Marsh, Analyt. Chem., 1952, 24, 1952.714 B. Levin and V. G. Oberholzer, ibid., p. 123.716 J. H. Freeman, Analyt. Chem., 1952, 24, 2001.716 A. C. Neish, Canad. J , Chem., 1951, 29, 552.717 D. F. Meigh, Nature, 1952, 170, 579.718 F. W. Denison and E. F. Phares, Analyt. Chem., 1952, 24, 1628; T. L. Parkinson,Analyst, 1952, 77, 438; V. K. M. Rao, J . Sci. I n d . Res., India, 1952, 11, B, 277; S.S.Phatak, A. P. Mahadevan, and V. D. Patwardhan, Current Sci., 1952, 21, 162.W. Baker, J. B. Harborne, and W. D. Ollis, J., 1952, 3215; J. M. Bremner andR. H. Kenten, Biochem. J . , 1951, 49, 651; A. Wickstrom and B. Salvesen, J . Pharm.Pharmacol., 1952, 4, 631; R. Schwyzer, Acta Chem. Scand., 1952, 6, 219.M. Zalokar, J . Amer. Chem. Soc., 1952, 74, 4213.721 Wen-Hua Chang, R. L. Hossfeld, and W. M. Sandstrom, ibid., p. 5766; G. M.Barton, R. S. Evans, and J. A. F. Gardner, NatuYe, 1952, 170, 249; S. A. Ashmore andH. Savage, Analyst, 1952, 77, 439.TZ2 J . L. Buchan and R. I. Savage, ibid., p. 401 ; N. Albon and D. Gross, ibid., p. 410;J. T. Edward and D. M. Waldron, J . , 1952, 3631; R. J. Dimler, W. C. Schaeffer, C. S.Wise, and C.E. Rist, Analyt. Chem., 1952, 24, 1411; L. Sattler, ibid., p. 1862; R. J .Bayley, E. J . Bourne, and M. Stacey, Nature, 1952, 169, 876; P. S. Rao and R. M.Beri, Proc. Indian Acad. Sci., 1951, 28, A , 368; A. Yoda, Sugar I n d . Abstr., 1952, 14,116; J. Saarnio, E. Niskasaari, and C . Gustafsson, Suomen Kem., 1952, 25, B, 25;J. Opienska-Blauth, E. Drozdowski, and M. Kanski, Ann. Univ. M . Curie-Sklowdowska,1951, 6, D, 27.723 L. F. Wiggins and J. H. Williams, Nature, 1952, 170, 279; R. Radhakrishna-murty and P. S. Sarma, J . Sci. I n d . Res., India, 1952, 11, B, 279.724 C. Klatzkin, Nature, 1952, 169, 422; H. N. Rydon and. P. W. G. Smith, ibid.p. 922; K. V. Giri and N. A. N. Rao, ibid., p. 923; A. C. Hulme and W. Arthjngton.ibid., 170, 659; A.R. Kemble and H. T. Macpherson, ibid., p. 664: K. V. Giri, A. N.Radhakrishnan, and S. V. Vaidyanathan, Analyt. Chem., 1952, 24, 1677 ; E. F. Welling-ton, Canad. J . Chem., 1952, 30, 581.725 H. Miller and D. M. Kraemer, Analyt. Chem., 1952, 24, 1371.7 2 6 T. Ando and S. Ishii, Bull. Chenz. SOC. Japan, 1952, 25, 106.T. Kariyone and S. Shimizu, Nature, 1952, 170, 422WILSON : MISCELLANEOUS. 339ions have been reported.727 More limited separations have been describedfor phosphates, 728 alkali metals, 729, 730 alkaline-earth metals, 730 zinc, 731uranium,733, 734 735 niobium and tantalum,736 andzirconium and hafnium. 737On theoretical considerations, partition methods have been extendedto partition between gas-liquid phases, and some separations based on thistheory, such as the separation of volatile fatty acids, are described.738Ionophoresis and Electrophoresis.-The methods of “ electrochromato-graphy ” have been re~iewed,~3~ and apparatus for carrying out ionophoreticor electrophoretic separations in filter-paper has been described.740 G.Manecke 741 has described the application of ionophoretic separations tomixtures of ions on ion-exchange columns. Copper has been separated anddetermined on paper by ionophoretic methods. 742 The methods normallyapplied in this field have utilised low voltages to achieve separations.Flavonoids and sugars have been separated by using high constant voltagesof the order of 100-1000 volts.7439. MISCELLANEOUS.Radiochemical Analysis.-An excellent account of the basis and ex-perimental aspects of radiochemical analysis has appeared in book form, 744and there have been other reviews of the subject 745 from the analyticalstandpoint. The precision counting of a-particles has been discussed 746 anda method of apportioning radioactivity between radioactive parents andJ .G. Surak and D. P. Schlueter, J . Chem. Educ., 1952, 29, 144; H. H. Fillingerand L. A. Trafton, ibid., p. 285; F. H. Pollard and J. I;. W. McOmie, Endeavour, 1951, 10,213; G. Venture110 and A. M. Ghe, Analyt. Claim. Acta, 1952, 7, 261, 268; A. Lacourt,G. Sommereyns, and J. Soete, Mikrochenz. Mikrochim. Acta, 1951, 38, 348; A. Lacourt,G. Sommereyns, and M. Claret, ibid., p. 444; A. Lacourt, G. Sommereyns, and G.Wantier, ibid., 1952, 39, 396; A.Lacourt, G. Sommereyns, J. Hoffmann, A. Stadler, andG. Wantier, Compt. rend., 1952, 234, 2365.728 J . P. Ebel and Y . Volmar, ibid., 1951, 233, 415; T. Ando, J. Ito, S. Ishi, and T.Soda, Bull. Chem. SOC. Japan, 1952, 25, 78.729 D. P. Burma, Analyst, 1952, 77, 382.730 H. Erlenmeyer, H. von Hahn, and E. Sorkin, He2v. Chim. A d a , 1951, 34, 1419.731 W. Hermanowicz and C. Sikorowska, Pam. Chem., 1952, 8, 238.732 M. M. Singh and J. Gupta, J . Sci. I n d . Res., India, 1951, 10, B, 289.733 W. Ryan and A. F. Williams, Analyst, 1952, 77, 293.734 A. F. Williams, ibid., p. 297.735 N. F. Kember, ibid., p. 78; G. W. J. Kingsbury and R. B. F. Temple, ibid., p. 307.736 F. H. Burstall and A. F. Williams, ibid., p. 983; F . H. Burstall, P.Swain, A. F.Williams, and G. A. Wood, J . , 1952, 1497; A. F. Williams, ibid., p. 3155; R. A. Mercerand A. F. Williams, ibid., p. 3399.737 N. F. Kember and R. A. Wells, Chem. and Ind., 1952, 1129.738 A. T. James and A. J. P. Martin, Biochem. J . , 1952, 50,679; Analyst, 1952, 77,915.73B H. H. Strain, Analyt. Chem., 1952, 24, 356; M. Lederer and F. L. Ward, Analyt.Chim. Acta, 1952, 0, 355.740 T. R. Sato, W. P. Norris, and H. H. Strain, Analyt. Chem., 1952, 24, 776; A.Tiselius, J . Gen. Physiol., 1951, 35, 89; R. Consden and W. M. Stanier, N a t w e , 1952,169, 783; 170, 1069; A. B. Foster, Chem. and Ind., 1952, 1050; I . Brattsten and A.Nilsson, Arkiv Kemi, 1951, 3, 337.741 G. Manecke, Naturaiss., 1952, 39, 62.742 J . R. A. Anderson and M.Lederer, Analyt. Chim. A d a , 1952, 6, 472.743 Y . Hashimoto, I. Mori, and M. Kimura, Nature, 1952, 170, 975.744 G. B. Cook and J. F. Duncan, “ Modern Radiochemical Practice,” Oxford, 1952.745 J. E. Hudgens, Analyt. Chem., 1952, 24, 1704; M. P. Sue, Bull. SOC. chim., 1951,746 R. Hurst and G. R. Hall, Analyst, 1952, 77, 790.18, D 9340 ANALYTICAL CHEMISTRY.daughters has been described. 747 Radio-tracers have been used for chrom-atographic separations. 748 Some reactions of thiosulphate and tetrathionatehave been studied 'by tracer methods. 749 Precautions necessary for re-producible results in the elementary analysis of organic compounds con-taining radio-tracers have been described. 750 Radioactivity measurementshave been employed for the determination of potassium, 7513 752 rubidium,752chromium, vanadium, and molybdenum, 753 astatine,7" francium, 755 andamericium. 756 Radioactive iron has been separated from biological materialsby precipitation with cupferron and subsequent extraction.757Radioactivation.-This important new technique for the determination,particularly, of microgram or sub-microgram amounts of materials, has beenconsiderably extended in its application. Conditions have been describedfor the determination of copper in luminescent solids,758 uranium in rocksand minerals, 759 indium, 760 arsenic, 761 antimony,762 and trace elements inhigh-purity aluminium 763 and in high-purity magnesium.764Non-radioactive Tracers.-Methods for the determination of deuteriumhave been discussed.765 Methods have been described for the isolationof hydrogen before isotopic assay,766 and for the dekermination of oxygenin organic compounds 767 and of hydrate-water.768 Combined chemicalanalysis and tracer assay in organic analysis has been discussed, and rapidand accurate methods making use of simple interlocked chemical andtracer procedures have been described. 769Gas Analysis.-The use of a simple apparatus for the detection of a widerange of gases has been described,770 and sensitivities for the reactions arequoted. A simple manometric gas-analysis apparatus for general quan-titative and the analysis of gas mixtures containing oxides of nitro-gen 772 have been described. A method of analysis depending on desorptionF. P.W. Win-teringham, A. Harrison, and R. G. Bridges, Analyst, 1952, 77, 19; E. L. Smith and D.Allison, ibid., p. 29.747 H. W. Kirby, Analyt. Chem., 1952, 24, 1678.748 0. G. Lion, E. A. Peterson, and D. M. Greenberg, ibid., p. 920,74s H. R. v. d . Heijde and A. H. W. Aten, J . Amer. Chem. Soc., 1952, 74, 3706.750 E. A. Evans and J . L. Huston, Analyt. Chem., 1952, 24, 1482.751 0. Gubeli and K. Stammbach, Helv. Chim. Acta, 1951, 34, 1245.7 5 2 Idern, ibid., p. 1253.753 J . Govaerts and C. Barcia Goyanes, Analyt. Chim. Acta, 1952, 6, 121.754 A. H. W. Aten, T. Doorgeest, U. Hollstein, and H. P. Moeken, AwaZysl, 1952,7 5 5 E . K. Hyde, J . Amer. Chem. Soc., 1952, 74, 4181.75~1 H. W. Miller, Nuclear Sci. Abstr., 1952, 6, 15.7 5 7 R. E. Peterson, Analyt.Chem., 1952, 24, 1850.7 5 * E. Grillot, Compt. rend., 1952, 234, 1775.75s A. A. Smales, Anal-yst, 1952, 77, 778.760 J . E. Hudgens and L. C. Nelson, Analyt. Chem., 1952, 24, 1472.7 6 1 A. A. Smales and B. D. Pate, ibid., p. 717; Analyst, 1952, 77, 188, 196.762 J. E. Hudgens and P. J. Call, AnaZyt. Cheln., 1952, 24, 171.763 P. Albert, M. Caron, and G. Chaudron, Compt. rend., 1951, 233, 1108.7 ~ 3 ~ G. J. Atchison and.W. H. Beamer, Analyt. Chem., 1952, 24, 1812.765 M. E. Reinders, Chem. Weekblad, 1951, 47, 785.7 6 6 1. Figeleisen, M. L. Perlman, and H. C. Prosser, Analyt. Chem., 1952, 24, 1356.7 G 7 A. V. Grosse and A. D. Kirshenbaum, ibid., p. 584; A. D. Kirshenbaum, A. G.768 H. J. Morowitz and H. P. Broida, ibid., p. 1657.769 R. C. Anderson, Y . Delabarre, and A. A. Bothner-by, ibid., p. 1298.770 H. Malissa, A. Musil, and R. Kreibich, Mikrochem. Mikrochim. Acta, 1951, 38,7 7 1 J. N. Pitts, D. D. DeFord, and G. W. Recktenwald, Analyt. Chem., 1952, 24, 1566.772 C. L. Johnson, zbid., p. 1572 ; G. Meyer and P. Vooge1,Rec. Trav. chim., 1951,70,833.77, 774.Streng, and A. V. Grosse, ibid., p. 1361.385, 403WILSON MISCELLANEOUS. 341followed by heat-conductivity measurements has been proposed. 773 Indirectanalysis of mixtures by the measurement of the gas evolved by a suitablereaction has been re~omrnended.7~~ Ethylenediamine is stated to be areadily purified absorbent for carbon dioxide, 775 possessing the advantagethat it is easily separated from its carbonate by vacuum distillation.Moisture Determination.-A micro-method for the deJermination ofhydrate-water in minerals has been described.776 The preparation and useof the Karl Fischer reagent has been discussed in and its use in thepresence of ferric salts 778 and with a dead-stop end-point apparatus 779 hasbeen described. A solution of bromine and sulphur dioxide in chloroformhas been recommended 780 as being more satisfactory in some determinationsthan the Karl Fischer reagent. Water in alcohols has been determined byusing high-frequency oscillators, 781 and this method is reported to giveparticularly good results in the system ethanol-water.Operations in Non-aqueous Solvents.-Acid-base 782 and general 783titrations in non-aqueous solvents have been reviewed. Apart from in-vestigations noted elsewhere in this Report, the titration of ammonium andamine salts of mineral and of a range of sodium and other metalsalts 785 and of amines 786 has been described. The electrochemical potentialsof a number of inorganic and organic redox systems in pyridine have beendetermined.787 It has been shown that by using a glass electrode acid-basetitrations in this solvent might also be possible. Ionophoretic separation ofdye mixtures in non-aqueous solvents has been achieved. 788Sedimentation Analysis.-Lead has been determined by centrifuging leadsulphate, 789 and the zinc-1 : 10-phenanthroline reaction already mentioned 73has been used in a sedimentation determination of vanadium.Catalysed Reactions-Both qualitative and quantitative methodsbased on catalysed reactions, in addition to those mentioned elsewhere inthis Report, have been proposed. Cobalt may be detected by a catalysedoxidation of manganese(I1) to manganese(~v).~~ The reducing power of themercurous ion is enhanced in the presence of thiocyanate, so that it can bedetected by its ability to reduce iron(II1) to iron(I1) (cf. p. 316).791 Coppermay be used for the catalytic reduction of nitrate to ammonia for quantitativedetermination. 792 Various catalysts have been employed in the iodometric773 H. Wirth, Mikrochem. Mikvochinz. A d a , 1952, 40, 15.774 N. I . Pyshkin and 0. M. Lukin, J . Anal. Chem., U.S.S.R., 1951, 6, 261.7 7 5 R. W. Swick, D. L. Buchanan, and A. Nakao, Analyt. Cheun., 1952, 24, 2000.776 E. B. Sandell, Mikrochern. Milirochim. Acta, 1951, 38, 48’7.777 E. Eberius, 2. anal. Chem., 1952, 137, 81.778 A. H. Laurene, Analyt. Chem., 1952, 24, 1496.779 W. A. Frediniani, ibzd., p. 1126.781 P. W. West, P. Senise, and T. S. Burkhalter, Analyt. Chem., 1952, 24, 1250.782 J. A. Riddick, ibid., p. 41.783 J . A. Riddick, J . S. Fritz, M. M. Davis, E. F. Hillenbrand, and P. C. Markunas,ibid., p. 310; T. S. West, I n d . Chem. Chern. Manuf., 1952, 28, 368, 415.784 J. S. Fritz, A m l y t . Chem., 1952, 24, 306.785 C. W. Pifer and E. G. Wollish, ibid., p. 519.786 R. J. Keen and J . S. Fritz, zbzd., p. 564.787 A. K. Gupta, J . , 1952, 3473, 3479.788 M. H. Paul and E. L. Durrum, J . Amer. Chern. SOC., 1952, 74, 4721.789 R. C. Jarnagin, J. T. Jones, 0. L. Willbanks, and C. T. Kenner, Analyt. Chem.,7y0 P. W. West and L. A. Longacre, Analyt. Clzina. Acta, 1952, 6, 485.;91 F. Lucena Conde, Mikvochem. Mzkrochzrn. A d a , 1952, 40, 8.7Q2 2. G. Szab6 and L. G. Bartha, Analyt. Chim. Acta, 1952, 6, 416.T. S. West, I n d . Chem. Chem. Manuf., 1952, 28, 491.1952, 24, 1115342 ANALYTICAL CHEMISTRY.determination of persulphate. 793 Copper in sub-microgram amounts maybe determined by its catalytic effect on resorcinol 0xidation,~~4 silver by asimilar effect on the persulphate oxidation of manganese(II),795 and iron by itscatalytic effect, when co-precipitated with a cobalt-copper hydroxide carrier,on the decomposition of hydrogen per0xide.7~6 The reduction of palladiumin the presence of selenium by hydrazine sulphate has been utilised for thedetermination of palladium. 797Miscellaneous Methods.-There are several methods which cannotproperly be classified under any heading, but which seem to present distinctpossibilities to the analyst. H. M. Powell 798 has shown that clathrate-formation may be used in the resolution of optical isomers, and a somewhatsimilar operation, the formation of urea and thiourea adducts, 799 has alsobeen found to encourage separation. The use of specific adsorbents, firstsuggested by L. Pau1ing,8O0 has been investigated, and some success has beenachieved with these.gOl There is some indication of a relation between thestructure of the substance adsorbed and specificity, but the results are notnearly extensive enough to allow any precise deductions to be made regardingthis. Finally, D. J. D. Nicholas has shown so2 that by altering the amount oftrace metal in a nutrient on which a fungus is growing, the amount of themetal may be assessed by growth of the fungus, over a range from zerocontent to sufficiency level.CECIL L. V71~soh’.793 Z. G. Szab6, L. Csanyi, and H. Galiba, 2. anal. Chem., 1952, 135, 269.794 R. H. Lambert, Analyt. Chem., 1952, 24,. 868.795 A. L. Underwood, A. M. Burrill, and L. B. Rogers, ibid., p. 1697.796 A. Krause, Roczn. Chem., 1952, 26, 3.797 F. Pino Perez and F. Burriel Marti, Anal. real SOC. esp. Fis. Quim., 1951, 47, B,798 Nature, 1952, 170, 155.790 W. Schlenk, Analyst, 1952, 77, 867.Chem. Eng. News, 1949, 27, 913.F. H. Dickey, Proc. N u t . Acad. Sci., 1949, 35, 229; U. Curti and U. Colombo,J . Amer. Chem. Soc., 1952, 74, 3961; S. A. Bernhard, ibid., p. 4046.Analyst, 1952, 77, 629.653, 657

ISSN:0365-6217    

DOI:10.1039/AR9524900298

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

CRYSTALLOGRAPHY.1. CRYSTAL GROWTH.THE remarkable outburst of interest in the mechanism of crystal growthappears to have been stimulated by the recognition that all crystals areimperfect and that dislocations can be self-perpetuating. In addition, therecent development of multiple-beam interferometry as a tool 1y 2y shouldbe mentioned. Since the Faraday Discussion in 1949 something like100 papers have appeared reporting observations relevant to the dislocationmechanism, or developing the mathematical theory of imperfect crystalgrowth. So striking are the results found, in certain cases at least, thatthere cannot now be any doubt of the important part played by screwdislocations in crystal growth, in these instances even if not more generally.Theoretical physicists have developed the theory of the perfect crystaland, in particular, of the nucleation of new phases4f5 This led to thepredictions, (1) that, given nucleation, growth rate should be proportionalto supersaturation, a relation which was found to hold rather wellexperimentally, and (2) that growth-rate, as determined by the rate offormation of fresh 2-dimensional nuclei on existing crystal faces, should beexcessively small for the principle faces of a perfect crystal, unless super-saturation were as high as, say, 50%. At 1% supersaturation, the rate ofgrowth should be about 10100* times less than at 50%.Burton hasremarked that this must be one of the largest known discrepancies betweentheory and experiment! It was recognised very early that the observedrate of growth of real crystals must be connected with their lattice im-perfections but as late as 1949 there was no clear conception of how thetheory should be modified.Crystal imperfections were by no means thecentral concern for the Faraday Discussion. that thecredit is due for pointing out that a screw-dislocation can be self-perpetuating, and that the classical conceptions of the critical nuclear size,etc., when applied to a growth step of this kind, predict a spiral-shapedgrowing edge, in agreement with certain well-known features of some crystalsurfaces. The self-perpetuating step allows growth of the crystal to proceedwithout fresh nucleation, as the continual winding upon itself of an infinitesingle layer of unit elements, thus avoiding altogether the need for freshnucleation of successive layers, and explaining the observed rate of growthof crystals in a most elegant fashion. Burton, Cabrera, Frank,', 8 y 9 7 lo andothers have been developing the theory of dislocations very considerably.The dislocation translation (Burgers' vector 11) may be either the unit cellIt is to FrankS.Tolansky and M. Omar, Nature, 1952, 170, 81.I. N. Stransky and R. Kaischew, Physikul. Z., 1935, 36, 393.R. Becker and W. Doering, Ann. Physik, 1935, 24, 719; W. K. Burton andW. K. Burton, N. Cabrera, and F. C. Frank, Nature, 1949, 163, 398. * Idenz, Phil. Trans., 1951, 243, A , 299; F. K. N. Nabarro, Adv. Physics, 1952, 1, 271.F. C. Frank, Phil. Mug., 1951, 42, 809; Adu. Physics, 1952, 1, 91.a S.Tolansky, 2. Elektvochem., 1952, 56, 263. Idem, Nature, 1952, 169, 445.N. Cabrera, Discuss, Fumduy Soc., 1949, 5, 33, 40. 13 F. C. Frank, ibid., p. 48.lo Idem, Actu Cryst., 1951, 4, 497 ; 2. Elektvochern., 1952, 56, 429.l1 J. M. Burgers, Proc. K . Ned. Akud. Wet., 1939, 42, 293344 CRYSTALLOGRAPHY.translation or some simple multiple thereof; screw dislocation may beright- or left-handed and, if several are present on one face (densities upto lo4 dislocations per mm.2 have been observed) , they will give characteristicand easily recognisable patterns on the surface. The new concepts havebeen applied to explain polytypism l2 and twin-formation.13What makes the Frank mechanism so convincing is the striking confirm-ation it has received from the study of crystal surfaces.The range ofcrystals on which markings consistent with Frank's theory have beenobserved includes graphite,14 corundum,15 haematite,16 pyrites,17 bery1,lsquartz,lg apatite,20 mica,21 and cadmium iodide ; 2* also, amongst the metals,A u , ~ ~ Mg,24 Cd,24 and Ti.25 AlBzZ6 gives evidence of screw dislocations inthe centre of the crystals, since the action of acid is to create a hole at thispoint; most elegadt of all, and incidentally the only organic compoundsrepresented in this list, the hydrocarbons C,,H,, 27 and C100H202,28 examinedin the electron microscope by Dawson and Vand, show well-marked spiralsof unimolecular step height.It is certainly too early to form any proper assessment of the generalityof the screw-dislocation mechanism in crystal growth.From the observ-ations so far available, it would seem to be more important in minerals,simple inorganic salts, and elements. The spreading of layers outwards overthe surface of a growing crystal has, of course, been observed in manyinstances, inorganic and organic, particularly by B ~ n n , ~ ~ but, as a generalrule, spiral patterns are not seen. Electron micrographs confirm theexistence of layers on protein crystal faces (e.g., the Rothamsted necrosisprotein 30) but show neither spirals nor the hole at the site of the dislocationitself, which in the case of protein crystals was predicted to be of the orderof 100 m ~ . ~ 1 The necessity for some form of %dimensional nucleation isclear ; but that it is always a screw dislocation cannot be said to have beenproved.Dawson and Vand have shown (for C,,H,,) 28 that twinning cangive rise to an indestructible step resulting in unimpeded growth in onedirection. Perhaps many other such mechanisms remain to be found.Possibly, too, the role of impurities may have to be taken more into account.l2 F. C. Frank, Phil. Mag., 1951, 42, 1014; V. Vand, Nature, 1951, 168, 783; Phil.Mag., 1951, 42, 1384; G. Honjo, S. Miyake, and T. Tomita, Acta Cryst., 1950, 3, 396;see also L. S. Ramsdell and J. Kohn, ibid., 1951, 4, 75, 111.13 A. H. Cottrell, and B. A. Bilby, Phil. Mag., 1951, 42, 573.l4 F. H. Horn, Nature, 1952, 170, 581.15 A. R. Verma, ibid., 1951, 167, 939; 168, 430, 783; 2. Elektrochem., 1952, 56, 268;Phil.Mag., 1951, 42, 1005; 1952, 43, 441; S. Amelinckx, Nature, 1951, 168, 431;H. E. Buckley, 2. Elecktrochem., 1952, 56, 275.16 A. R. Verma, Nature, 1952, 169, 540.l8 L. J. Griffin, Phil. Mag., 1951, 42, 775, 1337; 43, 827.19 C. S. Brown, R. C. Kell, L. A. Thomas, N. Wooster, and W. A. Wooster, Nature,1951, 167, 940; G. van Praagh and B. T. M. Willis, ibid., 1952, 169, 623; B. T. M. Willis,ibid., 170, 115. 2o S. Amelinckx, ibid., 169, 841; 170, 760.21 Idem, ibid., 169,580 22 A. J . Forty, Phil. Mag., 1951,42,670; 1952,43,72,377.23 S. Amelinckx, ibid.. p. 562; S . Amelinckx, C. C. Grosjean, and W. Dekeyser,Compt. rend., 1952, 234, 113. 24 A. J. Forty, Phil. Mag., 1952, 43, 481, 949.26 M. A. Steinberg, Nature, 1952, 170, 1119.z6 F.H. Horn, E. F. Fullam, and J. S. Kasper, ibid., 169, 927.27 I. M. Dawson and V. Vand, ibid., 1951, 167, 476; Proc. Roy. SOC., 1951, A , 206, 555.28 I. M. Dawson, ibid., 1952, A , 214, 72.20 C . W. Bunn, Discuss. Faraday SOC., 1949, 5, 119.30 R. W. G. Wyckoff, Acta Cryst., 1948, 1, 292 (Fig. 7).31 F. C. Frank, ibid., 1951, 4, 497.l7 A. F. Seager, ibid., 170, 425DUNITZ : THE TECHNIQUE OF STRUCTURE ANALYSIS. 