ISSN:0365-6217    

DOI:10.1039/AR94744FP001

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

ER,RBT IIMVOL. 43, 1946Page 261, ref. 178, for “ Dnnsk Tidwkr. Farm., 1946, 20, 288 ” read (‘ Laneef,1946, ii, 288 ”

ISSN:0365-6217    

DOI:10.1039/AR9474400004

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

ANNUAL REPORTSON THEPROGRESS OF CHEMISTRY.GENERAL AND PHYSICAL CHEMISTRY.1 . THE KINETICS OF ELECTRODE PROCESSES.THE Faraday Society Discussion on Electrode Processes,l in April 1947,showed how wide a range of problems in this field has attracted attention inrecent years. Without attempting a classification, it is possible todistinguish two rather different, though complementary, trends : ( a ) Theinvestigation of a greater variety of reactions, electrode materials, andsolvents, and the extension of measurements to higher current densities.( h ) The more intensive study of a few " classical " reactions, notably thcelectrodeposition of hydrogen on mercury 2, and p l a t i n ~ m , ~ in which,4. N. Frumkin and his colleagues have played tEe major part.T t is becoming increasingly evident that hydrogen and oxygen do nothold the outstanding position as regards high overpotential that has some-times been ascribed to them.Highly irreversible electrode reactions are notuncommon. Among others, the Kolbe and the Hofer-Moest reaction, forwhich equilibrium potentials are given by W. M. Latimer,4 the deposition ofthe azide ion (p. 30), and the large number of irreversible reductions dis-dosed by polarographic investigation^,^-^ may be noted.The quantity of available material makes i t impossible to review thewhole field adequately in this Report ; several subjects, in particular thedeposition and passivity of metals, have been omitted entirely. Thoseincluded have been chosen on the grounds of recent development or ofobvious, though long-standing, importance ; in the latter case a certainamount of recapitulation of an earlier Report is unavoidable.Many of thetopics with which the present Report is concerned have been discussed byJ. A. V. Butler in his book ; 10 recent work on hydrogen overpotential has alsobeen reviewed by J. W. Smith.llTram. Faraday SOC., 1947, 43, A , 111 the press (summerised by V. Gold, Nalwc,1847, 160, 306).Acta Physicochens. U.R.S.S., 1943, 18, 23.Trans. Faraday SOC., 1948, 44,I. M. Kolthoff and J. J. Lingane, " Polarography ", Interscience, 1941.J. Heyrovsky, " Polarographie ", Springer, 1941.F. P. Bowden and J. N. Agar, Ann. Reports, 1938, 35, 90.* " Oxidation Potentials ", Prentice Hall, 1938.' 0. H.Muller, Chem. Reviews, 1939, 24, 95. J. J. Lingane, ibid., 1941, 29, 1.11 Scirnce Progress, 1947, 35, 675. l" '' Electrocrtpillarity ", Methuen, 19406 GENERAL AND PHYSICAL CHEMISTRY,(i) Experimental Methods.The usual object of investigations of electrode kinetics is to elucidate themechanism of the reaction occurring at the electrode-solution interface. Ingeneral, therefore, it is necessary that experimental methods should be able todistinguish (a) '' activation overpotential " * (qR),Q9 l2 which has its origin insome " sluggish " stage(s) of the interfacial reaction, from " concentration "and " resistance " overpotentials. (qc and rlr), which arise from associatedprocesses in the solution iiettr the electrode; ( b ) the various stages possiblyresponsible for qa from one another.Both problems may be attacked by studying the behaviour of electrodesa t which the potential and/or current is varying with respect to time; suchexperiments may be made either by passing an alternating current throughthe cell, or by suddenly changing the current from one steady value toanother and following the subsequent change of potential.The electrodepotential generally lags behind the current, and the system is analogoup to anelectrical network containing resistances and capacities. The resistancesrepresent the various " slow " &ages in the overall process, and the chargeson the Capacities represent " accumulations " of certain components of thesystem at one or other of these stages.The early " commutator " method l3 of distinguishing qa and -qc from-qr is based on this principle, the assumption being made that the resistanceoverpotential decays almost instantaneously when the current is cut off,whereas t,he major part of other types of overpotential persists for anappreciable time.I n recent years, the availability of improved apparatus,combined with a better understanding of the nature of electrode processes,has made possible a considerable development of both oscillographic andA. C. methods.(a) The Use of Alternating Current.-The A.C. behaviour of an electrodemay be investigated by including the electrode, together with a suitable largeand relatively unpolarisable reference electrode, in one arm of an A.C.bridge and thus measuring its (complex) impedance.Various othermethods w 2 0 have also been used to compare the amplitude and phase of theE.M.F. between the working electrode and a reference electrode with that ofthe current flowing through the cell. A separate D.C. polarising circuit is12 J. X. Agar and F. P. Bowden, Proc. Roy. SOC., 1938, A, 169, 206.l 8 See S. Glasstone, " The Electrochemistry of Solutions ", Methuen, 1938, p. 423.l 4 G. Jones and S. M. Christian, J . Anier. Chenz. SOC., 1935, 57, 272.1 5 D. C. Grahame, ibid., 1941, 63, 1207.1 6 P. Dolin and B. Ershler, A c t a Physicochinz. U.R.S.S., 1940, 13, 747.17 B. Ershler, see ref. ( I ) . J. E. B. Randles, see ref. (1).Trans. Furaday Xoc., 1935, 31, 110; T. Borissova and M. Proskurnin, ActaPhysicoclLint.U.R.S.S., 1936,4, 819; 1940,12, 371.20 Conapt. rend. Acad. S c i . U.R.S.S., 1939, 24, 915.* " Overpotential ", 7, is defined as the potential difference between a workingelectrode and the appropriate reversible electrode in the same solution. I n this Report77 is taken to be a positive quantity, and is written 171 where any confusion regardingthe sign is likely to ariseAQAX : THE KINETIUS OF ELECTRODE PBOUEYYEY. 7usually incorporated, so that the D.C. or mean potential of the electrode maybe varied as desired.Although an electrode may be regarded as a network of resistances andcapacities, it should be noted that the system is likely to be highly non-linear,i . e . , the voltage across a resistance (capacity) is not proportional to thecurrent (charge).If a pure sinusoidal current flows through an impedance ofthis type, the resulting voltage generally contains a series of harmonics.The percentage of harmonics may be reduced to negligible proportions bykeeping the voltage amplitude sufficiently small, and amplitudes of a fewmv. (i.e., small compared to RT/F) have been found satisfactory.l6S l6, 18, l9The resistance and capacity associated with any stage of the electrodeprocess are thus " slope " or differential quantities, defined byR = aV/ai and C = ?q/aVwhere V represents the voltage drop associated with this stage, i thecorresponding current density, and q the corresponding charge per sq. cm. ;R (ohm. and C (VF. cm,-2) refer to 1 sq. em. of electrode surface.Of the systems so far studied, the simplest is the mercury electrode under" completely polarisable " conditions.Provided the solution contains noreducible solutes, there is a considerable range of potential in which noelectrolysis can take place, so that any current flowing through the electrode-solution interface in -these circumstances serves only to charge the doublelayer.* Under suitable conditions, concentration changes and the resistanceof the solution (&, Fig. la) may be neglected, and the electrode behavessimply as a condenser, having the double-layer capacity, C L (Fig. la). Thefirst reliabIe measurements of CL by this method, in which due regard waspaid tto possible contamination of the interface, were made by A. Frumkin andM. Proskurnin,lg using a stationary mercury surface and 50 cyclee/sec.A.C.M. Proskurnin and M. Vorsina20 subsequently extended the method tovery dilute solutions ( 10-4~) ; in these solutions the resistance Bs is no longernegligible in comparison with the impedance of CL a t 50 cycles/sec., but thedifficulty can be avoided by using very low frequencies (1 cycle/sec.).At more negative potentials the double-layer condenser develops a" leak ", since electrolysis, e.g., electrodeposition of hydrogen, becomesappreciable. This situation is shown in Fig. lb.al As before, Rs representsthe resistance of the electrolyte and concentration overpotential is neglected.A. Frumkin has pointed out 39 22 that a condenser (C,) in parallel with aresistance (Re) will represent the behaviour of any electrode a t which thereis only one slow stage; in such cases the rate of all stages of the reaction isalways uniquely determined by the instananeous value of the metal-solutionpotential difference. The slope resistance Re can thus be obtained from the21 Cf.B. Breyer and F. Gutmann, ref. (30); G. Falk and E. Lange, 2. Naturforscii.,1946, 1, 388.22 Acta Phy&ochitta. U.R.S.S., 1940, 13, 799.* This is the usual view, but there is no a p i o r i reason why other transient processes,e.g., deposition of adsorbed hydrogen atoms shouId not occur, even thongh continuouselectrolysis does not take place (see p. 26)8 GENERAL AND PHYSICAL CHEMISTRY.current-potential relation under steady current conditions ; for an electrodetvhich obeys the Tafel relahion :i = i0e~7~fl/R7' or yi = b(1og i - log io) .. . * (1)i.I(C)FIG. 1.where i (amps./cni.2) is the current density, i, is a constant, and b = 2.303ItTluP. we haveat rooin temperature, if u = 0.5.%Fig. l b has a particularly simple interpretation when the discharge ofions, rather than any subsequent stage, is the rate-determining step, becausethe capacity C, is then merely the double-layer capcity, CL. But if thedischarge process is rapid in comparison with some later stage, so thatz3 Cf. Frumkin, ref. (2), p. 41AGAR THE KINETICS OF ELECTRODE PRGCESSES. 9equilibrium is maintained between the ions and the (adsorbed) atoms formedby their discharge, e.g., H+ + E- + H(ads.), the capacity C, arises partlyfrom the accumulation of adsorbed atoms on the electrode, and will begreater than CL.It should be noted that the measured electrode capacity C,always includes CL, so that the reversible accumulation of adsorbed atoms williiot be detected unless the charge required to deposit them is comparable tothat required to alter the potential of the double layer.= If the value20 p ~ . c m . ~ is adopted for the double-layer capacity on a negativelycharged mercury surface, about 2 x coulomb/cm.2 are required tochange the double-layer potential by 0.1 v . ; this charge corresponds to1 or 2% of a monolayer of hydrogen.A.C. methods have been used by Dolin, Ershler, and others 16) lT> 25, 26 toinvestigate the kinetics of deposition of hydrogen ions on platinum.Theirexperiments refer to platinum electrodes at potentials more positive thanthe reversible hydrogen potential, and the conditions are such that (a) acoiisiderable fraction of the surface is covered with adsorbed hydrogenatoms, ( b ) the reaction Hr + E - =+ H(ads.), though fairly rapid, proceedswith measurable speed, and (c) the final stage (formation of free H2) does notoccur to any appreciable extent. The relation between the equilibriumpotential, V,,, of such an electrode and the amount of adsorbed hydrogen,q,[, expressed as coulombs per sq. em., is known from other investigations;it is thus possible to define a capacity C, = ?q,/aV,. Dolin and Ershler showthat the simplest possible picture of this system (for a homogeneous surfaceor a heterogeneous surface with unrestricted mobility of adsorbed atoms) isthat given in Fig. l c .As before, CL is the double-layer capacity, and Rd isthe “ resistance ” associated with the process H+ + E- + H(ads.). Ifthis process takes place a t the rates 5 J , in the two directions underequilibrium conditions (at the particular mean potential in question), it maybe shown l7 thatRd = RT/PJ, . . . . . . . . (2)Observations a t different hequencies 16, 25 indicated that Fig. l c did nottruly represent the A.C. impedance of the electrode ; the experimentalresults actually correspond to a more complicated circuit of the type ofFig. I d , which represents a heterogeneous surface, having different resistancesRd, Rd‘, Rd” . . , and capacities C,, C,’, Ca” .. . a t different points,together with restricted mobility, represented by resistances r , r’ . . .The influence of the local concentration changes produced by alternatingcurrents has been studied by J. E. B. Randles and by Frumkin, Dolin, andEr~hler.~’ It was shown theoretically many years ago 28 that a sinueoidalcurrent passing through an electrode would cause the concentration of anysubstance taking part in the electrode process to oscillate about a meanvalue, with the same frequency as the current but different phase. Theamplitude of the concentration change is a maximum at the electrode-’‘ -4. Hickling, Trans. Ir’araday SOC., 1941, 37, 532.l 5 K. Kosenthal, P. Dolin, and B. Ershler, Acta Physicockiwr. U.H.S.S., 1946, 21, 213.2b B.Ershler and 31. Proskurnin, ibid., 1937, 6, 196. 2 7 Ibid., 1940, 13, 793.A 10 GENERAL AND PHYSICAL CHEMISTRY.solution interface and falls off exponentially with distance from the interface.For a reaction having negligible activation overpotential and involving unitvalency change, and provided the amplitude of the concentration oscillationsis small, the A.C. component of the concentration overpotential isA- cos (at -;) . . . RT iylc=---l@ col/Da (3)where D is the diffusion coefficient of the reacting ion, co is the meanconcentration, and the alternating current density is i = iA cos at It willbe seen that the potential lags behind the current density a t all frequencies.The relation (3) is equivalent 17, 28 to a capacity C, and a resistance R, inparallel, or l8 to a capacity +C, and a resistance $Iic in series, where(in farads and ohm respectively).The fact that the system can be represented, at all frequencies, either by aseries or by a parallel arrangement of resistance and capacity is surprising;i t arises from the dependence of C, and R, on a.A similar result is obtained when the activation overpotential is notnegligible,l83 27 but it is now necessary to include an additional resistanceRe, characteristic of the interfacial reaction and related to the equilibriumexchange rate Jo in the same way as Rd (eqn.2). Ershler’s final expressions 17are equivalent to Fig. l e ; they have been applied to the systemHglHg2(C10,),, 0 . 0 1 ~ ; HCIO,, 2 ~ , using frequencies up to 5000 c.P.s.; tothe platinum-hydrogen electrode under conditions such that local changes inconcentration of dissolved hydrogen are important,27 and, in a rather morecomplicated form, to the determination of the rate of adsorption of ions onmer~ury.1~ Randles l8 has investigated the deposition of various metallicions a t amalgam electrodes, where there are two diffusion processes-in thesolution and in the mercury-and has evaluated the rate constant for thereaction Zn++ -+ Zn (amalgam) ; it is strongly dependent on the natureof the anion.-Further experiments, using 50 C.P.P. A.C. at a mercury-jet or droppingelectrode, have been carried out by J. Heyrovsky and his co-workers,6~29and by B. Breyer and F. Gutmanm30 Heyrovsky’s results indicate thatmost single-electron deposition processes and some two-electron processestake place very rapidly, although the deposition of Zn, of many other bivalentions, and also of Bi++-+, Sb +++, and In+++ from certain solutions, is distinctlyirreversible.(b) Charging Curves and Decay of Overpotential : Oscillographic Methods.-The first work in this field in which attention was paid to the elimination of28 F.Kriiger, 2. physikal. Chem., 1903, 45, 1 ; T. R. Rosebrugh and W. Lash Miller,J . Physical Chem., 1910, 14, 816.29 See ref. ( 1 ) ; 2. physikal. Chem., 1943, A , 193, 77 ; Coll. Czech. Chem. corm^., 1947,12, 11.30 Trans. Faraday SOC., 1946, 42, 644, 650; and see ref. (1)AGAR : THE KINETICS OF ELECTRODE PROCESSES. 11impurities appears to be that of F.P. Bowden and E. K. Rideal31 and ofE. Baars32 who measured the decay of hydrogen overpotential on opencircuit; Bowden and Rideal3l also studied the increase or decrease ofoverpotential when the current was increased or reversed. More recently,P. P. Bowden and K. E. G r e ~ , ~ 3 using very low current densities, havefollowed the correspondingly slow change of potential on a mercury cathodewith a quadrant electrometer, and several investigations have been made,with the aid of the cathode ray oscillograph,34f 35 of the more rapid changesof potential at higher current densities.The results for mercury cathodes may be interpreted in terms of Fig. l b ;if the conditions are correctly chosen, leakage through the resistance Re isnegligible, and a linear change of potential with time (at constant C.D.) isobserved, from which the electrode capacity may be derived.When thepotential of the electrode approaches its final steady value, Re can no longerbe neglected. A correction derived from the y-log (steady current) relationmay he applied; 31 an alternative method of deriving this correction, fromcharging and decay curves in combination, has been described by B.Kabanovand S. J ~ f a . ~ ~Similar methods have been used to study the deposition of monolayers ofhydrogen or oxygen on platinum.37It was shown by G. Armstrong and J. A. V. Butler 38 that the decay ofhydrogen overpotential on mercury at low C.D.s was in good agreement withan equation of the formwhere t is the time after stopping the current and B is a constant.Usingthe Tafel equation (1) in conjunction with Fig. l b , and assuming C, to beconstant, it may easily he shown thataF i,t eaqlF'Rl' - eaqlF,'R1' = -R T c ? * - - -where -ql is the initial overpotential and i, is defined by (1) ; this equationreduces to the logarithmic form (4) for large values of t . An analogousequation is given by F r ~ r n k i n , ~ who quotes unpublished experiments on amercury cathode by Fedotov in support of it ; the values of C, observed were18-20 P F ~ , and thus in good agreement with the accepted value of thedouble-layer capacity a t more positive potentials (see Table, p. 18).The decay of overpotential on other metals has been extensively studiedn 1 Proc. Roy. Soc., 1928, A , 120, 59.32 Sitzungsber.Ges. Beford. Naturwiss. Marbury, 1928, 63, 213.33 See ref. (1).34 E.g., Butler and Pearson, ref. (120) ; Barclay and Butler, ref. (73) ; Hickling,35 K. F. Bonhoeffer et al., 2. Elektrochem., 1941, 47, 147, 441, 536; E. Newbery36 Acfa Physicochim. U.R.S.S., 1939, 10, 617.37 See p. 26.R * Trans. Faraday Soc., 1933, 29, 12til ; cf. Butler, ref. (10).ref. (43).el al., l's-ar~s. Faradny SOC., 1947, 43, 12312 GEXERAL AND PHYSICAL CHEMISTRY.by A. L. Ferguson and his co-workers s99 40. *1 and by A. Hickling andP. W. Salt.42 From their results, there is little doubt tlhat the phenomenaare often more complex than the above equations suggest. There is. as yet,no adequate explanation of all the observations, but Hickling and Saltconclude that there are two distinct processes, one operative at high C'.D.sand responsible for the rapid, initial, part of the decay curve, and anotherresponsible for the slower, long-period, decay.High-speed charging and decay curves have usually been determilied by'' single-sweep " oscillographic methods, but a repetitive method, giving astationary picture on the oscillograph, has been used by A.H i ~ k l i n g . ~ ~Another instrument developed by the same author 44 makes i t possible tostudy rapid decay processes without an oscillograph. The instrumentmeasures the lowest potential attained during a known and adjustableinterval of time; for a continuously decreasing potential, this must be thepotential at the end of the interval.(ii) The Electrolytic -Double Layer.It is obvious that the structure of the double layer, i.e., t'he tlistributioiiof charged particles and of neutral molecules at the electrode-solution inter-face, is a question of major importance to the understanding of electrodereacti0ns.~~9 46 The methods of investigating the double layer may beclassified under five headings : 47 (1) Electrocapillary (including measure-ment of contact angles in the case of solid 48 (2) Measurement ofcharge per unit surface area by the dropping electrode.(3) Measurement ofelectrode capacity, by charging curves or A.C. methods. (4) Directmeasurement of adsorption from the solution. (5) Electrokinetic methods.Recent work on frictional 493 50 and other mechanical properties 51 ofmetals in aqueous solutions suggests the possibility of an additional methodof studying the metal-solution interface.Methods ( l ) , (2), and (3), which are closely related to one another by thefundamental equations of electrocapillarity, are at present the mostimportant, although mainly restricted to mercury electrodes.The exactthermodynamic treatment of the electrocapillary curve, due originally to39 ?'runs. Electrochletw. SOC., 1939, 76, 113.40 A. L. Ferguson and H. Bandes, ibid., 1942, 81, 103, 123.I1 See ref. ( 1 ) .4 2 Trans. Faraday Xoc., 1941, 37, 460.43 Ibid.. 1940, 36, 364; cf. T. Erdey-Grk and (1. Kromrey, %. physikal. Chew.,4 4 Trans. Faraday ~ o c . , 1937, 33, 340; see also ref. (421).4 5 A. Frumkin, " Coliche double, Electrocapillarite, Surtension ", ActualitPs4 6 A.Frumkin, Trans. Faraday Soc., 1940, 36, 117.4 7 Cf. Butler, ref. (10); Frumkin, ref. (46).4a See also A. Frumkin and A. Gorodetskaya, Acta Physicochisn. U.R.S.S., 1938, 9,48 F. P. Bowden and D. Tabor, dim. Reports, 1945, 42, 32.j0 R. E. D. Clark. Trans. Puruday SOC., 1946, 42, 449.1931, A , 157, 213.scientifiques et industrielles, No. 373 (1936).313, 327F. 0. Koenig 52 and to S. K. Craxford, 0. Gatty, J. StL. Philpot,and. H. A. McKay,= has been reviewed by Craxford,54 and a rather simplerderivation, following Koenig, has been given by D. C. Grahame andR. B. W h i t n e ~ . ~ ~ ? 55a Exact relations for concentrated solutions have beenworked out by S. Jofa and A. F r ~ m k i n , ~ ~ who refer potentials to a suitablereversible electrode in the same solution, e.g., a reversible hydrogen electrodein hydrochloric acid.The earlier discussions usually imply that the potentialis measured with respect to a standard reference electrode, and that theliquid-junction potential between this electrode and the solution underinvestigation can be eliminated.For a “ completely polarisable ” electrode 523 54, 55 the most importantrelation is the Lippman equation :(+/a+)s,c = - Q . . . . . (6)where y is the interfacial tension, C# the metal-solution potential difference,and q the charge per unit area on the metallic side of the interface; thesubscripts s and c imply constant area and constant composition of so1ution.sThe value of + is always ambiguous to the extent of an unknown additiveconstant, but this presents no real difficulty.The charge q is the differencebetween the number of positively charged univalent ions in t’he metal and thenumber of electrons.The differential capacity, C, of the electrode is defined byc = (a(I/aC#),, c . . . . . . . (7)(;2y/2+2)& c = - c . . . . . * (8)whence it follows thatThese equations are entirely general and do not involve any assumptionsabout the distribution of the charges at the interface; 54 they show (a) thatthe charge (I is always zero at the electrocapillary maximum; ( b ) thatmethods (l), (2), and (3) are to a large extent equivalent. ,4lthough theearlier work suggested discrepancies, recent experiments have confirmedthis inter-re1ati0n.l~~ st A.Frumkin and M. Vorsina 5 7 9 58 have pointedout that capacity measurements usually give more detailed information thanmethods (1) or (2), even for mercury surfaces; for solid metals theiradvantages are obvious.Further equations may be derived connecting y, 4, and the concentration51 E.g., P. Rehbinder and E. Wenstrom, Acta Physicochim. U.R.S.S., 1944,19,36.jn J . PhysicaE C’liesn ., 1934, 38, 1 1 1, 339 ; Wien-Harms, “ Handb. d. Experimental-physik ”, 12(ii), 380 (1933) ; N. K. Adam, “ The Physics and Chemistry of Surfaces ”,Oxford, 1938, p. 344.53 Phil. Mag., 1933,14,849; 1934,17, 54; 1935,19,965; 1936,22, 359.j4 Trans. Faraday SOC., 1940, 36, 85.55n D. C. Grahame, Chem. Reviews, 1947, 41, 441. (This review appeared while theprevent Report was in the press; it is not possible to deal fully with its contents, whichdiffer in some respects from the views of other workers.)5 6 Acta Ph?ysicochint.U.R.S.B., 1939, 10, 473; see also S. Jofa et al., J . PhysicalC ’ ? t p t ) i . Russia, 1939,13, 931, 934.* a .4( tn PhyRicochini, Tr,R.S,S., 1943. 18, 242.5 5 J . Amer. Chem. SOC., 1942, 64, 1548.j8 Ibid., p. 341. .14 GENERAL AND PHYSTCAL CHEMISTRY.or activity.52~ ** 55n- 56 The information to be obtained from the comparisonof electrocapillary and capacity data a t different concentrations has recentlybeen discussed in detail by GraharneeSEa It is possible, for example, tocalculate the adsorption of cations and anions, separately, at the metal-solution interface.The corresponding equations for non-polarisable or “ partially ” polarisahlcinterfaces are discussed by Craxford FA and by Grahame and Whitney.66At first sight, method (Ti) would appear attractive, but two difficultiesarise in its application : (a) The theory of electrokinetic effects at metallicsurfaces is at present unsatisfact~ry,~~ because it is not possible to allowadequately for the deflection of current from the solution to the metallicconductor; the well-known equations of D.C. Henry 60 are derived onthe assumption that it is determined by the conductivities of the two phases,but it has been pointed out that polarisation phenomena a t the metal-solutioninterface are probably more ( b ) The exact relation betweenthe electrokinetic < potential and other quantities concerned (e.g., thepotential discussed below) is not clear.6fIn the case of mercury or other liquid metal, there is an additionaldifficulty, since the motility of mercury droplets in an electric field ariseslargely from a circulation within the drop set up by the differing interfacialtensions a t various points of its surface.62 The subject is discussed byA.Frumkin and B. Levich.s3Direct measurements of adsorption, (4), have not been widely used, butthe method has been employed in the study of silver,64 charcoal,65 andplatinum surfaces. 66The detailed structure of the double layer is usually discussed in terms of0. Stern’s theory,67 which may be regarded as a synthesis of the earlierviews of Helmholtz with those of D.L. Chapman and G. G o ~ y . ~ ~ Sternintroduced three new concepts :(i) The overall potential difference between metal and solution is5s A. Frumkin and’ B. Levich, Acta Phyaicochint, IJ R.S.S., 1945, 20, 769; see alsoH. R. Kruyt and J. Oostermann, Kolbid-Beih., 1938, 48, 377.Proc. Roy. SOC., 1931, A , 153, 106.81 E.g., F. Urban and H. L. White, J . Physical Chem., 1932,36,3157; W. G. Eversoleet al., J . Chem. Physics, 1943,11, 63, 156.62 See B. Bruns, A. Frumkin, et al., Acta Physicochim. U.R.S.S., 1934, 1, 232;1938, 9, 359; H. J. Antweiler, 2. Elektrochem., 1937, 43, 596; 1938, 44, 719, 831, 888;M. von Stackelberg, ibid., 1939, 45, 466; T. Krjukova, Acta Physicochim. U.R.S.S.,1947, 22, 381.63 ] b i d . , 1946, 21, 193.64 M.Proskurnin and A. Frumkin, 2. physikal. Chem., 1931, A , la, 29; V. I.Veselovsky, Acta Physicochim. U.R.S.S., 1939, 11, 816; see also H. R. Kruyt andJ. T. G. Overbeek, Trans. Faruday SOC., 1940,36,110.6 5 A. Frumkin et al., Acta Physicochim. U.R.S.S., 1940, 12, 796.6 6 A. Slygin, A. Frumkin, and W. Medwedowsky, ibid., 1936, 4, 91 1 ; A. FrumkinSee also J. J. Bikerman, Phil. Mag., 1942, 33,and A. Slygin, ibid., 1936, 5, 819.384, and ref. (552).2. Elektrochem., 1924, 30, 608.68 See Butler, ref. (10)AGAR : THE KrNETICS OF ELECTRODE PROCESSES. lfidivided into two parts ; one, is the potential difference between a distantpoint in the solution and the centre of an ion in contact with the metal, whilethe other, (+ - is the potental difference between the centre of such anion and the interior of the metal.(ii) The charge in the metal, q per unit area, is given byq = K ( + - $ h l ) .. . . . (9)where K is the (integral) capacity of the “ Helmholtz ” part of the doublelayer.(iii) The charge in the solution, which amounts in all to - q per unitarea, is divided into two parts. The first, - ql, is supposed to consist of ionsoccupying adsorption sites on the electrode surface, and the number of suchions per unit area is evaluated by an application of Langmuir’s adsorptionequation, the adsorption energy being of the form @ & $lP, where I[, is the“ specific adsorption potential ” of the ion in question. The second, - q2,is a diffuse distribution of charge, of the type originally postulated by Gouy.This distribution is calculated 6 7 9 69 by methods similar to those employed inthe Debye-Huckel theory ; the non-linear Poisson-Boltzmann differentialequation in this case can be integrated directly without further approxim-ations.A. S. Coolidge and W. Juda 7O use a different method of calculation.It should be noted that the capacity K relates the total charge to a partof the potential difference-that between the metal and the layer of ions incontact with i t (the “ Helmholtz ” layer) ; K gives no direct informationabout the charge of the Helmholtz layer.68The two charges ql and q2 may be evaluated in terms of #1, the specificadsorption potentials, the concentration, c, and certain known constants ofthe system, and on equating (ql + q2) to - q a rather complicated relationbetween the various quantities is obtained.67 The equation can be simplifiedif the specific adsorption potentials may be neglected and if the ions in theHelmholtz layer occupy only a small fraction of the available sites.For ami-univaIent electrolyte, we then have 46q = K(+ - ,J~) = 2cdP sinh * 1 P + 4c - P sinh -L, * P . . (10) RT K 2Rlwhere K is the reciprocal of the Debye-Huckel characteristic length and dis the diameter of a water molecule, which appears in consequence of theassumption that the number of available dtes in the Helmholtz layer is equalto the number of water molecules in contact with the surface. According to(lo), + and t,hl are both zero at the electrocapillary maximum, where q = 0.Analogous equations may also be derived for electrolytes of other valencyty~es.5~9 7 1When 4 is not too close to zero, it follows from (10) that t,bl is practicallyindependent of 4, though dependent on c.Consequently, if the potential of apolarisable electrode is altered in a solution of constant concentration, the69 S. M. Neale, Trans. Faraday SOC., 1946, 42, 473.l o J . Amer. Chem. SOC., 1946, 68, 608.‘1 A. Frumkin, 2. physikd. Chem., 1933, A , 164, 121 ; see also ref. (57)1 t i C: ENERAL AND PHYSICAL CEIEMTSTRY.change of the Helmholtz potential, A(+ - $1), is practically equal to thechange of the total potential, A$. Furthermore, the observed double-layercapacity, CL = aq/2+, becomes equal to K , which may thus be found bymeasurement of C, in an appropriate range of potential.When K ia known,may be calculated by using (lo); alternatively, may be calculatedfrom (9), using experimental values of the total charge q and of K.463 575 58With the same restriction on the value of 4, i t may also be shown that= remainsconstant, becoming numerically greater as the concentration is reduced.These two well-known results are particularly important in applications tothe kinetics of electrode processes.(RT/F) A In c if the concentration is varied while (+ -K-*.I \I \I \ . - - _ - -IK+I I0.5 1.0FIU. 2 .Potentia/ v. N- ca/orne/ e/ectrode.The capacity of the electrode in the neighbourhood of the electrocapillarymaximum (+ = 0), where CL =i= K , may also be calculated from 573 58But a difficulty arises because the value of K for a negatively chargedelectrode, where the Helmholtz layer consists mainly of positive ions, differsfrom that for a positively charged electrode in contact with a layer of negativeions, and it is not clear which capacity should be used when the charge issmall and the layer contains comparable numbers of both ions.Expressionstaking the two capacities, K+ and K-, into account have been given byFrumkin 463 575 58 and by J. StL. P h i l p ~ t . ~ ~Measurements of the capacity of mercury electrode^,^^^ 573 583 737 74 and72 Phil. Mag., 1933, 13, 775.73 I. i\f. Barclay and J. A. V. Butler, Trans. Faraday Soc.. 1940, 36, 12s.D. C. Grehame, J . Anwr. Ghem. SOC., 1946, 68, 301ACAR : THE KINETICS OF ELECTRODE PROCESSES. I 7related electro-capillary investigations 54, 72 in solutions of ions that do notshow marked specific adsorption are in general agreement with Stern’stheory. The variation of capacity with potential in dilute solutions isusually of the type indicated in Fig.2.469 571 58 The values of K , and K - ,for cation and anion respectively, are given by the two *’ plateaux ”. I n theneighbourhood of the electrocapillary maximum there is a minimum, whichbeconies cieeper and wider as the concentration is reduced, in agreement withtheory. The actual value of the minimum, however, has been found to behigher than that given by the the0ry.4~9 57 The sharp rise in capacity on theextreme left-hand (positive) side probably indicates incipient formation of asolid salt or dissolution of the electrode, and in many solutions, particularlya t higher concentrations, it tends to obscure the true negative ion capacity.Grahame l5 has found i t impossible to fit the curve in this region by a Sternequation including a constant specific adsorption potential.*In more concentrated solutions (e.g., l.0N-potassium chloride) anomaliesappear in the region of the capacity minimum, including a subsidiarymaximum on the left-hand branch near the point of zero ~ h a r g e .l ~ l ~ ~ , 74At intermediate concentrations (e.g., 0-1N-potassium chloride) there is analmost uniform transition from K - to K , , without maximum or minimum.A subsidiary maximum on the right-hand branch appears in solutionscontaining multivalent cations, and is clearly observable in, e.g.,10-3~-HCl + 10-5N-LaC13.Such observations indicate that multivalentcations enter the Helmholtz layer in greater quantities than the Stern theorysuggests as soon as an appreciable negative charge is present on the metaI.The structure of the double layer is thus less diffuse than that pictured bySmall maxima on both sides of the usual minimum have recentlybeen reported 55a for 0.001N-perchloric acid and 0.001N-sodium fluoridesolutions without addition of multivalent ions.Rather different anomalies appear when the solution contains capillaryactive anions, such as iodide. They have been discussed by Vorsina andFrumkin 58 and by 0. Essin and R. Markov; 75 a somewhat differenttreatment of this subject was given by J.A. V. Butler.76 The capacity ofmercury electrodes in the presence of capillary-active organic molecules hasalso been in~estigated.1~~ 55a7 i 3 j 7 iData on the change of ymax with concentration are given by Craxford 54(KNO,, NaCl, KI, CaBr,) and by Frumkin and J ~ f a . ~ ~ From these values,the amounts of electrolyte adsorbed on an uncharged surface may becalculated by the Gibbs adsorption equation. For potassium nitrate andsodium chloride (N and 0 . 1 ~ ) they are positive, though small(< 1 x 10-l0 mol./cm.2) ; larger positive values are obtained when the salt(KI, CaBr,) contains a readily adsorbable anion.5P I n concentrated57A d a PILysicochinL. U.R.X.S., 1939, 10, 353. ’’ .l’r*OC.Ro?~. XOC., 1927, A , 113, 594.i i A . Ksenofontov, R t . Proskurnin, and A. Gorodetslmyn, Actn Physicor.liini. U.R.S.S.,* See also ref. (Eiha).1938, 9, 39; A. Gorodetskap, ibid., 1940,12, 3091s GENERAL AND PHYSICAL CHEMISTRY.hydrochloric acid the adsorption appears to be negative.56 Experimentalresults for sodium chloride solutions a t various concentrations and potentialshave been analysed by Grahame.55a He finds that the specific adsorptionof the chloride ion on a positively charged mercury surface may considerablyexceed the net negative charge of the solution side of the double layer.Some recent values of the capacities of mercury electrodes are given inthe Table.Capacities of mercury electrodes (VF./cm .2).Solution.K-. Minimum. K,. Mothod. Ref.0,00l~-HCl 39 * 8.0 (5.5) 17.2 A.C. (1 c.P.s.) stationary 6TO-OlN-HCl - 9 , 9 9 O-OO~N-HC~ + 39 * 12.9(7*2) 18.6-19.6 ,, ,,7.2 17.5 * I 7 , 58 0-001N-NaOH -0*001N-H2SO4 41 * 8.1 17.3 *0.1 N-KCl N 36 - - 19 460.1 N-NaCl - n!) 1 8-1 I) A.C. y240 to 500G'c.p.s.). 7 1Slowly-forming drop.-_ N 22 Single-sweep osc. (le3 73to lea see.). Exact1 .ON-H,SO,electrode area uncer-tain.C.D.electrode.14.7 (10.5) -0.00 IN-ThCI, (max. 27.8)} N 50 1 *ON-HCI0.2N-HsSO4 - - 20.2 5 2 Slow charging at low 33O-IN-KCI 42.2 - 22.3 Dropping electrode 780.001 to 0.16N-HCl 53.7 1.7 -- 23.3 & 0.5 9 , 9 , 72Hf, K+, Ca++, Al+ I + - - 19 E lectrocap. curve. 540- 1 N - NaC 1 57.3 _ - 23.6NO,- (0.001 to IN) 24 I , 9 ,c104- (0-2N) 26 9 1 9 , so,- (0.01 to 1N) 40 1 , 9 9Figures inparentheses in the third column are theoretical minimum capacities given by Stern'stheory.(iii) Theories of Hydrogen Overpotential.Since theoretical aspects of electrode reactions were last discussed in thesereport^,^ H.Eyring, S. Glasstone, and K. J. Laidler 79 have put forward anew theory of hydrogen overpotential, which may also be adapted to explainoxygen overpotential. Developing the ideas of J. Horiuti and M. Polanyi,sothey assume that the rate-determining step, at least for one class of electrode,is a prototropic reaction * in the neighbourhood of the electrodesolutioninterface. But whereas Horiuti and Polanyi envisaged the processrepresented byEyring, Glasstone, and Laidler suppose that : (i) the proton comes from anH,O molecule (not an H30+ ion), in both acid and alkaline solution; (ii) the- -- -- -* Indicates values derived from curves given in the references cited.OH3+ +Me--+OH, +H-Me .. . . (A)7 8 D. Ilkovic, Coll. Czech. Chem. Comm., 1936, 8, 170.i 9 J. Chem. Physics, 1939,7, 1053; Trans. Electrochem. SOC., 1939, 76, 145.Acta Physicochim. U.R.S.S., 1935, 2, 605; cf. A. Frumkin, 2. physikal. Chent.,1932, A, 160, 116; J. A. V. Butler, Proc. Roy. SOC., 1936, A, 157,423.* Prototropic reactions in general, and the various ways in which they may bepictured, are disciissed by R. P. Bell, " Acid-Base Catalysis ", Oxford 1941 ; see alsoR. P. Bell, Trans. Faraduy SOC., 1941, 37, 493AGAR : THE KINETIC'S OF ET,ECTRODE PROCESSES.19rate-controlling proton transfer occurs between an K,O molecule in thesolution and a layer of adsorbed water on the electrode; (iii) the adsorbedwater is more or less split up into H and OH, separately adsorbed on tiheelectrode. The complete scheme may thus be writtenIH2°-iMnH I - H- H i - 0- H- IH 0-H + 0- Me --+ 0-. . . H ~ . . .o- Me --+ I + HH-Initial state. Activated state. Final state.In their first ~apers,7~ Eyring, Glasstone, and Laidler supposed that theelectrode potential, V , including any overpotential, was developed betweenthe H20 in solution and the adsorbed HO and H on the metal, and assumedthat a fraction aV of the potential determined the free energy of the activatedcomplex; if the proton in the activated state is situated approximatelyhalf-way across the double layer, a will be about 0.5.By a simple applicationof the absolute reaction rate theory, it is shown that the rate of discharge isproportonal to e-aVRW',* whereas the rate of the reverse process isproportional t o efpVF/RT, where a + p = 1 . 7 In a later form of thetheory,Q 82 in order t o explain the fact that q (not V ) is independent of[Ht] in solutions of acids without added salts, it was assumed that : (iv) thepotential V is developed across two double layers; the overpotential iseffective over the inner or " electrode " layer considered above, while thereversible part of V operates over an outer or " solution " layer. Theinfluence of electrode material on y is ascribed to the differing strengths ofthe M-H and M-OH bonds assumed in (iii).The theory has been criticised by A.Frurnkin.,? 84 Although (iv)roughly corresponds to the diffuse and Helmholtz double layers of theStern theory in a solution containing an acid alone, it does not do so whensalts are present in excess. Under such conditions (see later), q definitelyvaries with [H+], and the experimental results indicate that the reactingspecies in acid solutions (though not in alkaline) is H,O rather than H,O.However, the substitution of H,O' for H20 in (i) does not, perhaps,fundamentally change the theory, and it remains to consider suppositions(ii) and (iii), which represent a profound modification of the usual ideasconcerning the structure of a mercury-solution interface.It is difficult t osee how they can be reconciled with electrocapillary and related data.,Eyring, Glasstone, and Laidler were originally led to postulate H,O as thereacting species by a comparison of a few observations for other metals inacid and alkaline solutions; the data on which they base their conclusionS. Glasstone, K. J. Laidler, and H. Eyring, " The Theory of Rate Processes ",Proc. Imp. Acad. Japan, 1939, 15, 39.81 G. E. Kimball, S. Glasstone, and A. Glassner, J . Chent. Physics, 1941,9, 91.McGraw-Hill, 1941 (Chap. X).84 Acta Physicochim. U.R.S.S., 1940, 12, 481.* European sign convention.t A more general relation between forward and reverse rates hrts been derived by.I . Horiuti and M. Ikusima.820 C4NN E RAT, AN 1) PHYSTCAT, CHEMISTRY.are very limited, and it has been criticised on other grounds byJ.A. V. Butler.85G. E. Kimball R6 has applied the theory of absolute reaction rates toion-discharge reactions in a more general manner and has considered theeffect of diffusion processes. Somewhat similar relations have also beenderived by R. A ~ d u b e r t . * ~ A different point of view has been advanced bj-.J. Weiss,8a who supposes that electronic transitions froin the interior of theiiietal to the solution arc sluggish because the electrons have first to beraised to the relatively high surface energy levels.Much attention has been paid to the * ‘ electro-chemical ” mechanismsuggested by Horiuti et aLs9 The reaction in question is usually writtenH,O 4- H-Me-+ H,O 4.- H, + Me .. . . (B)although Horiuti himself sometimes considers 90 a, different, bnt related,process :H, + Xe+ H, -{- MeTt was originally supposed 89 that the adsorbed hydrogen atoms, H-Me,are in equilibrium with the solution, i.e., that the reaction H,O 1- + Me- +H-Me is fast. This assumption leads to conclusions (values of or> 1) incontradiction to experiment if the fraction of the surface, 8, covered byhydrogen is small; 91* 92 it may easily be shown, however, that lower valuesof a are to bs expected if 8 is large.More recently, the possibility has been considered that the reactionsandH,O +Me-+H-Me . .+ H-Me- -+ H, -1 Me H,O. . . (A). . * (R)are both irreversible.l61 25, 91, 93- 94 Neglecting the interaction between theadsorbed atoms, it may be assumed (cf.9k93) that the two reaction rates(current densities), are given byi , == k., [H 3 ( 1 - 0) e-abP,RT *85 J .Chem Physics, 1941, 9, 279.8 7 J . .Phys. Radium, 1942, [8], 3, 81 ; see G. Champetier, “ La Recherche chimique88 See ref. ( 1 ) .89 J. Horiuti, G. Okamoto, and K . Hirota, S c i . Papers Inst. Phys. Chenz. Res. To~!Jo,1936, 29, 323; G. Okamoto, J . Pac. Sci. Hokkaido I m p . Univ., 1937, (iii), 2, 11.5;J. Horiuti, S c i . Papew Inst. Phys. Chern. Res. Tokyo, 1940, 37, 374.8 6 Ibid., 1940, 8, 199, 815, 820.en France ”, 1940-1945 ” (SOC. chimique de France, 1946).E.g., K. Hirota and J. Horiuti, Bull. Chenz. SOC. Japan, 1938, 13, 238.9 1 A. Frumkin, Acta Physicochim. U.R.S.S., 1937, 7, 475.92 A.Frumkin, Sci. Pdpers Inst. Phys. Chem. Res. Tokyo, 1940, 37, 473.93 P. Lukovtsev, S. Levina, and A. Frumkin, Acta Physicochim. U.R.S.S., 1939, 11,21 ; A. Legran and S. Levina, &id., 1940, 12, 243; see also P. Lukovtsev and s. Le\,ina,J . Physical Chem. Russia, 1947, 21, 589, 599.O‘ P. Dolin, B. Ershler, and A . Frumkin, Acta Pliy~icochi?>a. U.R.X.S., 1940, 13. 779.* Strictly speaking, these eqiiations are correct only when the difference betweenneed not be tftken into the overall potential 4 %nil the Helmholtz potential (4account,AGAR THE KINETICS OF ELECTR0I)E PROCESSES. 21andAs soon as a steady current is established, ill = ib, so thati,: k H [H’] f) e - a ’ P H l ’111 general, 8 inay either increase or decrease with 4, but if a’ = a , as inaywell be approximately the case, 0 becomes independent of-\ rather different situation arises if the reaction proceeds by thedtcrnativ-c “ catalytic ” mechanism : 895 95followed byand of i.H,O -+ Me- --+ H-Me (irreversible) (A)(irreversible) (C) 2H-Me ---+ H, + NC‘I’ht: rate of the latter is indepeiidcrit of the potential, so that thereshould cxist a maxiwzunz C.D., corresponding to 0 = 1.96 If‘ the current isincareased beyond this value, some other mode of formation of H,, e.g., (B),must come into action.A somewhat different, cliscwssiori of thc subject has been gil-cii byA.Hickling and F. W. Salt.g7 They assume that thc first stage (A) israpid and reversible, and that the amount of hydrogen adsorbed is determinedby either the Freundlich or the Langmuir isotherm.By suitable choice ofthe exponent in the Freundlich isotherm, it is possible to explain the observedvalues of the Tafel factor u on the basis that (C) is the slow stage, and i t issupposed that the reaction proceeds via (C) at low C.D. At high C.D. thcreaction (B) must also be considered. Assuming thnt it i.s equally probablethat a hydrogen ion will be discharged on an adsorbed H dona as on a vacant site,they conclude that q will become independent of C.D. at high C.D., theavailable adsorption area being 50 yo covered under these conditions.I t is clear from studies of adsorption of gaseous hydrogen on metals 98that the behaviour of the monolayer formed is profoundly affected by themiitual repulsion of the adsorbed atoms.As far as the hycirogen-electrodereachtioil is concerned, this factor uras first taken into awount by Horiuti~t r 1 1 . , ~ ~ 7 90, 95 who coilsidered the effect of repulsive forces 011 adsorbed atomsand on activated complexes of the type H - . . . Hall.., and Had<. . . . H<L,l..corresponding to (B) and (C) respectively. A simpler method hasbeen. developed by Dolin and Ershler, and by Frumkin andN. A41adjalova,16- 253 943 99 following M. Temkiii and V. Pyzhev.100 T t isasslimed (a) that repulsion between the adsorbed particles, or alternativelJ7,inhomogeneity of the suface, causes the energy of adsorption of H atoms toJ. Horiuti and G . Okamoto, Sci. Papers I n s t . Phys. C‘henr. lies. Tokyo, 1936, 28,231 ; Bull.Chem. SOC. Japan, 1938,13, 216.9G E q . , Butler, ref. (80).B* E.g., J. K. Roberts, “ Some Problems in Adsorption ”, Cambridge, 1939.99 Acta Physicochim. U.R.S.X., 1943, 19, 1.loo Ibid., 1940, 12, 327; see also J. Physical C‘hem. Russia, 1940, 14, 1153; 1941,97 Trans. Paruday Soc., 1942, 38, 474.15, 29022 GENERAL AND PHYSICAL CHEMISTRY.fall off linearly with 8, and (b) that the change in activation energy for thevarious processes considered is proportional to the change of adsorptionenergy. It follows from the first assumption that the activity (fugacity) ofadsorbed hydrogen is proportional to efe, where f is a constant,* and thisrelation has been confirmed experimentally by the electrochemicalinvestigation of the equilibrium properties of adsorbed hydrogen on platinum.If a numerical factor al, relating change in activation energy to change inadsorption energy, is introduced, it follows that the rate of deposition ofhydrogen on a partly covered surface (reaction A) isAnalogous relations may be derived for the reverse reaction, and for the" electrochemical " process (B) .94 In subsequent applications it has usuallybeen assumed that al = a, and in some cases, additionally, that al = a = 0.5.Calculations on these lines have led to several interesting results, of which thefollowing may be mentioned :(i) I n some cases the rate of deposition of hydrogen (reaction A) may beindependent of potential.l6> 25 This situation may arise if 8 increases as +become more negative, so that the changes in the two exponential terms in(12) compensate one another.More negative potentials tend to acceleratethe deposition, whereas an increase in 8 leads to an increased repulsiveenergy, which tends to make it slower.(ii) If hydrogen atoms are ultimately removed from the electrode bythe electrochemical mechanism (B), the conclusion that 8 should beindependent of i, already discussed for a simpler model in which interaction isneglected (cf. ll), also holds under certain conditions for the morecomplicated case.94(iii) If hydrogen atoms are ultimately removed by the catalyticmechanism (C), or by diffusion into the metal, the overpotential should beadditively composed of two parts, one characteristic of an equilibriumbetween the adsorbed hydrogen and the solution, and the other depending onthe kinetics of the deposition stage (A).99on the depositionof hydrogen ions (A), and on the corresponding reaction in which thereacting particle is a water molecule, has been further considered byFrumkin.21 37 46, 719 919 93 When the reacting particle is an H,O+ ion, it isassumed that the rate of deposition iswhere [H#Is is the hydrogen-ion concentration a t the interface, ($ - $J isthe potential across the Helmholtz layer, and F represents some function,which, on experimental grounds, may be expected to have the formi=k[H+]e-aIfee-aQFRT .. . . . (12)The influence of the diffuse double-layer potential,i = [H+lSw$ - $1)F(+ - = k: e- 4 4 - h)P/R2'* The relation given apparently implies that the difierential free energy of adsorptionis linearly dependent on 8 ; Temkin and Pyzhev actually consider the heat of adsorption,but the distinction is probably not important provided f is reasonably large and 6 is closeneither to 0 nor to 1AGAR : THE KINETICS OF ELECTRODE PROOESSES.23Provided that [H+lS is not too large, we have[H+Is = [H+], e-JllFIRTwhere [H'], is the bulk concentration. It follows that lo1RT . 1 - R RT 1 - RI'1-q I = --In z - (,-) ln[Ht]o + (,") t,hl - = I n k . (13):l: aPFor a mercury cathode, #1 is normally negative, and, as a < 1 , any reductionof its numerical value, e.g., by addition of neutral salts, should increase -4.On the other hand, if #1 remains constant while [ H - ; - ] , is varied, r ) shouldincrease by 2.303[(1 - a)/cr]RT/Pv. for each tenfold reduction in [H*],,.But if a solution of an acid alone is diluted with water, the ensuing changesin (cI1 and (RT/F) In [H+], cancel one another and q remains unaltered.If the reacting particle is H,O inst,ead of H,O-i, (13) no longer holds, andthe corresponding equat,ion isRT . RT RTaF P O aP 171 =-- In z + _ _ I n [H-'-] - # - -- ln k' .. . (14)The effects of change of [H+], (at constant +1) and of change of 1,h1 (at coiistttnt[H+l0) are thus in the opposite direction to those given by (13).These relations were originally worked out for the deposition of hydrogenand have been mainly used in connection with this reaction, but theprinciples involved should be applicable to other cases.45- l01The definition of the heat of activation in electrode reactions has beendiscussed by J.N. Agar,lol who also considers the possible temperaturevariation of a. It has been shown that the relation between heat ofactivation E' and overpotential discovered by F. P. Bowden : lo2and easily explicable if the rate-controlling stage is of the type (A), alsoholds if it is of the type (C).E = wo - aP(iv) Experimental Investigations of the Deposition of Hydrogen fromAqueous Xolutions.(a) Mercury Cathodes.-Although most investigators have confined theirattention to current densities between and amp./cni.2, somemeasurements have been made at lower and at higher C.D.s; the latter arediscussed in another section. Using a special technique to exclude oxygen,F.P. Bowden and K. E. Grew 103 studied the deposition of hydrogen from0*2~-sulphuric acid and found that the Tafel relation (1) held down to10" amp./cm.2, although the value of b was slightly greater than that usuallyobserved a t higher C.D. A. Mituya lo4 also made measurements in this1°3 See ref. (1).Io1 J. K. Agar, see ref. (1).lo2 Proc. Roy. Soc., 1929, A, 126, 107.lo4 Bull. Inst. Phys. Chem. Res. Tokyo, 1940, 19, 142; A . , 1940, I, 324.* Comparison of (1 3) or (14) with the empirical '1'afel equation ( 1 ) shows that the" a "s in the two cases are not strictly the The empirical a includes acontribntion, usually small,71 arising from the fact that 4, varies slightly with 4 (or v).'24 GENERAL AND PHYSICAL CHEMJSTRT.range, but his work has been criticised by Frumkin,2 who points out that hisresults for the higher C.D.s do not agree with established values and suggeststhat the electrode was contaminated by platinum, as appears possible in theapparatus used.I n the more usual range of current densities, 8.Jofa, A. Kolychev, andL. Shiftman lo5 have resolved a long-standing disagreement between theresults for stationary and dropping electrodes ; lo6 they show that identicalvalues of q are obtained by the two methods provided the dropping-electrodevalues are corrected for the non-faradic current and for changes in dropvolume as the potential becomes more negative. Measurements of hydrogenoverpotential on a mercury-jet electrode are also in agreement with those forstationary surfaces.lo7Several workers have confirmed 2y 33 l o 7 9 lo8 that the overpotential isindependent of concentration in dilute solutions of acids without added salts.On the view that the overpotential is due to reaction (A), this is in agreementwith (13), but it can also be explained in other ways.In more concentratedsolutions (> 0 . 1 ~ ) of hydrochloric, hydrobromic, sulphuric, and perchloricacids, a fall of -q is observed with increasing [H+],; l o 7 7 log, 110 in many casesthe q-log i curves are no longer linear, and there is a general tendency for theoverpotential to be more nearly independent of concentration a t thc morenegative electrode potentials., Frumkin and Jofa 2. 33 110 explain theseobservations as an effect of the penetration of anions into the double layer,giving rise to a more negative value of t,hl than the Stern theory, in its simpleform, predicts.in some of the solutions used, although the changes in ^r) are somewhat lessthan would be expected from the $i values.2Concentrated solutions of sulphuric and phosphoric acids have beenstudied by A.J. de Bethune and G. E. Kimball,los who also observe a fall ofoverpotential, which they ascribe to reaction of undissociated acid molecules.Such an effect is, perhaps, to be expected, but it would appear difficult toexplain the observations for perchloric acid in this manner.3The influence of addition of salts on the hydrogen overpotential was firstdemonstrated by S. Levina and V. Sarinsky,lll who added small amounts ofLaCI, to dilute HC1 solutions and observed an increase of overpotential,which is greater than that given by (13) when t,hl is calculated from Stern'stheory [eqn.(lo)] but somewhat less than expected if is obtained froincapacity data. The results have been discussed by Frumkin.2, 46The influence of additions of potassium and sodium chloride tohydrochloric acid solutions (constant [H '-I,,) has been investigated byThere is independent evidence of high negative values of105 Acta Physicochina. U.R.S.S., 1940, 12, 331 ; cf. Frumkin, rcf. (2).106 J. Heyrovsky, Chem. Reviews, 1939, 24, 125.107 A. Rius and J. Llopis, Anal. Fis. Quinz., 1946, 42, 897.108 J . Chem. Physics, 1945, 13, 63.1OQ 5. Jofa, Acta Physicochinr.U.R.S.S., 1939, 10, 903 ; J . Physical ChenL. Russia,110 Acta Physicochiin. U.R.S.S., 1943, 18, 183; see also J . Physical C'he7n. Russia,1939, 13, 1435.1944, 18, 268. ll1 Acta Physicoclbim. U.R.X.S., 1937, 7 , 485AGAR : THE KINETICS OF ELECTRODE PROCESSES. 25Bagotsky 112 and by J. Llopis and J. N. Agar.ll3 For these two salts verysatisfactory agreement with equation (13) is obtained when +1 is calculatedfrom Stern’s theory (or a modification of it).112 There also appears to befair agreement for additions of calcium ch10ride.l~~It has also been shown l l 2 9 113 that the overpotential in acid solutionsincreases by 0.058 v. per pH unit when [H-;], is decreased, provided the total(univalent) cation concentration, “a7, K+] + [Hi],, remains constant ;under these conditions is also constant, and, since u = 0-5, the result is inagreement with (13). Rather similar results have been obtained in moreconcentrated solutions (total cation concentration = 4M) by Jofa andFrurnkin,llo who also note that there is no correlation between the over-potential and the activity coefficient of hydrochloric acid, which dependsconsiderably on the nature of the salt (LiCI or KC1) present.The behaviour in alkaline solutions is entirely different. Kxperiments insuch solutions are difficult, owing to amalgam formation, and the observationsare less reliable, but i t has been confirmed 113 that a = 0.25 in NaOHsolutions, and an investigation of the influence of [OH-] in NaOH-NaClmixtures, with [OH-.] + [GI-] = constant ( O - ~ N ) , shows that -q in this casedecreases by 0.058 v.per unit increase of pH, a result to be expected if thereacting particle is H,O rather thaii H30 + [cf. eqn. (14)].Although addition of salts normally raises the overpotential in acidsolutions, the reverse effect may occur under some conditions if the anion ofthe added salt is strongly adsorbed on the electrode; 2. 11* an effect of thissort occurs with bromides a t low overpotentials. The influence of the iodideion has also been investigated ; 114 i t brings about a large lowering (ca. 0.2 v.)of q a t low C.D., but a t more negative potentials, where the iodide ions are nolonger adsorbed, the overpotential rises t o the usual value. A markedhysteresis effect is observed, which suggests that the adsorption anddesorption of iodide ions (on the negatively charged metal) is a relativelyslow process.Addition of certain capillary-active cations (e.g., tributyl-ammonium) to acid solutions raises the overpotential; 11* the effect may beascribed to the positive charge carried by the ions, but is possibly due in partto a siiiiplc blocking of the surface. J. O’M. Bockris and B. 1E. Conwayhave shown, however, that many alkaloids can Lower the hydrogen over-potential. 115The reliable experimental evidence now available indicates very stronglythat the rate-determining step in acid solutions is reaction (A), at least a t(2.D.s up to amp./cm.2.The main arguments leading to this conclusion may be summarised asfollows : 2 7 (i) Electrocapillary and capacity measurements over a wideraiigc of potential, both in acid and in alkaline solution, show that the112 Unpublished results quoted by Prumkin, ref.( 3 ) .113 Anal. Pis. Quin2. (in the press).llp S. Jofa, 13. Kabanov, E. Buchinski, and F. Chistyakov, Acta PhysicocltinL.115 Nature, 1947, 159, 711.U.R.S.S., 1939, 10, 31726 GENERAL AND PHYSICAL CHEMISTRY.mercury-solution interface corresponds closely to the ionic double layersenvisaged in Stern’s theory. There is no sign that adsorbed hydrogen atomsare at any time present in quantities even remotely approaching a completemonolayer. (ii) The only process that will give the observed value of aunder these conditions is (A). (iii) Measurements of the influence of changesin [H1 lo and of addition of salts show that in acid solutions H30+ participatesin the rate-controlling reaction.For alkaline solutions, the less extensiveevidence suggests that the corresponding particle is H,O.(b) Phtinum Cathodes.-Several recent investigations 947 116, 117 haveshown that the hydrogen overpotential on really clean, bright platinum ismuch lower than has generally been supposed. Platinum electrodes may becleaned or “ activated ” in situ by a brief anodic polarisation, and instringently purified solutions their activity does not change appreciably inperiods of the order of an hour. If the solution has not been purified, or iftraces of poisons (e.g., As203) have been added to it, the activity decays veryquickly, and the decay is accelerated by 117 This shows that theloss of activity is primarily due to deposition of some constituent of thesolution, and not to a slow “sintering ’’ of the metallic surface.Thenecessary purification of the solution may be carried out by leaving it incontact for some hours with large sheets of platinised pIatinum.At such electrodes, in acid solutions, the activation overpotential is of theorder of only 1 mv. a t 1 ma./cm2, and in unstirred solutions considerableconcentration overpotential is observed, arising from supersaturation of theliquid near the electrode with hydrogen. This overpotential can be decreasedby coating the electrode with a few monolayers of a long-chain fatty acid,which facilitates the removal of hydrogen as b~bb1es.l~~ The activationoverpotential in alkaline solutions is somewhat higher than in acid.94* 1 1 7The formation of adsorbed layers of hydrogen or oxygen on platinised andbright platinum a t potentials between the reversible hydrogen and thereversible oxygen value has been carefully investigated by Frumkin and hisco-workers,169 173 251 26, 66, 1181 119 by means of slow-charging curves and byother methods.Similar results have been obtained a t higher currentdensities, using a cathode-ray oscillograph to follow the more rapid changes ofpotential; 1 1 7 9 120, 121 this method has also been used to study gold 122 andsilver 123 electrodes, where rather different effects are observed. Althoughthe slow-charging curves approximate fairly closely to equilibrium conditions,comparison of observations made during deposition of the adsorbed film withthose made during its removal show that the process is not completelyreversible ; the irreversibility is probably more marked at higher currentI l 6 L.Kandler, C. A. Knorr, and C. Schwitzer, 2. physikal. Chem., 1937, A , 180, 281.1 1 7 G. C. Barker, private communication ; Diss., Cambridge, 1947.11* B. ErshIer and A. Frumkin, Trans. Furaduy SOC., 1939, 35, 464.119 A. Frumkin, A. Slygin, B. Ershler, and G . Deborin, Acta Physicochim. U.R.S.S.,lao J. D. Pearson and J. A. V. Butler, Trans. Furaday SOC., 1938,34, 1163.121 A. Hickling, ibid., 1946, 41, 333. 12? Idem, ibid., 1946, 42, 518.123 A. Hickling and D. Taylor, see ref. (1).1935,3,791; 1937,7,325; 1938,8,565; 1939,11,45AGAR : THE KINETICS OF ELECTRODE PJWCESSES.27densities. In acid solutions the equilibrium charging curves show threedistinct regions; starting with an electrode at or near the reversiblehydrogen potential they correspond to (i) removal of approximately amonolayer of hydrogen, (ii) charging the double layer on an almost baresurface, (iii) deposition of a layer of oxygen. I n alkaline solution thedistinction between the three regions is not so clear. The observed linearrelation between potential and quantity of electricity passed in region (i)shows that the heat of adsorption of hydrogen must decrease considerablyas the fraction of the surface occupied increases, and this has been confirmedby measurements of the differential heat of adsorption of gaseous hydrogenon platinum black.124 The bonds between the metal and the adsorbedhydrogen or oxygen atoms appear to have appreciable dipole moments, theiiegative ends being directed towards the solution.66 In the case of oxygenlayers the potential difference arising from the dipoles may .be greater thanthe overall metal-solution potential difference ; in consequence, the double-layer potential, and the 7: potential, are reversed, as may be shown byelectrokinetic e~perirnents.~~The distinction between the " double layer " region, and the two(hydrogen and oxygen) " adsorption " regions is shown very clearly by thecoefficient of friction between two platinum surfaces, which is much higher inthe double layer region than at lower or higher potential~.~~1 117The kinetics of formation and removal of adsorbed hydrogen have beenstudied by the alternating-current method 16, 1'9 25 (see p.9). In theregion of the reversible potential, the rate of deposition is almost independentof the potential [cf. p. 22, (i)] and is 10-20 times greater than the rate ofthe complete process H+ --+ H,, as measured with steady currents.94 Ittherefore appears that stages of the process subsequent to deposition ofadsorbed atoms have an important influence on the kinetics in this case.Similar investigations have been made in heavy water; 25 undercorresponding conditions, the rate of formation of adsorbed deuteriumproceeds a t about half the speed of formation of adsorbed hydrogen.( c ) Other Metals.-A careful investigation of hydrogen overpotential onlead cathodes in acid solutions has shown that the overpotential is evengreater than on mercury; 367 125 it also seems that clean lead electrodes givea value of cc close to 0-5, although earlier work 126 generally indicated lowervalues of a, and of the overpotential.36 Anomalous results are obtained ifthe potential of the electrode is allowed to become sufficiently positive foradsorption of anions (e.g., SO,=) or formation of lead salts to occur, or if highcurrent densities, which cause disintegration of the surface, are used.It appears that the reduction of lead salts (e.g., the sulphate), when oncethey have been formed, is a somewhat slow process, and this may explainI z 4 1,.Rfaidanowskaja and B. Bruns, Acta Physicochir,b. U.R.S.S., 1938,9, 927.lZB See also A. Frumkin and Y. Kolotyrkin, ibid., 1941, 14, 469; S. Jofa, J . PhysiculCheut. Russia, 1945, 19, 117; Y. Kolotyrkin and N. Bune, ibid., 1946, 20, 667; 1947,21, 581. alZ8 E.g., T. Erdey-Grriz and H. Wick, 2. physikal. Chem., 1932, A , 162,5328 GENERAL AXD PHYSICAL CHEMISTRY.the discrepancbies to be found in previous results for this metal. A similar'* slow reduction " effect may occur on iron e1e~trodes.l~'Lukovtsev, Levina, Legran, and Frumkin 93 have found that the hydrogenoverpotential on nickel cathodes increases with increasing pH in acidsolutions, but decreases with increasing pH in alkaline. Addition of neutralsalts lowers the overpotential in alkaline solutions, but may produce either aslight increase or a slight decrease in acid solntions, according to the currentdensity used.These observations show that the rate-controlling stagesinvolve H ' ions in acid solutions and, probably, H,O molecules in alkaline ;they can be explained qualitatively in terms of a slow deposition processfollowed by irreversible forination of H, by the electrochemicalniechanism (R) .Frumkiri and A l a d j a l o ~ a , ~ ~ and H. P. Stout,12* using a palladiu,i/diaphragm polwised on one side only as cathode, have demonstrated that aconsiderable part of the overpotential " comes through " the diaphragm tothe unpolarised side within a few minutes of starting the current ; similarobservations have been reported for irod29 Prumkin and Aladjalova showthat the overpotential 011 the polarised side is additively composed of twoparts, *tjl and rjZ; ql arises probably froiri the deposition of hydrogen aboms,is rapidly established, and is milch larger in alkaline than in acid solutions;q2 is characteristic of the concentration of hydrogen dissolved in the metal[cf. p.22 (iii)] and is transmitted to the unpolarised side of the diaphragm.Measurements of hydrogen overpotential on thallium have been made byT. M. Le Barrori and A. It. C h ~ p p i n , l ~ ~ using sulphuric acid solutions from04001 to 0 . 5 ~ ; the temperature coefficient of -q was also determined.Several less common metals (Ni, Cu, Pb, Mo, Tu, Nb, Be, In, and T1) havebeen studied by J.O'M. Bockris,l31 who has also shown that, for a largenumber of metals, there is a negative correlation between overpotential andthermionic work function. There is, as yet, no satisfactory explanation ofthe correlation.(d) High Cuwent Den,sities.-An extensive investigation of hydrogenoverpotential on many nietals at high ciirrent densities ( to 1 amp./cm.2)has been carried out by A. Hickling and P. W. Salt.42. 9s. 132 I n order toeliminate resistance overpotential, the potential was measured after thccurrent was cut off, using a specially designed electronic interrupter andmeasuring circuit. In many cases (notably for mercury) the ?-log i curvesare non-linear, and show a tendency to approach a limiting overpotentialat high C.D. It has, I n some cases (e.g., lead) the curves have a maximum.Iz7 8.Levina et al., J . Physical Chetji. Russiu, 1947, 21, 32.5 ; Frumkin, ref, (3).12@ H. H. Uhlig, N. E. Cam, and P. H. Schneider, Tram. Elecfrochcw. SOC., 1941,130 dbid., 1940, 77, 289.131 il'ature, 1947, 159, 539; Trans. Faruday Soc., 1917, 43, 417; see also V. S . Joffe,Cspekhi Khinr., 1943,12, 438.132 Trans. Faraday SOC., 1940, 36, 12%; 1941, 37, *24, 319, 333; see also Hickling,ibitl., 1937, 33, 1540.See ref. (1) ; also R. M. Berrer, 7 ' r a ~ s . Furada!j SOC., 1940, 36, 1235.79, 11AGAR : THE IEINE'I'ICS OF ELECTRODE PROCESSES. 29however, been shown that the decay of overpotential during the shortinterval between interruption of the current and measurement of thepotential may be considerable; 2 the exponential character of the decaymakes it impossible to extrapolate decay curves to zero time graphically,hut if the extrapolation is carried out by equation ( 5 ) , Hickling and Salt'sobservations for mercury agree with the usual linear ?-log i relation found a tlower current densities.2011 other inetals, the clec.,zy of overpotciltial limy be less i-ztpicl, and theerror in Hickling and Salt's measurements mny therefore be smaller.. 111support of this view, Bockris l31 has shown hhat for several metals theq-log i curves measured by the " direct " method also flatten off a t highcurrent densities.No such effect was, however, observed by B. K a b a n o ~ . ~ ~ Measurements have also been made of the hydrogen overpotential onplatinised platinum cathodes a t high current densities ; in this caseconcentration overpotential is important, but it does not provide 8 1 1explanation of the very high overpotentials sometimes observed.It hasbeen suggested 134ct that they may be due to a slight inequality in theconcentrations of positive and negative ions near the electrode.135(v) Anodic Processes.The evidence in favour of the hydrogen peroxide theory of anodicoxidation has been reviewed by S. Glasstone and A. H i ~ k l i n g , ~ ~ ~ who havealso disccused the Kolbe synthesis and allied reactions.137 A. Hickling 138has dram1 attention to the interesting fact that the potentials and pH atwhich the Kolbe reaction proceeds with good yield should also bring aboutrapid evolution of oxygen, which is not observed.In criticism of thehydrogen peroxide theory, it has been pointed out that hydrogen peroxide isformed anodically only in exceptional circumstances, and that i t is readilydestroyed by anodic oxidation.139The electrodeposition of oxygen from 0 . 1 N-sodium hydroxide on platinuinanodes: has been investigated by H. P. Sto1Lt,l4O who finds a linear -4-log irelation with o! = 1.0; the energy o€ activation a t the reversible oxygenpotential, derived from the temperature coefficient of overpotential, is25.3 kcals.Measurements of oxygen overpotential on several other metals in alkalinesolutions show that the behaviour of the electrodes is often very complicated,especially a t high current densities.141V. IT.Slender, J . Appl. Chem. Russia, 1946,19, 1303.133 Acts PhysicociLiw. U.R.S.S., 1936, 5, 193; see also A. G. I'echerskaya and134 ( a ) G. E. Coates, J . , 1945,484; ( b ) P. M. Bryant and G. E. Coates, see ref. (1).135 Cf. R. M. Fuoss and M. A. Elliott, J. Amer. Cheni. SOC., 1946,67, 1339.136 C'hem. Reviews, 1939, 25, 407.l S i T'rans. Electrochem. Soc., 1939, 75, 333.139 Eq., W. D. Bancroft, Tram. Electrochent. Soc.. 1937, 71, 1%; M. Haissinsky,140 See ref. ( 1 ) ; cf. -412n. Reporfs, 1938, 35, 101.l4I A. Hickling and 8. Hill, see ref. (2).13* See ref. ( 1 ) .see ref. (1)30 GENERAL AND PHYSICAL CHEMISTRY.The electrodeposition of the azide ion on platinum, palladium, andiridium anodes has been shown 142 to require an overpotential of about 4volts a t measurable current densities; this is probably the highest over-potential yet recorded. The value of a is approximately 1, but increasesslightly with rise in temperature, and the C.D.a t a given potential isproportional to [N3-]. The emission of light a t the anode during electrolysisof azides has been reported by R. Audubert.143(vi) Non-aqueous Solvents.In agreement with the observations of S. Levina and M. Silberfarb,lUI. S. Novoselski 146 has found that the hydrogen overpotential on mercurycathodes in ethyl and methyl alcohols is somewhat less than that in aqueoussolutions. A similar decrease of overpotential has also been reported fornickel cath0des.~3Hydrogen and oxygen overpotentials in mixtures of organic solvents andwater have also been 14’ In the case of hydrogen depositionfrom acid solutions in methyl alcohol-water mixtures,146 using a leadcathode, the overpotential is found to have a maximum value at ca.50% ofwater, and to be much lower in the pure alcohol than in pure water ; in someother solvent mixtures, minima are observed. On nickel cathodes, thesolvent effect is much smaller and the intermediate maxima or minima areeither absent or much less marked.At certain current densities, the oxygen overpotential on platinum inN-sulphuric acid solution in dioxan-water mixtures also appears to passthrough a maximum at intermediate concentrations ; 147 with pure dioxanor pure acetic acid as solvent, it is higher than in aqueous solution.Hydrogen overpotential on nickel cathodes in liquid ammonia has beenfound to be higher than in aqueous solutions ; 148 lead and mercury electrodesseem to be unsuitable in this medium, possibly owing to “amalgam ”formation.V. Pleskov has also discussed the anodic evolution of nitrogenfrom liquid ammonia.149(vii) Diffusion and Convection Processes.It has been customary to discuss mass (solute) transfer between thesurface of an electrode and a moving solution in terms of a “diffusionlayer ”; 1% this concept is useful because it circumvents some difficult142 H . P. Stout, Trans. Faraday SOC., 1945, 41, 64; see also R. Audubert andE. T. Verdier, J . Chim. physique, 1942,39, 48; C m p t . rend., 1941,213, 870.143 Bull. SOC. chim., 1940, 7 , 907; E. T. Verdier, Compt.rend., 1942, 214, 617; 1943,216, 183.144 Acta Physicochim. U.R.S.S., 1936, 4, 275; see also Bowden and Grew, ref. (1).145 J . Physical Chem. Russia, 1938, 11, 369 ; A., 1938, I, 576.146 J.O’M. Bockris, Nature, 1946, 158, 584; see ref. (1).14’ Idem, aid., 1947, 159, 401; see ref. (1).148 V. Pleskov, Acta Physicochim.. U.R.S.S., 1939, 11, 305.140 Ibid., 1945, 20, 578.160 W. Nernst, 2. physikal. Chem., 1904, 47, 52AGAR : THE KINETICS OF ELECTRODE PROCESSES. 31hydrodynamical problems, but it is unsatisfactory in several respects andseems also to have been frequently misunderstood. The original diffusion-layer theory implied that there was a stationary layer of liquid in contactwith the electrode.; within the layer only diffusion is operative, whereasoutside it the concentration is supposed to be kept uniform by convection,I n actual fact the liquid in the layer is not stationary, although its motionmay be largely parallel to the electrode surface, so that there is littleconvective transfer of solute to or from the electrode.A great advance has recently been made by B.Levich,l6191a who hasdeveloped the fundamental theory of convective diffusion a t electrodes,using modern hydrodynamical concepts, and following, in general, the lineson which the closely analogous problems in heat transfer have been treated.Dimensional methods have also been used ; 153,156 such methods do not givea complete solution, but the gaps may be filled by the use of comparativelyfew experimental results, including heat- transfer mea~urernents.~~~Calculations have been carried out for laminar and turbulent forcedc o n ~ e c t i o n , ~ ~ ~ ~ 152 and for natural convection arising from changes in thedensity of the solution near the electrode.l5l> The results are inagreement with experiment, particularly in the ease of a rotating-discelectrode, which is hydrodynamically simple.For such an eleotrode,Levich lS2 finds that the conventional Nernst diffusion layer thickness, 6 ,is given byD * + 8 = 1*62(--) (f) em.where D is the diffusion coefficient, v the kinematic viscosity, and w theangular velocity. This equation is in accordance with the more generaldimensionless equation : 163const.(Pr)-?h (Re)-m i =where I is a characteristic length (e.g., the radius of the disc), Pr (Praiidtl’snumber) = v/D, Re (Reynold’s number) = UZ/v, and U is a charaoteristiclinear velocity (e.g., the peripheral velocity).It appears that the valuesn = 4 and m = 3 hold for laminar motion and high values of Pr in manysystems ; the relation between the quantities is different when the motion isturbulent. J. N. A.151 Acts Physicochim. U.R.S.S., 1942,17, 257; 1944,19, 117, 133.162 See ref. (1).153 J. N. Agar, see ref. (1).154 N. Y. Buben and D. Frank-Kamenetsky, J. Physical Chem. Russia, 1946,20, 225.lS5 Cf. C. V. King and P. L. Howard, Id. Eng. Chem., 1937, 29, 76; S. Uchida,J. SOC. Client. Ind. Japan, 1933, B, 36, 416; A. W. Hixson, Ind. Eng. Cliem., 1944,36, -18833 GENERAL AND PItYSICAL CHEMISTRY.2.FAR ULTRA-VIOLET SPECTRA AND RELATED TOPICS.In recent years there have appeared a number of excellent reviews ofelectronic spectra in general and of work in the near ultra-violet region inparticu1ar.l Important reviews have also appeared of the far ultra-violet33 * Of these, the first is particularly useful for experimental methods,the second contains most useful tables of spectra reported before 1941, ttndthe third brings these tables up to date to 1944. Since 1044 a considerablefurther volume of work in the far ultra-violet region has been published,justifying a further review. Not since 1939 has a survey of the regionappeared in these report^.^ The present Report collects together some ofthe recent work on electronic spectra, with primary (but, since there is nosharp dividing line between spectra in the far and near ultra-violet regions,not exclusive) stress on the wave-length region below 2000 A.A summaryof attempted applications of some of the data to chemical problems hasappeared elsewhere,6 as has also a simplified account of far ultra-violetspectra and of the theory underlying their interpretation.’Two of the major developments since the last Report have been (1) theextensive determination of molecular ionisation potentials by Price and hisschool, and (2) the beginning of much greater stress on intensities ofabsorption. The ionisation-potential determinations have usually beencarried out by observation of Rydberg series, but have been helped byelectron-impact work performed in conjunction with the spectroscopictechnique; * the first method gives the greater accuracy, but the secondhas the advantage of indicating clearly the existence of an ionisation limit.W.C. Price gives a list of many of the ionisation potentials so far determined.The stress on intensities dates from a most important series of papers byR. S. Mulliken in 1939,lO in which he showed the great value of intensitymeasurements for interpreting spectra and in which he appealed for furtherdata. The war meant a lapse of some years before his cry could be answered,but, latterly, increasing numbers of workers have been turning their attentionto the experimental problem of absolute intensity measurements. Manyexamples of these two outstanding developments will be found scatteredthrough this Report.* E.J. Bowen, Ann. Reports, 1943,40, 12; W. R. Brode, “ Chemical Spectroscopy,”2nd ecltn., Wiley, 1943; R. N. Jones, Chern. Reviews, 1943, 32, 1 ; E. A. Braude, Ann.Reports, 1945, 42, 105; K. Bowden, E. A. Braude, and E. K. H. Jones, J . , 1946, 94s;A. Maccoll, Quart. Reviews, 1947, 1, 16.For experimental methods see also a J. C. Boyce, Rev. Mod. Physics, 1941, 13, 1.R . A. Sawyer, “ Experimental Spectroscopy,’’ Prentice-Hall, 1944.H. Sponer and E. Teller,’Rev. Mod. Physice, 1941, 13, 76.J. R. Platt and H. B. Klevens, ibid., 1944, 16, 182.W. C. Price, Ann. Reports, 1939, 36, 47.A. D. Walsh, V. Henri Memorial Vol., Desoer, Likge, 1947.Idem, Quart. Reviews, 1948, 2, 73.* T. 31.Sugden, in the press.lo .J. Chena. Physics, 1939, 7, 14, 30, 121, 339, 353, 356, 364, 670;Chenb. Reviews, 1917, 41,For summary, see R. S. Mulliken and C. -4. Rieke, Rep. Prog. Physics, 104857., 8, 331.940, 8, 234\VALSH : &AH. ULTRA-VlOLET SPECTEA ANL) RELATED TOPICS. 33Ethylene, Allcylethylenes, and Alkylation Red Shifts.-The far ultra-violet spectra of light and heavy ethylene, propylene, trans-but-2-ene,and trimethyl- and tetramethyl-ethylene were described by Price and W. T.Tutte.ll At low pressures the ethylene absorption begins abruptly at1745 A. with a series of bands which undoubtedly represent a first transitionof a Rydberg series leading to the ionisation potential at 10.50 v. Super-imposed upon these is a weaker region of absorption stretching from 2000 A.to beyond 1600 A.with a maximum a t 1630 A. Its characteristics agreewell with those expected for an N , V transition of a x electron,12 i e . , atransition from the ground state to an orbital with an extra node betweenthe carbon nuclei. With increasing methyl substitution, the r=-l ionisationpotential decreases and the N , V transition shifts to longer wave-lengths.The ionisation potential decrease can be attributed largely to the “ inductiveeffect” of the methyl group. This effect is sometimes called “ chargetransfer ”, because, when H in a bond H-X is replaced by CH,, the bondelectrons move nea.rer to X, i.e., transfer of negative charge to the regionround X occurs. The ionisation potentials of the group X will therefore bedecreased because of the repulsion between electrons.In the case ofethylene and propylene, in terms of hybridisation of valencies, the effectmay be described as follows.13 Replacement of H in C,H, by the lesselectronegative CH, group evokes more s character in the carbon vadencytowards the CH,, and therefore more p character in the carbon valencyinvolved in the CF bond of the C=C. The CF electrons of the C=C group thusbecome more weakly bound. The repulsion between them and the outlyingx electrons therefore increases, with the consequence that a x electron ismore easily removed. This raising of the ground state orbital in consequenceof charge transfer must be part of the reason for the N,V shift to longerwave-lengths. As Mulliken points out,12 one would expect the charge -t;rensfer effect to cause a smaller raising of the Y than of the iV state, becauseof the larger size of the excited orbital.Computation of the term valuesfor the V state readily shows that they d9 show decreases with alkylation,these decreases being smaller in absolute magnitude than the ground-statechanges. Consequently, since the effect means a diflerential raising ofthe two states, if we believe charge t,ransfer to be largely responsible forthe ground state changes we must believe that it plays a considerable partin the N,V shift to longer wave-lengths. Froin a theoretical point of viewanother effect is also expected to play a contributory part. This effect iscalled ‘‘ hyperconjugation ” and is due to a delocalisation of the electronsin thc CH, groups.That is, it results from the inadequacy of our traditionalboiid diagrams to represent the whereabouts of electrons. It would raisethe ground state and, by itself, lower (increase the term value of) the excitedstate. The inductive and hyperconjugation effects work in the samedirection on the ground level, but in opposite directions on the upper level.The observed decreases of excited level term values then prove the importance11 Proc. Roy. Soc., 1940, -4, 174, 207.l2 R. S. Mulliken, Rev. Mod. Physics, 1942, 14, 265.REP.-VOL. SLIV. 34 GENERAL AND PHYSICAL CHEMISTRY.of the effect of charge transfer on the excited state. There is little doubtthat this effect of hyperconjugation must occur : the only question is thequantitative one of how important it is relative to the charge transfereffect." Mulliken suggests that the red shift in the N,V transition may beentirely explained by hyperconjugation ; but as shown above, this does notaeem likely in view of his own agreement that charge transfer is largelyresponsible for the ground state raising.? In other cases (see discussionbelow on cyclic diems) i t seems clear that the effects of hyperconjugationhave been over-estimated.I n the effect of alkylation on systems largerthan the ethylene molecule, it is probable that hyperconjugation becomesmore important, relative to the inductive effect, than in ethylene; for, asW. C. Price and A. D. Walsh l4 have stressed, the inductive effect is shortrange, and therefore such a property as the activation of the p-position intoluene must be explained as due to hyperconjugation. Similarly, themarked lowering of r1 ionisation potential (9-24 to 8.92 v.) in toluenerelative to benzene must be explained as to a considerable extent due tohyperconjugation since the electron ionised previously spent only a part ofits time in the neighbourhood of the alkyl groups.The smaller value of theionisation potential lowering (0.32 v.) relative to the ethylene-propylenechange (0-80v.) agrees with the importance of a short-range effect in thelatter case. We shall return to these points in our discussion below of thespectra of the alkylbenzenes.These explanations of the ionisation potential decreases and AT, V redshifts are satisfyingly general, as indeed they must be since red shifts occuron methyl substitution of all types of chromophore. Exceptions do, how-ever, occur : for example, a-methylstyrene shows a violet shift of certainbands relatively to styrene,15 as does the monomethyl derivative of trans-stilbene relatively to its parent.16 These exceptions are probably due tosteric interference, on methyl substitution, with the co-planarity needed formaximum conjugation effects.That 1 : 4 steric interference with co-planarity may be considerable is shown by the propeller shape of 1 : 3 : 5-triphenylbenzene l7 and the probable lack of co-planarity in diphenyl itself.1813 A. D. IValsh, Faraday Society Symposium on The Labile Molecule, Sept., 1947.14 Proc.Roy. SOC., 1947, A , 191, 2 2 .16 G. N. Lewis and M. Calvin, Chem. Reuiews, 1939, 25, 273.17 L. Pauling, " Nature of the Chemical Bond," Cornell, 1940, 2nd ed., p. 219.18 (Migs) M. M. Jamison, (Miss) M. S. Lesslie, and E. E. Turner, Ann. Reports, 1946,43, 161. * The ideas of charge transfer and hyperconjugation are not entirely distinct. &IsPrice has shown [ref. (9), p. 2621, hyperconjugation has implicit in it the idea of cliurgetransfer in the ionised or excited state.Price 9 has developed a somewhat different approach to the simple idea of chargetransfer. Although some charge transfer occurs in the ground state, a much greatercharge transfer is supposed to take place in the excited or ionised state as a result ofalkyl substitution.The effect is to bring about relative stabilisation of the upperstates, thereby reducing excitation and ionisation energies.t He suggests that about 0.14 V. of the 0.80 V. decrease in 77-1 ionisation potential,in passing from ethylene to propylene, is attributable to hyperconjugation.l5 A. D. Walsh, ibid., p. 32WALSH: F'AR ULTRA-VIOLET SPECTRA AND RELATED TOPICS. 35Overlapping the long wave-length side of the first N,V absorption, allunsaturated hydrocarbons show a broad band of very low intensity whichappears as a " step-out " in the absorption curve. In the olefins the bandis structureless (or, as in ethylene, has only diffuse structure) but in thecyclic dienes and in benzene it reveals a sharp vibrational structure whichresembles that found in the first Rydberg tran~iti0n.l~ In view of this andof the very low intensity, E.P. Carr l9 has suggested that in all unsaturatedhydrocarbons the " step-out " represents a transition to a triplet analogueof the lowest Rydberg excited level. In ethylene itself, the 0 , O band appearsto be a t 2070 A.The singlet-triplet transition of the ground state probably occurs a tmuch longer wave-lengths. Phosphorescence requires a long-lived excitedstate. Since triplet-singlet transitions are well known to be of lowprobability, and since the ground states of most molecules are singlets, it isnatural to identify the upper, phosphorescent, state as (often) triplet. Bystudying the phosphorescence of organic molecules dissolved in rigid solvents,G. N.Lewis and M. Kasha 2o have succeeded in determining the heights ofthese triplet states for many organic molecules. trans-Dichloro-, -dibromo-,and -di-iodo-ethylene all give nearly identical heights of 74 kcals. Jf thisis near to the value for ethylene itself, a weak transition should occur aroundConsiderable progress has therefore been made in determining theprobable heights of the various possible excited electronic states of theethylene molecule. R. S. Mulliken and C. C. J. Roothaan21 have given atheoretical discussion of the twisting frequency and the barrier height forfree rotation in each of'the various electronic states of the ethylene moleculeand also for the lowest state of the ionised molecule. They conclude thathyperconjugation tends to make the 90" twisted form of the molecule morestable than it would otherwise be.Triple-bond Molecules.-The vacuum ultra-violet spectra of acetylene,methylacetylene, hydrogen cyanide, the cyanogen halides, diacetylene, anddimethyldiacetylene have been reported.22 The first, x-l, ionisationpotential of methylacetylene is 11-30 v.as compared with 11.41 v. foracetylene. That the reduction (0.11 v.) is very much smaller than forpropylene relatively to ethylene (0.80 v.) is a significant fact for theories ofalkylation red shifts. It cannot be explained by larger size of the chromo-phore as with toluene-benzene. It is probably due in part to the inductiveeffect being less with a triple than with a double bond. This is under-standable [cf.ref (5); p. 591 in general terms from the interpretation interms of hybridisation given above of the inductive efTect. It affectsdirectly the c bond of the C=C. Since this is sp-sp its electrons are much3900 A.In Chem. Reviews, 1947, 41, 293.so Ibid., p. 401; J. Anher. Chem. SOC., 1944, 66, 2100; 1945, 67, 994; M. Kasha,Chem. Reviews, 1947, 41, 401.21 Ibid., p. 219.22 W. C. Prim and A. D. Walsh, Trans. E'araday Xoc.. 1945, 41. 38136 GENERAL ANL) PHYSICAL CHKiMISTRY.more tightly bound than those in an sp2-sp2 bond. The repulsion betweenthese electrons and the outlying T; electrons is therefore smadl relatively toethylene. A slight change in thc CJ bond is not likely therefore to producemuch change in binding of the x electrons in C r C .As regards the hyper-conjugation effect, it is often supposed that this, so far from being lessimportant with methylacetylene than with propylene, is particularlyimportant with the former molecule. Such a supposition has it's difficulties,because the spectroscopic effects produced by conjugating a C5ZC withanother unsaturated group are Eess, not more, than those produced witlhC=C instead of C-C. Thus the 1790 A. peak in benzene (see below) isshifted to 1910 A. in phenylacetylene but to 1950 A . in styrene; while the2000 A . region of benzene moves to 2390-2200 A . in phenylacetylene*and2400-2300 A. in styrene. The conjugating power is reduced as we passfrom C=C to C-C, the reduction being a natural consequence of the tighterbinding in CCC cxpected theoretically and found experimentally.On theother hand, in CH,-C--C)- tlhe conjugation is in two planes, so that the C-Cbond is likely to be shortened more than the C-C in CH >C=c<, ofherthings being equal. This means that the x-type overlap, which is theessential phenomenon of all conjugation, will be more efficient across C-Cadjacent to C-C than adjacent to C=C, other things being equal. Buteven in diacetylene, where also the conjugation is two-dimensional, the firstionisation potential only drops from 11-41 in acetylene to 10.79 V. indiacetylene (i.e., by0.62 v.) as against a drop of 0 . 8 0 ~ . for propylene-ethylene.A belief that CH, conjugates more with CEZC than with C=C is thereforenot without its difficulties.A further argument against increased importanceof hyperconjugation in methylacetylene,23 zliz., that the C-C bond shows Eessand not more resistance to twisting than in ethane, is not valid, as has beenpointed out elsewhere; but there seems to be no chemical evidence insupport of the H atoins of CH, in methylacetylene having ail acidic functionand that of -CECH having an acidity less than in acetylene, as is required ifhyperconjugation structures such as H C:H2=C=CH are supposed veryimportant. The main evidence for great importance of hyperconjugation inmethylacetylene lies in the well-known marked shortening of the C -C bond.But i t should be remembered that this shortening and strengthening isattributable in part to the acetylenic, sp, nature of one of the carbon valenciesinvolved.* The shortening and strengtheningis marked and abrupt as we pass from H-C= t o H-CG, in the series CH,,C,H,, C',H2, in which there is no question of conjugation : it may be eveninore marked in passing from CH3--C'= to CH3-C= for the same reason.I n so far as the shortening of Cj-C! in methylacetylene is, however, attributablet o hyperconjugation, one needs to distinguish between the total hyper-Refs.13 and 26 explain this.23 J. D. Dunitz and J. M. Robertson, J . , 1947, 1152.24 J. Amer. Chem. SOC., 1939, 61, 927.2 5 V. Henri Memorial 1-01., Desoer, Liege, 1947.* L. Pauling, H. I). Springall, and K. J. Palmer 21 recognised this effect, but it mayhave a greater importance than they gave it.See also C. A. CouIson.2conjugation effect (which is important for the bond shortening) and thehyperconjugation-effect per x electron (which is important for the ionisation-potential changes) : in this way i t may be possible to reconcile smallionisation changes with a fairly large total effect. Obviously, too, thestabilities of the resulting ions, as well as one molecule with another, need tobe compared for a full discussion of the ionisation-potential change^.^Hutndiene, Hexatriene, a d Derivatives.-The far ultra-violet spectra ofbutadiene, isoprene, 97-clirnethylbutadiene, and chloroprene have heendescribed by W. C. Price and A. D. Wa1sh.l' The same authors 28 have HI)studied the spectra of hexatriene and divinylscetylene. H. Rastron, R.t4.Davis, and L. W. Butz 29 hac*e reported the spectra of alkyl and otherderivatives of divinylacetylene in the region 2300-2900 A .At room temperature butadiene gas appears to be mainly s-trans, i.e., tohave a trans-arrangement of the double bonds about the conventional singlebond ; but the spectroscopic evidence 2'7 30 shows the existence also ofappreciable amounts of the s-cis-form . Similarly, the spectroscopic evidenceindicates the existence of various forms of hexatriene.28 It is now reasonablycertain that the s-trans-form of butadiene is the lower-energy is0rner,~l9 32 sothat the proportion of s-cis increases with temperature.Price and Walsh28 showed that a graph of first ionisation potentialagainst frequency of the niaximum of the first N,V transition was linear forethylene, s-trans-butadiene, and hexatriene.This linear graph (Fig. 1) isalso quite well fitted by cyclopentadiene and cylohexadiene, furan, andpyrrole (see below). Isoprene, chloroprene, and $y-dimethylbutadiene donot lie far 08 it. One would expect therefore that i t would also be fitted bys-cis-butadiene. The first ionisation potential of s-cis-butadiene has beendetermined as 8.75 v . ~ O From Fig. 1 we should therefore expect themaximum of the N,Vl transition for s-cis-butadiene to lie a t about 44,500ein.-l or around 2250 A., i.e., slightly to long wave-lengths of the N,V1transition for s-trmts-butadiene (2200-2000 -4.). Direct observation ofS , V , for s-cis-butadiene a t room temperature is difficult because it isexpected to be a rather weak transition l2 and the much greater strengthof the s-trans-N,F", transition will tend to conceal i t : but i t is significant>that the weak absorption of butadiene gas around 2400-2200 a.is foundto be strongly temperature dependent ,33 increasing with temperature as i twould if i t were due to s-cis- present with the s-trans-form.The linearity of the ionisation potential--AT, Vl frequency graph with itsregular movement of the X, T', transition by about 1.2 v. to long wave-lengths2 6 -1. D. Walsh, J . , in the press.2 s Ibid., 1946, A , 185, 182.29 ,I. Anzer. Cheni. Soc., 1943, 65, 973.:'" T. 31. Sugden arid -4. I). Wal~li, l ' m n s . Fumcl(~!j Svc., 1945, 41, 76.2 i Proc. Roy. Soc., 1940, A , 174, 210.J.C. Aston, G. QZBSZ, H. 117. Woolley, and F. G. Hrickwedde, J . Chem. Plrysic.~,1946, 14, 67.32 A. D. Walsh, Nature, 1940, 157, 768.33 €3. 8. Rasmrissen, 1). I). Tunnicliff, and IC. I:. Brattitin. .7. C ' h P w . l'h+vics, 1943, 9,43238 GENERAL AND PHYSICAL CHEMISTRY.for every 1 v. drop in ionisation potential, is a significant empirical fact stillto receive a theoretical explanation.Cyclic Dienes.-W. C. Price and A. D. Walsh 34 have described the vacuumultra-violet spectra of cyclopentadiene, cyclohexadiene, thiophen, pyrrole,and furan. G. Milazzo has photographed, under high dispersion, the spectraoutside the vacuum region of p y r r ~ l e , ~ ~ N-de~teropyrrole,~~ N-methyl-pyrrole,36 and thi~phen.~' An important point is the appearance withN-methylpyrrole of a region (2600-2250 A , ) with no apparent analogue inthe spectrum of pyrrole.It is probably consequent upon the lone pair I$Bu tad i e n e (s -trans)&-Dimethyl -butadieneHexatriene\ First ionization potentia/s plottedagainst N-+ 5 transitions.I I I6L7 000 50,000 40,000 340N-+& Y rnax., cm.-l.FIG. I .9electrons in N-methylpyrrole being less tightly bound than in pyrrole(because of the electron-releasing properties of the methyl group) and soapproaching in strength of binding the CC x electrons with which nearlycomplete (" homocyclic ") conjugation therefore occurs : in that case thenew region is probably analogous to the 2600 A. region of benzene. Thio-phen 37 also shows regions of absorption probably closely analogous to thoseof benzene and appears to furnish, like N-methylpyrrole, a case of nearlyh oniocyclic conjugation.In dimethylfulvene, which has five equivalent x electrons in a ring ands4 Proc.Roy. SOC., 1941, A , 179, 301.35 Rend. Accad. Itul., 1942, 4, 87.37 Communication presented a t XIth International Congress of Chemistry, London,36 Gazzetta, 1944, 74, 152.1947WALSH : FAR UTATRA-VIOTdET SPECTRA ANT) RELATED TOPICS. 39one in a side chain, the first absorption region has moved right up to 3700 A.,38resulting in visible colour. Other absorption regions occur a t 2600 A.,382 1 0 0 ~ . , ~ * and a peak (probably Rydberg in character) a t 1 8 0 0 ~ . 3 ~ Thelongest-wave absorption is considerably weaker than the following absorptionas with all the cyclic dienes.cycZoPentadiene and cyclohexadiene show markedly lower first ionisationpotentials (8.62 and 8.4 v., respectively) and N , V , transitions a t markedlylonger wave-lengths than s-trans-butadiene.Since s-cis-butadiene alsoshows a markedly lower x-l ionisation potential and an N , V , transitionprobably at longer wave-lengths than in the s-trans-form, these characteristicsare evidently largely a property of the cis-arrangement of the double bondsrather than due to hyperconjugation via the CH, groups of cyclopentadieneand cyclohexadiene. The latter effect doubtless plays a part, but i t appearsless than was earlier th0ught.m Table I lists the probable N , Vl, N , V2, andN , V3 locations for the cyclic and open-chain hydrocarbon dienes. WhenPrice and Walsh wrote their paper in 1940 27 the N , V 2 and N , V3 transitionswere thought to lie together, but Mulliken l2 later showed that thesetransitions should be separated.TABLE I.First T-I I.P.Molecule.N,V, (A.). N , V , (A.). N,V3 (A.). (volts).s-trans-Butadiene . . . . . . 2200-2000 ? ? 9-07s-cis-Butadiene ......... 240CL-2200 1880 ? 1760-1650 ? 8.75cycZoPentadiene . . . . . . . . . 2400-2200 1980-1850 1660-1450 8-62cycloHexadiene . . . . . . . . . 2600-2400 2070-1 900 ? 8.4(max. 2320)(max. 2480)R. S. Mulliken40 discussed the “abnormality” of the cyclic dienehydrocarbons relative to s-trans-butadiene. Sugden and Walsh 3O showedthat the abnormality lay rather in the N,Vl location for s-cis-butadiene ifthis was supposed to occur a t the same wave-lengths as for s-trans.Theabove deduction that it probably lies a t bnger wave-lengths clarifies thispoint and gives to the N,Vl column of Table I the smooth order of theionisation potential column.Benzene and its Derivatives.-Price and Walsh 14 have published newspectrograms of the far ultra-violet spectrum of benzene. It is now wellknown that benzene exhibits absorption around 2600 A., rather strongerabsorption around ZOOOA., and a much stronger peak of absorption a t1790 A. The upper level a t 2600 A. is established as lBZzL [see ref. (3)’j andthat at 2000 A. is probably lBItt. The absorption a t 1 7 9 0 ~ . certainlyinvolves a Rydberg transition,14 for it has a sharp vibrational patternidentical with that accompanying other members of a Rydberg series lyingto shorter wave-lengths.The 1790 A . absorption probably also represents atransition to the lEl,l upper level. It has been suggested4l9 l4 that tjhe4 8 Quoted by R. S. Mulliken and C. A. Rieke, Rep. Prog. Physics, 1941, 8, 259.39 A. D. Walsh, unpublished spectrograms.4 1 G. Norclheim, H. Sponer, and E. Teller, ibid., 1940, 8, 455.*O J . Chem. Physics, 1939, 7, 339continuous background of the region is due to CH bond dissociation resnltingfrom transfer of energy by internal collision from the excited TC electron to aCH bond electron. T’ransition to each of the three states lB,,,, I B l u , and lEl,Lrepresents absorption that is X,V1 in type.42 It is noteworthy, however,that if benzene fits the linear graph of Fig. 1 it is the 2 0 0 0 ~ .region thatcorresponds to the N , V , transition of hexatriene, butadiene, etc. Similarly,with thiophen, which, we have seen, probably represents a case of nearlybenzene-like conjugation, i t is the 2200-2000 A. region that apparentlycorresponds to the N , V , transition of the other dienes and trienes.Lewis and Kasha 2o find a triplet state of benzene 85 kcals. above theground state. This fits with the earlier report by A. L. Sklar 43 of absorptionaround 3 4 0 0 ~ . (corresponding to -85 kcals.) so weak that it only showswith 20 em. of liquid benzene. Experimentally, it is difficult to be sure ofthe validity of such a report since very slight traces of impurity (e.g.,anthracene) would give rise to appreciable absorption around 3400 A .in such a long column of liquid; but the work of Lewis and Kasha nowprovides important corroboration.Sklar has interpreted the transition aslAl, --+ 3-E17,.43The far ultra-violet spectra of many derivatives of benzene have beenreported.14> 15, 44 A significant empirical fact is that with increasingconjugation between the side chain and the ring the 2000 A. transition ofbenzene moves much further to longer wave-lengths than does the 2 6 0 0 ~ .or the 1790 A. transition. In this respect the 2000 A. transition again showsgreater similarity to the N,V1 regions of open-chain dienes and trienes thando the 2600 A. and 1790 A. regions.The 2600 A. region in benzene represents absorption “ forbidden ” by thesymmetry.It would not occur if vibrations did not take place to destroythe symmetry. I n simple benzene derivatives the destruction of‘ thesix-fold symmetry means an intensification of the transition and importantchanges in vibrational structure. The very complete analysis of thevibrational structure in the benzene transition (explaining practically all thestrong bands, more than seventy in number) has made i t profitable to studyin detail the analogous region for benzene derivatives. Much careful studyhas been devoted to this : of monosubstituted benzenes, chloroben~ene,~~fluorobenzene,46 toluene,47, 48 phenol,49 aniline,50 and pyridine 51 have allbeen recently studied. The spectra can be interpreted4’ as due to acombination of the transition forbidden for the benzene structure (butappearing because of the occurrence of suitable vibrations) and of a transition4 2 R.S. Mulliken, J . Ghern. Physics, 1939, 7, 20, 353.4 4 A. D. Walsh, Trans. Faraday SOC., 1946, 42, 62.4 z H. Sponer and S. H. Wollman, J . Ghem. Physics, 1941, 9, S16.4(i S. H. Wollman, ibid., 1946, 14, 123.4i H. Sponer, ibid., 1942, 10, 672.4 8 N. Ginsburg, W. W. Robertson, and F. A. Matsen, ibid., 1946, 14, 51 1.49 F. A. Matsen, N. Ginsburg, and JV. W. Robertson, ibid., p. 511.43 Ibid., 1937, 5, 669.X. Ginsburg and F. A. Matsen, ibid., 1945, 13, 167.H. Sponer and H. Stucklen, ibid., p. 167allowed by the lowered symmetry caused by the migration of e1ect)rons to orfrom the side chain. The perturbation of the hexagonal benzene electronicsymmetry is the greater the greater the difference in clectroiiegativitybetween H and the atom or group that replaces it.Thus fluorobenzeneshows a greater change from benzene than does chlorobenzene. The nearultra-violet spectra of disubstituted benzenes have also been 52 ashave the spectra of certain trisubstituted benzenes in the vapour state,namely, the three trichlorobenzenes and 1 : 3 : 5-trimethylbenzene.%, j q 9 55A. L. Sklar 5G and K. P. Herzfeld 57 have discussed the intensities andwave-length shift,s of these various substituted benzenes relatively to benzeneitself in terms of energy changes consequent upon the migration of chargefrom the side chain into the benzene ring.F.A. Matsen, W. W. Robertson, and R. L. Chuoke 58 have comparedthe near ultra-violet spectra of toluene, ethylbenzene, isopropylbenzene,and tert.-butylbenzene. They find that the bands representing the transitionallowed by the lo$ered symmetry due to migration of electrons into the ringbecome stronger and shift to long wave-lengths as one passes from tert.-butyl- to isopropyl-benzene to ethylbenzene to toluene. They ascribe thisresult to increase of hyperconjugation between the side chain and the ring,as the side chain changes from tert.-butyl to . . , methyl; this effectswamping the inductive effect which should cause greater wave-length andintensity increases as one passes in the reverse direction. The hyper-conjugation must do this by tending to lower the excited state, since,according to Price,g the first x-l ionisation potential decreases as one passesfrom toluene to ethylbenzene to isopropylbenzene to tert.-butylbenzene. Theexplanation fits with the point made above that, with a large conjugatedsystem such as a benzene ring, the hyperconjugation effect should assume agreater importance relative to the inductive effect than in simple olefins.Experiments on chlorination and broniination 595 6o have similarly shown areactivity of the benzene ring in the order methyl > ethyl > isopropyl >tek-butyl.The same order is found in carcinogenic activity.61 That thehyperconjugation effect should decrease in the order inethyl . . . tert.-butylis understandable as follows.In CH,- the carbon valencies towards H haveconsiderable p character and therefore tend to give x-type overlap with a 2pvalency on the adjacent carbon atom : hence the fundamental reason for thehyperconjugation. Changing the H atoms for CH, groups has the effect l3 ofevoking more s character in the carbon valencies towards CH,; i.e., therewill be less x-type overlap between the CC bonds of tert.-butyl and anadjacent C=C than between the CH bonds of CH, and an adjacent C=C.j2 H. Sponer, Rev. Mod. Phywk.s, 1942, 14, 124..,.I H. Sponer, Cheni. Reviews, 1'347, 41, 281..A 13. Sponer and &I. H. Hall, V. Henri Meinorid Vol., Uesoer, LiGpe, 1947.jb J. ( ' h e m . I'?i~~sks, 1939, 7, 984.6i Cheni. Reviews, 1947, 41, 233. j8 l b i d . , p. 473.jY P.B. D. de la Mare and P. W. Robertson, J . , 1943, 279.uo E. Berliner and F. J. Bondhus, J . Anier. C'henL, ~YOC., 1946, 68, -73%.H. Sponer and M. J. Stallcup, ibid.-4. hllman, Conipt. r e d . , 1047, 225, 738,n 42 GENERAL AND PHYSICAL CHEMISTRY.J. R. Platt and H. B. Klevens 62 have measured the absoluteintensities of absorption (in n-heptane solution) of the 2000 A. and1790 A. regions in benzene and of the analogous regions in toluene, ethyl-benzene, and the three xylenes. Passage from benzene to tolueneconsiderably increases the intensity of the " 1790 A." and " 2000 A." regions.At the same time a shift to the red of these regions occurs greater than withthe " 2600 A." bands. Similar changes occur on passing from toluene to thexylenes.Since theoretical reasoning shows that the intensity of the" 2600 A." bands should be proportional to the intensity of the N , V transitionsa t shorter wave-lengths and inversely proportional to the square of theseparation of the 2 6 0 0 ~ . bands from those a t shorter wave-lengths, thesefactors alone should cause an increase of intensity in the toluene 2600 A.bands by a factor of about 1.5. The experimental increase is by a factorof 2-0. This suggests that breakdown of selection rules due to loweredsymmetry or charge migration may not be the most important factors indetermining the intensity of the 2600 A. bands ; and illustrates the danger ofexplaining effects in one band system without taking into account whathappens in all the other band systems.J.R. Platt, H. B. Klevens, and G. W. Schaeffer 83 have studied the absorp-tion of borazole (I). This molecule is interesting because it has an obvioussimilarity of structure to benzene. Indeed it has been called " the inorganicbenzene ". That considerable delocalisation of the N lone-pairelectrons occurs is shown by the BN distance, which at 1.44 A.in trismethylaminoborine. The absorption reveals (a) four\ N / ~ ~ diffuse bands starting a t 1995 A. which appear to be analogousto the 2000 A. bands of benzene, but of intensity about 10times smaller; ( b ) a strong continuum, like the 1 7 9 0 ~ .benzene peak, with a maximum a t 1720 A. or somewhat below. No bandsanalogous to the benzene 2600 A. system, however, were found, though theywould have been seen if their intensities had been only one-twentieth ofthose of the benzene bands.It seems to the Reporter that this absence ofan analogue of the benzene 2600 A. region is to be linked with its absence inpyrrole. I n both molecules not all the x electrons are equivalent : in pyrrolethe N lone pair and the C=C x orbitals have different binding energies, andin borazole the atomic orbitals contributed by the B and N atoms to themolecular x orbitals are not equal in binding energy. When, in benzene orN-methylpyrrole or thiophen, the participating atomic orbitals are made ofequal or approximately equal binding energy, the 2600 A. region appears.Halogeno-ethyZenes.-The vacuum ultra-violet spectra of the halogeno-ethylenes have been examined in detaiL6* They exhibit much sharpvibrational structure and bands which fit well into Rydberg series.The x-lionisation potentials are all less than in ethylene. It is difficult to explainthis except as due to conjugation of the C=C n electrons with the p x electronsHHN/ B \vH is considerably shorter than the single-bond distance (1.62 A.)HBH (I.)62 Chem. Reviews, 1947, 41, 301.64 A. D. Walsh, Trans. Faraday SOC., 1945, 41, 35.63 J . Chem. Physics, 1947, 15, 598WALSH : FAR ULTRA-VTOLET SPECTRA AND RELATED TOPICS. 43on the C1 atoms.6 This is important because there has been a tendency insome quarters to cite as evidence for the conjugation effect only such factsas the well-known shortening and strengthening of the CCI bonds relative toCC1 in the alkyl chlorides.This is hardly sound 65 because CH bonds showa similar shortening and strengthening in passing from alkyl-H to vinyl-H.In the latter bonds the effect can be explained in terms of the enhanced scharacter of the carbon valency towards H.13 It is all the greater when theC is part of a triple bond. That in the CCI bonds an additional effect ispresent, however, is shown by Table I1 which has been compiled byJ. Duchesne.66 Whereas for CH the change in force constant is only 15%TABLE 11.Bond BondCH adjacent force Bond CC1 adjacent force Bondto : constant. length. to : copstant. length.Single bond (CH,) 5.07 1.094 Single bond (CH,Cl) 3-30 1.77Double bond (C,H,) 5-4 1 48 Double bond (C,Cl,) 3.44 1-73Triple bond (HCN) 5.7 1.06 Triple bond (ClCN) 4-31 1.67in passing from top to bottom of the table and 3% in bond length, for CClthe corresponding figures are 30% and 6%.The argument from ultra-violet spectra is therefore corroborated. A further argument is as follows.The dipole moment (p) of propylene (0.35 D.) gives a rough measure of themoment to be expected on changing an sp3 C valency (as in C2H6) for sp2(as in C2H,). Now the difference of p(vinyl-Cl) (1-44 D.) and p(Et-CI)(2.05 D.) is considerably greater than 0.35 D. Since on changing from Et-Clto vinyl-C1, we should not expect a greater reduction in p by the hybridisationeffect than the value of 11 in propylene, there must be a second importanteffect a t work.*The spectroscopic evidence for conjugation between the C=C and C1 TCelectrons lies in part in the lowered ionisation potentials, and in part in thelong wave-length shifts suffered by the N , V transition in the chloro-ethylenes.One might explain these effects in terms of repulsion betweenthe C=C x and C1 p x electrons, but the thought content of this explanation isbasically only a different way of expressing that involved in the molecularorbital Ianguage of conjugation-for the node in the highest normallyoccupied x orbital of the conjugated system on the latter explanation is thetranslation of the repulsion on the former. An interesting, but somewhat(i6 A. D. Walsh, Trans. Paraday SOC., 1947, 43, 60.6 6 Private communication. 6 7 Trans. Paraday SOC., 1944, 40, 537.* The strength of bonds to such groups as vinyl or phenyl relative to methyl is areflection of their higher electronegativity.A. Burawoy 6 7 was one of the first todiscuss the reason for this raised electronegativity. He argued that replacement of uelectrons by n electrons meant a change from strongly bound to weakly bound electrons,with consequent decreased electron density at the carbon atom. It therefore permittedan increased hold by the carbon atom on the electrons of the other linkages. There isno doubt that, in general terms, this explanation is essentially correct : the discussionin ref. (13) puts the same thought content in different (qiiantum mechanical), butequivalent, languagepuzzling,64 point is that cis-dichloroethylene appears to have a lower dionisation potential but a shorter wave-length N , V transition tham the tmns-isomer.Carbonyl Compounds.-The far ultra-violet spectra of acetaldehyde,6Racraldehyde, crotonaldehyde and mesityl oxide, 69 benzaldehyde and furfur-aldehyde,44 and glyoxal 70 have all been recently reported.Broadly speaking,the observations fit well into the theoretical pictiire drawn by H. L. McMurrJ-and It. S. M ~ l l i k e n . ~ ~ Glyoxal, like bntadiene, appears to prefer to existin the s-trans-forni. 'Chis fits with recent work on the emission spectrum of'glyoxal in the near ultra-violet.72M. Lawson and A. R. F. 1)uncan 73 have obtained the spectrum of'deuteroacetorie and compared it with that of' acetone. In the spectra ofacetone and other carbonyl compounds, there occurs a vibrational frequencyca.1200 cm.-l which has been attributed in the past to a valence vibration ofthe C=O bond. No frequency of this magnitude, however, occurs in thespectrum of deuteroacetone around 1 9 5 0 ~ . A new explanation for thefrequency in acetone in this region must therefore be found : Lawson andDuncan suggest hydrogen bending in the methyl groups. The 1200 cm.-lfrequency in other carbonyl transitions of a t least such cases as formaldehydemust still be ascribed to the C=O valence vibration since no alkyl groups arepresent.It. S. Holdsworth and Duncan 74 have carried out intensity measurementson the absorption regions around 1950 and 1650 A. in aliphatic ketones.The intensity of the transition around 1950 A.decreases when the hydrogenatoms in acetone are replaced by methyl groups, whereas that of theabsorption around 16.50 A. increases. Whatever the explanation of theseeffects, they are probably to be linked with significant intensity differencesbetween acetaldehyde and acraldehyde F9 : in acetaldehyde the 1800 A . band(corresponding to the ketonic 1950 A. absorption) is weaker than the band at1 6 5 0 ~ . , but in acraldehyde the longer wave-length band (at 1750 A.) ismuch stronger than that at 1650 A. In acetone the 1950 A. are very muchstronger than the 1650 A.I. I. Rusoff, J. R. Platt, H. B. Klevens, and G. 0. Burr 75 have measuredthe absorption of various fatty acids in varions solvents as far as 1700 A.H. L. McMurry 76 has given a theoretical discussion of the spectra of saturatedcnrboxylic acids, esters, and salts,The first ionisation potentials of a considerable number of carbonylcompounds are now known or may be estimated with reasonable probability.These ionisation potentials refer to the removal of a lone pair electron frointhe oxygen atom of the >CEO group. The fact that thev lie below the396 8 A.D. Walsh, Proc.. Roy. SOC., 1946, A , 185, 176.(LB Idem, i b i d . , 1943, 41, 495.i l Proc. Nat. d m d . Sci., 1940, 26, 312; H. L. McMurry. J . Chen,. Physics, 1041, 9,i 2 A. G . Gaydon, Trans. Faraday SOC.. 1947, 43, 36.i 3 J. Chent, Physics, 1944, 12, 329.P 5 J . Amer. Chem. Roc.., 1943, 67, 673.i o Idem, ibid., 1946, 42, 62, 60.231, 241.i 4 Chena.Reviewd, 1947, 41, 311.7 G J . Chew. Ph!pic.v, 1942, 10, 655WALSH : VAR ULI'RA-VIOLET SPECTRA AN 1) REr,ATEU TOPIC'S. 45value estimated theoretically by Mulliken i i is explained by him, antigenerally accepted, as due to accumulation of negative charga on the oxygenatom, i.e., to the C-0 polaxity of the carbonyl bond. Consequently, byarranging carbonyl compounds in decreasing order of lone-pair ionisationpotential, it is possible to determine the order of increasing carbonyl bondpolarity.7s3 79 This is important because it is notoriously difficult to separatemolecular dipole moments into bond moments. An obvious prerequisitefor this technique is that a molecule shall be ~ ~ 1 1 represented by a boncldiagram.'I'hc establishrnciit in this ivay of a probable order of carbonyl boldpolarity has brought to light important correlations.As the bond polarityincreases, so the bond length increases, the bond stretching-force constantdecreases, and the bond energy decreases. In other words, as the bondpolarity increases, so the bond weakens.If wethink of any bond A B as containing two electrons in an orbital formed bythe overlap of two atomic wave functions {ha and +f;, then it is natural towrite the bonding wave function as a#.\ -+ b$,;. Remembering that the totnlprobability of finding one of the electrons of this orbital somewhere in spaceis just 1, we must " normalise " the wave function by writing (athi +b$I,)/da2 -k 2abS + b2 where X = J#Ll$udr over all space. Now the squaresof the coefficients of and $u give the probabilities of finding an electronaround the respective nuclei A and B ; consequently it is natural 80 to take theproduct of the coefficients of and #B as a measure of the probability offinding the electron in the shared region of the bond.Intuition tells us thatfor a strong bond the electrons must be shqred, i.e., spend most of theirtime between thc nuclei. The product Y = ab/(u2 4- 2abS $- b2) maytherefore be taken as a measure of tjhe strength of the bond. Nowd+ 6-One may ask why shouW increasing polarity weaken the bond?and, finding the masimuni of this function as a / b varies, w e can readilyshow that it occurs when a / b = 1. The maximum bond strength thusoccurs when a = b, i.e., when the bond is non-polar, and falls off as polaritydevelops-in agreement with the experimental fact.Put into ordinarywords, this calculation simply expresses the fact that as polarity increasesthe-bonding orbital comes to lie more and more on the side of the moreclectronegative atom that is remote from thc bond; and, in so far as i tdocs lic outsidc thc bond, obviously its bonding fuiiction is lost (Figs. 2and 3).This is not the inaiii fact or a t work, howcvc~, iii (.awing bond wnkcningwith increase of bond polarity. The calculation neglects any interactioiibetween the bonding electrons and neighbouring electrons. Yet it is justi i J . Chem. Phys.ics, 1933, 3, 664.i a A. D. Walsh, Trans. Faraday SOC., 3946, 42, 56.78 ldenr, ibid., 1947, 43, 158. C. A. Coulson, Proc.Roy. Soc., 1939, A , 169, 41346 GENERAL AND PHYSICAL CHEMISTRY.this interaction that causes change in binding of the lone-pair electrons asthe polarity changes. As the polarity increases the lone-pair electronsbecome subject to an increasing repulsion. At the same time the bondingelectrons become subject to an equal and opposite repulsion. The availablefigures 79 for the ionisation potentials of the bonding electrons bear this out.Now the more tightly bound are bonding electrons in a spectroscopic sense thegreater the contribution of their orbital to the bond in a chemical sense.81This is a general rule which can be made the basis of a useful definition ofbond order.82 The weakened binding of the bonding electrons as polarityincreases therefore means a weakened bond strength.Portion o f orbital/ost fur bond~ngFIG. 2.FIG. 3.Polar bonding orbital. Non-polar b o d i n g orbital.The binding of the bond electrons in a carbonyl bond also decreases asthe bond polarity increases for another reason. Increase of the polarity isdue fundamentally to the influence of other groups in the molecule in reducingthe effective electronegativity of the carbon atom towards the oxygen (thatof the oxygen atom being constant). Now reduction in carbon atomelectronegativity means a direct reduction in binding of the bond electrons,apart from the indirect reduction through the ensuing polarity : it is ageneral rule that, even in non-polar bonds, reduction in electronegativity ofthe atoms at either end of the bond means a reduction in bond strength.Thus the Si-Si bond is weaker than the C-C, and the S-S than the 0-0, andthe 1-1 than the Br-Br than the Cl-Cl.\V. Gordy 83 has recently stressedthis point. There are thus three reasons for the weakening of bond strengthwith polarity increase, which may be symbolised as on p. 47.The way in which changing carbon atom electronegativity works inchanging bond strength may be translated into an alternative language ofchanging hybridisation of ~a1encies.l~ This causes a direct change of 0bond strength and, via a repulsion of G and x electrons, also a change in xbond strength. By such a translation it should be possible to relate thebond strength changes to changes in magnitude of, say, CH bendingfrequencies in CHO of the various aldehydes.81 R.S . Mulliken, Physical Rev., 1934, 46, 551; J . Chenz. Physics, 1939, 7 , 121;82 A. D. Walsh, Trans. Paraday SOC., 1946, 42, 779.83 J . Chem. Physics, 1946, 14, 305, but see A. I). Walsh, ibid., 1947, 15, 688, for 8K . Fajans, ibid., 1942, 10, 760.qualificationWALYH : FAR ULTRA-VIOLET SPECTRA AND RELATED TOPICS. 47The weakening of bond strength with increasing polarity is almostcertainly of general application, a t least provided effects (1) and (2) workin the same direction. The idea is not entirely new, F. Arndt andB. Eistert 84 having put forward a similar idea on quite different grounds.Electrons in neighbouring bonds may play a similar part to the oxygenlone-pair electrons in carbonyl compounds in bringing about effect (3).Sometimes, of course, effect (1) may work in the opposite direction to effects(2) and (3).The introduction of hydroxyl into ethane to give CH,*CH,*OHmust increase the effective electronegativity of the carbon atom to whichi t is attached, but yet introduce polarity into the previously non-polar C-Cbond. In this case there is slight evidence that the polarity effect is thegreater.Z6 I n passing from (C-H)C21L, to (C-H)L$2112, however, we increasebinding of bond --+ Weakening of bond . ( 1 )electronsDirect reduction oflteduction of effective C ,xDirect reduction of bond 7 strength . . . * (2)‘xIncrease of polarity\ atom electronegativityIncrease of repulsiveinteraction with otherelectrons .1 Reduction in binding ofbond electronsIJ.W-eakening of bondstrength .. . - (3)the effective electronegativity of the carbon valency towards H,13 so at thesame time increasing the C-H polarity; and yet the C-H bond strengthdefinitely increases, showing that here effect (1) is more important than theeffects (2) + (3). Obviously there is need for further work to relate thevarious effects quantitatively to known parameters. In a series such asMe-Cl, Pri-C1, Bnt-Cl effects (1) and (2)-(3) work in the same direction as incarbonyl compounds and therefore predict unambiguously a weakening inthat order. [In this particular series, reduction of hyperconjugation acrossthe C-C1 bond as we pass from Me to tert.-butyl will be a small, additional,effect reinforcing the polarity weakening.]I n using the bond strength-polarity relation it is thus necessary to askfirst whether effects (1) and (2)-(3) reinforce each other. Secondly, it mustbe remembered that bond strength changes do not necessarily paralleldissociation energy changes : the latter involve the energies of the dissociationproducts, as well as of the original bond.* Thirdly, the relation applies to** Ber., 1941, 74, 423, especially pp. 442 ff. and 452.* For some discussion of the distinction of bond energies from dissociation energies,R - 61see L. H. Long and R. G. W. Norrish 8 5 and refs. (26) and (65).Proc. Roy. SOC., 1946, A , 187, 3374 8 GENEBAL AND PHYSICAL CHEMISTRY.bonds that are covalent in character : we cannot use it to predict that thedistance between the ions A and B- in an ionic lattice involving a largenumber of ions will be greater than the distance A-B in an isolated covalentmolecule-in fact the reverse is probably true.a6 Fourthly, the relationapplies to a particular bond modified only by the neighbours to which it isattached. It cannot be applied simply to compare a bond between nucleiA-B with one between nuclei C--B-for other effects [as well as effect (1)above opposing (2) + (3)] may well be very important. It thus has adifferent experimental basis from V. Schomaker and D. P. Stevenson'srule,87 which predicts a bond shortening with increase of bond polarity andis supported with comparisons solely of a bond A-B with C-B or C-D.Finally, we may note that it has become common to describe a polarbond (AB) as a resonance hybrid of an ionic and a covaleiit cxtreme ; and todeduce that its stability is greater than that of either extreme. This isincontrovertible, so long as i t is realised to refer to a resonancc hybrid ofA-B and AIB-, not in their normal conditions, but stretched or compressedto make their internuclear distances equal (at say, a distance 2). *4notherbond AB, of greater polarity, could also be described as a resonance hybridof A-R and A .B- ; Ijut these forms are not the same as before, having nowan internuclear distance that is the same for each but now equal to y. Theresonance energy for the more polar bond may be said to be greater, but thatbondisnot necessarilythe more stable-it alldependson therelative magnitudesof the resonance energies and the energies required to compress and extendA-B and A ' B- from x to y. In other words, the concept of a bond resonatingbetween a covalent and an ionic extreme does not necessarily help us tocompare the strengths of two bonds differing only in polarity-the extremesto which the bonds are related differ in tjhe two cases. The concept thereforedoes not imply-as has sometimes been supposed-that the more polar a bondthe stronger is its bond energy.Miscellaneous.-R. J. Thompson and A. B. F. Duncanss have madeabsolute intensity measurements on the absorption regions (at 52,500,66,000, and 77,000 cm.-l) of ammonia.W. C. Price s9 has photographed the vacuum ultra-violet spectra ofhydrogen selenide, hydrogen telluride, and the corresponding deuteriumcompounds. The spectra show we1 1-developed Rydberg series correspondingto excitation of one of the non-bonding electrons on the Se or Te atom.Roughly, the ionisation limits lie at 9.7 v. (H,Se) and 9.1 v. (H,Te).A review and discussion of the absorption spectra of certain gases inrelation to atmospheric physics and chemistry has been given byPrice has also photographed the absorption spectrum of diboranc dolvn t oZOO0 A . ~ ~ Other work by the same author has now finally established thatthe diborane molecule has a " bridge " rather than an ethaiie-like86 H. Bassett, Quart. Reviews, 1947, 1, 347.J . Amer. Chem. SOC., 1941, 63, 37.Private communication.J . Chenz, Physics, 1946, 14, 573.8o RepD. Prog. Physics, 1942-1943, 9, 10.91 J . Chem. Physics, 1947, 41, 207WALYH : YAK ULTRA-VIOLET SPECTItA AND liEI,ATEI> TOY1C;S. 4!)1%. S. Nulliken 92 has given an authoritative discussion of what this means iiiteriiis of molecular orbitals. From the point of view of the chemist, thec1 C1 c1simplest and most easily understood reprtwntation 93 is probably in t criiis ofco-ordinate links from B--H bonds to vacant boron orbitals, as (11), analogousto the formula (111) usually written for Al,Cl,. A. B. Burg 94 has shownthat the behaviour of diborane towards bases does not particularly accordwith the earlier suggestion 95 of a ‘‘ protonated double BB bond ”.A. D. W.,J. N. AGAR.A, D. WALSH.92 ( ‘ l i p t i ? . Reuiews, 1947, 41, 507; seo A. J. E. IVelr11, .Jm. Repork, 1945, 42, 67,93 A. I). Walsh, J . , 1947, S!).R4 J . L 4 ~ i t ~ r . Ohewk. Xoc., 1947, 69, 747.95 K . 8. Pitzer. ihid.. 1945, 67, 11%;.review of earlier work