345The case of CdI, is instructive. Initial crystallisation proceeds at first withgreat rapidity, excessively thin platelets being formed ; growth then slowsdown, the plates begin to thicken, and it is only then that terraced steps, etc.,begin to appear on the (0001) faces. CdI, affords some of the most beautifulexamples of spiral growth patterns.But if screw dislocations account onlyfor the second phase of its growth, what shall we postulate for the first?Buckley in particular has expressed scepticism in this c~nnection.~,Another line of evidence which must in due course be brought to bear onthe subject is the mosaic-block theory of crystal texture, strongly supportedby the intensities of X-ray reflection^.^^ Light scattering indicates anaverage grain diameter of about 2000 It is clear that beforemore can be said about the growth of crystals in general, very much moreexperimental work will have to be done.There is more work on related aspects of crystal growth much harder tosummarise. In this report only the briefest indication can be given of themain directions of such endeavours-the alterations of crystal form by thepresence of impurites, dyes,35 etc.; oriented overgrowths ; 36 and the studyby interferometry of cleavage surface^.^'for NaC1.34J. H. R.2. THE TECHNIQUE OF STRUCTURE ANALYSIS.Since 1949 when this subject was last reviewed considerable attentionhas been given to the development of methods for the determination ofcrystal structures directly from diffraction data. Trial and error methodshave been used for many years with great success and there is no doubt thatin the hands of a capable investigator, and especially when used in con-junction with molecular transforms, they can be very powerful. They haverecently been strongly implemented (at least in 2-dimensional cases) by thefurther development of optical methods utilising the correspondence betweenthe diffraction of X-rays and the diffraction of light.Lipson and hiscollaborators have pointed out that the original fly's eye procedure may begreatly simplified by the use of masks containing only a few, instead ofseveral hundred, unit cek38 The revised procedure is not only faster andmore convenient but also, in some respects, more useful, since the patterncan conveniently be compared with the molecular transform also obtainedoptically on the same scale. Positive and negative regions of the transformsmay be distinguished by inserting a " pseudoatom " at a centre of symmetry.It is evident that some otherwise laborious aspects of trial analysis may begreatly eased by use of optical methods, and applications to the solution of32 H.E. Buckley, Proc. Ph-vs. Soc., 1952, B, 65, 578; 2. Elektrochem., 1952, 56, 275.33 See, however, A. J. C . Wilson, Acta Cryst., 1952, 5, 318.34 R. Furth and S. P. F. Humphreys-Owen, Nature, 1951, 167, 715.35 J. Whetstone, ibid., 168, 663; H. E. Buckley, Mem. Manchester Lit. Phil. Soc.,1950-1951, 92, 77; H. Seifert 2. Elektrochem., 1952, 56, 331.3s L. G. Schulz, Acta Cryst., 1951, 4, 483; 1952, 5, 130, 264; D. W. Pashley, ibid.,p. 850; Proc. Phys. Soc., 1952, A , 65, 33; J. Willems, 2. Elektrochem., 1952, 56,345 ; A. Neuhaus, ibid., p. 453 ; E. Stanley, Research, 1951, 4, 293 ; A. A. Fuller, Nature,1951, 168, 471 ; D. M. Evans and H. Wilman, Acta Cryst., 1952, 5, 731.37 S. Amelinckx, Phil.Mag., 1951, 42, 342.38 H. Lipson and C. A. Taylor, Acta Cryst., 1951, 4, 485; A. W. Hanson and H.Lipson, ibid., 1952, 5, 145346 CRYSTALLOGRAPHY.several structural problems have been described.39 Optical methods havealso been applied to the summation of Fourier seriesM It is clear, how-ever, that, for complex crystals where the steric arrangement of the atoms isnot even approximately known, trial methods may become impossible, andit is evidently desirable to have more direct routes to the solution of suchstructures.Buerger 41 has described certain formal re€ations between the idealisedelectron density and the corresponding Patterson function. Regardingboth maps as being composed of sets of points, the fundamental set and thevector set, he has given systematic methods of obtaining the former fromthe latter.Since the Patterson map can always be obtained directly fromdiffraction data this is equivalent to a proof that, in principle at least, thecrystal structure may be solved directly from such data. The difficulty isthat in practical cases the density of peaks in the Patterson map may be sogreat and the degree of resolution so small (for X-ray wave-lengths incommon use) that the individual elements of the vector set are not separatelyrecognisable. The function may, of course, be sharpened by the use ofsuitable modification functions but only a t the cost of introducing spuriousdetail. Nevertheless, some degree of sharpening is certainly useful and anumber of fairly complex crystal structures have been solved by thesystematic interpretation of the sharpened 3-dimensional Patterson function ; adetailed description of such an analysis has been given for hydroxy-~-proline.~~Provided that some of the atoms in the structure can be located, severalmethods of determining the positions of the other atoms are available.Oneof these (the “ heavy atom ” method) based on Fourier synthesis withcoefficients F, and phase angles uc, is well known and has been of greatimportance in solving some very complex structures. Luzzati 43 has givena useful critical examination of the method and has shown that its power isgreatly increased by the presence of a centre of symmetry. Other methodsbased on the systematic analysis of the Patterson function have now beenproposed for such cases.Beevers and Robertson have described the“ vector convergence diagram ” and have applied it with success to thestrychnine hydrobromide structure.45 The method involves a summationof superimposed Patterson functions, appropriately weighted if necessary,with their origin displaced to the known atomic positions; it is usuallyapplied graphically but it may easily be shown that this process is equivalentto calculating the Fourier series with coefficients FO2Fc and with phaseangles ac. Buerger 46 has made use of a Product function and a minzimumfunction in place of the previous summation over Pattersons’ and it isclaimed that the minimum function provides the best convergence to theelectron density. Other forms of Fourier coefficients have been proposed 4739 A.W. Hanson, C. A. Taylor, and H. Lipson, Nature, 1952, 169, 1086; C. A. Taylor,ibid., p. 1087.40 A. W. Hanson, C. A. Taylor, and H. Lipson, ibid., 1951, 168, 160; A. W. Hansonand H. Lipson, Acta Cryst., 1952, 5, 362.42 J. Donohue and K. N. Trueblood, ibid., 1952, 5, 414.43 V. Luzzati, ibid., in the press.44 C . A. Beevers and J. H. Robertson, ibid., 1950, 3, 164.4 5 J. H. Robertson and C. A. Beevers, ibid., 1951, 4, 270.4 6 M. J . Buerger, ibid., p. 531.4 7 D. McLauchlan, Proc. Nat. Acad. Sci., 1951, 37, 115; I. D. Thomas and41 M. J. Buerger, ibid., 1950, 3, 87.D. McLauchlan, Acta Cryst., 1952, 5, 301 ; D. Rogers, Research, 1951, 4, 295DUNITZ : THE TECHNIQUE OF STRUCTURE ANALYSIS.347but, in the Reporters’ view, it remains to be shown that any of the methodsdiscussed above are superior to the original heavy-atom method.A great deal of interest has centred on direct methods in which theproblem is handled in transform space rather than in crystal space. Theapproximate structure can be recognised from a Fourier series containingcomparatively few strong terms, provided that the correct phase angles(or signs) can be assigned to these, and the problem becomes one of devisingmeans of fixing or of limiting the possible phase relations amongst thestrongest terms. The Harker-Kasper (H-K) inequalitie~,~~ derived byapplication of Schwartz’s inequality to the structure factor expression, havenot only been of some practical importance, but have also provided thestimulus for further theoretical development.have shown that inequality relations result from the conditions that theelectron density be everywhere positive and have given a general formula forderiving all such relations.No symmetry properties are required but theymay readily be introduced to give the H-K inequalities as special cases.It is shown 50, 51 that if the U’s (unitary structure factors) rather than theF’s are considered, then some of the inequalities reduce to equalities, specialcases of which have been reported p r e v i ~ u s l y . ~ ~ A method of deriving theH-K inequalities for any space group has been described.53 Additionalphase limitations are imposed if the electron density is known over a portionof the unit cell 54 or if it is restricted to a maximum possible value; 55 nosuch limitations are imposed, however, by the condition that atoms must beseparated by a certain minimum distance.54 Some linear inequalties havebeen derived for centrosymmetric crystals; 56 these are not quite sorestrictive 57 as the H-K inequalities (which involve quadratic relations) butthey are easier to apply and may prove very useful.Methods for thesystematic application of inequalities have been described 58 and they havebeen used to solve the crystal structures of oxalic acid d i h ~ d r a t e , ~ ~decaborane,60 a- and P-seleniumG13 62 p-di-tert.-b~tylbenzene,~~ ethylene-diamine ~ u l p h a t e , ~ ~ and realgar.64For the H-K inequality relation to produce definite restrictions on thesigns, the F values involved must be greater than some minimum value.Their usefulness thus decreases as the unit of structure becomes larger until,a t a certain stage, no limitations whatsoever are imposed.65 In principle,high-order determinantal inequalities 51 could be used in such circum-stances, but their practical application is likely to be rather difficult.Karle and Hauptmann 4934 8 D.Harker and J. S. Kasper, Acta Cryst., 1948, 1, 70.49 J. Karle and H. Hauptman, ibid., 1950, 3, 181.50 H. Hauptman and J. Karle, Phys. Review, 1950, 80, 244.51 J. A. Goedkoop, Acta Cryst., 1950, 3, 374.52 I<. Banerjee, Proc. Roy. Soc., 1933, A, 141, 188; M. J. Buerger, Proc. Nut. Acad.54 J. A. Goedkoop, C. H. MacGjllavry, and R.Pepinsky, ibid., 1951, 4, 491.5 5 R. Pepinsky and C. H. RlacGiUavry, ibid., p. 284.5 6 Y. Okaya and I. Nitta, ibid., 1952, 5, 564. 5 7 K. Sakurai, ibid., p. 697.58 I d e m , ibid., p. 546; J. Gillis, ibid., 1948, 1, 174; E. Grison, ibid., 1951, 4, 489.59 J . Gillis, ref. 58.6o J . S. Kasper, C. M. Lucht, and D. Harker, Acta Cryst., 1950, 3, 436.61 R. D. Burbank, ibid., 1951, 4, 140.63 €3. S. Magdoff, ibid., 1951, 4, 176, 268.64 T. Ito, N. Morimoto, and R. Sadanaga, ibid., 1952, 5, 775.6 5 E. W. Hughes, ibid., 1949, 2, 34.Sci., 1948, 34, 277. 53 C. H. MacGillavry, Acta Cryst., 1950, 3, 214.Idem, ibid., 1952, 5, 236348 CRYSTALLOGRAPHY.For a crystal composed of atoms whose atomic numbers do not differtoo greatly, the electron density p(x) and its square p2(x) have approximatelythe same form.Sayre has shown that, as a consequence, F(h) must equalits self-convolution C,F(p)F(h - p); the phase angles (or signs) must besuch as to satisfy this set of equations. The equations hold in twodimensions provided that the atoms are well resolved and they have beenapplied to the [loo] projection of hydroxy-L-proline. The equations implya tendency for the sign of F(h + p) to be the same as that of F(h)F(p).This result has also been derived by considering the extent to which aFourier series containing only a few large terms can represent p(x),G7 andalso by a statistical argument.68 The relation (1) S(h -/- p) = S(h).S(p)which can be proved from inequalities to be true when the correspondingstructure factors are sufficiently large, is thus Probably true in other circum-stances, as indeed is suggested by a simple trigonometric manipulation ofthe structure factor expression.When some signs can be obtained frominequalities, the probable validity of (1), especially when appliedstatistically,68 provides a useful extension by which more signs may bediscovered. The structures of glutamine 69 and of metaboric acid 68 havebeen solved by this method. I t has been suggested that the statisticalapplication of (1) may be valid even for structures containing up to 200 atomsin the unit cell but, from the Reporters’ experience, this would appear tobe a highly optimistic estimate.A new approach to direct structure analysis has been introduced byHauptman and Karle.’O Each structure factor is regarded as a closedvector polygon; the magnitudes of the vectors ( t i ) are known, but theirorientations (+i) are to be found.For each observation of F(h), theapplication of the random-walk analysis leads to a distribution functionfor the +i’s, and hence for the atomic co-ordinates. The strict couplingbetween the polygons is ignored and the individual distribution functionsare multiplied together to yield a resultant probability distribution functionfor the co-ordinates. I t remains to be seen whether this method, in itspresent form, will be of practical importance ; the calculations are excessivelylengthy and it is shown too that the final probability function is closelyrelated to a “ super-sharpened ” Patterson, exp [ P ( x ) ] .The introductionof coupling between the vector polygons must necessarily strengthen therelations and we understand that this extension is being developed.None of the methods so far described seems generally applicable tomolecules of very high molecular weight. For these, rather specialisedmethods of restricted application are likely to be required. Vand 71 hasdescribed one such method for compounds containing structural periodicities,where the crystal unit cell may contain sub-cells. The structure may, infavourable cases, .be inferred from the relations between the structure factorsof the main cell and those of the sub-cell, as in the analysis of t r i l a ~ r i n . ~ ~13ragg and Perutz 73 have applied knowledge of the general shape of thehzmoglobin molecule to the absolute F values a t various shrinkage stagesand are well on the way to a direct projection of the electron density.6 6 D.Sayre, ActaCryst., 1952,5,60.W. H. Zachariasen, ibid., p. 68.70 H . Hauptman and J . Karle, ibid., p. 48.7 1 V. Vand, ibid., 1951, 4, 104.73 Sir W. I,. I3ragg and M. F. Perutz, Yvoc. Roy. SOC., 1952, A , 213, 425.6 7 W. Cochran, ibid., p. 65.72 V. Vand and 1 . 1’. Bell, ibzd., p. 465.\V. Cochran and B. R. Penfold, ibid., p. 644DlTKITZ THE TECHNIQUE OF STRUCTURE ANr\LYSIS. 349The statistical treatment of X-ray intensities is capable of yielding muchinformation concerning crystal structures. One of the earliest applicationsgave an easy method of placing relative intensity measurements on anabsolute scale.74 A very important new development has been to providean X-ray method of distinguishing between centrosymmetric and non-centrosymmetric crystals.75 The method is quite simple and dependsessentially on the different characteristics of the one- and two-dimensionalGaussian functions which describe the distribution of real and complexstructure factors respectively. Centrosymmetric molecules arranged centro-symmetrically give a “ hypercentric ’’ distribution 76 distinguishable fromthe ordinary centric one. Other symmetry elements may also bere~ognised.~’ I t is noteworthy that all of the 219 distinguishable space-groups may now be recognised from X-rayWe come now to the questions of determining the degree of reliabilityto be associated with a structure analysis a t any given stage.Luzzati 79has extended some earlier arguments of Wilson and others and has derivedrelations between the reliability index R and the mean value of cos 2 x ( A r . s)where Ar is the error in an atomic co-ordinate and s = 2 sin O/h. For thesame degree of precision of the atomic co-ordinates, K is lower in non-centrosymmetric than in centrosymmetric structures, I t is shown that ifthe Ar’s are normally distributed about zero, then R plotted against sin 8must lie on a family of curves corresponding to different values of I r I .This thus provides a much more delicate test for the approximate correct-ness of a structure than the value of K itself, for, if the errors are notdistributed normally, the proposed structure is incorrect, but it may never-theless yield K values as low as approximately correct, though unrefined,structures.Examples of structures which gave reasonably low R values,but which had to be radically modified because they were found incapableof further refinement, are “ cis-naphthodioxan ” 80 (where an incorrect ringstructure was first tested) and purpurogallin 81 (where one translationalparameter of the molecule was wrongly estimated). I t is possible thatother examples are to be found in the literature.The accuracy of the final co-ordinates obtainable by the Fourier and theleast squares method has been discussed by 1300th and by Cruickshank.82The relation between the two methods has been examined by the latter,83who finds an exact similarity between the equations for co-ordinate refinement.The convergence of the Fourier method has been discussed by Luzzati,84 whoconfirms some of Cruickshank’s conclusions.The principal results are asfollows : (1) The same corrections (provided they are sufficiently small) aregiven by both methods. (2) Under identical conditions the final errors inatomic positions are twice as great for the non-centrosymmetric as for the74 A. J . C. LVilson, Nature, 1942, 150, 152.7 5 I d e m , A d a Cvyst., 1949, 2, 318; E. R. Howells, 11. C. Phillips, and D. Rogers,7 7 D. Rogers, ibid., 1950, 3, 455.79 V. Luzzati, ibid., 1952, 5, 802.*O S. Furberg and 0. Hassel, Acla Chem. Scand., 1950, 4, 1584.J .11. Dunitz, Nature, 1952, 169, 1087.n2 -4. D. Booth, Proc. R o y . Soc., 1947, A , 188, 77; A , 190, 482, 490; A , 193, 305;D. W. J. Cruickshank, Acla Cryst., 1948, 1, 92 ; 1949, 2, 65.O3 D. \V. J . C,ruickshank, ibid., 1950, 3, 10; 1952, 5, 511.84 V. Luzzati, ihid., 1051, 4 ,367.78ibzd., 1950, 3, 210. 7 6 H. Lipson and M. M. Woolfson, ibid., 1952, 5, 680.M. J . Buerger, ibid., p. 465350 CRYSTALLOGRAPHY.centrosymmetric cas?. Cochran 85 has given a detailed discussion of the(F, - F,) synthesis. In the early stages, this type of synthesis may bevaluable in indicating the need for structural revisions of a drastic character ;Cochran has shown that it possesses a number of properties which make ituseful for accurate structure analysis.One advantage of the method is thattermination of series errors are largely eliminated; another is thattemperature-factor parameters as well as atomic co-ordinates are refined.The method seems particularly useful for the unequivocal placing ofhydrogen atoms, and for investigation of the fine detail of the electrondistribution (e.g., in bonds).For very accurate results it is of course necessary to have data of thehighest accuracy. With photographic recording and visual estimates it isdifficult to obtain intensities more accurately than to within about 10%.Considerable advances have taken place in the techniques of using Geiger 86and proportional 87 counters for the measurement of intensities. Absorptionconstitutes another serious source of error and methods of applyingcorrections have been described 88 although perhaps the best procedure is toeliminate such errors as far as possible by using either uniformly shaped orvery small crystals where practicable. Indeed, experimental measurementsof the electron distribution can only be regarded as meaningful providedthat they include all the above precautions for ensuring the accuracy of thedata, and have been carried out at sufficiently low temperatures.J.D. D.3. STRUCTURAL CHEMISTRY.1ntroduction.-In this report, we have tried to cover three years ofinorganic and two years of organic structure analyses by X-raycrystallographic methods. Metal and alloy structures have been omitted-it seemed preferable to leave them for a subsequent report than to deal withthem inadequately in the space available this year.But limited space is aproblem which future Reporters will have to face more and more in futureyears. Acta Crystallographtica alone in 1948 contained 348 pages, whichincluded 61 papers and 15 short communications; in 1952 the figures were860, 150, and 67 respectively. Several factors seem to have contributed tothis remarkable expansion.The more widespread adoption of modern computing techniques hasbrought with it a corresponding increase in the use of three-dimensionalmethods. This is important for high-precision work but it also means thatstructures of very great complexity are now being attacked by X-raymethods. One molecule, whose structure is slowly being elucidated,contains about 100 atoms, and already more than ten three-dimensionalPatterson and Fourier series have been computed in the course of thisanalysis alone; a few years ago the labour involved would have beenconsidered pro hi bi t ive.Structural problems concerning substances which are gaseous or liquid85 W.Cochran, Ada. Cryst., 1951, 4, 408.8 7 A. R. Lang, Nature, 1951, 168, 907; PYOG. Phys. SOG., 1952, A , 65, 372; U. W.Arndt and D. P. Riley, ibid., p. 74.8 8 R. G. Howells, Acta Cryst., 1950, 3, 366; D. GrdeniC, ibid., 1952, 5, 283;H. T. Evans and M. G. Ekstein, ibid., p. 540.8 6 I d e m , ibid., 1950, 3, 268DUNITZ AND ROBERTSON STRUCTURAL CHEMISTRY. 