ISSN:0365-6217    

DOI:10.1039/AR9474400005

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

INORGANIC CHEMISTRY.1. INTRODUCTION.INORGANIC chemistry is slowly-too slowly perhaps-changing from adescriptive and preparative science to one concerned with valency, structure,and reaction mechanisms-reaction mechanisms which frequently have cometo show many stages and to involve transient atomic groupings. Speakingof these entities in his Presidential Address, C. N. Hinshelwood says " Anew inorganic chemistry of such equilibria is now due, in which the theory ofstructure will become more closely linked than ever to the theory of kinetics.The latter has, so far, often taken the lead in indicating the existence ofunexpected species in small concentration (for example N,O,, S,O,, and soon) but perhaps the compliment may now be returned and a more carefulstudy of the inorganic chemistry of unstable species may help us to predictthe most probable kinetic mechanisms in examples as yet unexplored ".This engaging subject of reaction intermediates from the inorganic angleprovides the theme of the second part of this report : the more generalearlier part deals briefly with other topics of current interest.P.L. R.2. GENERAL.The literature has contained some articles of a general nature whichshould be mentioned. Vapour-pressures for about 300 inorganic compoundshave been tabulated by D. R. Stull,2 E. Rinck has reviewed the equilibriumbetween metals and fused salts, and U. R. Evans oxidation and corrosion.The importance of structure as an essential adjunct to chemistry has beenstre~sed.~5 6,Nuclear physico-chemistry up to 1941 has been dealt with by J.Mattauchand S. Fluegge,s whose comprehensive tables are preceded by a text whichrenders them intelligible to the non-specialist. I n the Liversidge lecture for1946, H. C. Urey treated a special aspect of nuclear chemistry in reviewingthe thermodynamic properties of isotopic substances. These are applicableto the concentration and separation of isotopes and provide an insight intothe temperature conditions in remote geological time.Missing EEements.-F. A. Paneth l o has provided a needed summary ofthe work involved in the discovery and properties of elements 43, 61, 85, 87,93, 94, 95, and 96. It willbe generally accepted that the right to name should rest with the discovererof the first isot,ope (naturd or artificial) but that a name should not surviveRules for naming a new element are advanced.J., 1947, 698.Ann.Chine., 1945, 20, 444.J. 10. Bernal, J., 1946, 643.J., 1947, 562.I n d . Eng. Chein., 194i, 39, 540.J., 1946, 207.A. F. Wells, Nature, 1945, 155, 468.5 J. W. Smith, Science Prog., 1946, 34, 764.* " Nudear Physics Tables ", Interscience, N.Y., 1946.lo Nature, 1947, 159, 8DODD AND ROBINSON : GENERAL. 51repudiation of the discovery. It is not always easy to decide between rivalcla.imants and there should be some court of aesthetic reference. Ifmasurium represents an unfortunate observation, albeit in good faith,nevertheless the name is preferable to technetium, regrettably cacophonous,yet fulfilling all the above criteria.Thenames proposed for them are : 43, technetium, Tc (to replace masurium)from the Greek, 2 ~ ~ ~ 6 5 , artificial, being the first artificially made element ; l185, astatine, At from the Greek diarcr~o~, unstable, being the only halogenwith no stable isotope; l2 87, francium, Fr (to replace actinium-K whichis only suitable for one isotope occurring in a natural radioactive family),proposed by Mlle.Perey , who was responsible for its undisputed discovery.13Examples of the generation and subsequent history of these elements are asfollows :There is little to add to the chemistry of elements 43, 85, and 87.a-decay @-decay2i;Ac ----+ ';,3Fr (Ac-K) 2i:Ra (Ac-X). 13.5 hrs.Isotopes of technetium also occur in the fission products of uranium, a5U.15The most stable occurs thus :&sion B--dec:iy f?--clecay 23aU -----+ ",&to -------+ :9,Tc zo'yrs./ ;:Ru (stable).6.274, 67 hrs.Atomic Weighb.-The twelfth and thirteenth reports of the committeeon Atomic Weights of the International Union of Chemistry are nowavailable ; l6 modifications are restricted to sulphur and copper.That the determination of isotopic abundance ratios can be of highaccuracy l7 is illustrated in the tables of Mattauch and Fliigge.8 Theinternational reports quote mass-spectrographic determinations of theatomic weights of, e.g., potassium, silver, and radium which are in excellentagreement with gravimetric values. M. G. Inghram has determined theabundance ratios for boron, silicon, and tungsten, from which, with dueregard to packing fraction and to the Smythe factor of 1.000275 for conversionl1 C.Perrier and E. Segr6, Nature, 1947, 159, 14.l3 J . Pkp.9. Radium, 1939,10, 435, 439, and ref. (10) where Paneth quotes theproposed name from private communication with Mlle. Perey.la B. Karlik and T. Bernert, Naturwiss., 1946, 33, 23.l5 " The Plutonium Project ", J. M. Siege1 (Ed.), J . Amer. Chern. Soc., 1946,68, 2411.l6 G. P. Baxter, M. Guichard, 0. Honigschmid, and R. Whytlaw-Gray, J . , 1947,1' Ann. Reports, 1946, 43, 315.D. R. Corson, K. R. Mackenzie, and E. Segri., ibid.980 ; G . P. Baxter, M. Guichard, and R. Whytlaw-Gray, ibid., p. 983.Physioal Rev., 1946, 70, 65352 INORGANIC CHE:MIHTR.Y.from the physical to the chemical atomic-weight scale, the chemical atomicweight may be calculated.Boron : IsotopeAbundanco, 0; ...................................Silicon : IsotopeAbundance, 0; (Inghram) ..................(D. Williams, P.Yuster) 30 ......(E. P. Ney, J. H. McQueen) l9 ...Tungsten : Isotope 189. 182.Abundance, 3; ......... 0.122 25-77183.1 i.24LO.18.8329.4.672.694.68182.30.68I I .Sl.1';1 Yci.29.17Atomic weight.10.821 (Calc.)10.82 (1917)2s-086 (Calc.)28.08i (Calc.)28-06 (1947)The new " pykno-X-ray method ", developed after the method employedfor fluorine by C. A. Hutchison and H. L. Johnston,21 is noteworthy. Itinvolves a determination of the ratio of molecular weights of some crystallinecompound of the element, say lithium fluoride, and of some crystallinereference compound such as calcite.This is derived from the densities ofthe two substances and the cell dimensions. T n this way T. Batuecas 2zobtained a value of 28-07.5 for the atomic weight of silicon by coniparison ofsilica with both calcite and rock-salt. Internal accuracies of thc order of1 part in 400,000 parts are obtainable, but the ultimate accuracy dependsupon that of the reference atomic weights. Batuecas's determination hasthe advantage that SiO,: CaCO, and SiO, :NaCl involve oxygen as theonly other element common to both ratios, which, nevertheless, yieldconcordant values. The similar determinations by C. A. Hutchison,D. A. Hutchison, and Johnston23 of the atomic weights of calcium andfluorine, though yielding concordant values, have either carbon, or lithiumand carbon, as common elements in each set of four ratios measured.Electron-dejicient i l l ~ l e c u l e s .~ ~ ~ 25-Further interest in the hydroboroiw,borohydrides, and allied compounds has been mainly dcvoted to cx tcndiiigH H H'\ / /'(I.) \B BH H\ @ B \B./H(111.)H H H\e/ 8' B ( t \ - . )H/ '\ \H Hthe appliwtjiorr of the hydrogeii-bridge h k , but there rt.iiiains in questioii t IN'nature of the link between the two boron atonis in diborniic. The argumentsl9 E. P. Ney and J. H. McQueen, Phjsicol Rec., 1946, 69, 41.2o D. Williams and P. Yuster, ibid., p. 556.21 J . Amer. Chem. Soc., 1941, 63, 1580.2s Physical Rev., 1943, 62, 3 2 ; 1944, 66, 144; J .Chena. Physics, 1942, 10, 489;24 Cf. Ann. Reports, 1943, 40, 62.22 T. Batuecas, Suture, 1947, 159, 706.1945, 13, 383.2 s Cf. ibid., 1945, 42, 67inay be summarised : It. P. Bell and H. C. Longuet-Higgins 26 proposed aresonance involving canonicals, such as (I)-( IV), and K. S. Pitzer 27 suggesteda " protonated double bond " which may be described as a a-bond betweenthe two borons, plus a x-bond in whose antinodes are imbedded two protons.Recently, A. D. Walsh 28 has suggested a third formulation (V), similar insome respects to the generally accepted structure (VI), of Al,C16, in that theelectron pair involved in the weak covalent link to the inner hydrogen atomsis supposed to be iitilised also for the co-ordinate link. Walsh notes that theconception that bonding electrons are capable under certain conditions offorming co-ordinate links, embraces the idea of " x-bonds " put forwardindependently by M.J. 8. D e ~ a r . ~ ~ A further suggestion,30 whereby each(11 C:l x x x\ / \ /M M I? x-yx '\*( L /' A1H/ \ / ''x c1 X X \ / \ / \H H H C1 c1(V.) WI.) (VII.) (VIIT.)bridge-hydrogen atom is supposed to use an electron-pair and its 1s orbitalin forming two " half bonds ", would appear to be identical with the originalresonance bridge structure (I) and (11). Without implying bias in favourof either formulation the bond may he conveniently written as (VII).Some ground has been cleared by the examination which Bell andLonguet-Higgins 31, 32 have made of the normal vibrations of the bridgedmolecule (VIII), and in which they find quantitative agreement with theRaman spectruni of liquid diborane33 and the infra-red spectrum of thevapour.34 This agreement is only obtained when using their symmetricalbridge model and not when using the ethane-type model, thus reducing theprobability35 of an electrostatic hydrogen bond, B-H .. . B, which wouldnecessarily dispose the hydrogens unsymmetrically between the two borons.Incidentally, Pitzer 36 concludes on theoretical grounds that entropymeasurements can make no useful contribution to the solution of the problem.The extension of the bridged-link (protonated or resonating) to theallied molecules, (a) higher hydroborons, ( b ) metallo-borohydrides, ( c ) covalenthydrides, and (d) metal alkyls, has been made as follows :(a) Pitzer 27 has shown that the higher hydroborons can be formulatedfrom the structural units BH,, BH,*BH,, BH,*BH*BH,, etc.-the so-calledhorines.Each hydrogen in each borine is potentially capable of formingit hydrogen-bridge link between two such units, and does so subject to thefollowing three conditions, (i) such a group is no longer free for the purpose? G *7., 1943, 250.!!& *7., 1947, 89.30 H. E. Rundle, J . Amer. Cllteni. SOC., 1917, 69, 1327.31 Proc. Roy. SOC., 1945, 183, A , 357.33 T. 1'. Anderson and A. B. Burg, J . Client. Physics, 1938, 6, 586.:!4 E'. Stitt, ibid.. 1941, 9, 780.36 . I . Attier. Chen,. SOC., 1947, 69, 194.2 7 , J . - 4 t n p r . C'ttew. S o c . . 1945, 67, 1126.49 J ., 1946, 406.32 Nature, 1948, 155, 328.35 A. Bumwoy, Nature, 1945, 155, 32'854 INORGANIC CHEMISTRY.of linkage if it becomes adjacent to two bridge links [as Bd‘ in the structure(IX) of B,H,], (ii) each boron participates in one bridge only, and (iii) ringscontaining less than five members are unstable. Thus all the hydroborons inStock’s original classification can be formulated and no others are predictedwhich would fall within the adequately studied range. High-molecular-weights polymers are known which may be assigned formulae (BH,*BH,),, or(BH,*BH,), + 2BH3.Longuet-Higgins 37 has pointed out that Stock’s classification has thesignificance in Pitzer’s theory that the more stable B,H, , , members possessonly two borine units each and include all but one of the cyclic structures,whereas, the less stable B,,H,, t 6 types comprise three borine units.Theproperties of the hydroborons, so far as they are known, fit in with these ideas,though information is as yet largely restricted to diborane. The structure( I X) of B,H, does, however, agree well with electron diffraction data.3*HRH2\ 14\e /” H \ A13i--BH2\B/B*\,/H HH /B<T- \H ( X - 1HI Li@ IHIH H /B\H H /(XI.)B,HIH\B/B*\,/H I I H\ A/” H \tH,H’I(XI.) BH,-Be-B-H”/ \H’ H’H’I(b) The preparation and properties of the borohydrides of lithium,beryllium and aluminium were reported in 1941,3B as were the electron-diffraction measurements of J. Y. Beach and s. H. Bauer *O on the aluminiumcompound, AlB,H,,.Where the chemical evidence indicates the covalentcharacter of that compound in contrast to the marked ionic character ofLiBH,, the structures (X) and (XI) might reasonably be e~pected.~’G. Silbiger and Bauer 41 have, however, observed the electron diffractionof beryllium borohydride, and re-examined the corresponding data of Beachand Bauer for the aluminium compound in the light of the suggested bridgestructures (as XI). Although confirming that the Al, Be, and B atoms aredisposed as shown and that the bridge structures predict correct positions ofmaxima, the overall picture is, in their opinion, better interpreted on thebasis of structures (XII) and (XIII). I n each BH, group, three hydrogenatoms (H’) form a symmetrical girdle about the straight line joining themetal, the boron, and the fourth hydrogen atom(H”).I n Be(BH,),, they findthat Be-B-H’ = 85” & 5” and the distance Be-B is. 1.66 & 0-04 A . Here, /\3i J . , 1946, 139.3 8 S. H. Bsuer and L. Pauling, J . Amer. Chena. SOC., 1934, 58, 2403.39 Ann. Reports, 1941, S, 65.40 J . Amer. Ghem. SOC., 1940, 62, 3440. * I Jbid., 1946, 68. 312DODD AND ROBINSON : GENERAT,. 55at least, i t appears that a resonance formulation, involving ionic andone-electron bonds, is appropriate. I n this connection, it would beinteresting to have the structure of the analogous compounds dimethyl-gallium borohydride, GaMe2BH,,24? 42 and dimethyldiborane.( c ) Hydrides of gallium, indium, thallium, and aluminium have beenreported, the first three being volatile, and the last non-volatile, and nodoiibt polymerized, (AlH3),.241 43 Longuet-Higgins and Bell 26 haveadvanced formula (XIV) for the volatile hydrides, and Longuet-Higgins 37has since put forward a two-dimensional giant molecule arrangement (XV)for (AlH3)n, the aluminium atoms being disposed in layers a t the verticesof a hexagonal tessellation and joined together by hydrogen bridges.H H(XIV.) \M-H-M/ / I1 \ (M = Ga, In, Tl.)H' 'H/AI--:-A~H / \ H\ /~i-;-~i€I/ \ n\Al- \H / /=\ H-A1 / H ~i-;-~i"\H/ \I3/ u AI-E-A~ H \H / \ HAl- /= H \ /" "\ AI-E-A~/ \ H H / \ H H //" / H Ir\/ \ i \Al<l-Alu \~i-:-~i A~-~-AI\(XV.)(d) There has been considerable speculation about the constitution ofVarious bridge45 including a " methylated double bond "37Pitzer and H.S. Gutowsky 46 havethe dimers which apparently exist in aluminium alkyls.structures have beenanalogous to Pitzer's protonated bond.recently prepared the following aluminium alkylsAlMe,. ,41Et,. AlPr,. AlPP,.20 M. .p. ........................ 150" -52.5" -107'd:! .......................... 0.752 0.823 0.837 -and some mixed alkyls. By X-ray, infra-red, and cryosopic measurementsthey find dimerization in all the above-formulated alkyls except theisopropyl compound. No higher polymers are found. It is concluded,from these compounds and the mixed alkyls, that one methyl per aluminiumatom will suffice to form stable dimers, though an a-methylene group willallow dimers of less stability.No dimer is possible with only one hydrogenatom on the a-carbon atom. These findings are embodied in the proposedstructure (XVI).4 2 H. I. Schlesinger, H. C. Brown, and G. W. Schliffer, J . Anaer. Chem. SOC., 1943, 65,43 0. Stecher and E. Wiberg, Ber., 1942, 75, 2003.44 L. 0. Brockway and N. R. Davidson, J . Amer. Chem. SOC., 1941, 63, 3287.4 5 A. Burawoy, Nature, 1945, 155, 269.1838.46 J . Amer. Chem. SOC., 1946, 68, 2204Tn this connection it is noteworthy that X-ray determinations showtetramethylplatinum to be tetrameric in the solid Structure(XVII) indicates the position of the platinum atoms and methyl groups :the distances are such that bonding through the four inner methyl groups isalmost certain.Ionic bonds through methyl ions are unlikely, and thepossible bridge link formulation shown (XVII I) occiirs to the R'eporters.Me,II (XVI.)RCH Pt(XVII.) (XVlII.)Lanthnons and Actinons.-For the double misnomer, " rare earths ",more recent practice has been to use '. lanthanides " or '* lanthanates ".J. K. Marsh 48 shows the unsuitability of the terminations and proposes themuch better term lanthanon ; and, now that the trans-uranium elements arecoming to be recognised as a second " rare-earth " transitions series, theyshould properly be called actinons.Marsh 48 has presented the chemistry of the lanthanons from a modernviewpoint, with emphasis on their separation; and B. S. Hopkins 49 hasreviewed the electro-chemical isolation of lanthanons.The properties ofLa, Ce, Pr, Nd, Sm, and Y have been summarised. D. L. Simonenko a hasdescribed a method of producing metals from difficultly reducible oxides,which is applicable to zirconium and the lanthanons. The lanthanonsform soluble complexes 51 with sodium nitrilotriacetate, N(CH,*CO,Na),.With excess of the reagent and of ammonium oxalate, acid precipitateslanthanum at pH 6, then przeseodymium and neodymium; samarium atpH 5 ; gadolinium a t pH 4-5, and erbium at pH 4.0. Four fractionationsQuart. Reviews, 1947, 1, 126.47 R. E. Rundle and J. H. Sturdivnnt, J . Amer. Cheur. ~!!oc., 1917, 69, 1561.4g B. S. Hopkins, Trans. Electrochem. SOC., 1946, 89, preprint S, 113.50 Compt. r e d . Acad. Sci. U.R.S.S., 1946, 51, 303.5 1 0.Beck, Helv. C/tht. -Actti. 1946, 29, 357give pure lanthanum. Hydrated orange ceric oxide is precipitated fromiiitriloacetate solution by hydrogen peroxide, the reaction being specific,sensitive to 8 pg. of Ce per c.c., and useful for purification. T. Moeller 52finds that slight hydrolysis of sulphates of tervalent lanthanons increaseswith decrease in the ionic radius.53 In the separation of uranium minerals, alarge part of the actinium would be concentrated by adsorption on the leadand barium sulphates. Fractional crystallisation of the double nitrates ofthe lanthanons and magnesium is recommended, whereby most of thelanthanum is removed. The actinium may then be separated by fractionalprecipitation of the hydroxides, which gives bett&r results when lanthanumis absent!.Though i t may havebeen under investigation previously,j5 the first positive identification wasannounced in April 1946 by C.D. Coryell lo (who has not yet suggested aname to replace ilkinium). The names of N. E. Ballou, L. E. Glendenin,B. L. Goldschmidt, F. Morgan, and J. A. Marinsky are particularly associatedwith the discovery.15 They have identified several radio-isotopes of whichthe most stable, 14’61, may be produced artificially from the stableneodymium isotope, ‘4,6,Nd, or as the result of p-deca,y of the nucleus l;7,Nd,which occurs as 2.6 yo of the fission products ~f‘ura~nium, 235U.The chemistry of element 61 has been ~onsiderect.~~Much of the work on the trans-uranium elements is known only throughreviews 56-59 which give some of the chemical and nuclear properties ofthese elements 60 and a table of isotopes of elements 90-96.These may bereferred to for further details and for the names of the workers in this field.The more important transmutations involved in generating the new elementsare shown in the accompanying figure, where the sort of nuclear reaction isto be inferred from the direction of the arrows in the key.Neptunium Ti?Np, the first trans-uranium element whose isotope wasdefinitely established,61 derives its name from the first trans-Uranus planet.Of its two isotopes subsequently found, 2iiNp is an a-emitter 57 (2.25 >: 106yrs.) and 1;:Np is a p-emitter (2.0 days).62Plutonium was discovered in 1940 as the very active a-emitter ?i?Puj2 J .Physical Chem., 1946, 50, 242.53 ill. Bachelet, J . Ci~inz. physique, 1946, 42, 98.64 S. Takvorian, Ann. Chitic., 1945, 20, 113.5 5 M. L. Pool, L. L. Quill, D. C. Macdonald, and J. D. Kurbatov, PJj,+~icd Rev.,1!142, 61, 106; C. S. Wu and E. Segrb;, ibid., p. 203.-s6: 1,. S. Foster, J . Chent. Edtic., 1945, 22, 619.j7 C. T. Seaborg, Chem. Eng. News, 1945, 23, 2190.j3 Idem, ibid., 1946, 24, 1192.ba Idem, Science, 1946, 104, 379.6 1 E. 31. McMillan and P. H. Abelson, Physical Rev., 1940, 57, 1186.5p Ident, ibid., 1947, 25, 358.1. Yerlman, Chenz. Eng. S e w s , 1946, 24, 3032; G . T. Seaborg, E. M. McMillan,A. C. Wahl, and J. W. Kennedy, PI/y+al RPV., 1946, 69, 36658 INORGANIC CHEMISTRY.(50 yrs.) and is named after the second trans-Uranus planet.A less activeisotope ";Pu (30,000 yrs.), identified 63 in 1941, decays into ",","U, the parentAc-U of the natural radioactive actinium family. Both 239P~~ and 235U are" fissionable " isotopes, the former being more important because it is moreeasily separated from uranium than is 235U from non-fissionable 23eU.Atomic No. 92 93 94 95 96Seaborg and M. L. Perlman 57 have found plutonium in small quantity( 1 part in 1014) in pitchblende and carnotite; 64 this might arise by way of238U by capture of neutrons whose emission from uranium products isattributed to U-X, (2,3tA~). The spontaneous fission of 238U (half-life,1 0 1 6 yrs.) may be an alternative source of neutrons.59 The atomic-bombproject prevented publication of these findings before 1946.6570, 555.63 J.\V. Kennedy, G. T. Seaborg, E. Segr6, and A. C. Wahl, Physical Rev., 1946,dl M. I. Corvalen, ibid., 1947, 71, 132.Oir See, however, H. D. Smyth, " Atomic Energy ", H.M.S.O., 1945; e..q., pp. 60, 77DODD AND ROBTNSON : GENERAT,. 59The trans-uranium elements form a group resembling the lanthanons andbeconling known as the actinon series. Elements 95 and 96 are the latestto be d i s c ~ v e r e d . ~ ~ High-energy bombardments with 4 0 4 MeV. He+ +ions of 238U and 239Pu using the 60-inch Berkeley cyclotron enabled Seaborg,R. A. James, L. 0. Morgan, and A. Ghiorso t o identify the isotopes of 95 and96. The nomenclature, americium and curium, follows that employed forthe corresponding members of the lanthanon series, vix., europium andgadolinium.Cerium recalls the Curies just as gadolinium honours Gadolin.Several hundred milligrams of neptunium have been worked up as purecompounds, and sufficient plutonium has been recovered for the physical andchemical properties to be accurately known.60, 61, G6 Neptunium exhibitsvalency states 3,4,5, and 6, with the shift in stability, in contrast to uranium,towards the tervalent state. NpT1 resembles uranium and is precipitatedwith sodium uranyl acetate. NpLV shows great similarity to thequadrivalent lanthanons and NplI1 is quantitatively carried down asfluoride with cerium. The chemistry of plutonium has been comprehensivelysurveyed by B. G. Harvey, H. G. Heal, A. G. Maddock, and (Miss)E.L. R ~ w l e y , ~ ~ and valency states 3, 4, and 6 have been established. Theirrelative stabilities are illustrated by the following scheme :(a) ~e+++ I , K2crso, ‘ purr 0, \ puIv ( b ) hot acid KMnO,, KeS,O,so,, U+++, I’ ‘ SO,, [Fe(CN),]‘-, H,O,Pllr’I ~where (a) and (71) refer to different concentrations of plutonium solution,(a) at tracer concentrations and (b) at about 1 mg. per C.C. PuTTr formsbright blue solutions, the sulphate, chloride, and perchlorate being readilysoluble in dilute acids, and the fluoride insoluble. PiiT17 forms pale pinksolutions (except the nitrate, which is green) and PuTv ions are morereadily hydrolysed than PuIrl ions. In the sexivalent state plutonium,like neptunium, resembles uranium and forms a brownish-yellow ammoniumplutonate, orange plutonyl nitrate, pale mauve sodium plutonyl acetate, andforms a complex compound with “ oxine ” in which the plutonium contentshows i t to be the analogue of uranyl “ oxinate ”.PurL- forms complexeswith the commoner organic reagents more readily than PnI1 I, which wasnot well precipitated by any of the reagents used.The a-radioactivity of the available isotopes of americium and curiumprecludes any attempt to obtain and handle amounts of more than 1 mg.Hence much of this work has involved ultramicrochemical techniques, ofwhich the acknowledged pioneers were P. L. Kirk and A. A. Benedetti-Pichler. The order of magnitude is illustrated by R. B. Cunningham a.ndL. B. Werner’s preparation of a pure plutonium compound from a 2microgram sample of the element, and by Cunningham’s isolation of pureamericium hydroxide, Am(OH),, from even smaller samples of startingn ~ a t e r i a l .~ ~ So far it appears that in aqueous solution only tervalentamericium is stable. Curium presents similar difficulties in even greaterF. Xtrrtssmm and 0. Hnhn, Naturwiss., 1942, 30, 256. G7 J . , 1947, 1010degree. Its intense a-activity induces decomposition of the water in whicahit is dissolved, and recoil effects are marked. Pure preparations have notbeen reported, but the only stable state of curium in aqueous solutionappears to be the tervalent one.The strong evidence that these elements belong to an actinon transitionseries has been reviewed by V. ST. Goldschmidt,68 by G.E. Villar,69 andby Seaborg.GO This would involve utilising the 5f orbitals as under A in theaccompanying table, rather than the ‘‘ standard ” configuration givenunder R.-4. €3.7 -____- L--- r-------_hl----- 7811ell. 0. 13. 0. 0. T’. 0.2 ILrt 88 = 78 + - 2 Ci -- 2 _- 2 (j __- 1 ~ 89 = 78 + - 2 t i 1 2 - - - 0 1 2 -)Th 9 0 = 78 f 1 d 6 1 2 -. - ’ L ( j d 2Pa 9 1 = 7 8 + 2 s G 1 2 _ _ , 6 3 2 .)U 9 2 = 7 8 + 3 2 G 1 2 __ 2 6 4 2Np 93 = 7 8 + 4 2 6 1 2PI1 9 4 = 78 +- 5 2 6 I 2Am 95 = 78 -i- A 2 0 1 2Cm 96 = 7 8 -I- 7 2 (i I 2Orbitals. 5j’. (is. Gp. &I. 7s. 5f. t k . 611. Btl. i s .Since the difference in energy between 5f and 6d shells is no doubt less thanbetween 4f and 5d and may well be of the order of chemical binding energies,the starting pointt of the actinon series may be less marked than that of thelanthanons, as appears from the variety of points chosen by different authorson chemical grounds.In its sexivalent state a t least uranium supportsthe “ standard ” configuration rather than the transition configuration ofits less stable tervalent state. Proceeding from uranium to higher atomicnumbers the tervalency clearly asserts itself at elements 95 and 96. A moreimportant criterion for accepting the actinon series, as such, than theoccurrence of lower valencies in earlier members, or even the possiblepresence of a single 5f electron in thorium, is the predominance of tervalencyin americium and cnrium.R. E. D.P. L. R .3 . SOME INTERMEDIATE COMPOUNDS IN IK‘ORG ANIC REA4CTIONS.This section deals with a number of unstable intermediate compoundsappearing in many inorganic reactions which have been investigated par-ticularly in recent years and have not been reviewed in detail.W. A.Waters’s book deals mainly with organic free radicals and discussesbriefly SL few inorganic radicals. Although relatively few intermediates havebeen ‘. isolated ” in a “ pure state ” their existence can be deduced fromkinetic measurements and is often made probable by some circumstantialNorsk Fysisk Tidsskr., 1941-1042, 3, 179.69 Bol. facultad in,q. Montevideo, 1946, 3, No. 2.“ The Chemistry of Free Rrtdirds ”, Clarendon Press, Oxford, 1940evidence, such as absorption spectrum, electrical conductivity, or magneticsusceptibility. These compounds are discussed here primarily from theirinorganic aspect without necessarily entering into full discussion of thekinetics of the reactions concerned.The unstable intermediates which play ail important r6le in the mechanismof many chemical processes are normally present in low concentration sinceinstability is the essence of chemical reactivity.They fall roughly into twogroups : (1) Free radicals or radical ions (" odd ions "), which, on accountof a free (unpaired) electron, enter into reactions with low heat of activationand thus appear in low stationary concentrations in a pseudo-equilibrium orstationary state. (2) Unstable addition or complex compounds which,though their ordinary valency requirements are generally satisfied, appearonly under suitable conditions in certain chemical equilibria ; examples areNO, and SnCli -.(1) Free Radicals.Free radicals are generally ephemeral and their presence is soiiietiiiiesdifficult to establish and usually rests on evidence derived from the kineticstudy of a number of chemical reactions.Cases in point are HO, and OH.Their importance springs from the fact that many chemical processes proceedin a sequence of simple elementary reactions which consist individually ofno more than univalent changes, such as the breaking of a single bond,the transfer of a hydrogen atom, or the transfer of an electroi~.~ These" univalent changes " being admitted, it is clear that the reaction must gothrough unstable intermediates each possessing an odd number of electrons.The Radical HO,.-Among the simplest, and probably most importantradicals are those compounded of hydrogen and oxygen which appear forinstance in the reactions between these elements.Here, following the ideasset out above, HO, would be expected to appear as a precursor in theformation of H,O, from niolecular oxygen. The existence of this radicalwas suggested first by H. S. Taylor,* and F. Haber 5 inferred that i t playedaii essential part in the reaction of hydrogen with oxygen. Its formationseems to take place according to the equation H + O,(+ M) = HO,(+ M)(M is a third body). Thus the formation of HO, is to be expected in thereaction between hydrogen atoms (e.g., from a discharge tube) with molecularoxygen.P. Harteck and K. H. Geib,6 who studied this reaction from apreparative point of view, found that i t leads eventually to the formation ofa very unstable compound of the composition of hydrogen peroxide whichdcconiposes into water and oxygen at teniperatures above - 115". Thereis evidcncc to suggest t h t HO, radicals are formed from oxygen ailti hydrogeniitoiiis produced photochemically by means of excited niercury atoins :Hg* -l- H, = HgH + H. Hydrogen peroxide, which is a product in thesereactions, is generally attributed to the interaction of the two radicals :C. N. Hinshelwood', J . , 1947, 691.3 J. Weiss, Naturwiss., 1935, 23, 64.Natunuias., 1931, 19, 450.2. phyaikal. Chem., 1926, 120, 183.Ber., 1932, 05, 155162 INORGANIC CHEMISTRY.2H0, = H,O, + 0,.7 The formation of HO, has been held responsible forthe inhibiting action of molecular oxygen in the photochemical interactionbetween hydrogen and chlorine,* in which hydrogen atoms appear a8 one ofthe chain carriers; and similarly, in the inhibition of the photochemicaldecomposition of hydrogen iodide by molecular ~ x y g e n .~ G. C. Eltenton lohas attempted to show the presence of HO, radicals in low-pressure flames ofoxygen and simple aliphatic hydrocarbons, by coupling the reaction chamberto a Dempstw type of mass spectrometer. Under these conditions thedetection of HO, is rendered difficult by presence in great quantity of normalmolecules of oxygen (mass 32) and by the contribution of 160170 of massidentical with the radical.This author actually found some indication ofHO, in that, after ignition of the gaseous mixture which reduces the con-centration of the two interfering species there was an increase in the ioncurrent for the mass corresponding to HO,. Recently G. J. Minkoff l1 hassummarised some of the chemical evidence for the existence of the HO, in t,hcgas phase, particularly with regard to some recent work of (Sir) A. Egertonand G . J. Mii&off,l2 and he has also discussed certain possible energy surfacesconnected with the formation of HO,.Additional inforination comes from reactions in the solid state and insolution. HO, is presumably formed as an intermediate when molecularoxygen reacts with hydrogen dissolved in palladium metal,13 and also inelectrolysis, by the depolarising action of molecular oxygen a t a metalcathode, since in both cases the hydrogen atoms present on the surface canreact with oxygen molecules.When molecular oxygen is passed over molten potassium a t 300°, a deeporange-coloured peroxide is formed corresponding to the general formula(KO,), which was previously given the formula K,O,.I4 Recently, E.W.Neuman l5 investigated the compound, a t the suggestion of Pauling, whopointed out that the only reasonable electronic structure for the 0;- ionwould be : 0 : 0 : 0 0 : , but an ion of this constitution should be dia-magnetic and presumably colourless. However, the peroxide proved to beparamagnetic with a Bohr magneton number of 2.04 at room temperature.This is close to the value of 1-73 B.m.which corresponds to the spin momentof an unpaired electron, and to the value of 1.83 B.m. as calculated byvan Vleck for a molecule with doublet separation. The discrepancy has beenattributed to experimental error or, possibly, to a mutual interaction of themagnetic dipoles in the condensed phase. The investigation leads to theformula KO, and hencc to the assumption of 0,- ions in the crystal lattice, a. . . . . . . .. . . . . . . .7 J. R. Bates and D. I. Salley, J . Arner. Chena. SOC., 1834, 56, 110.8 31. Bodenstein and P. W. Schenclr, 2. physikal. Chern., 1933, B, 20, 420.0 G. A. Cook and J. R. Bates, J . Amer. Chetn. SOC., 1935, 57, 1775.10 J . Chem. Physics, 1947, 15, 456.11 Faraday SOC. Discussion on " The Labile Molecule ", Sept.1947 (in the press).12 Proc. Roy. SOC. (in the press).13 J. Weies, Tram. Farachy SOC., 1935, 31, 668.14 W. Traube, Ber., 1912, 45, 2201, 3319. l5 J . Ghem Physics, 1934, 2, 31WEISS : SOME INTERMEDIATE COMPOUNDS IN INORGANIC REACTIONS. 63fact confirmed by W. Kassatochkin l6 who, from X-ray diffraction, found thati t was an ionic crystal coinposed of K+ and 0,- ions, somewhat similar instructure to the lattice of potassium chloride, but elongated in one directionon account of the shape of the 0,- anion. A. Baeyer and V. Villiger l7 foundthat the oraiige-red peroxide is also formed from ozone and solid potassiuinhydroxide and that i t is decomposed rapidly by water, giving off oxygen.F. Haber and H. Sachsse l8 have found that the reaction between sodiumvapour and oxygen at low pressures, which they studied by the method ofdiffusion flames, involves the intermediate formation of NaO, according to(i) Na + O,(+ M) = NaO,(+ M) (If = a third body)(ii) NaO, + Na = 2Na0 -- Na,O,.A study of the absorption spectrum of ozone in solution in the presence ofacids and bases, and particularly in concentrated solutions of potassiuinhydroxide (down to temperatures of - 40°), has furnished evidence l3 thatthe ozone presumably interacts in these solutions according to the equations(i) 0, + KOH = KO, + HO,, (ii) 0, + OH- = 0,- + HO,.The secondreaction is probably of importance for all the reactions of ozone in aqueoussolution, particularly for that between ozone and hydrogen peroxide.Thereis some evidence l39 19 to show that the following chain reactions play asignificant part : (i) 0, + HO, = 20, + OH, (ii) 0, + OH = 0, + HO,.I?. Haber and R. Willstatter 2o and F. Haber and J. Weiss 21 have assumedthe presence of HO, in the photochemical and thermal reactions of hydrogenperoxide which are discussed on p. 66.The study of a number of the reactions of molecular oxygen in solution(e.g. , processes of autoxidation and the quenching of fluorescence by molecularoxygen) has made it very likely that the first step in these reactions consistsin the univalent reduction of 0, by a single-electron transfer, to give the0,- ion. In autoxidation in solution the electrons are transferred successivelyfrom the reducing agent (electron donor) according to 0, + electron ---+ 0,-.22In aqueous solution the latter ions are in equilibrium with HO,.These nowtake up a second electron from the donor, HO, + electron .+ HO,-, thusleading to the formation of H,O, which has been isolated in many autoxid-ation processes. Whether or not H,O, is actually found depends entirely onthe rate of any subsequent reactions in which it is involved. This isillustrated by the autoxidation of various acceptors (e.g., leuco-dyes, 39 22 23s ,4C'oinpt. rend. U.R.S.S., 1946, 47, 193; W. Kassittochkirl and W. Kotov, J . (:lteijt.Phgsics, 1936, 4, 458.l7 Ber., 1902, 35, 3038.l8 2. physikal Chern., Bodenstein Vestband, 1931, 831.l9 H. Taube and W. C. Bray, J . Anher. ChnL. SOC., 1940, 62, 3357.2o Ber., 1931, 64, 2844.21 (a) Naturwiss., 1932, 20, 948; ( b ) Proc. Roy.SOC., 1934, 147, A, 338.2 3 J. Weiss, Nature, 1934, 135, 648.23 J. E. Lu Valle and A. Weissberger, J . Anzer. Clwn. SOC., 1947, 60, 1567, 1576,24 J. H. Baxendale and S. Lewin, Tram. Paraday SOC., 1946, 43, 126.182164 INORGANIC CHEMISTRY.metal ions) which have been studied by various authors.ferrous ions the reactions are as follows : 3,22I n thc cas0 ofFe2’ -1- 0, + Fe3 + 0,-0 - H-- A 2 + -HO,Fe2 + HO, =+ Fe”- + H0,-H02- + H- =+= H,O,Here the 11)-drogen peroxide is decomposed further by the ferrous ions (seeApart from the interaction of two HO, radicals, giving H,O, and O,,there is also the possibility of an interaction according to 2H0, = 0, + H20.It is possible that the traces of ozone which are sometimes observed inautoxidation processes are due t o this cause.I n the quenching of fluores-cence of, e.g., polycyclic hydrocarbons (anthracene, benzpyrene) by molecularoxygen 25-28 the electron is donated by the excited molecule (A*), on theabsorption of a light quantum, and this may either return to the ground statcwith the emission of light, thus emitting fluorescence, or else may reactwith molecular oxygen : A*[+ $1 + O,[+ +]+A [.f] + O,-[.fJ-][.f]. Thearrows in the brackets indicate that this and similar processes proceed withouta change in the multiplicity and therefore should take place with an enhancedp r ~ b a b i l i t y . ~ ~ I n accordance with this scheme, products of the formula AO,have frequently been isolated.In view of the importance of 0,- and HO,, attempts have been made toobtain values for the electron afinity of the 0, inolecule and for the bindingenergy of the H atom.The first is not yet known with much certainty;calculations from a cycle process 30 have yielded ca. 2-7 e.-v. ; D. T. Vierand J. E. Mayer 31 found 3-2 e.-v. by some direct measurement’s. The bondenergy 0,-H is also not known accurately.estimated it at 44 kcals. According to thc gencral theory given byW. Heitler,32 it is possible to estimate the energy values of the reactions0, + H = HO, + Q1 kcals; HO, + H = H,O, + Q2 kcals.on the assumption that the oxygen atom is in a 3S ground state and that theoxygen-oxygen bond is a pure spin-valence.Although the values of Q1 and&, depend on the amount of Coulombic energy assumed, t,hey are not greatlyinfluenced by this factor.1). 65).Bodenstein and SchenckThis is illustrated by the following figures : 33Coulombicenergy, 7;. Q1, kcals. Q 2 , kcals.33 53 10120 48 042 5 14;. J . Jj~owur~ a i d A. Nortoil, Tra)hs. 2f’uruday Soc., 1‘339, 35, 44.2 6 15. J . Bowen and A. H. JVilliams, ibid., p. 765.2 7 H. W’eil-Malherbe and J. Weiss, Nature, 1942, 149, 471.$ 8 J. Weiss, Trans. Faraday SOC., 1946, 42, 133.29 A. Terenin, Acta Physicochim. U.S.S.R., 1943, 18, 211.30 J. Weiss, Traits. Faraduy SOG., 1935, 31, 966.32 “ Handbuch der Kadiologie,” Yol. 11, Akadem. Verlagsgosellsch., Leipzig, 1934.35 J. Weiss, Faradey SOC. Discussion (see ref.1 1 ) .31 J . Cheni. Physics, 1944,12, 28WEISS : SOME INTERMEDIATE COMPOUNDS IN INORGANIC REACTIONS. 65The Hydroxgl Radical (OH).-This radical was postulated in themechanism of the reaction between hydrogen and oxygen by Haber et uL3'Subsequently, K. F. Bonhoeffer and H. Reichhardt 34 established its presenceby the absorption spectrum of heated water vapour in excess of oxygen,where the following equilibrium holds : 40H 2H,O + 0,. The absorp-tion spectrum of OH radicals in the gas phase was then investigated in greaterdetail by Oldenberg et ~ 1 . 3 ~ with spectroscopes of high resolving power. Inthis way OH radicals were shown to be present in such systems as the H,-0,flame and the electric discharge through water vapour. These authorsdetermined also the transition probabilities of the lines of the OH bandspectrum (f-values) and were thus able to measure quantitatively theconcentration of the OH radicals.By this means they obtained thedissociation constant, and the heat of dissociation, of water vapour withconsiderable accuracy : 36H + OH ---+ H,O 1- 118.2 0.7 kcals. (at 0" K.)0 + H ---+ OH + 110.1 -j= 0.9 kcals. (at 0" K.)"he absorptioii spectrum is at present undoubtedly the best method for thedetection of OH radicals in the gaseous phase, but as Eltenton lo has pointedout, OH is very difficult to detect by the mass spectrometer.Hydroxyl radicals presumably appear in a great number of reactions inthe gas phase and in solutions, some of which have been cited already in thediscussion of the HO, radical.Among the most important and frequentlyinvestigated of these is that between hydrogen and oxygen. In his recentBakerian Lecture, C. N. Hinshelwood 37 has represented the principalelementary processes by the following scheme :H = 2HOH + H, = H20 + HH + 0, = OH + 00 + H, = OH + HH + 0, + M = HO, + MHO, + H, = H20 + OHHydroxyl radicals play an important part in the reactions of hydrogenperoxide in solution, and consequently also in autoxidation processes whereinhydrogen peroxide is formed as an intermediate. One of the better knownis that between hydrogen peroxide and ferrous iron salts which, after thevery early work of Sohonbein, was investigated later by W. Manchot andG . Lehmann,38 with the following results : (a) I n the presence of excess ofj'errous s d t .A given amount of dilute hydrogen peroxide was added slowlywith stirring to a solution containing an excess of ferrous sulphate. Underthese conditions, when the ferrous concentration in the reaction space was31 2. physikal. Chem., 1928, 139, 75; K. F. Bonhoeffer and F. Haber, ibid., 1928,137, 263; K. F. Bonhoeffer and T. G. Pearson, did., 1931, B, 14, 1.35 0. Oldenberg and F. F. Rieke, ibid., 1938, 6, 169, 779; 1939, 7, 487;L. Avramenko, Acta Physicochim. U.S.S.R., 1943, IS, 58; G. Damkohler and R. Edse,Naturwiss., 1943, 31, 310.36 R. J. D y e r and 0. Oldenberg, J . Chem Physics, 1944, 12, 351.37 Proc. Roy. SOC., 1946, A , 188, 1. 38 Annalen, 1928, 460, 179.REP.-VOL. XLIV.66 INORGANIC CHEMISTRY.always high compared with the concentration of the H,O,, the reaction wasrepresented by 2FeS0, + H,O, + 4H20 = 2Fe(OH), + 2H2S0,. ( b ) In thepresence of excess of hydrogen peroxide. A given amount of a dilute solutionof ferrous sulphate was added to a dilute solution of hydrogen proxide sothat the latter always remained in excess. For these conditions the reactionchanged to 2FeS0, + 3H202 + 2H,O = = 2Fe(OH), + 2H,SO, + 0,.I n order t o explain their results these authors assumed the intermediateformation of a quinquevalent iron oxide (Fe,O,) which was supposed t o reacteither (a) with excess of ferrous salt yielding ferric salt, or ( b ) with excess ofperoxide to give ferric salt and oxygen. It has been shown, however, thatthis explanation cannot be correct, for under suitable conditions (i.e,, highratio of [H202]/[Fe2+] in the reaction space), much more than the one moleof oxygen demanded by Manchot's equation is produced in the oxidationof one mole of ferrous t o ferric salt.This led to the formulation of thereaction as a chain mechanism. It is found that, as a first approximation,the reaction can be described in its main course by the following fourelementary processes :Fe2+ + H,O, = Fe3+ + OH- + OH . . ( 1 , 1 )Fe2+ + OH = Fe37 + OH- . . . . . (1, 2)I n the case when the ferrous salt is in excess, no oxygen is formed. I n thepresence of excess of peroxide the latter competes with the Fe2 for tlhe OHradicals and the following two chain reactions come into operation :H202 + OH = HO, + H20 .. . . ( 1 , 3 )H 2 O 2 + H O , = 0 , + H 2 0 + OH . . . (1, 4)The possibility of a chain in the hydrogen peroxide decomposition is clearlydemonstrated by the photochemical decomposition where quantum yieldsup to 100 have been observed.39 The photochemical primary process due toabsorption (in the near ultra-violet) consists in the formation of OH radicals :H,O, + hv --+ 20H.4" Chain-breaking processes are represented here bythe interaction of two radicals and their consequent disappearance from thesystem :The interaction of radicals is also of importance in the ferrous salt reaction,particularly at sufficiently low ferrous-ion concentrations, since the abovescheme is evidently inadequate as it is known that the chain length decreasessomewhat with increasing hydrogen-ion concentration. This could point toa Participation of H0,- or 0,- in the chain reactions, but it is also possible thatsome of the chain-breaking processes are favoured by hydrogen ions in thatthese might lead t o the formation and subsequent participation of H20,T(from the equilibrium HO, -t Hi + H,O,- ) or of H,O (from the equili-brium HO + H' + H,O* ) in these processes.HO, + OH = 0, + H20 .. . . (1, 5)39 G . Kornfeld, 2. physikal. Chein., 1936, B, 29, 208.40 H. C. Urey, L. H. Dawsey, and F. 0. Rice, J . Amer. Chem. Soc., 1929, 51, 1371WEISS : SOME INTERMEDIATE COMPOUNDS IN INORGANIC REACTIOXS. 67If one starts with ordinary '' neutral " solutions of ferrous salts andhydrogen peroxide, hydrogen ions are used up in the course of the reactionand basic ferric salt is precipitated and eliminated from the reaction.I nsufficiently acid solutions, however, where ferric ions are present, the rapidoxidation of the ferrous salt is followed by the slow decomposition of hydrogenperoxide which, under these conditions, assumes the character of a catalyticprocess, in the course of which ferric ions are periodically reduced. Accordingt o Haber and Weiss,21 the ferric-ion catalysis is not a chain reaction underordinary conditions. It can be indicated by the schemeFe3I +H0,---+Fe2++H0, . . . . ( 1 , 6)which is followed by the chain reaction (1,4) and reoxidation of the ferrous ionsaccording t o ( 1 , 2). Originally the reaction Fe3+ + HO, = Fe2 + + H + + 0,was thought to be responsible for the formation of oxygen under theseconditions, but recent investigations 41 have shown that this reaction isprobably unnecessary.The system hydrogen peroxide-ferrous salt, known as Fenton's reagent,is of considerable interest in that according to the above discussion itgenerates hydroxyl radicals in solution.This has been demonstratedrecently by M. G . Evans et u Z . , ~ ~ who showed that the system is capable ofinitiating the chain polymerisation of certain monomers (methyl meth-acrylate, acrylonitrile) in aqueous systems and also that hydroxyl groups areactually taken up into the growing polymer chains.I n the presence of water, cobaltic ions give rise to the formation of oxygenat room temperature. It has been suggested3 that this is due t o theintermediate formation of OH radicals according toCo3' + OH- = Go2' + OH; Co3' + H20 = CO'.+ H20.followed by H20 + OH + H ', 20H = H,O + 0, 20( + M) = O,( + M)Ceric ions which do not react under ordinary conditions, are capable ofundergoing a similar reaction 43 on irradiation in the near ultra-violet, whenpresumably an electron is transferred to the excited ceric ion (Ce4' *) fromone of the water molecules in its hydration shell, resuIting again, as above, inthe formation of H20i and eventually molecular oxygen. It is also verylikely that OH or H,O' is a precursor in the anodic formation of molecularoxygen in electrolysis.@Recently it has been suggested45 that, if water is irradiated by X-rays,y-rays, cc-particles, or neutrons (recoil protons), these ionising radiations cause;t splitting of the water molecules into radicals : H,O ---+ H + OH.? This4 1 J.Weiss, Paraday SOC. Discussion (see ref. 11).42 J. H. Baxendale, M. G. Evans, and G. S. Park, Tram. Faruduy SOC., 1946, 42,43 D. Porret and J. Weiss, Nature, 1937, 139, 1019.IQ 0. J. Walker and J. Weiss, Truns. Furaday SOC., 1935, 31, 1011.t The sign +has been adopted in radiation chemistry following recent American155; J. H. Baxendale, M. G. Evans, and J. K. Kilham, ibid. p. 668.J. Weiss, Nature, 1944, 153, 748; Trans. Faraduy SOC., 1947, 45, 314.practice68 INORGANIC CHEMISTRY.presumably is brought about by the intermediate formation of H,O+ andH,O-, the latter decomposing according to the equilibriumH20- s H + OH-.In agreement with this view are some experiments of F.S. Daintjon,*6 whowaa able to initiate the chain polymerisation of acrylonitrile in aqueous systemsby irradiation with y-rays.More recently it has been shown 47 that simple organic substances(benzene, nitrobenzene, benzoic acid) undergo hydroxylation if treated withhydrogen peroxide and a, ferrous salt and also by irradiation with y-rays,X-rays, or neutrons in aqueous systems, thus giving further support to theformation of hydroxyl radicals under these conditions.The SH Radical.-According to Forbes et u1.,** absorption of ultra-violetlight by hydrogen sulphide in the gas phase or in chloroform solution corres-ponds to the photochemical primary process :H2S + h v + HS + H followed by, e.g., H -t HS --+ H, -1 S ant12HS --+ H,S2 or 2HS -+ H2S + S.Very similar results had been obtained 49 in the investigation of tlwphotochemical primary process corresponding to the light absorptlion ofSH- ions and S2- in aqueous solutions, which can be represented by ( i )SH- + H20 + h v --+ SH + H,O-, (ii) S2- + H,O + h v I_, 8- + H20-(S -+H+ +Z SH)The Radical NOH.-The existence of this radical was assumed byA.Angeli 50 and later by F. Raschig 51 in the reaction between nitrous acidand sulphur dioxide. M. L. Nichols and C. W. Morse 52 assumed its form-ation in certain reduction processes involving oxides of nitrogen, and similarviews were put forward by L. Cainbi,53 who also assumed the intermediateformation of NOH in the decomposition of the so-called " blue acid ".54According to L.Andrussow 55 and M. BodensteinYb6 NOH is one of tlicprimary products in the catalytic oxidation of ammonia on platinum catalysts.Bodenstein found nitrous oxide and nitric acid among the reaction productsand suggested that these were formed according to (i) 2HN0 = N20 + H20,(ii) HNO + 0, = HNO,.The formation of NOH has been assumed if nitrogen oxide is added to astream of hydrogen atoms from a discharge This was confirmed by4 6 Nalure, 1947, 160, 268.4 7 G. Stein and J. Weiss, in course of puhlicRt,ion.' 8 W. H. Avery and G. S. Forbes, J . Anier. Ckeire. A'oc., 1!)38, 80, 1003; CX. S.Forbes, J. E. Cline, and B. C. Bradshaw, ibid., p.1431.4 * H. Fishgold and J. Weiss, Nature, 1936, 137, 71.51 " Schwefel und Stickstoff Studien ", Verlag Chemie, 1924.52 J. Physical Chem., 1931, 35, 1239.53 Atti R. Accad. Lincei, 1933, 17, 204.s p E. Bed, K. Winnacker, and H. H. Saenger, 2. aiaorg. Chem., 1933,211, 379.5 s Ber., 1926, 59, 458; 1927, 60, 536. 5 6 2. EZektrochem., 1935, 41, 466.57 H. M. Smallwood, J . Amer. Chenz. SOC., 1929, 51, 1985.Ber., 1904, 37, 2396WETS : SOME INTERMEDIATE COMPOUNDS IN INORGANIC REACTIONS. 69P. Harteck,58 who showed that if hydrogen atoms are allowed to react withnitrogen oxide at liquid-air temperatures a compound is formed of thegeneral formula (HNO),, which decomposes with the formation of nitrousoxide and water.It is very suggestive that the first product of reduction of NO in solutionis the NO- ion formed by an electron transfer from a suitable reducingagent (donor) according to NO + electron+ NO-, followed by NO- +H i +NOH, and leading thus to the formation of nitrous oxide accordingtjo the above equation.This is in agreement with the formation of nitrousoxide if nitrogen oxide is acted on by reducing agents such as Ieu~o-indigo,~~alkaline pyrogallol,60 sulphur dioxide,6 or stannous chloride.62Similarly NO- is presumably formed in the quenching of fluorescence ofvarious substances by nitrogen oxide in solution 63 (e.g., polycyclic hydro-carbons). This is analogous to the quenching action of molecular oxygenwhich is thereby converted into 02-. Just as in the latter case, where more orless stable peroxides are formed, the quenching of fluorescence by nitrogenoxide can lead to the formation of " nitroxides " of the general formula(A, NO); these are generally less stable than the peroxides, but they can beisolated under suitable conditions.64The N, Radical.-Alkali azides in aqueous solution show an absorptionspectrum in the ultra-violet which is simiIar to that of the alkali bromides oriodides.It has been suggested 65 that the photochemical primary processis connected with the electron-affinity spectrum as proposed earlier byJ . Franck and F. Haber 66 for the halogen ions, vix., N,- + H20 + h v N, -+ H,O-. This leads to the intermediate formation of the azide radical, whichis probably also formed by chemical oxidation, for example, in the transferof an electron to the ceric ion, N3- + Ce4' j N, + Ce3'.The N, thenbreaks up, ultimately giving molecular nitrogen.The Monothionic Acid Radical (SO,H).-Franck and Haber 66 suggestedthat this radical plays an essential part in the thermal and photochemicaloxidation of sulphites in solution. The autoxidation of sulphite can beinitiated by metal ions, e.g., cupric ions, or by irradiation 67 in the ultra-violet, where the SO;- and HS0,- ions show strong absorption.68 Thephotochemical primary process corresponding to this light absorption can berepresented by the equations S@- + H,O + h v + SO,- + H20-, followedby H,O- -+ OH- + H and 2H = H and the equilibrium SO3- +HBer., 1933, 66, 423. 59 W. Manchot, Ber., 1906, 39, 3510.61 G.Lunge, Ber., 1881, 14, 2196. 6o C. Oppenheimer, Bet-., 1903, 36, 1744.62 G . Chesneau, Compt. rend., 1899, 129, 100.61 Idem, J . , 1944, 541.65 J. Weiss, Tram. Faraday SOC., 1947, 43, 119.6 6 J. Franck and F. Haber, Sitzungsbe?.. Preuss. Akad. Wiss., 1931, 250.6 7 H. L. J. Backstrom, Me&. Vente,nsk. Akad. Nobelimt., 1927, NO. 16, 6, 22;J . Anher. Chem. SOC., 1927, 49, 1460; H Alyea and H. L. J. Biickstrom, ibid., 1929, 51,90.H. Weil-Malherbe and J. Weiss, Nature, 1943, 151, 449.** H. W. Albu and P. Goldfinger, 2. physikal. Chent., 1932, B, 16, 33870 INOWANIC CHEMISTRY.A -HSO,. .This has been confirmed by the work of F. Haber and 0. H.Wansbrough- Jones,69 who found that irradiation of sulphite solutions gavedithionic acid, resulting from recombination of the radicals, ZHSO, = H2S,06,and molecular hydrogen.Some of the radicals may also undergo dismutation :2HSO, = SO, + H,SO,, leading to the production of some sulphate. Theaction of cupric ions in initiating the autoxidation is connected with theformation of the same radical : Cu2. + SO:- + Cu $- SO,-. Previousexperiments 70 had shown that the reaction between copper sulphate and analkali sulphite, in the absence of oxygen, leads to formation of dithionate. Inthe presence of molecular oxygen, SO,H can initiate a chain reaction. Beliefin the chain character of this autoxidation reaction is supported by the fact thatvery small amounts of cupric ions are capable of starting the reaction, and alsoby the characteristic action of inhibitors.Furthermore, this is confirmed bythe photochemical autoxidation initia$ed by light absorption in the ultra-violetwhere, according to the foregoing discussion, SO,H radicals are produced. Aswas found by H. L. J. BackstrOmys7 several tens of thousands of oxygenmolecules are used up per one light quantum absorbed by the sulphite. Thesehigh quantum yields (10,000 or more) clearly establish the chain character ofthis reaction. Other reactions in the autoxidation chain reaction can berepresented by the following elementary processes : 71(i) HSO, + 0, ---+ SO, + HO, (iii) SO,- + H20, + SO, + OH- + OH(ia) (SO,- + 02+ SO, + 02-) (iv) SO:- + OH + SO,- + OH-(ii) HO, + SO:- + SO,- + HO,-- (v) SO,H + OH --+ SO, + H20The UO,.Radical Ion.-The existence of this radical ion has been sug-gested by A. H. Carter and J. Weiss 72 in the quenching of the fluorescenceof uranyl salts in solution and in the photosensitised decomposition andoxidation of various substances by uranyl salts.Absorption of light by uranyl salts leads to formation of an excited ionaccording to UO: + + hv -+ UO$+ * ; the latter can either return to theground state with the emission of fluorescence, UOpt * --+ UOg + hv’, or,in the presence of a suitable electron donor (e.g., iodide or oxalate ions), thefluorescenee is quenched. This process consists in the transfer of an electronfrom the donor t o the excited uranyl ion, leading to the formation of UO,’ ,UO; * + I- -+ U02+ + I, and represents the primary process of thequenching of fluorescence which is identical with the photosensitised formationof iodine.More recently W.E. Harris and I. M. Kolthoff 73 have suggested that theformation of this radical ion occurs in the polarographic reduction of uranyl6s 2. physikal. Chem., 1932, B, 18, 103.70 H. W. Albu and H. D. Graf von Schweinitz, Ber., 1932, 65, 729 ; H. Baubigny,Compt. rend., 1912, 154, 701; Ann. Chim. Phys., 1914, 1, 1.P. Goldfinger and H, D. Graf von Schweinitz, 2. piqsikal. Chem., 1933, B, 22,211; H. L. J. Backstrom, ibid., 1934, B, 25, 122.72 Proc. Roy. SOC., 1940, A , 174, 351.73 J . Anter. Ghem. SOC., 1945, 87, 1484WETSS SOME INTERMEDIATE COMPOTJNDS IN INORGANIC REACTIONS. 7 1salts, where it is supposed to represent the first stage : UO; ~ + electron +UO, ' .This has also been confirmed by H. G. Heal.'*(2) Ions derived from Cation-Anion Complexes.According to the classification given above, these complexes belong tothe second group of unstable intermediates. They appear in ionic equilibriaand their stability varies greatly. It has been pointed out recently byC. N. Hinshelwood2 that complexes of this nature are probably of greatimportance as intermediates in the mechanism of many reactions.(i) Complexes between Cations and Halogen Ions.-The identification of thesecomplexes in solution is based on some evidence from kinetic data, but a tpresent rests mainly on the study of absorption spectra in solution. Theinterpretation of the absorption spectra is sometimes rather ambiguous, andi t is necessary to study the spectra systematically under different conditions.H.Fromherz and Kun-Hou Lih 75 analysed the spectra of dilute solutionsof lead halides in terms of superimposed band due to Pb2" and PbX(X = halogen ion). The corresponding association constants K,, defined byK , = [PbXr]/[Pb2i][X-], are given in the following table. They wereB ssociation constants (K,) and absorption maxima of lead h.alidecomplexes, PbX .K , * An,,,. (mp).PbCl i- ........................... 12.9 226PbBrt ........................ 14.1 236.8Pb1'- ........................... 29.0 364.5determined by H. Fromherz 76 from the change in the relative intensity ofthe short-wave band due to Pb2 ions and the long-wave bands which could beassigned to the PbXt ions.Higher association complexes are not presentunder these conditions. This was confirmed by experiments on solutions oflead bromide and iodide in the presence of a large excess of Pb2] added aslead perchlorate. Under these conditions the equilibrium of any higherassociates should be shifted towards the formation of PbX , but no appre-ciable change was observed.However, in the investigation of absorption spectra of the lead halides inconcentrated solutions of alkali halides, more highly associated species werefound which were attributed to the formation of PbX:-. On dilution, theseparticular bands diminished in their intensity, but no other bands wereclearly distinguishable until the spectrum was gradually transformed intothat of a mixture of Pb2+ and PbX .The authors have discussed thesechanges in terms of a gradual dissociation of the PbXi- complex, passingthrough PbX,- and PbX, to PbX+ and Pb2+. A similar explanation wasgiven by H. Fromherz et al. for the bands of the halides of Cu2+, Hg2+, Zn2 b,7p Nature, 1946, 157, 228.75 2. physikal. Chem., 1931, A , 153, 321; 1933, A , 167, 103; see also E. Doehlemann7R Ibid., 1931, A , 153, 376.and H. Fromherz, ibid., 1934, A , 171, 35372 INORGANIC CHEMISTRY.Cd2 , and Sn2 which were investigated in solutions containing alkali halides,where equilibria of the type MeX, + 2X-In many spectra of these complexes the extinction curves in the far ultra-violet rise to very high values not encountered in the spectra of the freeanions or of the binary associates. Analysis of the extinction curves of thestannous halides in solution in the presence of alkali halides shows clearly theabsorption bands due to the SnXS- ions.There is a regular shift towardslower frequencies in the series chloride-bromide-iodide in the spectra of thesecomplexes. 'l'he following t!al)le i R has4 on figiires given by H. Fromherzand H. J .MeX2,- are established.Wave-length (mp) of bund maxima of the complexes of the form Mexi-.Co-ordinating ion. Zn2+. Cd2+. fin2+. HgZi. C U ~ ~ . Pbzt'.c1- ........................... - 187-5 218.5 228.5 250 272........................... 215.5 245 250 98 1 304 Br -I- .............................. 238.5 2557 "0 ..d '3 9 3 I 363.3-In the crystalline state the co-ordinately " saturated " complexes arefavoured a t the expense of the " non-saturated " forms, a condition arisingprobably from reasons of symmetry, but in solution this would not generallybe expected to be the case.In solutions of FeX,, E. Rabinovitch andW. Stockmayer 78 found that the intermediate forms FeX2 +, FeX,+, and FeX,predominate over the Fe3 + and FeXi- species throughout a wide range ofconcentrations. This view was reached from a study of the spectra ofsolutions of ferric perchlorate, chloride, and bromide a t different acidities,ionic strengths, concentrations, and temperatures. These observationsenabled the authors to determine the extinction curves and the associationconstant for the first three ionic complexes FeC12 +, FeCl,+, and FeCl,.All thespecies possess intense bands in the ultra-violet which extend into the visibleand contribute to the colour of ferric chloride solutions. Their associationconstants, at 26.7" and an ionic strength p = 1, are given by the expressionsKPeC12+ = [FeC12+]/[Fe3 k][Cl-] = 4.2, KPeCl,+ = [FeC12+]/[FeC12 t][Cl-] = 1.3,KF,.Cl, = [FeCl,]/[FeCl,+][Cl-] 0.04. Of these constants, KFeC12t can beconsidered as fairly accurately determined, but the other two are only roughestimates.The absorption curve of FeC12+ can be obtained practically free from thoseof the higher associates [although " contaminated " by the extinction due tothe products of hydrolysis Fe(OH),+ and Fe(OH),+] by using a low, constantconcentration of hydrochloric acid, and comparatively large concentrationsof Fe(ClO,),. If HClO, and NaC10, are added in quantities required tomaintain constant acidity and ionic strength, the resulting curves show theaverage extinction coefficients as a function of the ferric-ion concentration.The curve8 can be represented by a formula for a single association equili-brium and thus allow the calculation of the extinction coefficient of FeC12 + .(ii) Ions derived from the Interaction of Oxy-acids and Hydrogen Ions.--Itis well known that certain reactions, particularly many oxidation reactions in7 7 2.phyaikal. Chem., 1936, A , 178, 29. J . Amer. Chem. SOC. 1942, 64, 335WEISS : SOME INTERMEDIATE (!OMPOIJNDS I N INORGANIC REACTIONS. 73solution involving oxy-acids, are dependent on an acid medium and are oftengreatly accelerated by hydrogen ions.At present only relatively fewpositive ions, e.g., those derived from nitrous and nitric acid, have beeninvestigated sdiciently thoroughly by chemical and physical methods fortheir existence to be regarded a fully established.In many other cases certain conclusions regarding the presence andstability of such ions can be drawn from kinetic measurements. However,in this group, there is relatively little additional evidence available at present.Nevertheless, there is, perhaps, some justification in discussing a few of theseions, even if it only results in providing a summary of some revelant facts.In 1909, from observations basedon cryoscopic measurements in sulphuric acid solutions A.Hantzsch 79suggested that nitrosyl ions were present in solutions of the so-called" nitrosylsulphuric acid " as nitrosyl sulphate, to which he gave the formulaNO+,HSO,-. Later, with K. Berger,so he took up this problem and preparednitrosyl perchlorate in a fairly pure form and attributed to it the ionicstructure NO+,C10,-, since it behaved as an electrolyte in nitromethanesolutions. Subsequently, their opinion was supported by the study of theRaman spectra of nitrosyl perchlorate and of the sulphate (in solutions ofsulphuric acid), and the Raman shift 2330 cm.-l which appears very pro-minently in these spectra was assigned to the NO+ ion.81 Recently, L. J.Klinkenberg has confirmed this by X-ray analysis of the crystal structuresof nitrosyl perchlorate and nitrosyl borofluoride.In these crystals the NO +ion was found to be about the same size as the H,O+ ion and smaller thanthe NH,+ ion.Nitrosyl perchlorate can be preparediby the action of dinitrogen trioxideon a 707' perchloric acid solution, N,O, + 2HC104 = 2NO,C10, + H,O,and drying over phosphoric oxide. According to E. Wilke-Dorfurt andG . Balz,a nitrosyl borofluoride (N0,BF4) can be made similarly by treatinga concentrated solution of borofluoric acid with liquid trioxide.A. Hantzsch also has pointed out that nitrous acid does not existat, all in acid solutions as the equilibria NO,- +LH+ HNO, andHNO, + H+ =+= H,NO,+ + NOL + H,O are displaced in favour of theNO+ ion. It is noteworthy that, according to these equilibra, the con-centration of the nitrosyl ion in solution is given by [NO +] oc [NO,-][H+I2, andthe appearance of this expression in kinetic equations suggests the possibleintervention of NO+.It is also to be expected that nitrosyl ions play animportant part in the mechanism of the decomposition of nitrous acid inaqueous solutions.Nitrous Acid .- the nitrosyl ion (NO+)..79 Z . physikal. Chent., 1909, 65, 57.go Z . anorg. Chem., 1930, 190, 321.a1 W. R. Angus and A. H. Leckie, Proc. Roy. SOC., 1935, A , 149, 327 ; A , 150, 615 ;s2 L. J . Klinkenberg, Rec. Trav. chim., 1937, 56, 749.f'taw. Paraday SOC., 1935, 31, 958.2. anorg. Chenz., 1927, 159, 197; see also G. Balz and E. Mailander, ibid., 1934,Zl7, 161.c 74 TNORC: ANIC CHEMISTRY.Nitric acid : the nitracidium ion (H,NO,+) and the nitronium ion (NO,+).In his work on the optical absorption of mixtures of nitric and sulphuricacids, A.Hantzsch 84 found that the absorption bands in the ultra-violet, dueto the nitrate ion and to the undissociated nitric acid, were absent from thesesolutions. As a result of this and from his work on the electrical conductivityof these mixtures, he concluded that the nitric acid is largely convertedinto nitracidium ions H,NO,+ and possibly H,NO,’ formed accordingto (i) HNO, + H,SO, = H2N03~ + HSO,- and (ii) HNO, + 2H,SO, =H,NO,’ He also claimed to have isolated the correspondingnitracidium perchlorates ( H2N03 1 )( ClO,-) and (H,NO,I )( ClO,-), and hecarried out migration experiments on these systems and on nitracidiumperchlorates dissolved in nitromethane solutions.All these indicated thatthe nitric acid is present as a positive ion and that in pure nitric acid onepresumably has the equilibrium 2HNO,=+ H2N03 + NO,-. Recentinvestigations discussed below have shown that in anhydrous nitric acid andother anhydrous media H,NO,- is in fact dehydrated to NO,I according tothe equilibrium : H,NO, - NO, + H,O. The nitronium ion NO,+ is ofconsiderable interest, as i t has been recognised that it functions as theprimary nitrating agent in the mixed acids, as was suggested by H. Euler 85and P. Walden 86 and later by C. C. Price.8’ More recently, this workhas been taken up by C. K. Ingold 88 and G. M. Bennett 89 and theirrespective collaborators and by F.H. Westheimer and M. S. Kharasch.wThe evidence of the formation and existence of NO,’ has been carefullyreinvestigated and re-examined by these authors and who find that it isformed in the mixture of nitric and sulphuric acids : NO,*OH + 2H,SO, =NO, . + OH, + ZHSO,-. This is analogous to the formation of NO’ whennitrous acid is dissolved in sulphuric acid : NO*OH + ZH,SO, = NO +OH, ’ + ZHSO,-. In an equimolecular mixture of water and sulphuric acid,nitric acid is present mainly in the form of NO,*OH. An excess of waterconverts it into NO,- ions but an excess of sulphuric acid prodiices NO, ions.That the nitric acid is in a different form is obvious also from the very lowvapour pressure of nitric acid over these solutions.Extensive studies of theRaman spectra of mixtures of nitric and sulphuric acids have been made byJ. Ch6din,g1 who showed that these spectra are characterised by two prominent(polarised) lines at 1050 and 1400 cm.-l, which do not belong to the spectrumof either the nitric or the sulphuric acid molecule. The same line appeared-t 2HSO,-.Ber., 1925, 58, 941 ; see also A. Hantzsch and K. Berger, Ber., 1928, 61, 1328;2. phyYika1. Chein., 1930, A , 149, 161.85 2. angew. Chem., 1922, 35, 580. *’ Chem. Reviews, 1941, 29, 51 ; see also 34. UssanoGitch, Acta Physicochim.8 8 E. D. Hughes, C. K. Ingold, and R. I. Reed, Nature, 1946, 158, 448; E. S.13’ G . M. Bennett, J. C. D. Brand, and G. Williams, J., 1946, 869, 875.‘O J .Amer. Chem. SOC., 1946, 68, 1871.91 Ann. Chim., 1937, 8, 243; . J . Physiqzte, 1939, 10, 445; Mkna. Service china. de8 6 Ibid., 1924, 37, 390.U.S.S.R., 1935, 2, 239.Halberstadt, E. D. Hughes, and C. K. Ingold, ibid., p. 514.Z’E’tat, 1944, 31, 113WEISS : SOME INTERMEDIATE COMPOUNDS IN INORGANIC REACTIONS. 75if dinitrogen pentoxide or phosphoric oxide was added to pure nitric acid.The line of 1400 cm.-l is present also in the spectrum of 100% nitric acid butit is stronger in the mixed acids, its intensity increasing with diminishingwater or increasing oleum content. Chkdin assigned these lines to a specialform of dinitrogen pentoxide since in organic solvents it gave a differentRaman spectrum. Bennet, Brand, and Williams 89 interpreted these resultson the basis of the formation of NO,+, to which they assigned the line1400 cm.-l, comparison with the isoelectronic molecule CO, having shownthat a polarised Raman line is to be expected in this region.C. K. Ingold,D. J. Millen, and H. G. Poole 92 proved definitely that the Raman line a t1400 cm.-l is due to NO,', its this line could be obtained in solutions of nitricacid in perchloric and selenic acid, neither of which possesses a Ramanfrequency in this region, without the line a t 1050 cm.-l, which is actually dueto the NO,- and HS0,- ions.Cryoscopic measurements of nitric acid in sulphuric acid have been carriedout, particularly by A. Hantzsch and a number of other workers. Thequestion has been carefully re-examined by C. K.Ingold et CLZ.,~~ who showedthat nitric acid dissociates in sulphuric acid to produce a nearly fourfolddepression of the freezing point (van't Hoff factor = 3.82). This is inagreement with the formation of according to the above equation.Addition of dinitrogen pentoxide to fuming sulphuric acid also leads to theappearance of the Raman frequency at 1400 cm.-l, which presumably is due tothe reaction N,O, + H2S20, = NO, + HS,O,- + HO*NO,, which is followedby-additional formation of NO," from the nitric acid. Hantzsch had previouslycarried out migration experiments on nitracidium perchlorates in nitro-methane and on solutions of nitric in sulphuric acid, obtaining some evidencethat the nitric acid was present in a cationic complex. Bennett, Brand, andWilliams 89 confirmed this; they determined the distribution of nitric acidafter electrolysis and found a general accumulation of the nitric acid at thecathode and a deficit at the anode.They also showed that this was not dueto cataphoresis effects. As mentioned above, Hantzsch had claimed tohave prepared two nitracidium perchlorates. R. Goddard, E. D. Hughes,and C. K. Ingold 9* were able to isolate salts of the nitronium ion. Theyrepeated Hantzsch's work, employing an improved technique excludingatmospheric moisture and working a t low enough temperatures to preventthe formation of and contamination by nitrosoniurn perchlorate. They wereable to isolate pure NO;' C10,- by fractional recrystallisation from nitro-methane or by treatment of the original product with dinitrogen pentoxide.Nitronium perchlorate has been prepared also by W. E.Gordon and J. W. T.Spinks,95 who obtained a deposit of the composition NClO, by mixing gasstreams of ozone, nitrogen dioxide, and chlorine dioxide. According toIngold et U Z . , ~ ~ the compound NO,C10, has a low vapour pressure, scarcely9 2 Nature, 1946, 158, 480.O 3 R. J. Gillespie, J. Graham, E. D. Hughes, C . K Ingold, and E. R. A4. Peeling,94 Ibid.ibid.95 Cunadian J . Res., 19.10, B, 18, 93976 INOROANIO CHEMISTRY.fumes in air, and dissolves in water with slight liberation of heat. Apartfrom analysis, the constitution of the solid salt was confirmed by its Ramanspectrum, which consists of the known spectra, of NO2+ and ClO,-. Ingoldet aZ.g3 also established the formation of NO2+ in sulphuric acid solutions ofthe nitrogen oxides N20, and N204.These oxides produce an approximatelysix-fold depression (i = 5-85) of the freezing point, corresponding to theequations (i) N,06 + 3HiS0, = 2N0,. + H30+ + 3HS04-, (ii) N,O, +3H,SO, = NO,' + NO- + H30+ + 3HS04-. The authors were able toconfirm this by the Raman spectra of these solutions. J. Ch6ding1had already obtained the lines at 1400 and 1050 cm.-l from solid nitrogenpentoxide. On the basis of this Ingold et aLg2 suggested an ionic structureN0,+N03- for this compound. There can be hardly any doubt that,apart from nitration reactions the ions NO 1- and NO,+ are also of importancein the mechanism of other reactions involving nitrous and nitric acid.Forinstance, the behaviour in acid solutions can be represented by the simplemechanism HO*NO + H+ + H,O + NO and NO $- NO3- + NO+N03-of other nitrates of weak bases : NO NO3- + H20 = HNO, + H + NO,-.Hydrogen Peroxide.-A. Simon and F. F6her 96 suggested some time agothat some hitherto undescribed forms might be present in solutions ofhydrogen peroxide. They were unable, however, to get any clear evidencefrom a study of the Raman spectra which they investigated up to con-centrations of 99.5% hydrogen peroxide. The Raman spectrum of hydrogenperoxide still lacks a satisfactory interpretation. From a study of the Ramanspectrum of deuterium peroxide,97 i t has been concluded that the lines3395 and 1421 cm.-l in the H,O, spectrum are connected with O-H vibra-tions, and these lines, which become weaker on dilution, may have somebearing on this problem.Kinetic evidence rests on the accelerating effect of hydrogen ions on someof the reactions of hydrogen peroxide.This can be interpreted on theassumption that in the presence of hydrogen ions, hydrogen peroxide isconverted to some extent into peroxide acidium ion, H30,+ and posHibly OH Iaccording to the equilibria : 98A -- N204, and the hydrolysis of dinitrogen tetroxide falls into line with that'Equilibrium const.H,O,+H+ z$ H30,+ (K,) . . . . (4H302+ z$ H20+ OH+ (Kb) . . . . (PIH,02 e OH++OH- ( K J . . . . (Y)These equations are closely analogous to those for the H20 molecule (H,O,breplacing H30b and OH+ instead of H+) and they suggest that in con-centrated solutions of hydrogen peroxide the equilibrium 2H,02 + H302+ +H0,- may exist.The rate of the reaction between hydrogen peroxide and iodide ions inacid solution, leading to formation of iodine, can be represented by the9 6 2.Elektrochern., 1935, 41, 290.98 J. Weiss, unpublished results.9 7 F. FehBr, ibid., 1937, 43, 663WEISS : SOME INTERMEDIATE COMPOUPJDS IN INORGANIC REACTIONS. 7’7kinetic equation : 99 rate CC [H202][I-](1 + k[H ‘I}. This suggests two parallelinitial processes, wiz., (a) between H202 and I- and ( b ) between H302+ and I-.From this i t is possible to get a rough idea of a set of pos-sible values forK,, Kg, and K,. One obtains, for instance, with certain plausible assump-tions K , - Kg - 10-2, K , - 10-l8 (at 25’).A study of the Ramangpectra and of absorption spectra of hydrogen peroxide in the presence ofstrong acids might give some further information on these points.Chromic Acid-The rate of oxidat,ions by chromic acid in solution, whichhave been investigated by a number of authors, depend on the hydrogen-ionOH + concentration. More recently a very carefulinvestigation has been carried out by F. H.Westheimer and A. Novick,l who studied theoxidation of isopropyl alcohol in acid solution. [ lfe----j;Me *n ] Taking into account the equilibrium Cr,O;- +H,O + 2HCrO,-, they found the followingequation for the rate of the reaction : rate oc [HCr0,-][H+12[C,H7*OH], andmggested an activated complex of the forin shown in the inset.This can be represented also by the forination of a positive ion according10 H2Cr0, + H ‘ =+ H,CrO,l, or possibly of its dehydration productHCrO,’ , followed by the process H3CrO,I + C,H,*OH ---+ H,CrO, +CH,*(JOH)*CH, + H &, with the formation of a quinquevalent chromiumcompound (H,Cr04 or HCrO,).There can be hardly any doubt that, ingeneral, the conversion of the sexavalent into the tervalent chromium saltproceeds in stages. It has been found that manganese dioxide is formedif the reaction is carried out in the presence of manganous salt, and aschromic acid does not bring about this oxidation, the authors concludedthat an intermediate labile quinque- or quadri-valent chromium compound isformed which does so. Similar evidence for the intermediate formation ofthese compounds has been presented by other authors.2Permnganate.-It is possible that the ion H2Mn0,” is present in acidsolutions of permanganate which, as is well known, behave differently fromneutral or alkaline solutions in oxidation processes.There is perhaps somesignificance in the fact that permanganate in concentrated sulphuric acid orin oleum gives dark green or blue solutions, and it has been suggested thatin these solutions (MnO,),SO, might be present which could also imply thepresence of the cation MnO, +.Perchlmic Acid .-Certain physical properties indicate that perchlor i cacid exists in the aci-form, HClO,, and the pseudo-form, HO-ClO,, a i dalso that in highly concentrated solutions an acidium salt is formed :ZHClO, *( H,ClO, ) + (C104-).According to R. Fonteyne? the Raman/H--°Cr-oH(a) J . A. Christiansen, 2. physikal. Chem., 1925, 117, 433, 448; ( b ) J. Brode,F. H. Westheimer and A. Novick, J . Chem. Physics, 1943,ll. 506.C. Wagner, 2. anorg. Chem., 1928, 168, 279; V. F. Stefanoskii and A. M. Zanko,T. E. Thorpe and E. J. Hambly, J., 1888,53, 175, 182. ‘ Nature, 1936, l a , 886.ibid., 1901, 37, 257; 1904, 49, 208.Acta Physicochirn. U.S.S.R., 1938, 9, 635; R. Lang, Mikrochim. Acta, 1938, 3, 11378 INORGANIC CHEMISTRY.spectrum of absolute perchloric acid is different from that of the aqueoussolution; he also attributed the line at 422 cm.-l to the presence of anacidium salt. A. Simon has pointed out that this cannot be justified on theevidence of the Raman spectrum alone, although it is clear that there is aprofound change in the Raman spectrum of perchloric acid on dilution.According to the more recent work of R.Fonteyne and 0. Redlich,E. K. Holt, and J. Bigeleisen,' Raman spectra certainly confirm theexistence of HOC10, (symmetry C3J when the concentration exceeds 73 ?(, .Raman lines found for the C10, group are also present in the spectrum ofdichlorine heptoxide which points to the ionic structure ClO, ' ClO,-.Recent investigations 8 of concentrated solutions of perchloric acid haverevealed ultra-violet absorption in the region of 2 2 0 0 ~ . which cannot bedue to the C10,- ion as this does not absorb appreciably above ca. 1900 A.gThis increased absorption must be due either to the undissociated acid orpossibly to the ClO,+ ion.Periodic Acid.-It has been found lo that in the reaction between periodicacid and iodide ions in acid solutionthe rate is given by : rate OC [I04-1[H 'I2[I-1,which suggests the formation of an acidium ion according to : (i) 10,- +H r =+ HIO,, (ii) HIO, + H t + H2104', followed by : (iii) H2104+ +I- .+ H,IO, + I, (iv) H2IO4+ 10, + H,O, (v) 10, + I- --+ 10,- + I,leading first of all (in two steps) to the formation of iodate.Ramanspectra of solutions of periodic acid are not available at present. Recentexperiments l1 show that aqueous solutions of periodates and periodicacid show strong absorption in the ultra-violet from 2300 A. onwards.Solutions of periodic acid in concentrated sulphuric acid do not absorbnearly as strongly.This could he due either to the undiasociated acidor to the formation of H,IO,' or 10,' in these solutions, which is suggestedby the somewhat analogous behaviour of nitric acid in concentrated sulphuricacid. It is possible also that the H4105+ ion is present in the mesodiperiodatesIodic Acid.-The Raman spectrum of iodic acid l2 contains a greatnumber of lines, but the experimental evidence is inadequate for itsinterpretation, although several authors believe that iodic acid is polymerisedin solution. H,IO,i- + 10,-exists. The formation of an ion H,IO,+ or 10, is suggested by kineticevidence on the oxidation by iodate in acid solution which is found l3 to beproportional to [H+]., A similar state of affairs seems to exist with regard(H,IO,T ,IO,- ).It is possible that the equilibrium 2HI032. anorg.Chenz., 1938, 239, 329.Nattiurwetensch. Tijds., 1939, 21, 6 ; 1938, 20, 275.J . Anaer. Chem. Xoc., 1944, 66, 13.H. Fromherz and W. Rlenschik, 2. physikal. Chem., 1929, B, 3, 18; H. Ley and* J. Weiss (in preparation).B. Arends, ibid., 1929, B, 6, 240.lo E. Abel and R. Siebenschein, ibid., 1928, 130, 631.l 1 ,J. Weiss (in preparation).l2 R. Fonteyne, A'atzitcrwete,i.srh. IT;'&., 1'339, 21, 141; C. S. Rao, Current Sci.,l3 S. Dushman, J. PhysicaZ Chenz., 1904, 8, 453.1942, 11, 429WEISS : SOME INTERMEDIATE COMPOUNDS IN INORGANIC REACTIONS. 71)t o bromic acid, where i t is found that the rate of reaction between bromateand iodide ions in acid solutions l4 is proportional to [Br0,-][H+]2[I-]2,suggesting the primary process H2Br0,1 + I- ---+ H,BrO, + I which isbased on the formation of H,BrO,T or BrO,+ ions. The interaction of theundissociated molecules (ion-pairs) cannot, of course, be excluded.Hypobromic Acid and the Br+ Cation.-The HBrO molecule occurs in theniechanism of a number of reactions in solutions involving Br, or Br .Recently, C.N. Hinshelwood 15 has made the important and far-reachingsuggestion that many of these reactions could be explained more satisfactorilyby the action of the Br+ cation formed thus :Br, Br- + Br- . . . . . . . . (2, 1)It is clear that, as for instance in the case of nitrous acid, the exclusivepresence of HBrO in acid solutions is very unlikely, for the equilibriumHBrO+H & Br'-+H,O .. . . (2, 1 4is probably shifted considerably towards tho right.alkaline solutions, where BrO- is formed by the reactionThis is different illHBrO -+- OH- =+= Br0- -+ H,O . . . (2, l b )Aocording to Hinshelwood, the initial reaction between bromine and oxalicacid can be represented by the simple electron-transfer process, HC,04- +Rr -+ HC,O, + Br, which accounts very wcll for the experimentalfacts. l6Similarly, in the reaction between bromine and hydrogen peroxide,H,O, + Br, = 2HBr + O,, the initial primary process can be representedbyleading to the formation of HO, which, according to (1, 4), is capable ofgiving molecular oxygen and hydroxyl radical.H0,-+ Br'+HO,+ Br . . . . (2,2)The latter can then react :Br-+OH+Br+OH- . . . . . (2,3)followed by 2Br = Br, . . . . . . . ( 2 , 4 )One can show easily that the mechanism involving the reactions (2, l ) ,( 2 , 2), (2, 3), (2, 4), and (1, 4) leads to the correct kinetic equation. On theassumption that the equilibrium (2, 1) is practically always established oneobtains the equation for the rate of the reaction which is in agreement withthe experimental facts.l7Hypoiodous Acid and the I Cation.-This case is similar to that of bromine,and the equilibria corresponding to (2, l ) , (2, la), and (2, Ib) are probablystill further shifted towards I . There is also some other chemical evidencefor the I - ion. L. Birkenbach and J. Goubeau l8 have suggested the inter-l4 A. A. Noyea and W. 0. Scott, 2. physikal. Chew., 1895, 18, 118.l5 J., 1947, 694.l6 R. 0. Griffith, A. bIcKeown, and ,4. G . Winn, Trans. Faraday SOC., 1932, 28, 107.W. C. Bray, Chem. Reviews, 1932, 10, 161. Ber., 1932, 65, 39580 INORGANIC CHEMISTRY.mediate formation of I +,ClO,- if iodine is treated with silver perchlorate.This compound is a very effective agent for iodination in the benzene nucleus.I. Masson and C. Argument l9 have suggested that Chrbtien's yellowsulphate should be represented as (IO),SO, and that IO+ cations are present.According to I. Masson,20 these can react in solution in the presence of iodineas follows : (i) 10' + H,O =+= 13+ + 20H- (ii) 13+ + I, 3I+. Intro-duction of I+ into the mechanism of some of the reactions of iodine leads tointeresting results.The older work of J. R. Roebuck 21 on the oxidation of arsenious acid byiodine is not capable of a straightforward interpretation on these lines as theexperiments were not carried out at well-defined hydrogen-ion concentrationsand it is not clear whether H,AsO, or H,AsO,- enters into the mechanism.22The reaction between hydrogen peroxide and iodide ions in the absenceand in the presence of iodine has been studied by a number of w ~ r k e r s . ~ ~ @ The existing theories, which are all based on the intermediate formation ofHIO, lead to complex rate equations which are difficult to reconcile withcertain experimental facts.= Recently, it has been found25 that theessential features of the mechanism of this reaction can be represented by thefollowing six simple processes :Rate constantsH,O,+I-+I+OH- +OH . . . * (k1)21 ---+ I,123,1+ +I- . . . . (kII, 6 1 )H 0 2 - + I - - 3 H 0 , + I . . . . . . (kIII)I-+OH + I + O H -+ +H,O, + HO, ---+ 0, + H,O + OHI n strongly acid solution the hydrogen-ion catalysed, primary process,which has been discussed in connection with the formation of H,O,+, mustbe added. However, this is not an essential point in the mechanism as awhole. The above equations lead to the following simple expressions forthe formation of iodine and oxygen in the stationary state := k,[H,O,][I-] - 1 d[O,I dtThe two well-known limiting cases are easily obtained as follows : (a) Inacid solutions only iodine is formed (without evolution of oxygen), ie.,J., 1938, 1702. 2o Ibid., p. 1708.21 J . Physical Chem., 1908, 6, 365; 1905, 9, 727.22 Cf. P. Goldfinger and H. D. Graf von Schweinitz, 2. phyaikal. Chem., 1932,23 Cf. E. Abol, ibid., 1928, 138, 16.26 H. A. Liebhafsky, ibid., 1931, A , 155, 289.B, 19, 219.26 J. Weiss, unpublished reaultsWEISS : SOME INTERMEDIATE COMPOUNDS I N INORGANIC REACTIONS. 81d[O,] /dt = 0, whence d[I,]/dt = EI[H202][I-] (neglecting the acid-catalysedparallel process H302+ + I- + I + H,O + OH). ( b ) In neutral solutionsthe case of " pure catalysis " can be realised, i.e., d[12]/dt = 0, and one obtainsfrom the above equations for the rate of oxygen evolution : d[O,]/dt =J. W.R. E. DODD.P. I,. ROBINSON.J. WEISS

ISSN:0365-6217    

DOI:10.1039/AR9474400050

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

ORGANIC CHEMISTRY.1 . INTRODUCTION.THE subjects chosen for review include an account of recent work on organiccompounds containing fluorine, a comparatively new field of study on whichgreat progress has been made within recent years, and from which importantresults are being obtained of both theoretical and practical interest. Somerecent developments in aromatic chemistry are reviewed, such as Reppe'swork on cyclooctatetraene, the controversy over the constitution of thediazocyanides, and the mechanism of the Bucherer reaction. Recent workon acyclic terpenes containing isoprene units in irregular union and onsesquiterpenes is reviewed. Further developments in the steroid field arereported, which include a reference to Miescher's total synthesis of oestroneand to recent progress towards the total synthesis of sterols themselves. Thechemistry of marrianolic and doisynolic acids and related compounds is alsodiscussed.Two methods are availablc for the formation of fully fluorinated hydro-carbons.Fluorination can be carried out either witrh fluorine in the presenceof a catalyst such as silver or gold under conditions which dissipate thetremendous heat of formation, or with an inorganic fluoride such as cobaltfluoride. Both methods replace all hydrogen atoms by fluorine andsaturate any double bonds. The products formed are called ~fluorocarbons,and their carbon " skeletons " are believed to correspond to those of theoriginal hydrocarbon. By the application of these methods benzene isconverted into perfluorocycbhexane CGF12, n-heptane into perfluoro-n-heptane %C,F16, and toluene into perfluoromethylcychhexane CF3*C6Fl1.In similar manner naphthalene, tetrahydronaphthalene, and decahydro-naphthalene are converted into perfluoronaphthalene C,,Fl,.Fluoro-carbons are unique among organic substances in their stability towardschemical reagents, and arc decomposed only when heated with fluorineitself or with sodium at 300400". Prolonged boiling with concentratedmineral acids or alkalis is without effect upon them, and they seem to beinert towards all other chemical reagents. Because of their stability,fluorocarbons are best characterised by their physical constants. Theyhave low boiling points, low surfacc tensions, low refractive indices, highdensities, and high viscosities.For cornpounds of relatively high molecularweight fluorocarbons have remarkably low boiling points ; with the exceptionof CF,, C,F6, C3F,, and C,F,, the fluorocarbons have boiling points lower thanthe parent hydrocarbons, a phenomenon which is believed to be due to thelack of hydrogen bonding.Partly fluorinated organic compounds may be obtained by a number ofmethods. Controlled fluorination by fluorine itself is not yet a procedureof wide use, but replacement of one or more halogens (Cl, Br) byfluorine can be effected by the use of an inorganic fluoride or a8BAKER AND HEY : INTRODUCTION. 83mixture of fluorides (KF, HF, SbF,, SbF,Cl,, SbF,, HgO + HF), e.g.,EX, --+ XF,. Replacement of halogen and addition of hydrogen fluorideto a double bond can also be carried out, e.g., -CX=CH- --+ -CF,-CH,-.Another method involves the addition of hydrogen fluoride to acetyleniccompounds, e.g., R-CiCH --+ R*CF,-CH, (R = alkyl or halogenatedalkyl).Addition of fluorine to a double bond can also be accomplished bythe agency of lead tetrafluoride (prepared in situ from PbO, and HF), e.g.,2HF> C = K 3 >y-y<F F aThe effect of the >CF, )CF, and -CF, groups on such processes aschlorination and polymerisation is discussed, and reference is made to theprofound effect which one or more of these fluorinated groups has uponthe properties of unsaturated systems and upon the function of such groupsas H, OH, X (halogen), NH,, CO,H, and C,H,. The suggestion is putforward that research in this new branch of organic chemistry will furnishresults which should either confirm some present ideas of the electronicinterpretation of organic reactions or necessitate the development of new ones.Reference is also made to the industrial importance of organic fluorides andtheir derivatives. The solid polymers (CF,*CF,), and (CF,*CFCl),, stableto boiling concentrated mineral acids, are excellent materials from which tomake apparatus required to resist corrosive chemicals.These solid polymershave good insulation properties, and the intermediate polymeric fluoro-carbon oils are useful as heat-transfer agents, transformer oils, and lubricatingoils.I n spite of the vast amount of work which has been carried out onaromatic compounds, much of our knowledge is still unsatisfactoryand incomplete, but, by the application of new methods, improvedtechnique, and modern theory, considerable advances have been madewithin recent years, and many important problems cleared up.It issurprising that, although cyclooctatetraene is a compound of unusualtheoretical interest and considerable doubt has been expressed as to whetherin fact it had been synthesised, some thirty years passed without any attemptbeing made to repeat Willstatter’s work. This state of affairs has now beenremedied, and as the result of the work of W. Reppe cyclooctatetraene can beobtained in quantity and has been thoroughly investigated by chemical andphysical methods. Willstatter’s work has been confirmed and extended,and cyclooctatetraene has been shown beyond all doubt to be a highlyunsaturated cyclic polyene.Its chemical properties are even more variedand interesting than had been suspected, and its ease of aromatisationopens up considerable possibilities for industrial as well as laboratorysynthesis. There is still controversy as to its fine structure, the balanceof the evidence being in favour of a non-planar slightly resonating moleculewith alternate single and double bonds.Our knowledge of the fine structure of aromatic compounds has beenincreased by the quantitative ozonisation of o-xylene, 2 : 3-dimethyl-naphthalene, and similar compounds, by the X-ray determination of the bon84 ORGANIC CHEMISTRY.lengths in pyrene, 1 : 2 : 5 : 6-dibenzanthracene, and other hydrocarbons,and by the application of theoretical considerations and physical measure-ments to indrtne and its derivatives : the results are interpreted in terms ofthe theory of resonance.Other notable work on aromatic hydrocarbonsincludes ring-closure by cyclo-dehydrogenation and cyclo-dehydration, anddetailed investigations on the reduction of the polycyclic compoundsanthracene, phenanthrene, and pyrene. The structure of the diazocyanideshas been studied by means of their infra-red spectra, and strong evidenceis adduced to show that both the cis- and the trans-forms are true nitriles andnot isonitriles. Structural isomerism is thus excluded, and the Hantzschtheory would appear to be confirmed.The mechanism of reactions continues to attract attention. TheBucherer reaction has been investigated kinetically, and the results obtainedwere found to be in harmony with the commonly accepted mechanism ofFuchs and Stix.Structures have been assigned to the intermediates formedby the action of a bisulphite on sodium naphthionate. The homogeneousCannizzaro reaction is found t.0 be not influenced by t'he addition of peroxidesor peroxide inhibitors, and objections to the postulated intermediat'eformation of benzyl benzoates have been removed. Aldehydes which do notundergo the change under the usual conditions do so in presence of an activesilver catalyst. The synthetic possibilities of the Stobbe reaction have beendemonstrated, and attention has been drawn to the frequent occurrence ofdimeric products in the Clemmensen reduction.Nearly ten years have passed since the mono- and sesqui-terpenes werelast reviewed.Although this period includes the war and immediate post-war years, there has been so much activity in this field that a comprehensivereview is not possible. The monoterpene section has therefore beenrestricted to acyclic terpenes containing isoprene chains in irregular union.A new alcohol, lavandulol, has been isolated from oil of lavender ; it closelyresembles an isomer of geraniol previously synthesised by L. Ruzicka andhis collaborators. The structure of lavandulol has been put on a firm basisby an unequivocal synthesis of the ( f)-alcohol. The irregular structure ofartemisia ketone has recently been confirmed by synthesis.The out-standing problem of the structure and synthesis of irone, the perfume fromorris root, a t long last seems to have been solved. L. Ruzicka, and hiscollaborators, having disposed of the cycloheptene skeleton, established the6-methylionone structure by extensive degradative experiments, followed bya synthesis of (f)-a-irone. hone is regarded as being a mixture of a-, P-,and y-isomers, the y-isomer, coilfaining an exocyclic methylene group,predominating in natural irone.Much interesting work has been accomplished in the sesquiterpene group.The structures of several cadinene hydrocarbons have been revised, followingthe application of a new method for locating the double bonds. Thisconsists in treating the sesquiterpene oxide with inethylmagnesium iodidefollowed successively by dehydration and dehydrogenation.The positions ofthe additional methyl groups in the resulting homocadalene are found bBARER AND HEY : INTRODUCTION. 85degradation and synthesis, thereby locating the positions of the double bonds.The eudslenic sesquiterpene ketone, eremophilone, has been shown by J. 1;.Simonsen and his collaborators to possess the 1 : 9-dimethyl-7-isopropyldecalinskeleton. Despite much study, the structure of caryophyllene has not yet beencomplebly elucidated, although the bicycZ45 : 2 : Olnonane skeleton seemsestablished. The adduct with maleic anhydride now appears to be asubstitution product at an ally1 position. Similarly, a bridged bicyclo-[5 : 3 : Oldecane structure appears likely for cedrene.A comprehensivereview of recent work on the azulenes is given. Following the establishmentof the structures of guaiazulene and vetivazulene, P. A. Plattner and hiscollaborators have elucidated the structures of guaiol and vetivone,representatives of the bicyclo[5 : 3 : Oldecane sesquiterpenes.In the steroid field the total synthesis of the natural estrogenic hormone,(+)-estrone, has been reported by G . Anner and K. Miescher, and anadvance which holds promise of further achievements is the total synthesisby J. W. Cornforth and Sir Robert Robinson of the tricyclic diketone (I),obtainable as a by-product from the oxidative degradation of methyl diacetyl-deoxycholate and of cholesteryl acetate ilibromide.The addition of ring Dpresents no difficulties in principle, and the way is now open to the totalsynthesis of saturated and unsaturated derivatives of androstane andztiocholane, such as androsterone, testosterone, progesterone, corticosterone,lithocholic acid, and cholesterol. A direct proof ofthe (@)-orientation of the hydroxyl group in cholesterolhas been given by C. W. Shoppee; this applies to all3-hydroxy-steroids which, directly or indirectly, havebeen correlated with cholesterol in respect of configur-ation a t C3, and is subject to qualification only in so faras future determination of the absolute configuration at some centre ofasymmetry may show the actual stereochemical arrangement of the steroidniicleus to be the mirror-image of that at present accepted by convention.A method of possibly general application for the introduction of radioactivecarbon into the steroid skeleton at position 3 has been worked out by R.B.Turner in the case of cholest-4-en-3-one.Recent syntheses of (+)-oestrone, " o! "-estradiol, equilenin, and iso-equilenin are summarised, and the available evidence indicating that theC/D-ring union in the natural estrogenic hormones is of the same type(trams) is discussed. The physiologically active cardiac glycosides and thephysiologically inactive albglycosides both possess cis-C/D-ring unions, andhave been shown by T. Reichstein to differ only in configuration at Cl,. Thebile acids constitute one of the most important sources of starting materialfor steroid partial syntheses; a summary has therefore been given of theN-bromosuccinimide method introduced by K.Miescher for the degradationof the side-chain with removal of three carbon atoms in one stage.Results of the highest chemical and biological iniportance have accruedfrom the work of K. Miescher and his co-workers on the marrianolic anddoisynolic acids. Biologically, the most striking results are the productionc\( I . ) CI i386 ORGANIC CHEMISTRY,from (+)-equilenin and by total synthesis of a compound, (-)-" ct "-bisde-hydrodoisynolic acid, and the total synthesis of a racemic doisynolic acid,the estrogenic activities of which are about ten times greater in the rat thanthat of diethylstilboestrol. Dimethylethylallenolic acid, which shows someformal structural resemblance to the doisynolic acids, is reported to bealmost as active as the foregoing intensely estrogenic acids.In an attemptto discover some relation between estrogenic potency and constitution, avery large number of analogues of the doisynolic acids has been described;the results obtained have been summarised and the methods used for theirsynthesis reviewed.W. B.D. H. H.2. ORGANIC COMPOUNDS OF FLUORINE.Introduction.The chemistry of organic and inorganic fluorides has undergone anunexpected expansion during the last seven or eight years, mainly becauseof the exigencies of war. This expansion, which is still continuing, requireda plentiful supply of good-quality fluorine. Once a laboratory curiosityand regarded as a dangerous substance, it is now readily available for eitherlaboratory or manufacturing purposes.Though still a dangerous chemical,its properties are so well known that it can be handled with relative ease,and it is used a t the present time for the production of a large variety oforganic substances which serve as lubricants, insulators, corrosive-resistantapparatus, and media for the transmission of power.The unique character of fluorine is due to the fact that it is the mostelectro-negative element. It is also remarkable because the fluorine atomnot only acquires and holds an electron with tenacity but shows a markedtendency to attract still more. Both these characteristics of fluorine playan important r6le in the preparation and the properties of organic fluoro-compounds.The electrophilic effect of fluorine atoms on the propertiesof organic compounds is so pronounced t h a t their study is likely to providefurther information concerning the theory of the electronic interpretationof organic reactions. Fluorine compounds show extremes of chemicalbehaviour: some are very reactive and unstable, and others display aninertness comparable only with that of the so-called rare gases. Someorganic fluoro- and chlorofluoro-compounds can be inhaled without any illeffect, while others, of which some are completely fluorinated, are extremelytoxic, and there is reason to believe that some of these perfluoro-compoundsmay display anesthetic properties.Events during the recent war were largely responsible for the develop-ment of this vast and comparatively new field of chemistry. From whatmay be said now of this progress, it may seem to the reader that thework done by the pioneer workers in fluorine chemistry is insignificant.Nothing could be further from the truth, for the recent rapid progresSMTTH : ORGANIC COMPOUNDS OF F1,IJC)RTNE 87could not have been made had it not been for the early work of Moissan.Ruff, Swarta, and others in a relatively difficult field.Fluorocarboit.9.The availability of large supplies of good-quality fluorine and theknowledge that it can be handled in aluminium, magnesium, iron, silver,copper, and nickel apparatus a t temperatures up to about 50O0, and insilica or “ Pyrex ” glass a t room temperature has enabled much progressto be made in studies of direct fluorination.It is in this field of directfluorination that perhaps the greatest advance has been made recently.The indirect method of fluorination is dependent upon the fact that aninorganic fluoride such as antimony trifluoride will replace the halogen inorganic halides by fluorine, a reaction often named after F. Swarts, ttdistinguished pioneer in this field. Except in the case of a few inorganicfluorides like CoF,, AgF,, MnF,, or CeF,, which require elementary fluorinefor their preparation,21 the metal fluorides by themselves do not give riseto completely fluorinated substances. From an examination of the experi-mental facts there is reason to believe, however, that a combination of theindirect with the direct method of fluorination has great possibilities forthe production of fully fluorinated substances of all types on a large scale.Fluorine, having a standard electrode potential of -2.85 volts (chlorinehas a standard electrode potential of - 1 ~ 3 6 volts) can be expected to bemuch more reactive than other electronegative substances, and this differenceis likely to lead not only to unique reactions but to unique products.Becauseof the great difference in reactivity between fluorine and chlorine theirbehaviour in organic reactions is so different that a knowledge of the reactionsof chlorine is of little use in predicting those of fluorine. Fluorine combineswith all the elements except the inert gases.The molecule of fluorine isextremely stable, but under some conditions it is highly reactive, so much sothat once it enters into a reaction, the combination may proceed either at anuncontrollable rate or even with extreme violence.5* 6* Many of itsreactions are accompanied by the liberation of a great deal ‘of energy, andthey involve high activation energy. Such is the case when fluorine combineswith organic substances. Normally there is complete decomposition, theonly identifiable product in any quantity being CF4.** The reason forH. J. Emelbus, J . , 1942,441 ; S. G. Osborne and M. M. Brandegee, Ind. Eng. Chem.,1947, 39, 273; J. F. Froning et at., ibid., 1947, 39, 275; A. V. Grosse and H. F. Priest,ibid., p. 279 ; R. Landau and R.Rosen, ibid., p. 281 ; A. F. Benning et al., ibid., p. 286.R. Keim and 0. Ruff, 2. anorg. Chem,., 1931, 201, 245; cf. B. Brauner, Ber., 1881,14, 1944; J . , 1882, 41, 68; J . , 1894, 65, 392; Z. arwrg. Chein., 1894, 7, 1.3 R. D. Fowler et al., Id. Eng. Ckem., 1947, 39, 343.4 W. M. Latimer and J. H. Hildebrand, “ Reference Book of Inorganic Chemistry,”’6 H. Moissan, Ann. Chim. Phys., 1891, 24, 224.6 H. Moissan and G. Chavanne, Compt. rend., 1905, 140, 407.7 M. M. Meslans, Ann. Chim. P h p . , 1894, 1, 346.8 B. Humiston, J . Physical Chem., 1919, 23, 572.9 A. Damiens and P. Lebeau, Compt. rend., 1926, 182, 1340 ;p. 474, Macmillan, 1940.1930, 191, 939When the 3-hydroxy-7 : 17-diketone (LXIII) is acetylated, there isobtained the enol-diacetate (LXVII), in which the position of the new doublebond between c6 and C, is established by the absorption spectrum, and whichby hydrogenation with palladium black in acetic acid and subsequentalkaline hydrolysis gives the 17-keto-3 : 'I-diol (LXVI; R = H).52 This isconverted by treatment as the 3-monobenzoate with phosphorus penta-chloride (1 mol.) in the presence of calcium carbonate into a 7-chloride,dehydrochlorinated by use of sodium iodide in pyridine to give, after removalof the benzoyl group by alkaline hydrolysis, A6-cestrone (LXV).64 Theposition of the new double bond in (LXV) is established by the absorptionspectrum, and hydrogenation with palladium black in ethanol a t 20" gives(+)-oestrone as the sole product.% This sequence of reactions avoids thehigh temperature Wolff-Kishner reduction, and again links (+ )-cestrone(XLIVa) with (+)-equilenin (LXI) in respect of configuration a t both C,,and C14.Transformations analogous to the foregoing have recently been carriedout 55 on " E "-dihydroequilin (LX with -OH for :O at C,,), which as the3 : 17-" a "-diacetate is hydroxylated by treatment with osmium tetroxideto a 3 : 7 : 8 : 17-" a "-tetrol (LXIV with -OH for 10 a t C17) also obtainedby reduction of (LXIV) with sodium-ethanol.The tetrol either bydistillation a t 200" in a high vacuum or by treatment with hot 8% sulphuric54 W. H. Pearlman and 0. Wintersteiner, J . Biol. Chem., 1940, 132, 605.5 5 E. Schwenk, E. Bloch, and B. Whitman, U.S.P. 2,418,603, abstracted in Chem.Abs., 1947, 41, 4518182 ORGANIC CHEMISTRY.acid undergoes pinacolic dehydration to give a good yield of a 7-keto-3 : 17." a "-diol (cf.LXIII), which by Wolff-Kishner reduction or by removal ofthe 7-carbonyl group by the sequence involving a 7-chloride, gives" a "-cestradiol (XLIVa, with -OH for :O a t C,,), a reduction product of( + ) - ~ s t r o n e . ~ ~From compounds recently prepared by Ruzicka et aZ.,57 Reichsteinet aE.,S* and K. M e ~ e r , ~ ~ the molecular rotation difference for inversion ofconfiguration at C14, A14i,qr, - 14-nomaz, is about + 200".60 If we accept theabove evidence that (+ )-cestrone and (+ )-equilenin possess correspondingconfiguration at C,, and C1, we can writ,e the following set of formulse for(+)-equilenin and (+)-14&oequilenin, and for (-)-equilenin and (-)-14-i~0-equilenin :( + )-Equilenin (+)-14-isoEquilenin ( -)-Equilonin ( -)-14-iso-Equilenin(LXIU.) (LXVIIIa.) (LXIb.) (LXVIIIb.)[MID f 224" + 391" - 224" - 391" + 224" t 224"A14iso - I4nOrmal + 167" A13880 - 13mrmal - 615"_.-It will be seen that the molecular rotation difference for inversion at C,, is& 167", which is not far from 200", whilst for inversion at CI3,AI3-bo - 13normal = 615", which is in good agreement with the figure of 570"given above.A new andingenious synthesis of (&)-equilenin and (&-)-14-isoequilenin hasbeen described by W.S. Johnson, J. W. Petersen, and C. D. Gutsche,G1 theprincipal stages of which are given below. The hydroxymethylene-ketone(LXIX) with hydroxylamine gives 96% of the crystalline isooxazole (LXX),which by treatment with sodium methoxide and methyl iodide undergoesfission, ketonisation, and methylation to give 92% of the crystallinecyano-ketone (XXI).Condensation with methyl succinate furnishes by aThorpe reaction the unsaturated 17-imino-ester-acid (LXXII), which losescarbon dioxide and ammonia to yield 83% of the 17-keto-ester (LXXIII);this by hydrolysis with barium hydroxide yields 98% of the keto-acid(LXXIV) , decarboxylated with pyridine hydrochloride-hydrochloric acid5 6 E. Schwenk and F. HiIdebrandt, Naturwiss., 1933, 21, 177; B. Whitman,0. Wintersteiner, and E. Schwenk, J . Bid. Chem., 1937,118, 789.5 7 P. A. Plattner, L. Ruzicka, H. Heusser, J.Pataki, and K. Meier, Helv. Chim. Acta,1946, 29, 942, 949; 1947, 30, 1342.5 8 J. von Euw and T. Reichstein, ibid., 1944, 27, 1851 ; P. Speiser and T. Reichstein,ibid., 1947, 30, 2143.58 Ibid., 1946, 29, 718; 1947, 30, 1977, 2025.6o W. Klyne, Nature, 1948, 181, 434.61 J . Amer. Chem. s'oc., 1945, 67, 2274; 1947, 69, 2942SROPPEE : STEROIDS AND RELATED COMPOUNDS. 183to give 66% of A14(1S)-equilenin methyl ether (LXXV). Reduction of theC,,,,,,-double link affords 32% of ( j - ) - 14-isoequilenin methyl etherNaOMe(LXXI.)I(LXIX .) (LXX.)(LXIa. ) (LXIb.) 10+J(LXVIIIb.)' (LXXIII.)(LXXV.) (LXXIV.)(LXVIIIa + LXVIIb; R = Me) and 63% of (&)-equilenin methyl ether(LXIa + LXIb : R = Me), demethylated with hydrochloric acid-aceticacid in 98% yield to (-j-)-equilenin (LXIa + LXIb ; R = H).The parent hydrocarbons of ( j - ) -equilenin and ( & ) - 14-isoequilenin, termed-equilenane, have been prepared from the " p "- and" a "-equilen-l'l-ones by Clemmensen or Wolff-Kishner reduction ; the" p "-hydrocarbon is also obtained from (-j-)-equilen-l6-0ne.~~ A single(&)-2-hydroxy-analogue of (A)-equilenin or (-J-)-14-isoequilenin has been~ynthesised.~~Oxidation of ( + )-cestrone acetate (XLIVcc) with alkaline hydrogenperoxide or peracetic acid in acetic acid 64 gives a 3-acetoxy-lactone(LXXVII), which by alkaline hydrolysis gives the sodium salt of a 3-hydroxy-acid.Acidification to pH5 gives the free 3-hydroxy-acid, called oestrolicC < p I ) _ and C < a Y Y0(XLIVa.) (LXXVI.) (LXXVII.( LXXVIII. )acid (LXXVI), whilst excess of acid and heating leads to the3-hydroxyl-actone (LXXVII). Methyl estrolate is readily hydrolysed by62 A. L. Wilds, L. W. Beck, and T. L. Johnson, J . Amer. Chem. SOC., 1946,68,2161.63 W. E. Bachmmn and W. J. Horton, ibid., 1947, 69, 58.64 R. P. Jacobsen, J . Bwl. Chem., 1947, 171, 61184 OKC; .4 N IC' CH EM TS'I'KV.warin sodium hydrogen carbonate to the 3-hydroxy-lactone7 so tlhat formula(LXXVII) is preferred to (LXXVIII) involving a tertiary carboxyl group.The lactone (LXXVII) and its derivatives h a ~ e in. p.s closely similar tothose of the h ydroxy-lactone and its derivatives obtained byW. W. Westerfeld 65 from (+)-@shone by oxidation with hydrogen peroxide,but their identity is unlikely because Westerfeld's hydroxy-lactone is sixtimes more cestrogenically potent than (LXXVII) and stimulates thepituitary, whilst cestrolic acid and its lactone inhibit secretion of gonadotropichormone by the pituitary.Analogous acids and lactones have beenobtained 66 corresponding to androsterone, isoandrosterone, dehydroiso-androsterone, testosterone, and androstane-3 : 17-dione ; they all lackandrogenic activity but stimulate pituitary growth and secretion. Ahitherto unknown polymorph of isoandrosterone acetate, m. p. 116-5-1 17')was encountered.66 Finally a bisdehydro-aestrolic acid and lactone havebeen prepared 67 from (+)-equilenin acetate.The classical method associated with the names of Barbier 68 andWieland 69 for the stepwise degradation of the bile-acid side-chain has beenthe subject of several proposed modifications with a view to improving theoverall yield from C,,-acid to C,,-ketone.A new method used byT. F. Gallagher and V. P. Hollander 70 eliminates two carbon atoms a t onetime :R-CHMe-CH,*CH,-CO,H synthe4is -+ R*CHMe*CH,-CH,*COGH,N, diazoketone kIR*C!HMe*CH,*CH,*CO*CH, +-"- RXHMe*CH,*CH,*CO*CH,ClBr2 - U R rCrO, .1R*CHMe*CH=CH*CO*CH, ---3 R*CHMe*CO,H .Another new and elegant method devised by Miescher et aZ.71 eliminatesthree carbon atoms a t one time :PhNgBr R*CHMe*CH,*CH,*CO,Me ---+ R*CHMe*CH,*CH,*CPh,*OH20 21 '32 '33 24I 4- X-homo- R*CHMe*CHBr*CRrCPh, +----,z-- R*CHMe*CH,*CHXPh,22ICrO R-CHMeX!H*CHrCPh, --:* R-COMe -1- OCH*CH=CPh,.'Lo "1(iL .I.Biol. Chem., 1942. 143, 177.( i 7 It. P. Jacobsen, C. 31. Picha, and H. Levy, ibid., p. 81.68 P. Barbier and R. Locquin, Compt. ?*end., 1913, 156, 1443.8u H. Wieland, 0. Schlichting, and R. Jacobi, 2. physiol. CIwm., 1926, 161, SO.70 J . Biol. Chem., 1946, 162, 549.71 C. Meystre, H. Frey, A. Wettstein, and K. Mioscher, Helv. Chim. -4cta, 1944,27,18 15.(jG R. P. Jacobsen, ;bid., 1947, 171, 71Bromination of the olefin from deoxycholic acid with N-bronio-succiiiimide gives a 38% yield of the 22-bromo-olefin, increased by irradiationto 75% ; 72 N-bromophthalimide may also be used. The overall yield frommethyl deoxycholate to 3(a) : 12(a)-dihydroxypregnan-20-one (6 stages) is186% ; 'il using the Barbier-Wieland procedure (17 stages), the overallyield is from 3.8 73 to 7.1%.7* The recognition of diphenylacraldehyde asthe other product of the final oxidative fission is interesting theoretically, andof practical importance because its removal as the bisulphite compoundfacilitates the isolation of the steroid methyl ketone in a state of p~rity.7~The method has been applied to cholic acid 76 which furnishes a 30% yield of3(a) : 7(a) : 12(a)-pregnan-20-one, whilst 5-aZZocholanic acid,76 which hasnot previously been degraded by the Barbier-Wieland procedure,gives 5 -aZZopregnan-2O-one.3 ( p ) -Hydroxy- 5-aZEocholanic acid 77 furnishes3( p)-hydroxy-5-aZEopregnan-20-oiie, a constituent of the corpus luteurn ;this is reduced by sodium-ethanol to 5-aZZopregnane-3( p) : 20-a-diol, the20-p-epimeride of which has been identified as a component of ox bile.783( a)-Hydroxycholanic acid (lithocholic acid) 77 gives 3( a)-hydroxypregnan-20-0ne, previously isolated &om pregnancy urine, and reduced by sodium-ethanol to a mixture of the pregnane-3(a) : 20-a-diol of G.F. Marrian 79 andthe pregnane-3(a) : 20-p-diol of R. E. Marker et aLa0 3(a) : 6(a)-Dihydroxy-cholanic acid (" a "-hyodeoxycholic acid) a1 is degraded by the Barbier-Wieland method as used by W. M. Hoehn and H. L. Mas0n,7~ and byMiescher's new method to the same 3( a) : 6( P)-dihydroxypregnan-20-onewhich differs from the compounds previously stated 8 2 ~ 83 to have this(LXXIX.) (LXXX.) (1XXXI.)structure. Use of' 3(~)-hydroxychol-5-enic acid,84 wherein the double bondhas been protected by addition of hydrogen chloride to give (LXXIX) leads72 C.Meystre, L. Ehmann, R. Neher, and K. Miescher, Helo. China. -4cta, 1945, 28,'3 P. Hegner and T. Reichstein, ibid., 1943, 26, 715.SB K. Xescher and J. Schmidlin, Helv. Chim. Acta, 1947, 30, 1405.7 6 C:. Meystre and K. Miescher, ibid., 1945, 28, 1497.7; C. lieystre and K. Miescher, ibid., 1946, 29, 33.7 8 W. H. Pearlman, J . Riol. Cheni., 1946, 166, 473.7 y Hiochem. J . , 1947, 41, 193; 1929, 23, 1090.IU J . A4rner. Chem. ~Soc., 1937, 59, 2291.81 R. B. Moffet, J. E. Stsfford, J. Linsk, and W. M. Hoehn, ibid., 1046.68, 1857.8" T. Kimura and G. Sugiyama, J . Biochenz. Japan, 1939,29,409.B3 1:. 3:. Marker and J. lirueger, J . Amer. Chern. Xoc., 1940, 62, 79.1252.W.M. Hoehn and H. L. Mason, J . Amer. Chern. SOC., 1938, 60, 1195186 ORGANIU UHEMISTRY.to pregnenolone (LXXX) and thence to progesterone (LXXXI) ; threedifferent routes are elab0rated.8~By bromination with N-bromosuccinimide, 3-keto-5-do-steroids yieldthe 2-bromo-derivatives, and 3-keto-steroids give the 4-bromo-derivati~es,~~whilst 3-keto-A4-steroids (e.g., testosterone, progesterone) yield the 6-bromo-compounds ; 86 it has, however, been found that by use of N-bromosuccinimidewith irradiation bromination at C,, of 24 : 24-diphenylchol-23-enes proceedsso rapidly that 3-ketones and A4-unsaturated 3-ketones are unaffected.87Thus (LXXXII) gives the 22-bromo-compound (LXXXIII), dehydro-brominated to (LXXXIV), which by oxidation gives progesterone (4throute) .88 Alternatively, the acetoxychloro-diene (LXXXV) can behydrolysed by hydrochloric acid to the hydroxychloro-diene (LXXXVI),oxidised to the 5-chloro-diketone (LXXXVII), which affords progesterone(LXXXI) by simple treatment with potassium carbonate (5th route) ; thesequence of hydrolysis and oxidation can be reversed via (LXXXVIII)(6th(LXXXII.) (LXXXIII.) (LXXXIV.)(LXXXI)\/\I1 HO C1 (LXXXVI.) CPh,AAC(LXXXV.) ciyH--' (LXXXVII.)ACO' C1 (LXXXVIII.)When the 24 : 24-diphenylchola-20 : 23-diene (LXXXIX) is treated withN-bromosuccinimide in either the absence or the presence of light,substitution of the C,, -methyl group occurs to give the 21-bromo-compound(XC) ; this is readily hydrolysed t o the 21-hydroxy-compound (XCI) whichcan be reconverted into the parent bromide.*', 89 By treatment withC.BTeystre, H. Frey, R. Neher, A. Wettstein, and K. Miescher, Helv. Chirn. Acta,1946, 29, 627.8 5 C. Djerassi and C. R. Scholz, Experieiztia, 1947, 3, 107.8 6 C. Meystre and A. Wettstein, ibid., 1946, 2, 408.88 C. Meystre, A. Wettstein, and K. Miescher, Helv. Chim. Acta, 1947, 30, 1022.6 R Idem, ibid., p. 1037.8 7 Idem, ibid., 1947, 3, 186SBOPPEE : STEROIDS AND. REIIATED COMPOUNDS. 187potassium acetate or sodium ethoxide, the bromo-compound furnishes bhe21-acetoxy-diene (XCII) or the 21-ethoxy-diene (XCIII) from which theside-chains may be removed by oxidation. Less satisfactorily, the side-chain can be eliminated first by oxidation of the 21-bromo-diene (XC) to givethe 21-bromo-20-ketone (XCIV), in which the bromine atom can be replacedby acyloxy- or alkyoxy-groups.I n this way deoxycholic acid is readilytransformed into the 3(a) : 12(a) : diacetoxy-20 : 21-ketol acetate (XCV)prepared previously by H. G. Fuchs and T. Reichstein and by L. Ruzicka,P. A. Plattner, and J. Pataki ; 91 the analogous 3-keto-compound and thecorresponding 21 -ethyl ether (XCVI) have also been obtained.89AcO'(LXXXIX.)AcO CrO,\ (XCI.)(XCV.) (XCIV.) (XCVI.)The method has been extended to the production from 3(P)-hydroxychol-5-enic acid 92 of 11 -deoxycorticosterone acetate and 11 -deoxycorticosterone21-methyl ether, and from 3(a)-hydroxy-ll-ketochoIanic acid 93 of ll-keto-progesterone and 11 -dehydrocorticosterone acetate.(XCVII.) (XCVIII.) (XCIX.) (C.)90 Helv.Chim. Acta, 1943, 26, 511.e2 C. Meystre and A. Wettstein, ibid., 1947, 30, 1256.O 1 Ibid., 1944, 27, 988.93 Idem, ibid., p. 12621 HH ORGANIC!. CHE'MISTRY.By contrast with the ready 22-bromination undergone by 24 : 24-di-phenylchol-23-enes (as XCVII), 20-bromination of the 23 : 23-diphenyl-norchol-22-ene (XCVIII) does not occur ; 72 again, whilst 21-brominatlion of24 : 24-diphenylchola-20 : 23-dienes (as XCIX) occiirs readily, 21-brominationof tjhe 22 : 22-diphenylbisnorchol-20-ene (C) docs not take place.89 When22- bromo- 3 ( p ) -acetoxy-24 : 24 -diphenyl-5-aZZochol-23-ene (CI) is oxidisedwith chromium trioxide, the expected 22-bromo-noracid. (CIII) isaccompanied by the broinine-free bisnor-acid (CII) which may arise byanionotroyy (CI + CIV) followed by oxidation, or by hydrolysis of (CI) to(CV) followed by oxidation.94 With sodium-potassium hydroxide a t 200",the bromo-ncicl (CIII) gives 3( ~)-h~ciroxy-ri-aZZonorchol-20-enic acid (CVI) .94coo H Br Hr(CII.) (CI.1 (CIII. )OH\/\\I,/$ CBrYh, I ,,TL ,I-- /;- /;-H (CIV.) H (CV.) H (CVI.)Another method for shortening side-chains is that of H. HunsdieckerR*CH,*C02Ag -'A R*CH2Br ---+ R*Meand C. Hunsdiecker : 95Zn,AcOHAccording to I>. 31. Clark, N. G. Brink, and E. S. the diacetates ofdeoxycholic, nor-, and bisnor-deoxycholic acids as the dry silver salts giverespectively 25%, 40%, and 65% of the corresponding bromides, which arereduced in 90yo yields t o 3(a) : 12(a)-diacetoxynor-, -bisnor-, and -trisnor-cholanes.In the hands of B. Koechlin and T. Reich~tein,~' the Hunsdieckerreaction failed with 3( ~)-acetoxyaetio-5-aZZocholanic acid.Deoxycholic acid is an important starting material for partial syntheses ;attention may therefore be directed to papers dealing with its preparation,98purification,S9 and chromatographic separation from cholic acid.lO0Conversion of cholic acid into lithocholic acid,lol and the preparation of5-rtllocholanic acid froin 3( p)-hydroxychol-5-enic acid, have been described. 7gy4 Y. Wieland and K. Mieseher, Hclz,. Ghim. Acta, p. 1576.9 L Ber., 1942, 75, 291.y i Helv. Chinz. Acta, 1944, 27, 549.9s V. P. Basu and P. Gupta, J . Sci. I d . Res. India, 1946, 5, B, 83.99 R.Charonnat and B. Gauthier, Compt. rend., 1946, 223, 1009; 1947, 224, 279.100 H. Silbermaii and S. Silberman-Martyncewa, J . Biol. Chent., 1946, 165, 359.lU1 H. Heusser and H. W7uthier, Helti. C'him. Acfa, 1947, 30, 2165.O 6 .7. Riol. Clzem., 1946, 162, 095SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 189Steroid keto-groups can readily be eliminated by reduction of the mercaptalswith Raney nickel. Ethylenedithiol condenses with keto-groups at C,, C,,CI2, and C1,, but monothiols react only at C,; 3 : 7 : 12-triketocholanic(dehydrocholic) acid can thus give either cholanic acid or 7 : 12-diketo-cholanic acid, whilst 3( a)-bydroxy-7 : 12-diketocholanic acid gives3(a)-hydroxycholanic (lithocholic) acid.lo2 A new method for reduction ofthe carboxyl group : -CO,H 4 -COCl~-- -CO*SMe 5 -CH,*OH, hasbeen described by V.Prelog et aZ.lo3 3-Iodo-7 : 12-diketocholanic acid hasbeen prepared 1°4 for use as a radio-opaque substance for X-ray diagnosticvisualisation of the gall-bladder, but is ineffective because unabsorbed.D-Homotestosterone and its 17a-epimeride have been synthesised ; lo5the former is 15-20 times more active than the latter, and two-thirds asactive as testosterone, which itself is 30 times more active than its17-epimeride ; D-homoandrost-4-ene-3 : 17a-dione is half as active astestosterone. The codguration of the hydroxyl group attached to ring Dis clearly more important in regard to biological activity than the size oft'his ring, and it has been suggested lo5 that in testosterone the hydroxylgroup has the (p)- rather than the (a)-configuration formerly assigned.The influence of configuration on physiological activity is further exemplifiedby the active cardiac glycosides and the inactive isomeric alloglycosides.That these differ only in configuration a t C,, was originally suggested byR. Tschesche,lo6 was rendered highly probable by L.Ruzicka's synthesis of~Zlouzarigenin,~~~ and proved by T. Reichstein's degradation of periplogenin(CVIII) and albperiplogenin (CIX) to ~tio-5-aZlocholanic acid (CVII) and14-iso-17-iso-~tio-5-~ZZocholanic acid (CX) respectively ; lo8 in periplogeninall the functional groups are thus ((3)-orientated.R-SIT(CVIL) (CVIII. ) (CIX.) (CX,)11~2 H. Hauptmann, J . Anher. C%em. Soc., 1947, 69, 663.l o 3 0.Jeger, J. Norymberski, S. Szpilfogel, and V. Prelog, Helv. C'hitti. Actu, 1948,lo4 R. P. Jacobsen, G . M. Yicha, C. Weinstein, and L. Ittomanoff, J . Bid. C ' l ~ c ) t ~ . ,1°5 M. W. Goldberg, J. Sice, H. Robert, and P. A. Plattner, Helv. (?him. Acla, 1947,106 R. Tschesche and K. Bohle, Ber., 1938, 71, 654; R. Tschesche, K. Bohle, and10' P. A. Plattner, L. Ruzicke, H. Heusser, and E. Angliker, HeEv. Chim. Acta, 1947,108 P. Speiser and T. Reichstein, ;bid., p. 2143.29, 683.1947, 171, 87.30, 1441.W. Neumann, ibid., p. 1927.30, 1073190 ORGANIC CHEMISTRY.An adequate account of the synthetic work from the Ziirich laboratoryand of the degradational work from the Basle laboratory on cardiacglycosides and aglycones would require a separate article and must bedeferred.Eight hydrocarbons, C21H36, epimeric at C,, C14, and C,, should exist;four of these are now known-pregnane (CXI), 5-allopregnane ((3x11) ,14-iso-17-isopregnane 109 (CXIII), and 14-iso-17-iso-5-allopregnane l10 (CXIV)which is identical with the hydrocarbon, diginane, obtained byC.W. Shoppee ll1 by degradation of the physiologically inactive cardiacaglycone, diginigenin. The identity of R. E. Marker's urane,l12 C2,H,,,m. p. 127-128", remains obscure, but it may prove to be one of the fourremaining isomeridea.(CXII.) (CXIII.) (CXIV. ) ( C X I . )m. p. 83", rn. p. 84", m. p. 103 and 105" m. p. 76",[ a ] ~ + 19.6" [.ID f 12.7" [.ID + 19" [alu + 24"In conclusion reference should be made to the application of infia-redspectroscopy to steroid chemistry; 113 by this means, in combination withchromatographic analysis, no fewer than 42 steroids, of which 28 have beenidentified, have been detected in the keto-steroid fraction from normal andpathological urines.l14 Some of these are steroids with oxygen (:O or -OH)at Cll, or A9(11)-steroids clearly derived from cortical precursors, andemphasise the importance of the adrenal gland in the bodily economy inhealth and in disease.Because of lack of space an account of recentdevelopments in the synthesis of 11 -oxygenated steroids and adreno-corticalhormones must be held over.Marrianolic Acids, Doisynolic Acids, Allenolic Acids and Related Compounds.by fusion of cestriolwith potassium hydroxide obtained a dicarboxylic acid, C, 8H2205, alsoisolated by D.W. MacCorquodale, S. A. Thayer, and E. A. DoisyY2 and nowIn 1932, G. F. Marrian and G. A. D. Haslewoodlog K. Rieyer, Helv. Chim. Acta, 1947, 30, 2024.110 Idem, ibid., p. 2127.112 It. E. Marker, 0. Kamm, T. S. Oakwood, E. L. Wittle, and E. J. Lawson, J . Awer.C'hesri. SOC., 1938, 60, 1061 ; W. Klyne and J. Y. F. Paterson, Biochenz. J., 1948, 42,Yroc. ii.llS R. F. Furchgott, H. Itosenkraritz, and E. Shorr, J . Biol. Chem., 1946, 163, 3751946, 164, 621 ; 1947,167, 627 ; 1947, 171, 523.114 K. Dobriner, 112th Meeting of the Ainerican Chemical Socioty, New York City,September 1947; K. Dobiiner, S. Lieberman, C. P. Rhoads, B. R. Hill, L. F. Fieser,It. N. Jones, V. Z. Williams, and R. B. Barnes, J .BioZ. Chenz., 1948,172, 241, 263, 297.Ibid., 1944, 2'7, 246.J . SOC. Chm. Id., 1932, 51, 2 7 9 ~ . a J . Bwl. Chem., 1933,9@, 327SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 191known as marrianolic acid. In 1933, D. W. MacCorquodale, L. Lewin,S. A. Thayer, and E. R. Doisy 3 subjected estrone to fusion with potassiumhydroxide and obtained a moiiocarboxylic acid, C,,H,,O,, now known asdoisynolic acid, which appears also to have been isolated in an impure stateby H. A. Weidli~h.~ The American workers claimed3 that these acidspossessed biological activity several times greater than that of cestrone in theestrus test in rats, but this claim was subsequently withdrawn.6 In 1937and 1939, W. Hohlweg and H. H. Inhoffen in association with Schering A.-G.filed patents 6 describing the production by fusion with potassium hydroxideof cestradiol, dihydroequilin, equilin, or equilenin of the same acid as hadbeen obtained from cestrone, or of analogous monocarboxylic acids.Theseacids were regarded as hydrophenanthryl-1 -acetic acids, and it was claimedthat they possessed threshold activities by oral administration in the estrustest in rats of 1-67, whereas the corresponding figure for oestrone is 20-3Oy.The chemical and biological aspects of the matter have now beeninvestigated and extended by K. Miescher and his collaborators; the moststriking results are the production from (+)-equilenin and " 01 "-dihydro-equilenin, and by total synthesis, of a compound, (-)-'< cc "-bisdehydro-doisynolic acid, and the total synthesis of a racemic doisynolic acid, theestrogenic activities of which both by a single subcutaneous application andby a single oral administration are about 10 times greater than that ofdiethylstilbestrol.Porrrzution, Stereochemistry, and Physiological Activity.-In addition to theoriginal preparation from cestriol by potash fusion, alternative routes to(+)-marrianolie acid (IVu) as the 7-methyl ether (IVb) have been describedinvolving permanganate oxidation of astrio1 3-methyl ether (Ib) 3 andconversion of (-J-)-cestrone 3-methyl ether (IIb) into the 16-oximino-derivativeand subsequent ring-fi~sion.~ An improved preparation has now beendescribed,8 whereby (+) -estrone 3-benzyl ether (IIc) is oxidised withpotassium hypoiodite at 20" to give (+)-7-benzylmarrianolic acid (IVc), whichis readily converted into (+)-marrianolic acid (IVa) by hydrogenation withnickel at 20".(+)-Marrianolie acid (IVa) passes into the anhydride at 180"/0-15 mm.;esterification with diazomethane gives the dimethyl ester, one ester group ofwhich is very readily hydrolysed and the other very resistant to hydrolysis[cf. the dimethyl ester of (IVb) '1. The pure dimethyl ester benzoate giveswith tetranitromethane a faint but distinct yellow coloration which must beattributed to the aromatic double-bond system. The constitution isestablished by dehydrogenation with selenium to 7-hydroxy-1 : 2-dimethyl-phenanthrene (V; R = OH), converted by distillation with zinc intoJ. Bid. Chem., 1933, 101, 753.S.A. Thayer, D. W. MacCorquodale, and E. A. Doisy, J . Pharm. Exp. Ther.,D.R.-PP. 705,862 (Dee. 19, 1937), 719,578 (Jan. 20, 1939).F. Litvan and R. Robinson, J., 1938, 1997.J. Heer and K. Miescher, Helv. Chirn. Actu, 1945, 28, 156.Dissertation, Gottingen, 1934.1937, 59, 48192 ORGANIC CHEMISTRY.1 : 2-dimethylphenanthrene (V ; R = H).9 (+)-Marrianolic acid by oral orsubcutaneous administration is completely inactive in doses of 1 mg. in theOHBOH(IVa; R = H.)(IVC; R = CR,Ph.)(IVb; R = Me.)(VIa; R1= R2 = H.)(VIb; R1= H, R2 = Me.)(VIc; R1 = Bz, R2 = Me.)1tV.1 tm-)estrus and uterus test in rats; lo this confirms the revised results of Doisyet a1.5(+)-l)oisynolic acid (VIa) is obtained in SOYo yield by fusion of either(+)-oestrone (IIa) or " o! "-oestradiol (111) with potassium hydroxide at275" ; its constitution as a 7-hydroxy-2-methyl-l-ethyloctahydro-phenanthrene-2-carboxylic acid follows from its dehydrogenation withpalladised charcoal in acetone at 320" in 54% yield to 7-hydroxy-2-msthyl-l-ethylphenanthrene 8 (VII; R = OH), converted by distillation with zincinto 2-methyl-l-ethylphenanthrene l1 (VII; R = H).-The acid (VIu)cannot be esterified with alcoholic hydrochloric acid, but with diazomethanegives the methyl ester (VIb) characterised as the benzoate (VIc) ; (VIc) withhot 2N-alcoholic potassium hydroxide gives (VIb), which can only behydrolysed with potassium hydroxide at 180". The pure ester-benzoate(VIc) gives a pale yellow oolour with tetranitromethane, but is unaltered bytreatment with osmium tetroxide or monoperphthalic acid.The ultra-violetabsorption spectrum of (VIb) is practically identical with that of dimethylA. Butenandt, H. A. Weidlich, and H. Thompson, Ber., 1933, 66, 601; J . SOC.Chern. Id., 1933,52,289~.lo J. Eeer, J. R. Billeter, and K. Mie~cher, Hdv. Chirn. A&, 1946,28, 991.l1 R. D. Haworth, J., 1934, 460SHOPPEE STEROIDS AND RELATED COMYOUSDS. 19::(+)-marrianolate, and the absence of unsaturation, apart from the aromaticsystem, is shown by its resistance to hydrogenation with platinum oxide inacetic acid; under these conditions, the free acid (VIa) gives n mixture ofhexahydro-acids which is biologically inactive.( +)-Doisynolic acid is highly estrogenic ; l2 this confirins the originalclaim of Doisy et aZ.3 which was later ~ i t h d r a w n .~ By subcutaneousadministration only 0.7-1 y is required, so that the acid is practically asactive as (+)-cestrone; given orally the threshold dose is 1.5 y, in goodagreement with the value (2.5 y ) reported by Hohlweg and Inhoffen.6 rH PI10II /\I. * ; ?\ I /,A- /\'\4RO{A/ p HOk>{/i H (IX.) ' --I KOH(VIIIa; P, = H.)(VIIIb; R == CH2Yh.)(VIIIc; It == Me.)(XU; It = H.)( X b ; R = CH,Ph.)(Xc; R = Ale.)(XIU; R'= H2 = H.)(XIb; I t 1 -- Rz = Me.)(XTc; R1 = Me, HZ = H.)(XIIa; It' = R2 = H.)(XIIb; R1 = R2 = Me.)(XIIc; R' = Me, It2= H.)rd-c i11 ~ , C O at 3200 \ A / A;:,. ""'fH d \,A/(VII.)( +)-Equilenin benzyl ether (VIIIb) by oxidatioii with potassiumhypoiodite at 20" gives ( +)-7-benzylbisdehydromarrianolic acid (Xb), whichwith acetic anhydride-pyridine at 20" readily affords the anhydride( X I I I ; X = 0), from which the imide ( X I I I ; X = NH) is obtained.Hydrogenolysis of (Xb) with palladium-calcium carbonate gives an 89 yoyield of ( +)-bisdehydromarrinnolic acid 10 ( X a ) .(+)-Equilenin methylcther (VIIIc) 137 l4 with potassium hypoiodite similarly gives the inethylcther of ( +)-bisdehydromarrianolic acid (Xc), demethylated by pyridinchydrochloride l5 a t 170" to (+)-bisdehydromarrianolic acid ( X u ) , which bycontrast wit'h its henzyl ether ( X b ) does not furnish an anhydride butI f K. Miesclier, Hrliv. P h i t ) t . A c t u , 1916, a, 1727.l 3 (:. Sandulescw.\Ir. \Ir. rrschlIng. and .A. Giratrd, ( ' U / t ! ] J t . ~ d . , 1933. 196, 13'7.'I \V. E. Bachmann, LV. C'ole. and .-\. I,. LViIdq, J . Awer. Chem. SOC., 1940. 62, 824.l 5 V. Prey, Ber., 1941, 74, 1219.1tEP.