351under ordinary conditions have also now been brought within the rangeof crystallographic analysis by recent advances in low-temperaturetechniques.89 Phase transitions, residual entropy, and dielectric anomalieshave already been extensively studied ; hydrogen cyanide,g0 carbonylchloride,s1 1 : Z-dichlor~ethane,~~ methanol,93, 94 n-propylammonium halides,95cycl~pentane,~~ n e ~ h e x a n e , ~ ~ ne~pentane,~' and thiophen 98 are among thecompounds examined and others will be discussed later in connection withaspects of molecular structure. Some points from the analysis of methanolillustrate the problems involved. The two independent investigations ofthe high-temperature modification, carried out within approximately thesame temperature range, lead to different results. One,93 based on single-crystal data, gives an orthorhombic cell in which the molecules are linked byinfinite zig-zag chains of hydrogen bonds; the other,s4 based on powderdata and therefore perhaps not completely reliable, leads to a hexagonal cellof a somewhat related structure.The situation is evidently more complexthan had been thought and may be clarified by further X-ray work,especially as another transition point (at 156.3" K) has now been detected s9in addition to the well-marked one a t 159.2" K. Tauer and Lipscomb havealso succeeded in interpreting the data for the low-temperature modification.The infinite zigzags of hydrogen bonds are preserved, but they becomesomewhat more puckered. It is concluded that the residual entropy iszero, and that the dielectric anomaly is associated with puckering of thehydrogen-bond chains.Carbonyl chloride, at -160" c, is found to have acompletely ordered structure, so that the residual entropy of 1-63 e.u.remains unexplained and presents an apparently very serious problem.Structuralproblems concerning the location of light, in the presence of heavy, atomsmay now be attacked. The most extreme example of this kind, thestructure of uranium hydride, UH,, has already been solved.loO Thehydrogen atoms lie in distorted tetrahedra equidistant (at 2.32 A) from foururanium atoms and not, as previously thought, between the pairs whoseseparation is 3.71 A. Thorium and zirconium hydrides lol have deformedfluorite structures with similarly large M-H distances, 2.41 A. Earlierviews on thorium carbide must be completely revised; lo2 the cell is nottetragonal but monoclinic, the C-C distance is 1.5 A, and the Th-C bondsseem to have considerable covalent character.In ammonium chloride(room temperature phase) the N-H bonds (1-03 A) are directed towardsS. C . Abrahams, R. L. Collin, W. N. Lipscomb, and T. B. Reed, Rev. Sci. Inslr.,1950, 21, 396; H. S . Kaufman and I. Fankuchen, ibid., p. 733; B. Post, R. S. Schwartz,and I. Fankuchen, ibid., 1951, 22, 218.W. J. Dulmage and W. N. Lipscomb, Acta Cryst., 1951, 4, 330.Neutron diffraction extends the range in other directions.g1 B. Zaslow, M. Atoji, and W. N. Lipscomb, ibid., 1952, 5, 833.92 M. E. Milberg and W. N. Lipscomb, ibid., 1951, 4, 369.93 K. J. Tauer and W. N. Lipscomb, ibid., 1952, 5 , 606.0p B.Dreyfus-Alain and J.-M. Dunoyer, Compt. rend., 1952, 234, 320; B. Dreyfus-n5 M. V. King and W. N. Lipscomb, Acta Cryst., 1950, 3, 222, 227.96 B. Post, R. S. Schwartz, and I . Fankuchen, J . Amer. Chem. SOC., 1951, 73, 5113.9 7 A. H. Mones and B. Post, J. Chem. Phys., 1952, 20, 755.98 S. C . Abrahams and W. N. Lipscomb, A d a Cryst., 1952, 5, 93.9B L. A. K. Staveley and M. A. P. Hogg, personal communication.loo R. E. Rundle, J . Amer. Chem. SOC., 1951, 73, 4172.lol R. E. Rundle, C . G. Shull, and E. 0. Wollan, Acta Cryst., 1952, 5, 22.lo2 E. B. Hunt and R. E. Rundle, J . Amer. Chem. SOC., 1951, 73, 4777.Alain and R. Viallard, ibid., p. 536352 CRYSTALLOGRAPHY.four of the surrounding chlorine ions, the two possible orientations beingoccupied at random.103 In potassium hydrogen fluoride] the hydrogen atomis at the centre of the F-H-F bond.lo4 Another type of result beyond thepower of X-ray diffraction is the establishment of the relative positions ofMg2+ and A13+ spinel as the normal rather than the inverse arrangement.lo5Fairly accurate location of hydrogen atoms can also be given by X-rayanalysis, if the data are sufficiently accurate and the other atoms presentare not too heavy.Cochran106 has provided an elegant demonstrationthat in the hydrogen bonds of salicylic acid the hydrogen atom is a t nearlythe normal covalent distance from one oxygen atom and that O-H-*.OFIG. 1. (Fo - Fc) synthesis for saliczlic acid projected on (001). The carbon and oxygenHydrogen atoms and bonding electron density may atoms have been " subtracted out.be recognised in the residuai function.is approximately collinear (Fig.1). The whole question of hydrogenbonding in organic crystals has been discussed by Donohue lo' who hasshown that strong hydrogen bonds are only formed when the H atom isapproximately collinear with the bonded atomx ; he estimates that symmetricO*.*O hydrogen bonds will occur only when the O - - - O distance is about2-3 A. In the several recent cases where a symmetric 0 * * H * * 0 bond appearsto be demanded by the crystal symmetry] e.g., in sodium sesquicarbonatedihydrate,loS in potassium hydrogen bisphenylacetate, log and in potassiumGoldschmidt and D. G. Hurst, ibid., p. 797.la3 H. A. Levy and S.W. Peterson, Phys. Rev., 1952, 86, 766.lo4 S. W. Peterson and H. A. Levy, J . Chem. Phys., 1952, 20, 704.lo5 G. E. Bacon, Acta Cryst., 1952, 5, 684.lo7 J. Donohue, J . Phys. Chem., 1952, 56, 602.lo8 C . J. Brown, H. S. Peiser, and A. Turner-Jones, Ada C v ~ s t . , 1949, 2, 167.loo J . C . Speakman, J . , 1949, 3357.See also G. H.lo6 W. Cochran, ibid., in the pressDUNITZ AND ROBERTSON STRUCTURAL CHEMISTRY. 353hydrogen bis-P-hydroxybenzoate hydrate,llo the O-H * * * 0 distance is greaterthan 2.5 A and Davies and Thomas have shown,lll for the second exampleat least, that the spectroscopic data are in marked disagreement with thesymmetric hypothesis. I t seems likely that these bonds are not reallysymmetric, but rather, that the crystal symmetry arises as a result ofrandomness in the structure.Entropy measurements would be of con-siderable interest. In two cases, however, the possibility of a O-..H---Obond cannot be excluded. In nickel dimethylglyoxime an 0 - - 0 approachof 2-42 A occurs and no absorption maxima corresponding to free 0-H ornormally bonded O-H*..O are detected in the infra-red spectrum.l12 Inmaleic acid, an intramolecular 0 * * - 0 distance of 2.46 A is observed ; 113 herethe bond distances in the carboxyl groups (Fig. 2) show fairly conclusively(a) (b)FIG. 2. Interatomic distances (in A) in (a) nickel dimethylglyoxime and(b) maleic acid.that the hydrogen atom is more firmly associated with one oxygen atom thanthe other. In the singly ionised maleate ion the negative charge should tendto be equally distributed between the two carboxyl groups and the protonshould therefore adopt a more symmetric position.The infra-red absorptionspectrum of potassium hydrogen maleate has been examined and nocharacteristic O-H - * - 0 bands seem to occur.114Together with the widening of the range of crystal analysis comes asignificant increase in depth. It is only within the last few years that allthe diffraction data available from a given crystal have been exploited to thefull in the course of analysis. Urea, one of the first organic compounds tohave been studied by X-ray methods, has been the subject of a recentreinvestigation ; 115 the final molecular parameters and probable errorsreported are : C-0, 1.262 & 0.011 A ; C-N, 1.335 & 0:009 A ; N-C-N,118" 0.9"; N-C-0, 121" 3 0.45".While probable errors close to theabove have been claimed for many years, it may be useful to call attentionto the length of the refinement process considered necessary for this simplestructure in which only four parameters define the atomic positions. Of120 reflections accessible with Cu-K, radiation, the intensities of 11 1 could110 J. M. Skinnerand J. C. Speakman, J., 1951, 185.111 M. Davies and W. J. 0. Thomas, ibid., p. 2858.l1* L. E. Godycki, R. E. Rundle, R. C. Voter, and C. V. Banks, J . Chem. Phys., 1951,113 M. Shahat, A d a Cryst., 1952, 5, 763.11* H. M. E. Cardwell, J. D. Dunitz, and L. E. Orgel, unpublished.l15 P. Vaughan and J. Donohue, Acta Cryst., 1952, 5, 530.19, 1205.REP.-VOL.XLIX. 354 CRYSTALLOGRAPHY.be estimated, the remaining 9 being negligibly small. The final parameterswere obtained after 12 Fourier sections and 2 least-square analyses in whichhydrogen atom contributions and variation of the atomic form factors wereboth taken into account. In this report we shall mention about a dozenother analyses, many of them much more complex than this, for which similarcalculations have been carried out.Meanwhile theoretical chemists have been calculating bond lengths onthe basis of various quantum-mechanical approximations, particularly forconjugated and aromatic molecules, and it is claimed 116 that, in favourablecases, they may be estimated to within 0.015 A. We shall be discussingsome of the results in later pages, noting here only that while in some cases(e.g., anthracene) the agreement between observation and theory is good,in others (e.g., naphthalene, dimethyltriacetylene) quite serious discrepanciesappear to occur.One tends to question whether comparison between bond lengths andangles derived from crystal measurements and from theoretical calculationsis really valid when applied a t this order of refinement.In crystals,molecules are packed in fairly close contact with one another and it seemsquite likely that the attainment of the most favourable packing arrange-ment may, in some cases, be associated with small displacements from theequilibrium state of the molecule considered in isolation. In the fatty acidsand soaps, the mean carbon-carbon repeat distance appears to vary fromcompound to compound-in strontium laurate it is 2-610 A, but in lauricacid 117 2.521 & 0.007 A.Decreases of about 2% in bond length fromthe gas to the crystal have been noted for hexamethylenetetramine 118 andfor pentab0rane.1~~9 I2O Such changes may well depend on the compressionforces within the crystal. As yet, the nature and magnitudes of the inter-molecular forces involved are not well understood but Lowdin's recentcalculations 121 on lattice energies may point the way for future development.Elements.-The analysis of solid chlorine provides a good example ofthe increased power of modern low-temperature techniques. The structurehad been reported to contain a Cl-C1 bond of length only 1.82 A, considerablyshorter than the distance (2.01 A) found in the gas by electron diffraction,122and also an unusually short intermolecular approach of 2.52 A.With newsingle crystal data obtained at -160" c, Collin 123 has shown that the earlierresults were incorrect ; the structure is similar to that of bromine and iodine,with Cl-C12-02 A and Cl.*.C13-34 A.The morestable a-form is shown 61 to contain %membered puckered rings of symmetryDdd as in the rhombic sulphur S, molecule. The Se-Se distance is 2-34 A,considerably longer than the 2-19 A found in the gaseous Se, molecule [thecorresponding distances for sulphur are 2.07 A (S,) and 1.89 A (S2)], andLSe-Se-Se is 105". For the second, less stable, p-modification, Burbank 62The two monoclinic varieties of selenium have been studied.116 C.A. Coulson, J . Phys. Chem., 1952, 56, 311.11' V. Vand, W. M. Morley, and T. R. Lomer, Acta Cryst., 1951, 4, 324.11* P. A. Shaffer, J . Amer. Chem. SOC., 1947, 69, 1557.llg W. J. Dulmage and W. N. Lipscomb, Acta Cryst., 1952, 5, 260.leo K. Hedberg, M. E. Jones, andV. Schomaker, J . Amer. Chem. Soc., 1951, 73, 3538.121 P. 0. Lowdin, J . Chem. Phys., 1951, 19, 1570, 1579.122 For a compilation of electron-diffraction results see P. W. Allen and L. E. Sutton,Acta Cryst., 1950, 3, 46. Iz3 R. L. Collin, Acta Cryst., 1952, 5, 431DUNITZ AND ROBERTSON STRUCTURAL CHEMISTRY. 355proposed a molecule which may be described as an &membered ring inwhich one bond has been broken; we understand, however, that his datamay be re-interpreted in terms of a normal &membered ring.lM Whitephosphorus has a cubic cell containing 56 P, molecules but the completestructure has not yet been e~tab1ished.l~~Very carefulmeasurements of the unit-cell size appeared to show a systematic decreaseof c with increasing quality of crystallinity (size of crystallites, measuredby line broadening).226 It has now been established fairly definitely thatthe variation is only apparent, the observed spacing being the mean valueof two inter-layer spacings, 3.35 k for graphitic carbons and 3.44for " non-graphitic carbons ".I279 128 The a-axis remains ~ 0 n s t a n t .l ~ ~Various modifications of the graphite lattice have been put forward,lZ9 toexplain extra reflections that appear, e g ., indicative of a cell twice as largein the basal plane, or of orthorhombic symmetry. I t has been suggested,however, that these effects arise from impurities; at least, the effects cancertainly be reproduced by the addition of bromine.130 The nature ofgraphites in general has been studied, particularly by Franklin,lz83 131 whohas been able to estimate the proportions of the material in the crystallineand the non-crystalline state, and to postulate grouping of the crystallites,as well as to determine their average dimensions. The crystalline perfectionof graphite can be reduced by grinding : the crystallite size is reduced fromabout 400 x 1200 to about 100 x 400 A (thickness and diameter).132Graphite flakes in cast iron can be shown to be more perfect near their corethan near their e ~ t e r i 0 r .l ~ ~Of particular interest in the case of graphite is the evidence concerningthe distortion of the outer electron shell of the carbon atom owing to bonding.Neutron diffraction intensities agree so well with calculated values that theBernal structure is certainly correct, though deformation from strictlyhexagonal symmetry is still a p6s~ibility.l~~ X-Ray intensities do not agreeso well. But therecan be no doubt as to the agreement of the observed data with McWeeny'snew scattering f ~ n c t i o n , l ~ ~ derived from Duncanson and Coulson's wavefunctions.136 Strong support for the McWeeny curve is also given byBrill's results on diamond.237 The graphite results point to the existence ofabout 0.08 electron in the region of each C-C bond.134 Brill had earlierestimated 0.5-0-75 electron/bond for diamond.But the latest results ofCochran's very accurate work appear to confirm the lower value.106For boron nitride, Hassel's long accepted structure,138 thoughlZ4 L. Pauling, personal communication.lZ5 D. E. C. Corbridge and E. J. Lowe, Nature, 1952, 170, 629.126 G. E. Bacon, Acta Cryst., 1950, 3, 137.127 Idem, ibid., 1951, 4, 558, 561.12g G. E. Bacon, ibid., 1950, 3, 320; J. Hoerni and J. Weigle, Nature, 1949, 164, 1088;J. S. Lukesh, Phys. Reviews, 1950, 80,226; 1951, 84,1068; J . Chem. Phys., 1951,19,383.130 J. S. Lukesh, J . Chem. Phys., 1951, 19, 1203.131 R. E. Franklin, Acta Cryst., 1950, 3, 107.132 G.E. Bacon, ibid., 1952, 5, 392. 133 E. Matuyama, Natuve, 1952, 170, 1123.134 G. E. Bacon, Acta Cryst., 1952, 5, 492.136 R. McWeeny, ibid., 1951, 4, 513; 1952, 5, 463.136 W. E. Duncanson and C. A. Coulson, Proc. Roy. SOL. Edinburgh, 1944, 63, 37.137 R. Brill, Acta Cryst., 1950, 3, 333.138 0. Hassel, Norsk. geol. Tidsskr., 1926, 9, 266.A good deal of attention has been given to graphite.This is now clearly due to the f-curves used hitherto.lz8 R. E. Franklin, ibid., p. 253356 CRYSTALLOGRAPHY.correct in outline, must be modified in favour of a pseudo-graphitic 0 n e . 1 ~ ~Hexagonal networks of B3N3 rings (B-N, 1-45A) are stacked in directregister (B above N), not shifted laterally as in graphite. This stackingsequence is undoubtedly due to the polarity of the B-N bonds.An analysisof BBB-trichloroborazole,140 B,N3H3C13, furnishes a fairly accurate valueof the B-N distance, 1.41 A, somewhat shorter than the value (1-44 A)reported earlier for borazole itself. 122 Some striking similarities existbetween these boron-nitrogen compounds ;and the isoelectronic carboncompounds (e.g., the chemical behaviour of borazole and benzene) but onthe other hand, B3N3 and graphite differ markedly both in electric propertiesand in colour. The electronic band structures of both graphite and boronnitride have been discussed.141FIG. 3. Arrangement of atoms in (a) elementary boron, (b) boron carbide,( c ) decaborane, (d) calcium b o d e , and (e) pentaborane.A structure has at last been presented for elementary boron.142 In thetetragonal unit cell 48 B atoms occur a t the vertices of four nearly regularicosahedra which pack so that every atom forms 6 bonds in a pentagonalpyramid arrangement.Two extra atoms in special positions form tetra-hedral bonds. The B-B distances are 1.75-1.80 A, which agree well withdistances found in boron hydrides and in the diborides of Al, Cr, Ti, Zr, Nb,Ta, and V, where the boron atoms form graphite-like nets.143 The eicoso-hedral arrangement of boron atoms occurs also in boron carbide and (lesstwo atoms) in decaborane. Some quite striking relations may now berecognised in several structures containing boron (Fig. 3). The structure oflSg R. S . Pease, Acta Cryst., 1952, 5, 356.l40 D.L. Coursen and J . L. Hoard, J . Anzer. Chem. SOC., 1952, 74, 1742.C. A. Coulson and K. Taylor, Proc. Phys. SOC., 1952, 64, A , 815, 834.1'8 J. L. Hoard, S. Gellar, and R. E. Hughes, J . Amer. Chem. SOC., 1951, 73, 1892.143 J. T. Norton, H. Blumenthal, and S. J. Sindeband, J . Metals, 1949, 1, Trans. Sect.,749; R. Kiessling, Acta Chem. Scand., 1949, 3, 595DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY. 357stable pentaborane, which can now be regarded as firmly established,llg9is clearly related to that of calcium boride. Boron and its compounds arecontinuing to supply theoretical chemistry with problems of a uniquecharacter ; Longuet-Higgins has discussed some of the electron-deficientcompounds in terms of non-localised molecular orbitals and Hedberg 145has given a detailed discussion of the bond lengths in the boron hydrides andrelated molecules.It is tetragonal with twoparallel but dissimilar planar sheets between which lie other atoms, bound,not to one another, but only to the sheets on either side.It is suggested thatthis relatively complex arrangement is stabilised by the presence of a nearlyfull Brillouin zone. Essentially the same structure is found in the 0-phaseof the Fe-Cr,14’ C O - C ~ , , ~ ~ and V-Ni 149 systems.Simple Inorganic Molecules.-Low-temperature studies are reported forhydrazine 150 and for hydrogen peroxide,151 two molecules important in anyscheme of standard covalent radii. The X-ray results are 1.49 A for 0-0and 1.46 for N-N, in pleasing agreement with earlier values from spectro-scopic and electron-diff raction evidence.lZ2 In hydrogen peroxide thearrangement of the hydrogen atoms, inferred from the intermolecularhydrogen bonding, is that predicted from theoreticdl ~onsiderations.1~~ Thehydrogen bonds form infinite helices round the 4, screw axes of the crystal togive a rather compact structure (the density is 1.70 g.~ m . - ~ ) . In any onehelix there are only two possible arrangements of hydrogen atoms and,since a given helix must retain the same arrangement throughout the crystal,no measurable residual entropy is to be expected at absolute zero. Forhydrazine the possibility of residual entropy due to randomness of orientationin the solid has been suggested in view of the small discrepancy (0.44 e.u.)between the entropies calculated from calorimetric data and from structuralparameters and spectroscopic assignments,153 but here again the structuredoes not appear to permit the retention of any measurable entropy a t lowtemperatures.Hydrogen bonds occur in infinite zig-zag chains in such away as to suggest that the molecules must have either the CZv eclipsed or theC, semi-eclipsed configuration, instead of the staggered as usually assumed,and the same configuration must be retained throughout the length of thechains. Spectroscopic evidence, while not in serious disagreement with theeclipsed forms, has been interpreted as favouring the C, staggeredconfiguration ; a trans(C2h)-configuration has also been suggested, on thebasis of infra-red and Raman spectra, for the solid at -190°.155 It is likelythat there is only a small difference in stability between the various formsThe p-uranium structure has been s01ved.l~~144 H. C.Longuet-Higgins, J., in the press.145 K. Hedberg, J . Amer. Chem. SOC., 1952, 74, 3486.146 C. W. Tucker, Acta Cryst., 1951, 4, 425; 1952, 5, 389, 395.147 B. G. Bergman and D. P. Shoemaker, J . Chem. Phys., 1951, 19, 515.148 D. J. Dickens, A. M. B. Douglas, and W. H. Taylor, J . Iron Steel Inst., 1951, 167,149 J. B. Pearson and J . W. Christian, Acta Cryst., 1952, 5, 157.lSo R. L. Collin and W. N. Lipskomb, ibid., 1951, 4, 10.lS1 S. C. Abrahams, R. L. Collin, and W. N. Lipscomb, ibid., p. 15.162 W. G. Penney and G. M. B. Sutherland, Trans. Faraday SOC., 1934, 30, 898.153 D.W. Scott, G. D. Oliver, M. E. Gross, W. N. Hubbard, and H. M. Huffman,lg4 P. A. Giguere and E. A. Jones, J . Chem. Phys., 1952, 80, 136.155 E. L. Wagner and E. L. Bulgozdy, ibid., 1951, 19, 1210.27; J . S. Kasper, B. F. Decker, and J. R. Belanger, J . AppZ. Phys., 1951, 22, 361.J . Amer. Chem. SOC., 1949,- 71, 2293358 CRYSTALLOGRAPHY.and that the eclipsed molecules are stabilised in the crystal by hydrogenbonds.In hydrazine dihydrogen sulphate (N,H,,+) (SO,,-) 15G the hydrogenatoms have the staggered arrangement, as in the dihydrofluoride 15’ anddihydroch10ride.l~~ In all three salts the N2He2+ ion shows a shortening ofthe N-N distance, from 1.47 to 1.40-1-42 A. has beenreported for this distance in the N,H,+ ion.159that the shortening is caused by increased coulombic attraction between theextra formal charge on the nitrogen atoms and the charge of the surroundingelectronic cloud, but this mechanism has been criticised 15* on the groundsthat the expected degree of shortening would be much smaller than thatactually observed.I t is difficult to make a quantitative estimate of theeffect; the coulomb attraction is increased but so is the internuclearrepulsion, and it is certain that the latter will predominate for very largecharges. Theoretical calculations do indicate that, in a hydrogen-likemolecule, the internuclear distance is decreased as the positive charge on thenuclei increases from unity,160 and ample spectroscopic evidence is availableto show that the internuclear distance invariably decreases (and often by aconsiderable amount) in passing from a diatomic molecule to the corre-sponding isoelectronic positive ion, where the latter exists.IG1 Thesecomparisons are not strictly analogous to that between N,H, and N,H6++,but they appear to suggest that the formal charge effect may well be largeenough to account for the observed shortening. lG2The value 1.45It has been suggested(a) (b) (c)FIG. 4. Arrangement of atoms in (a) diamond, (b) “-cage ” molecule, e.g., As,S6, and( c ) “ cradle ” molecule, e.g., As&. Sulphur occupies the square positions in As$,but the tetrahedral positions in N,S,.Two very interesting molecular crystals, sulphur nitride 163 and realgar(arsenic sulphide),a whose structures have long defied analysis, have nowbeen solved and found to be closely related.Both contain tetrameric“ cradle ”-shaped molecules (Fig. 4) as found by Lu and Donohue 16* for166 I. Nitta, K. Sakurai, and Y . Tomiie, Acta Cryst., 1951, 4, 289.157 M. L. Kronberg and D. Harker, J . Chem. Phys., 1942,10,309.158 J. Donohue and W. N. Lipscomb, ibid., 1947, 15, 115.15B K. Sakurai and Y . Tomiie, Acta Cryst., 1952, 5, 289, 293.160 T. L. Cottrell and L. E. Sutton, Proc. Roy. SOC., 1951, A , 207, 49.161 Compare, for example, internuclear distances for ground states of : LiH 1.595 Awith (BeH)+ 1.312 A ; NaH 1.887 A with (MgH)+ 1.649 A ; BeH 1-343 A with (BH)+1.215 A ; N, 1.094 %I with (NO)+ 1.066 A ; NO 1.151 A with (0,)f 1.123 A : extractedfrom the compilation of.G. Herzberg, “ Spectra of Diatomic Molecules,” Van Nostrand,1950, pp. 501 et seq.16P See also L. Pauling, “ Nature of the Chemical Bond,” Cornell Univ. Press, 1940,p. 169.164 C. S. Lu and J. Donohue, J . Amer. Chem. Sot., 1944, 66, 818.D. Clark, J., 1952, 1615DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY. 359the vapour state. The bond distances, S-N 1-60, S-S 2.58 (in N,S,), and S-As2-24, As-As 2.59 A (in As,S,) agree fairly well with the electron diffractionresults. The vapour of another arsenic sulphide, orpiment, contains “ cage ”-shaped As,& m01ecules.l~~ It is worth remarking that the “cradle”molecule is derived from the “ cage ” by removal of two atoms at oppositevertices of an octahedron. The “ cage” molecule is itself derived byisolating a portion of the diamond lattice, with distortion if necessary, andoccurs in a wide variety of substances, adamantane (CloH16), hexamethylene-tetramine (CloH12N4), P,O,, As40,, As,S,, and also in the A1,0, moleculeswhich have been shown to constitute the film on the surface of aluminiummetal.lG5a The orpiment crystal does not contain discrete rnole~ules.