-VOL. XLTV. 194 ORGANIC CHEMISTRY.decomposes when sublimed in a high vacuum. The acids ( X a and Xc) withdiazomethane give dimethyl esters, one carbomethoxy-group of which ishydrolysed with extreme ease. ( +)-Bisdehydromarrianolic acid by sub-cutaneous or oral administration is completely inactive in doses of 1 mg. inthe estrus and the uterus test in rats.10( +)-7-Methylbisdehydromarrianolic acid ([.ID + 102") (Xc) is clearlyone of the four enantiomorphs comprised by the racemic " a "- and" p "-7-methylbisdehydrornarrianolic acids synthesised by Bachmann, Cole,and Wilds.14 Since the oxidation (VIII--+ X) occurs under mildconditions, and presumably without disturbance of the stereochemicalarrangement, configuration a t C, and C, in " natural " (+)-bisdehydro-marrianolic acid (Xa) should correspond with configuration a t C,, and C,,in ( +) -equilenin (VIIIa). A similar configurational relationship should holdbetween " natural '' (+)-marrianolie acid (IVa) a t C, and C, and (+)-estrone(IIa) a t C,, and C1,, and it has been shown l6 that (Xc) is in fact t,he( +)-enantiomorph of the racemic " p "-7-methylbisdehydromarrianolic~acid, m.p. 213", of Bachmann et aZ.,14 from which (-J-)-equilenin wassynt hesised.(+)-Equilenin (VIIIa) or '' a "-dihydroequilenin (IX),17 m. I>.24X",by fusion with potassium hydroxide a t 275" both yield 70--80% of a mixtureof acids from which (normal) * (-)-" a "-bisdehydrodoisynolic acid (XIa)and (iso) * (+)-" "-bisdehydrodoisynolic acid (XIIa) are obtained in 10%yield.10 After removal of phenolic material, the acids are isolated byfractional precipitation of the sodium salts a t given pH. The crude acid(XIa) is highly estrogenic (threshold value in rats by oral application,0.1-0.15 y).; it is purified by conversion with diazomethane and methylsulphate into the methyl ether-methyl ester (XIb). This, after chromato-graphic purification, is hydrolysed with potassium hydroxide at 180" to themethyl ether (XIc), which cannot be esterified with alcoholic hydrochloricacid, and is demethylated by pyridine hydrochloride at 180" to give(-)-" u "-bisdehydrodoisynolic acid (XIa).Similar treatment of the crudeacid (XIIa) gives (XIIb), (XIIc), and finally (+)-" p "-bisdehydrodoisynolicacid (XIIa). " a "-Dihydroequilenin l7 by fusion with potassium hydroxidea t 275" gives the same acids (XIa, XIIa), which are formed in roughly equalproportion and in overall yields of S-lO%. The constitutions of the acidsJ. Heer and K. Miescher, Helv. Chin$. Acla, 1946, 29, 1895.1' L. Ruzicka, P. Muller, and E. Morgeli, ibid., 1938, 21, 1394; R. E. Marker el al.,J . Auaer. Chem SOC., 1937, 59, 768.* I n Parts I-XI1 inclusive of the series entitled " f:ber aestrogene Carbonsauren "(Helv. Chim. Acta, 1944, 27, 1727 et seq.) these acids were distinguished by the prefixesiwrnaal and is0 because it was thought that, despite contrary rotatory powers, thebiologically active acid corresponded configurationally with the biologically activeequilenin, and the physiolopic.ally inactive acid with the physiologically inactiveli-isoequilenin. Tn Part XIIL (ibid., 1946, 29, 1x95; ref.16) it was shown that thisassumption waa untenable ; the terminology previously used was abandoned for thetrivial indices " a "-(= normal) and " /I "-(= iao), and the formulR previously employedwere interchangedSHOPPEE : STEROIDS AND RELATED COMPOUPITDS. 195follow from their conversion by dehydrogenation with palladium-charcoalinto the phenanthrol (VII), and have been proved by total synthesis; forconfigurations, see below.(+)-" p "-Bisdehydrodoisynolic acid (XIIa) is inactive by oraladministration in the estrus test in rats in doses of 5OOy, but (-)-" a "-bis-dehydrodoisynolic acid (XIa) is fully active in rats a t the threshold dose of0.05~; it is thus the most potent estrogen known,1° and is only equalledby one of the synthetic (-+)-doisynolic acids (see below).The (-)-7-methyl-" a "-acid (XIc) is equally active.1°By contrast with the marrianolic acids, the " natural " doisynolic acidsare obtained from (+)-oestrone, " a "-estradiol, (+)-equilenin, and" rx "-dihydroequilenin by very violent treatment-potassium hydroxide a t275" ; inversion of ( +)-equilenin and " a "-dihydroequilenin must occur a tone of the asymmetry centres C,, or C,,, because two diastercoisomerides-the (-)-" a "- and (+)-.' 3 "-bisdehydrodoisynolic acids-are produced.Itmay be noted that tlhe action of potassium hydroxide a t 275" on estriolproceeds without disturbance of configuration a t C,, or CI4, because only asingle (+)-marrianolie acid (IVa) is obtained, which is identical with thatproduced from (+)-estrone by oxidative fission at 20" ; likewise,(+)-estrone and " a "-cmtradiol with potassium hydroxide a t 275" give onlya single ( +) -doisynolic acid (VIa), which should correspond stereochemicallywith (+)-oestrone." Natural " (+)-marrianolic acid (IVa), as the 7-methyl ether-2-methylester, with oxalyl chloride gives the 1-acid chloride reduced by theRosenmund method with palladium-charcoal to the 1-aldehyde (XIV),which is converted by low pressure Wolff-Kishner reduction l8 into( +)-7-methyldoisynolic acid, also obtained less satisfactorily from (XIV) byClemmensen reduction ; this by complete hydrolysis yields ( +)-doispolicacid (VIn),lG identical wit,h the " natural " acid from (+)-estrone (IIa) or" a "-estradiol (111).1Similarly, the 3-methyl ether of (-)-lumioestrone (XV), obtained in 33%yield by irradiation * of (+)-oestrone methyl ether,l6? l9 has been oxidisedM.D. Soffer, &I. B. Soffer, and K. \Ir. Sherk, J . Amer. CIhtttL. Soc., 1945, 67, 1435.* Irradiation of the 3-methyl ether of (+)-equilenin gives only traces of the 3-methylether of ( -)- 14-isoequile~i~, 1196 ORGAN 1C CHEMISTRY,with potassium hypoiodite a t 20" to a (+)-lumimarrianolic acid (XVI);this, by conversion into the 1-aldehyde, Wolff-Kishner reduction of this, andfinally complete hydrolysis, gives ( + ) -1umidoisynolic acid (XVII) .16The doisynolic acids (VIa, XVII), as the 7-methyl ether-methyl esters,by dehydrogenation with palladium-charcoal in acetone a t 250°, giverespectively the 7-methyl ether-methyl esters of (+)-" p "-bisdehydro-doisynolic acid (XIIa) and ( +)- " u "-bisdehydrodoisynolic acid (XVIII) .,O(XIIa.) (XVIII.)(+)-14-isoEquilenin (XIX), which was prepared 2o from ( +)-oestroiieby dehydrogenation with palladium-charcoal, so confirming the original'observation of Butenandt,19 as the 3-methyl ether by oxidation withpotassium hypoiodite a t 20" gives the 7-methyl ether of (-)-" u "-bis-dehydromarrianolic acid (XX),,O which was also obtained 2o by resolution ofthe 7-methyl ether of the (*)-" u "-bisdehydromarrianolic acid of Bachmannct ~ 1 .~ ~ from which (&)-14-isoequilenin was synthesised. Application of thereaction sequence : -CH,*CO,H + -CH2*COC1+ -CH,*CHO -+ -Et,to the marrianolic acid (XX) gives the 7-methyl ether of (-)-" a "-bis-dehydrodoisynolic acid (XIa), so that ( +)-equilenin with potassiumhydroxide a t 275" and (+)-14-isoequilenin by stepwise degradation afford thesame (-)-" u "-bisdehydrodoisynolic acid.20 (&)- 14-isoEquilenin has alsobeen converted 16~ 2o via (-J-)-'' u "-bisdehydromarrianolic acid into (-&)-" a "-bisdehydrodoisynolic acid ; in effect, therefore, it is known that (-)-( 14)-iso-equilenin (XXI) is transformed via ( +)-" a "-bisdehydromarrianolic acid(XXII) into (+)-" o! "-bisdehydrodoisynolic acid (XVIII), so that the enantio-inorphs of 14-isoequilenin give, each to each, the rotationally oppositeenantiomorphs of '' u "-bisdehydrodoisynolic acid [( $)-M-iso --+ (-)-" a ' I ,Finally, the natural ( +)-bisdehydromarrianolic acid (Xu), obtained bymild oxidative fission of (+)-equilenin,lo has been converted by the reactionsequence : -CH,*CO,H -+ -CH,*COCl-+ -CH,CHO ---% -Et,* into the( - ) - i 4 - i ~ --+ ( + I - ' ~ oL y .2 0A . Butenantlt et al., B e y . , 1941,74, 1308; 1942, 75, 1931 ; 1944, n, 393, 394."O J . Heer and K. Rlieschcr. t f d t 9 . C?~;M. --ldu, 1917, 30, 350.* Since this report was writteii. this conversion h:is nlso hscn ~cliieved, n\wicling theI1ig.11-temperature Wolfl-Kishner reduction stage, by hyclrogenation of the benzylinercaptttl : -CH;OH --+ CH;CH(S-CH,Pli), -+ Et, with Raiiey nickel in itqtleorlsethanol a t 100" (k.Heer and K. Jliescher, Helv. C'?L~/~L. .4ctu, 1918, 31, 405)SITOFPEE : S'I'EROT1)S AND RELATED COhlPOUN DS. 197biologically inactive enantiomorph ( +)- " p "-bisdehydrodoisynolic acid(XIIa) .I6 Clearly, (-)-equilenin (XXIII) should give a (-)-bisdehydro-inarrianolic acid (XXIV), which in turn should furnish the (-)-" p "-bis-dehydrodoisynolic acid (XXV), which is already available in principlesince the (&)-" p "-acid has been prepared by total synthesis (see below) ;this conversion has not yet been accomplished but is included for the sake ofcompleteness in the following set of formulae, which give a complete andconsistent picture of the foregoing transformations 21 on the basis that(-t)-cest,rone and ( f-)-equilenin possess the same configuration a t C,, and9(- )-Equilenin0I1(XXIII.)HOI II I €3 \A/( + )-EquileninRisdahydromarrianolic Hisdehydrodoisynolicacids.ncids.CO,H(+I-" B "(.-)-C' p "(XXV.)f (VIIIU.) (XU.)(XIX.) WX.1 (XIU.)0C0,H C0,H3( - ) - 1 1 ~ iso Eqii i leriin (L)-'. Q " (+)-" a "(XXI.) (XXTI.) (XVIII. )The production of the diastereoisomeric acids (XIa) arid (XIIa) from(-1-)-equilenin (VIIIa) by potash fusion may involve inversion a t C14 ; theobservation 2o that the acids ( X u ) and (XIIa) undergo interconversioni n the presence of potassium hydroxide at 295" or of the sodium derivative21 C.W. Shoppee, Xature, 1947, 160, 64. 22 Idem, ibid., 1948, 161, 20719s ORGANIC CHEMISTRY.of ethylene glycol at 190" (eOCH,-CH,Oe, cf. CH,Oe, being more effectivethan OHe for extraction of He) suggests, however, that the primary reactionundergone by ( +)-equilenin with potassiuni hydroxide a t 275" is hydrolyticfission to the (+)-" p "-bisdehydrodoisynolic acid (XIIn), which thenundergoes reversible conversion into the diastereoisoineric ( -)-" a "-acid( X u ) with inversion of configuration at C,.Support for the relationships given in the foregoing table is provided 23by conversion of the 7-methyl ethers of (&)-" a "-bisdehydrodoisynolicacid * (XIa + XVIII) and of (&)-" p "-bisdehydrodoisynolic acid *(XLIa + XXV) via the sequence --COCl+ -CHO --+ -Me, intothe same (&)-7-methoxy-2 * 2-dimethyl-l-ethyl-1 : 2 : 3 : 4-tetrahydrophen-4- (XXV.)(XIIa.)anthrene (XXVI + XXVII).If corresponding transformations were carriedout with the diastereoisomeric (-)-" a "- (XIu) and (+)-" p ')-acids (XIIa)and yielded respectively the enantiomorphs (XXVI) and (XXVII), thiswould prove the postulated occurrence of inversion of configuration a t C,.(&)-" ct "-Bisdehydrodoisynolic acid (XIa + XVIII) is also obtained 24when the (&)-" a "-monodehydrodoisynolic acid (XXVIII and its mirror-image) (prepared by total synthesis, see p. 210) is dehydrogenated as theinethyl ether-methyl ester ; when the 11 : 12-double bond of' this(&)-" a "-monodehydrodoisynolic is reduced, there are obtained two (&)-7-methyldoisynolic acids, (XXIX and mirror-image) and (XXX and mirror-image), which differ only in configuration a t C,, and C,,.24 Both undergodehydrogenation to give ( &)-" a "-bisdehydrodoisynolic acid (XIa $- XVIII),so that the stereochemical arrangement, C,-Et/C,-CO,H : cis, is assured ;the acid (XXIX), m.p. 187-188", is intensely estrogenic (threshold dose0*05y, oral or subcutaneous), whereas the acid (XXX), m. p. 213", isrelatively so inactive (threshold dose, 1OOy) that this small activity may bedue to mere traces of the isorueride.%The liquid keto-ester (XXXI) of R. Robinson and J. Walker 25 andz3 J. Heer and K. Miescher, Helv.Chim. Acta, 1947, 30, 777.24 Idem, ibid., p. 1422.* In the original paper, formula (XVIII), which actually represents the (4- )-'' a "-enantiomorph, is used t o represent the (&)-" a "-acid; likewise, formula (XIIa),corresponding to the (+)-" j? "-enantiomorph, is used to represent the (&)-" j? "-acid.2s J., 1936, 747SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 199Bachman et u E . , ~ ~ with 3 asymmetric centres, should exist in 4 racernicmodifications (XXXI A, B, C, and D) of which 3 have now been obtained(XXVIII.) (XXIX.) m. p. 187" (XXX.) m. p. 713"Pd-C in bleOH ttt 290" or Ni in MeOH a t 110"/41) atms.A XI^ + 'XVIII)~rystalline,~~ and one (XXXI A) has been converted into (+)-oestrone.aThese racemic keto-esters have been converted (for details see p.212) into6 crystalline (j-)-7-methyldoisynolic acids (XXXII A " a ", A " p " ;XXXII B " a " ; XXXII C " a ", C " p ").-4, m. p. 133-135" B " fi ", ----B, m. p. 87-89' D, - A " fi ", m. p. 227" C " u ", m. p. 179"C " fi ", m. p. 189"C , m. p. 127-128" A " a ", m. p. 187"B " u ", m. p. 213"The doisynolic acid structure (XXXII) with 4 asymmetric centres(C2, C,, CI1, C12) can exist in 8 racemic forms corresponding to 16 opticalc, Cl C l l c12CO,H Et H H(XXXIIB.)I ''f" I I iI I II t IIIIIL L > >"' B "Ic2 c, Cl, Cl,CO,H Et H HI I II I (Me) IIIIII (Me)I I 12 . l ~ G . Anner and K. Miescher, Experientia, 1948, 4, 25.20 W. E. Bachmann, S. Kushner, and A. C. Stevenson, J . Anaer.Chem. SOC., 1942,64, 974200 ORCiANIC CHEMISTRY.isomerides; these are shown in horizontal pairs in the accompanyingdiagrams, in which the usual convention of broken and full lines for represent-C', (3, CIl C12CO,H Et H HII (Ale)I II II I1 I (Me)I '1 'ation of (a)- and ($)-orientated groups is employed. As a convenientreference point, the angular methyl group at C, (=C,, of the originalsteroid skeleton) is also shown." Natural " ( +)-7-methyldoisynolic acid is represented by the left-handmember of the enantiomorphous pair (XXXII A " p "), and the synthetic7-methyldoisynolic acid, m. p. 227", is regarded as the racemate (XXXII A" p "). The intensely active (-J-)-7-methyldoisynolic acid, m. p. 187"(XXIX), is identical with the racemate represented by (XXXII A " cc ") ;it thus possesses the stereochemical arrangement at C,, and CI2 shown in(XXXIII), corresponding to the trans-B/C ring-union present at C, and C, inthe natural steroids (as XXXIV).CO,HThese configurational assignments are confirmed by dehydrogenation ;(XXXII A " a ") gives the intensely estrogenic (-J-)-" a "-7-methylbisdehydro-doisynolic acid (XIa + XVIII), whilst (XXXII A " p ") gives the relativelynon-cestrogenic (A)-" p "-7-methylbisdehydrodoisynolicacid (XIIa + XSV) .2*The (&-)-7-methyldoisynolic acid (XXX), in.p. 213", is identical with theracemate (XXXII B " a "), which appears to be that of (+)-7-methyl-umidoisyiiolic acid (XVII), which is itself the right-hand member of thSHOPPEE STEROlDS AND RELATED COMPOUNDS.20 1enantiomorphous pair. The (-J-)-7-methyldoisynolic acid, m. p. 189",by dehydrogenation gives (-J-)-" p "-7-methylbisdehydrodoisynolic acid(XIIa + XXV), and is therefore to be represented by either the racemate(XXXII C " p ") or the racemate (XXXII D " p "); these differ only inorientation at C,, and CI2, which would correspond in either case with acis-B/C steroid ring-union.Compound. M. p.( +)-" a "-Bisdehydrodoisynolic acid (syn-thetic), ..........................................(-)-" a -Bisdehydrodoisynolic acid (syn-thetic!, ..........................................( -)-" a -Bisdehydrodoisynolic acid[from ( + ) -equilenin] .....................( +)-" /3 "-Bisdehydrodoisynolic acid[from ( +)-equilenin] .....................( 4-) -" a "-Bisdehydrodoisynolic acid (syn-thetic) ..........................................( f )-" "-Bisdehydrodoisynolic acid (syn-thetic!,. .........................................( + ) - " a -7-Methylbisdehydrodoisynolicacid (synthetic) ..............................( - ) -" a "- 7-Methylbisdehydrodoisynolicacid (ynthetic) ..............................( - )-" a -7-Methylbisdehydrodoisynolicacid [from (+)-equilenin] ...............( f )-" a "-7-Methylmonodehydrodoisynolicacid (synthetic) ..............................( &- )-" /3 "-7-Methylmonodehydrodoisynolicacid (synthetic ) ..............................(-/-)-D,$synolic acid [from (+)-cestrone or(+)-Lumidoisynolic acid [from (-)-lumi-cestrone J .......................................( f )-7-Methyldoisynolic acid (XXIX) (syn-thetic) ..........................................( f)-7-Methyl-lumidoisynolic acid (XXX)(synthetic) ....................................( + )-Bisdehydromarrianolic acid [from( + ) -equilenin] ..............................(+)-Marrianolie acid (from (+)-aestroneor cestriol) ....................................(+)-(Estrone ...................................." a "-CEstradiol .................................Diethylstilbaestrol ..............................a -cestradiol] ..............................159-1 61 O159-160161-1622 5 6-2 5 8204238-240220-2212 19-22 12 1 9-22 1168-170171-173199-200152-154187213243-245223-224 -ICEstrus thresholdvalue in rats.BY a[ a l y 2 "in single sub- By oralEtOH.cutaneous adminis-adminis- tration :tration : y. y.+ 115"-116-117+ 27--+ 100-5- 99.5- 103--+ 102+ 70--+ 103100.050.05200-3000.1-0.15> 100150.050.05--0.7-1.02500.05100> 1000+ 90 >loo0- 0-7- 0.3-0.4- 0.3-0.4100.050.05-0.1-0.15> 500150.050-050.131.5-0-05100> 1000> 100020-3020-300.7-1.0Compiled mainly in respect of biological data from refs. 10, 12, 23, 24, 27, and 28;cf. also E. Tschopp, Schweiz. med. Woch., 1944, 74, No. 51, 11; HeEv. Physiol. Actu,1946, 4, 271, 401.Following alteration of the nomenclature (ref. 16), n became " a ", {S~O became " /3 ' 7 .The Table summarises the chemical and biological properties of theniarrianolic and doisynolic acids ; for comparison, the threshold activitiesof (+)-cestrone, " a "-cestradiol, and diethylstilboestrol are included.The2 7 R. Rometsch and K. Miescher, Helv. Chim. Actu, 1946,29, 1231.28 G. Anner and K. Miescher, ibid., p. 1889; Experientia, 1946, 2, 409203 ORGANIC CHEMISTRY.bisdehydrodoisynolic acids are notable in possessing the same activity in ratswhether administered orally or subcutaneously ; moreover a single dosegives the full effect. The sodium salt of racemic " a "-7-methylbisdehydro-doisynolic acid has been introduced for clinical use under the name" fenocyclin," but up to now the required dosage has not been definitivelysettled.R2 CO,H "/ K2 CO,H /\I.*' ItL CO,H p y o z H /Jg:.../yy,,,-l<l q . ) \ i g R 1 #A/\/ II I H '. *I3'RO\?/\//(-)-" fl "R d \/v Rok,\/ l%,,/(-)-'' 0. "- (+)-" 0. " (+)-" fl ''Bisdehydrodoisynolic acids. Bisdehydrodoisynolic acids.In the bisdehydro-series, high estrogenic activity appears to depend oncis-orientation of C1-Et/C,-C02H ; it is, however, a most striking fact that,in addition, such a cis-relationship must involve (a)- and not (@)-orientatedgroups. Thus the (-)-" a "-bisdehydrodoisynolic acid (which correspondsin regard to configuration a t C, with the configuration a t C,, in aEE the steroidhormones) is some 200 times more potent than the enantiomorphous(+)-" a "-acid. The homologous racemic " a "-bisdehydrodoisynolic acidsin which R1 = R2 = Me, and R1 = Et, R2 = Pra, are almost as active as racemic" a "-bisdehydrodoisynolic acid itself (R1 = Et, R2 = Me), but the activityfalls to about one half when R1 = R2 = Et.29 If alkyl groups are absent fromthe 1- and 2-positions, or only from the l-position, estrogenic powerlargely disappears,29 so that activity appears also to be connected with thepresence of trans-orientated alkyl groups. Inversion of configuration atposition 1, from CL-Et/C,-CO,H : cis in (-j-)-" CL "-bisdehydrodoisynolic acid toC,-Et/C2-C02H ; trans in ( j-)-" p "-bisdehydrodoisynolic acid is here sufficientto depress activity by a factor of more than 1000; of the homologous(5)''' p "-bisdehydrodoisynolic acids, only that with R1= R2 = Me showsappreciable activity (oral threshold value, 7 0 ~ ) .~ ~ The (&)-7-methyl-l : 2-cyclopentano- (XXXV) and - 1 : 2-cycEohexano-bisdehydrodoisynolic acids(SXXVI), which correspond stereochemically with the (&)-" p "-bisdehydro-acids in that the cis-orientated alkyl groups of the latter (R1 = Et ; R2 = Me, orR1 = R2 = Et) have become united in a ring, have little potency (thresholdvalue 200-700yy by a single subcutaneous injection) .30/\I-CO,H /)A(&--bX/ (XXXVII * )f/ sz ,, \(' /V\A p 5 31eol 11 I \/\/(XXXVI.)Numerous derivatives of ( &)-" a "-bisdehydrodoisynolic acid have beenprepared; 31 these include the 7-Me, -Et, -Pr', -Bus, -CH,*CH:CH,,29 J. Heer and K. Miescher, Helv. Chim. Acta, 1945, 28, 1504.3O L. Ehmanri and K.Miescher, ibid., 1947, 30, 413.31 G . Anner, J . Heer, and K. Miescher, ibid., 1946, 29, 1071.If0*\A/(XXXV.SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 203-isoamyl, and -CH,*CH,*NEt2 ethers and the corresponding methyl esters,the Me, Et, Pray Bus, and -CH,*CH,*NEt, esters of the 7-methyl ether,and the P-diethylaminoethyl ester of the 7-p-diethylaminoethyl ether.Increasing chain-length of the group R in RO- (at position 7) or of thegroup R in -CO,R (at position 2) leads to decreasing activity; in the basicderivatives (R = CH,*CH,*NEt,) activity is much decreased. Finally, deriv-atives of ( &)-" a "-7-methylbisdehydrodoisynolic acid containing variantsof the carboxyl group -CO*R, where R = C1, Me,* CHN,, CH,*OAc,f. 31 orNH2,23 and the analogues in which this group is replaced by -CN23 and-CH,*CO,H,31 exhibit activity only at very high dosages ; on the other handthe derivatives in which the carboxyl group is modified to -CHO, -CH,*OH,and -CH,*OAc are almost as active by oral or subcutaneous application asthe parent acid, and double the duration of the estrus state.= Even the(&)-phenanthrol methyl ether (XXVI + XXVII), in which the originalcarboxyl group has become a methyl group, is fairly active (threshold value5-2Oy, by oral or subcutaneous application) with a strikingly protractedaction (> 55 days after injection of 1007, cf.11-13 days after injection of1 0 9 of (&)-" a "-bisdehydrodoisynolic acid).= The analogous aldehyde andalcohol from ( &) -" p "-7-methylbisdehydrodoisynolic acid are practicallyinactive.,3In the (-J-)-" CL "-bisdehydro-series, the 7-methyl ethers possess the sameactivities, by oral or by subcutaneous administration, as do the freehydroxy-acids; this is in striking contrast to the activity ratios of(+)-oestrone, " a "-oestradiol, and (+)-equilenin to their 3-methyl ethers(1 : 14, 1 : 29, and 1 : 3.3 respectively). In fact, the presence of a 7-hydroxylor 7-methoxyl group appears t o be less important than that of the properalkyl groups at C, and C, properly orientated [ ( a ) ] ; $ thus the synthetic(-j-)-7-deoxybisdehydrodoisynolic acid (XXXVII) 33 is active at a level of57, i.e., is only 50 times weaker than (&)-" cc "-bisdehydrodoisynolic acid,and is provisionally assi&ed to the " a "-series.In the monodehydro-series, the (-+)-" a "-7-methyl acid (XXVIII)(CI-Et/C,-CO,H : cis) is active at a level of 0.17, whilst the (j-)-" p "-7-methylisomeride (C,-Et/C,-CO,H : tram) is active at a level of 37, so that hereinversion of configuration at C, only decreases activity by a factorof 30.Various analogues of the bisdehydrodoisynolic acids with modifiedring-systems have been prepared and tested for biological activity. Thetwo stereoisomeric ( j-)-C-norbisdehydrodoisynolic acids represented by(XXXVIII) are both active by a single subcutaneous injection, but only at32 W.E. Bachmann and A. L. Wilds, J . Amer. Chem. SOC., 1940, 62, 2084.33 G. h e r and K. Miescher, Helv. Chim. Acta, 1946, 29, 586.* This ketone has no progestational activity.*f This ketol-acetate has no cortical activity.Racemic 3-deoxyequilenin is inactive at a level of 500y; 32 the activity of( &)-equilenin has apparently not been determined, but may be roughly estimated atitbout 6% from the known activities l4 of the enantiomorphs [( +)-equilenin, 30y;( -)-equilenin, 40OyI204 ORGANZC OHEMTSTRY.a level of about 1000y.34 Surprisingly the ( &) -B-normonodehydrodoisynolicacid (XXXIX), which may also be formulated as (XL), is highly active bothas the hydroxy-acid and as the 7-methyl ether at a level of about ly; thelower homologue (XXXIX with Me for Et) is also active at a level ofabout 7y.35(XXXVIII.) (XXXIX.) (XL.)Attempts to simplify the tricyclic structure generally lead to inactivecompounds. The two stereoisomeric ( 5)-tetrahydronaphthalenecarboxylicacids represented by (XLI) are both inactive at a level of 1oOOy,33* 363 37whilst the isomeric (&)-acid (XLII) is inactive at a level of 1OOy.On the otherhand, (&-)-dimethylethylallenolic acid (XLIII; R1 = R2 = Me, R3 = Et),which bears a formal resemblance to G-norbisdehydrodoisynolic acid(XXXVIII), and its methyl ether are highly active (threshold value1--1*5y, by single subcutaneous or oral application), and evoke the samephysiological responses as the natural oestrogenic hormone^.^' The methylethers of dimethyl-, trimethyl-, and methylethyl-allenolic acids (XLIII ;R1= R2 = Me, R3 = H ; and R1= H, R2 = Me,R3 = Et) are inactive at IOOOy, active at 1Oy, and very active at lOOyrespectively, whilst the unsaturated analogue (XLIII; R1 = R2 = Me,R3 = XHMe) is also active at a level of 25-50~.3~R1= R2 = R3 = Me;Rl-.:CO, /yyH-R3 C ; - C 0 2 H/ --Et>red\, II H I /I 13(XLIII.)A??(XLI.) (srm.)In the doisyliolic acid series, information bearing on the relationshipbetween structure and biological activity is less extensive.“ Natural ”(+)-doisynolic acid (VIa or XXXII A “ p ”; left-hand member ofenantiomorphous pair) is highly active (threshold value about l y ) , despitepossession of the unfavourable C,-Et /C,-CO,H : trans-arrangement . Theorientations of the hydrogen atoms at C,, and CI2, however, correspond withthose at C, and C, of the natural steroids. In (+)-lumidoisynolic acid(XVII or XXXII B “ o! ” ; right hand member of enantiomorphous pdr)(threshold value, 250y), the favourable C1-EtjC2-C0,H : cis configuration ispresent but involves the unfavourable ($)-orientation ; again configurationat C,, and C,, corresponds with that at C, and C, in the natural steroids.34 J.R. Billeter and K. Miescher, Helv. CI~irn, Acta, 1946, 29, 859.35 G. Anner and K. Miescher, ibid., 1027, 30, 544.36 J. H. Hunter and J. Kormrtn, J . L4??ier. Ckem. SOC., 1947, 69, 21%4.31 R . Courrier, A. Horeau, and J. Jncques, Compt. rend., 1946, 222, 961, 1113; 1946,224, 862, 1401 ; Compt. rend. SOC. Biol.. 1947, 141, 159, 747SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 205Synthetic (&)-7-methyl-lumidoisynolic acid (XXX or XXXII B " a ") isactive at a level of lOOy ; if this activity is really attributable to the racemicIumi-acid (cf.p. 198) it suggests that the as yet unknown (-)-lumidoisynolicacid (XXXII B '( a " ; left-hand member of the racemic pair) must be activea t a level of about 50y. This seems unlikely, because although the( - )-lumiacid has the favourable C,-Et/C,-CO,H : &-arrangement with thoadvantageous (a)-orientation, configuration a t C,, and C,, is enantiomorphouswith that present a t C, and C, in the natural steroids.(XXXIIA " /3 ".) (XXXII B " a ¶'.)Left-hand member Left -hand member Right-hand memberof raceinic pair of racemic pair of racemic pairThe synthetic (~)-7-inethyldoisynolic acid (XXIX or XXXII A " a "),m. p. 187", is active a t a level of 045y and so equds (-)-" 0: "-bisdehydro-doisynolic acid as the most potent estrogen yet discovered; both theenantiornorphs possess the favourable C,-Et /C,-CO,H : cis-arrangement,but one has the favourable (a)-orientation and the other tho unfavourablc(P)-orientation.If, as is suggested by the available evidence, configurationa t C,, and C,,, corresponding with that present at C, and C, in the naturalsteroid hormones, is important for high oestrogenic activity, then it seemsprobable that the left -hand member of the enantiomorphous pair(XXXII A " a ") will be found to be active at a level of about 0*025y, whilstthe right-hand member will be found to be relatively inactive.(XXXII A " a ".)Reduction of the 7-methyl ether of (+)-doisynolic acid (Vlu or XXXIl A" p " ; left-hand member of the enantiomorphous pair) to the correspondingaldehyde and alcohol leads to decreased activity (threshold doses 4-77 and40-6Oy respectively23).It is not known whether a 7-hydroxyl group isessential for oestrogenic activity ; the synthetic ( &)-" 01 "-7-deoxydoisynolicacid 24 represented by (XLIV) should be active, whilst the isomeric(-+)-7-deoxydoisynolic acid 24 (XLV) may bc expected to be inactive.(XLIV.) /ykJH""t 4 'Polyhydro-analogues of the inarrianolic and doisynolic acids l1ai.e alsobeen prepared ; dehydroisoandrosterone (XLVq and isoandrosteron206 ORGANIC CHEMISTRY.(XLVII) by oxidation with potassium hypoiodite give the polyhydro-marrianolic acids (XLVIII) and (XLIX) which, after conversion into the7 -acetoxydime t hyl esters, hydrolysis to the 7 - hydroxy-2 -met hyl esters, andreacetylation, are converted by the reaction sequence a t C, : -GH,*CO,H --+-CH,*COCl _f -CH,*CHO -+ -Et, into the polyhydrodoisynolic acids(L) and (LI), from which the related acids (LII), (LIII), and (LIV) areobtained.The acids (L-LIV) are all androgenically inactive (comb test),and the acid (L) has also no ceshogenic a~tivity.~80 0KIOI1 \/.:CO,H/i-CH2*C0,H +H(XLVIII.) (XLIX. )(XLVII.)HO(XLVI.), HO HO H HO H(L.) (LIII.) w.1(LII.) (LIV.)Syntheses.-The total synthesis of the bisdehydrodoisynolic acids 39commences with Cleve's acid (LV) which is converted via l-iodo-6-methoxy-naphthalene (LVI) and 6-methoxy-l-(2-bromoethyl)naphthalene (LVII)in six stages into the keto-ester (LVIII) of Bachmann, Cole, and Wilds,l* thecarbonyl group only of which reacts with ethylmagnesium bromide to give in80% yield a mixture of the l-epimeric carbinols (LXa) and (LXb) in which(LXa) largely predominates.An alternative route involving addition ofsodium acetylide in liquid ammonia to (LVIII) gives, in the ratio of about20 : 1, the epimeric carbinols (LIXa) and (LIXb), which are convertedrespectively into (LXa) and ( L X b ) by hydrogenation with platinum inethanol.Iodine in chloroform or, better, 90% formic acid for a few minutes a t100" dehydrates the carbinol (LXa) to a mixture of stereoisomeric olefins38 J. Heer and K. Miescher, Helv. Chint. .4cta, 1947, 30, 786.39 J. Hem, J. It.Billeter, and K. Miegcher, ibid., 1945, 28, 1342SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 207(LXIa) and (LXIB); either pure individual by treatment with 90% formicacid at 100" gives a mixture containing approximately equal amounts ofboth isornerides. The olefins (LXIa) and (LXIb) are hydrolysed bypotassium hydroxide at 160" to the corresponding acids (LXIIa) and (LXIIb),either of which as the sodium salt by hydrogenation with nickel in aqueous-alkaline solution furnishes a mixture of (&)-" a "- and (&)-'' p "-7-methyl-bisdehydrodoisynolic acids (XIc) * and (XIIc); * hydrogenation in thepresence of excess of sodium hydroxide leads to the (-J-)-" u "-acid almostexclusively, whilst in sodium carbonate solution the (-+)-" u "- and (&)-" p "-/CH,Br'?HZ I NH,/\/\ /\A /\AM ~ O I 11 I + JIeol 11 I + HO,SI 11 1 \A/ \A,/ \/\/(LVII.) (LVI.) GV-1L5 t 11 g I%r.I.A --C'(?,Me pp,&3 : I //\/ \fo* ---CGCH // /\JIed 11 \/\/11 6 stitgesI ')I f O H31eo\/\/\/\/ I H H 0(XIC.) (XIIC.) -> (XIIa.) (Xla.)ROH at 'Loo 1 or Iyridine hydrochloride at 1 8i0° +acids are formed in the ratio of 2 : 3.The mixture of acids obtained byhydrogenation in excess of sodium hydroxide solution is dernethylated byenantiomorph in racemates.* In this section a single formula will be used to represent the individual and it208 ORGANIC CHEMISTRY.potassium hydroxide at 200" or by treatment with pyridine hydrochloride at180" t o give, after removal by fractional precipitation of traces of (&)-" p "-bisdehydrodoisynolic acid (XIIa), an 84% yield of (3)-" a "-bisdehydro-doisynolic acid (XIa), the ultra-violet absorption spectrum of which isidentical with that of the (-)-enantiomorph from (+)-equilenin or" O! "-dihydroequilenin and resembles that of (+)-equilenin and ofp-naphthol.The pure racemates (XIc) and (XIIc) have also beendemethylated to (*)-" a "- (XIa) and (*)-" p "-bisdehydrodoisynolic acid(XIIa) respectively ; the reverse transformations are accomplished byesterification with diazomethane, methylation, and hydrolysis of the tertiarycarbomet'hoxy-group with potassium hydroxide at 160".An alternative route proceeds by combined hydrolysis and demethylationof the mixed olefinic methoxy-esters (LXIa) and (LXIb) with ethanolicpotassium hydroxide under pressure a t 200", whereby only a single olefinichydroxy-acid (LXIII) can be isolated.This acid is also the sole product ofcorresponding treatment of a mixture of the olefinic methoxy-acids (LXIIa)and (LXIIb); it is related in respect of configuration to the olefins (LXIb)and (LXIIb), since, by methylation and esterification (diazomethane), theolefinic methoxy-ester (LXIb) is regenerated. Hydrogenation of the acid(LXIII) with nickel in excess of sodium hydroxide gives an 86% yield ofalmost pure (5)'" a "-bisdehydrodoisynolic acid (XIa).(LVII.) (LXIV.) (LXn, LXb.)A simplified synthesis has been described by Anner and Miescher;6-methoxy-l-(2-bromoethyl)naphthalene (LVII) by treatment witha-propionylpropionic ester gives an 80% yield of the keto-ester (LXIV),which in 800/, sulphuric acid a t 0" undergoes an intramolecular additionreaction to give both the epimeric carbinols (LXa) and (LXb) with smallquantities of the corresponding olefins (LXIa) and (LXIb). The reaction isnotable as furnishing principally the primary product of cyclisation ; neitherketonic nor acid hydrolysis of the keto-ester (LXIV) occurs to any appreciableextent.For preparative purposes, the crude cyclisation product isdehydrated and hydrolysed to the acids (LXIIa) and (LXIIb), and themixed acids are reduced with nickel in strongly alkaline solution to givemainly the highly estrogenic ( &)-" 01 "-7-methylbisdehydrodoisynolic acid(XIc) accompanied by a little of the biologically inactive (A)-'' /3 "-7-methyl,The (3)-" a "-bisdehydrodoisynolic acid (XIa) obtained synthetically hasan estrogenic threshold value of 0 - l y by oral administration in rats, i.e., itsactivity is about one-half of that of the (-)-enantiomorph (threshold value0.05y) obtained from (+)-equilenin.It seemed probable that almost thewhole activity of the racemic mixture is dire to the (-)-enantiomorph ; this,acid (XIIC)SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 200has been shown to be so by resolution of the synthetic product.27 (A)-'' a "-7-Methylbisdehydrodoisynolyl chloride 31 is converted by being heated withL-menthol a t 100-110" in nitrogen into the L-menthyl esters, the solubilitiesof which in acetone differ by a factor of 20. The (+)- and the (-)-L-menthylesters are hydrolysed by n-propyl-alcoholic potassium hydroxide at 170" and155" respectively without racemisation ; the (-)-" a "-7-methylbisdehydro-doisynolic acid so obtained is identical with the 7-methyl compound (XIc)from ( +)-equilenin. Demethylation of the (+)- and (-)-" ct "-7-methyl-bisdehydrodoisynolic acids with hot hydrobromic-acetic acid gives the( +)- and (-)-" a "-bisdehydrodoisynolic acids, of which the latter is identicalwith the acid (XIa) from natural (+)-equilenin.By using the route [LVII + LVIII --+ LX + (XIa + XIIa)], andcombining the modified keto-esters (LXV; R2 = Me, Et, Pr"; cf.XVII)with alkylmagnesium bromides (R1 = Me, Et), Heer and Miescher 29 havesynthesised various homologues, (LXVI) and (LXVII), of the (&-)-" a "- and" P "-bisdehydrodoisynolic acids.The lower homologues (LXVIII), inwhich there is no substituent a t the 1-position so that the " a "- and" p "-series coalesce, are obtained by Clemmensen reduction of the keto-esters (LXV), hydrolysis, and demethylation.R2Zn-Hg, HCl, etc. ___, //\/\/(LXV.) (LXVIII.)MeOl 11 I (3 stages)\/\/R'MgBr, eta.(5 stages)R2 = H or Me(LXVI.) (LXVII.)R1= = Me or Et; R1= Et, R2 = PraSimilarly, by use of the simplified route [LVII + LXIV --+ LX ---+(XIa + XIIa)], Anner and Miescher, employing ethyl acetoacetate, obtainedthe keto-ester (LXIX; R1 = Me), which undergoes cyclisation withsimultaneous hydrolysis to give the acid (LXXI), although some isdehydrogenated to the phenanthrenecarboxylic ester (LXX) ; the acid(LXXI) by reduction in strongly alkaline solution gives a single acid(LXXII ; R = Me) demethylated to yield the (5)-bisnorbisdehydrodoisynolicacid (LXXII ; R = H).A further variant used by Anner and Miescher 33utilises the keto-esters (LXIX), which, after introduction of the " angular "methyl group, are treated with alkyl- or aryl-magnesium bromides to yieldcarbinols (LXXIII) ; these by cyclisation give directly (&)-l : 1-disubstituted7 -met hylbisdehydrodoisynolic acids (LXXIV) 210 ORGANIC CHEMISTRY,Miescher and Anner also describe the preparation from 1-(2-bromo-ethy1)naphthalene (LXXV) of a single ( 5 ) -7-deoxybisdehydrodoisynolic acid(LXXVI) thought to belong to the " a "-series, and, from m-methoxyphenyl-bromide (LXXVII), of two stereoisomeric ( &)-tetrahydronaphthalene-carboxylic acids represented by (LXXVIII) .The (A)-" a "- and (-J-)-"p' "-monodehydrodoisynolic acids (XXVIII,LXXXI; R = H) have been synthesised by Anner and Miescher; 28 theketo-ester 26 (LXXIX) with ethylmagnesium iodide gives a single olefin(LXXX; R = Me), also obtained by dehydration of the carbinol(LXXXII) ; the olefin by hydrogenation with nickel in an alkaline mediumyields the highly estrogenic (&)-" a "- (XXVIII ; R = Me) and relativelyinactive (A)-'' p "-7-methylmonodehydrodoisynolic acid (LXXXI ; R = Me) ;these are demethylated by pyridine hydrochloride at 170" to the respectivehydroxy-acids (XXVIII, LXXXI; R = H).Hexahydrophenant hrene compounds with an unsaturated side chain arefound to pass very readily into tetrahydrophenanfhrene derivatives withmigration of the extracyclic double bond into the ring system.Thus theketo-ester (LXXIX) with ethylmagnesium bromide gives not only thSHOPPEE : STEROIDS AND RELATED COMPOUNDS. 21 1carbinol (LXXXII) [also obtained from (LXXIX) by addition of acetyleneand reduction of the resulting ethinyl compound] and the olefin (LXXX;R = Me), but also themethyl esters of both (-+)-" a "- and (&)-" c3 "-7-methyl-bisdehydrodoisynolic acids (XIb) and (XIIb). Attempts to dehydrate thecarbinol (LXXXII) invariably involve migration of the resulting unsaturatedlinkage, and the rearranged compound may form the main product ; thus thecarbinol (LXXXII) and the olefin (LXXX; R = Me) by treatment witha trace of iodine in boiling chloroform solution give exclusively (afteralkaline hydrolysis) (&)-" a "- and (-J-)-" p "-7-methylbisdehydrodoisynolicacids (XIc) and (XIIc). Similarly, although demethylation of the methoxy-olefin (LXXX; R = Me) with pyridine hydrochloride a t 170" gives thehydroxy-olefin (LXXX; R = H) without rearrangement of the extracyclicunsaturated linkage, alkaline hydrolysis a t 170" induces isomeric change togive mainly (&)-" a "-bisdehydrodoisynolic acid (XIa).The acid, m. p.218", obtained in this way by Hunter and Hogg40 is probably a mixture of(&)-" a "- (m. p. 204") and (*)-" p "-bisdehydrodoisynolic acid (m. p. 238").(LXXXII.) (XI-) (LXXXIII.)Catalytic reduction of the 11 : 12-double bond in (LXXXI) is difficultbut proceeds by means of palladium-acetic acid to give a non-crystallinemixture of stereoisomeric acids (LXXXIII; R = Me) together with some(&)-" a "-7-methylbishydrodoisynolic acid (XI ; R = Me) ; the amorphousmixture of doisynolic acids (LXXXIII ; R = H) obtained by demethylationis highly estrogenic, but this activity may be due to contamination by smallamounts of (&)-" a "-bisdehydrodoisynolic acid (XI ; R = H).The synthesisof (LXXXIII; R = H) by hydrogenation of the olefin (LXXX; R = Me)and subsequent complete hydrolysis has also been reported by Hunter andHogg; 4o the high estrogenic activity of their amorphous product couldsimilarly be due to the presence of (j-)-" a "-bisdehydrodoisynolic acid (XT).'O J.H. Hunter and J. A. Hogg, J . Arner. Chenz. SOC., 1946, 68, 1676212 ORGANIC CHEMISTRY.Reduction of the 11 : 12-double bond of the methyl ester of (&)-" a "-7-methylmonodehydrodoisynolic acid (XXVIII) with sodium in ethanol-liquid ammonia a t - 40" leads, after hydrolysis of the neutral reactionproduct with potassium hydroxide at 170", to the intensely estrogenic(&)-" a "-7-methyldoisynolic acid (XXIX), m. p. 187", and the less active(&)-'' p "-7-methyldoisynolic acid, m. p. 213" (XXX) : 24(XXVIII.) (XXIX .) (XXX.)These acids are also obtained, inter alia, when the crystalline (&)-7-methoxy-keto-esters (XXXI A, B, and C) are converted into (&)-7-methyldoisynolicacids (XXXII) by the following route, (XXIX) being identical with(XXXII A " a ") and (XXX) with-(XXXII R " a ") : 24(XXXI A, B, and C.)I,,,,(,~=cHM~ A ' - - C O , H -+ lT,,Pt1(XXXII ,4 " a " , m.p. 1X7".)(XXXII A " fly', m. p. 217".)(XXXII B " a " , m. p. 213'.)(XXXIIC " a " , m. p. 179'.)(XXXII C '* p", m. p. IW".)Reduction of ( &)-" a "-7-methylmonodehydrodoisynolic acid (XXVIII)with Rupe nickel a t 80"/15 atms. in presence of sodium hydroxide leads toloss of the methoxyl group with production of (&)-'' a "-7-deoxydoisynolicacid (XLIV) ; 24 under the same conditions the methyl ether of " natural "( +)-doisynolic acid gives a (+)-7-deoxydoisynolic acid (XLV).= Moredrastic conditions (Rupe nickel a t 110"/48 atms.; absence of alkali)dehydrogenate (XXVIII) to (&)-" a "-7-methylbisdehydrodoisynolic acid6-Methoxy- 1 - (2-bromoethy1)naphthalene (LVII) by condensation withthe potassium derivative of ethyl cyclopentan-%one- or cyclohexan-%one-1 -carboxylate gives the keto-esters (LXXXIV) and (LXXXV), which hgcyclo-dehydration in ether with 80% sulphuric acid at - lo", hydrolysis,and subsequent hydrogenation with platinum in acetic acid, give respectively( rf)-l : 2-cyclopentano- and -1 : 2-cyclohexano-7-methylbisdehydrodoisynolic(XI) .SHOPPEE : STEROIDS AND REIJATED COhIPOUNDS.213acids (XXXV) and (XXXVI) ; hydrolysis with aqueous-methanolicpotassium hydroxide a t 210" gives the corresponding hydroxy-acids.mCO,Xti C0,Et CO,Ho='- '1 f\il SO% H,SO,at - loo -- + Me01 II I \V\/(XXXV.)COzEt(LXXXV.) (XXXVI.)A single ( -+)-B-normonodehydrodoisynolic acid (XXXIX or XL) hasobtained35 by application of the method of Heer, Billeter, andMiescher 39 to methyl 1-keto-7-methoxy-2-methyl-1 : 2 : 3 : 4-tetrahydro-fluorene-2-carboxylate (LXXXVI), which was synthesised from ethylm-met hoxyphenylmet hylmalonat e and the ethyl ester-chloride of glutaricacid.35 The lower homologue (XXXIX or XL wit'h Me for Et) has alsobeen prepared.(LXXXVI,) (XXXIS.) (XL.)Proin 6-methoxy-1 -chloromethylnaphthalene (LXXXVII) Billeter andMiescher a have obtained the pair of stereoisomeric ( +) -P-norbisdehydro-doisynolic acids represented by (XXXVTU).H,CI(LXXXVII.) (LXXXVIII.) (LXXXIX.)(XC.) (XCI.) (XXXVIII.)The ketone (LXXXVIII) from (LXXXVII) gave the glyoxylate(LXXXIX), but this could not be caused to lose carbon monoxide214 ORGANIC CHEMTSTRY,Condensation of (LXXXVII) with methyl a-propionylpropionate yielded(XC), cyclised by sulphuric acid with simultaneous dehydration to twostereoisomeric olefins (XCI) ; hydrolysis, reduction, and demethylation ofthese gave respectively the two (A) -C-norbisdehydrodoisynolic acidsrepresented by (XXXVIII). The same pair of olefins (XCI) have alsobeen prepared from l-keto-7-methoxy-1 : 2 : 3 : 4-tetrahydrophenantlirene(XCII) ; 149 4 1 ring fission of this cannot be achieved with hypoiodite,permanganate, or chromium trioxide, but is smoothly accoinplished byconversion into the hydroxymethylene compound (XCIII) and oxidation ofthis with alkaline hydrogen peroxide.The resulting acid as the dimethylester (XCIV) by the Dieckmann reaction gives the keto-ester (XCV). Acidhydrolysis of this gives the ketone (LXXXVIII) from which the keto-ester(XCV) can be regenerated by condensation with methyl carbonate.42Angular methylation of (XCV) yields the keto-ester (XCVI) from which bythe use of ethylmagnesium bromide, or, better, by condensation with sodiumacetylide in liquid ammonia a t - 60" and hydrogenation with platinum, thecarbinol (XCVII) is obtained. Dehydration of (XCVII) with hot 90%formic acid gives the two stereoisomeric olefins (XCI).(XCII.) (XCIII.) / (XCIV.)Coumarones analogous to C-norbisdehydrodoisynolic acid (XCVII) havebeen synthesised ; 43 2-( 1 -hydroxynaphthyl) ethyl ketone condenses withethyl a-bromopropionate to give the ester (XCVIII) which during distillationpasses into the ketone (XCIX); this is cleaved by hot alcoholic potassiumhydroxide to yield the olefin (C) which does not yet appear to have beenreduced to the acid (CI)./\ J+gY2" \/id0~-~-CO,Et I1 ' y = C H M e o--I- CO,H-CHMe ?--[A_j ,\,==I -+ -+ ( I 1 I H/\A,/ -I \/\/(XCIX.) (C.1 (CI.1I II I\A/(XCVIII.)A. Butenandt and G. Schramm, Ber., 1935, 68, 2083; G. Huberland, ibid., 1937,70, 169.42 N. A. Preobrajenski, N. N. Schtschukina, and R. A. Lapina, ibid., 1936,69, 161.5.43 D. Molko and C. Mentzer, Compt. rend., 1946,223, 333SHOPPEE : STEROIDS AND RELATED COMPOUNDS. 215The phenanthrene-1 : 2-dicarboxylic acid anhydrides (CII, CIII, CIV ;ft = H) were stated 44 to possess some degree of estrogenic activity, but thisclaim was later withdrawn ; 45 (CIV ; R = H) wa,s also found to be inactiveby Cohen and Warren.46 The methoxy-anhydrides (CII, CIII, CIV ;R = OMe) and the hydroxy-anhydride (CIV; R = OH) have now beenprepared and all found to be inactive a t a level of 1 mg. by subcutaneousapplication in the Allen-Doisy test in r a t ~ . ~ 1/v\(CII.) (CIII.) (CIV.)(+)-Dimethylethylallenolic acid (XLIII; R = H, R1 = R2 = Me,R3 = Et), which exhibits intense estrogenic activity and bears a formalresemblance to C-norbisdehydrodoisynolic acid (XCVII), is prepared from2-cyano-6-methoxynaphthalene (CV) which by the Reformatsky reactionwith ethyl a-bromoisobutyrate (1 mol.) gives the keto-ester (CVI), convertedby ethylmagnesium bromide into the carbinol-ester (CVIII), also obtaineddirectly from 2-(6-methoxynaphthyl) ethyl ketone (CVII) by theReformatsky reaction. Dehydration of (CVIII) furnishes the olefin (CIX),which by hydrogenation and subsequent hydrolysis gives the methyl etherof (&)-dimethylethylaIlenoIic acid (XLIII; R = R1 = R2 = Me, R3 = Et),demethylated by hot pyridine hydrochloride to the free hydroxy-acid.By suitable modification of this procedure methyl ethers of homologous(&)-allenolic acids (XLIII ; R1= R2 = Me, R3 = H ; R1= R2 = R3 = Me ;and R1 = H, R2 = Me, R3 = Et) are obtained3'/\ - m d I( 1 I___,>1ed C:Me,Br*('O,Et \,A/WV.) (CVI.) (XLIII.)EtMgBr(CIX.)/\/\- I, I COEt Meo4A//(CVII.) (CVIII.)On account of the intense estrogenic activity of the doisynolic acids,carboxylic acids of the cxp-diethylstilbene series have been prepared.474 4 L. F. Fieser and E. B. Herschberg, J. Arner. Chern. SOC., 1936, 57, 1508, 1867.4 5 Idem, ibid., 1936, 58, 2315.4 7 R,. Neher and K. Miescher, HeLv. Chim. Acta, 1946, 29, 449.46 J., 1937, 1315216 ORGANIC CHEMISTRY.The acid (CX; R1 = R2 = Et), regarded as the truns-form, possesses someactivity [threshold value 10-20 y (subcutaneous), 20-30 y (oral)]. Varioushomologues of (CX) [R1 = R2 = H (cis- and trans-forms), Me, or Pr";R1 = H, R2 = E t ; R1= Et, R2 = HI have been synthesised; thedi-n-propyl acid exhibits slight activity ; the dimethyl acid is inactive, butits methyl ester shows a weak but protracted action. The m-isomeride of(CX ; R1 = R2 = Et) and the triphenylethylene analogue (CXI) arep -HO C6H4*CR1~CR2*C6H ,*C02H ( p ) ( CX . )(p-MeO~C6H,-)2C~CR~C6H4*C02H ( p ) (CXI.)completely inactive. Replacement of a p-hydroxyl group by a carboxylgroup thus leads to aconsiderable decrease in estrogenic potency.c. w. s.W. BAKER.N. CAMPBELL.S. H. HARPER.D. H. HEY.C. W. SHOPPEE.F. SMITH

ISSN:0365-6217    

DOI:10.1039/AR9474400082

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

BIOCHEMISTRY.1. INTRODUCTION.?'HE recent practice has again been adhered to of selecting topics which byvirtue of their importance and interest are suitable for review in thebiochemistry section. An eye has also been kept upon the now numerousreview publications so that the same subject matter is not included here;rather has the aim been to bring forward subjects which have been ill-servedin the matter of review notwithstanding their intrinsic importance for thescience of biochemistry. C. R.2. ENZYMIC in vitro SYNTHESES OF NATURAL GLYCOSIDIC DERIVATIVES.The object of this Report is to summarise the state of our presentinformation on the biological mechanisms for synthesising glycosidic links.I t is in part a continuation of previous Reports 1 and in part a review ofsome of the numerous gaps in our knowledge, It seems now more logicalto deal initially with the synthesis of a single link and from that point toproceed to the production of polysaccharides, than to adopt a strictlyhistorical approach.The mechanisms all appear to belong to a common typewhere the energy associated with a preformed glycosidic link is used to forma new link by exchange of the originally substituting radical with a new one.The process may be termed generally, " transglycosidation ". There areapparently three known types, (1) a reversible reaction concerned with amonosaccharide-1 phosphate, e.g., syntheses of amylose and sucrose (andalso of inosine and guanosine) :\(/H---0-d?/ \OR + H,PO,A 7 - - - O \ w H -h/ \O*PO,H, -4- H0.RI(2) an irreversible transglycosidation through sucrose, e.g., syntheses ofbacterial levans and dextrans ; (3) the in vitro reversible mechanism wherethe fructofuranose radical of sucrose undergoes an exchange reaction withanother ketose .2The Initiation of Gluco- and Fructo-polysaccharide Syntheses.-It is nowevident that the natural hexoses glucose and fructose, and probably mannoseas well, are relatively metabolically inert in the tissues of animals, andprobably also in the green plants.This is not necessarily so among micro-organisms, which often possess powerful zrobic systems for sugar oxidation.Glucose, fructose, and inannose can, however, be brought into the metabolicAnn. Reports, 1940, 415; 1941, 167; 1942, 232; 1944,230; 1946, 189.W.Z. Hassid, M. Doudoroff, H. A. Barker, and W. H. Dore, J . Amer. Chem. Soc.,1945, 67, 1394; 1946, 68, 1465; 3T. Doiidoroff, H. A. Barker, and W. Z. Hassid,J . Biol. Chem., 1947, 168, 72521 8 BIOCHEMISTRY.Bll1.T~ : SYNTHESES OF NATURAT, GLYCOSIDTC DRRTVATTVES. 219scheine through the intervention of adenosine triphosphate (AI’P) and thewidely distributed hexokinases, as represented in the following diagram :Amylose,Amylopectin,Glycogen,+H,PO,*u.-Glucose-1 ~phosphate ---/I;!II ,I 1I ,I I ,FructoseIiGLUCOSE FRUCTOSE$- ATP $- ATPJ, tierotitlose 1 RwokinuscGlucose-6 ..I Fructofuranose-Aphosphate -- phosphate 11 (Glycolysis)2 Pyruvate + [4H] Fatty acids’I I (oxidation thO2Lgh tricarboxylic acid cycle)Amino-acids !i i;.< ;xXtrsSucroseG. T. Cori and M. W. Slein consider that yeast hexokinase will catalyse thephosphorylation of glucose, fructose, and mannose, but these authors haveproduced evidence that, in mammalian tissues, separate enzymes are requiredfor each sugar.Hexokinase Inhibition : the Functions of Insulin and Adrenaline.-Workersin the laboratories of C. F. Cori and F. G. Young have produced evidencethat the anterior pituitary elaborates an unstable substance which, if addedin vitro to the system glucose-ATP-hexokinase, inhibits the phosphatetransfer. When insulin is added to the inhibited system the hindrance toglucose phosphorylation is removed. If we assume that such reactions occurin vivo, then we have a logical explanation for the elevated blood-glucoselevels found in insulin-deficient animals, the tissues of which will experiencedifficulty in abstracting glucose from the circulation.In confirmation of this hypothesis, J.A. Cohen has recently shown thatanaxobic diaphragm muscle of rats previously injected with adrenaline,utilised less glucose than controls from uninjected animals. Afterhypophysectomy, on the other hand, adrenaline injection did not lead tolessened glucose utilisation.J. A. Cohen and D. M. Needham 56 have also been able to demonstrate ndecreased anaerobic glycolysis in extracts of rat skeletal muscle subsequent toinjection of the animals with adrenaline. These authors are not yet preparedto say whether this decreased utilisation is in fact due to hexokinaseFed. Proc., 1947, 6 , 245.S.Colowick, C. F. Cori, and M. W. Slein, J . Biol. Chern., 1947, 168, 583; E. Reid,It. H. Smith, and F. G. Young, Biochem. SOC. Proc., 1948, 42, XIX.5a Nature, 1947, 160, 87 1.5b Bioch.em. Xoc. Proc., 1948, 42, XXI220 BTOCHEMISTRY.inhibition ; nevertheless it affords strong evidence that the pituitary isinvolved in a " chemical reffex " mechanism.Nucleotide Synthesis.-H. M. Kalcka'r has demonstrated, in the cases ofguanosine and inosine, that the following reversible enzymic reaction can takeplace under the influence of liver nucleosidase :Hypoxanthine 1 Inosineor + " Ribose-1 Phosphate " + or + H3PO4Guanine 1 GuanosineThe constitution of the presumed " Ribose-1 phosphate ", in which thesugar radical might be expected to possess the furanose configuration is asyet unknown.This synthesis of nitrogen glycosides differs from thesynthesis of oxygen glycosides (Le., sucrose, glycogen, and the starchcomponents) in that a derivative having the P-configuration (as far as isknown) is formed.have produced evidence that tissueextracts phosphorolysing nucleotides can convert some of the intermediary" ribose-1 phosphate " into glucose-6 phosphate. This seems of interest inconnection with the biological origin of D-ribose. The only known naturalmonosaccharides having a similar configuration of three D- adjacent hydroxylgroups are : D-allulose isolated from sugar-cane molasses by F. W. Zerbanand L. Sattler,sa and D-altroheptulose *b from Sedum.Sucrose Synthesis by Bacterial Phosphorylase.-It is now well establishedthat phosphorylase from Pseudomonas saccharophik catalyses the reversiblereaction :Natural fructofuranosides are, however, p.F.Schlenk and M. J. Waldvogela-D-glucose-1 phosphate + D-fructose (in solution) sucrose + H,P04It is obvious that fructose in solution must exist to an appreciable extent inthe furanose form. Further work on the enzyme has revealed certainremarkable facts. First, while the enzyme is specific for the a-glucose-1phosphate component, certain other ketoses have been found to be able totake part in the reaction, e.g., L-sorbose, L-ketoarabinose,ll u-ketoxylose.10By this means two new disaccharide analogues of sucrose have been formed.A further remarkable enzymic condensation has been performed, this timebetween a-glucose-1 phosphate and L-arabinose, an aldose sugar.ll Thedisaccharide has been shown l1 to have the structure 3-a-~-glucosido-L-arabinose. The authors concerned in the above series of investigationsFed. Proc., 1945, 4, 248; Nutwe, 1947, 160, 143, J .Biol. Chem., 1947, 167, 477;S. Colowick and W. H. Price, Fed. Proc., 1946, 5, 130.7 Arch. Biochevc., 1946, 9, 455; Fed. Proc., 1947, 6, 288.* ( a ) J . Amer. Chenz. Soc., 1942, 64, 1740; ( b ) F. B. LaForge and C. S. Hudson,J . Biol. Chem., 1917, 30, 61.9 M. Doudoroff, N. Kaplan, and W. Z . Hassid, ibicl., 1943, 148, 67; M. Doudoroff,ibid., 1943, 151, 351; W. Z. Hassid, Ji. Doudoroff, and H. A. Barker, J .Amer. Chern.SOC., 1944,66, 1416.10 W. Z. Hassid, 31. Doudoroff, H. A. Barker, and W. H. Dore, ibid., 1945, 87, 1394;1946, 88, 1465.11 11. Doudoroff, W. Z . Hasaid, and 1%. A . Barker, J . Biol. Cheni., 1947,168, 733BELL : SYNTHESES OF NATURAL GLYCOSIDIC DERIVATIVES. 221have also succeeded in effecting what they term " transglycosidation "between sucrose itself and sucrose analogues and free ketose sugars, in theabsence of phosphate,l2 e.g.D -glucosido-D-fructofuranoside + L-sorbose +=~~-g~ucosido-~-ketoxyloside + D-fructose +D-glucosido-L-sorbofuranoside + wfructoae.D -glucosido -D -fructofuranoside + D -ketoxylose.A process of transglycosidation which requires no phosphate has alreadybeen suspected from work on cell-free bacterial enzymes which produce levansand dextrans from sucrose (Fee below).So far, it must be emphasised, wehave no evidence for the mechanism used for the synthesis of sucrose inplants.Bacterial Levans and Dextrans.12(1--It has long been known that theso-called " viscous fermentations " and allied phenomena are caused by theproduction of polysaccharides by a large variety of micro-organisms actingon sucrose (and sometimes raffinose). The polysaccharides are of twodistinct types : destrans, whose characteristic radical is 1 : &linked~-D-g~UCOpyraIlOSy~, and levans, based on 2 : &linked u-fructofuranosylradicals. E. J. Hehre and G . Y. Sugg 13 were the first to demonstrate thoproduction of such polysaccharides, using cell-free enzyme preparations.M. Stacey l4 has likewise obtained dextran formation using a cell-freeexocellular enzyme.On the levan side of the problem S. Hestrin,S. Aveniri-Shapiro, and these authors with M. Aschner l5 have made anTABLE I.GlucoseDextran- Products from liydrolysed radicals informing methylated dextran unit chainsorganism. (mols., approx.). (nvera ge) . ,iutiiors.2 : 3 : 4 : 6.Me4 glucose (1 mol.) L e ttconostoc 550 S. Peat, E. Schluchterer,dextranicwn 2 : 3 : 4-Xe3 glucose (ca. 500 and 31. Stacey I6mols.)Me, glucose (ca. 40 mols.)2 : 3 : 4 : 6-RIe4 glucose ( 1 mol.)2 : 3 : 4-Me3 glucose (3 mols.)2 : 3-Me2 glucose (1 mol.)Leitconostoc 6 I. Levi, IV. L. Hawkins,and H. Hibbert l? iuesenteroidesBetabacterium 2 : 3 : 4 : 6-Me4 glucose ( 1 mol.) 25 W.D. Daker and M.Betacoccus W. Z. Hassid and H. A.uermiformd 2 : 3 : 4-Me3 glucose (24 mols.) Staceyarabinoszis2 : 3 : 4 : 6-Me4 glucose ( 1 mol.)2 : 3 : 4-Me3 glucose (24 mols.)Me2 glucose (1 mol.)26Barker lol2 31. Doidoroff, H. A. Barker, and W. %. Hasaid, J. Biol. C'hent., 1947, 168, 725.lBCl T. H. Evans and I€. Hibbert, Adu. Carbohydrate Chem., 1946, 2, 203.l 3 S c i p r i v r , 1941, 93, 237; J. Exp. -Wed., 1943, 75, 339.l h J., 1939. 581.l 8 J., 1939, 585.I J -Yotiire, 1943, 149, 63;). * j LZioc./,e,//. J . , 1943, 37, 450; 1944, N, 2.l 7 J . Aluer.. Chem. Soc., 1942, 64, 2959.l9 J. Biol. Chem., 1940, 134, 163222 BIOCHEMISTRY.exhaustive study of the formation of this type of fructosan and have shownthat phosphate plays no part in the reaction.So far the enzyme, called bythe authors " levan-sucrase " has been shown to work only in the syntheticdirection.Unfortunately no structural studies have yet been reported on these" synthetic " polysaccharides. As regards the dextrans, using the large-scale end-group assay methods the Birmingham School, and others, haveshown that, chemically speaking, a variety of dextrans, formed by the wholemicro-organisms, can exist (see Table I).It is therefore evident that branching of the dextran chain by means of aglycosidic link other than between 1 and 6 can take place. Presumablydifferent enzymes may be required to generate the different links. Thatthis 1 : 6-glucose linkage is not confined to bacterial polysaccharides is ofcourse well known in the instance of gentiobiose, and W.Z. Hassid20 hasisolated from barley roots a 1 : 6-linked glucose polysaccharide.A number of bacterial levans have been studied, e.g., by R. R. Lyne,S. Peat, and M. Stacey.21 Although differences in physical properties werenoted between different specimens, no evidence was reported of definitedetection of " branching " points ( i e . , di- or mono-methyl fructoses) amongthe hydrolysis products of the methylated polysaccharides. It seemshowever likely that such branching does occur since bacterial levans behaveas large molecules, although the length of the unit chains of 2 : 6-linkedD-fructofuranoside radicals is 11-12.Here again, although the unitchain is of the order of 12 radicals in length, no evidence is as yet availableas to whether or not it may be branched.References occur so often in theliterature to the alleged presence of glucose radicals in plant fructosans thatthey may well be an expression of fact. (A useful summary has beenprovided by H. K.. Ar~hbold.~~) All the known non-reducing tri- andtetra-saccharides+ .g . , gentianose, raffinose, melizit ose, and st achyose-can be represented as derived from sucrose. It appears to the Reporter thatsuch a formulation could also be possible for fructosans. Relatively smallamounts of glucose can now be easily separated from fructose.24Starch and i t s corn~onents.~~ There is now no doubt that native starchcontains two distinct components , the presumably unbranched amylose andthe branched amylopectin. Among the starches of the " waxy " cerealsthe proportion of the amylose fraction appears to be negligible.On theother hand, S. Peat, E. J. Bourne, and M. J. Nicholls25u have found thatstarch isolated from a variety of " wrinkled " pea consists of 98% of theninylose component. So far as chemical investigations have gone, it ispossible by the ordinary methylation technique to determine (a) whetherAn analogous levan is found in grasses.222o J . Amer. Chem. SOC., 1939,61, 1223.22 S. W. Challinor, W. N. Haworth, and E. L. Hirst, J . , 1934, 1560; W. N. Haworth,23 New Phytologist, 1940, 39, 186.z5 S. Peat, Ann. Rev. Biochem., 1946,15, 75,21 J . , 1940, 237.€3. L. Hirst, andR. R. Lyne, Biochena. J . , 1937,31, 786.24 D.J. Bell, J., 1947, 1461.25a Nature, 1948, 161, 207BELL : SYNTHESES OF NATURAL GLYCOSIDIC DERIVATIVES. 223end-groups exist ( b ) whether there are branch-points (manifested bydimethyl glucose appearing among the products of hydrolysis of themethylated polysaccharide), and (c) the average length of the unit chain.The Reporter believes that the term “ unit chain ” is a better descriptionof a chain of radicals possessing a common type of linkage (in this case1 : 4-cc) than “ repeating unit ” which seems to infer regularity in respect tochain length. There is no evidence in favour of such a regularity.Since C. S. Hanes 26 first demonstrated the synthetic action of vegetablephosphorylases on or-glucose-1 phosphate, it has become apparent that thephosphorylases acting alone produce a long unbranched 1 : 4-a-linkedpolysaccharide, in so far as revealed by present analytical methods,27 whilephosphorylase .acting in conjunction with another catalyst (or catalysts)produces a branched polysaccharide with unit chains of 1 : 4-a-linked radicalsof much shorter (ca. 24-20) average length.28 An analogous mechanismhas been found for the synthesis of polysaccharide in muscle (see below).The “ fine structures ” of amylopectins from both natural and syntheticsources have been to some extent successfully compared. The averageTABLE 11..Hydrolysed bymaltogenicSource of amylopectin. Chain length. amylase, %.Maize .................................... 27 4560 * - ,, ....................................- ,) .................................... 19Waxy maize ...........................20Potato .................................... 25 54-- ,, ................................. 23-24,, .................................... 20-23 -Synthetic .............................. 20 46Sago .................................... 1sBanana ................................. 21Sweet potato ........................... 27Arrowroot .............................. 2 3Pearl manioc ........................... 20Tapioca ................................. 20Rice ....................................... 20Wheat .................................... 20-____-__I-* Residual dextrin had chain length - 12.Ref.29, 3034333331323328333333333333333326 Proc.Boy. SOC., 1940, B., 128, 421.2 7 W. N. Haworth, R. L. Heath, and S. Peat, J., 1942, 55; W. Z. Hassid and2 a W. N. Haworth, S. Peat, and E. J. Bourne, Nuture, 1944,154, 236; E. J. Bourne29 K. H. Jleyer, Nuticrwiss., 1940, 28, 564.30 K. H. Meyer, M. Wertheim, andP. Bernfeld, Helv. Chim. Acta, 1940,23, 866.31 W. Z. Hassid and R. M. McCready, J. Amer. Chem. SOC.. 1943, 65, 1157.34 K. Hess and B. Krajnc, Ber., 1940,73, 970.33 F. Brown, S. Dunstan, T. G . Halsall, E. L. Hirst, and J. K. N. Jones, S u t u r e ,34 R. H. Meyer, M. Wertheim, and P. Bernfeld, Helv. Chim. Acta, 1941,24, 212.R. 31. McCready, J. Anzer. Ghem. Soc., 1941, 63, 2171.and S. Peat, J., 1945, 877 ; E. J. Bourne, a. Macey, and S.Peat, J., 1945, 882.1945, 156, 785 ; T. G. Halsall, E. L. Hirst, and J . K. K. Jones, J . , 1947, 1399224 BIOCHEMISTRY.lengths of the unit chains are of the same order, and the branch points mustoccur a t closely similar positions in the unit chains, as shown by the actionof the maltogenic (“ (3 ”) amylase which hydrolyses 50% of the unit chainlength to maltose. It is useful to compare the results so far obtained bydifferent workers on the action of maltogenic amylases on differentamylopectins of known chain length (Table 11).The above results indicate that (a) there may be small but significantdifferences in the chain lengths of different specimens of amylopectin, and( b ) there may be differences in the position of the branch points. Thesepossibilities, however, depend on the accuracy of the methods employed ;in the degradations by maltogenic amylases there is the difficulty of preparingthe active enzyme free from other amylases.There is no doubt that the twomain types of amylase, maltogenic (“ p ”) and dextrinogenic (“ a ”) maywell, according to their origins, possess differing actions on their substrate^,^^and may also be associated with glycosidases of various types in t’he form ofinseparable impurities. These questions have been exhaustively consideredby R. H. Hopkins.36The structure of the interchain linkage in some natural amylopectins isstill in some doubt, and as it has considerable bearing upon the nature ofsynthetic amylopectins, it will now be considered in some detail.C.C. Barker, E. L. Hirst, and G. T. Young 37 gained conclusive evidence thatin fully methylated disaggregated rice starch the great majority of dimethylglucose radicals (the “ branch-point radical ”) were methylated in positions2 and 3, indicating a 1 : 6 inter-chain link. By a different analyticaltechnique, K. Freudenberg and H. Boppe13* had obtained like evidence ofsuch a 1 : 6-linkage. By the action of acid and of malt dextrinogenicamylase on maize starch K. Myrback and his collaborators 39 have obtainedproducts which after methylation and hydrolysis were shown to contain ana-1 : 6-link. A preliminary communication from E. M. Montgomery,F. B. Weakley, and G. E. Hilbert 4O reports that treatment of waxy maizestarch (i.e., almost entirely amylopectin) by a preparation of amylase fromAspergillus oryxce leads to the isolation of an a-1 : 6-linked disaccharide inrather more than one-quarter of the yield expected if either ( a ) 1 : 6-linkageswere totally unattacked by the enzyme used, or ( b ) the inter-chain linkageswere all of the 1 : 6-type and were also unattacked.A recent communicationfrom E. L. Hirst’s laboratory should, however, be noted.41Table I11 compares the chain lengths of natural and synthetic amyloseSwith their hydrolysis limits by maltogenic amylase.35 S. Rodfern and Q. Landis, Cereal Chew., 1046, 23, 1 ; C. S. Hnnes iind 11. Cattle,36 Adv. Enzymol., 1946, 6, 389.37 Nature, 1941, 147, 296.38 Ber., 1940, 73, 609.39 K. Myrback and B. Ortenblad, Biochena.Z., 1941, 30’1, 69; I(. Ahlhorg andI’YOC. ROY. SOC., 1938, B, 125, 387.K. Jlyrbiick, ibid., 1941,308, 187 ; K. Myrback and K. Ahlborg, ibid., 1042,311, 31 3.J . Amer. Chena. Soc., 1947, 69, 2240.4l T. G. Halsall, E. L. Hirst, J. K. N. Jones, and A. ltoudier, Nuttire, 1947,160, 900HELP, : SYNTHESES OF NATURAL crxcosmIc DERIVATIVES. 225TABLE 111.Chain length,Source of polysaccharide. approx.Potato ............................................. 230-25031 aim ............................................. 300Synthet<ic (plant phosphorylase) ............ 80-90,, ............................................. 300-400Synthetic (muscle phosphorylase) ......... 200Hydrolysed bymaltogenicamylase, yo. Ref.99-6 32, 28100 31- 30100 28100 42GZycogen.-Glycogens isolated from a wide variety of animal tissues, bothvertebrate and invertebrate, belong to the branched type of polysaccharide.As in amylose and amylopectin, 1 : 4-a-linked.glucosyl radicals form thebasis of the unit chains. On the other hand the ground plan of thestructure of glycogen appears somewhat different. The average lengthof the unit chains is of the order 12 or occasionally. 18 radicals, andmaltogenic amylase is said to hydrolyse some 50% of the chain. The inter-chain link must therefore be situated at a mean distance of approximatelynot less than 6 radicals from the end of the chains, whereas in amylopectinthis link is situated at about 10-12 radicals from the ends. It is regrettablethat so far only one example of degradation of a glycogen of known chainlength has been rep0rted.~3When examined on the ultracentrifuge, glycogen specimens are alwayspolydisperse.It is therefore not possible to calculate reliable molecularweights from data other than direct determinations of the mean mass of themolecuies composing the heterogeneous system From diffusion andsedimentation data the mean molecular weights in Table I V have beenderived,TABLE IV.Source of glycogen. M (mean). Ref.Liver, rabbit (a) ................................. 4 x lo6 45,, ( a ) , ( b ) .............................. 4.3-4.4 x 106 46Muscle, rabbit (a) ................................. 2.6 x lo6 46,, horse ( a ) ................................. 2-9 x loG 46,, man (a) ....................................2.4 x lo6 46Ascaris lurlzbricoides (a) ........................ 0.7 x lo6 46Mycobact. tuberculosi ( c ) ........................... 12-13 x lo6 47Y Y(a) Extraction of tissue by hot alkali hydroxide.( b ) 9 9 9 , ,, water.( c ) 1 , 7 , ,, cold trichloroacetic acid.The above results demonstrate that glycogens from different sourcesDefinite evidence regarding the nature of the inter-chain links is not yet4 2 W. Z. Hassid, G. T. Cori, and R. McCready, J. Biol. Chena., 1943,148, 89.43 K. H. Meyer and M. Fuld, Helu. Chim. Acta, 1941,24, 376.4 4 P. Johnson, Ann. Reporls, 1947,63, 30.4 5 W. B. Bridgeman, J. Anter. Chem. SOC., 1942, 64, 2349.* 6 D. J. Bell, H. Gutfreund, R. Cecil, and A. G. Ogston, Biochern. J., in the press.4 7 E.Chargaff and D. H. Moore, J. Biol. Chena., 1944,155,493.REP.-VOL. XLIV. Hdiffer among themselves a t least with regard to mean molecular weights226 BIOCHEMISTRY,available. MT. N. Haworth, E. L. Hirst, and F. A. I s h e r ~ o o d , ~ ~ onadmittedly tentative evidence, have suggested a 1 : 6-linkage for a sample ofglycogen from rabbit liver. On the other hand, for other material from thesame source D. J. Bell 49 has obtained evidence for a 1 : 3-link. At presentit is impossible to state fa) whether different glycogens are branched at thesame mean positions in the unit chains, ( b ) if the inter-chain links are all ofthe same type, and ( c ) the precise structure of these links.No attempts to isolate a small portion of the glycogen molecule containingthe inter-chain link, as has been done for amylopectin, have yet beenreported.It would seem that enzymic experiments are the most likely tolead to a satisfactory solution, since direct methylation of glycogen does notyield a sufficienfly completely etherified product to render certain theidentification of the branch-point radicals as dimethyl gluco~es.~~Unpurified phosphorylases from liver, yeast, and heart-muscle, acting ona-glucose-1 phosphate, all produce glycogen-like ~ubstances.~~ On theother hand, crystalline muscle phosphorylase forms an amylose-like material(see Table 111). The analogy between muscle and plant phosphorylases isstrong, in that, when the former is allowed to act on glucose-1 phosphate inthe presence of an additional heat-Iabile catalyst, a glycogen-likepolysaccharide is formed.51 The structures of these synthetic glycogenshave not so far been examined by chemical methods.Only when we knowmore exact details of the structures of glycogens both natural and syntheticcan we be sure that the same chemical substances are formed by both thein vitro and the in viuo syntheses. D. J. B.3. HXMATIN COMPOUNDS IN PLANTS.This subject has not previously been reviewed here or elsewhere : it istherefore desirable to draw on material from quite an early date. It isfitting to mark the passing of Professor Hans Fischer by acknowledging hisoutstanding contribution to the chemistry of these materials and to recallhis pioneer extractions of porphyrins from yeast and other plant tissues.lRecent reviews by H.Theorell on haemoproteinsz and S. Granick andH. Gilder on the tetrapyrroles 3 deal with the chemical aspects of thesecompounds. D. Keilin’s original description of cytochrome in tiauesset the stage for developments in the plant kingdom no less than in theanimal : his identification of cytochrome, free intracellular hzematin,and the ‘‘ plant haemochromogen ” in the colourless parts of many plants,48 J., 1937, 577.so R. S. Bear and C. F. Cori, J . Biol. Chem., 1943,151, 57.61 G. T. Cori and C. F. Cori, ibid., p. 57 ; G . T. Cori, M. A. Swanson, and C. F. Cori,H. Fischer and H. Orth, “ Die Chemie des Pyrrols,” Edward Bros. Inc., AnnAdv. Enzymol., 1947, 7, 265.(a) Proc. Roy. SOC., 1925, B, 98, 312; ( b ) 1926, B, 100, 129; ( c ) 1928, B, 104, 206;49 J ., in the press.Fed. Proc., 1945, 4, 234.Arbor, 1943.Ibid., p. 305.( d ) Comnpt. rend. SOC. Biol., 1927, supplement, p. 39SCARTSBRICR : HBMATIN COMPOUNDS IN PLANTS. 227potatoes, grains, beans, stamens, bulbs, etc., has expanded into an increasingnumber of physiologically important compounds in an ever widening rangeof material.The haernatin compounds of yeast, of plant tissues generally and of leavesin particular, and the hzemoglobin of root nodules, will be described underseparate headings. For convenience all concentrations will be quoted asiiiolarities referred to the dry weight of material concerned (molaritiesof hzem compounds will refer to the molarity of haematin present irrespectiveof the number of hematin nuclei per molecule).Yeasts.-The high concentration and more intensive investigation ofhaematin in yeasts singles them out for special mention.Considerabledifferences, correlated with their respective environments, occur amongthe three main types of yeast investigated, top and bottom brewer’s yeastand baker’s yeast. valueswithin the range 500-5000 x Baker’s yeast grown in amedium low in iron content is pale in colour, has low total iron and no in-organic iron, low cytochrome content and low &. Addition of iron to themedium increases the rate of growth and the cytochrome content, particularlythe u component and increases the Qo,. Copper increases this effect. Theiron concentration of the yeast rose from 530 x 10-6 M.for the “ anemic ”yeast to 4100 x M. for yeast grown in a medium containing an ironsupplement. The respiration, originally sensitive to cyanide, has at the endof 7 days growth become cyanide-insensitive.6 Continued sub-culture ofyeast in cyanide gives rise to a stable strain showing no cytochrome oxidaseactivity towards the tests used.’ A similar result has been obtained by treat-ment of yeast with ethylene oxide.sRelatively few determinations of total hzmatin in yeasts are available,atid the results, owing to deficiencies in the methods and the possibility ofinherent variations, show a wide scatter : values from 2 4 t o 500 x M.:we recorded y, 12, 48 with ratios of total iron to hBm of 160 to 2.5 : 1. Theimportant fodder yeast, ToruZopis utilis, when grown under highly serobicconditions has a very high hzmatin content.1°Quantitatively, the most important of the recognised hematin compoundsin yeast are the cytochromes.Keilin observed much greater concentrationof cytochrome in baker’s than in brewer’s yeast, and correlated it with theirrespective environments. H. Fink classified yeasts into the baker’sThe iron content of yeasts is very variable;M. are usual.M. A. Joslyn, H‘allerstein Lub. Corn., 1941, 4, 49 ; P. P. Gray and 1. Stone, ibid.,1912, 5, 193. C. A. Elvehjern, J . Biol. Chem., 1931, 90, 111. ’ T. J. B. Stier and J. G. B. Castor, J . Gen. Physiol., 1941, s, 229.* ( a ) A. Treibs, 2. p h y ~ i o l . Chem., 1927,168,68; ( b ) n1. L. Anson and A. E.Mirsky,J . Gen. Physiol., 1929, 12, 401; (c) H. von Euler, iH. Fink, and H. Hellstroem,is. physiol. Chein., 1927, 169, 10.R. Whelton and N. J. Phaff, Science, 1947, 105, 44.lo Professor D. Keilin, personal communication.2. phpiol Chem., 1932, 210, 197; H. Fink and E. Berwald, Biochem. Z., 1933,258, 141.l2 H. von Euler, H, Fink, and G. Gunther, 2. physiol. Chem., 1939, 258, 47228 B IOOHEMTSTRY.group containing the four bands of cytochrornes a, b, and c, arid the brewer’sgroup containing no cytochrome a, and showing a fused b and c band;alteration in cultural conditions would convert one group into the other :the hamatin concentration of two different types may be similar?cI>. Keilin l3 describes a brewer’s yeast I with a modified Q component (a1 at5 8 6 0 ~ .) and a brewer’s yeast I1 with similar modified a component andmodified b and c components present as a single band ( b , a t 5570 A.). Quanti-tative measurements of cytochronie c in yeast vary from 3 to 150 x M . ~ *Borei and Sjodh 14c have shown the dependence of the cytochrome c con-centration on the degree of aeration of the medium : the crowded conditionsunder which pressed yeast starts to grow result in a local anmobosis in themedium and a corresponding low cytochrome c concentration in the yeast :this passes to a vigorously mobic condition which is accompanied by anenhanced cytochrome c content of the yeast.Bach, Dixon, Keilin, and Zerfas l5 investigating the lactic dehydrogen-ase of yeast, found that a hematin compound, present in amounts toosmall to be visible spectroscopically in yeast cells, accompanied the enzymein all their attempts to purify it.The parallelism between dehydrogenaseactivity and the strength of the absorption band of the hzemochromogenwas quantitative a t all stages of purification although different methods ofpurification had to be used for Delft and for Manchester yeast. The spec-trum of the compounds is of the hsmoehromogen type, a band 5563 A.,band 5300 A. max. : the prosthetic group is protohematin : the materialis slightly autoxidisable : and because of similarity with cytochrome b,the authors have termed it cytochrome b,. The oxidised cytochrome b, isimmediately reduced by the addition of lactate to the enzyme. The pre-paration reacts with cytochrome c, but the rate of reaction is relativelyfaster in the crude preparations, indicating that some additional factor isnecessary for the reduction of cytochrome c though not for the reduction ofinethylene-blue.Owing to the increasing instability of the enzyme withpurification the authors were unable to decide whether cytochrome b, isidentical with the lactic dehydrogenase itself or whether it forms anintermediate carrier between the dehydrogenase and methylene-blue.They recall the fact that succinic dehydrogenase of heart muscle, a dehydro-genase of the same class as the lactic dehydrogenase of yeast, is intimatelyassociated with cytochrome b. The concentration of cytochrome b, inyeast is of the order of 1.5 x M.and its turnover number 2900 (comparecytochrome c with which presumably it would eventually react in the cell,having a concentration of about 50 x N. and a turnover number, inliving yeast, of 3850).14bl3 Nature, 1934, 133, 290.14 ( a ) T. B. Coolidge, J . Biol. Chem., 1932, 98, 756; ( b ) D. Keilin and E. F. Hartree,Proc. Rog. SOC., 1941, B., 129, 277; (c) H. Borei and A. S j o d h , Naturwiss., 1943,31, 324; Arkiv Kemi, Min. CTeol., 1943, 16A, No. 19, p. 17.lS M. Dixon and L. G. Zerfas, Nature, 1939, 143, 557; S. J. Bech, M. Dixon, andD. Keilin, ibid., 1942, 149, 21; S. J. Bach, M. Dixon, and L. G. Zerfas, ibid., 1942,149, 45 ; S . J. Bach, hl. Dixon, and I,. G. Zerfas, Bioclzein. J . , 1946, 40, 229SCARISBSICK : HBMATIN COMPOUNDS Ih’ PLAXTS.229A peroxidase specific for cytochrome c was found in yeast by Altschul,Abrams, and Hogness.16 The activity of the enzyme preparations is pro-portional to their haematin content, which, in the purest preparation,amounts to 0.3%. The spectrum differs from that of horse-radish peroxidase,showing absorption maxima at 4100 A., 5000 A., and 6200 A. On reductionthese give place to maxima at 4375 A. and 5600 A. The enzyme forms acompound with one molecule of hydrogen peroxide developing a three-banded spectrum (4200 A., 5300 &4., 5600 -4.). The activity is inhibited bypotassium cyanide and also by catalase; i t 6 concentration in yeast is 250times greater than is that of catalase. 1. Hnszak 1’ has described thepresence in the suprarenal body of a h*mochromogen spectroscopically similar.to that of Bach’s cytochrome b, and also a peroxidase oxidisirig cytochrome,though the latter is not specific for cytochrome c and yeavt remains so farthe only source of the cytochrome c specific peroxidase.Catalase has long been recognised in yeast : one yeast cell has beencalculated to contain 20,000 molecules; l8 its very high turnover number(5,000,000) compensates for its apparently low concentration (approxi-mately 0-012 x 10-6 M.) so that the catalytic activity of yeast is of the sameorder of magnitude as the respiration.The amount of peroxidase in yeastis uncertain, for thermolabile reducing systems are present which preventthe appearance of purpurogallin.In experiments on the intracellular location of enzymes, H.Chantrenne 2ohas shown that granules derived from yeast ceUg contain cytochrome oxidase,succinic dehydrogenase, cytochromes a and b, and peroxidase, whereasthe supernatant liquor contains catalase, cytochrome c, lactic dehydrogenase,and carboxylase (compare Hill and Bhagvat 41).There are reports 21 that extracts of yeast are capable of accelerating theaction of various respiratory enzymes and of antagonising the influence ofcertain inhibitors on them, e.g., the cyanide inhibitions of cytochromeoxidase and of catalase and the azide inhibition of peroxidase. The authorsbelieve there is present in the extracts some iron compound of size inter-mediate between that of ferric iron and haematin : such extracts exhibita slight but definite peroxidatic activity.J. B. Sumner and E. B. Sisler 22have been unable to obtain any accelerating effect of yeast extracts preparedin the same way on catalase, either as a crude rat liver or a crystallinepreparation.l6 A. 11. Altschul, R. Abrams, and T. R. Hvgiiess, J . Biol. C’heirz., 1940, 136, 777;l 7 Biochent. Z., 1942, 312, 330. D. €3. Hand, Ergebn. Enzgrnforsch., 1933,2, 272.J. B. Sumner and G. F. Somers, ‘(Chemistry and Methods of Enzymes,”H. Abrams, A. M. Altschul, and T. R. Hogness, &id., 1942, 142, 303.Academic Press Inc., New York, 1947, p. 208.ao Enzymol., 1944, 11, 213.31 C. W. Kreke, M. D. Bartlett, and 31. St.A. Suter, Nature, 1944, 154, 268; C. W.Kreke, M. D. Bartlett, and M. A. Smalt, J . Biol. C‘hem., 1945, 158, 469; C.W. Kreke,and M. St.A. Suter, ibid., 1945, 160, 105; C. W. Kreke and M. D. Bartlett, Studies I n s t .Diui Thorn@, 1945,4, 1, 15; E. S. Cook and G. Perisutti, J . Biol. ChenE., 1947, 167, 827.22 Ibid., 1946, 165, 7230 BIOCHEMISTRY.Plant Tissues Generally.-Few estimations of total ‘ hzmatin in planttissues have been made. T. Mann 23 discusses the method of estimation :his figures show wide variation in the hzmatin content of different partsof the plant thus (all x M.) : pith 1.5, bark 6, petals (chrysanthemum)9, roots (parsnip) 6-15, seeds 35; onion bulbs, outer leaves 7, inner leaves50, second bulb 250. A high haematin content is associated with regionsof high metabolic activity (compare the gradient of increasing respiratoryintensity occurring in barley roots as the tip is approached).24 Sugar beet,with several rings of cambium, shows corresponding rings of higher hzmatincontent; greater respiratory activity of cambial tissue in the wood of ashand maple compared with the adjoining secondary phlcem and xylem hasbeen demonstrated by R..H. Goodwin and D. R. G ~ d d a r d . ~ ~ These observ-ations are soon to be more fully reported by Keilin and Mann.R. H. Common 26 has used the luminal test 27 for the detection of haematinin plant tissues. The nodules of legumes give a good reaction, but otherplant tissues respond only weakly; the test may have some use in detectinglarge concentrations of haematin when a spectroscope is not a t hand.The concentration of hzmatin in apple rootstocks has been used asan index of the amount of living tissue present, which is correlated with vigaurin experiments on the influence of scion and stock in grafting.28 A highperoxidase and catalase activity in the roots of the kok-saghyz plant isaccompanied by a low rubber content ; a consequent spontaneously develop-ing pink coloration can be used to differentiate plants of low and high rubbercontent.29A major part of the plant hzrnatin may be present as peroxidase : 23in a particular horse-radish root total haematin concentration was 46 x M.and peroxidase haematin about 28 x M.Other tissues may containsimilar large amounts of peroxidase ; thus the peroxidase concentration inthe sap of the fig tree is recorded as being 54 times that of horse-radish,mwhile in rye sprouts it reaches 80% of the latter, in wheat sprouts 70%,sprouting barley 30%, turnips 6y0, sugar beet 3%.31 Determinations ofperoxidase activity based on its reaction with hydrogen peroxide must,however, be treated with reserve, for all iron compounds exhibit both per-oxidatic and catalytic activity in small degree : this is enhanced in thehematin compounds, so that the peroxidatic activity of the intracellularhzmatin and cytochrome may be appre~iable.3~ On the other hand sub-stances may be present in tissue or extract which interfere with the pro-23 D.Phil, Thesis, Cambridge, 1937 ; Archiv. Towarzystwa ATawlcozcego We Lwowic,24 L. Rfschlis, Amer. J . Bot., 1944, 31, 183, 281.2 5 Ibid., 1940, 27, 234.27 J.McGrath, Brit. Med. J., 1942, ii, 156.2 * R. Hill and A. B. Beakbane, J . Powzol., 1947, 23, 117.yo J. B. Sumner and S. F. Howell, Enzymol., 1936, 1, 133.:I2 D. Keilin, Ergebn. Enzymforsch., 1933, 2, 239.1938, 9, 1.26 Natare, 1945, 155, 604.S. 0. Grebinskij, Biokhimiya, 1945, 10, 379.R. Willstatter, “ Untersuchungen uber Enzyme,” Berlin, 1938, quoted by 18SCARISBRICK : €IfiMATIN COMPOUNDS IN PLANTS. 23 1duction of purpurogallin. Mann’s spectroscopic determinations, thoughapproximate, are free from these objections.H. Theorell 33 claims to have separated horse-radish peroxidase intotwo enzymes, peroxidase I present in small amounts and precipitated bypicric acid, and peroxidase 11, the main component, which has been crystal-lised; these results, however, are not accepted by other workers.34 Thephysiological role of this important plant constituent is obscure : i t is widelydistributed in the plant kingdom 35 often in very high concentrations.Theorell and Swedin 36 have identified peroxidase as the dihydroxymaleicacid oxidase of Szent-Gyorgyi; 37 if dihydroxymaleic acid occurred in planttissues this system would constitute a very powerful oxidase, but theinstability of the acid is such that its presence has not been demonstrated.Peroxidatic activity in plant materials is correlated more or less empiricallywith various qualities (keeping, flavour, etc.) of importance in the foodindustry.38 Methods continue to be developed for the determination ofperoxidatic a~tivity.3~The presence of the cytochrome system in plants has been describedmany times.Keilin deacribed the spectroscopic appearance of cytochromein the colourless parts of the plant. K. Bhagvat *O extended the range ofthese observations. R. Hill and K. Bhagvat *l were able to make fromgerminating seeds a preparation showing the complete cytochrome spectrumand exhibiting cytochrome oxidase activity ; the cytochrome content isgiven as &th of that of yeast; W. 0. James was able to repeat this usingbarley embryos.42 The work of Goddard& on the cytochrome system,especially his isolation in quantity of cytochrome c from wheat germ (4.6mg./kg. corresponding to a calculated concentration of 0.4 x M. in thegerm), deserves special mention. Investigation has proceeded along twomain lines : one, the spectroscopic identification of the cytochrome systemin different plant tissues, which though often difficult because of the low33 Arkiv Kemi, Min. (Teol., 1940, 14B, No.20, 1.3 3 M. W. Onslow, “ Principles of Plant Biochemistry,” Cambridge UniversityPress, 1931.36 H. Theorell and €3. Swedin, Naturwiss., 1939, 27, 96 ; B. Swedin and H. Theorell,Xntirre, 1940, 145, 71.37 I. Banga, E. Philippot, and A. Szent-Gyorgyi, Nature, 1938, 142, 874; I. Bctngaand A. Szent-Gyorgyi, 2. physiol. Chem., 1938, 255, 57; I. Banga and E. Philippot,ibid., 1939, 258, 147.3 8 J. Sugihara and W. V. Cruess, Fruit Products J . , 1945, 24, 297; M. A. Joslyn,Food Industries, 1946, 18, 1204, 1334.39 J. Erkama, Suomen Kem., 1946, 19B, 32; I.Banga and B. Gyorffy,Magyar Biol. Kutalointezet Munkai, 1945, 16, 1 ; A. 51. Altschul and 11. L. Karan,Arch. Biochem., 1947, 13, 161; E. H. Lucas and D. L. Bailey, Food Ind?tstries, 1945,17, No. 9 , 32, 138.34 D. Keilin, in the prem4o D. Phil. Thesis, Cambridge, 1939.4 p Ann. Rev. Biochem., 1946, 15, 417.43 P. B. Marsh and D. R. Goddard, Amer. J . Bot., 1939,26, 724; J. Merry and D. R .Goddard, Proc. Rochester Acad. Sci., 1941, 8, 28; A. H. Brown and D. R. Goddard,Amer. J . Bot., 1941, 28, 319; D. R. Goddard, ibid., 1944, 31, 270.R. Hill and K. Bhagvat, Nature, 1939. 143, 726232 BIOCHEMISTRY .concentrations of the substances concerned and the presence of obscuringpigments, may yield unequivocal evidence of function within the livingplant; the other, the circumstantial assessment of the activity of thecytochrome system by measurements of respiration before and after theaddition of cytochrome oxidase inhibitors.The subject has been reviewedrecently by James 42 and by W. Stiles 44 where the importance of the threemain oxidase systems in plants, the cytochrome, catechol, and ascorbicacid oxidases, is discussed. There are several plant tissues, for examplemature leaves of wheat, barley, and carrot, in which the respiration isuninfluenced by cyanide; it would seem that other systems developed inplants can surpass the cytochrome system in importance.Leaves.--In the leaves of green plants the relation between haem andchlorophyll presents an important field as yet unexplored ; the dependenceof the green plant on iron for the production of the chlorophylls and thealmost universal occurrence of haematin in living matter suggests that haematincompounds, perhaps even of a different type, may be concerned in thesynthesis of these pigments.The experiments of Rittenberg 45a, showing, bythe feeding of isotlopically labelled compounds, that glycine and acetic acidare the sources of pyrrole in haem synthesis in the mammal, and the de-monstration by C. Rimington 456 of the synthesis of coproporphyrin by cell-free preparations of yeast, may provide useful leads here. The processof photosynthesis, far outweighing in magnitude the respiratory process,invites investigation into the possibility of the participation in it of hEmatincompounds.The presence of a high concentration of chlorophyll in thechloroplasts, obscuring the visibility of any possible haematin absorptionbands, together with the peculiar nature of the leaf proteins, present difficultiesnot met elsewhere. R. Hill and H. Lehmann46 followed throughout a seasonthe chlorophyll- and iron-content of a number of flowering plants; iron inleaves was greater than in other parts of the plant and was found to precedechlorophyll in appearance and disappearance. Spectroscopic investigationis possible in the non-chlorophyll parts of variegated or yellow leaves.D. Keilin 4d describes a haemochromogen spectrum in euonyrnus leaves.1%. Hill 47 and R. Scarisbrick 48 measured this spectrum in euonymus andother leaves.In euonymus there is a broad band in the region 5500-5650 A . with an intensity equivalent to a concentration of 200 x loA6 M.,but it is more usual in other leaves to see a considerably narrower band(5600-5650 A.) of an intensity ten times less. By fractionation withammonium sulphate of the water-soluble proteins of broad bean leaves twoOne, withrn band situated at 5500 A., seemed to be cytochrome c. The other, withater-soluble substances of haemochromogen type were obtained.4 4 Bot. Rev., 1946, 12, 165.45a I<.. Block and D. Rittenberg, J. Biol. Chem., 1945, 159, 45; D. Shemin mid451, Nature, 1943, 15.1, 793 ; T. E. Kench and T. F. Wilkinson, ibid., 1945, 155, 579.a 4 Biochern. J . , 1941, 35, 1190.D. Hittenberg, ibid., 1946, 166, 621, 627; K.Block, Physiol. Rev., 1947, 27, 574.4 7 Biochent. SOC. Proc., 1943, 37, XXIII.D. Phil. Thesis, Cambridge, 1940SCARISBRICK : H2EEMATIW COMPOUNDS IN PLANTS. 233band situated a t 5600 A., is somewhat autoxidisable but does not combinewith carbon monoxide. This substance, though not confined to the greenparts, seems t o be characteristic of the tissues of higher plants.ChZoroplasts.-The technique recently developed 49 for the isolation inbulk of chloroplasts from leaves affords suitable material for their biochemicalinvestigation. Measurements on chloroplasts show them to be richer iniron than the leaves from which they were d e r i ~ e d . ~ ~ , ~ ~ ~ Haematin showssimilarly a concentration in the chloroplast^.^^ Catalase seems to be presentalmost entirely in the chloroplast^,^^^^ though this is denied : 49h certainlythere seems to be a genetical relationship between catalase and chlorophyllconcentration.m The presence of catalase in the chloroplasts (5 x 1 0 - 6 ~calc.), together with the sensitivity ofphotosynthesis to oatalase poisons, hasoften occasioned speculations as towhether catalase plays some r61eduring photosynthesis.The matteris weighed carefully by I. E. Rabino-witch who argues that most of theexperiments in support of the hydrogenperoxide-catalase hypothesis must beconsidered indecisive ; furthermore,he considers that the production ofhydrogen peroxide is unlikely onthermodynamical grounds. Moreoverthe isolated chloroplast probably re-tains intact the mechanism for thephotochemical production of oxy-gen,4*749a7 6u but it is relatively un-influenced by catalase poisons suchas cyanide, azide, and hydroxylamine.Peroxidase, on the other hand, occursL eaf €uonymus7 7 SambucusCytochrome c ~ 5500A.Cytochrome f 7 5550A.P/ant 17 560 -7 5600A.Cytocbrome 6 -7 5640A.Yeast 19 556 *I 5563APosition of hcentochromogen spectra of leavcsand a-bands of plant cytochroutes.mainly in the water-soluble parts of the leaf.49'1By extraction with aqueous alcohol 4'9 ** another hemochromogen can beisolated from elder leaves in considerable amounts. This substance, termedcytochrome f, is present in all leaves which have so far been examined.(a) R. Hill, Nature, 1937,139, 881 ; (6) W.Menke, 2. Bot., 1938,32, 273; ( c ) A. C .Neisch, Biocheni. J . , 1939, 33, 293, 300; ( d ) S. Granick, Artier. J . Bof., 1938, 25, 558; (e.)C'. L. Comar, Bot. Gaz., 1942, 104, 122; (f) A. W. Galston, Artier. J . Bot., 1943, 30, 331 ;( 9 ) E. A. Boychenko, Biokhimip, 1947, 12, 153; ( h ) G . Krossing, Biochem. Z . , 1940,305, 359.50 G. Drouineau and P. Gouny, Ann. Aqrom., 1946, 16, 34; H. von Euler et al.,1929-35; see Rabinowitch, ref. 51 (a), p. 431.51n " Photosynthesis," Vol. I, Interscience Publishers Inc., N.Y., 1946.51b R. Hill, Proc. Roy. SOC., 1939, By 127, 192; R. Hill and R. Scarisbrick, ibid.,1940, B , 129, 238; Nature, 1940, 148, 61 ; C. S. French, A. S. Holt, R. D. Powell, and31. L. Anson, Science, 1946, 103, 505; C. S.French andG. S. Rabideau, J . Uen. Physiol.,1945, 28, 329234 BIOCHEMISTRY.It is apparently present in no other type of tissue, and further seems to occurmainly, if not entirely, in the chloroplasts, in which it accounts for approxi-mately one-third of the haematin. The spectrum is very sharp, showing,even a t room temperature, several maxima in both the 01- and p-absorptionbands. The principal maximum of the a-band is situated a t 5550 A.Cytochrome f is non-autoxidisable, does not combine with carbon monoxide,and has a slightly higher oxidation-reduction potential than cytochrome c.Root-nodule Hcemog1obin.-Of great interest is the red pigment found inthe root nodules of nitrogen-fixing legumes. Originally described byK. Mothes and J. Pietz 52 as an intermediate product in the oxidation ofdihydroxyphenylalanine by tyrosinase, it was later shown to be a haematincompound similar to haemoglobin by H.Kubo 53 who prepared from ithzemjn crystals and a pyridine hzemochromogen both identical with thosederived from horse haemoglobin. He observed oxygenation of the reducedpigment arid described a number of derivatives similar to those given byhzmoglobin.R. H . Rurris and E. Haas 64 confirmed and extended Kubo's identificationof the pigment as a haematin derivative, principally by their investigationof the Soret band, but they were unable to oxygenate the pigment, obtaininginstead a compound resembling Kubo's methaemoglobin. They suggested, ashad Pietz, that the pigment was functioning in an oxidation-reductioncapacity, but were unable to couple it t o Co I or Co I1 in suitable systems.D.Keilin and Y. L. Wang 55 pointed out that quinones produced concomitantlyfrom the plant tissue by polyphenol oxidase will interfere both by their owncolour and by oxidation of the pigment : they purified the compound furtherand confirmed its haemoglobin nature, measuring its affinity for oxygen(<0.1 mm. Hg for 50% sat.) and for CO ( K = HbCO x po2/Hb x pco =37 at 15"). H. N. Little and R. H. Burris 56 have now confirmed theseobservations.A. I. Virtanen 57 also confirmed Kubo7s observations and describedthe presence in the nodules of brown methzemoglobin which, as the nodulesdegenerate, is followed by a green pigment, resembling choleglobin.He,too, thought the pigment acted in an oxidation-reduction capacity in thefixation of nitrogen, linking it with his other view on nitrogen fixation in thefollowing scheme :Oxaloareta t e N, + MetHb 1 Hb + NH,*OH Oxime -+ Aspartic acid.The equilibrium Fe"/F"', and hence the nodule colour, would then be in-fluenced by the concentration of oxaloacetate diffusing from the leaves,.i2 Naturwiss., 1937, 25, 201.j4 J . Biol. Chem., 1944, 155, 227.j6 J . Amer. Chem. SOC., 1947, 69, 838.5 7 Nature, 1945, 155, 747 ; A. I. Virtanen, T. Laine, and H. Linkola, Szcomen Kem.,194.5, B, 18, 36 ; A. I. Virtanen and T. Laine, ibid., p. 38, ; A. I. Virtanen, J. Jorma, andT. Laine, ibid., p. 49; A. I. Virtanen and T. Lsine, Nature, 1946, 157, 25; A. I.Virtanen, Suornen Kem., 1946, B, 19, 48,53 Acta Pkytocibiin., 1939, 11, 196.j5 Nature, 1945, 155, 327SCARISBRICK : HBMATIN COMPOUNDS I N PLANTS. 235being thus, as Virtanen claims to have observed, dependent on the brightnessof the day.D.Keilin and J. D. Smith 58 disagree point by point with Virtanen'sexperimental results and conclusions and emphasise again the complicationslikely to arise from the formation of quinones. By direct spectroscopicalexamination of the nodule the reduced and oxygenated forms of the pigmentcan be seen but no methaemoglobin. A. I. Virtanen 59 has recently reviewedthe subject of nitrogen fixation and now agrees that oxygenation is the mostlikely role of the pigment.Summarising, a pigment occurs in the larger cells of the root nodulesof nitrogen-fixing legumes with the general properties of a haemoglobin.Its presence in every effective nodule in a wide variety of legumes tested 6oleads one to believe that it plays some part in the process of nitrogen fixation.It would seem more justifiable to consider that the pigment is acting in itsefficient role as oxygen carrier or oxygen store rather than to invoke itsinefficient performance as an oxidation-reduction catalyst'.There is someevidence that diffusion of oxygen into the root nodules may be limiting.6lAddition of the pigment to suspensions of nodule bacteria oxidising sodiumsuccinate increases their oxygen uptake a t low pressures of oxygen,59 56 aproperty shown to a greater degree by pig hamoglobin 56 (this phenomenonoccurs with the other organisms).A. I. Virtanen has claimed that additionof an extract of nodules to a culture of rhizobium promoted a fixation ofnitrogen, whereas purified pigment was unable to do so, but later experimentsdid not confirm such a fixati0n.5~The foregoing shows that in the plant kingdom is to be found a widerange of specific proteins combining with and influencing the tetrapyrrolegrouping. The root hamoglobin shows some properties intermediate betweenthe intracellular hamatin compounds and the circulating haemoglobins ofanimals.62 It shares with gastrophilus hEmoglobin and the myoglobinsthe phenomenon of a truly intracellular location. It undergoes reversiblt:oxidation and reduction a t low oxygen pressures, but methzmoglobiiiformation takes place more readily than is usual with haemoglobins,showing that the protection from oxidation by molecular oxygen normallyconferred on the haem by its specific protein is here incompletelydeveloped.Neither the plant nor the bacterium alone can make thisspecific protein; it appears as though the bacterium exerts some influenceevoking the formation by the plant of the protein.The wide variety of cytochromes which have been described, in plants,animals, and bacteria, would seem to the Reporter to make it desirable thatsome uniformity be introduced into the nomenclature. The term cytochromehas, in general, referred to a haemochromogen type of compound occurring in,5 8 Nature, 1947, 159, 692.6o H. G . Thornton, Nature, 1945, 156, 654.61 F.E. Allison, C. A. Ludwig, S. R. Hoover, and F. W. Minor, Bot. Gaz., 1940,62 D. Keilin and Y. L. Wang, Biochern. J., 1946, 40, 855.59 Biol. Rev. Cumb. Phil. SOC., 1947, 22, 239.101, 513236 BIOCHEMISTRY,or isolated from, living matter in undenatured state, in which the linkingof its specific protein to the hsm nucleus has to a greater or less extentprotected it from oxidation by molecular oxygen and from co-ordinationwith carbon monoxide. Such a compound possemes three principal differenti-ating features, its structure (an important aspect of which is its absorptionspectrum), its function (in many cases largely unknown), and its source oforigin. The last, though it may subsequently prove to be of trivial import-ance, nevertheless when incorporated in a name imparts information as wellas definition.Its use is established in the nomenclature of the hsmo-globins. The other distinguishing feature, the spectrum, could readily beincorporated in the name, as the wave-length-in mp for euphonism-of thecc-band : thus, yeast cytochrome 556, plant cytochrome 560. Cytochromesa,, b, and c would still retain their names acknowledged by usage, and othercompo1inds when shown to have universal occurrence and/or definite functionswould soon acquire less clumsy names.R. S.4. PYR~DOXINE AND ITS CONGENERS.Previous Reports have dealt with the determination of the structure ofpyridoxine and two methods of synthesis,l a new route to pyridoxine,2 andvarious biochemical aspects?A new approach to the synthesis of 3-hydroxypyridine derivativesrelated to pyridoxine has been described by A.C ~ h e n . ~ Esters ofN-benzyl-a-amino-acids were condensed with alkyl a-formylsuccinates. togive substituted aminoitaconic esters (I) which, on Dieckmann cyclisationand dehydrogenation of the resulting hydrochloride, gave the pyridiniumchloride (11). Hydrogenolysis of (11) gave the pyridine derivative (IIl),p2R7H2*C02R C C02RRO,V G*CO2R H O*$/ \R*UO&R’-HC R’*C CH \&L - - -C1-CH2Ph(1.1 (111.)which when R’ = Me, can be converted into pyridoxine by methodspreviously ~utlined.~ Points of interest about this synthesis are (a) itpermits the synthesis of pyridoxine from the natural amino-acid alanine,paralleling the replacement of pyridoxine by alanine in the work of SneIl (seepage 238), and ( b ) by the use of various amino-acids, the synthesis ofanalogues of pyridoxine differing only in their 2-substituents is possible.R.D. Haworth, Ann. Reports, 1939,36, 326.H. T. Openshaw, ibid., 1943, 40, 163.Ibid., 1939: 36, 344,372; 1940,37,432,439,440; 1942,39,231; 1944,41,264.Jubilee Volume Emil Barell, 1946, 71.R. Kuhn, K. Westphal, G. Weedt, and 0. Westphal, Natuwiss,, 1939,27,469HTlCfHES : PYRIDOXINE AND ITS CONGEKERd. 237Pyridoxine in Nutrition and Medicine.-Assessment of the significance ofpyridoxine in human nutrition and in clinical medicine has not advanced toany great extent in recent years. The elegant researches, to be describedlater, on the role of pyridoxine in the metabolism of various organisms willprobably bear fruit in determining knowledge of t’he function of pyridoxinein human nutrition.S.G. Smith and D. W. Martin 6 have described the use of intravenouspyridoxine for the successful treatment of cheilosis accompanying pellagra,sprue, and other diseases. The relation of pyridoxine to anemia has beenreviewed previously.7 No human anaemia corresponding to the anaemia ofpyridoxine-deficient animals has so far been described. W. Antopol andC. E. Schotland * have used pyridoxine successfully in progressive musculardystrophy, but J. W. Ferrebee, W. 0. Klingnian, and A. M. Frantz andothers have seriously disputed this finding.In one field, the therapeutic value of pyridoxine appears to have beenestablished.B. B. Weinstein, Z. Wohl, G. J. Mitchell, and G . F. Sustendal loadministered pyridoxine without toxic effects to sufferers from nausea andvomiting of pregnancy; relief was considerable or complete. B. F. Hart,W. T. McConnell, and A. N. Pickett l1 found that this effect is improved ifaneurin is com bined with the pyridoxine. Radiation sickness, accompanyingradiological treatment, has been studied by various workers ; if the sicknesscan be controlled, the daily dosage of X-rays to the average patient can beincreased, thus reducing the necessary duration of the X-ray treatment.W. B. Bean, T. D. Spies, and R. W. Vilter l2 suggest that disturbedrespiratory enzyme systems form the basis of the disorder. Treatment ofmore than 50 cases of radiation sickness with pyridoxine hydrochloride byJ.R. Maxfield, A. J. McIlwain, and J. E. Robertson l3 gave good results,and this has been confirmed by later workers. In the most recent paperavailable, J. J. Wells and W. C. Popp l4 obtained good results in more thanhalf their patients with 100-300 mg. of pyridoxine hydrochloride injectedintravenously before treatment.A further therapeutic use of pyridoxine was shown by the finding ofG. M. Higgins l5 that the toxic effects of promin (sodium pp’-diaminodi-phenylsulphoiie-NN’-didextrose sulphonate) administered orally could becounteracted by the simultaneous administration of aneurin, riboflavin, andpyridoxine.Pyridoxine deficiency in animals leads to several important symptoms.’ J.R. P. O’Brien, Ann. Reports, 1944, 41, 254.Proc. SOC. Exp. Biol. iiIed., 1940, 43, 660.J . Anter. Med. ASSOC., 1940, 114, 1088.Ibid., 1941, 116, 1895; A. M. Doyle and H. H. BIerritt, Arch. Neurol. Psychfiat.,1941, 45, 672; G. Fitzgerald arid B. NcArtlle, Brain, 1941, 64, 19; A. McBryde andL. D. Baker, J . Pediat., 1941,18, 72i.lo Amer. J . Obstet. Qynecol., 1944,47,389.l2 Amer. J . Med. Sci., 1944, 208, 46.l 5 -4 nier. .7. filed. Sci.. 1944,207, 239.l1 Ibid., 1944,48, 251.l3 Radiology, 1943, 41, 383.Proc. Sta8 Meetings Mayo Clinic, 1947, 22, 482238 BIOCHEMISTRY,H. E. .Axelrod, A. F. Morgan, and S. Lepkovsky l6 found that pyridoxine-deficient dogs excreted kynurenine and xanthurenic acid, but, after intakeof tryptophan, only xanthurenic acid was excreted ; xanthurenic acid fedto normal or deficient dogs was excreted unchanged.Similar results forswine have been reported by G. E. Cartwright, M. M. Wintrobe, P. Jones,M. Lauritsen, and S. Humphreys.17 B. S. Schweigert and P. B. Pearson 18found decreased excretion of nicotinic acid and N’-methylnicotinamide inrats and mice on pyridoxine-deficient diets, and F. Rosen, J. W. Huff, andW. A. Perlzweig l9 confirmed that in pyridoxine-deficient rats the excretionof N’-methylnicotinamide is decreaaed and the conversion of tryptophaninto xanthurenic acid increased.The relationship of pyridoxine to fatty acid metabolism has not beendetermined. H. Schneider, H. Steenbock, and B. R. Platz 2O found that theacrodynia of deficient rats could be cured by administration of either“ essential fatty acids ”, which cure is independent of pyridoxine, or byadministration of rice bran concentrate, the activity of which is dependent onpyridoxine and an accessory factor.E. W. McHenry and G. Gavin21demonstrated that in protein metabolism in the rat, pyridoxine is essentialfor the conversion of protein into fat.Chemical Microbiology .-The micro biohgical assay of pyridoxine hasbeen reported previously.22 The results of assays with yeast and those withNeurosporu sitophila have been found to agree with those from rat assays byL. E. Carpenter and F. M. Strong,23 who recommended the yeast assayprocedure. R. H. Hopkins and R. J. Pennington,% following on the resultof earlier workers, have confirmed the usefulness of Saccharomycescarzsbergensis, for which the three forms pyridoxine, pyridoxal, andpyridoxamine, to be described later, have equal activity, whileJ.B. Rabinowitz and E. E. Snel125 have described an improved assaymethod, using Strep. fecalis, which permits assays of pyridoxal andpyridoxamine.The most important recent researches on pyridoxine and relatedcompounds lie in the field of microbiology. In 1942, E. E. Snell,B. M. Guirard, and R. J. Williams 26 showed that addition of pyridoxine to abase medium was necessary for the growth of Streptococcus Zactis R, but theuse of this medium for the assay of the pyridoxine content of various naturalsources gave values several hundred to several thousand times thoseobtained by yeast growth, rat growth, or colorimetric methods.The activeagent was found to be similar to pyridoxine and was named“ pseudopyridoxine ” and its presence was found to parallel the presence ofpyridoxine, from which it was therefore assumed to be derived. E. E. Snell 27l6 J . Biol. Chem., 1945,160, 155.l 8 J . Biol. Chem., 1947, 168, 555.3o J . Biol. Chem., 1940, 132, 539.z4 F. W. Noriis, Ann. Reports, 1944, 41, 262.23 Arch. Biochem., 1944, 3, 375.2 5 J . Biol. Chem., 1947, 169, 63.2 7 Proc. SOC. Exp. Biol. Med., 1942, 51, 356.Bull. Johns Hopkins Hosp., 1944, 75, 37.l9 J . Nutrition, 1947, 33, 561.21 Ibid., 1941, 138, 471.24 Biochem. J., 1947, 41, 110.2 6 Ibid., 1942, 143, 519HUGHES : PYRIDOXINE AND ITS CONGENERS.239showed that the growth-promoting activity of added pyridoxine for S. Zactis Rwas greatly increased by autoclaving of the medium or autoclaving pyridoxinewith amino-acids, especially cystine and glycine ; the basis of this conversionwas considered to be partiaJ amination or oxidation.Carpenter and Strong 23 showed that mild oxidation of pyridoxine gave asubstance with heightened activity for I;. casei. Detailed experiments byE. E. Snel12* showed that two active substances were produced, one anamine and the other an aldehyde. Various proposed derivatives ofpyridoxine were synthesised by S. A. Harris, D. Heyl, and I<. Folkers z9 andtested microbiologically, and the active compounds were found to be3-hydroxy-4-formyl-2-methyl-5-hydroxymethylpyridine and 3-hydroxy-2-methyl-d-aminomethyl-5-hydroxymethylpyridine, and these were namedpyridoxal and pyridoxamine respectively.The active amine was bestobtained by amination of 3-hydroxy-2-methyl-5-hydroxymethyl-4-methoxy-methylpyridine ; the isomeric 5-aminomethyl compound was also synthesised,but was without significant activity. Pyridoxal was prepared by oxidationof pyridoxine with alkaline potassium permanganate, and the product wasisolated as the oxime; treatment of this with nitrous acid and then withethyl alcohol gave the cyclic acetal (IV), which on acid hydrolysis gavepyridoxal, which may be represented by the open (V) or the cyclic ether (VI)structure.EtO*CH--i CHO CHI0Hk-iHO(>CH,--O IMeCatalytic hydrogenation of pyridoxal oxime yielded pyridoxamine,establishing the 4-position for the formyl group.E.E. Siiell and A. N. Rannefeld 3O investigated the activity of pyridoxine,pyridoxal, and pyridoxamine for a variety of organisms and found thatp.yridoxa1 has 5000e8000 times, and pyridoxamine 6000-9000 times, theactivity of pyridoxine as a growth factor for S. Zuctis B ; for other organismse.g., L. casei, pyridoxal wits found to be highly active, and pyridoxine andpyridoxamine almost inactive ; again, for other organisms such asSaccharomyces carlsbergensis, all three forms have approximately equalactivity, and these variations in activity for different organisms are assumedto indicate the ease with which the various organisms convert pyridoxine andpyridoxamine into pyridoxal.For this reason, it is preferable to useorganisms such as Sacch. carlsbergensis or Neurospora sitophila which respondequally to the three members of the group.E. E. Snell 31 showed, by differential microbiological assay in conjunctionwith chemical treatments, that all three members of the B, group occur innatural tissues. He also showed that autoclaving pyridoxal with hydrolysedE8 J . Biol. Chent., 1944, 154, 313; J . Amer. Chenz. SOC., 1944, 66, 2082.29 J . Biol. Chem., 1944, 154, 315; J . Anier. Chem. SOC., 1944, 66, 2088.30 J . Biol. Chew?., 1946, 157, 473. 