~~Instead, we have superimposed layers of S-shaped chains in which each As issurrounded by three S atoms, each shared by two As atoms.The structureis nevertheless related geometrically to that of realgar, and also to that ofClaude tite, As,O,. 16%A single-crystal analysis of nickel carbonyl, Ni(C0),,166 confirms thatthe molecule is tetrahedral with linear Ni-C-0; the bond distances, Ni-C1.84 and Ni-0 2.99 A, agree well with the electron-diffraction results.122Oxides and Oxy-acids of the Non-metals and Related Compounds.-Oxides and oxy-acids of nitrogen have received much attention.Nitricoxide crystals contain dimeric molecules N,02, with N-0 1-10 and N-m.02.38 A, rectangular in shape.167 The electron densities are interpreted assupporting a random distribution of the two possible arrangements inN...o o . . . N agreement with the observed residual entropy of nearlyI I 1 I QR In 2 per mole. A statistically arranged dimer with theo ’ * ‘ N N’’’o short N-0 groups parallel would also satisfy the data butone would hardly expect this arrangement to give even approximatelyrectangular molecules.It seems difficult to reconcile these results withthe infra-red and Raman results which indicate the absence of a centre ofsymmetry. 168Nitrogen pentoxide has been examined a t -60” and a t +20° c ; apartfrom an expansion of the lattice the structure does not change within thistemperature range; 169 it is of an ionic type and may be represented as[NO,J+[NO,]-. apart,and the nitronium ions are placed perpendicular to the sheets with theirnitrogen atom in the plane of the sheet. The low-temperature analysis hasbeen carried out with a high degree of accuracy, and the N-0 distances aregiven as 1.154 and 1-243 A in the positive and the negative ion respectively.The nitronium ion occurs also in nitronium perchlorate and in the crystallinesolids isolated from nitric-sulphuric acid mixtures.170Two independent refinements of Ziegler’s early work 171 lead to widelydiffering results for the dimensions of the nitrite ion. Truter 17, has reportedThe planar nitrate ions are arranged in sheets, 3-28165e H.G. F. Wilsdorf, Nature, 1951, 168, 600.l e S b K. A. Becker, K. Plieth, and I. N. Stransky, 2. anorg. Chem., 1951, 266, 293.167 W. J . Dulmage, E. A. Meyers, and W. N. Lipscomb, J . Chem. Phys., 1951, 19,1432.16* A. L. Smith, W. E. Keller, and H. L. Jonston, ibid., p. 189.170 K. Eriks, Thesis, Amsterdam, 1952.171 G. E. Ziegler, Phys. Review, 1931, 38, 1040.172 M. R. Truter, Nature, 1951, 168, 344.J. Ladell, B. Post, and I. Fankuchen, A d a Cryst., 1952, 5, 795.E. Grison, K. Eriks, and J.L. de Vries, Acta Cryst., 1950, 3, 290360 CRYSTALLOGRAPHY.1-14 A for N-0 and 132" for LO-N-0, while Carpenter,173 on the basis ofa least-squares refinement, finds 1-23 A and 116". A high degree of accuracyis claimed for both analyses and it seems very difficult to reconcile theresults. Carpenter's result is more likely on theoretical grounds since it givesa sensible sequence for the three molecules NO,' (1.15 A, 180"),169NO, (1-20& 132"),17* and NO,- (1-23 A, 116"). The nitronium ion with16 valency electrons is expected to be h e a r and the bond angle shoulddecrease from 180" as each extra electron is added,175 with diminishingdegree of N-0 bonding.In the gas phase, one bond in nitric acid is markedIy longer than theothers (N-OH, 1.41 A ; N-0, 1.22 A) 122 but in condensed phases, wherehydrogen bonding is possible, the proton becomes less firmly associated withany one oxygen atom and the distances tend to become more nearly equal.A very good example of this is found in the structure of ammonium tri-nitrate, NH,N0,,2HN03.176 The two protons from the acid molecules areinvolved in hydrogen bonds to form a trimer diagramatically representedin Fig. 5.The bond distances are sufficiently accurate to indicate significantshortening of the N-OH distance in the acid molecules. It is also to benoted that the 3-fold symmetry of the nitrate ion is destroyed by theFIG. 5. Trimer formed by two nitric acid molecules and one nitrate ion inNH,N0,,2HN03.perturbation produced by the close approach of protons to two oxygen atomsbut not to the third.Other interesting examples of the way in which nitricacid molecules may be linked are found in anhydrous nitric acid 17' (a verycomplex structure), in nitric acid r n o n ~ h y d r a t e , ~ ~ ~ and in nitric acidtrihydrate. 179Borates and Silicates.-A structure for boron trioxide, B203, has beenderived from powder photographs.180 The rather open 3-dimensionalframework is built of distorted BO, tetrahedra with one B-0 distance muchlonger (about 2-1 A) than the other three (about 1.5 A), an apparentcompromise between trigonal and tetrahedral co-ordination. Cobalt 181and magnesium 182 pyroborate, M2B205, contain discrete (B,O,)*- ions,formed by two BO, triangles with one oxygen in common.B,O,.groupsoccur together with BO, tetrahedra in endless chains in metaborlc acid,HB02.68 Boron is triangularly co-ordinated also in the mineralswarkwickite, ludwigite, and pinakiolite,'= where the structural type is173 G. B. Carpenter, ActaCryst., 1952, 5, 132.174 S. Claesson, J . Donohue, and V. Schomaker, J. Chem. Phys., 1948, 16, 207.1 7 5 A. D. Walsh, Nature, 1952, 170, 974.1 7 6 J. R. C. Duke and F. J. LIewelIyn, Acla Cryst., 1950, 3, 305.1 7 7 V. Luzzati, ibid., 1951, 4, 120.1 7 0 Idem, Compt. rend., 1951, 232, 1428.181 Idem,Acta Chem. Scand., 1950,4,1054.178 Idem, ibid., p. 239.lab S. V. Berger.ActaCryst., 1952,5,389.182 Y.TakCuchi,AcSaCrysl., 1952,5,574.Y. Takkuchi, T. WatanabC, and T. Ito, ibid., 1950, 3, 98DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY.361determined mainly by the packing of oxygen atoms in bands, boroncementing these bands together. One may compare the boroferrites.lsqBoron is tetrahedrally surrounded by four OH’S, however, in teepleite,2NaC1,Na2B,0,,H,0,185 and in bandylite, CuC1,,CuBq04,4H,0 1859 lS6 [wherethe Cu atoms are in planar 4-fold co-ordination, as in malachiteCu,(OH),CO, l 8 7 and basic copper nitrate, CU,(OH),(NO,),~.~~~ In boracite,CIMg,B,Ol,,lsg high, and low-temperature forms, boron is found in tetra-hedra and in BO,-O pyramids, the latter built on a nearly planar BO,triangle. The tetrahedra and pyramids share all their corners, so forming arigid unbroken boron-oxygen network in which relatively large spaces areleft for Mg and C1 ions.Isolated SiO, groups exist in chloritoid, (Fe,Mg),Al(OH) 4A120,(Si0,),,190where the arrangement is in layers similar to those in muscovitebut without fusion of the SiO, groups into sheets.Like moscovite,this mineral contains an OH group; it was identified (by balancing theelectrostatic valencies) but the position of the hydrogen atom was notinferred. Infinite chains of tetrahedra are found in sodium silicate,Na2Si0,,lg1 where the structure is essentially similar to that of diopside. Inthe mineral axinite, Ca,A1,(Fe,Mn)B0,SiO120H,192 the SiO, tetrahedraassociate into rings of Si,012, similar to the P40,, rings of the tetrameta-phosphate ion.lg3 This is the first time that independent Si, rings havebeen observed (in beryl, for example, they are fused with Si,Ol, rings).The BO, g.roups are planar and symmetrical.The OH group identified byelectrostatic considerations is situated almost equidistantly between theFez+ and one Al3+ ion. Its distances from four oxygen neighbours includeone of 2.5 A, while the others exceed 2-9 A, from which the position of thehydrogen bond might well be deduced. But unfortunately the accuracy ofatomic parameters is not sufficient to allow certainty in this : at least fourother 0-0 distances are apparently below 2-5 A. The Si6Ol8 ring isexemplified by tourmaline. The original note by Buerger and Hamburger,mentioned in 1949, has been followed by a full account of their analysis ofthis complex and beautiful stru~ture.1~4 In the meantime Japanese workershave given a detailed report of an independent analysis,lg5 the first announce-ment of which was as early as 1947.There are no essential differences inthe results obtained, although some atomic parameters differ by asmuch as 0-5 A. Another very beautiful structure is that of milarite,~,~a,~e,~~,~~,,~,o,~2~,196 where double rings, Si,,O,o, have been found,formed by the fusion of six additional SiO, tetrahedra, by edges, to theSi,018 ring. These rings are linked into three-dimensional framework by(Be,Si) atoms, with K+ and H20 in the centres of the double rings, and Ca2+ions in the spaces between the rings. The peculiar optical properties oflS4 E. F. Bertaut, Acta Cryst., 1950,3,473.lS6 R. L. Collin, Acta Cryst., 1951, 4, 204.lS8 W.Nowacki and R. Scheidegger, Helv. Chim. Acta, 1952, 36, 375.lS9 T. Ito, N. Morimoto, and R. Sadanaga, Acta Cryst., 1951, 4, 310.lg0 G. W. Brindley and F. W. Harrison, ibid., 1952, 5, 698.lol A. Grund and M. M. Pizy, ibid., p. 837.lQ2 T. Ito and Y . Takkuchi, ibid., p. 202.lv3 C. Romers, J. A. A. Ketelaar, and C . H. MacGillavry, ibid., 1961, 4, 114.lg4 G. Donnay and M. J. Buerger, ibid., 1950, 3, 379.lQ5 T. Ito and R. Sadanaga, ibid., 1951, 4, 385.lg6 T. Ito, N. Morimoto, and R. Sadanaga, ibid., 1952, 5, 209.lS5 M. Fornaseri, Ric. sci., 1951,21, 1192.A. F. Wells, ibid., p. 200362 CRYSTALLOGRAPHY.this mineral were attributed to “ incipient ” twinning; but it is probablethat this requires further investigation. A continuous layer structure isfound in the mineral amesite, long thought to be a chlorite, but now clearly akaolin-type crystal.lg7Several calcium silicate minerals occurring in cement have been studiedrecently, with interesting results. Isolated SiO, tetrahedra are found ineach case. The dicalcium Ca,SiO, has a, a’, p, and y forms,in order of temperature stability. The second, stable a t moderatetemperatures, has a P-K2S04 structure; the @-form is only slightly distortedfrom this. The y-form, into which the p-crystal changes slowly, has anolivine structure. Tricalcium silicate lg9 also has .a number of distinctforms, but with more marked pseudo-hexagonal symmetry, rather moretendency to disorder and, relatively to the dicalcium salt, a somewhat moreopen structure which is thought to explain its much more rapid rate ofhydration by water.The structures of two hydrates are reported. InCa2Si0, cc-hydrate,m the 50, groups are arranged so as to accommodateone water molecule per formula unit. From consideration of thetemperature required to dehydrate the crystal, the water is thought to bepresent as hydroxyl ion, with loss of a proton to an SiO, group.Unfortunately, owing to the limited data available, it is not possible todiscuss the hydrogen bonding. Hydrogen bonding has been studied withgreat care, however, in the afwillite crystal, Ca,(Si0,0H)22H20,201 occurringin cement. The combined evidence of the electrostatic balance and inter-atomic distances establishes the presence of 6 hydrogen bonds, which fallstrikingly into two groups, of mean length 2.52 and 2.72 A.They are allsituated near the plane across which cleavage is thought to occur.Before leaving the silicates, mention should be made of the observationrecently made, that, at a controlled temperature, acid will remove the A1atoms from tetrahedral and octahedral sites at quite different rates202Also there is the important study of the Iaminated structure of certainsilicate minerals, m i c r o c l a ~ e , ~ ~ ~ anorthocla~e,~~ and chrysotile,m where twodifferent crystal structures have been found associated on a sub-microscopicscale. Stacking disorder, where successive layers suffer rotational andtranslational displacements, is very frequent among the silicates. The caseof the chlorites has been given detailed attention.205Phosphates and Sulphates, etc.-An interesting phosphate structure isthat of tervalent cerium (and the rare earths La, Pr, Nd).206 The hexagonalcrystal has oxygen-lined channels containing zeolitic water.The opencharacter of the structure is emphasised by the startling increase in density-25y0-on passing to the monoclinic modification monazite. The hydratediron phosphate minerals, vivianite 207 (and the isomorphous arsenate) andludlamite,2O* have related structures in which FeO, octahedra, some sharingedges and corners, are linked by PO, groups into bands. These are held197 G. W. Brindley, B. M. Oughton, and R. F. Youell, Acla Cryst., 1951, 4, 552.198 C. M. Midgley, ibid., 1952, 5, 307.200 L. Heller, ibid., p.724.202 G. W. Brindley and R. F. Youell, ibid., 1951, 4, 495.203 T, Ito and R. Sadanaga, ibid., 1952, 5, 441.204 E. J. W. Whittaker, ibid., 1951, 4, 187.206 G. W. Brindley, B. M. Oughton, and K. Robinson, ibid., 1950, 3, 408.206 R. C . L. Mooney, ibid., p. 337.207 H. Mori and T. Ito, ibid., p. 1 .J . W. Jeffery, ibid., p. 26.201 H. D. Megaw, ibid., p. 477.208 Idem, ibid., 1951, 4, 412DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY. 363together in vivianite only by hydrogen bonds between the water molecules, inludlamite by the sharing of water molecules. A synthetic mineral, ironlazulite, Fe,(PO,),(OH) ,,m9 has a similar, though closer packed, arrange-ment. Potassium, ammonium, and czsium hexafluorophosphates have anNaC1-type structure formed of K+ and (PF,)- ions.210An interesting thiosulphate structure is that of sodium thiosulphateNa,S,0,,5H20; sodium is surrounded by a distorted octahedron of watermolecules and oxygen atoms, and columns of linked octahedra are heldtogether laterally by the thiosulphate groups (which are approximatelytetrahedral, S-S 1.97 A).,ll It is instructive to compare the Na co-ordination in this salt and in Na3SbS,,9H,0.212Inpotassium sulphamate the S-N distance, 1.60 A, indicates considerablex-bonding corresponding to H,NzSO,--.In potassium and ammoniumdinitrososulphite S-N is 1.79 A, exceptionally long even for a single bond(Tables of covalent radii give 1-74 A). Within the planar N,O, groups thebonds lengths are shortened, in fair agreement with results of molecular-orbital calculations. For sulphamic acid itself,214 S-N is 1.73 and S-01.48 A.Here, as expected from the high melting point, 206" c (cf. sulphuricacid loo), the molecule is a zwitterion, H,N=S03-. The S-0 distance isratherJonger than is usual in molecules of this type. This distance remainsremarkably constant in systems involving d orbitals on the central sulphuratom (see ref. 213), a point which is emphasised by a recent low-temperaturestudy of sulphur dioxide where the value 1-430A is in perfectagreement with micro-wave and electron-diffraction results.The C1-0 distance in systems involving d orbitals on the central atomlikewise seems constant, 1-49 A in C10, and 1.48 A in LiC10,,217 the onlycases for which accurate results are available.With selenium as central atomthe corresponding distance varies much more. and inSeO, vapour it is 1.61 but in selenious acid 219 and in crystallineSeO, 220 the bonds are much longer, between 1-72 and 1.78 A.Metallic Oxides and Related CompQunds.-In discussing these com-pounds, it is convenient to note the transition from low to high co-ordinationnumber ; in particular, from tetrahedral to octahedral environment of themetal atom.Tetrahedral CrO, groups are found in chromium trioxide,,,l linked inchains by sharing of corners. The complex oxide, Th(OH),CrO,,H,O 222contains discrete CrO, tetrahedra situated between infinite zig-zag chainsDetailed analyses are reported for three sulphuric acid derivatives.++In selenic acid20g L.Katz and W. N. Lipscomb, Acla Cryst., 1951, 4, 345.H. Bode and H. Clausen, 2. anorg. Chem., 1951, 265, 229.211 P. G. Taylor and C. A. Beevers, Acta Cryst., 1952, 5, 341.A. Grund and U. Preisinger, ibid., 1950, 3, 363.213 G. A. Jeffrey and H. P. Stadler, J., 1951, 1467.214 F. A. Kanda and A. J . King, J . Amer. Chem. SOC., 1951, 73, 2315.215 B. Post, R. S. Schwartz, and I. Fankuchen, Acta Cryst., 1952, 5, 372.217 R. E. Gluyas, 10th Ann. Pittsburgh Diffraction Conference, 1952.218 M. Bailey and A. F. Wells, J., 1951, 968.220 J. D. McCullough. J. Amer. Ckem. SOC., 1937, 59, 789.2z1 A. Bystrom and K. A. Wilhelmi, Acta Chem. Scznd., 1950, 4, 1131.a22 G. Lundgren and L. G. Sillen, Arkiv Kemi, 1949, 1, 277.J . D. Dunitz and K.Hedberg, J. Amer. Chem. SOC., 1950, 73, 3108.Idem, ibid., 1949, 1282364 CRYSTALLOGRAPHY.of Th(OH),. [Similar chains occur in Th(OH)2S0,.223] The ferrate ion,FeOg2-, as found in BaFeO, etc.,224 has almost the same dimensions as theCrO, grpup. The Cr0,Cl- ion is very similar too; 225 the Cr-C1 distance,2.16 A, incidentally, agrees with that in chromyl chloride.122 In carnotite,KU02VOg(H20) i.5, and the synthetic compound, KU02V0,,226 2-dimensionalsheets are formed by linear U02+ groups and tetrahedral V042- groups, withthe K+ ions and water of crystallisation between the layers.Nickel complexes are commonly square coplanar ; the BaNiO, structureprovides a further example. In NiO,BaO, planar 4-fold co-ordinationoccurs, although the magnetic moment shows two unpaired electrons.A quite unusual planar %fold arrangement is shown by NiO,SBaO,however.22An unusual formation with 5-fold co-ordination exists apparently invanadium pentoxide, V,05, where the octahedron of oxygen atoms around thevanadium is so much distorted (longest bond 2-81, others between 1.54 and2.02 A) that the group is virtually a trigonal bipyramid.228 Tetrahedraoccur, however, in heavy metal orthovanadates, M3V04, such as the rare-earth salts (all of which are isomorphous) which have the zircon structure,with M in 8-fold co-~rdination.~~~As regards octahedral complexes, much attention has again been givento such structures as those built up by the oxides of Mo and W.A numberof these, notably the near-trioxides Mo,02, and were described inthe previous Report.(The structure of the trioxide itself, known since1931, has been confirmed and refined.230) A still more complex oxide,W02.g0, has been e~amined,~,l as well as a mixed oxide (MO,.,~W~.,~)O,.,.~~All these near-trioxides may be written as Mn03n-1. In this type of structure,octahedra are linked by corners infinitely in three dimensions (whichwould give the composition MOO,) except that, in one direction, after everyn octahedra, edges are shared instead of corners, thus giving riseto the ratio of metal to oxygen, n : 3n - 1. The pdramolybdate ion[ M O ( M O ~ O ~ ~ ) ] ~ - , as it exists in the salt (NH,),Mo?0,,,4H20, has beenfound 233 to be slightly different from the corresponding ion Te(M0602p)6-whose structure, a regular hexagon of MOO, octahedra round the telluriumatom, was obtained by Evans.234 In the homopolyacid anion, the 7 octa-hedra do not lie in a single plane; instead, three lie in a plane a littleseparated from that of the remaining four; this distortion gives the ion agreater compactness.The paratungstate ion, however, in the compound5Na20,12W0,,28H20,235 consists, not of 6, but of 12 tungsten atomsassociated with 46 oxygen's rather than the 41 needed to give the ion acharge equal and opposite to 10Na+. The tungsten atoms themselves appear223 G. Lundgren, Arkiv Kemi, 1951, 2, 635.Z z 4 H. Krebs, 2. anorg. Chem., 1950, 263, 175.226 L. Helmholz and W. R. Foster, J . Amer. Chem. Soc., 1950, 72, 4971.226 P. Sundberg and L.G. Sillen, Arkiv Kemi, 1950, 1, 337.227 J. J . Lander, A d a Cryst., 1951, 4, 148.z28 A. Bystrom, K. A. Wilhelmi, and 0. Brotzen, Acta Chem. Scand., 1950, 4, 1119.220 W. 0. Milligan and L. W. Vernon, J . Phys. Colloid Chem., 1952, 56, 145.230 G. Anderson and A. MagnCli, Acta Chem. Scand., 1950, 4, 793.231 A. Magnkli, Nature, 1950, 165, 356.s33 I. Lindquist, Acta Cryst., 1950, 3, 159; Arkiv Kemi, 1950, 2, 325.234 H. T. Evans, J . Amer. Chem. Soc., 1948, 70, 1291.236 I. Lindquist, Acta Cryst., 1952, 5, 667.232 Idem, Research, 1952, 5, 394DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY. 365to be grouped as a hollow cage ; but the oxygen atoms of their octahedra areactually all in contact, in hexagonal close packing. Incidentally thedisposition and function of the water molecules in these structures is still anopen question.Another ion, Mo,O,~- (and the corresponding W207") , hasbeen found to be an infinite chain made up of MOO, tetrahedra andMOO, octahedra.,36 MOO, (or WO,) tetrahedra are not common, but dooccur in such compounds as M,MoO, where M = Ag, Na, gCa, etc. A six-membered ring of WO, octahedra, is formed in the tungsten bronzes,M,WO,.237 Continuous sheets of octahedra are found in yellow molybdicacid, Mo0,,2H20, the octahedra sharing corners in two directions to give thelayers the composition (Moo,),. The remaining oxygen atom must liebetween the layers and the very interesting speculation has been advancedthat, by analogy with BaUO,, a doubly charged ion H,02+ is present.238In lithioph~rite,~~~ MnO, octahedra form sheets stacked alternately withsheets of (Al,Li)(oH)G octahedra. The layers are bound to one another byhydrogen bonds very much as in hydrargillite. A three-dimensional frame-work of continuous tubes is built up by MnO, octahedra in psilomelane,(BaH,O),Mn,O,,.The arrangement is reminiscent of the zeolites and,indeed, dehydration properties are closely similar.240The co-ordination of titanium with oxygen, as illustrated by bariumtitanate, can vary enormously-from a perfect octahedron with all oxygenatoms shared, to a trigonal pyramid with no sharing of oxygen. Bariumtitanate has received much attention, owing to its very importantferroelectric properties. The structures of the cubic 241 and the tetragonal 242forms have been examined-as also have the structures of the ferroelectricniobates and tantalate~.~,~ Twinning and polymorphism in these andother ferroelectrics has been discussed.2u A comprehensive study of theorigin of ferroelectricity in BaTiO, in particular, and covering PbZnO,,NaNbO,, KNhO,, NaTaO,, KTaO,, RbTaO,, and WO,, has been made by-mega^.^^ There are also more complex titanates and niobate~.~~,Another structure determination from powder photography is that ofNa,Pt,O, ( x < l).247 Pt atoms, in continuous rods, surrounded by oxygenin square array, form an infinite cubic stage structure, with the Na ions atthe centre of each cubic hole, between 8 oxygen atoms.As to oxides ofvery low oxygen content, it has been found that those of the formulaM,Ti,O, where the metal is Mn, Fe, Co, Ni, or Cu (but not V, Cr, or Zn) , havethe high-speed steel carbide structure, Fe3W3C, and show metallicproperties.%*Halide Structures.-The fluorides present cases of very varyingcomplexity.The simple hydrate, KF,2H20, consists of distorted octahedraabout both K+ and F- ions, and distorted tetrahedra of two positive and236 Idem, Acta Cheun. Scand., 1950, 4, 1066. 237 A. Magndli, Nature, 1952, 169, 791.23E I. Lindquist, Acta Chena. Scund., 1951, 5, 670.258 A. D. Wadsley, Acta Cryst., 1952, 5, 676. 240 Idem, Nature, 1952, 170, 973.e41 J. W. Edwards, R. Speiser, andH. L. Johnston, J. Amer. Chem. SOC., 1951, '43,2934.*42 H. T. Evans, A d a Cryst., 1951, 4, 377.243 P.Vousden, ibid., p. 68, 373, 545; 1952, 5, 690; R. Pepinsky, ibid., p. 288.244 E. A. Wood, ibid., 1951, 4, 353; R. G. Rhodes, ibid., p. 105.245 H. D. Megaw, ibid., 1952, 5, 739.*46 B. Aurivillius, Arkiv Kemi, 1950, 1, 499; 1951, 2, 519; 1951, 3, 153.247 J . Waser and E. D. McClanahan, J. Chem. Phys., 1951, 19, 413; 1952, 20, 199.249 N. Karlsson, Nature, 1951, 168, 558366 CRYSTALLOGRAPHY.two negative ions about the H20 molecules.2P9 In K2TiF6, titanium isoctahedrally surrounded by fluorine (Ti-F 1-91 A) while the potassium has12 fluorine neignbours.250 Quite simple structures are also found forMnF2,251 MoF,, and TaF,.252 In VF3253 the structure may be regarded asbuilt up of alternate planes of fluorine and vanadium atoms. In C S S ~ , F , , ~ ~however, the antimony is approximately tetrahedrally surrounded byfluorine (Sb-F 2.2 A); two tetrahedra sharing corners form the anionSb2F,-.A more complex situation appears to exist in the salts MSb,F,,(M = K, Rb, Cs, NH,, or Tl).255 The Sb is linked to three F’s by threeshort bonds (pyramidal, Sb-F, 2.0 A) and then through three more fluorineatoms at about 3-0 A to three other SbF, tetrahedra forming in this way afinite complex Sb,F13-. Some double fluoride structures have been brieflysurveyed and the relationships between them and oxide structuresdiscussed.256 The oxyfluoride of actinium has the fluorite structure ;LaOF, YOF, and PuOF are closely related.257Like potassium cuprochloride, the compounds (NH,),CuCl,, (NH,),CuBr,,and K2AgI, have been found to be based on MX, tetrahedra sharing cornersto form long chains of composition MX,, with the positive ions situatedbetween them.258 Copper is tetrahedral also in CSCUC~,.~~~ Indiummonobromide, InBr, has a rather unusual double-layer structure with oneIn-Br distance 2-80, and four others 3.29 A, indicating considerablecovalency.260 InBr is isostructural with orthorhombic TlI, which isinteresting, in view of the similar electronic configuration of indium andthallium.However, TI1 can also crystallise with a CsC1- or NaC1-typestructure.261 Another markedly covalent halide is ThBr,, with two Th-Brdistances of 2.57 A.262 NaAlCl, forms an ionic lattice of Na+ and AlC1,-ions (Al-Cl 2.13 A),263 in marked contrast to the octahedral arrangementin aluminium chloride ; presumably the strongly electro-positive sodiumis responsible.The bridged structure for fused aluminium chloride, Al,CI,,has been confirmed. For fused indium(Ir1) iodide the X-ray analysis doesnot distinguish clearly between the monomeric and the dimeric form;fused tin(1v) iodide, as expected, contains monomeric tetrahedral molecules.264In K,Ru2Cl1,O,H2O, the anion is a double octahedron composed of twoRu atoms joined by 0 and surrounded each by five C1 atoms (Ru-O-Ruis linear).265 The compounds Co(NH3),,T1C1, and Co(NH,),,TlBr, havea simple NaC1-type lattice, with Co and T1 surrounded by octahedra249 T. H. Anderson and E. C. Lingafelter, Acta Cryst., 1951, 4, 181.260 S. Siegel, ibid., 1952, 5, 683.251 M. Griffel and J. W.Stout, J . Amer. Chem. Soc., 1950, 72, 4351.258 V. Gutmann and K. H. Jack, Acta Cryst., 1951, 4, 244.253 Idem, ibid., p. 246.254 A. nystrom and K. A. Wilhelmi, Arkiv Kemi, 1951, 3, 373.255 Idem, ibid., p. 17.2s6 W. L. W. Ludekens and A. J. E. Welch, Acta Cryst., 1952, 5, 841.257 W. H. Zachariasen, ibid., 1951, 4, 231.258 C. Brink and H. A. S. Kroese, ibid., 1952, 5, 433 ; C. Brink and A. E. van Arkel,260 N. C. Stephenson and D. P. Mellor, Austral. J . Sci. Res., 1950, 3, A , 581.261 L. G. Schulz, Acta Cryst., 1951, 4, 487.263 N. C. Baenziger, Acta Cryst., 1951, 4, 216.264 R. L. Harris, R. E. Wood, and H. L. Ritter, J . Amer. Chem. Soc., 1951, 73, 3161 ;266 A. McL. Mathieson, D. P. Mellor, and N. C. Stephenson, Acta Cryst., 1952, 5, 185.i b i d ., p. 506. 259 L. Helmholz and R. F. Kruh, J . Amer. Chem. SOC., 1952, 74, 1176.262 R. W. M. D’Eye, J . , 1950, 2764.R. E. Wood and H. L. Ritter, ibid., 1952, 74, 1760, 1763DUNITZ AND ROBE~TSON : STRUCTURAL CHEMISTRY. 367(Bond lengths in A.)of ammonia and halogen respectively ; 266 the bismuth compound,Co(NH,) ,,BiCl6, is i s o m o r p h o ~ s . ~ ~ ~ In the lead which isdiamagnetic, the lead appears to exist in two valency states; PbCl, octa-hedra of differing dimensions are indicated by extra lines in the powderphotographs. The structure of K,ReBr, is of the K,PtCl, type, asexpected.268 Other halide anions which have been studied by X-raydiffraction of their solutions include PtC16, PtBr,, Ta6Br,,, and Ta6C1,,.269Another bromide recently studied is FeBr,.270, The mixed halide PCl,I has been shown to be tetrachlorophosphoniumdichloroiodide, where the cation [PCl,] + is tetrahedral and the anion[Cl-I-ClI- is linea1-.~~1 A series of polyiodide anions, I,-, 15, 17-, and evenIg-, may be obtained by dissolving iodine in aqueous potassium iodide. TheI,- ion has been found to be linear with 1-1 distances 2-82 and 3-10 272(cf. 2.67 A in 12).In NMeJ, 273 we have two sets of almost squarenets of iodine atoms (represented diagramatically below) separated by43A. The cations are situated in the large empty spaces between the1 1I II 3-14 I----I-I-I 1-I !I 3.55 I 2-93 I I__-. I-I--I 1-i 3.11 2.93 3.55 fnets (see inset). The distances vary sufficiently so that discrete V-shapedI,- ions may be recognised.I t seems very probable that these complex ionsarise from the polarisation of I, molecules by I- ions to give 1-1 - * - I-,1-1. - I- - . - 1-1, etc. The high members are formed only with very largecations and it would be very interesting to know their structures.Mercury Compounds.-Several interesting compounds of mercuryremain -to be described. Aminomercuric chloride and bromide containzig-zag chains -Hg-NH,+-Hg-, linear about Hg, tetrahedral about N, withthe halide ions between the chains.274 The structure of Millon's base,Hg2N*OH,2H,O, must be rather similar, although here the -Hg-N-Hg net-work is of the cristobalite type.275 Cinnabar, HgS, has infinite spiralchains, -Hg-S-Hg- with an angle of 105" a t S, and the bonds nearly collinearat Hg (172°).276Chelate Compounds.-Chromium has provided some rather interestingexamples of chelate co-ordination in the oxalato-complexes.InK3[Cr(C,0,),)],3H,O, the chromium is surrounded octahedrally by the sixoxygen atoms (Cr-0 1.90 A) of the three oxalate groups, and the complex so2 6 6 T. WatanabC, M. Atoji, and C. Okazaki, Acta Cryst., 1950, 3, 405.2 6 7 M. Atoji and T. WatanabC, J . Chern. Phys., 1952, 20, 1045.268 D. H. Templeton and C. H. Dauben, J . Amer. Chenz. SOC., 1951, 73, 4492.269 P. Vaughan, J. H. Sturdivant, and L. Pauling, ibid., 1950, 72, 5477.270 N. W. Gregory, ibid., 1951, 73, 472.271 W. F. Zelezny and N. C. Baenziger, ibid., 1952, 74, 6151.272 R. C. L. Mooney, 2. Krist., 1935, 90, 143.27s R.J. Hach and R. E. Rundle, J . Amer. Chem. SOC., 1951, 73, 4321.274 W. h'. Lipscomb, A d a Cryst., 1951, 4, 266; L. Nijssen and W. N. Lipscomb, ibid.,276 K. L. Aurivillius, A d a Chem. Scand., 1950, 4, 1413.1932, 5, 604. 276 W. N. Lipscomb, ibid., 1951, 4, 156368 CRYSTALLOGRAPHY.formed is packed by ionic and hydrogen bonding with the K 1 ions and theH20 molecules. The rubidium salt is isomorphous but not the ammoniumsalt, owing, probably, to the ability of NH,+ to form tetrahedrally directedhydrogen bonds resulting in a more open structure. In the red dioxalato-complex, trauts-K2[Cr(C204)2(H20)2],3H20, the two oxalate groups lie in asingle plane and the two co-ordinated water molecules are above and belowat slightly greater distances (Cr-0 1.92 for carboxyl oxygen, 2.02 A forwater).277Copper is in roughly planar co-ordination with two molecules of ethylene-diamine in the compound Cu{en),,Hg(SCN),; here the sulphur atoms aretetrahedrally arranged round the mercury but the LS-C-N reported differsfrom 180" by as much as 24°.278 In copper 279 and nickel dimethyl-glyoxime 112 the entire molecule is planar with nitrogen in a square aboutthe metal atom (Ni-N 1.87; Cu-N 1.92 A).The nickel compound containsan unusually short 0 - 0 0 approach of 2-42 A, and the possibility that thehydrogen bond might be symmetric has been discussed.In the copper-DL-proline complex, Cu(C,H80202N),,2H20, copper againforms square coplanar bonds.280 The amino-acid molecules are attachedby N (Cu-N 1-99 A) and by 0 (Cu-0 2.03 A).Two longer bonds, 2.52 A,to water molecules complete the distorted octahedron so frequent in copperco-ordination. In cupric acetate [Cu(CH3*C02),,H20],, the two Cu atomsform a pair, bridged by the four carboxyl ions (Cu-0 1.97 A), which arearranged symmetrically about the Cu-Cu axis. The octahedron is com-pleted by two water molecules (at 2-20 A), one on either side of the copperatom.2s1 Particularly striking is the Cu-Cu distance, 2-64 A, very close tothat found in metallic copper (2-56 A).An organic base is involved in co-ordination, though not in chelation,in MnC12,2(CH2)6N,,2H20.282 The Mn, at a centre of symmetry on thecommon three-fold axis of the two hexamethylenetetramine molecules, issurrounded by two chlorine atoms (at 2.47 A), two water molecules (at2.00A) and two nitrogen atoms (at 2-40 A).The bonding is sp3d2 andmagnetic susceptibility measurements indicate five unpaired electrons.Hexamethylenetetramine forms complexes with a variety of simple salts ;in CaBr2,2(CH,),N4, 10H,O, however, the organic molecule is not involvedin co-ordination round the calcium atom.283Molecular Compounds.-A series of complete structure determinationsof molecular compounds of boron trifluoride with ammonia, methylamine,trimethylamine, and methyl cyanide has been made and the results havebeen discussed in relation to the relative stabilities of the complexes.2MThe methyl cyanide compound is much less stable than the others, and in it2 7 7 J.H. van Niekerk and I;. R. L. Schoening, Acta Cryst., 1951, 4, 35; 1'352, 5, 196,278 H. Scouloudi and C. H. Carlisle, Nature, 1950, 166, 357.279 E. Bua and G. Schiavinato, Gazzetta, 1951, 81, 212, 847; S. Bezzi, E. Bua, and280 A. McL. Mathieson and H. K. Welsh, Acta Cryst., 1952, 5, 599.2 8 1 J . N. van Niekerk and F. R. L. Schoening, Nature, 1953, 171, 36.282 Y . C. Tang and J . H. Sturdivant, Acta Cryst., 1952, 5, 74.283 A. Addamiano and G. Giacomello, Ric. sci., 1951, 21, 2121.284 J. L. Hoard, S. Geller, and W. M. Cashin, A d a Cy-yst., 1951, 4, 396; S. Geller andJ . L. Hoard, ibid., p. 399 ; J. L. Hoard, S. Geller, and T. B. Owen, ibid., p. 405 ; S. Gellerand J . L. Hoard, ibid., 1950, 3, 121; J - L. Hoard, T. B. Owen, A. Buzzell, and 0. N.Salmon, ibid., p.130.475, 499.G. Schiavinato, ibid., p. 856DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY. 369(1) the B-N distance, 1.635 A, is significantly longer than in the others (1.67-1.60 A) and (2) the BF, molecule undergoes much less alteration in shape(compared with free BF,). Preliminary data are also reported for methylcyanide-BCl,, methyl cyanide-BBr,, trimethylamine-BH,, and dimethyl-amine-BF,. 285Clathrate compounds (complexes in which molecules of one kind form aframework within which molecules of a second kind are trapped) havecontinued to provide interesting results. The magnetic susceptibility ofthe oxygen-quinol complex has been measured and it is found that practicallyno magnetic interaction occurs between the oxygen Thedielectric properties of some quinol clathrates have been st~died.~87 Theexistence of= optically active clathrate-type frameworks 2880 has been utilkedfor the resolution of racemic mixtures of asymmetric molecules capable ofentering the enclosures.sec.-Butyl bromide has been resolved by formationof its complex with trithymotide 2886 (here the exact nature of the enclosureis not yet known), and optically active derivatives of long-chain hydro-carbons have been resolved2S9 by formation of complexes with urea andthiourea (here the void spaces are channels rather than completelyenclosed cages as in the quinol and ammonia-nickel cyanide 291 compounds).Resolutions have also been achieved by formation of addition compoundswith c y c l o d e ~ t r i n s .~ ~ ~It now appears that the crystalline hydrates formed by many gases(Kr, Cl,, SO,, H,S, CH,Cl, etc.) constitute a further example of clathratecompounds in which the " inert gas " molecules are enclosed within polyhedraformed by the oxygen atoms of interlinked water molecules. Severalalternative structures have been proposed 293 but we shall mention only onedue to Pauling and Marsh who have obtained X-ray evidence for it in thecase of chlorine hydrate. In the cubic cell 46 water molecules are arrangedto form two pentagonal dodecahedra and six tetrakaidecahedra ; formolecules as large as chlorine only the latter are occupied, to give theformula 6C12,46H,0 or very nearly Cl,,8H20.Organometallic Compounds.-Dimethylberyllium has been examined bySnow and R ~ n d l e .~ ~ ~ Linear chains >Be(CH,),*Be(CH,),*Be < in whichthe CH, groups are tetrahedrally arranged about the Be atoms are found,showing the tendency of the metal atoms to use all their low-energy orbitalsfor bond formation even though combined with elements or groups containingno unshared pairs. A similar structure is found for beryllium d i ~ h l o r i d e . ~ ~ ~The very unusual " sandwich " structure (I), first suggested by Woodwardz 8 5 S. Geller and 0. N. Salmon, Acta C~yst., 1951, 4, 379; S. Geller, R. E. Hughes,z86 D. F. Evans and R. E. Richards, Nature, 1952, 170, 246.287 J. S. Dryden and R. J. Meakins, ibid., 1952, 169, 324.288a A. C. D. Newman and H. M. Powell, J., 1952, 3747.2886 €3. M. Powell, Nature, 1952, 170, 155.289 W. Schlenk, Internat.Congr. Analyt. Chem., Oxford, 1952.zg0 Idem, Annalen, 1949, 565, 204; A. E. Smith, Acta Cryst,, 1952, 5, 224.291 J. H. Rayner and H. M. Powell, J., 1952, 319.292 I;. Cramer, Ajigew. Chewz., 1952, 64, 136.2s3 L. Pauling and R. E. Marsh, Proc. Nut. Acad. Sci., 1952, 20, 112; M. vonStackleberg and H. R. Miiller, Natuvwiss., 1951, 38, 456; J . Chem. Phys., 1951, 19,1319; W. I;. Claussen, ibid., pp. 259, 1425.294 A. I. Snow and R. E. Rundle, Acta Cryst., 1851, 4, 348.2*5 R. E. Rundle and P. H. Lewis, J . Chem. Phys., 1952, 20, 132.and J. L. Hoard, ibid., p. 380; S . Geller and M. E. Milberg, ibid., p. 381370 CRYSTALLOGRAPHY.et aZ.296 for the remarkable new aromatic molecule dicyclopentadienyliron(ferrocene) has been confirmed by X-ray analysis.297 Accurate bondlengths are not yet available but the indications are C-C 1.4 and Fe-C2-0 A.Non-localised molecular orbitals give perhaps the best description ofthese molecules. It is not possible to write a simple 10-bonded structurefor (I), but Dunitz and Orgel have shown that its stability can be attributedto bonding between an atomic d orbital of the iron atom and a molecularorbital associated with the pair of cyclopentadienyl radicals.(1) (11)Hydrocarbons.-Among the hydrocarbons we have three analyses ofoutstanding accuracy to report but, before proceeding to these, it isconvenient to mention some other analyses which have been carried out withrather less attempt at precision. The structure of P-di-tert.-butylbenzenehas been investigated in connection with a study of hyperconjugation; nomarked shortening of the bonds connecting the phenyl with theattached groups is observed.63 In 3 : 4-5 : 6-dibenzophenanthrene (11)steric cwsiderations prevent the molecule from adopting a planar configur-ation ; In octamethyl-naphthalene, mutual interference of the methyl groups, which lie alternatelyabove and below the mean molecular plane, occurs; 'the ring system itselfappears to be slightly distorted but the bond lengths are normal.2mthe individual rings are but little distorted.298FIG.6. Interatomic distances (in A) observed (and calculated) in naphthalene andanthracene.The 3-dimensional X-ray data for naphthalene and anthracene have nowbeen corrected for termination-of-series The resultant changes inthe bond lengths are not large, the maximum being 0.018 and the mean0.0068.The new averaged lengths are given in Fig. 6 together with (inparentheses) results of the most recent calculations based on molecular2*6 G. Wilkinson, M. Rosenblum, M. C. Whiting, and R. B. Woodward, J . Anzev.Chem. SOC., 1952, 74, 2125.297 E. 0. Fischer and W. Pfab, 2. Naturforsch., 1952, 7, B, 377; P. F. Eiland andR. Pepinsky, [. Amev. Chem. Soc., 1952, 74, 4971 ; J. D. Dunitz and L. E. Orgel, Nature,1953, 171, 121.298 A. 0. McIntosh, J. M. Robertson, and V. Vand, Nature, 1952, 169, 322.*09 J. M. Robertson, personal communication.300 F. R. Ahmed and D. W. J. Cruickshank, Acta Cryst., 1952, 5, 852DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTKY.371orbital theory ; 301 for anthracene the agreement is good, but for naphthalenethere are still significant discrepancies.Jeffrey and Rollett 302 have taken full advantage of an opportunity forunusually accurate structure analyses in the case of dimethyltriacetylene(Fig. 7). The rod-shaped molecules lie on %fold axes, and the atomicFIG. 7. Interatomic distances (in A) in dimethyltriacetylene.positions are defined by only four parameters. In the calculations allowancehas been made for tennination-of-series corrections, free rotation of themethyl groups, thermal anisotropy, and for bonding-electron density. Thefinal R factor is 0.08 and the estimated standard deviation of the bond lengthsis less than 0.01 A.But here again marked discrepancies seem to existbetween theory and the observed bond distances. One difficulty concernsthe length of the triple bonds, which in conjugation should be greater thanthat of an isolated triple bond. In dimethyltriacetylene (and in other similarmolecules) they are rather shorter than the acetylene value, 1.204 A. I t ispossible, of course, that a smaller value than this should be adopted asstandard triple bond because of the stretching effect of H C=C H ; Jeffreyand Rollett suggest 1.185 A, but it can be estimated that, for stretching of0.02 A, the improbably large charge of about 0-4 electron per carbon atomwould be required.The results of structure analysesof small alicyclic rings are in some respects rather puzzling.Owen andHoard 303 have determined the structure of octachlorocyclobutane and haveshown that the ring is non-planar with markedly long C-C bonds. Non-planar ring systems are also found by electron diffraction in octafluorocyclo-butane 304 and in cyclobutane it~elf,~05 although in the latter a planarequilibrium configuration with large amplitude of out-of-plane bending isalso compatible with the evidence. Planar, centrosymmetric, four-membered rings are found in tetraphenylcyclob~tane,~~~ in dinaphthylene-~yclobutane,~O7 and in dimethylketen dimer.308, 299 In all these cyczobutanederivatives the ring C-C distances are 1-56-1-60 A, i.e., markedly longer thannormal. The obvious interpretation of this elongation as being due toweaker bonding as a result of Baeyer strain is, however, quite unacceptablesince, in 3-membered rings where the strain is much more severe, the ring-C-C distances are consistently shorter than normal.Coulson and Moffitt 309have suggested that, since the bonding orbitals do not point in the bonddirections, some degree of X--x bonding must exist in addition to the usual301 C. ,4. Coulson, R. Daudel, and J . M. Robertson, Proc. Roy. Soc., 1951, A , 307, 306.302 G. A. Jeffrey and J . S. Rollett, ibid., 1952, A, 213, 86.303 T. B. Owen and J . L. Hoard, Acta Cryst., 1951, 4, 172.304 H. P. Lemaire and R. L. Livingston, J . Amer. Chem. Soc., 1952, 74, 5732.305 J . D. Dunitz and V. Schomaker, J . Chem. Phys., 1952, 20, 1703.306 J . D. Dunitz, Acta Cryst., 1949, 2, 1 .307 J .D. Dunitz and L. Weissman, ibid., p. 62.308 W. N. Lipscomb and V. Schomaker, J . Chem. Phys., 1946,14, 475.30e C. A. Coulson and W. E. Moffitt, Phil. Mug., 1949, 40, 1.+ - - +Carbocyclic Compounds.-Small YZngs372 CRYSTALLOGRAPHY.0-0 bonding, and that this might lead to bond shortening. Dunitz andSchomaker305 have drawn attention to the fact that cyclobutane is thermo-chemically much more unstable than would be expected, and have tentativelyascribed this to repulsion of the non-bonded atoms (separated by only 2.2A), which may also result in elongation of the bonds. A combination ofthe two effects, one leading to shortening, the other to lengthening, mightseem to offer one interpretation of the bond-distance evidence, but it cannotbe said that the situation has been satisfactorily explained.cycloHexane rings.The halogen derivative, 1 : 2-dibromo-4 : 5-di-chlorocyclohexane, has the configuration KKEE 310 and is isomorphous with the1 : 2 : 4 : 5-tetrachloro- and -tetrabromo-compounds.3~~ Of particularchemical interest is the fact that elimination of hydrogen chloride from6-hexachlorocyclohexane by alkali removes that chlorine atom whichprotrudes most directly from the ring, as shown by X-ray analysis of theresulting pentachlorocy~Zohexene.~~~ a-Phloroglucitol, a 1 : 3 : 5-hydroxy-cyczohexane with the configuration KICK, gives a dihydrate and a diammoniatewhich are i~omorphous.~1~ The dihydrate of 1 : 3 : 5-triaminocyclohexanehas, it seems, the same structure also, so that, curiously enough, replacementof the O-H.