31 Ibid., p. 491240 HIOC!HEMIYTRY.casein increased its activity for 8. fcecdis, presumably by formation ofpyridoxamine ; autoclaving pyridoxamine with a-ketoglutaric acid greatlyincreased its activity for L.casei, but decreased it for S. lactis, thus indicatingthe formation of pyridoxal.Pyridoxal Phosphate and Amino-acid Decarboxylases.-The existence ofenzymes capable of producing amines from certain amino-acids has beenrecognised for many years; recently many bacteria have been tested fortheir power to decarboxylate the common amino-acids, but only six amino-acids have so far been attacked-L-lysine, L-ornithine, L-arginine, I;-tyrosine,L-histidine, and L-glutamic acid-and six enzymes, each specific for oneamino-acid, bave been isolated by E. F. Gale and his co-workers.32Resolution of these enzymes into apo- and co-enzymes is spontaneous forL-lysine decarboxylase a t an alkaline pH and for L-tyrosine, L-arginine, andL-ornithine decarboxylases is accomplished by precipitation.Gale and hisco-workers were unable to resolve histidine or glutamic acid decarboxylases,but W. W. Umbreit and I. C. Gunsalus 33 claim a resolution of L-glutamicacid decarboxylase by dialysis. Using the four apoenzymes which they hadprepared, Gale and his co-workers were able to reactivate them bythe addition of preparations of codecarboxylase, which they found to bewidely distributed, and by this reactivation technique a number of naturaland synthetic products were tested for codecarboxylase activity.E. S. Taylor and E. F. Gale34 presented data on the inhibition ofdecarboxylases by keto-fixatives (hydrazine, etc.), indicating that thecodecarboxylase enzymes possess a keto- or aldehyde group which is essentialfor enzymic activity.W. D.Bellamy and I. C. Gunsalus35 found that the addition to themedium of pyridoxine and nicotinic acid, as well as tyrosine, was necessaryfor the production of tyrosine decarboxylase by S. fcecalis. These workers 36found that pyridoxal stimulated the production of tyrosine decarboxylaseby S. fuxulis R, but pyridoxamine did not ; if the cells were dried, pyridoxalwas no longer effective as an activator unless adenosine triphosphate wasadded or the pyridoxal was phosphorylated by treatment with thionylchloride and silver dihydrogen ph~sphate.~' This method of phosphorylationwould indicate esterification of the 5-hydroxyl group. J. Baddiley andE. F. Gale38 showed that the apoenzymes of their four decarboxylases wereactivated towards their substrates almost as effectively by phosphorylatedpyridoxal (prepared as above) as by codecarboxylase concentrate.Aboutthe same time W. W. Umbreit and I. C. Gunsalus39 also found that thecoenzyme required to activate arginine and glutamic decarboxylases wasthe same as that previously identified as necessary for lysine and tyrosinedecarboxylases, and that phosphorylated pyridoxal was active with each32 For references see Gale, Adv. Enzymol., 1946, 6, 1.33 J . Biol. Chern., 1945, 159, 333.35 J . Bact., 1944, 48, 191.3 7 Ibid., p. 685.3s J . Biol. Chern., 1945, 159, 333.34 Biochem. J . , 1945, 39, 62.36 J . Biol. Ckenx., 1944, 155, 357.38 Nature, 1945, 155, 7 2 7 HUGHES : PYRIDOXINE AND ITS CONGENERS.24 1apoenzyme. W. W. Umbreit, W. D. Bellamy, and I. C. Gunsalus thenreported the phosphorylation of pyridoxal with phosphorus oxychlorideand sodium hydroxide to yield a non-crystalline, impure product with 5%coenzyme activity; they also showed that the activity of naturalcodecarboxylase decreased on acid treatment, but could be restored byenzymatic treatment with adenosine triphosphate. These workers andC. E. Foust 41 described the purification of this pyridoxal phosphate as itsbarium salt, which contained one mole of phosphorus per mole of pyridoxal ;they reported that acid hydrolsysis of this pyridoxal phosphate preparationrestored the characteristic absorption band of pyridoxal, and the positivephenol reaction, using the chloroimide method of J.V. S ~ u d i . ~ ~ They alsoshowed that pyridoxine phosphate was without coenzyme activity, whichappeared on permanganate oxidation ; again, phosphorylation of pyridoxaloxime, followed by nitrous acid treatment, led to definite coenzyme activity ;ultra-violet absorption spectra indicated that in this product the 3-phenolicgroup was free. D. Heyl, S. A. Harris, and K. Folkers 44 also prepared anamorphous coenzyme from pyridoxal and phosphorus oxychloride, andcharacterised it as a crystalline oxime which on nitrous acid treatment gavea 40 to 50% yield of coenzyme activity; they claim that this excludesformula (VII) for the coenzyme; they also claim that structure (VIII)H,O,PO*CH----l CHO(VII.) (VIII.) (IX.)was eliminated, since when the ethyl acetal of pyridoxal (IV) wasphosphorylated with phosphorus oxychloride and pyridine, and the productconverted into the oxime of structure (VIII), this oxime was different fromthat derived from the coenzyme.P. Karrer and M.Viscontini45 phosphorylated the cyclic ethyl acetal ofpyridoxal with phosphorus oxychloride in pyridine, obtaining the crystallinecompound (IX), and they claimed to show 46 that this acted as a coenzymefor lysine and arginine decarboxylases as well as for tyrosine decarboxylase.However, I. C. Gunsalus and W. W. Umbreit 47 have emphaticallyreaffirmed that the 3-phosphate of pyridoxal is not identical withcodecarboxylase ; they presented evidence obtained with the tyrosinedecarboxylase apoenzyme for the activity of their pyridoxal phosphate andfor the lack of activity of the 3-phosphate; they attributed the differencebetween their findings and those of Karrer and Viscontini to the enzymepreparations used.In addition to their rBle in the breakdown of amino-acids, pyridoxine and* O Arch.Biochem., 1945, 7 , 185.4 1 J . Biol. Chem., 1945, 161, 743.43 Abstr. 110th Meeting Amer. Chem. SOC., 1946, 34B.44 Ibdd., 1946, 35B.4 6 Ibid., p. 524.42 Ibid., 1941, 139, 707.45 Helv. Chim. Acta, 1947, 30, 52.4’ J . Bwl. Chem., 1947, 170, 415242 BIOCHEMISTRY.its derivatives probably play a part in the synthesis of amino-acids bycertain bacteria. The requirement of L. delbruckii for lysine, alanine, andthreonine could be eliminated by adding pyridoxamine to the medium,according to J.L. Stokes and M. Gunness; 48 similar results were reportedfor L. arabinosus and L. casei. C. M. Lyman, 0. Moseley, S. Wood, B. Butler,and F. Hale 49 showed that the presence of carbon dioxide and pyridoxineor its derivatives was necessary to replace certain amino-acids, and theysuggested that pyridoxine or a derivative forms part of an enzyme systemwhich in these organisms carries out amino-acid synthesis by a reversal ofthe amino-acid decarboxylase reaction.Pyridoxine Derivatives in Transamination.-A further aspect of thefunction of pyridoxine derivatives has been revealed by a study of the partwhich they play in biological transamination. Snell 28 had suggested thata possible interconversion of pyridoxal and pyridoxamine by transaminationreactions might play a role in biological transamination; he showed 31 thatautoclaving pyridoxamine with a-ketoglutaric acid greatly increased itsactivity for L.casei but decreased that for S. fa?calis, suggesting that thepyridoxamine was converted into pyridoxal; again 51 he showed thatpyridoxal and glutamic acid react reversibly on heating to give pyridoxamineand a-ketoglutaric acid. W. D. Bellamy, W. W. Umbreit, andI. C. Gunsalus 52 reported that pyridoxine, pyridoxal, and pyridoxamine areconverted into codecarboxylase by various organisms, and that cellsuspensions of 8. faxalis convert pyridoxamine into codecarboxylase inpresence of a keto-acid. F. Schlenk and E. E. Snell 53 showed that tissuesfrom pyridoxine-deficient rats possessed decreased transaminase activity,and that in some cases this activity could be stimulated by the addition ofpyridoxal and adenosine triphosphate. F.Schlenk, A. Fisher, andE. E. Snell 54 found that glutamic-aspartic transaniinase is inactivated bysunlight and ultra-violet light, and this inactivation parallels the destructionof pyridoxine. E. Cunningham and E. E. Snell 55 had previously found thatpyridoxine, pyridoxamine, and pyridoxal were all inactivated for yeastgrowth by light, most rapidly at pH > 7, but pyridoxamine was rapidlydestroyed by direct sunlight, even in acid solution.H. C. Lichstein, I. C. Gunsalus, and W. W. Umbreit 56 found thatpyridoxal phosphate functioned as the coenzyme of glutamic-aspartictransaminase ; cells from a pyridoxal-deficient medium gave a transaminaseapoenzyme which was activated by pyridoxal phosphate, and the cell-freeenzyme, from a medium containing pyridoxal, was resolved and the activityof the apoenzyme restored by pyridoxal phosphate.D. E. Green,J A . F. Leloir, and V. Nocito 57 showed that boiled purified preparations oftransaminase from pig heart could replace the coenzyme of dihydroxyphenyl-4 8 Science, 1945, 101, 43.50 Ibid., 1947, 167, 177.52 J . Biol. Chenz., 1945, 160, 461.O4 Proc. Soc. Exp. Bwl. iMed., 1946, 61, 183.4 9 J . Biol. Chent., 1946, 162, 173.51 J . -4mer. Chein. SOC., 1945, 67, 194.53 Ibid., 1945, 157, 425.5 5 J . Biol. Chem., 1945, 158, 491.j6 Ibid., 1945, 161, 311.5 ; lbill., p. 669HUGHES : PYRIDOXINE AND ITS CONGENERS. 243alanine decarboxylase, which could be replaced in turn by pyridoxalphosphate or the codecarboxylase preparation of Gale. A. E. Braunstein,M. G. Kritzmann, E. F. Gale, and H. M. R. Tomlinson58 agreed thataspartic co-aminopherase is different from, or more complex than, pyridoxalphosphate, although the natural codecarboxylase preparation possessedsome co-aminopherase activity. P. Karrer and M. Viscontini 59 found thatthe phenol phosphate of pyridoxal acetal does not increase the glutamic-oxalacetic transamination effected by the apoenzyme in 8. fcecalis powder,though this result must be interpreted in the light of the controversy on thestructure of " codecarboxylase pyridoxal phosphate " mentioned above,F.Schlenk and A. Fisher,6o working with the glutamic-aspartictransaminase isolated from pig-heart, found the enzyme difficult to resolvebut were able to establish that the prosthetic group usually containedpyridoxal phosphate, but, in a few cases, a pyridoxamine derivative, Theysuggested that the enzyme system probably acts by the reversible conversionof pyridoxal into pyridoxamine in the prosthetic group, and they postulatedthe reversible scheme :IproteinI 11 proieinprotein proteinD. E. O'Kane and I. C. Gunsalus 61 were able to resolve this glutamic-aspartic transaminase and obtain the apoenzyme in a higher state of puritythan that previously obtained, and they confirmed that pyridoxal phosphateserves as a coenzyme for this transaminase.S.R. Ames, P. S. Sarma, and C. A. Elvehjem,62 using the heart andkidney tissues of pyridoxine-deficient rats whose transaminase activity wasonly 40% of that of normal rats, showed that the addition of pyridoxal orpyridoxamine, with or without added adenosine triphosphate, was withouteffect at low levels, but the addition of pyridoxal phosphate or pyridoxaminephosphate at the same low level resulted in a substantial reactivation of thetransaminase activity. Succinic oxidase activity is also slightly reduced inpyridoxine-deficient rats, but the added agents had no effect on this system.J. B. Rabinowitz and E. E. Snell 63 converted pyridoxal phosphate intopyridoxamine phosphate by heating it with glutamic acid, an interconversion5R Nature, 1946, 158, 102.6o Arch.Biochem., 1947, 12, 69.6 y Ibid., 1947, 167, 136.59 Helv. Chisn. Acta, 1947, 30, 528.61 J . Biol. Chem., 1947, 170, 425.63 Ibid., 1947, 169, 643similar to that of the urrphosphorylated compounds. They found asubstance in natural extracts with properties similar to those of pyridoxaminephosphate. Pyridoxamine phosphate was found to be much less active:before than after hydrolysis for Sacch. carlsbergensis and L. mei, while for5'. fmcatis the activity before hydrolysis is 0.7-2 times that after hydrolysis.were able to reduce the number oftransaminase systems when they discovered that the activity of the aspartic-slanine system of A. E. Braunstein 65 could be reproduced by a mixture ofpurified glutamic-alanine and glutamic-aspartic enzyme6 in the presence ofpyridoxal phosphate and glutamic acid or of pyridoxal phosphate and heartconcentrate, and they confirmed that this aspartic-alanine transaminasesystem is an artifact.To summarise, while the structures of pyridoxal phosphate andpyridoxamine phosphate are still undecided, it appears that cyclic inter-conversion of these compounds is responsible for various enzyme activities ;in an acid environment pyridoxal phosphate acts as codecarboxylase ; in analkaline medium as co-transaminase.Pyridoxine and Derivatives in other Microbiological Reactions.-Anotherfunction of pyridoxal phosphate has also been described; W.W. Umbreit,W. A. Wood, and I. C. Gunsalus 66 isolated and resolved a cell-free enzymefrom Xeurospora sitophila which converts indole plus serine into tryptophan,and they found pyridoxal phosphate to reactivate the apoenzyme.B. S.Schweigert 67 concluded that L. arabinosus could synthesise tryptophanfrom indole or anthranilic acid in the presence of pyridoxine or a derivative,and that serine and acetate enhanced this synthesis. From E. coli,W. W. Umbreit, W. A. Wood, and I. C. Gunsalus 68 obtained a cell-freetryptophanase which catalyses the breakdown of tryptophan to indole,pyruvic acid, and ammonia, though, since no serine is formed, this reactionis not the reversal of the tryptophan synthesis mentioned above; theyproved that pyridoxal phosphate acts as the coenzyme for this tryptophanase.Since vitamin B, has been shown to be complex in nature, the questionnaturally arises whether more than three compounds are involved ; however,J.B. Rabinowitz and E. E. Snell, who describe 69 an improvement of theassay method for B, (pyridoxal and pyridoxamine), using S. fcecuEis as thetest organism, found that the use of this method for the determination of theB,-contents of natural materials gave values uniformly less than thoseobtained with Sacch. curlsbergensis, which responds to all three forms, andthis finding does not support the existence of a fourth unidentified memberThe microbiological synthesis of pyridoxine has also been investigated ;I,. W. McElroy and H. Goss showed by rat assay that vitamin B, can besynthesised in the rumen and reticulum of the sheep and the rumen of theD.E. O'Kane and I. C. Gunsalusof the B, group.64 J. Biol. CILem., 1947, 170, 433.6 6 J . Biol. Chem., 1946, 165, 731.68 Ibid., 1947, 170, 313.'io J. Nufrition, 1940, 20, 541.6 5 Biokhimiya, 1939, 4, 667.Ibid., 1947, 168, 283.6 9 Ibid., 1947, 169, 631HUGHES : PYRIDOXINE AND ITS CON(;ESF;HS. 345cow. E. E. Snell and B. M. Guirard 71 have suggested that alanine isinvolved as an intermediate in the synthesis of pyridoxine by certain lacticacidlbacilli, but for L. casei alanine cannot replace pyridoxine. J. L. Stokes,J. W. Foster, and C. R. Woodward 72 found that in alkaline media apyridoxine-requiring mutant of Neurospora sitophilcc could synthesisepyridoxine if supplied with ammonium compounds. E. E. Snell 73 foundthat a substance contained in an enzymatic digest of vitamin-free caseinwas necessary to allow alanine to replace vitamin B, for L.cmei; underthese conditions u-alanine promoted growth, while L-alanine was inactive ;for AS'. fcecu2is R, alanine alone replaced B,, the u-isomer being a t least sixtimes as active as the L-, though both forms were apparently necessary forgrowth. It is interesting to note, in connection with this replacement of B,by alanine, that the Cohen synthesis mentioned a t the beginning of thisreview also utilises alanine as a starting material for the synthesis ofpyridoxine derivatives.O t h r Pyridoxine Derivatives and A nulog?tes.-Harris, Heyl, andYolkers 29 synthesised the 5-aminomethyl isomer of pyridoxamine, but thiscompound was without significant activity in microbiological assay.J.W. Huff and W. A. Perlzweig '4 oxidised pyridoxine with bariiitnpermanganate in neutral solution and obtained the lactone (X) of 3-hydroxy-2-methyl-5 - hydroxymeth ylpyridine -4- carboxylic acid, designated4-pyridoxic acid; treatment of this lactone (X) withalkali gave the free acid which was identical with theHO/kCH,-O substance isolated by them from the urine of personsAIe(N) ingesting pyridoxine. Both the acid and the lact'onefluoresce, the lactone more intensely, enabling a fluori-metric determination of either compound. L. Velluz and G . Amiard 75have described an alternative synthesis of 4-pyridoxic acid from ethyl3 -amino -5 - cyano -2 -met hylpyridine-4- car box ylat e .B.C. Johnson, T. S. Hamilton, and H. H. Mitchell 76 also isolatedpyridoxine, " pseudopyridoxine ", and 4-pyridoxic acid from the urine andsweat of normal individuals. S. A. Harris, E. T. Stiller, and K. Folkers 77synthesised 5-pyridoxic acid, and the lactone of this, designated p-pyracin,was found by M. L. Scott, L. C . Norris, G. F. Heuser, W. F. Bruce,H. W. Coover, W. D. Bellamy, and I. C. Gunsalus 78 to promote the growthof chicks and have anti-anemic action, causing hemoglobin incream.M. L. Scott, L. C. Norris, L. W. Charkey, L. J. Daniel, and G. F. Heuser 79showed that p-pyracin is not required for the prevention of chick anmniawhen free folic acid is present, but is necessary with folic acid conjugates, andthey suggested that i t acts in an enzyme system for the liberation of folic acidfrom its conjugates.31. L. Scott, L. C. Norris, G . F. Heuser, anti'0-1(xJ71 Proc. ,Vat. dcud. Sci. U . S . , 1943, 29, 66.72 Arch. Biochem., 1943, 2, 235.74 Ibid., 1944, 155, 345. Bull. SOC. chin&., 1947, 136.76 J . Biol. Ghena., 1945, 158, 619.78 J . Biol. Chein., 1944, 154, 713.i.7 .J. BioE. Chem., 1945, 158, 497.i 7 J . Amer. Clteni. SOC., 1039, 61, 1242.i 8 Ibid., 1946, 164, 403246 BIOCHEMISTRY.W. F. Bruce synthesised a-pyracin frompyridone-4-carboxylate, and showed that theeffective as the p-pyracin in promoting growthchicks.ethyl 5-cyano-2-methyl-6-a-lactone was at least asand preventing anzmia inG. Schwartzman and A. Fischer 81 investigated the antibacterialproperties of irradiated pyridoxamine and found activity, related to theconditions of irradiation, against various Gram-negative aerobics and to alesser degree against Staph.strain H and one Strep. hcemolyticus.A. 0. Seeler 82 found that large doses of pyridoxine counteracted theeffects of mepacrine or quinine on P . Zophurce in chicks, and surmised thatpyridoxine is necessary for the growth of this parasite. Following thissuggestion, G. E. McCasland, D. S. Tarbell, R. B. Carlin, and N. Shakespeares3synthesised compounds in which the characteristic substituents of pyridoxinewere attached to a pyrimidine ring, namely 4-hydroxy-2-methyl-6-hydroxy-methylpyrimidine hydrochloride (XI) and 4-hydroxy-5-methyl-2 : 6-bishydroxymethylpyrimidine hydrochloride (XII) .The second compound was tested for pyridoxine and anti-pyridoxineactivity against Succh.cerevisice, but the results were negative.OH OH Me CH,*OMe”\ ”\Me HO/\CH,*OH II IMeLN/!CH,*OH HOCH, II ,N/2H2*OH I Me,N4HC1 HC1(XI.) (XII.) (XIII.) (XIV.)Some interest has been displayed in deoxypyridoxine (XIII) and04-methylpyricloxine (XIV) .04-Methylpyridoxine has some vitamin activity in the rat, according toK. Unna,84 while deoxypyridoxine has none ; the latter finding was confirmedby E. F. Moller, 0. Zima, F. Jung, and T.W. H. Ott 86 found, in assays on pyridoxine-deficient chicks, that 2 molesof deoxypyridoxine annul the vitamin activity of 1 mole of pyridoxine.W. H. Ott later 87 found 04-methylpyridoxine to possess the same orderof anti-pyridoxine activity.C. W. Mushett, R. B. Stebbins, andM. N. Barton 88 reported that deoxypyridoxine in various experimentalanimals led to atrophy and degeneration of blood-forming organs, but theeffects varied ; in young dogs it aggravated some B6-deficiency symptomsbut postponed others, while one large dose stopped increased irritability andcramp in R6-deficient animals. C. C. Porter, I. Clark, and R. H. Silber 89J . Amer. Chena. SOC., 1945, 67, 157.Proc. SOC. Exp. Biol. Med., 1944; 57, 113.83 J . Amer. Chenz. SOC., 1946, 68, 2390, 2393.Proc. SOC. Exp. Biol. Med., 1940, 43, 122.85 Naturwiss., 1939, 27, 228.8 6 Proc. Soc. Exp. Biol. Med., 1946, 61, 125.89 J . Biol. Chem., 1947, 167, 573.81 J . Biol. Chem., 1947, 167, 345.Ibid., 1947, 66, 215.88 Amer. J . Med. Sci., 1947, 213, 509RIMINGTON AND IiAWSON ANTI-THYROIT) T)RTTC;S. 247found that deoxypyridoxine increases xanthurenic acid excretion afteradministration of tryptophan, presumably by interfering with some phase oftryptophan metabolism. O4-Methy1pyridoxine may act in a similar manner,but cleavage of its ether linkage to yield pyridoxine occurs in therat ; administration of 04-inethylpyridoxine was followed by increasedexcretion of 4-pyridoxic acid.found deoxypyridoxine ineffective as aninhibitor of tyrosine decarboxylase, but when it was phosphorylated itdisplaced pyridoxal phosphate in the tyrosine decarboxylase system.It is evident that pyridoxine and its congeners are of great, though asyet not fully evaluated, importance in many biological and microbiologicalprocesses. E.G . H.J. M. Beiler and G. J. Martin5. ANTI-THYROID DRUGS.The present report is not intended to be a comprehensive survey of tlhesubject of the anti-thyroid drugs, as much of this material was dealt wit’hby E’. G. Young in the Annual Report for 1944. Since this date, work hasbeen devoted mainly to the discovery of new goitrogenic agents and theiruse in the elucidation of the mechanism of iodine fixation and thyroxinesynthesis and the use of the radioactive isotopes of iodine in investigationsof thyroid function.Practical interest in substances with anti- thyroid activity may be saidto date from the observation of J. B. Mackenzie, C. G. Mackenzie, andE.V. McCollum that administration of sulphaguanidine to rats causedenlargement of the thyroid gland. A similar goitrogenic effect of dietscontaining rape seed was reported by the New Zealand workers,2 and in thesame year phenylthiourea was found by C. P. Richter and K. H. Clisby tobe goitrogenic to rats.Since then it has been shown that the goitrogenic agents conform tothree types, vix., alkali thiocyanates, organic thiocarbamyl derivatives ofthe thiouracil type, and the less active p-aminophenyl derivatives, such asp-aminobenzoic acid. In all, nearly 600 different compounds belonging tothese three types have been in~estigated.~ Of the thiouracil type, 6-n-propyl-2-thiouracil is probably the most active compound so far tested onrats; its activity is about eleven times that of the parent compound.Amongst the p-aminophenyl derivatives, 4 : 4’-diaminodiphenylmethane andOn J .B i d . Chenz., 1947, 169, 345.J. B. Mackenzie, C. G. Mackenzie, and E. V. McCollum, Science, 1941, 94, 618.T. H. Kennedy and H. D. Purves, Brit. J. Exp. Path., 1941, 22, 241 ; W. .E.Griesbach, ibid., p. 245; W. E. Griesbach, T. H. Kennedy, and H. .D. Purves, ibzd.,p. 249.C. P. Richter and I<. H. Clisby, Proc. SOC. Ezp. Biol. filed., 1941, 48, 684.E. B. Astwood, J. Pharm. E x p . Ther., 1943, 78, 79; 4)) I). A. McGinty t+11(1W. G. Bywater, ibid., 1945, 84, 342; 4c W. G. Bywater, D. A. RicGinty, and N. D.Jenesel, ibid., 1915, 85, 14; 4d U. A. McGinty and W. G. Bywater, ibicl., p. 129.G. W. Anderson, I.F. Halverstadt, W. H. Miller, and R. 0. Roblin, J . rlwier.Chein. Xoc., 1945, 67, 2197248 BIOCHEMISTRY.2-amino-5-sulphanilylthiazole are probably the most active of those tested,having about 25% of the activity of thiouraciL6Selective Concentration of Iodine by the Thyroid.-It has been known fo+many years that the thyroid gland possesses an extraordinary power ofconcentrating iodine. In normal rats maintained on an adequate iodineintake, the iodine concentration in the thyroid gland is 10,000 times as greatas that in plasma,' a finding that illustrates the quite remarkable iodine-concentrating capacity of this tissue. Absorbed iodine is normally trans-formed very rapidly into thyroid hormone, di-iodotyrosine, and possiblyother organic iodine compounds, so that an analysis of the gland revealsthat most of the total iodine is present in organic combination.The anti-thyroid drugs, with the exception of the thiocyanates (whichappear to interfere with the iodine-concentrating mechanism), seem to havelittle effect upon the initial uptake of iodine by the gland, but markedlyinhibit its retention as organically bound iodine (see Table I).8TABLE I.Iodine in Thyroid Glands of Rats 1 Hour after Injection of 500 pg.ofPotassium Iodide.Total iodine,mg./100 gm. Soluble in Insoluble inof wet tissue. water, yo. water, Yo.Normal thyroid glands ..................... 109.8 28-0 72.0Thiouracil-treated glands after KI . . . . . . 30.8 96-7 3.3A close study of the effect of added iodide on the iodine content of thethyroids of rats either fully or partly inhibited by thiouracil has been madeby several workers.I n animals fully inhibited by daily administration of thiouracil in thediet for 10 days, addition of potassium iodide to the drinking water inamounts of 10-1000 mg./l.was followed by increases in the total iodine of'the gland which were roughly proportional to the dose of iodine. A singledose of potassium iodide to a prepared rat caused the thyroid iodine toreturn from nearly nil to half the normal value within 15 minutes.The time relations and proportion of inorganic to total thyroid iodineafter injection of a tracer dose of radio-iodine to propylthiouracil treated ratsare depicted in Fig. 1.' It is seen that in the treated animals the initialsharp rise in inorganic iodine is not maintained.Far from being diminished,by the exhibition of goitrogen, the iodine-concentrating power of the glandmay be increased as much as 30 times although there is not unanimity onthis point.1° That the iodine taken up by the gland under these conditionsE. B. Astwood, A. Bissell, and A. M. Hughes, Endocrin., 1945, 37, 456. ' A. Taurog, I. L. Chaikoff, and D. D. Feller, J . BioZ. Chmz., 1947, 171, 189.* E. B. Astwood, The Harvey Lectures, 1944-1945, Ser. 40, 195.Endocrin., 1947, 40, 403.lo R. A. Larson, F. R. Keating, W. Peacock, and R. W. Rawson, ibid., 1945, 36,149; F. R. Keating, R. W. Rawson, W. Peacock, and R. D. Evans, ibid., p. 137RIMINGTON AND LAWSON ANTI-THYROID DRUGS.249is in tJhe inorganic form has been still further demonstrated by J. E.Vanderlaan and W. P. Vanderlaan9 who observed its rapid expulsionfollowing an injection of thiocyanate. The total iodine uptake, however, isdependent on the t,iine interval elapsing after administration of the iodideand this aspect of the problem has been closely studied by Vanderlaan andVanderlaan and by Taurog, Chaikoff, and Feller,’ using radioactive iodine.These findings help to explain the discrepancies in the results of differentworkers regarding the uptake of iodine by thiouracil-treated animals.Inorganic0 TotalPropykhhurac i/- treatedr a t s Normal rats I1 I f I l l t l I3 6 9 72 15 78 Z f 24 3 6 9 72 15 I8 21 24Hours a f t e l . I-+ injection.FIG. 1 .Y‘ke uptake of a trnver c l o ~ of radioactive iodide by the thyroids of nortttal and prqvyI-fhiouracil-trewted rats.The latter received a diet containing 0- loo/, of propylthiouruciljor 17 d a p .The total quantity of iodine present in the glands of animals used forassay purposes will, of course, be closely related to thc iodine level of thefood ; when such animals are maintained upon a partly inhibitory dose-levelof thiouracil, a reduction in their iodine intake is found to increase markedlythe anti-thyroid action of the drug (see Table 11, from 8 ) and vice ?:prs(c.TABLE 11.Responsiveneus of the Thyroid Glwnd of the Rut to a Svttnll Do.se ofThiouracil for 10 Days.Thyroid weight, Iodine,Treatment. mg./100 8. mg./100 g .body wt. of wet tissue.Normal diet ................................................... 5.8 58-8Low iodine diet ............................................. 9.2 3 ! ) 4Normal diet + 0.01 yo thiourachil........................ 12.4 8.4Low iodine diet + 0.01% thiourucil .................. 31.1 0.260 BIOCHEMISTRY,These relations between dietary iodine and drug action are of muchpractical importance, bearing as they do on the experimental assay ofanti-thyroid activity and therapeutic application of the drugs.Biogenesis of Thyroxin.-No clue was forthcoming as to the biogenesis ofthyroxin until W. Ludwig and P. von Mutzenbecher l1 reported thatincubation of casein with iodine under carefully controlled conditions led tothe production of an iodinated protein possessing thyroid activity andfrom which small quantities of thyroxine could be isolated.Furtherinvestigation l2 has confirmed and extended this work (cf. Annual Reports,1944) and shown t h t , in all probability, the mechanism of the reaction is aunion of two molecules of di-iodotyrosine with oxidative removal of one sidechain to yield thyroxine. The requisite conditions for oxidation are suppliedby iodine itself in the faintly alkaline medium. A similar process may occurin vivo, three steps being envisaged, thus :(a) Liberation of free iodine from iodide in the thyroid gland by an( b ) Iodination of the tyrosine residues in the cellular protein forming( c ) Union of two di-iodotyrosine residues with oxidative eliminationThe nature of the oxidising mechanism at (c) has been the subject ofsome dispute, E.W. Dempsey l3 believing that a peroxidase is present inthe thyroid follicular cells and that this enzyme catalyses the conversion ofdi-iodotyrosine into thyroxine. He claims that it is inhibited by dilutesolutions of thiouracil. C. R. Harington,l& on the other hand, supports thesimplest view, namely, that “ the essential biochemical reaction leading tothe synthesis of thyroxine may be the liberation of iodine from iodide byan oxidizing system; if this were to occur conditions would be set up,namely, the presence of iodine in a faintly alkaline medium, which wouldnot only be suitable for the iodination of tyrosine but would be analogouswith those which will effect the formation of thyroxine from di-iodotyrosinein vitro.”C.R. Harington and R. V. Pitt Rivers 14b found that the spontaneousformation of thyroxine from di-iodotyrosine in alkaline solution is greatlyinfluenced by pH, a maximum yield of 2.776 (based on the di-iodotyrosinenot recoverable) being obtained at pH 10. R. V. Pitt Rivers 14c hasextended this observation and shown that, if the amino-group of the di-iodotyrosine is acetylated, the yields are improved, and that when bothamino- and carboxyl groups are combined, as in the peptide N-acetyl-m-di-iodotyrosylglutamic acid, as much as 36 % of N-acetyl-DL-thyroxyl-glutamic acid is obtained after allowing for recovered starting material. Itoxidative process.mono- and di-iodotyrosine derivatives.of a side chain.l1 2.physiol. Chem., 1939, 258, 195.l2 C. R. Harington, J . , 1944, 193. l3 Endowin., 1944, 34, 27.Proc. Roy. SOC., 1944, B, 132, 223; 14* Biochem. J . , 1945, 39, 157; 14c Personalcommunication, 1947RIMINGTON AND LAWSON : BNTI-THYROID DRUGS. 25 1is also highly significant that the optimum reaction for this transformationwas found to be pH 7.5 suggesting that biological synthesis of thyroxinemight well take place in an analogous manner.If one accepts Harington's view, the point of interference by the anti-thyroid drugs, such as thiouracil, with the biosynthesis of thyroxine isalmost certainly stage (a) in the above scheme, the liberation of iodine frominorganic iodide. This stage may well be accomplished by an enzyme suchas the peroxidase described by Dempsey and found by him to be inhibitedby dilute solutions of thiouracil. Further evidence on this point is alsoavailable from the results of E.De Robertis and I. M. Goncalves l5 on thechange of the redox potential of glands treated with thiouracil from+0.05 to -0.20. Since, however, it has been shown that the in vitroiodination of casein is inhibited by thiouracil, a direct chemical removal offree iodine by the thiol cannot be excluded. The simple explanation thatthose anti-thyroid drugs which arc thiols might act by undergoing oxidationto the disulphide form, 2RSH + I, RS*SR + 2H1, is not applicable inthe case of the sulphonamide derivatives which have no free SH group.There are, moreover, SH-containing substances which are either only weaklyactive or devoid of goitrogenic actlion.H. Schachner, A. L. Franklin, and1. L. Chaikoff l6 suggest that the oxidation of iodide is coupled to someother oxidative process involving the cytochrome-cytochrome oxidasesystem and they note that the synthesis of thyroxine by thyroid slices invitro is inhibited by exclusion of oxygen or addition of small quantities ofsubstances such as azide, cyanide, sulphide, and carbon monoxide, all ofwhich are known to inhibit the cytochrome catalysts. It is noteworthythat the collection and retention of iodine in the inorganic form was notinterfered with by these reagents-still further evidence that the thyroidinechanism for the collection of inorganic iodine can be diffesentiated fromthat for the conversion of icdine into the organic form.The evidence onthe effect of the thiol goitrogens on the cytochrome-cytochrome oxidascsystem is, however, c0nflicting.l'Whatever the mechanism of the primary conversion of iodide into iodinthas a preliminary to the synthesis of thyroid hormone, this mechanism wouldnot appear to be confined to thyroid tissue since extra-thyroidal formationof thyroid hormone has been abundantly demonstrated.ls Adequate drugtreatment seems to be more effective than total thyroidectomy. The veryvarying effect of anti-thyroid drugs in different species-mammalian,amphibian, etc.-and the apparently complete insensitivity of some speciest,o those goitrogens most active in others,s even if allowance be made forpossible differences in absorption of the materials, both from the gut andl 5 Edocrin., 1945, 36, 245.l 8 J .Biol. Chem., 1943, 151, 191.S. It. Lerner and I. 1,. C'l-iaikoff, Endocrii~., 1943, 37, 362; K. E. Paschkis,18 M. E. Morton, I. L. Chaikoff, \Y. 0. Reinhardt, and E. ,hderson, J. Biol. ('hem.,,4. Cantarow, and E. K. Tillson, Proc. SOC. ESP. Biol. M e $ . , 1943, 60, 118.1943, 147, 757252 BIOCHEMISTRY.~~40 - 700.-----Iodine concemtration 07 5 I I I 1 I I Ifrom the blood stream, suggest that it would be injudicious to conclude thatthe same mechanism of thyroid hormone production is operative in all cases.Methods for the Assay of Anti-Thyroid Drugs.-The facts mentioned aboverender it very difficult to devise any method for assaying anti-thyroidpotency; at best the results refer only to that species of organism employed.Since iodine content of the diet, environmental temperature, age, etc., allaffect the outcome, these factors should also be maintained constant andclearly defined in any expression of potency.When a substance such as thiouracil is added to the stock diet of youngrats, changes occur in the basal metabolic rate, weight, and iodine contentof their thyroid glands.The progression of such changes with time isillustrated by the curves of Fig. 2 (from 8).%- 0-10-20-30-40-50I A - 6 UIf dosing is commenced at a sufficiently early age and continued for asufficient time, general retardation of grow-tti also occurs accompanied byother structural changes.19 Any of these effects of the drug might be usedfor assay purposes, but it was soon found that determination of total iodinecontent of the thyroid gland offered a sensitive and sufficiently rapid meansof assessment.The iodine remaining in the gland will be mainly inorganica t dose levels producing complete or nearly complete inhibition, and will, inthe light of what has been said above, be influenced by the intake of iodinelQ A. M. Hughes, Erdocrin., 1944, 34, 69; R. H. Williams, A. R. Weinglass, G. W.Bissell, and J. B. Peters, ibid., p. 317; A. M. Hughes and E. B. Astw-ood, ibid., p. 138;C . P. Leblond and H. E. Hoff, ibid., 1944, 35, 229; E. D. Goldsmith, It. F. Nigrell,A. S. Gordon, H. A. Chctreffer, and M. Gordon, ibid., p.132in the food. It appears to the Reporters that this variable might becliniinated by administration of thiocyanate to the test animals just beforetheir sacrifice and reinoval of the glands.McGinty and Bywater4b have proposed ail assay technique based ontleterminations of total thyroid iodine and find that a linear relation existshetween iodine content/mg. thyroid tissue and log dose up to the point of~naxinium iodine depletion. Moreover, the slope of this line is the sainefor compounds of similar type, which probably indicates a similarity ofpharmacological action. For certain other drugs the linear relationshipholds, but, the slope, i.e., increase of action wit3h incrementl of dose, departswidely from that characteristic of series such as the thiocarharnpls.Quantitative comparison is, therefore, almost impossible.More recently, &l.M. Stanley and E. B. Astwood20 have introduced amethod in which a dose of radioactive iodine is given to the normal subjectand, by nieans o f a specially designed Geiger counter, the rate of accumulationof this iodine in the thyroid gland is measured. Having established thenormal slope, the drug t o be tested is administered and any deviation frointjhe initial rate of iodine accumulation is recorded by the counter. In thisway, the direct effect of the drug on man can be assessed. Stanley and,4stw0od~~ have shown that the results obtained with this technique forcompounds previously used clinically are in accordance with those whichwould have been expected froin the known therapeutic efficiency of thematerials, thus indicating that the method is a valid one for assessing anti-thyroid action in the human subject.Kevertheless, it will be seen that i tdepends essentially upon an interference by the drug with the uptake ofiodine by the thyroid gland from the bloodstream which, as we know, is notof primary consideration in assessing the effectiveness of ant i-thyroidsu hstances. A comparison of potencies estimated by the radioactive iodinem3thotl and the rat assaj- method 2o reveals that, in many cases, vastlytiifferent results are obtained, some drugs, e . g . , 6-n-propylthiouraci1, highlypotent in the rat test (as compared with thiouracil) being only weakly activewhen tested by the radioactive iodine technique.The inverse relationshipholds for 2-aminothiazole. One must not, however, lose sight of possiblespecies idiosyncrasies, as many factors such as detoxication, differences inpermeability, rate of elimination, etc., are involved before the drug reachesits site of action in the gland.No discussion of anti-thyroid drugs would be complete without areference t o the long-recognised beneficial effects of iodine itself in tliyro-tosicosis, a fact which has always been difficult to explain. We would callattention, in this connection, to the work of E. De Robertis and W. W.RTowinski,21 showing that the proteolytic activity of toxic goitres may be asmuch as lOOq/, above normal and demonstrating that this activity issusceptlible t o inhibition by iodine in vitro.The suggestion is made that theaction of iodine may be due to an inhibition of the enzyme proteolytic20 Efidocrin., 1947, 41, 66. 2 x Rev. SOC. Argent. Biol., 1945, 21, 12025% BIOCHEMISTRY.system which brings about the fragmentation of the thyroid globulin complexnecessary for the liberation of the active hormone into the bloodstream.22The hding by A. Lawson and C. Rimington z3 that ergothioneine, whichis a norinal constituent of blood, exerts an anti-thyroid action in the rat,raises the interesting possibility that a relation may exist between the levelof this substance in the bloodstream and the functional activity of the gland.Unfortunately, published methods for the determination of ergothioneine inbiological fluids have proved inadequate, and the question must remainopen until satisfactory analytical techniques have been developed.A.r,.C. R.6. THE BIOCHEMICAL EFFECTS OF MUTATION.To the biochemist cell metabolism is essentially a series of integratedenzymic reactions, to the geneticist the cell is a self-reproducing unit controlledby genes. Interest in the effect of gene mutation on metabolism was a t firstconfined to the study of inborn errors of metabolism in man,l but has graduallyextended to other animalsY2 to plantsY3 to insectsY2, to micro- organism^,^ andto viruses.6When mutation results in the excretion of an unusual metabolite thedifficulty always exists of assessing the significance of that metaboliteas an intermediate of normal metabolism.A. Neuberger, C. Rimington,and J. M. G. Wilson' suggest from a detailed study of alcaptonuria thatoxidation of phenylalanine and tyrosine to homogentisic acid representsthe main, but probably not the only, catabolic pathway for these twoamino-acids both in the alcaptonuric and in the normal individual.in flowers suggested that chemicalreactions were under the control of individual genes. Interpretation ofmutation in terms of biochemistry in Drosophila melanogaster has provedconsiderably more difficult, despite rapid progress in relating phenotypecharacter to chromosome structure in mutant flies. Failure to breedDrosophila on a pure synthetic medium has been onc limiting factor. Con-siderable progress has now been made towards definition of the nutritionalStudy of anthocyanin synthesis 3-1 2 Cf.L. C. Junqueira, Endocrin., 1947, 40, 286.14 Lancet, 1947, i, 586; E. B. Astwood, ibid., 1947, ii, 905; A. Lawson and1 A. E. Garrod, " Inborn Errors of Metabolism," 2nd ed., Henry Frowde and2 S . Wright, Physiol. Rev., 1941, 21, 487; P. B. Sawin and D. Glick, Proc. Nat.R. Scott-Noncrieff, Ado. Enzymol., 1939, 8, 277; W. J. C. Lawrence and J. R.C. Rimington, ibid., p. 906.Hodder and Stoughton, London, 1923.Acacl. Sci., 1943, 29, 55.Price, Biol. Rev., 1940, 15, 35.4 B. Ephrussi, Quart. Rev. Riol., 1942, 17, 327.5 G. W. Beadle, Physiol. Rev., 1945, 25, 643; C. C. Lindegren, Bact. Rev., 1945, 9,6 Cold Spriwg Harbor Symp., 1946, 11.8 G . M. Robinson and R. Robinson, ibid., 1931, 25, 1687; 1932,26, 1647; 1933, 27,111 ; S.E. Luria, ibid., 1947, 11, 1.Biochem. J . , 1947, 41, 438.206; 1934, 28, 1712WORK : THE BIOCHEMICAL EFFECTS OF bIUTATION. 255requirements of insect larva^^ The so-called v+ hormone which producesbrown pigment in Drosophila eyes and also in the eyes of the flour moth,Ephestia Euhniella, has been identified its kynurenine, a product of tryptophanmetabolism.1° Kynurenine has the structure (111) and is probably formedfrom tryptophan (I) through the intermediate (II).llApparently brown eye and white eye strains differ with respect to genescontrolling kynurenine synthesis ; thus, a white eye strain of Ephestia aa ishomozygous wifh respect to gene a which causes lack of kynurenine. It wasclaimed 12 that oxidation of tryptophan to a-hydroxytryptophan was themissing step in an an strain, since injection of a-hydroxytryptophan causedpigment formation, but E.Caspari l3 found that a tissue homogenate of anEphestia larvz oxidised tryptophan as readily as a similar extract froma+ a+ larvae. In both cases the product had the character of an ommochromepigment.14 suggest that in aa strainsconversion of tryptophan into kynurenine takes place a t a reduced rate so thatkynurenine does not accumulate. This result is reflected in the abnormallyhigh tryptophan content of protein from an aa strain. Kynurenine-deficientMutation in Moulds.-The introduction of methods for isolation andgeiietic analysis of radiation induced mutants of Neurospora has led since1941 to a sudden blossoming of biochemical genetics.16 Wild type Neuro-spora requires, for growth, a source of organic carbon, such as glucose, a sourceof ammonium ion, inorganic salts, and one specialised molecule, biotin.Systematic study of induced mutants has led to the isolation of strainswith requirements for each of the B vitamins except folic acid and of otherstrains requiring one or other of a dozen amino-acids.17 Inability to carryRecent results of E.Caspari 1 5 3Drosophila did not show a similar high tryptophan content.l5G. Fraenkel and M. Blewett, Biochern. J., 1947, 41, 469, 475.lo E. L. Tatum and G. W. Beadle, Science, 1940,91, 458 ; A. Butenandt, W. Weidel,and E. Becker, Naturwiss., 1940, 28, 63 ; E. L. Tatum and A.J. Haagen-Smit, J. Bio2.(-'hem., 1941, 140, 575.11 -4. Butenandt, W. Weidel, and W. von Derjugin, Naturwiss., 1942, 30, 51 ; Z.physiol. Chem., 1943, 279, 27; -4. Butenandt and R. Weichert, ibid., 1944, 281, 122;cf. Chem. Abs., 1947, 41, 3800.A . Butenandt, W. Weidel, and E. Beclrer, Natiirwiss., 1940, 28, 277.13 Nature, 1946, 158, 555.l4 E. Becker, Biol. Zentr., 1939, 59, 597.1 6 G. W. Beadle and E. L. Taturn, Proc. Xat. Acad. Sci., 1941, 27, 499; G. W.1' D. Bonner, Cold b'pring Harbor Syinp., 1946, 11, 14.l5 Genetics, 1946, 31, 454.Beadle, Physiot. Rev., 1945, 25, 643256 BIOCHEMISTRY.out the synthesis of an essential metabolite is inherited as though differenti-ated from normal by a single gene, and the working hypothesis has beenproposed that each step in a series of linked biochemical reactions is controlledby a single gene.One apparent exception in which a double requirement for isoleucineand vnline was associated with a single gene mutation has been reconciledwith the original hypothesis.l* The isoleucine-less mutant is able to syn-thesise ketoisoleucine (or-keto-P-methyl-n-valeric acid) but is unable to con-vert it into leucine, and the keto-acid accumulates and acts as an effectiveinhibitor for the conversion of ketovaline into valine; thus, although themould lacks only one synthetic mechanism, the end result is a requirementfor two amino-acids.In several cases, only a single strain unable to carry out a particularbiosynthesis has been isolated, but for several metabolite deficiencies anumber of genetically distinct strains have been obtained, each apparentlyunable to carry out a single step in a metabolic chain of reactions leading toa single essential metabolite.Such genotypically different strains requiringthe same growth factor may furnish valuable evidence for the consecutivesteps of a biosynthetic pathway.Induced mutants of Neurospora have been isolateii which require nicotinicacid or nicotinamide for growth. Genetic analysis indicated that nicotinicacid synthesis might be blocked a t a t least three separate loci. Pyridine,p-picoline, y-picoline, piperidine, piperidine-3-carboxylic acid, trigonelline,ornit hine, proline, or -amino -n-valeri c acid , and a - amino -n - hexoic acid,possible precursors of nicotinic acid, were all unable to replace nicotinic acidfor growth of any of the mutants and are, therefore, not likely intermediatesin nicotinic acid ~ynthesis.1~ The observation that in growing rats tryptophancan replace nicotinic acid 2o and that the two compounds are interchangeablein counteracting the pellagra-like effects of 3-acetylpyridine 21 suggestedthat tryptophan might be a precursor of nicotinic acid.Two nicotinic acid-less mutant strains of Neurospora (A) and (B) differing from the normal by asingle gene have been found to be able to convert tryptophan into nicotinicacid. Both these strains utilised kynurenine as well as tryptophan.22Two other genetically distinct nicotinic acid-less strains (C) and (D) failed touse kynurenine or tryptophan.When supplied with minimal quantitiesof nicotinic acid, strain C produced, in the medium, two growth factors whichcould replace nicotinic acid in the nutrition of strain B. These growthfactors were isolated in crystalline form.lS Elementary analysis, equivalent-weight determinations, and chemical properties suggest that the two com-Is D. Bonner, E. L. Tatum, and G. W. Beadle, Arch. Biochem., 1943, 3, 71;Is D. Bonner and G. W. Beadle, Arch. Biochem., 1946,11, 319.f o W. A. Krehl, P. S. Sarma, L. J. Tepley, and C. A. Elvehjem, J . Nutrition, 1946,2! D. W. Woolley, J . Biol. Chew&., 1946, 162, 179.D. Bonner, J . Biol. Chem., 1946, 166, 545.31, 86.G. W. Beadle, H. K. Mitchell, and J. F. Nye, Proc. Nut. Acad. Sci., 1947, 33, 155WORK : TI-IE BIOCHEMICAL EFFECTS OF MUTATION.267pounds are closely related heterocyclic carboxylic acids, possibly hydroxy-p yridiiiecarboxylic acids. 8'OH r OH I(VI.) IOH zIf it is accepted that tryptophan (I) and kynurenine (111) are precursorsof nicotinic acid (VIII), then some intermediate quinoline derivative such as(VI) must be postulated in order to produce a pyridine-3-carboxylic acid(VII) which could be converted into nicotinic acid. According to this schememutants (C) and (D) would lack enzymes necessary for the conversion of (VII)into (VIII) and might be expected to accumulate hydroxypyridinecarboxylicacids when grown in minimal concentrations of nicotinic acid. Quinoline-carboxylic acids of type (VI) might be formed from kynurenine sinceanimals reared on a pyridoxin-deficient diet excrete xanthurenic acid (IX) .23'rransformation of tryptophan through kynurenine to nicotinic acid cannot,however, be accepted at present as a general mechanism.A nuniber ofworlws 24 have shown that, in animals, oral administration of tryptophangives increased urinary excretion of nicotinic acid derivatives but F.nosen, J. I%'. Huff, and W. A. Perlzweig 25 have failed to find any increase23 s. Lepkovsky, E. Roboz, and A. J. Haagen-Smit, J . Biol. Chem., 1943, 149, 196." F. Rosen, J. W. Huff, and W. A. Perlzweig, ibid., 1946,163, 343 ; B. S. Schweigertand P. €3. Pearson, ibid., 1947, 168, 6.55,; W. A. Perlzweig, F. Rosen, N. Levitas, andJ. Robinson, ibid., 1947, 167, 511.z5 J .Xutrilion, 1947, 33, 561.* Note added in Proof.-One of these compounds has now been identified ns3-hydroxyanthranilic acid (H. K. Mitchell and J. l?. Nye, Proc. Nut. A c d . Sci., 1948,34, 1 ; D. Bonner, ibid., p. 5). The suggested reaction scheme may therefore hemodified, (VI) and (VII) being replaced byrespectively.be inactive in promoting growth of the test strain.Several hydroxypyridinecarhoxylic n,cic]s were synthesisen and found toREP.-VOL. XLTV. 268 BIOCHEMISTRY.in urinary N-methylnicotinamide after administration of kynurenine (111))kynurenic acid (X), or xanthurenic acid (IX).The assumption is frequently and justifiably made that the main metabolicpathways are identical in Neurospora and in other living cells. Some degreeof caution should, however, be exercised in this respect.In Neurospora,tryptophan synthesis proceeds by the series of reactions : 26+ Serine Anthranilic acid (IV) --+ indole (V) .-> tryptophan (I)A cell-free enzyme preparation can be extracted from Neurospora whichcarries out the coupling of serine and indoline using pyridoxal phosphateas coenzyme.27 The suggestion was made that the well-known degradationof tryptophan to indole by Escherichia coli was the reverse of the serinecoupling.26 Evidence has now accumulated that this argument by analogywas wrong. I n the presence of mepacrine, alanine and not serine accumulatesfrom decomposition of tryptophan by E. coZi.28 The presence of mepacrinemay favour a slightly abnormal reaction or halt a normal reaction, since acell-free preparation of E.coli tryptophanase can be obtained 29 whichcatalyses the reaction :Tryptophan --+ indole + pyruvic acid + ammonia.The enzyme can be resolved into an inactive apo-enzyme and a coenzyme.The apo-enzyme was fully reactivated by pyridoxal phosphate. Thepurified enzyme does not deaminate serine or alanine; thus, neither oft,hese amino-acids is an intermediate.Induced mutants of Neurospora have provided fresh evidence for thefollowing biosynthetic pathways :(a) aminoethanol -+ methylaminoethanol -+ dimethylaminoethanolcholine 30( b ) hypoxanthine --+ adenine 31( c ) ornithine + citrulline -+ arginine 32(d) cysteine -+ cystathionine -+ homocystine -+ mcthionine 33It should be remarked in connection with arginine-less Neurospora thatobservation of a series of gene-controlled reactions involving ornithine,citrulline, and arginine only provides evidence for the route of argininesynthesis and does not, as has been suggested,34 provide evidence in favour ofZ G E.L. Tatum and D. Bonner, Proc. Nat. Acad. Sci., 1944, 30, 30; E. L. Tatnm,D. Bonner, and G. W. Beadle, Arch. Biochem., 1944, 3, 477.27 W. W. Umbreit, W. A. Wood, and I. C. Gunsalus, J . Biol. Chem., 1946, 165, 731.28 E. A. Dawes, J. Dawson, and F. C. Happold, Biochem. J . , 1947, 41, 426.29 W. A. Wood, I. C. Gunsalus, and W. W. Umbreit, J . Biol. Chem., 1947, 170, 313.30 N. H. Horowitz, D. Bonner, and M. Houlahan, ibid., 1945, 159, 145; N. H.31 H. K. Mitchell and M.B. Houlahan, Fed. Proc., 1946,5, 370.32 A. M. Srb and N. H. Horowitz, J . Biol. Chem., 1944,154, 129.33 N. H. Horowitz, ibid., 1947, 171, 255.3 4 G. W. Beadle, Physiol. Rev., 1946, $36, 643.Horowitz, ibid., 1946, 162, 413WORK : THE BIOCHEMTCATA EFFECTS OF MUTATION. 259the Krebs-Henseleit cycle. Recent evidence suggests that this cycle asoriginally proposed is not necessarily either the only or the main pathwayfor urea synthesis in aninials.S5 The presence of arginase and urease inNeurospora shows that such a cycle is possible, but it does not necessarilyshow that it actually takes place.Although particularly suitable for genetic studies, Neurospora is by nomeans the only mould for which induced mutation has been analysed internis of loss of biosynthetic enzymes ; thus, D.Bonner 36 reported the isoln-tion of mutant strains of Penicillium notatum and P . chrysogenum whichfailed to synthesise one or other of nine amino-acids and seven B vitamins.Induced mutants of penicilliurn have also been useful in the selection ofcommercially valuable strains for penicillin prod~ction,~' but have not givenany indication of the biogenesis of penicillin beyond the fact that lysine-lessstrains are frequently unable to synthesise peni~illin.~* The biogenesis ofbiotin has been studied using mutant peni~illium.~~Mutations in Bacteria.-Absence of recognisable nuclear division or ofany apparent sexual phase which would permit analysis by classical methodshas retarded study of the genetic and biochemical character of strainvariation in bacteria.Any attempt at analysis must be made, not inthe individual cell, but upon a cell population, so that to the plasticityof the individual must be added the plasticity and possible heterogeneityof the population as a whole ; nevertheless, the biochemical versatilityand speed of reproduction of bacteria make them in some respects almostideal material for a study of the biochemistry of variation.It is a characteristic of gene mutation that it occurs spontaneously with adefinite frequency and is fairly permanent. Various physical and chemicalagencies can be used to increase the frequency of mutation in geneticallydefined organisms. The same agencies produce strain variation in bacteria ;thus, exposure of bacteria to X-rays 40* 41 produces new strains showingspecific growth-factor deficiencies analogous to those reported in Neuro-spora.Un-irradiated strains produce similar variants with a lower fre-quency than irradiated cultures.41 Re-exposure of a nutritionally deficientstrain to X-rays may produce cells with multiple deficiencies. Exposureto ultra-violet light , another mutation-producing agency, also inducesspecific growth-factor deficiency in bacteria,42 and increases the frequencyof occurrence of phage resistance in Escherichia C O Z ~ . ~ ~761 ; H. Borsook and J. W. Dubnoff, ibid., 1947, 169, 461.35 P. P. Cohen and 31. Hayano, J . Biol. Chem., 1947, 170, 687 ; S. Ratner, ibid., p.36 Amer. J . Bot., 1946, 33, 788.3 i M. P. Backus, J.F. Stauffer, and M. J. Johnson, J . Ainer. Ckem. SOC., 1946,68, 152.38 D. Bonner, Arch. Biochenz., 1947, 13, 1.39 J . Biol. Chem., 1945, 160, 455.40 R. R. Roepke, R. L. Libby, and M. H. Small, J . Bact., 1944,48, 401 ; C. H. Gray41 E. L. Tatum, ibid., 1945, 31, 215.4 2 J. S. Lederberg, quoted by E. L. Tatum, Cold Spring Harbor Synp., 1946, 11, 278.43 M. Demerec, Proc. Nut. Acad. Sci., 1946, 32, 36.and E. L. Tatum, Proc. Nat. Acad. Sci., 1944, 30, 404260 BTOCTIEMISTRY.Chemical induct ion of iiiutatkm in Drosophila and in Neurospora by5chloroethyl sulphides or 2-chloroethylamines has been conclusively demon-strated.P4* 45 Exposure of Penicillium notatum to methyldi-2-chlorethyl-amine also gave rise to mutant strains.46 Di-2-chlorethylamine has beenfonncl to be as effective as X-rays in producing biochemically altered strainsof Escherichia C O Z ~ .~ ~ This work was facilitated by the introduction ofan ingenious new method for. the isolation of biochemically dcficicntvariants.4*Synthetic deficiencies induced in bacteria by exposure to radiation or to2-chlorethyl sulphides or 2-chloroethylamines were exactly similar to thoseknown to be associated with gene mutation in higher organisms. It woulcl,therefore, appear to be a reasonable working hypothesis that bacteria,like higher organisms, possess a gene-like mechanism for the control ofheredity and of individual biochemical reactions. This view is considerablystrengthened by the itnportant work of ,J. Lederberg and F,. L. Tatum 49on gene recombination in E .coli. Genetically marked strains of E . coliwere obtained by multiple induced mutation. These strains, when kept inpure culture, bred true and did not revert to the ’‘ wild ” type, but, whentwo strains were mixed and cultured together, new strains arose whichhad regained the ability to live on the simplest media and were biochemicallyindistinguishable from the original ‘ . wild ” strain. Ultra-violet spectrographyand Feuglen staining technique also suggest that some bacteria possess anuclear mechanism which is similar in function, if not in morphology, to thatof metazoan cells.50Although the biochemical conversion of phenylalanine intc tyrosine hasbeon demonstrated in animals, S. Simmonds, E. L. Tatum, and J.S.Fruton 51 suggest from a study of the nutritional requirement,s of phenyl-nlanine-less and tyrosine-less mutants of Escherichia coli that conversionof phenylalanine into tyrosine does not occur in this organism; a con-clusion a t variance with other work based on inhibition studies with (3-2-thi-enylalanine. 53 Phcnylalanine-less E. coli was able to w e simple peptidesof phenylalanine for growth but was iinahlc to use dehydrophenylalanine oracetyldehydrophenylalanine .51Arginine-less mutants of E . coli analogous to arginine-less Neurospora4 4 C. -4uerbach and J. JI. Robson, Xature, 1946, 157, 302; C. Auerbach, J. M.Robson, and J. G. Cam, Scimce, 1947, 105, 243; C. Auerbach, Genetics, 1917, 32, 3 ;cf. also A. Gilman and F. S. Philips, Science.1946, 103, 409.45 N. H. Horowitz, -11. B. Houlahan, 3l. C : . Hungate, and B. Wright, ibid., 1946,4 6 -11. A . Stnhmann and J. F. Stauffer, ibicZ., 1017, 106, 35.4 7 E. L. Taturn, Cold Spring Harbor S y m p . , 1946, 11, 278; S . Simmonds, E. L.48 J. Lederberg and E. L. Tatum, ibid., 1946, 165, 381. ‘@ Nature, 1946, 158, 558; E. L. Tatum and J. Lederberg, .I. Rncf., 1947, 53, B73;104, 233.Taturn, and J. S. Fruton, J . BioZ. Chem., 1947, 169, 91.J. Lederberg, Genetics, 1947, 32, 508.B. Malmgren and G. G. Hedtin, Kutitw, 1947, 159, 578.51 J . Riol. Chem., 1917, 169, 91.5p E. Beersteelier and 11’. Shive, ibid., 1917, 167, 49WORK THE BlOCHEMlCAL EFFECTS OF MUTATION. 26 1substantiate the biosynthetic sequence proposed for arginine.% Otherinduced mutants of E.coZi provide evidence for the occurrence of the follow-ing biosynthetic reactions : anthranilic acid + indole + tryptophan ;glutamic acid --+ proline ; serine --+ gljcine ; vitamin B,-thiazole -+thiamin ; adenine -+ guanine.53, 55 A part,icularly complete series ofbiochemical mutants of E. coZi concerned with sulphur metabolism indicatethe following sequencc :SO4 -+ SO,= -+ S= --> cystcinc --+ [cystathionine] --+homocxsteine -+ met hi on in^.^^Thenormal strain cannot grow on succinate, fumarate, malate, or oxalacet'att ,but, it produces a mutant which can. Metabolism of acetate or lactateby the normal strain is not inhibited by the four'dicarboxylic acids.A. Lwoff and ,4. Audureau 56 suggest that the mutant utilises dicarboxylicacids by an abnormal metabolic route involving phosphorylative degrada-tionof inalate or possibly oxalacetate to pyruvate.Mutation occurs spon-taneously but the mutation rate can be increased by exposure t o X-rays.57lnst,ability of biochemical and morphological character has been regardedas an argunient against the niutational nature of bacterial variation, 58but when it is remembered that a single organism may give rise in less than24 hours to more than 10 lo descendants this instability is not surprising.Spontaneous mutation in genetically defined micro-organisms is by no mcansrare .59Spontaneous reverse mutation from leucine-less t o leucine-independent11as been demonstrated in Neurospora. As might be expected ontlieoretlical grounds, a double mutant with two combined nutritional de-ficiencies reverted to a non-exacting form with almost zero frequency.60It i s particularly significant that, in the presence of sufficient leucine. thelcucine-less strain had a growth advantage over its leucine-independentmutant. A methionine-less mutant of Escherichin coli has also been reportedwith a growth rate greater than the non-deficient strain.61 If an increasedgrowth rate in a, rich medium can be acquired by loss of synthetic function,the poor synthetic ability of highly parasitic micro-organisms becomes atonce understandable. Conversely, " training " of a nutritionally-exactingA novel type of mutation has been reported in Mos.areZZa Zwo#.j3 R. R. Roepke, J . Bact., 1946,52, 504; cf. E. L. Tatum, Cold Spring Harbor Symp.,54 J. 0. Lampen, R. R. Roepke, and 31. J. Jones, Arch. Biochem., 1947, 13, 56;55 E. L. Tatum, Proc. Nut. Acad. Sci., 1945, 31, 215; Cold Spring Harbor S y i ~ p . ,5 6 Ann. Inst. Pasteur, 1947, 73, 517.5 7 R. Croland, Compt. rend., 1943, 216, 616.G8 W. Braun, Bact. Rev., 1947, 11, 7 5 .C. C. Lindegren, ibid., 1945, 9, 111.IT. J. Ryan, Cold Spring Harbor Symp., 1946, 11, 216.1946, 11, 278.A. Lwoff, Proc. Soc. Gen. Microbiol., Oxford, Sept. 1947.1946, 11, 278.61 J. Monod, Ann. I m t . Pasteur, 1946, 72, 879262 BIOCHEMISTRY.pathogenic strain to be independent of a particular nutrient can probablybe regarded as a process of selection of spontaneously-occurring backmutants; 61! 62 however, a true chemical guidance of mutation is by nomeans excluded. 769 76 Spontaneous back mutation in Escherichia colifrom histidine dependence to histidine independence has been reported tooccur with a frequency of lo-* per cell per generation.6OThe now classical analysis of bacteriophage-resistant mutation iiiEscherichia coli initiated by S. E. Luria and M. Delbruick 63 has been followedby application of similar methods to studies of the origin of drug resistance.The conclusion has been reached that, in many cases, drug resistance developsby a mechanism akin t o mutation and is independent of the presence of thedrug which acts solely by a selective mechanism.64 It is by no means certain,however, that all examples of development of drug resistance are of this type .65A biochemical basis for bacteriophage resistance in Escherichia coli has beenindicated by the observations of E. H. Anderson,66 T. F. Anderson,67 andE. Wollman 68 that resistance is associated with loss of ability to synthesisetryptophan or proline. The specificity requirement of the phage for trypto-phan is not absolute and other p-aryl-a-amino-acids can replace it to someextent in promoting phage attack.67Mutations induced by radiation or by 2-chloroethyl sulphides or 2-chloro-ethylamines are random, but the type transformation of pneumococcusinduced by a nucleic acid extract of the S-form of another type has thecharacter of an induced non-random mutation.69 This is not an isolatedand exceptional case since similar type transformation has been reported inEscherichia ~0Ei.70 In each case transformation involved acquisition by theorganism of new synthetic abilities. S. Spiegelman suggests that theenzymic constitution of one strain of yeast may be influenced by a nucleo-protein extract of another strain.71There is no a priori reason to assume that mutation cannot be guided aswell as induced by suitable chemicals. The carcinogenic hydrocarbons6 2 S . E . Luria, Bact. Rev., 1947, 11, 1.63 Genetics, 1943, 28, 491 ; M. Demerec and U. Fano, ibid., 1945, 30, 119.64 M. Demerec, Proc. Nut. Acud. Sci., 1945,31, 16; Ann. Missouri Bot. Gdn., 1945,32,131 ; E. Oakberg and S. E. Luria, J . Bact., 1946, 52, 152; M. Klein and L. J. IZimmel-man, $bid., p. 471 ; M. Klein, ibid., 1947,53, 463 ; C. A. Chandler and E. B. Schoenbach,Proc. SOC. Exp. Biol. Med., 1947, 64, 208 ; H. E. Alexander and G . Leidy, J . Exp. Med.,1947, 85, 329.6 5 c. N. Hinshelwood, " The Chemical ICinetics of the Bacterial Cell," Oxford,1946.6 6 Proc. Nut. Acad. Sci., 1944, 30, 397 ; 194f3, 32, 120.Cold S&ng Harbor Symp., 1946, 11, 1.Ann. Inst. Pasteur, 1947, '43, 348. '@ M. McCarty, Bad. Rev., 1946, 10, 63.'O A. Boivin, A. Delaunay, R. Vendrely, and Y. Lehoult, Conhpt. rend., 1945, 221,718; A. Boivin, R. Vendrely, and Y . Lehoult, ibid., p. 646; R. Vendrely and Y. Lehoult,&id., 1946, 222, 1357; A. Boivin, A. Delaunay, It. Vendrely, and Y. Lehoult, Experi-e n t k 1946, 2, 139.Cold Spring Harbor Syirrp., 1946, 11, 266WORK : THE BIOCHEMICAL EFFECTS OF MUTATION. 263induce mutation in Drosophila,72 in mice,73 and possibly in bacteria.74Dibenzanthracene-induced mutation in the mouse may be a guided ratherthan a random mutation.75 On the basis of guided mutation chemo-therapeutic contlrol of cancer seems at least a distinct possibility.T. S. W.D. J. BELL.E. G. HUGHES.A. LAWSON.C. RIMINGTON.R. SCARISBRICK.T. S. WORK.7 2 M. Demerec, Nature, 1947, 159, 604.73 L. C. Strong, Proc. Nut. Acad. Sci., 1945, 31, 290; J. G. Carr, Brit. J . Cuncer,74 P. A. Ark, J . Bact., 1946, 51, 699.7 5 J. G. Carr, Brit. J. Cancer, 1947, 1, 152.i G C. C. Lindegren and C. Raut, Ann. Missouri Bot. Gdn., 1947, 34, 86.1947, 1, 152