-*O bonds, which hold the structure together, by bonds of thetype N-H * - 0 or O-H * * N leaves the arrangement of the moleculesunaffected.Naphthalene tetrachloride (a preliminary examination of whichwas made by W. H. Bragg as long ago as 1927) can be regarded as 1 : 2 : 3 : 4-tetrachloro-5 : 6-benzocyclohexene, in which the chlorine atoms have theconfiguration l c , Z K , 3 K , 4 ~ . ~ ~ ~ Analyses of a- and p-l-chloromercuri-2-methoxycyclohexane have shown that, contrary to earlier opinions based onchemical evidence, the a-form has the trans-configuration, while the p-formis c Z S . ~ ~ ~A well-resolved projection of the cupric tropolonestructure provides confirmation 316 of the planar 7-membered ring system(111) which is supported also by electron-diffraction e~idence.~l' Thechemical structure of purpurogallin (IV) has also been ~onfirmed.~l*Several papers pertaining to the structure ofcyclooctatetraene have appeared.The D2d or " tub " model withunequal bond lengths is supported by two electron-diffraction studies ofcyclooctatetraene itself ,319 by an X-ray analysis of the monocarboxylica~id,3~0 and also by theoretical consideration^,^^^ in addition to the earlierSeven-membered rings.Eight-membered rings.310 The notation used is due to 0. Hassel (Tidsskr. Kjemi, 1943, 5, 32); E and Kcorrespond to the p (polar) and e (equatorial) of K. S. Pitzer and C. W. Beckett ( J .Amer. Chem. Soc., 1947, 69, 977). The co-existence of these two nomenclatures oftenleads to confusion.311 0.Bastiansen and 0. Hassel, Acta Chem. Scand., 1951, 5, 1404; 0. Hassel andE. W, Lnnd, ibid., 1952, 6, 238.812 R. A. Pasternak, Acta Cryst., 1951, 4, 316.313 P. Anderson and 0. Hassel, Acta Chenz. Scund., 1951, 5, 1349.314 M. A. Lasheen, Acta Cryst., 1952, 5, 593.315 A. G. Brook and G. F. Wright, ibid., 1951, 4, 50.316 J. M. Robertson, J . , 1951, 1222.3 1 7 E. Heilbronner and K. Hedberg, J . Amer. Chem. SOC., 1951, 73, 1386.318 J. D. Dunitz, Nature, 1952, 169, 1087.319 I. L. Karle, J . Chem. Phys., 1952, 20, 65; K. Hedberg and V. Schomaker, 115thAmer. Chem. SOC. Meeting, San Francisco, 1949.320 D. P. Shoemaker, personal communication.321 W. B. Person, G. C. Pimentel, and K.S. Pitzer, J . Amer. Chem. SOC., 1952,74,3437DUNITZ AND ROBERTSON STRUCTURAL CHEMISTRY. 373X-ray evidence.322 The D, (crown) model and the D,d (tub with equalbonds) model have also been proposed323 but the balance of the evidenceseems to favour D,d.HO 0Heterocyclic Compounds.-Compounds containing oxygen. A chemicalproblem has now been settled by a low-temperature X-ray analysis ofdiketen.324 The arrangement of carbon and oxygen atoms corresponds toa p-lactone structure ; the but-3-eno-p-lactone formula (V) is supported bythe distribution of the bond lengths.Structures assigned to two other molecules on chemical grounds must bealtered in the light of X-ray evidence. The compound previously-known asI' cis-naphthodioxan " (VI) has been shown by Furberg and Hassel 325 to bedi-1 : 3-dioxacycEopent-2-y1 (VII).The molecule is centrosymmetric, the ringsare non-planar (ascribed to mutual interference of neighbouring methylenegroups), and the bond distances are quite normal (C-C 1.52; C-0 1.41 A).GrdeniC 326 has shown that the compound supposed to be l-oxa-4-mercura-cyclohexane (VIII) has actually a structure corresponding to the 12-memberedring formula (IX). The angle C-Hg-C is close to 180".CH,*HgCH,*CH,OCH, I OCH, II I CH,*CH,*Hg*CH, (IX)Compounds containing nitrogen. A very careful refinement of theadenine hydrochloride structure has been undertaken by C ~ c h r a n , ~ ~ ' usingthe (F, - F,) synthesis, and taking into account anisotropic temperaturevibration for every atom.Geiger-counter intensity data were employed.The result, showing individual peaks for all the hydrogen atoms, allowsunequivocal decision as to the particular tautomer present in the crystal (X),a conclusion reached independently by Donohue lo' by consideration of thehydrogen bonding. The structure of the hydrochloride of guanine, theother purine base occurring in nucleic acid, is closely related to that of theadenine salt, despite the different symmetry of the crystals.328 A322 H. Kaufman, I. Fankuchen, and H. Mark, Nature, 1948, 161, 165.323 0. Bastiansen and 0. Hassel, Acta Chem. Scund., 1949, 3, 209; B. D. Saksena andH. Narain, Nature, 1950, 166, 723 ; E. R. Lippincott, R. C. Lord, and R. S. McDonald,J. Amer. Chem. Soc., 1951, 73, 3370.s24 L.Katz and W. N. Lipscomb, A d a Cryst., 1952, 5, 313.835 S. Furberg and 0. Hassel, Acta Chem. Scund., 1950, 4, 1584.S t 6 D. Grdenid, Acta Cryst., 1952, 5, 367.sa7 W. Cochran, ibid., 1951, 4, 81. 328 f . M. Broomhead, ibid., p. 92374 CRYSTALLOGRAPHY.substituted pyrimidine, 5-bromo-2-metanilamidopyrimidine, an active anti-malarial, has been studied, and the crystal structure reported.329A 3-dimensional analysis for tetramethylpyrazine (XI) shows that theN\ H c(H/ I MeHN NHH > q M e (XIV)molecule is planar and centrosymmetric. Within the ring C-C is reportedto be 1-44 and C-N 1.31 A, and the external C-C bonds are 1.50Presumably the x-electrons are concentrated more in the C-N bonds than inC-C because of the greater electronegativity of the nitrogen atoms.Forphenazine (XII), a 2-dimensional study does not reveal such large differencesin the bond lengths; C-N is given as 1.32-1.34 and C-C as 1.38-1.39 A.331A preliminary announcement of a refinement of the cyanuric acidstructure (XIII) has appeared.332 In the earlier analysis one C - 0 bondlength had been reported to be different from the other two but the newmeasurements show that the approximation to %fold molecular symmetrymust be very close indeed. The C-0 distances are virtually identical ; thosefor C-N are also very nearly equal. The mean values are 1-21 and 1.355 A,respectively, indicating some contribution of resonance structures in whichNH is positively charged. In “ aldehyde ammonia,” according to L ~ n d , ~ a reduced triazine ring (XIV) has the chair form, with the methyl groups inmK-configuration.The water, hydrogen-bonded to the nitrogen atoms,forms what are effectively puckered six-membered rings of H,O molecules(0.. 00 2.71 A)-a striking and unusual arrangement.The material previously thought to be quinocol (XV) has been shown byDavies and Powell 334 to be quinaldil (XVI). The arrangement in the crystalis very curious, since the cis-configuration is adopted, and the moleculesall point in the same direction to give a highly polar structure. The quinolinering is coplanar with its neighbouring carbonyl group, and the moleculetwists about the central C-C bond to achieve steric clearance.szs J. Singer and I. Fankuchen, Acta Cryst., 1952, 5, 99.330 D.T. Cromer, A. J. Ihde, and H. L. Ritter, J . Amer. Chem. SOC., 1951, 73, 5587.331 F. H. Herbstein and G. M. J. Schmidt, Nature, 1952, 168 323.332 E. H. Wiebenga, J . Amer. Chem. Soc., 1952, 74, 6156.833 E. W. Lund, Acta Chem. Scand., 1951, 5, 678.asp D. R. Davies and H. M. Powell, Nature, 1951, 168, 386DUNITZ AND ROBERTSON STRUCTURAL CHEMISTRY. 375Compounds containing sulphur or selenium. The structures of piazselenole,piazthiole, and benzofurazan (XVII; X = Se, S, and 0 respectively) havebeen determined.335 The molecules are planar and appear to possess theexpected symmetry. The distance N-X is given as 1.83, 1.60, and 1.20 Arespectively and N-C is close to 1.34 A in all three compounds. The mostinteresting feature of the bond lengths, however, is the very short distancequoted for C(1)-C(2) 1-30A and 1-29A in the selenium and the sulphurcompound respectively.The other C-C distances are all greater than 1.4 A.If these results are significant, they indicate almost complete double-bondfixation in the 1 : 2-position. It is noteworthy, though, that in a recentrefinement of the structure of p-isoprene sulphone, termination-of-serieserrors alone were found to cause changes in the atomic co-ordinates of asmuch as 0-06 A.336In the crystal the ring adopts the chairform; the angle C-Se-C is 99” and C-Se is found to be 2-01 A, rather longerthan the value (1.94A) based on Pauling’s covalent radii. The expectedvalue is found in diphenyl diselenide, where the planes of the phenyl groupsare almost normal to one another.338Benzene Derivatives.-9-Dichlorobenzene is isostructural with thedibromo-analogue; the crystal packing is of the parallel disc t ~ p e .3 ~ ~ In+-aminophenol,340 a polar structure, the rings are packed in layers, and theplane of the rings is almost normal to the layer plane ; three hydrogen bondsper molecule are formed. A three-dimensional analysis shows that theC-N bond distance is about 1.39 A, shorter than normal; C-0 is 1.47 A,longer than in other phenols. In m-tolidine,=l no hydrogen bonds areformed and the structure is very open. As in m-tolidine hydrochlorideand 2 : 2’-dichlorobenzidine, the phenyl groups are nearly normal to oneanother; such molecules must be rather awkward for packing purposes.Like diphenyl itself, 4 : 4‘-dihydroxydiphenyl must be planar, at least in thecrystal where a molecular centre of symmetry is imposed.342Carboxylic Acids.-The most common form of association in crystals ofthe monocarboxylic acids, dimerisation of type ( A ) , is now found to occur inp-chlorobenzoic a ~ i d , ~ ~ 3 salicylic acid,3& lauric acid, 117 “ isopalmitic acid,” 345and trans-p-ionylidenecrotonic acid (related to vitamin A) ,346 in addition toearlier examples. It is found also in potassium hydrogen carbonate, wherepairs of bicarbonate ions are linked as in (A).347 Formic acid, although itforms dimers in the gas phase,122 is associated in the solid, to form infinitechains of type (B).”* End-to-end bonding of type ( A ) , is also usual fordicarboxylic acids, though here, by association at both ends, infinite chainsDiselenan has been studied.33733s V.Luzzati, Acta Cryst., 1951, 4, 193.337 R. E. Marsh and J. D. McCullough, J . Amer. Chem. Soc., 1951, 73, 1106.338 R. E. Marsh, Acta Cryst., 1952, 5, 458.339 U. Croatto, S. Bezzi, and E. Bua, ibid., p. 825.3p0 C. J. Brown, ibid., 1951, 4, 100.341 F. Fowweather, ibid., 1952, 5, 820.342 S. C. Wallwork and H. M. Powell, Nature, 1951, 167, 1072.343 J. Toussaint, Acta Cryst., 1951, 4, 71.344 W. Cochran, ibid., p. 376.345 E. Stenhagen, V. Vand, and A. Sim, ibid., 1952, 5, 695.346 C. H. MacGillavry, A. Kreuger, and E. L. Eichhorn, Proc. K . Ned. Akad. We#.,347 I. Nitta, Y. Tomiie, and C. H. Koo, Acta Cryst., 1952, 5, 292.348 F.Holtzberg, B. Post, and I. Fankuchen, J. Chem. Phys., 1952, 20, 198.336 G. A. Jeffrey, ibid., p. 58.1951, 54, 449376 CRYSTALLOGRAPHY.rather than dimcrs are formed. Type (B) occurs too, in a-oxalic acid, forexample. Maleic acid 113 is an interesting case. One hydrogen atom formsa strong internal bond, so that, for intermolecular hydrogen bonding, wehave two carboxyl groups but only one hydrogen atom per molecule. Onceagain we find infinite chains, but of type (C}.Careful re-investigations have been made of the structures of a-oxalicacid,349 oxalic acid d i h ~ d r a t e , ~ ~ and ammonium oxalate m0nohydrate.~51The oxalic acid molecule is planar in both structures but the oxalate ion isnon-planar, the angle between planes of opposite carboxyl ions being 28".In none of these structures is the central C-C bond distance significantlydifferent from 1.54& so that the earlier interpretation of the evidence asfavouring a somewhat contracted central bond in the dihydrate must now bediscarded.As Jeffrey and Parry have indicated,352 the absence ofappreciable shortening is presumably due to removal of x-electrons from thecentral bond towards the more electronegative oxygen atoms. The relativestabilities of planar and non-planar forms of the molecules will thereforedepend only to a minor degree on the x-conjugation; the formal chargedistribution may be of greater importance.Amino-acids and Peptides.-There is no doubt that the amount ofprecise structural information available for amino-acids and peptides isgreater than for any other comparable class of molecules.The Pasadenagroup alone, in addition to providing several standard analyses, havecontributed no less than 7 determinations (for urea,115 ~-threonine,~5~ DL-alanine,3" N-a~etylglycine,~~~ hydroxy-~-proline,3~~ ~ ~ - s e r i n e , ~ ~ ? glycyl-L-asparagine 358) in which the full force of structure analysis has been broughtto bear on three-dimensional data. Other structure studies, for DL-methionine,359 g l ~ t a m i n e , ~ ~ and ~ysteinylglycine,~~~ have also added to theevidence. The results are, of course, of particular importance in connectionwith the recent Pauling-Corey protein models, and we shall mention one ortwo points which seem especially interesting.(1) theinvariable occurrence of zwit terions (acetylated glycine being an obviousexception) and (2) the tendency towards planar configurations.In the freeTwo main features seem to emerge from these structures :Sd0 E. G. Cox, M. W. Dougill, and G. A. Jeffrey, J., 1952,4854.360 F. R. Ahmed and D. W. J. Cruickshank, Acta Cryst., in the press.351 G.A Jeffrey and G. S. Parry, J . , 1952, 4864.363 D. P. Shoemaker, J . Donohue, V. Schomaker, and R. B. Corey, J . Amer. Chem.366 G. B. Carpenter and J . Donohue, ibid., p. 2315.JC* J. Donohue and K. N. Trueblood, Acla Cryst., 1952, 5, 419.557 D. P. Shoemaker, R. E. Barieau, J . Donohue, and C. S. Lu, 2nd Internat. Congr.'68 L. Katz, R. A. Pasternak, and R. B. Corey, Nature, 1952, 170, 1066.359 A.McL. Mathieson, Acta Cryst., 1952, 5, 332.360 W. Cochran and B. R. Penfold, ibid., p. 644.S6l H. B. Dyer, ibid., 1951, 4, 42.Idem, Nature, 1952, 169, 1105.SOC., 1950, 72, 2328. 554 J. Donohue, ibid., p. 949.Cryst., Stockholm, 1951DUNITZ AND ROBERTSON : STRUCTUR-41, CHEMISTRY. 377amino-acids one may distinguish two possible planar groupings. Thecarboxylgroups may lie coplanar with either the amino-group as in (a) (Fig. S),or the P-carbon atom (b). Type (a), shown by hydroxy-L-prolone, acetyl-glycine , serine, glycylglycine, and nearly so by threonine, alanine, andglutamine, is clearly favoured by the opposite charges of the NH,+ and the0FIG. 8. Planar groupings possible in amino-acids ( a and b) and peptides ( c ) .carboxyl-oxygen atom.It does not occur, however, in a- or p-methionineor the peptide glycyl-L-asparagine, which show instead planarity of type ( b ) .Both of these molecules contain carbon side chains and it seems possible thatthe preference for arrangement (b) may be associated with the tendency ofcarbon chains to adopt the planar zig-zag configuration, as, for example, inRFIG. 9. Some interatomic distances (in k ) and bond angles for glycyl-L-asparagine,with Corey-Donohue dimensions (in parentheses).the long-chain hydrocarbons and de~amethylenediamine.~~~ In peptides,planarity is found for the five atoms of the peptide group, of the type (c).This planar configuration, expected theoretically and already found inN-acetylglycine and in p-glycylglycine, has been confirmed again by theanalysis of glycyl-L-asparagine.Indeed, this molecule , lying almostexactly in two planes, simultaneously illustrated cases ( b ) and (c). Thecombination of planarity ( b ) and (c), if general in polypeptide structure,would impose a certain limitation on the mutual disposition of adjoiningpeptide groups, but more peptides must be studied before the importanceof this can be properly assessed.Turning to finer details, it is gratifying that the evidence of the last twoyears leaves the Corey-Donohue model 363 substantially unchanged. InFig. 9 it is compared with the results for glycyl-L-asparagine.The variation of the C-0 distances in the carboxyl ions is interesting.362 A. 0. McIntosh and J. M. Robertson, ibid., 1952, 5, 149.363 R.B. Corey and J. Donohue, J . Amer. Chem. SOC., 1950, 72, 2899378 CRYSTALLOGRAPHY.The isolated ion should be symmetrical ; in different crystal environments,double-bond fixation in one or other C-0 link is often present, to a greateror less degree, according to the symmetry of the hydrogenbonding with respect to the two oxygen atoms. Generallywe find that the oxygen with the longer link forms two,'O-.--. and that with the shorter only one, hydrogen bond (XVIII).Glutamine is exceptional here, as in this case it is the oxygen(XVIII) with the shorter link which has two hydrogen bonds, and theother only one, all being of roughly equal strength.The dimensions of the amide group as found in asparagine (C-0 1-22,C-N 1-38A) are similar to those in acetamide; but in glutamine the C-0and C-N distances are almost identical (1.28 A) , indicating considerabledouble-bond character in the C-N linkage. This is thought to be connectedwith the susceptibility of glutamine to hydrolysis or attack by nitrous acid.For asparagine, hydrolysis is slower and the amide group is not affected bynitrous acid.Incidentally, the petide analysis shows the asparagine residueto be an extended chain, and not cyclic as proposed recently,364 notwith-standing the fact that the amide and carboxyl groups are still free tointeract.0ximes.-Pitt 365 has drawn attention to the fact that, while thehydrogen atoms could not be located with certainty, application of stereo-chemical rules to the hydrogen-bonding arrangement in syn-@-chloro-benzaldoxime leads to the conclusion that the bonds are N-H*--O, whichwould imply that oximes are to be represented as RR'C:iH6, rather than,as usually written, RR'CN-OH.Although two new structure determinations are now available, it is stillnot possible to settle this point with certainty. In a ~ e t o x i m e , ~ ~ ~ themolecules are linked into trimers; the angle O-N-.-O is 129" andN-0-a.N is 111" so that the arrangement is compatible with eitherdisposition of hydrogen atoms.In dimethylgly~xime,~~~ each oxime groupis linked by hydrogen bonds to another related by a centre of symmetry.An obvious error occurs in the published paper where theangles N-0. - * N' and O-N - * * 0' are both given as 75.9".I 1.38A The centre of symmetry, however, requires that their sumbe 180".It would appear that N-O.*.N' is indeed about75", so we assume for the present that the published value75.9" refers to that angle and not to O-N-.*O', which is therefore 104.1".The arrangement is thus probably N-H * - * 0', in agreement with Pitt's sug-gestion and contrary to the usually accepted view. The dimethylglyoximeanalysis has been carried out in considerable detail with the use of full 3-di-mensional data. The refinement process was, however, effected by least-squares analysis only and it is to be regretted perhaps that the more orthodoxFourier method was not employed in this case since an (F, - F,) synthesismight have provided a quite unambiguous determination of the positionsof the hydrogen atoms.In dimethylglyoxime (and acetoxime), C-N is given as 1-27 A (1.29 A),0 ....--c/2-83 AN .. . . . 0'I 0.. . . . N'364 F. C. Steward and J . F. Thompson, Nature, 1952, 169, 739.365 G. J . Pitt, Ann. Reports, 1950, 47, 458.366 T. K. Bierlien and E. C. Lingafelter, A d a Cryst., 1951, 4, 450.367 L. L. Memitt and E. Lanterman, zbzd., 1952, 4, 811DUNITZ AND ROBERTSON : STRUCTURAL CHEMISTRY. 379N-0 as 1-38 A (1.36 A), quite consistent with double and single bondsrespectively. In dimethylglyoxime the central C-C bond is 1.44 A, slightlyshorter than the corresponding distance in buta-1 : 3-diene,122 and about0.1 A shorter than in oxalic acid.349Carbohydrates.-The crystal structure of a-D-glucose was reviewed in1950 but a fuller publication 368 allows us to mention several finer pointsrelating to the structure.Of the five hydrogen atoms available for hydrogenbonding, all are utilised in intermolecular bonds, four in inter-hydroxyllinkages, 2-70-2-78 A, and one in a hydroxyl-ring-oxygen link, 2-86 A. Itmay be noted that in the long bond the donor hydroxyl group does notitself accept hydrogen bonds from another atom, as in the other bonds.Another point of interest is the shortening, by about 0-1 A, of the C-0distance in the primary alcohol group-a feature shown also in cytidine andconnected possibly with the somewhat different chemical behaviour of theterminal CH2*OH. The a-OH in the reducing group position exhibits asimilar contraction. Unfortunately, the results for sucrose are notsufficiently accurate for a study of the details of bond distances, but thestereochemical configuration is given.369 The general shape of the sucrosemolecule in the sodium bromide compound is similar to that in sucroseitself, except that the molecule is rather more tightly curled, and oneterminal hydroxyl group is differently oriented.More accurate analysesof the sugars, comparable with those now available for several amino-acidsand peptides, would be of the greatest value.Steroids.-Following on the analyses of cholesterol and calciferol, twomore analyses, also by the " heavy atom " technique, have furthered ourknowledge of the steroid field, providing a detailed stereochemical picture oflanostenol 370 and l u m i ~ t e r o l .~ ~ ~ (Lumisterol is one of the compoundsformed during the photochemical transformation of ergosterol intocalciferol.) The inversion of the methyl group at C(lo) has been confirmed.In addition, the chair form of rings A and c has been found, together withthe &-configuration of the hydroxyl group. This is in agreement withrecent infra-red In the case of lanostenol (dihydrolanosterol)chemical evidence was considerably confused as to the D-ring system andthe point of attachment of the side chain. The X-ray evidence now showsring D to be &membered, and the c8 chain to be attached in such a waythat the molecule does not fit the isoprene rule. The latter result wouldsuggest that this and related triterpenes should really be considered astrimethylated steroids-a possibility emphasised by the co-existence oflanostenol and sterols such as ergosterol and cholesterol in Nature.Alkaloids.-The simultaneous confirmation of the strychnine structureby the chemical work and by two independent groups of crystallographerswas described in the 1950 report; fuller details of the analyses have nowappeared.373 A 2-dimensional analysis 374 of a colchicine adduct withCH,X, (X = Br or I) yields a projection which appears to confirm Dewar's3b8 T.R. R. McDonald and C. A. Beevers, Acta Cryst., 1952, 4, 654.369 C. A. Beevers, T. R. R. McDonald, J. H. Robertson, and F. Stern, ibid., p. 689.370 R. G. Curtis, J. Fridrichsons, and A. McL. Mathieson, Nature, 1952, 170, 321.371 D.C. Hodgkin and D. Sayre, J., 1952, 4561. 372 A. R. H. Cole, ibid., p. 4969.s7s J. H. Robertson and C. A. Beevers, Acta Cryst., 1951, 4, 270; C. Bokhoven,sT4 M. V. King, J. L. de Vries, and R. Pepinsky, ibid., 1952, 5, 437.J. C. Schoone, and J. M. Bijvoet, ibid., p. 275380 CRYSTALLOGRAPHY.ring structure 375 with the substituents placed according to Cech andS a n t a ~ y . ~ ~ ~ The structure of ergine is confirmed, also by %dimensionalanalysis, but with much better resolution of the individual at0ms.3~~ Thesolution of the structure was obtained from a difference Patterson mapprepared from the isomorphous hydrochloride and hydrobromide.Antibiotics.--A 3-dimensional analysis of chloramphenicol (and ofbromamphenicol) 378 confirmed the chemical structure of this well-knownantibiotic. The molecules adopt a curled configuration in the crystal,owing to a fairly strong intramolecular hydrogen bond between the twohydroxy-oxygen atoms. Attention is being given to terramycin and aureo-mycin, the close relation between this pair having been noted.379 Thecrystal structure of potassium benzylpenicillin has been refined by a second3-dimensional synthesis based on improved intensity data.380 Koj ic acid,a substance of mild bacteriostatic activity, has been studied, and itsconstitution confirmed.381Protein Structures.-As a comprehensive and far-reaching review of thisfield was given last year, we propose to mention in only the briefest termssuch developments as were not already covered in that report. X-Rayanalysis is being applied to a variety of proteins : a " carbonmonoxy-haemoglobin " ; 382 silk fibroin ; 383 p-lactoglobulin 384 and actinomycin 385(for the molecular weight); and others. Knowledge of the external formof the haemoglobin molecule 386 is being applied to sign determination; 73interpretation of the Patterson function is being contin~ed.~S~ Informationof a general kind as to the arrangement of polypeptide chains in the crystalhas been sought from 3-dimensional Patterson syntheses, notably forlysozyme hydrochloride 388 (using nearly 200 reflections) and for acid insulinsulphate 389 (where about 100 reflections were available).Of very great interest is the continuing discussion concerned with thenow well-known " 3-7 helix," the non-integral spiral structure proposed byPauling and Corey for the polypeptide chain. Cochran, Crick, and Vand 390have shown that the intensities of X-ray reflections given by poly-y-methyl-L-glutamate are in remarkably close agreement with the intensity distribu-tion predicted from the helix. The best agreements is obtained when thep-carbon atom is assumed to be in position 2.391 This is true also of bovine375 M. J . S. Dewar, Nature, 1945, 155, 141.376 J. tech and F. Santavy, Coll. Trav. Chim. Tchecosl., 1949, 14, 532.3 7 7 J. L. de Vries and R. Pepinsky, Nature, 1951, 168, 432.378 J. D. Dunitz, J. Amev. Chem. SOC., 1952, 74, 995.379 J . D. Dunitz and J. H. Robertson, ibid., p. 1108; R. Pepinsky and T. Watanabe,380 G. J. Pitt, Acta Cryst., 1952, 5, 770.381 H. A. McKinstry, P. F. Eiland, and R. Pepinsky, ibid., p. 285.383 Y. C. Tang, ibid., 1951, 4, 564.383 F. Happey and A. J. Hyde, Nature, 1952, 169, 921.s8p I . M. Dawson and D. P. Riley, ibid., 1951, 168, 241.s86 H. Sarlet, J. Toussaint, and H. Brasseur, ibid., p. 469.386 Sir W. L. Bragg and M. F. Perutz, Acta Cryst., 1952, 5, 277, 323.387 Sir W. L. Bragg, E. R. Howells, and M. F. Perutz, ibid., p. 136; F. H. C. Crick,388 R. B. Corey, J . Donohue, K. N. Trueblood, and K. J . Palmer, ibid., p. 701.388 B. W. Low, Nature, 1952, 169, 955.390 W. Cochran and F. H. C. Crick, ibid., p. 234; W. Cochran, F. H. C. Crick, andaD1 H. L. Yakel, L. Pauling, and R. B. Corey, N u t w e , 1952, 169, 920.Science, 1952, 115, 541.ibid., p. 381.V. Vand, ActaCryst., 1952, 5, 581DUNITZ .4ND IiOBERTSON STRUCTURAL CHEMISTRY. 381serum albumin, where the method of radial distribution curves was applied.392One rather important objection to the 3.7 spiral in poly-y-methyl-L-glutamate, the density discrepancy,393 seems to have been overcome by anew measurement of the unit-cell parameters.391 Another apparentdiffic~lty,~g~ that the dichroism of the C=O absorption band is not as markedas that of N-H, may have been removed by calculations which show that thedirection of the transition moment of the 1650-cm.-l band should be inclinedby about 20" to the C-0 direction, leading to a dichroic ratio comparablewith that experimentally observed.394 I t has been suggested that a coiledcoil is perhaps a general feature of polypeptide and protein structure, sincehelices inclined a t about 18" should pack together more effectively; themeridian reflection at 5.2 A given by a-keratin would be explained by thishypothesis.395 A symposium on the structure of proteins was held at theRoyal Society on May lst, 1952,396 and a Faraday Discussion on the bio-chemistry of proteins in August of the same year. Despite the bafflingcomplexity of this field, substantial progress is undoubtedly being made.We gratefully acknowledge assistance from Dr. B. Oughton, Mr. E. Wait,and Mrs. D. Crowfoot Hodgkin in the preparation of this report.J. D. DUNITZ.J. H. ROBERTSON.392 D. P. Riley and U. W. Arndt, Nature, 1952,169, 138.393 C. H. Bamford, L. Brown, A. Elliott, W. E. Hanby, and I. 1;. Trotter, ibid.,394 R. D. B. Fraser and W. C. Price, ibid., 170, 400.395 F. H. C. Crick, ibid., p. 882; L. Pauling and R. B. Corey, ibid., 1953, 171, 59.396 J . T. Edsall, ibid., 1952, 170, 53.p. 357

ISSN:0365-6217    

DOI:10.1039/AR9524900343

出版商:RSC    

年代:1952

数据来源: RSC

摘要:

INDEX OF AUTHORS' NAMES.Aamodt, L. C., 7.Abadir, B. J., 173.hbbey, S., 308.Abdel-Akher, M., 236, 244.Abd-el-Halim, F. M., 93.Abel, E., 47.Abell, P. I., 134.Ablondi, F., 227.Aboul Wafa, M. H., 232.Abrahams, S. C., 85, 351,Abrahamson, E. W., 324.Acampora, M., 327.Achhammer, B. G., 62, 332.Ackermann, H., 81.Ackermann, W. W., 259.Acland, J. D., 335.Adam, J. A., 305.Adam, N. K., 18, 24.Adams, E. G., 319.Adams, G., 332.Adams, M., 238.Adams, R., 157, 158.Adams, R. N., 323.Adams, T. J., 322.Adamson, A. W., 29, 42, 44.Addamiano, A., 368.Addison, C. C., 96.Adelberg, E. A., 252, 262.Aditya, S., 324.Agazzi, E. J., 319.Agius, P., 57.Ahlbrecht, A. H., 154.Ahmad, F. R., 370.Ahmad, R., 137, 140, 153,Ahmed, F. R., 376.Ahmann, D.H., 91.Ahrens, E. H., 202.Airoldi, R., 312.Ajtai, N., 116.Akino, H., 173.Albert, A., 216, 291.Albert, P., 340.Alberti, C. G., 268.Albenesius, E. L., 53.Albon, N., 243, 338.Alder, K., 177, 231.Alder, M. G., 70.Aleksandrov, S. N., 323.Alexander, E. R., 111.Alexander, P., 79.Alford, W. C., 320.Alfrey, T., 64.Aliminosa, L. M., 138.357.156.Allan, W. J., 314.Allen, A. O., 67, 72, 73, 79.Allen, C. F. H., 169.Allen, E., 326.Allen, M. B., 44.Allen, M. J., 135.Allen, P. W., 354.Allison, D., 340.Allsopp, C. B., 79.Allsopp, W. E., 323.Alper, T., 77.Alperowicz, I., 320.Aloisi, M., 272.Alter, H. W., 31, 95.Altermatt, H., 244.Altshuller, A. P., 30.Alvarez Querol, M. C., 303,Alves, F. A., 187.Amelinckx, S., 344, 345.Ames, D.E., 206.Ames, D. H., 158.Ames, S. R., 271.Ames, T. R., 188.Amiard, G., 267.Amis, E. S., 45.Amos, M. D., 315.Amphlett, C. B., 67, 75.Anand, N., 218.Anchel, M., 161.Anderson, A. G., 175, 176.Anderson, A. S., 249.Anderson, G., 333, 364.Anderson, G. W., 147.Anderson, H. H., 92.Anderson, J. A., 332.Anderson, J . R., 318.Anderson, J . R. A., 339.Anderson, J . S., 94.Anderson, P., 372.Anderson, R. B., 22.Anderson, R. C., 31, 194,Anderson, R. D., 40.Anderson, R. E., 337.Anderson, T. H., 366.Anderson, V. S., 50.Anderson, W., 250.Anderson, W. K., 325.AndG, T., 173, 174, 338,Andrews, E. A., 257.Andrews, P., 243.An&, E., 154.Angier, R. B., 217.313, 316.340.339.3 82Angus, W.R., 8.Angyal, C. L., 208.Angyal, S. J., 208.Anliker, R., 194, 195.Anning, S. T., 270.Antonucci, R., 198, 199.Aoyama, M., 267.Arai, T., 173.Archer, J. G., 290.Argersinger, W. J., jun., 30.Arkel, A. E. van, 94.Arlman, E. J., 135.Armen, A., 214.Armitage, J . B., 151.Arndt, U. W., 350, 381.Arnett, L. M., 58, 59, 116.Arnett, R. L., 13.Arnold, M., 319.Arnold, W., 155.Arond, L. H., 64.Arth, G. E., 192.Arthington, W., 338.Arthur, H. R., 189.Arthur, P., 322, 324.Arthur, T. E., 323.Artigas, J., 310.Ascenzi, A., 272.Asero, EL, 215.Ashley, S. E. Q., 300, 321.Ashmore, S. A., 338.Askonas, B. A,, 285.Asmis, H., 140, 199.Asmus, E., 328.Asprey, L. B., 104.Assarsson, G. O., 325.Asselineau, J., 161.Astasheva, A.A., 307.Atchison, G. J., 340.Aten, A. H. W., 340.Athanassiu, G., 271.Atkins, D. C., 308.Atkins, D. C., jun., 44, 82.Atkinson, B., 57.Atkinson, D. E., 261.Atkinson, R. O., 162.Atoji, M., 351, 367.Attenburrow, J., 140, 151.Attridge, C. F., 174, 210.Audrieth, L. F., 85.Augood, D. R., 119, 121,Auerbach, V. H., 275.Aurivillius, B., 365.Aurivillius, K. L., 367.Aven, M., 337.123INDEX OF AUTHORS’ NAMES. 383Avener, J., 264.Avison, A. W. D., 277.Axford, D. W. E., 13.-4ycock, B. F.. 134.Ayengar, P., 264.Aynsley, E. E., 98, 101Ayres, A., 244.Ayres, G. H., 329, 330.Babcock, J. C., 198.Bach, R. O., 336.Bachrach, J., 244.Bachtold, J . G., 245.Backeberg, 0. G., 319.Bacon, A., 311, 327.Bacon, G. E., 352, 355.Bacon, J .S . D., 243.Bacq, 2. M., 270.Badami, G. N., 320.Baddiley, J., 162, 207, 280,Bader, F., 223.Badger, G.M., 112, 113, 124.Badoz, J., 322.Bachli, P., 242.Baenziger, N. C., 366, 367.Baer, H., 203.Baes, C. F., jun,, 49.Bahner, C. T., 154.Baier, E., 161.Bailar, J . C., 308.Bailar, J. C., jun., 82, 109,Bailey, F. E., jun., 29.Bailey, G. L. T., 24.Bailey, J. L., 140.Bailey, J . M., 239.Bailey, M., 363.Bailey, N. H., 313.Baker, B. B., 322.Baker, B. R., 141, 227.Baker, W., 143, 165, 166,168, 169, 232, 233, 338.Balder, A., 325.Balenovid, K., 162.Balis, E. W., 336.Ball, G. T., 138.Ball, J. S., 136.Ball, S., 142.Ballard, C. W., 320.Ballard, S. A., 204.Ballczo, H., 302, 336.Ballinger, D. G., 324.Ballou, C.E., 236.Balston, J. N., 337.Bamford, C. H., 61, 381.Banerjee, K., 347.Banewicz, J. J . , 305.Bangham, D. H., 18, 19, 20.Banholzer, K., 219.Banks, C. V., 353.Banks, J., 305, 307, 317,Banks, W. H., 32.Bannerjee, D. K., 193.Banus, M. D., 88.Barb, W. G., 58, 61, 75.295.144.327.Barbezat, S., 161.Barcia Goyanes, C., 340.Barcsay, J., 319.Bardos, T. J., 257.Bardsley, H., 63.Barefoot, R. R., 314.Barger, G., 223, 228, 293.Barieau, R. E., 376.Barker, G. C., 323.Barker, G. R., 249.Barker, H. A., 253.Earker, I. R. L., 143.Barker, S. A., 203, 235, 239,Barker, S. B., 291, 294.Barltrop, J. A., 209.Barnartt, S., 28.Barnes, C. S., 184.Barnes, G. T., 34.Barnes, J. D., 269.Barnes, J. H., 294, 295.Barney, J.E., 330.Barnicot, N. A., 269.Barnum, D. W., 317.Barr, J. T., 154, 308.Barratt, R. W., 244.Barrer, R. M., 22.Barrett, B. J., 240.Barrett, E. P., 23.Barrett, K. E. J., 117.Barrow, G. M., 17.Bartell, I?. E., 24, 26.Bartell, F. G., 24.Bartels-Keith, J . R., 172.Bartha, L., 315.Bartha, L. G., 341.Bartindale, G. W. R., 72.Bartlet, J . C., 326.Bartlett, M. F., 163.Bartlett, P. D., 60, 115, 125,129.Barton, D. H. R., 37, 179,180, 181, 183, 184, 185,187, 188, 189, 198.242.Barton, G. M., 338.Barton-Wright, E. C., 252.Bartram, K., 137.Basford, P. R., 27.Basolo, F., 49, 82, 308.Bassett, H., 87, 90.Bastiansen, O., 372, 373.Basu, S., 60.Bateman, L., 117, 129, 136.Bates, R. G., 33, 317.Batey, H.H., 98.Batres, E., 194.Battegay, J., 226.Baudler, M., 100.Bauer, B. T., 27.Bauer, C. D., 274.Bauer, J. M., 270.Bauer, L., 89.Bauer, R., 307.Baumann, C. A., 201, 270.Bawn, C. E. H., 116, 135.Baxendale, J . H., 75, 136.Baxter, J. G., 270.Baxter, S., 24.Bayer, L., 100.Bayly, R. J., 235, 338.Baysal, B., 59.Beach, G. W., 267.Beach, J . Y., 7.Beamer, W. H., 340.Beamish, F. E., 311, 314,Beaty, R. D., 119.Beaumont, R. H., 328.Beaven, G. H., 218.Bebbington, A., 239.Beck, M., 316.Becker, B., 155, 219.Becker, E. I., 202.Becker, K. A., 359.Becker, R., 343.Beer, R. J . S., 127, 214.Beevers, C. A., 346, 363,Begtrup, W., 273.Behrens, H., 106.Behringer, H., 163, 215.Belanger, J. R., 357.Belcher, E. P., 206.Belcher, R., 312, 314, 318,319, 321, 325.Bell, D. J., 240, 243.Bell, E.E., 9.Bell, E. R., 126, 128.Bell, G. H., 269.Bell, I. P., 348.Bell, R. K., 329.Bell, R. N., 85, 324.Bell, R. P., 15, 16, 51.Bell, S. H., 26.Bell, W. E., 333.Belle, J., 103.Belt, M., 253.Belyakov, A. A., 332.Bendigo, B. B., 329.Benedetti-Pichler, A. A.,Benesi, H. A., 105.Benington, F., 141.Bennett, R., 292.Behnett, V., 292.Bennett, W. E., 89.Benson, S. W., 36, 54.Benstead, J. C., 234.Bentley, H. R., 226.Bentley, J . A., 215.Bentley, K. W., 221, 222,Beppu, I., 233.Berenbaum, M. B., 115,116, 132,Berg, A., 336.Berg, C. P., 144.Berg, D., 29.Berg, E. W., 330.Berger, S. V., 360.Bergman, B. G., 357.Bergmann, E. D., 174.Bergmann, F., 329.Bergmann, J .G., 49.329.379.311, 332.223384 INDEX OF AUTHORS' NAMES.Bergmann, M., 146.Bergmann, W., 202.Bergstrom, S., 159, 271.Berguer, Y., 214.Beri, R. M., 338.Berlie, M. R., 39.Berlin, T. H., 28.Berlingozzi, S., 338.Bermejo Martinez, F., 310.Bernal Nievas, J., 324.Bernard, W. J., 104.Berne, E., 336.Bernhard, S. A., 342.Bernhart, F. W., 274.Bernsohn, E., 103.Bernstein, I. A., 125.Bernstein, R. B., 9, 35, 45,I3ernstein, S., 198, 199, 274.Berquier, F. le, 305.Berry, M. E., 261.Bersin, T., 189.Berson, J. A., 166.Bertaut, E. F., 361.Berthier, G., 174.Berthed, H., 174.Bertiaux, L., 330.Bertin, C., 322.Besso, 2.. 323.Besson, J., 313.Betz, L. D., 327.Bhillard, P., 309, 312.Hevington, J.C., 41, 59, 116.Bewick, H. A., 326, 327.Beyer, G. H., 94.Reyler, R. E., 190, 192.Beyles, R. G., 313.Bezdek, M., 309.Bezzi, S., 368, 375.Bhar, C., 233.Bhatia, D. S., 79.Bianchi, F., 309.Biava, F. P., 319.Bick, I. R. C., 221.Bickel, A. F., 115, 116, 117,Bide, A. E., 267.Biel, J. H., 207.Bierlien, T. K., 378.Bigeleisen, J., 44, 52, 340.Bigelow, L. A., 154.Biggs, D. A., 326.Bijvoet, J. M., 379.Bikerman, J. J., 18.Bilby, B. A., 344.Biletch, H., 115.Bill, J. C., 174.Billeter, J . R., 193.Billmeyer, A. M., 302.Binks, J. B., 80.Birch, A. J., 168, 189, 193.Birch, S. F., 150, 212.Bird, 0. D., 254.Birdsall, C . M., 315.Birkofer, A., 130.Birkofer, L., 139.Bisen, R., 328.59.122.Bishop, E., 324.Bittel, R., 327.Bjerrum, J., 48.Bjorklund, C.W., 24,Blacet, F. E., 55, 333.Blachly, C . H., 326.Black, S., 278.Blackmore, A. P., 314.Blackmore, B., 273.Bladon, P., 145.Blaedel, W. J., 302, 324,Blaha, F., 311.Blair, M. G., 241.Blanchard, M. L., 256.Blanchard, P. H., 243.Blanchette, J . A., 204.Blandau, R. J., 271.Blanquet, P., 80.Blasco L6pez-Rubi0, F.,Blasius, E., 336.Blaxted, K. L., 2'70.Blewett, M., 274.Blicke, F. F., 207.Bliss, C. I., 267.Block, K., 201, 219, 286.Block, M. IZ., 315.Block, R. J., 337.Block, W., 219.Blodinger, J., 147.Blomberg, B., 333.Blomfield, G. W., 291.Blomquist, A. T., 59, 125,Blood, C. T., 174, 175.Bloom, B. M., 155, 219.Blumenthal, H., 99, 356.Boag, J . W., 76, 79.Boardman, H., 114.Boarland, M.P. V., 208,Boaz, H., 209, 253.Bobtelsky, M., 327.Bode, H., 329, 363.Bockley, E., 106.Bohm, H., 176.Boehm, R., 189.Boekelheide, V., 225.Boer, H., 111.Boer, J. H. de, 94.Boesch, T. F., 236.Boeseken, J., 139.Bogert, V. V., 210.Boggiano, E., 265.Roggiano, E. M., 264.Boggs, L. A,, 338.Bogorad, A. S., 323.Bohlmann, F., 137, 141,Bohonos, N., 254, 264, 266.Bohrer, J . C., 177.Boissonnas, R. A., 146, 147,Roit, H. G., 226.Bokhoven, C., 379.Boldebuck, E. M., 88.325.327.156, 177.209.151, 210.148, 149.Bolger, J . W., 234.Bolland, J . L., 129, 136.Bolliger, H. R., 141.Doltz, D. F., 328, 329.Boman, H. G., 250, 335.Bond, T. J., 257.Bonet-Maury, P., 73.Bonetti, E., 272.Bonnafous, L., 322.Bonner, D., 262, 265.Bonner, D.M., 262.Bonner, 17.. 44.Bonner, L. G., 11.Ronner, N. A., 43.Bonner, 0. D., 30.Bonner, W. A., 138.Bonnet, J., 336.Bonsall, E. P., 61, 117, 135.Boord, C. E., 150, 177.Booth, A. D., 349.Booth, E., 305.Booth, G. H., 56.Boothe, J. H., 217.Borek, E., 263.Borrows, E. T., 295.Borsche, W., 296.Bortolotti, T. R., 305.Borzee, A., 51.Bosch Ariiio, F. de A., 316.Boscott, R. J., 334.Bose, A. K., 179, 203.Bosshardt, D. K., 264.Boston, C. R., 49.Bothner-By, A. A., 33, 48,Boughton, B. W., 158, 274.Bourdon, D., 312.Bourne, E. J., 150, 203, 235,Bourns, A. N., 52, 53, 205.Bowden, F. P., 21.Bowden, K., 207, 219.Bowen, T. J., 246.Bower, J. E., 24.Bowman, R. E., 146, 158,Box, G.E. P., 302.Boyack, G. A., 270.Boyd, A. M., 272.Boyd, D. R. J., 10.Boyd, G. E., 18, 105.Boyd, J. R., 327.Boyd, M. J., 257.Boyd, W. L., 256.Boyer, P. D., 270, 271.Boyland, E., 170.Boyle, A. J., 305.Boyles. H. R., 53.Bradbury, R. B., 233.Braddock, L. I., 332.Bradfield, A. E., 231.Bradley, C. A.. 14.Bradley, D. C., 82, 93.Bradlow, H. L., 197.Bradshaw, G., 328.Brady, A. P., 29.Bragdon, R. W., 88.340.239, 242, 248, 338.206INDEX OF AUTHORS’ NAMES. 385Bragg, J. D., 17.Bragg, J. K., 59.Bragg, (Sir) W. L., 348, 380.Brain, F. H., 86.Brandstatter, M., 318.Brandt, G. A. R., 101.Brandt, W. W., 49, 108, 307.Brasseur, H., 380.Brasted, R. C., 311.Brasted, R. 0.. 316.Brattsten, I., 339.Braude, E. A,, 139, 142,Brauer, G., 92.Braun, B.H., 158.Braun, K. C., 327.Bravo, j. B., 105.Bray, R. H., 305.Brayne, M. K., 294.Breck, D. W., 92.Bregman, J . I., 83.Breil, B., 100.Brcitenbach, J. W., 58, 59.Breithaupt, L. J., jun., 85.Bremer, R. F., 135.Bremner, J. M., 338.Brenner, A., 179.Bretschneider, H., 116.Brctton, R. H., 71.Brewer, P. I., 305.Brewerton, H. V., 234.Brewster, D. A., 326.Bricker, C. E., 322, 329, 331.Bridges, R. G., 340.Briggs, L. H., 227, 231, 232.Bright, H. A., 327, 329.Brill, R., 355.Brindle, T., 303.Brindley, G. W., 361, 362.Brink, C., 366.Brink, N. G., 218.Brinkley, S. R., 9.Brinton, R. K., 38, 40.Britton, H. G., 314.Broach, W. J., 326.Broadhurst, T., 127, 214.Brockman, J. A., 158, 209,Brockman, J .A., jun., 253,Brockmann, H., 170, 171.Brockway, L. O., 7.Bromer, W., 309.Broh-Kahn, R. H., 285.Broida, H. P., 340.Bromund, W. H., 311.Brook, A. G., 372.Brooker, E. G., 227.Brookes, W., 11.Brooks, C. J . W., 188.Broomhead, J. M., 373.Broquist, H. P., 217, 253,256, 257, 258.Brotzen, O., 364.Brouns, R. J., 322.Brown, C. A., 88, 89.Brown, C. J., 164, 352, 375.143, 152.217, 226, 227.257.REP.-VOL. XLIX.Brown, C. S., 344.Brown, D. J., 216.Brown, D. M., 204, 217,Brown, E. D., 327.Brown, E. V., 204.Brown, F., 53, 270.Brown, G. M., 264.Brown, H. C., 56, 90, 117,Brown, J. A., 338.Brown, J. B., 215.Brown, J. F., jun., 89.Brown, J . J., 212.Brown, J. S., 326.Brown, K. D., 250.Brown, L., 381.Brown, M., 197.Brown, M.J., 24.Brown, R. A., 267.Brown, R. D., 124, 171, 174.Brown, S. A., 219.Browne, C. L., 202.Brubaker, C. H., jun., 100.Brubaker, M. M., 126.Bruce, G. T., 235.Bruin, P., 117.Brumblay, R. O., 327.Brunauer, L., 23.Brunings, I<. J., 138.Brunisholtz, G., 336.Brunner, M. P., 195.Bruson, H. A., 203.Brustier, V., 330.Bruun, T., 152, 180, 181,Bryant, B. E., 304.Bryant, F., 335.Bryer, W. M., 9.Rua, E., 368, 375.Buchan, J . L., 338.Buchanan, D. L., 341.Buchanan, R. H., 321.Buchi, G., 125.Buck, R. P., 322.Buckingham, R. A., 14.Buckles, R. E., 318.Buckley, E. S., 305.Buckley, H. E., 344, 345.Buckley, M. I., 243.Budd, M. S., 326.Budde, G.. 170.Buddecker, I., 109.Budenz, R., 313.Budziarek, R., 187, 194.Buell, M.V., 239.Buerger, Rii. J., 346, 347,Buisman, J. A. K., 267.Bukin, V. N., 267.Bulgozdy, E. L., 357.Bullock, M. W., 158, 209,Bu’Lock, J. D., 214.Bumsted, H. E., 326.Bunce, B. H., 249.Bunn, C. W., 344.246, 247, 248.132.189.349, 361.253.Bunton, C. A,, 50, 52.Burawoy, A., 12.Burbank, R. D., 347.Burchenal, J. H., 258.Burchuk, I., 203.Burg, A. B., 88, 97.Burg, C., 274.Burg, M., 176.Burge, R. E., jun., 177.Burger, A., 141, 177.Burger, M., 234.Burgers, J. M., 343.Burgess, A. K., 62.Burgess, J . F., 272.Burltat, S. E., 332.Burket, S. C., 236.Burkhalter, T. S., 325, 335,Burkitt, F. H., 12, 123.Rurley, R. A., 332.Burma, D. P., 339.Burn, I)., 229.Burnelle, L., 9.Burns, W.G., 55.Burriel, I?., 301.Burriel Marti, F., 316, 323,325, 331, 342.Burrill, A. M., 342.Burrows, S., 335.Burstall, F. H., 99, 107,Burton, M., 40, 65, 66, 68,Burton, R. B., 334.Burton, T. M., 154.Burton, W. K., 343.Buscar6ns, F., 310, 320.Bush, I. E., 202, 334.Butenandt, A., 163.Butler, B., 255.Butler, J . A. V., 249.Butler, J . ID., 29, 322.Buzzell, A., 368.Byerrum, R. U., 219.Bystrom, A., 363, 364, 366.Bywater, S., 41.Cabannes, J., 17.Cabell, M. J., 306.Cabrera, N., 343.Cadle, R. D., 39.Cagle, F. W., jun., 52.Cahill, A. E., 50, 100, 130.Cahill, J. J., 218.Cahnmann, H. J., 328.Cain, C. K., 216.Cairns, T. L., 158, 209.Calbert, C. E., 274.Caldas, E. F., 321.Caldwell, M. L., 238.Caliezi, A., 179.Calkins, D.G., 218, 259.Call, P. J., 340.Callis, C. F., 308.Callomon, H. J.. 11, 15.Calvert, J. G., 54.Calvin, M., 52, 209.341.304, 339.69, 70.386 INDEX OF AUTHORS’ NAMES.Calvo, C., 85.Cama, H. R., 152.Camerino, B., 268.Cameron, A. 1;. B., 140, 151.Camien, M. N., 255.Campbell, A. D., 174, 175.Campbell, G. W., jun., 88.Campbell, H. C., 176.Campbell, J . A., 267.Campbell, 31. E., 327.Campbell, N., 170.Campbell, P. N., 239.Campbell, R. B., 172.Campbell, T. IV., 123, 127,Campen, W. A. C., 328.Campillo, A. del, 256, 279.Candela, G. A., 21.Canham, R. G., 33.Canna, H. R., 142.Cantoni, G. L., 287.CArceles, F., 313.Cardone, M. J., 329.Cardwell, H. M. E., 353.Cardwell, P. H., 24.Carini, F. F., 305.Carlin, R.B., 213.Carlisle, C. H., 368.Carlson, A. B., 307, 327.Carlson, W. W., 242.Carlton. J . K., 335, 337.Carmo Anta, M., 76.Carmody, W. R., 302.Caron, M., 340.Carpena, O., 324.Carpenter, D. L., 322.Carpenter, F. H., 146.Carpenter, G. B., 360, 376.Carroll, B., 238.Carson, J . F., 190.Carter, H. E., 162.Carter, P. R., 46.Cartwright, N. J., 166.Casaletto, G. A., 138.Casey, R. S., 308.Cashin, W. M., 368.Casini, A., 309.Cason, J., 168.Cass, R., 93.Cass, W. E., 125.Cassel, H. M., 21.Cassidy, H. G., 337.Cassie, A. B. D., 24.Castor, C. R., 324.Castrillh, J. A., 219.Caunt, A. D., 14.Cavalieri, L. F., 217.Cave, G. C. B., 323, 327.Cech, J., 380.Cefola, M., 333.Celmer, W. D., 160, 210.Celsi, S . A., 315.Cerar, D., 162.Certa, A.J.. 305.Chaberek, S., 307.Chaberek, S., jun., 30, 81.Chaikoff, I. L., 292.219.Chakravarti, D., 233.Chalkley, L., 57.Chalmers, J . R., 295.Chalmers, R. A., 314.Chamberlin, E. M., 138,Chambers, J . W., 269.Champ, P., 314.Chance, J., 326.Chanda, S. K., 245.Chandler, A. B., 330.Chang, F. N.-H., 272.Chang, H. C., 28.Chanley, J. D., 140.Chantrenne, H., 286.Chao, H. C., 268.Chapiro, A., 68, 70, 71.Chapman, D. W., 146.Chapman, J. H., 140, 151.Chapman, R. A., 326.Chargaff, E., 249, 250.Charlot, G., 322.Charpy, J., 269.Chase, B. H., 209.Chateau, H., 324.Chatt, J., 83.Chaudron, G., 340.Chaves Lavin, L. R., 309.Cheesman, G., 216.Chekhoskaya, V. A., 61.Chemerda, J. M., 138, 194,Chen, P.S., 327.Chen, Y. T., 92.Chen-Chuan Tu, 235, 244.Chenery, E. M., 327.Cheronis, N. D., 318.Chesney, G., 275.Chevallier, A., 274.Chevrel, M. L., 271.Chia, C. L., 29.Childers, C. W., 29.Chin, L. J., 193.Chopard-dit- Jean, L. H.,Choppin, G. R., 89.Chrisp, J. D., 326.Christen, K., 186.Christensen, B. E., 211.Christian, J. W., 357.Christian, W., 217.Christiansen, J. A., 47, 50.Christie, M. I., 53.Christie, S. RI. H., 218.Christman, A. A., 264.Christman, J. F., 256.Chu, E. C., 259.Chu, H. I., 268.Chuylto, V. T., 328.Ciaranfi, E., 329.Clabaugh, W. S., 93.Claesson, S., 360.Claflin, E. F., 210.C.laiborne, I., 30.Claret, M., 339.Clark, D., 166, 358.Clark, R. K., 210.194, 195.195,175.Clark, S. J., 321.Clark, V.M., 218.Clarke, J . T., 124.Clarke, P., 318.Clarke, R. L., 332.Claus, C. J., 210.Clausen, H., 363.Clauson-Kaas, N., 201.Claussen, W. F., 360.Clayton, J . C., 293, 295.Clemo, G. R., 180, 182.Cleveland, I;. C., 237.Cleveland, I;. I?., 9.Clow, A., 85.Clunie, J . C., 51.Clusius, K., 213.Coates, G. E., 86, 87, 93.Cobble, J . W., 29, 105.Cochand, C., 151.Cochran, W., 348, 350, 352,373, 375, 376, 380.Cockaday, R. E., 314.Cockburn, W. F., 220.Cocker, W., 180, 183.Codell, M., 330.Coderre, R. C., 193.Coffman, D. D., 61, 126.Cohan, L. H., 23.Cohen, A., 207.Cohen, A . J., 85.Cohen, D., 34.Cohen, J. A., 285.Cohen, L. A., 193.Cohen, P. P., 286.Cohen, S. G., 115.Cohen, S. S., 249, 290, 291.Colclough, R.O., 63.Cole, A. R. H., 145, 184,Coleman, J . E., 127, 143.Coles, J . A., 142.Collentine, G. .E., 273.Collin, R. L., 351, 354, 357,Collingsworth, D. R., 195.Collinson, E., 71, 72, 78.Colman Porter, C. A., S O ,GAG, IT., 215.Colombo, U., 144, 342.Colonge, J ., 154.Colton, F. B., 196.Comombi, L., 179.Compton, J., 329.Comte, C., 50.Conbere, J . B., 196.Conduit, C. P., 96.Connick, R. E., 34, 103.Conroy, H., 234.Conroy, L. E., 102.Consden, R., 236, 339.Constantin, J . M., 190.Conway, B. E., 68, 249.Cook, A. H., 190.Cook, C. L., 151.Cook, G. B., 339.Cook, G. L., 333.201, 379.361.33INDEX OF AUTHORS' NAMES. 387Cook, J . LV., 141, 170, 173,174, 210, 212, 224.Cooke, W. D., 322.Coolrson, R. C., 294.Coon, M.J., 258.Coop, I . E., 16.Cooper, G. D., 120.Cooper, H. R., 136.Cooper, S. R., 315, 324.Cooper, W., 59, 124, 128.Cope, A. C., 176.Copello, M. A., 315.Copp, D. H., 269.Coppinger, G. M., 123, 12'7.Coppins, W. C., 326.Corbridge, D. E. C., 355.C.orby, N. S., 218.Corey, XI. M., 271.Corey, R. B., 376, 377, 380,Cori, G. T., 237, 240.Cormier, M., 271.Cornec, P., 330.Cornforth, J . W., 315, 219.Corrin, M. L., 22.Cortell, R. E., 294.Corvin, I., 332.Cosgrove, S. L., 123, 130.Cos:ilich, D. N., 217, 257.Cotman, J . D., 129.Cottin, M., 46, 76.Cotton, F. A., 172.Cottrell, A. H., 314.Cottrell, T. L., 358.Coulson, C. A,, 11, 15, 17,122, 123, 354, 355, 356,371.381.Coulson, D. &I., 135.Coulter, L.V., 21.Courrier, R., 293.Coursen, D. L., 88, 366.Coursier, J., 322.Courtney, R. C , 81, 307.Cousin, C., 70.Covey, G. W., 270.Covo, G. A., 275.Cowdrey, W. A., 120.Cowley, P. R. E. J., 58, 62.Cox, E. G., 376.Cox, H. E., 267.Cozzi, D., 323.Craggs, J . D., 65.Craig, J . A., 254.Craig, L. C., 202, 337.Craig, L. E., 176.Cram, D. J., 111, 164.Cramer, F., 369.Crane, R. I<., 284.Crank, J., 35.Crawford, B. L., 7, 9, 13, 15,Crawford, J . W. C., 61.Crawhall, J . C., 208.Creasey, N. H., 239.Cremer, E., 54.Cresson, E. L., 212, 256.Crick, F. H. C., 380, 381.16.Criegee, R., 112, 1-34, 127,Cristol, S. J., 202.Croatto, U., 375.Cromartie, R. I . T., 215.Crombie, L., 146, 153, 159,Cromer, D. T., 374.Cron, XI.J.. 246.Cross, B. E., 180, 183.Cross, PI. J . , 258.Cross, 1'. C., 16.Cross, I<. J . , 276.Croutharnel, C. E., 328.Crow, W. D., 173.Crowell, r\. IV., 135.Crowfoot, D., 268.Crozier, R. N., GO.Cruickshank, 13. 'Llr. J.,349, 370, 376.CsAnyi, L., 315, 342.Cubicciotti, D., 87.Cuculo, J . PL., 154.Cuendet, L. S., 338.Cuezzo, J . C., 327.Culbertson, H., 213.Culbertson, J . O., 37.Cullum, T. V., 212.Cumming, L. W., 317.Cunningham, B. R., 34, 103.Cunningham, S. T>., 331.Curless, IV. T., 324.Curme, H. G., 42, 55.Currah, J . E., 320.Curti, R., 144.Curti, U., 342.Curtin, D. Y., 132.Curtis, H. A., 26.Curtis, R. G., 184, 201, 379.Curtius, T., 146.Culforth, H. G., 136.Cuthbertson, 14'. F. J., 294.Cutter, 3 .O., 26.Cutts, N. S., 258.Cvetanovic, R. J., 41.Cymerman, J , , 206.Daane, A. H., 91.Dacons, J . C., 235.Dallenbach, H. R., 194.Dahl, S., 320.Dahlerup-Petersen, B., 148.Dahlstrom, R., 18.Dailey, 13. P., 17.Dainton. F. S., 46, 55. 58.178.160, 180.61, 65; 66, 68, 71, 72, 73;76, 77, 79, 135.Dale, W. M., 77, 79.Dalen, E. van, 319.Dalgliesh, C. A., 215.Dalgliesh, C. E., 144, 162.Dalvi, P. D., 142, 152.Dam, H., 270, 273, 275.D'Rmico, J. J., 154.Danby, C. J., 37.Danielli, J . F., 290.Daniels, D. G. H., 123.Daniels, F., 53.Daniels, T. C., 272.Dannley, R. L., 123.Danowski, T. S., 270.Darling, B. T., 11.Darling, T. A., 22.Darwent, B. de B., 51, 56,Das Gupta, A. K., 339.Dasler, W., 274.Dauben, C. H., 367.Dauben, W.G., 145, 197,Daudel, P., 46.Daudel, R., 371.Dautzenberg, \Y., 327.David, S., 190.Davidson, A. W., 30, 89.Davidson, J., 327.Ua\:idson, X., 46.Davidson, S., 40.Davies, A. G., 127.Davies, C. W., 31, 32, 33,Davies, D. R., 374.Davies, D. S., 120.Davies, J . A., 29.Davies, J. V., Ti.Davies, &I., 353.Davies, M. 7., 218.Davies, N. S., 26.Davies, 12. E., 2YC.Davies, T. W., 73.Davies, W. C., 323.Davis, A., 9.Davis, B. D., 206, 253, 254,Davis, H. C., 31 1 .Davis, M. M., 341.Davis, P., 122.Davis, R. C., 202.Davis, R. H., 159, 272.Dawson, 1. M., 269, 344,Dawson, J., 270.Dawson, J . I<., 103.Dawson, L. I<., 33.Dawson, T. L., 180.Day, 17. P., 209, 253.Day, M. J., 68, 72, 78.Dayhoff, M.O., 29, 30.Dean, F. M., 230.Dean, L. A., 33'7.Dean, R. A., 212.Dean, R. B., 317.Debney, E. W., 305.De Busk, B. G., 209, 253,Decius, J . C., 8, 11, 211.Decker, B. I?., 357.Decker, C. E., 9.Dee, P. I., 66.De Ford, D. D., 340.De Haas, I3. MI., 161.Deibner, L., 318.Dekeyser, W., 344.Dekker, C. A . , 217, 348, 260.57.199.31.259, 260, 262, 266.380.254388 INDEX OF AUTHORS’ NAMES.Delabarre, Y., 340.Delahay, P., 322.De la Mare, H. E., 126.Delluva, A. M., 264.Deltour, G. H., 292.Demarteau, H., 161.Denison, F. W., 338.Denk, G., 89, 315, 316.Denney, T. O., 30.Dennison, D. M., 7, 10, 11.Deno, N. C., 192.Denyer, R. L., 212.Deparade, W., 114, 115.Depke, F., 127.Derbyshire, D. H., 50, 134.Derfer, J.M., 150, 177.De Rose, A. F., 210.Deshmukh, G. S., 315, 317.DeTar, D. F., 118, 119, 121,Deuel, H., 244.Deuel, H., jun., 274.De Vries, G., 166, 319.De Vries, J . L., 172, 359,De Vries, T., 30.DeWalt, H. A., 210.Dewar, M. J. S., 111, 112,122, 172, 380.DeWatt, C. W., 335.Dewey, D. L., 261.Dewhurst, H. A., 75, 76.D’Eye, R. W. M., 94, 366.Diamant, E., 134.Dibeler, V. H., 333.Dickel, G., 336.Dicltens, D. J., 357.Dickens, F., 290.Dickey, F. H., 202, 342.Dickson, G. T., 294, 295.Di Domenico, J., 141.Diehl, H., 322, 328.Dieke, G. H., 331.Dierichs, W., 156.Dietrich, P., 183.Di Giacomo, Al, 172.Dijk, J . van, 111.Dijksman, D. J., 212.Dijkstra, R., 53.Dillon, R. T., 328.Dilts, R. V., 322.Dimler, R. J., 338.Dinges, K., 114.Dingle, J., 244.Dinsmore, H.L., 16.Dion, 13. W., 218, 259.Dippel, W. h., 331.Dirks, H. B., jun., 294.Diskant, E. M., 304.Dismukes, E. B., 29, 83.Dittmer, K., 256.Diuguid, L. I., 156.Dixon, J. S., 249.Djerassi, C., 143, 194, 195,196, 198, 200.Doadrio, A., 317.Doak, G. O., 121.122.379, 380.Doan, U. At, 313.Dobeneck, H., 214.Dobres, R. M., 113, 114.Dobriner, K., 145, 197, 201.Dobrowsky, A , , 219.Dodd, R. E., 55.Dodson, R. W., 43.Doering, W., 343.Doering, W. von E., 133,166, 172, 173.Doisy, E. A., 211.Dole, M., 50, 100.Donahue, J . F., 322.Donaldson, K. O., 335.Donau, J., 299.Done, J., 162.Donk, E. C. van, 274.Donnay, G., 361.Donohue, J., 346, 352, 353,358, 360, 376, 377, 380.Doody, E., 308.Doorgeest, T., 340.Dorfman, L., 274.Dorfmann, L.hq., 126.Dorlars, A., 170.Douglas, B. E., 304.Dorp, D. A. van, 196.Dortmann, H. A., 177.Dostrovsky, I., 100.Doty, P., 249.Doudoroff, M., 241Dougill, M. W., 376.Douglas, A. M. B., 357.Douglas, C. D., 231.Doukas, H. M., 200.Dousmanis, G., 7.Dowdy, A. H., 66.Dowling, G. B., 269.Downes, A. M., 53.Dox, A. W., 115.Drain, L. E., 21, 22.Dratz, A. F., 289.Dreyfus-Alain, B., 351.Drost-Hansen, W., 47.Drozdowski, E., 338.Druey, J., 141.Dry, J . L., 157.Dryden, J. S., 369.Dubbs, C. A., 331.Dubnoff, J. W., 259.Dubois, 1;. W., 30.Dubois, M., 338.Dubuisson, M., 288.Duchesne, J., 9, 11, 12, 17.Dunnenberger, M., 186.Diirst, O., 184.Duff, R. B., 242, 245.Duff, S.R., 183.Duhamel, J., 80.Duke, I?. R., 135.Duke, J . R. C., 360.Dulmage. W. T., 351, 354,Dulon, R., 186.Duncan, J. F., 339.Duncan, J . &I., 90.Duncan, N. E., 38.359.Duncanson, W. E., 355.Dunicz, B. L., 315.Dunitz, J. D., 172, 177, 268,349, 353, 363, 370, 371,372, 380.Dunleavy, R. A., 310.Dunlop, A. P., 204.Dunn, G. E., 52.Dunn, M. S., 255.Dunoyer, J.-M., 351.Dupont, G., 186.Durbin, G. T., 274.Durham, R. W., 40.Durrum, E. L., 341.Durso, D. F., 242.Durst, A., 315.Dutina, D., 325.Dutoit, C. H., 282.Duval, C., 311, 312, 313,Du Vigneaud, V., 256.Dwyer, F. P., 34, 107, 108,Dyer, E., 60.Dyer, H. B., 376.Dyggve. H., 273.Dyne, P. J., 57.Dziewiatkowski, D. D., 271.Eakin, R. E., 255, 259.Eastham, J.F., 199.Ebel, J . P., 339.Eberhardt, G., 139, 155.Eberius, E., 341.Eberle, A. It., 328.Eberle, H., 147.Ebert, M., 76, 77.Ebnother, A., 233.Ebnother, C., 217.Eckel, R. E., 327.Eckstrom, H. C., 22, 33.Eddy, C. R., 200.Edelman. J., 243.Edmonds, J. T., 201.Edmonds, M., 264.Edsall, J. T., 250, 381.Edward, J. T., 226, 338.Edwards, F. G., 125.Edwards, J . D., 157.Edwards, J , O., 60.Edwards, J . W., 365.Eeckhout, J., 317.Egerton, M. J., 161.Eggers, D. F., 16.Eglinton, G., 153.Ehrenberg, L., 67.Ehrenfest, E., 282.Eichenberger, K., 194.Eichhorn, E. L., 375.Eidinoff, M. L., 197.Eigen, M., 28.Eiland, P. F., 84, 171, 370,Eimer, L., 43, 44.Eimers, E., 117.Eirich, F. F., 124.Eirich, F. R., 59, 60.314.308.380INDEX OF AUTHORS’ NAMES.389Eisner, H. J., 267.Eiszner, J. R., 56.Ek, A., 214.Ekstein, M. G., 350.El-Badry, H. M., 312.Elderfield, R. C., 203, 210.Elentukh, M. P., 311.Eley, D. D., 63.Elion, G. B., 216.Elisberg, E., 142, 204.Elks, J., 294, 295, 296.Elliott, A., 381.Elliott, D. F., 149, 208.Elliott, J . R., 88.Elliott, W. H., 211, 286.Elming, N., 204, 228.Elmore, D. T., 218.El-Nawawy, A. S., 165.El Ridi, M. S., 232.El-Sabban, M. Z., 9.Elton, G. A. H., 25, 26.Elvehjem, C. L4., 218, 256Elvidge, J. A., 152, 159.El Wakkad, S. E. S., 325.Ely, J. O., 290.El’yashevich, 11.Embleton, H. W., 205.Emelkus, H. J., 101.Emerson, W. S., 204.Emery, J. E., 307.Emich, F., 299.Emmett, A. D., 26i.Emmett, P.H., 21, 22.Emslie, A. R. G., 267, 268.Enderby, J., 166.Engelbrecht, A., 102.Engelhardt, V. *4., 158.Enghag, P., 325.Englesberg, E. E., 261.Englis, D. T., 329.Entwhistle, N., 151.Epars, L., 323.Epple, R. P., 46.Eppstein, G. H., 195.Erdey, L., 316.Erdtman, H., 172.Erickson, A. E., 194.Erickson, R. L., 138.Ericson, R. P., 91.Eriks, K., 359.Erlenmeyer, H.. 336, 339.Erspamer, V., 215.Erulkar, S. D., 285.Eschenmoser, A., 158, 181.Essex, H., 68.Estellks, I., 46.Etienne, A., 57.Ettlinger, M. G., 177.Eugster, C. H., 138, 152.Euler, U. S. von, 338.Evans, D. F., 83, 369.Evans, D. M., 345.Evans, E. A., 44, 340.Evans, E. A., jun., 264.Evans, H. T., 350, 364, 365.Evans, J. I., 31.283.Evans, M.G., 122.Evans, R. M., 140, 151.Evans, R. S., 338.Everest, D. A., 90, 95.Everett, D. H., 21, 23, 31.Everson, H. E., 30.Ewart, R. H., 64.Ewing, D. T., 27, 267.Ewing, G. W., 207.Ewing, J., 221.Eylenburg, R., 273.Eyring, H., 35, 52, 68, 79.Eyring, L., 34, 103.Faaborg-Andersen, K., 271Fadeeva, 2. A., 308.Falirenbach, M. J., 217, 257Fairbrother, F., 105.Falkenhausen, E. H. F. vonFalterman, C. W., 54.Fankuchen, I., 101, 102,333, 351, 359, 363, 373,374, 375.Fanta, P. E., 202.Farber, M., 133, 145.Farenhorst, E., 41, 123, 133.Farid, M. K., 189.Farlon, P. F., 9.Farmer, E. H., 126, 128.Farnsworth, D. W., 213.Farrar, K. K., 142, 152.Farrington, P. S., 31, 322.Fauconnier, P., 314.Faust, J . A., 207.Favre, H., 180.Fawcett, F.S., 134.Fawcett, J . S., 184, 185.Fedoseev, P. N., 319.F6her, F., 100.Fehnel, E., 205.Feigelson, hl., 276.Feigl, F., 109, 309, 310, 330.Feiler, C. E., 301.Feist, F., 17’7.Feites, E. M., 50.Feldcott, G., 284.Feldman, H. G., 175.Felix, K., 273.Felley, D. L., 212.Fellig, J., 238.Fenton, S. W., 176.Ferguson, J., 58.Ferigle, S. hl., 9.Fernaholz, H., 173.FernAndez Caldas, E., 331.Fernando, Q., 307.Fernelius, W. C., 304.Fernholz, E., 199.Ferraro, J. R., 30, 106.Ferris, A. F., 125.Feske, W., 296.Fialkov, Ya. A., 98.Ficini, J., 202.Fickett, W., 202.Field, A. C., 152.Field, F. H., 64.170.Fieser, L. F., 138, 197, 198,199, 202, 208, 219, 221.Fieser, M., 199, 221.Figdor, S. K., 163.Figgis, B., 329.Figueras, J., 213.Fildes, (Sir) P., 263.Fillinger, H.H., 335, 339.Finch, C. A., 273.Findlay, S. P., 225.Fink, K., 292.Fink, R. M., 292.Fischel, A., 329.Fischer, E., 174.Fischer, E. H., 238.Fischer, E. O., 106, 370.Fischer, H. 0. L., 153.Fischer, J., 91.Fischer, R., 332.Fish, V. B., 320.Fisher, E. E., 213.Fisher, 1:. R., 326.Fisher, G. S., 134.Fisher, N., 161.Fisher, S. A4., 336.Fitting, C., 241.Fitzgerald, D. M., 230.Fivian, W., 305.Flam, A., 223, 224.FIanders, C. A., 244.Flaschka, H., 304, 305, 306,Fletcher, J . l?., 234.Fletcher, W. H., 7.Flett, M. St. C., 62.Fling, M., 261.Flitter, D., 143.Flom, D. G., 325.Flood, A. E., 231.Flores de Ligondks, J., 310.Flory, P. J., 241.Flynn, E.II., 257.Flynn, R. M., 260.Foa, P. P., 285.Fodor, G., 208, 219.Fog, J., 326.Foldes, P., 285.Folkers, K., 212, 218, 219,Follres, J. P., 283.Fong, C. T. O., 209, 253.Fonken, G. S., 146.Fonnesu, A., 320.Fono, A., 126, 129, 131.Fontaine, T. D., 200.Forbes, W. F., 142.Forchheimer, 0. L., 44,Ford, M. C., 117, 120, 125,Fordham, D., 253.Fordham, J. W. L., 129, 130.Fordham, W. D., 146.Toreman, J . K., 314.Tornaseri, M., 361.?orster, R. P., 289.?ort, R., 321.312, 315.256.46.143390 INDEX OF AUTHORS’ NAMES.Forty, A. J., 344.Foss. O., 101.Foster, A. B., 236, 339.Foster, A. G., 22, 23, 24.Foster, F. C., 64.Foster, J . F., 236.Foster, R. L., 210.Foster, W. R., 364.Fowden, L., 162.Fowkes, F. A., 24.Fowkes, F.M., 26.Fowler, R., H., 14.Fowles, G. W. A., 99.Fowweather, F., 375.Fox, H. W., 25.Fox, J . J., 208, 217, 250.Fox, M., 79.Fox, S. W., 261.Fraenkel, G., 274.Fraenkel-Conrat, H. L., 228.Fram, P., 63.Francis, P. S., 267.Francis, S. A., 17.Frandsen, M., 99.Frank, A., 94.Frank, F. C., 343, 344.Frank, S., 150.Franklin, A. E., 292.Franklin, J. L., 42.Franklin, R. E., 355.Franzke, C., 309.Fraser, R. D. B., 16, 381.Frediniani, W. A,, 341.Fredrick, W. G., 305.Fredrickson, D. R., 315.Free, A. A., 293.Freed, A. M., 274.Freed, S., 105.Freedman, A. J., 87.Freedman, L. D., 121.Freeman, H. C., 57.Freeman, J. H., 338.Freeman, N. K., 144, 145.Freiling, E. C., 39.Freiser, H., 81, 302, 307,Freitag, E., 81.Freund, H., 329.Freund, W., 204.Frey, A., 158.Frey, H., 336.Freyberg, R.H., 270.Freytag, H. E., 331.Frick, G., 250.Fricke, H., 75.Fridrichsons, J., 184, 201,Fried, J., 200, 230.Friedberg, F., 335.Frieden, E., 292, 294.Friedenson, O., 27 1.Friedkin, M., 277.Friedlander, H. N., 125, 133.Friedman, H. L., 207.Friedman, L., 48, 139.Fritz, J , S., 341.Frost, A. A,, 42.312, 324, 336, 337.379.Frost-Jones, R. F. U., 327.Fruton, J. S., 263.Fry, A., 52.Fuchs, E. G., 216.Fuchs, H., 162.Fuchs, J., 315.Fudge, A. J., 46.Furth, R., 345.Fugger, J., 127.Fuginaga, T., 323.Fugmann, It., 189.Fujita, A., 267.Fuks, Z., 162.Fulruda, M., 335.Fukuda, S., 232.Fukui, T., 274.Fukushima, B., 232.Fukushima, D. K., 197.Fullam, E.F., 344.Fuller, A. A,, 345.Furberg, S., 349, 373.Furman, C., 255.Furman, N. H., 322, 323,Furman, S. C., 43.Furness, W., 323.Fuson, R. C., 164.Gabrielson, G., 337.Gage, T. B., 231.Gagliardi, E., 312, 313, 314.Gal, G., 167.Gale, E. F., 283.Gale, P. H., 321.Galiba, H., 342.Galimard, J . E., 273.Galinovsky, I?., 220.Galkowski, T. T., 33.5.Gallagher, T. F., 142, 196,Gallup, G. A., 36.Galmks, J., 308.Gamlen, G. A,, 96.Gammill, A. M., 94.Gammon, J. N., 240.Gampp, H. W., 208.Gandelman, B., 240.Gandolfo, N., 312.Gannon, J , A., 59.Garbers, C. F., 135, 152.Garden, L., 231.Gardner, 3 . A. F., 338.Gardner, P. D., 175.Garibaldi, J. A., 239.Garkina, I. N., 267.Garlick, 13’. R., 294.Garmaise, D. L., 196.Garmendia, A.A,, 336.Garner, A. W., 30.Garner, C. S., 82, 308.Garrett, A. B., 98, 158.Garrison, W. M., 76, 79.Garvin, D., 39.Gates, M., 221.Gauguin, R., 322.Gauss, K., 149.Gauthier, B., 267.325, 331.197, 204.Gauvain, S., 269.Gayer, K. H., 98.Gaylord, N. G., 59, 60, 124,Geerling, H., 328.Gebhardt, L. P., 245.Gee, G., 61, 136.Gee, R., 234.Geffroy, E., 325.Geiersberger, I<., 315.Geissman, T. A., 214, 230,Gelin, R., 154.Geller, S., 356, 368.Gensler, W. J., 150.Gentry, C. H. I<., 330.George, P., 75.Gerding, H., 88.Gergely, J., 280.Gericlte, S., 326.Gerold, C., 195.Gerrard, W., 146.Getzendauer, 11.1. E., 253,Gevantman, L., 69.Ghe, A. M., 339.Ghigi, E., 183.Ghormley, J . A., 73.Giacomello, G., 368.Giancola, D., 198.Gibb, A.R. M., 173.Gibb, T. R . P., jun., 85.Gibbons, D., 305, 312, 313,Gibby, (3. W., 30.Gibson, C. S., 86.Gibson, F., 258.Gibson, J . C., 30.5.Gibson, J . D., 154.Gibson, N. A., 329.Gierlinger, W., 326.Gies, H., 120.Giguere, 1’. A , , 357.Gilbert, B., 143, 165.Gilbert, C. W., 77, 291.Gilbert, G. R., 238, 239.Gilbert, R. D., 61.Gilbert, W. S., 206.Gilchrist, R., 93.Gilkerson, Vi. R., 36.Gill, N. S., 107, 308.Gillam, A. I<., 105.Gillis, J., 100, 309, 347.Gilman, H., 210.Gilmour, EI., 52.Gilpin, V., 332.Gippin, M., 123.Girandel, B., 46.Giri, K. V., 338.Gish, D. T., 146.Gjems, O., 325.Glacet, C., 204.Gladstone, G. P., 263.Glass, J. R., 323.Gledhill, J. A., 29.Glemser, O., 327.Glenn, R.A., 335.202.234.259.318INDEX OF AUTHORS' NAMES. 391Gleu, K., 109.Glew, D. N., 51.Glock, G. E., 290.Glockler, G., 9, 91.Glockling, F., 87.Gloppe, K. E., 232.Glover, J., 152, 269.Glover, M., 269,Gluyas, R. E., 363.Godsell, J . A., 168.Godycki, L. E., 353.Goebel, A., 91.Goedkoop, J . A,, 347.Goehring, M., 98.Goering, H. L., 134.Goser, C., 100.Goettsch, M., 271.Goldacre, R. J., 288.Goldbeck, C. G., 314.Goldberger, H., 318.Goldblatt, H., 271.Goldblatt, L. A., 134.Goldschmidt, D., 146.Goldschmidt, G. H., 352.Goldsmith, H. L., 51.Goldstein, J. H., 17.Goljmov, V. P., 160.Gomer, R., 39.Good, R. J., 24.Goodwin, R. H., 234.Goodwin, T. W., 142.Goransen, E. S., 285.Gorbach, G., 326, 330.Gordon, A.H., 292.Gordon, A. R., 29.Gordon, H. T., 329.Gordon, I., 208.Gordon, L., 311.Gordon, hf., 175, 259.Gordon, S., 31, 70, 77, 78,Gordj;, W., 10, 17.Gore, €2. C., 331.Gorham, JV. F., 174.Gorka, B., 271.Gorter, K., 220.Gorvin, J . H., 120.Gots, J., 264.Gots, J . S., 259.Gott, A. D., 82, 144.Gottlieb, A., 328.Goubeau, J., 88.Gould, D. H., 200.Goulden, J . D. S., 208.Gourley, D. R. H., 289.Goutarel, R., 223, 225.Govaert, F., 190.Govaerts, J ., 340.Govier, W. M., 271.Govindachari, T. R., 157.Graaff, G. B. R. de, 174.Grab, W., 291.Graber, R. B., 196.Graber, R. P., 142.Gracheva, E. G., 302.Graf, R., 131.Graham, P. L., 207.106, 227.Graham, R. P., 323.Gran, G., 324, 327, 328.Granados, H., 270.Granatelli, L., 332.Grassie, N., 62.Grassner, F., 319.Graue, G., 322.Grauer, A., 318.Graven, W.M., 54.Gray, D. J . S., 327.Gray, J. A., 56.Gray, L. H., 77, 79.GrdeniC, D., 350, 373.Greaves, M. C., 315.Greef, H. F., 175.Green, D. E., 275, 279. 286Green, H., 290.Green, J., 267.Green. P. N.. 207.Greenberg, D. M., 268,Greenberg, G. R., 264.Greenberg, M., 285.Greenberg, S. M., 274.Greenfield, M. A., 66.Greenlee, K. ?V., 9,Greenstein, J . P., 206.Greenwood, N. N., 98.Gregg, S. J., 18, 20.Gregory, G. I., 1G1.Gregory, J . D., 280.Gregory, N. W., 367.Greif, R. L., 245.Gresham, T. L., 1.56.GrevilIe, G. D., 282.Grieg, ii., 338.Grieger, P. F., 29.Griel, J . V., 328.Grieve, \V. S. M., 118.Griffel, M., 366.Griffin, L. J., 344.Griffith, E.J., 33.Griffiths, J,, 336.Grillot, E., 340.Grimaldi, F. S., 330.Grimm, F. V., 27,Gripp, V. E., 150.Grisolia, S., 286.Grison, E., 85, 347, 359.Griswold, E., 105.Groom, H., 325.Grob, C. A., 161.Grosiean. C. C.. 344.340.177.269,150,Gro& D:, 338.'Gross, J., 291, 292, 293.Gross, M. E., 357.Gross, P. M., 30.Srosse, A. V., 102, 154, 203,Grossweiner, L., 86.Srossweiner, L. I., 66.C;roszos, S. J., 115.Srove, C. S., 308.Srove, J. F., 230, 235.Sruber, W., 186.Sriitter, H., 153, 179, 180.340.Grunbaum, B. W., 336.Grund, A,, 361, 363.Grundmann, C., 209.Grundon, M. F., 225, 232.Grundy, W. E., 210.Grylls, F. S. M., 335.Gubelbank, S. M., 316.Gubeli, O., 340.Giinthard, Hs.H., 177, 180,Guggenheim, E. A., 14.Guill, A. P., 318.Guillemot, E., 326.Guirard, B. M., 252.Gulland, J. M., 249.Gullstrom, D. K., 49, 307.Gullstrom, D. L., 108.Gump, J . R., 314.Gundermann, K.-D., 162.Gunn, E. L., 326.Gunnar, K., 94.Gunness, M., 255.Gunsalus, I. C., 158, 209,253, 255, 279.Gunstone, F. D., 159, 180.Gupta, A. K., 341.Gupta, J., 327, 329, 339.Gusev, S. I., 313.Guss, C. O., 202.Gustafsson, C., 338.Gutmann, H., 183.Gutmann, V., 101, 366.Gutsche, C. D., 193.Guttag, N. S., 330.Guymon, J. F., 329.Guzman, G. M., 59.Gyarfas, E. C., 34, 107, 108,Gyorgy, P., 270, 271.Gysel, H., 320.Haag, H., 92.Haas, H. C., 61.Hame, H., 322.Habgood, T., 225.Hach, C. C., 91.Hach, R.J . , 367.Hader, R. J., 302.Haflinger, O., 164.Haendler, 13. M., 85, 93,Hagdahl, L., 335.Hague, E., 256.Hague, J . L., 327.Hahn, F. L., 305.Hahn, H., 314.Hahn, H. von, 339.Hahn, R. B., 325.Haight, G. P., jun., 47.Haines, R. L., 41.Kaines, W. J., 195.Haissinsky, M., 44, 46, 71,72, 73, 76, 78.Haksar, C. N., 168.Hale, D. K., 337.Hale, F., 255.Halenda, P. P., 23.181, 184.30s.104392 INDEX OF AUTHORS’ NAMES.Halfpenny, E., 50, 97, 122.Hall, C. J., 329.Hall, G. R., 339.Hall, J. L., 89, 325.Hall, R. H., 218.Hall Ratcliffe, A., 272.Hallett, L. T., 298.Halmi, G., 167.Halperin, A., 330.Halperin, J., 47.Halsall, T. G., 187, 188.Halsey, G. D., 22.Ham, A. J., 330.Hamer, H. S., 29.Hamill, W. H., 55, 56, 69.Hamilton, J.G., 79.Hamilton, J . K., 236.Hamilton, W. C., 310.Hamlet, J. C., 142, 152.Hamlin, A. G., 328.Hammaker, E. M., 326.Hammond, G. S., 52, 115,Hanby, W. E., 381.Hancock, D. C., 93.Handler, P., 289.Hanes, M. E., 210.Hanhart, W., 150.Hanna, C., 141.Hannan, R. S., 79.Hanok, A., 303, 305.Hansen, A. E., 274.Hansen, G. E., 10.Hansen, J. E., 61.Hansen, R. S., 94.Hanson, A. W., 345, 346.Hansuld, M. K., 205.Happey, F., 380.Haraszti, J., 167.Harborne, J . B., 338.Harborne, J . H., 233.Hardwick, T. J., 67, 68, 78.Hardy, H. R., 136.Hardy, W. B., 123.Hare, G., 325.Hargrave, K. R., 75.Harington, (Sir) C. R., 291,292, 293, 294, 296.Harker, D., 347. 358.125.Harkins, W. D.; 18, 19, 20,Harkness.M. L. R.. 245.21, 22, 24, 25, 27.Harley-Mason, J., 203, 214,Harman, J. W., 276.Harned, H. S., 29, 32.Harper, S. H., 180.Harrap, B. S., 240.Harris, E. F. P., 117.Harris, G., 190, 207.Harris, G. M., 45, 53.Harris, G. W., 53.Harris, J. O., 182.Harris, P. L., 270, 275.Harris, R. J. C., 236.Harris, R. L., 366.Harris, W. F., 305.215.Harrison, A., 340.Harrison, F. W., 361.Harrison, H. C., 268.Harrison, H. E., 268.Harrison, J. S., 238, 240,Hart, E. J., 67, 68, 73, 75,Hart, E. N., 314.Hartley, F. K., 91.Hartley, G. S., 29.Hartmann, H., 87.Hartwig, E., 173.Harvey, A. E., 307.Harvey, W. E., 172, 227.Harvey, W. P., 273.Hashimoto, Y., 333, 339.Haslam, J., 328.Hassel, O., 349, 355, 372,Hasselbach, W., 288.Hasselmann, M., 330.Hassid, W.Z., 236, 239.Hassinen, J. B., 274.Hasted, J. B., 65.Hastings, S. H., 332.Haszeldine, R. N., 101, 133,Hatch, L. F., 154.Hatchard, C. G., 328.Hattori, S., 232.Haupt, G. K., 326.Hauptmann, H., 197, 347,Hauptschein, M., 154, 203.Hauserman, F. B., 158.Haven, A. C., 176.Havens, R., 15.Hawkins, E. G. E., 124, 128,Hawkins, J. D., 277.Hawkins, P. J., 39, 206.Hawley, J. E., 330.Haworth, J. W., 207.Haworth, R. D., 166, 173,Hay, A. S., 110.Hayashi, K., 232.Hayek, E., 94.Hayes, A. M., 48.Hayes, D. H., 180.Hayes, J. R., 336.Haymond, H. R., 79.Haynes, H. F., 224.Haynes, L., 203.Hazel, J. F., 328, 329.Hazlegrove, L. S., 322.Hazlett,