ISSN:0365-6217    

DOI:10.1039/AR9474400217

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

ANALYTICAL CHEMISTRY.1 . INTRODUCTION.ANALYTICAL chemistry is relatively, but not absolutely, an esact science.All determinations are subject to errors, and it is essential to have a properappreciation of their magnitude; it is important to know what real weightcan be placed upon such terms as accuracy and precision. Statisticalmethods are being increasingly applied for this assessment, and in additionthey are used both as a guide when designing an experiment to obtain thedesired information with a minimum expenditure of time and material, andas a tool when the experiment is completed to abstract maximum informationfrom the data. It is appropriate, therefore, that a substantial part of thisReport should be devoted to the application of such methods to chemicala iialysis .During recent years an enormous amount of work has been directed tothe application of X-rays for analytical purposes.This subject was dealtwith ten years ago and short references have appeared in other Sectionssince. It seemed desirable, however, to enumerate the more importantinstances where information of value has been obtained, as this mill suggestpossibilities in other directions.The introduction of a variety of new surface-active agents has raisedmany analytical problems. This field impinges on that of the oils and fatsand the common ground leads in several directions. A survey has thereforebeen made of some of the work in both fields. J. R. N.2. THE APPLICATION OF STATISTICS TO CHEMICAL ANALYSIS.The use of statistical principles both in designing experiments and inextracting from them the information sought has been common practicefor many years among thosc employing biological methods of assa8S;.Theinherent variability of the dosc-response rehtionship from aniinal to animal,and even from day to day in the same animal, is so large that the recognitionof effects genuinely caused by controlled factors, as distinct from those dueto the random fluctuation of uncontrolled factors, is hardly possible unlessstatistical methods are employed. On the. other hand, it is characteristicof chemical and physical methods of analysis as a class that the inherentprecision is relatively high and the relation of the quantity actually measuredto the parameter it is desired to estimate is constant, or sufficiently so toneed only occasional checks.In consequence, while an estimation of thevitaniin-D content of a food may necessitate simultaneous observations on40 or more rats, a determination of its nitrogen content will often mean butone observation, even duplimte analyses being regarded in many laboratoriesas an unnecessary and time-wasting refinement\VOOL) : APPIIICATION OF STATISTICS TO CHEMICAL ANALI-SIS. 265It will not be surprising, therefore, if a report of progress in the applic-ation of statistics to chemical analysis appears to contain a disproportionatenumber of‘ references to biological methods. Nevertheless, there is a growingappreciation of the need for attention to a t least the more fundamentalstatistical principles in all analytical investigations.The Society of PublicAnalysts and Other Analytical Chemists held a joint meeting with theFood Group of the Society of Chemical Industry in December 1946 to discuss“ The application of statistics to food problems ”, and while three of thepapers 1, 2, described the use of statistical techniques in elucidating andinterpreting analytical results, the introductory paper * stressed even morethe value of a stat’istical approach when designing the experiment.Appreciation by experimenters of the need for calling the statisticianinto consultation before rather than after the experiment is a growth ofrecent years-largely stimulated no doubt by R. A. Fisher’s well-knownbook 5-b~t analysts are beginning to realise how this can ensure the maxi-mum return for their experimental work.So often the devising of a newanalytical technique involves an investigation of the iiifluence of manyrariables-the concentration of one or more reagents, the temperature ofreaction, the time factor at this or that stage of the analysis, and SO on.The type of experimental design known to statisticians as “ factorial ”, inwhich the effect of changing several variajbles simultaneously can be examined,offers many advantages over the older type of experiment in which onefactor is varied a t a time, all others being held constant, so that “inter-action ” effects cannot be detected, much less measured. The Rfinistry ofSupply has published a book by K. A. Brownlee in which this point isvery clearly made, and it is stressed in another recent book by a team ofworkers employed by I.C.I.Ltd. This also summarises the statisticaltechniques and computations most likely to be useful to laboratory workers,with a clear exposition of the conditions in which each is applicable.An instance of an analytical investigation with a well-planned designis afforded by a paper on the correct empirical factor to be used in thedetermination of pyrethrin I by the mercury method. Five observerstested the effect of many variables on the factor obtained, and the analyseswere so randomised (duplicate analyses never being performed on the sameday, for instance) * that the influence of each factor, the relative precisionof the workers, and the standard errors attaching to each set of conditions,could be separately evaluated.In consequence, those details of the tech-nique which need to be rigidly standardised could be identified and anW. B. Adam, Anal@, 1948, 73, 7.E. H. Shiner, ibid., p. 15.“ The Design of Experiments ”, Oliver and Boyd Ltd., 4th edition, 1947.“ Industrial Experimentation ”, H.M.S.O., 2nd edition, 1947.“ Statistical Methods in Research and Production ”, editecl by 0. L. Daviesa G. T. Bray, S. H. Harper, I<. A. Lord, E’. Major, :m(L E’. 13. Tresttciern, J . ~ 5 ’ ~ .D. I<. L. Blnxter, ibid., p. 1 1 .D. J. Finney, ibid., p. 1.Oliver and Boyd Ltd., 1947.C ‘ ? L C ~ . IME., 1947, 66, 275.* On this point, see also refs. (17)-(21)266 ANALYTICAL CHEMISTRY.empirical factor stated with known and high precision.N. T. G~idgeman,~in order to estimate the relative potencies of vitamins-D, and -D3, devisedspecial designs adapted to the subsequent use of covariance analysis toimprove the precision of the results. In all analytical research the valueof modern experimental designs can hardly be overstated ; too many papersstill appear in which a most painstaking investigation involving perhapshundreds of analyses has not yielded anything like the amount of inform-ation that the investigator’s labours deserved-and could have achieved,if he had given to the planning of the experiment a fraction of the timedevoted to the practical work.Once the experiment has been planned, the work of the analyst beginswith the taking of the sample.The necessity for the sample to be trulyrepresentative of the bulk has often led to the drawing of a sample fromevery container. The U.S. Customs Regulations of 1937, for example,called for this method when sampling imported raw sugar in bags. Theprocess is time-consuming and damages the bags. Experiments weretherefore conducted 10 to examine the possibility of sampling a proportiononly of the bags without thereby incurring an excessive risk of error in thefinal result. The standard Customs trier was first compared with twoalternative patterns ; they were found to give almost identical standarddeviations and offered no advantages, and the standard trier was used forall subsequent tests. Knowing the standard deviation, it was now possibleto determine what proportion of bags would need to be sampled for anygiven sampling error, and calculation indicated that to sample 1 in 7 of theaverage cargo of 20,000 bags should be satisfactory.This was verifiedexperimentally; in a series of 5 cargoes, the maximum difference betweenthe revenues as estimated from sampling all the bags and from 1-in-7sampling was $68 in a total of $124,000. A method for mixing sampleswas developed experimentally which was less laborious than the older handmethod and did not lead to any loss of precision.A novel approach to the question of sampling made by A. Wald l1 hasresulted in the creation of a new technique known as “ sequential sampling ”which has many advantages in certain circumstances, while the sequentialprinciple, of which a lucid exposition has been given by G.A. Barnard,12is capable of wide application. Instead of taking a fixed number of samples-more generally, instead of making a fixed number of observations-thenumber of observations is determined by the results obtained. At eachstage after making the lst, 2nd, . , , etc., observation, calculations aremade which enable one of three decisions to be taken-to take action 1,which may be the acceptance of the material under examination; to takeaction 2, which may be its rejection ; or to make another observation. Theexperiment terminates with the taking of one of the f i s t two decisions,Quart. J . Pharm., 1945,18, 15.lo E. F. Kenney, I d .Eng. Chem. Anal., 1946,18, 684.l1 Ann. Math. Stat., 1945, 16, 117; J . Arner. Stat. ASSOC., 1945, 40, 277.l2 J . Roy. Stat. SOC., Suppt., 1946, 8, 1WOOD : APPLICATION OF STATISTICS TO CHEMICAL ANALYSIS. 267which happens as soon as enough information has been accumulated topermit of the acceptance or rejection of the material with a predetermineddegree of confidence, and no more work is done than is sufficient for thispurpose. The average sample size over a period using this technique isalways less-sometimes much less-than the size of the fixed sample requiredin the usual technique for equal improbability of wrong decisions.An example is afforded by C. W. Churchman’s application l3 of thcsequential principle to the problem of discriminating with as few analysesas possible between alternative empirical formule for an organic compound.In the simplest instance, only one element is determined, the theoreticalpercentages of this element for the two formule being a, and u, respectively.An element should be chosen for which (a, - a2)/s is as large as possible,where s, the standard error of the determination, is assumed to be knownfrom previous experience.After n determinations the results are summedand the total compared with two quantities A , and A , which are simplefunctions of n and the known quantities, a,, u,, and 9. If the sum of theresults is less than A,, then a, is accepted as correct; if it is greater thanA,, then u, is accepted. If the sum lies between A, and A, another analysisis performed. A somewhat more complicated procedure is necewary iftwo or more elements are determined, but the principle is the same.F.Yates pointed out in 1935 l4 that the precision with which a numberof small objects could be weighed was much improved for a given numberof operations by weighing them in combinations rather than singly.H. Hotelling l5 has examined the general problem both for the type of balancewith which objects may be placed in either pan and for the spring balanceor other type in which one pan only is available. The principle involvedapplies whenever the weights of n objects are of the same order and lightenough for their sum to be within the capacity of the balance. It is assumedthat s, the error of one weighing, is constant whether the objects be weighedsingly or in groups.Then the n weighings which must be made in anyevent can be used to better advantage than merely weighing each objectseparately. As an illustration, consider the weighing of four objects, a,b, c, d, on a balance not needing a zero correction. The variance of a singleweighing is s2, whether one object be weighed or four. Let the followingfour weighings be made :a + b + c + d = y,;a - b + c - d =g3;a + b - c - d =y,;a - b - c + d = yq.Objects with a minus sign in these expressions are placed in the right-handpan and those with a plus sign in the left-hand pan. The weight of objecta is now given by t(y, + y, + y3 + yq), with similar expressions for theweights of the other three objects.The variance of any one y/4 is s2/16,so that the variance of the weight of a is $/4, which is a quarter of thevariance of a single weighing of u by itself. It is not possible, however, togive schemes for p weighings of n objects with minimum variance for all14 J. Roy. Stat. SOC., Suppt., 1935, 2, 211. l3 I n d . Eny. Che~ra. Anal., 1946,18, 267268 ANALYTICBL CHEMISTRY.values of p arid n though solutions have been given 15y16 for several specialcases. The technique is interesting and elegant but does riot appear tohave much practical application to analytical work. Apart from otherconsiderations, the error of a single weighing is nearly always so much lessthan other experimental errors that its reduction would not modify appre-ciably the combined error of an analysis, and against such reduction as iseffected must be offset the risks of experimental mistakes in selecting theobjects for each group-weighing, and of arithmetical mistakes in the calcul-ations ! In gravimetric work of high precision, however, or if analyses areto be carried out on quantities which are smaller than is desirable havingregard to the sensitivity of the balance to be used, the group-weighingtechnique may be of value.The improvement in precisioii which theoretically results from replication,and the insistence of statisticians that there should always be some estimateof the error of an analysis, has led to a commendable spreading of thepractice of performing analyses in duplicate or even in higher replication.There is a trap here, however, to which attentionwas drawn over 30 yearsag0.17 An apparent concordance between duplicates may give a misleadingimpression that all is well if the anaIyses are not independent.The differ-ence? between pairs of truly independent analyses may contain componentsdue to differences between the samples analysed, the techniques of theindividual workers, the days of the week or the months of the year whenthe analyses were performed, the reagents or the apparatus of different-laboratories. So-called duplicate analyses are, however, often made bythe same worker in the same laboratory on the same day, so that the lastthree components disappear. Sometimes, howibile dictu, only one portionof one sample is weighed out and the alleged duplicates are but aliquotparts of the same filtrate! In such circumstances, there may be a largesystematic error which will completely escape detection.R. F. Moran l8points out that, since the ratio of the standard error of a single determinationto that of the mean of two independent determinations is theoretically \'2,a test of the independence of duplicate analyses is afforded by examiningthe ratio actually obtained in practice. In one example which was investi-gated from this point of view the ratio was foiind to be not 1414 but 1.05.The duplicates were thus highly correlated ; the additional genuine in-formation that was being obtained in return for the extra work involvedin duplication was quite negligible, while the true magnitude of the errorsinvolved was as unknown as if only single analyses had been performedJ.Mandel19 has extended this argument to cover the estimation of thevalue of AT-fold replication in terms of the ratio of the variance of one deter-mination to that of the mean of AT determinations, which he calls the PO-efficient of improvement. It will clearly vary from 1 for no improvementto N when the analyses are quite independent. A proper examination ofAnn. Math. Stat., 1944, 15, 297. l8 I(. Kishen, ibid., 1945. 16, 294.l9 Ibid., 2946, 18, 280.l 7 " Student ", Riometrika, 1909, 7 , 210; 1914, 10, 179.l8 Ind. Eng. C1m.m. Anal., 1943, 15, 361tihc matter, however, woiild require a fairly full investigation by a " researchanalyst ", to use Mandel's phrase, and if in a particular instance this weredeemed to be worth while, the experimental design ought to be such thatthe results could be used for an analysis of variance.The practical moral of these considerations is that replicate analysesshould as far as is practicable be so performed that none of the possiblecomponents of error is suppressed in the results.If, for example, ananalyst is to make triplicate analyses on each of 3 samples, it is far betterthat he should perform one analysis on every sample on each of 3 days than3 analyses of sample 1 on day 1, 3 of sample 2 on day 2, and 3 of sample 3on day 3.20 Checks by independent workers, if possible in another laboratory,are always useful and sometimes revealing, as is shown by H.G. MacColl 21in describing a system of controlling the accuracy of routine analyses.From a large number of analyses of the same sample the standard deviations of the determination is first estimated. A4nalyses of a reference sampleof known composition are then made daily and plotted on a control chartof the kind familiar to users of " quality control " methods in industry,with a line drawn a t the true value and other lines either side of it at distances&29 and 3 3 9 apart. Determinations falling outside the outer or " action "lines suggest investigation of the reason. The averages of the 6 analysesmade every week are also plotted on a control chart with lines &2s/1/6and 3s/& apart; divergences shown on this chart call for more seriousattention as being indicative of persistent causes.Samples are regularlyinterchanged between laboratories and the differences plotted on a similarchart with a central line at zero. The method of setting up such controlcharts, and their uses in general analytical work, have been discussed byG . Wernimont 22 and J. A. MitchellY23 while others have described theirapplication in special case^,^*^ 25 including organoleptic tests.26 Theyinvolve little labour once the necessary initial data have been obtained,and enable both occasional sudden alterations and slow persistent driftsin accuracy or precision t o be detected before damage is done.The use of the range of a set of observations as a measure of their " spread "or dispersion about the mean is a time-honoured practice.Statisticiansprefer the calculation of the standard error, on the ground that (given anormal distribution) it is the only fully efficient statistic in the sense that italone utilises the whole of the information available in the data. It is truethat the range is inefficient, for i t measures the difference between 2 only ofthe observations, the magnitude of the others being immaterial. It hasthe merit, however, of requiring no calculation other than a single subtractionand is sometimes quite suitable as a quick check in analytical ~ o r k . ~ ' An?O J. W. Tukey, Anal. Chem., 1947, 19, 957.22 I n d . Eng. Chena. Anal., 1946, 18, 587.2-1 W. N. W. MTallace, J . Proc. Austral. Chem Inst., 1945, 12, 239, 243.2.i J.D. Heide, India Rubber World, 1946, 114, 653, 66s.46 S. Marcuse, J . ditter. Stat. -4ssoc., 1945, 40, 214.2 7 1%. G . Newton, P?iem. and Id., 1945, 322.21 Chemn. and Irzd., 1944, 418.p3 Anal. Ghen,., 1947, 19, 961270 ANALYTICAL CHEMISTRY,est'imate s1 of the true standard deviation c can be made by dividing therange w by a factor d, where d depends on the size of the sample a n d hasbeen tabulated by 0. L. Davies and E. S. Pearson.as Compared with theestimate of 0 afforded by the standard error s as usually calculated, s1 isa t its best when the set of observations is broken up by the experimentaldesign into m sub-sets of n observations each. The range is then calculatedfor each of the m sub-sets separately and the mean range ii? is divided bythe correct value of d to give sl.When n is in the neighbourhood of 2-6,this estimate is reasonably efficient, and E. C. Wood 29 has pointed oiit thatthese conditions obtain in microbiological assays, in which about this numberof observations is usually made a t each of several dose-levels. A checkcan thus be kept with very little trouble on the error of routine assays andany tendency to loss of precision noted and investigated. The estimatea1 may also be used as is the standard error s for testing the significance ofthe difference between two means; just as the ratio of a difference to itsstandard error s is the bmis of " Student's " well-known t-test, 80 an analogousstatistic G is obtained by dividing the difference by the estimate sl, and itsefficiency is little inferior to the t-test when the sample size is less than ten.30E. Lord 31 has given tables of the distribution of G for various values of mand n which can be used in the same way as tables of the distribution of t .The quantities actually observed or measured in the course of an experi-ment are not necessarily suited as they stand to the computation by standardstatistical processes of the result and its standard error.For reasons whichare discussed below, it may be desirable to transform the independentvariate x, the dependent variate y, or both, into other functions. A familiarinstance, or rather class of instances, is the use of the logarithm of the doseas the dose metameter * in biological assays. J. H. Gaddum 32 has collectedmany examples from widely varied fields of investigation in which thetransformation X = log x or its alternative X = log (x & x,,) has beenfound valuable for the reason that the distribution of X is normal whereasthat of x is not. He refers to the distribution of x in such cases as " log-normal ", and suggests that, whenever the variance is relatively large, thetransformation can do little harm and may facilitate interpretation of thedata.N. T. Gridgeman33 has also discussed the handling of assays inwhich this transformation is made, with special reference to vitamin-Dassays, while E. C. Fieller 3* has surveyed the principles involved in applyingtransformations not only to the dose but also to the response in biologicalassays.There is a fundamental distinction between these two possibilities ;the transformation of the independent variable x may affect the wholedesign and method of' computation of the experiment, whereas the trans-28 J . Roy. Stat. SOC., Suppt., 1934,1, 76.30 J. F. Daly, Ann. Math. Stat., 1946, 17, 71.31 Biometrika, 1947, 84, 41.33 AnaEyst, 1946, 71, 376. * A word introduced by A. L. Bacharach at the suggestion of L. Hogben to meanthat function of a quantity actually measured in an experiment which is iised in thesubsequent calculations.2Q Chem. and Ind., 1947, 334.82 Nature, 1945, 156, 463.34 Ibid., 1947, 72, 37WOOD : APPLICATION OF STATISTICS TO CHEMICAL ANALYSIS. 271formation of the dependent variable y may-subject to considerationsdimmed below-be regarded as a purely arithmetical device without effecton the experimental or statistical techniques used.An excellent summaryof the uses of transformations in general has been given by M. 8. Bartlett,35and D. J. Finney36 has emphasised the essential unity of the principlesunderlying all biological assays by bringing together the transformationsused in different types of assay and laying down certain generalisationscovering them all.Whatever method is used for calculating the result of an assay, twoassumptions are implicit-that the dose and response metameters are sochosen as to be linearly related to each other within the range used in thecomputations, and that the response metameter is normally distributed a tall dose-levels.These may be referred to as the assumptions of linearityand normality. A moderate degree of departure from normality is notvery important ; * but the assumption of linearity is necessary if the calcul-ations are to be reasonably simple, and the transformations used in practiceare in nearly every instance chosen from this point of view. Usually,however, the formula.? and computations then applied have been based on athird assumption, namely, that the variance of the response metameter isindependent of the dose-level, or in other words that no more weight is tobe attached to observations a t any one dose-level than a t any other. Ifin any instance this assumption is untrue, then the results obtained may beto that extent erroneous. In consequence, Fieller 34 advocates that thattransformation should be sought which leads to stability of variance, withlinearity as a desirable but secondary consideration.The reverse approachmay be dangerous if a transformation which achieves excellent linearitycauses the variance to become unstable. Fieller gives a method for deter-mining the correct transformation to stabilise the variance in any instancein which the law connecting the variance with the mean response is known.On the other hand, if a transformation is found which stabilises thevariance but gives a marked deviation from linearity, the efficient estimationof the result and its standard error will be very difficult and even impossible,and Pinney36 suggests that the better line of attack is to make linearitythe primary objective.If as a result the variance is found to alter fromone dose-level to another, then the appropriate weights should be attachedto the observations in the ensuing calculations. This may complicatematters somewhat, but the complications are not excessive, and at leastthe conclusions reached will be trustworthy.In certain circumstances, moderate departures from linearity may havelittle effect on the accuracy of the results-as in the well-known " 4-point "design used in biological assays 37-though unless the linearity can bechecked there may be no criterion of the validity of the so that morecomplex designs are sometimes desirable. The general method of computing35 Biornetrics, 1947, 3, 39.37 E. C.Wood, Nature, 1944, 153, 84. * See the concluding paragraph of this section.36 J . Roy. Stat. SOC., Suppt., 1947, 9, 46.38 D. J. Finney, ibid., p. 284272 ANALYTICAL CHEMISTRY.the result of assays in which the response metameter is linearly related tothe “ logdose ” has been given by, iizter a h , J. 0. Irwin,39 and for assay?of the cross-over type a complete description of the computations is givenby K. W. Smith, H. P. Marks, E. C. Fieller, and MT. A. Br0om.~0 Morerecently, L. I. Pugsley 41 ha9 well summarised the calculations of ’’ logdose ”assays both by Irwin’s method and vin a11 analysis of variance; the secondmethod is particularly useful for symmetrical 6-point designs since i t enables5 components of the “ between-doses ” variance to be examined separatelyfor significance.I n quanta1 assays, where the response is of the “ all-or-none ” type, thetransformation of the response to the normal equivalent deviate or “ probit ”as suggested originally by C.I. Bliss42 has been widely used to convertthe typical sigmoid logdose-response curves into approximations to linearity.D. J. Finney43 has recently published a book on the many applications ofprobit analysis. C. W. Emmens44 found that the relation between thelogdose of a hormone and its effect on the growth of an organ \vas oftenbetter fitted by the “ logistic ” curvewhere IY, p, and L are constants. In consequence, J. Berkson 45 has proposedthe use of “ logits ”, based on this curve just as probits are derived from thenormal curve; the logit of y = log(1 - y) - log y.He finds that logitsfit certain examples better than probits. \V, R. Thompson 46 has describeda method based on interpolating between two adjacent “ moving averages ”,these being the means of k consecutive values of the response metameter(it is assumed that logdoses are equally spaced) ; k is chosen from experienceof the type of assay being performed and will often be 2 or 3, and the twomoving averages used are those which bracket a probability of responseof 0.5. The method is fairly simple, but the calculation of the standarderror of the result can only be performed approximately. The well-triedprobit iiiethod is by no means as laborious as those who have not muchexperience of it tend to think ; with practice, the process becomes automatic,and most of the work involves little more than the intelligent use of tables.The various procedures discussed above are none of them applicableto microbiological assays, in which other relationships are found to prevailbetween the dose and the mean response.In a few types of assay, thesequantities are linearily related to each other, and no transformation isneeded. The potency of the Test Preparation (T.P.) relative to that ofthe Standard Preparation (S.P.) is then calculated from the ratio of theslopes of the T.P. and S.P. dose-response lines, so that these may conveniently39 J . Roy. Stat. Soc., Suppt., 1937, 4, No. 1 ; J . Hyg., 1943, 43, 121.4 O Quart. J . Pharm., 1944, 17, 108.42 Ann. App. Biol., 1935, 22, 134.43 “ Probit A4nalysis ”, Camb.Univ. Press, 1947.4 5 .J. =Imer. Stat. ASSOC., 1944, 39, 357; 1046, 41, 70.4 6 Rnct. RPP., 1917, 11, 115.‘l E17docriuology. 1946, 39, 161.44 t7, Endoc~in., 1940-41, 2, 194WOOD APPLICATION OF STATISTICS TO CHERITCAT, ANALYSIS. 27.3be referred to as slope-ratio assays.47 The most efficient experimentaldesign, with the correct methods of computing the result and the fiduciallimits of such assays, and of testing their validity have been discussed fairlycompletely both for the case in which there is only one T.P.48349.50 and alsowhen several T.P.s are to be assayed sim~ltaneously.~~Tn most microbiological assays, however, the dose-response relationshipis curved throughout its length. The transformation of both the dose undthe yesponse to the corresponding logarithm was found 52 to linearise therelationship for assays of many amino-acids and some vitamins.It is truethat the variance after transformation appears to be no longer independentof the dose-level, an effect which, as stated above, is theoretically disastrous.The high precision of microbiological assays fortunately reduces the dangerconsiderably, and D. J. Finney 53 has found in two assays he has testedthat, when due allowance is made for the heterogeneity of the variance, theresulting rabher lengthy computations give a result negligibly different fromthat given by the usual simple calculation assuming constant variance.The same '' log-log " transformation has also been found to linearise therelation between dose and diameter of the zone of inhibition in a method ofpenicillin assay; between concentration of disinfectant and time to effectsterilisation under standardised conditions ; 55 and between titration andconcentration of sugar in the well-known Lane and Eynon volumetricmethod.56 G.E. P. Box and H. Cullumbine 57 found in experiments withcertain toxic substances that the dose was linearly related to the reciprocalof the survival time and that this linearising transformation also normalisedthe distribution and stabilised the variance-an unusually complete set ofadvantages.A few papers have appeared recently in which the inherent errors ofmalybical methods have been statistically investigated. A. C. Oertel andH.C. T. Stace 58 have examined the various factors contributing to the errorof apectrochemical (flame) analysis of cations. It was found that evenwith an element&ry technique the standard error was less than 4%, and thatmost of this was due to the variations in the photographic plates used.J. Geffner 59 has investigated the same question. 0. L. navies, C. H.Giles, and T. Vickerstaff 60 have compared the precision obtainable with4 7 33. C . Wood, Nature, 1945, 155, 633.4 0 D. J. Finney, Quart. J. Pharm.. 1945, 18, 77.4s E. C. Wood, Analyst, 1946, 71, 1 .j0 E. C. Wood and D. J. Finney, Qtcurt. J . PJLarm., 1946, 19, 112.j1 C. I. Bliss, Ann. Math. Stat., 1946, 17, 232.62 E. C. Wood, Nature, 1946, 158, 835; Analyst, 1947, 72, 84.53 Private communication.'* F.81. Goyan, J. Dufrenoy, 1,. A. Strait, and R. Pratt, J . A w p r . Pharm. Assoc.,6 5 R. C. Jordan and S. E. Jacobs, J. Hyg., 1944, 43, 275 and subsequent papers. '' I!'. T;c'. Zerban, W. J. Hughes, and C . A. Nygren, Ind. Eng. ClrenL. Anal., 1946,G 7 Brit. J . Pharnzncol., 1947, 2, 27.** Anal. GItP?)b., 1947,1g, 1053,1947, 36, 65.18, 64.5 0 .I. LSOC. Chent. Ind., 1946, 65, 350.so J . Xnc. Dyprs Col., 1947, 63, 80274 ANALYTICAL CHEMISTRY.the Hilger photoelectric absorptiometer, the Hilger-Nu t ting spectra-photometer, and a Duboscq-type colorimeter, in determining the strengthsof various dye solutions. The coefficients of variation in the three case8 were1-00, 1-35, and 2.49, respectively. The accumulation of sound data con-cerning the inherent errors of analytical techniques and apparatus is asine qua non for any objective evaluation of the relative merits of alternativemethoda, and it is greatly to be hoped that these papers will inspire verymany more investigations of the same sort.W. J.Youden 61 has pointed out that, whenever an analytical investig-ation involves replicate estimations of a ratio (as, for instance, when theaccuracy of a proposed analytical technique is to be assessed by comparingthe results obtained by its use with those obtained on the same samplesby a standard method), the regression line should be calculated. The slopeof the line is then the best estimate of the ratio sought, while any systematicerror is detectable as a failure of the regression line to pass through theorigin.Several interesting exampIes are given; this paper is worth theattention of every analyst.Finally, a letter from V. J. Clancey 62 should be mentioned which raisesan important point. He has examined the results which have accumulatedin the course of analysing chemically a wide variety of metals, chemicals,and other industrial products, with the view of ascertaining if‘ the distributionof the results was or was not ‘( normal ” in the statistical sense. He foundthat only l0-15% could be so regarded; the remainder were significantlynon-normal. Some 15% were truncated normal curves,* while others wereleptokurtic, J-shaped, or skew. His main conclusion is that great cautionshould be used in applying ordinary statistical tests to the data of chemicalanalysis. The matter needs further enquiry, but the danger seems to theReporter to be small so long as attention is directed, as it usuallyis, primarilyto the mans of a series of observations, for it is well known that the dis-tribution of the means of a series of samples drawn from a population willusually approach closely to normality even if that of the population is widelydifferent from normal.W. G. Cochran 63 gives a thoughtful discussion ofthe consequences to be expected if the assumptions made in an analysis ofvariance are not satisfied, and concludes that while extreme skewness maylead to serious errors, the cases in which the departures from normality aresufficiently serious to give misleading results should be detectable from aknowledge of the nature of the data and from a careful scrutiny of the figuresbefore the statistbal analysis is begun.of some actual experimental data found to be distributed non-normally asshowing that ( ( no serious error is introduced by non-normality in theHe summarises an investigationG 1 Anal.Cheira., 1947, 19, 946.63 Biometrics, 1947, 3, 22.* The Reporter has experieaced this kind of distribution in the moisture content ofmalt extract; it was found to be due to the rejection by the manufacturers of batcheshaving a content above or below the specification limits set by the consumer, so thatthe “ tails ” of the normal curve never reached the consumer’s laboratory.62 Nature, 1947, 158, 339.G4 G.B. Hey, Biometrika, 1938, 30, 68DOTHTE : X-RAY ANALYSTS. 275significance levels of the P-test or of the two-tailed t-test." In any event,it would be foolish to allow the arbitrary 5% level of significance to createa rigid line between conclusions on which, because " significant ", immediateaction is taken and those which, because " not significant ?', are completelyignored. Tests which lead to a result expressed as P = 0.05 " will cor-respond to relative frequencies of exactly 1 in 20 only if certain underlyingdistributions are truly normal (at least for the large majority of statisticaltests in common use), a point of which we can never be certain. In practice,however, we need seldom worry that sometimes we work at a 4% significancelevel and sometimes at a 6% level." 65 Provided the user of statisticalmethods employs the same intelligent judgment and knowledge based onexperience that he brings to bear on his use of chemical and physical methods,the decisions to be taken on the results obtained will be as sound in the onesituation as in the other, while the consequences arising from a mechanicaland unthinking application of text -book rules are equally fraught with danger.Statistics is the tool of the intelligent man, but that is a reason why analystsshould welcome its addition to their workshop.E. c. w.3. X-RAY ANALYSIS.No Report in this series has been exclusively devoted to X-ray analysissince 1938,' though it has been usual to touch upon this subject in Reportscovering other analytical methods.2This period has witnessed developments, not only in technique, but alsoin the evolution of new methods of X-ray analysis.The methods havebecome firmly established, particularly those based on X-ray powderdiffraction, and are well recognised as offering valuable applications tochemistry and metallography, especially where used in conjunction with otherphysical or chemical method^,^, and with a due regard to their limitations.It is important to remember that X-ray technique fills a position in thegeneral scheme of analysis, and brings its own contributions towards aproblem which may be completely solved only with the aid of other methods.Thus, spectroscopy, microscopy, analytical chemistry, diffraction, andphysical testing all have their parts to play,5 and, in addition t o theinformation provided by X-ray methods alone, such properties as refractiveindex, hardness, and density should be used wherever possible.Side by side with advances in X-ray diffraction analysis, other methodsof attack have come to the fore, such as X-ray spectroscopy where greatsensitivity is required, and microradiography where problems relating totexture are involved, and these aspects have contributed to the study of therarer elements and to microanalysis.e 5 D.J. Finney, private communication. Ann. Reports, 1938, 35, 381.Ibid., 1939, 36, 404; 1942, 39, 87; 1943, 40, 32; 1944, 41, 32, 92; 1946, 43, 332.L. K. Frevel, Ind. Eng. Chem. Anal., 1944, 16, 209.C. S. Smith and R.L. Barrett, J. Appl. Physics, 1947, 18, 177.D. Goodman, Iron Age, 1946, 158, 63276 ANALYTICAL CREMISTRY.In this Report) it is proposed to deal with each of these three methods,(a) powder diffraction, ( b ) spectroscopy, and ( c ) microradiography.The literature on the subject of X-ray analysis is widely scattered, asamply illustrated by the references which follow. This underlines the needfor a ceiitralised medium of publication, parallel to the proposed ActnCrystullogruphicn which is to deal with strwctnres and physical and chemicalproperties closely allied to structiwe.G(a) Powder Diffraction.Qualitative A ~ialysis.--'rhe particular value of the X-ray powderdiffraction method lies in its ability to detect chemical compounds or alloyphases and to distinguish between the different polymorphic forms in whichit substance may exist,' whereas many other analytical methods yield noinformation regarding the state of combination of the elements present.Following the work of J.D. Hanawalt, H. W. Rinn, and 1,. K. Frevel,8the outstanding event during the period under review has been thepiiblication by the American Society for 'resting Materials, in co-operationwith the American Society for X-Ray and Electron Diffraction and theInstitute of Physics, of the X-Ray Diffraction Index.g The first issue (June1945) comprises some 4000 cards and gives data for 1300 elements andcompounds, and the first supplement (August 1945) covers an additional1500 substances.Each card shows the interplanar spacings of the three strongest powderdiffraction lines given by a substance, followed by a list of all the lines forwhich data are available, together.with their relative intensities. Theprocediire for identifying an unknown substance 4 9 8 y is to compare thespacings of the three strongest lines with those given in the index, and thento check the remaining lines both for spacing and for relative intensity. Itis possible in this way to identify mixtures of two or three components.In the future there will be a tendency towards using the innermost line,i.e., the line of greatest spacing, irrespective of its intensity, in addition tothe three strongest lines. In this case it will be necessary also to specify the'' cut-off )', or greatest spacing measurable on the apparatus used.14'Fables of diffraction data for minerals have also been pub1ished,l5-l8 inJ .C'herrL. Physics, 1947, 15, 847; J . Xci. Instr., 1947, 24, 280.H. 1'. Hooksby, J . Roy. SOC. Arts, 1942, 90, 673.l i d . Eng. Cheiri. Anal., 1938, 10, 437.Data Cards for the Identification of Crystalline Materials by the Hanawalt X-RayDiffraction Method, A.S.T.M., Philadelphia, Pa.lo -4.S.T.M. Standards, 1948, Part 1, 1537.11 H. P. Itooksby, (2. E. c'. Journal, 1940,11, 83.l3 W. P. Davey, J . Appl. Physics, 1939, 10, 820.1 4 A . J. C. Wilson, J . Sci. Instr., 1947, $34, 304.l5 A. K. Boldyrev, V. I. Mikheev, G. A. Kovalev, and V. N. Dubinina, -4nn. ???st.l6 M. Mehmel, Portschr. Min., 1939, 23, 91.1 7 V. I. lllikheev and V.N . Dubinina, Ann. Inst. M i r t e s (Leningrad), 1939, 13, I .18 G . A. Harcoiirt. -4nzer. &fir/., 1912, 27, 63.l 2 A.S.T.M. gtandards, 1946, 1R.Mines (Leningmd), 1938,11, Part 2 , 1DOTHIE : Ly-RAY ANALYSIS. 277some of which the indices of the reflections are listed. Further data areavailable for alkylnted phenol derivatives,lg calcium phosphates,20mont bray it e,Z1 delafossi te ,22 vreden b ~ r g i t e , ~ ~ manganosite , p,yrochroite andstilpnomelane ,24 magnesiurii tungstates,25 uranium compounds,26 manganeseminerals ,27 cement clinker components and cementl hydration products ,281)DT,29 hexadecyl trisulphide and tetrasiilphide,30 cobalt carbide,31tantalite,32 lead orthosilicate, rhombic lead oxide (PbO), lead metasilicate,arid basic lead silicate (Pb,SiO,) ,% her~ynite,~* sodium ~ u l p h a m a t e , ~ ~ opiumalkaloids,3, explosi~es,3~ lithium and barium silicates,38 nluminium-copper,silver-copper, aluminium-zinc and copper-beryllium alloys,39 c e l l ~ l o ~ e , ~ ~$-sodium disilicate (Na,Si,0,),41 tantalum, tantalum nitride and columbiumhpdride~,,~ l u z ~ n i t e , ~ ~ cobalt ancl zinc oxide hydrates,44 hea~leu-oodite,~~t x o forms of fr~hbergite,~’ ramnielsbergite,48 glauco~lot,~~hiitchinsonite,50 c h a r n o ~ i t e , ~ ~ and aniIides of aliphatic a ~ i d s .1 ~ ~.In interesting extension of diffraction analysis to the problem ofla ,J. B. McKinley, J. E. Nickels, ancl 8. S. Sidhu, Itbd. Eng. Chew. - ~ ? L c L ~ . , 1944,16,304.20 \I-. F. Rale, J. P’. Bonner, 11.C . Hodge, H. Adler, A. R. JVreath, and R. Bell,a 1 51. A. Peacock and R. M. Thompson, A?/zcr. J l i n . , 1946, 31, 515.2 3 A. Pabst], ibid., p. 539.23 S. Deb, Quart. J. Geol. iMiniitg Met. SOC. Ittdia, 1943, 15, 137.2 4 W. Epprecht, Beitr. Geol. Schuteiz, Geolecir. Xer., 1946, Lief 34.**j S. J. Dunning and H. D. Megau. 7’ram. Faraday ,SOC., 1946, 42, 705.i b i d . , 1945, 17, 401.H. S. Peiser and T. C. Alcock, I.C.I. Ltd., Alkali Div., Research Dept., Winnington,1945.2 i R. JI. Foose, P e m n . Topographic aid (reol. Survey, Brill. M27, 1945.2 5 R . H. Rogue, “The Chemistry of Portland Cement ”, Reinhold Pub. Corp.*@ G. L. Clark and F. W. Cagle, Science, 1945, 101, 465.30 J. 0. Clayton and D. H. Etzler, J. Amer. Chem. SOC., 1947, 69, 974.” L.J. E. Hofer and W. C. Yeebles, ibid., p. 893.’? S. I<. Chakravarty, Quart. J. Geol. Mining Met. Soc. lndia, 1943, 17, 91.33 H . Jagitsch and R. Bengston, Arkiu Kenii, M i n . Geol,, 1946, A22, No. 6.34 .I. Michel-LBvy, J. Wyart, and J i . Michel-LBvy, C’onzpt. rend., 1947, 225, 83.3i S. H. Laning and P. A. \-ail der RIeulen. .I. ,4 nier. Shenr. Boc.. 1947, 69, 1828.s x S. T. Gross and F. W. Oherst. J . Lob. C‘li)?. Mctl.. 1947. 32, 94.3 i -1. 11. Soldate and R. I€. Noyes, l n d . Ewg. Chew. Anal. 1947. 19, 442.38 A. F:. Austin, J. Amer. Ceravk* SOC., 1947, 30, 21 8.39 M. I,. V. Gaylor, J . Iizst. Metals, 1947, 73, Part 2 , Paper No. 1070.4 0 G. Peyronel, Chin). e Z’Ind., 1943, 25. 71.4 1 I,. A. Burkardt and C. E. Imhoff, Ind. Eng. C h c ? ~ ., 1947, 39, 1427. ’’ F. H. Horn and M’. T. Ziegler. J . Anzer. Chew. SOC.. 1947, 69, 2763.43 I<. Hocart and R. Weil, Compt. Tend., 1947, 225, 194.4 4 -1. Nicol, ibid., 1947. 224, 1355.” 11. -4. Peacock, TJniv. Toronto Studies, Geol. Ser., 1946, No. 51, 59.“ D. S. Belyankin, P. V. Lapin, and Y. P. Siinanov, Conzpt. rend. Acad. I%;.‘’ R. M. Thompson, Uniu. Toro)bfo Studies, Geol. Ser., 1946, No. 51, 35.S. Kaiman, ibicl.. p. 49.’” R . 11’. Nuffield, ibid., p. 59.j1 T. Sudo, J . Qeol. SOC. ,7apan, 1941, 48, 433.S.Y., 1947.U.R.S.S., 1947, 55, 6%.Q B R. B. Fergusoii. ibid., p. 41278 ANALYTICAL CHEMISTRY.isomorphous substances has been developed by L. K. Frevel and his co-worker~,~~ 52 who give tabulated data for cubic and tetragonal isomorphs.%,The whole question of a code for the tabulation of X-ray diffraction data isgone into by F.W. Matthews and A. 0. McIntosh,55 who also suggest the useof punched-card indexes.The applications of X-ray diffraction analysis with regard to t,heircapabilities and limitations are reviewed in a book by E. Brandenberger,56who also deals thoroughly with the preparation of specimens and theinterpretation of photographs, A. Guinier 57 gives a comprehensive reviewof the theory of diffraction and experimental techniques, together withuseful examples of applications and the choice of suitable wave-lengths.Applications to metallography are covered by A. Taylor 5~3 and H. Hirst 59who deal with alloy systems, identification of new phases, and t,hermalequilibrium diagrams.Powder-diffraction technique is described byC. W. Bunn.GO W. T. Sproull 61 gives a review of experimental andtheoretical diffraction, industrial applications, and a useful table of absorptioncoefficients.The basic principles and theory of X-ray diffraction are also reviewed byF. G. Firth,G2 and applications by Firth,62 E. E. Vain~htein~~3 G. L. Clark,640. Binder,65 and W. G. Burgers.66and applications to minerals are dealt with by M. A. Peacock,68 W. P a r r i ~ h , ~ ~and G. Nagelschmidt and D. Hicks,'O and to metallurgical problems byC. S. Barrett.'ISt. J. Thugutt 72 draws attention to limitations in the X-ray method inthe case of certain minerals; lublinite and calcite give identical X-raydiagrams, whereas their densities, solubilities, and other physical propertiesA symposium has also been52 L.K. Frevel, J. Appl. Physics, 1942, 13, 109.53 L. K. Frevel, Ind. Eng. Chem. Anal., 1942, 14, 687.5 4 L. K. Frevel, H. W. R h , and H. C. Anderson, ibid., 1946, 18, 83.55 Can. Chem. Process Inds., 1947, 31, 63, 67, 71.56 ' ' Rontgenographisch-analytische Chemie : Moglichkeiten und Ergebnisse vonCntersuchungen mit Rontgeninterferenzcn in der Chemie ", Base1 Verlag E. Birkhauser8z Cie, 1945.5i " Radiocristallographie ", Paris, Dunod, 1947.5 8 " An Introduction to X-Ray Metallography ", Chapman & Hall Ltd., London,59 " X-Rays in Research and Industry ", Melbourne, Tait Pub. Co., 1942.60 " Chemical Crystallography ", Oxford, 1946.61 " X-Rays in Practice ", New York, McGraw-Hill Book Co., Inc., 1946.62 Petroleum ReJiner, 1945, 24, No.4, 114, No. 6, 11 7, No. 6, 11 1.63 Uspekhi Khimii, 1944, 13, 64.G 5 Mkcanique, Suppl. Tech. ind. chim., 1939, No. 284, 125.6 6 Tech. Rundschau, 1940, 5, 157.6 7 Id. Eng. Chem. AnaE., 1941, 13, 695.G 8 Trans. Roy. SOC. Canada, 1941, 35, 105.69 Anales le. Congr. Panamericano Ing. Minus y Geol., 1942, 3, 1074.70 Yroc. Conf. Ultra-fine Structure of Coals and Cokes, B.C.U.R.A., 1944, 240.7 1 " Structure of Metals ", New York, McGraw-Hill Book Co., Inc., 1943.7 2 Arck. Il.;lineralogicxne, 1945, 15, 250.1945.64 J . Amer. Ceramic Xoc., 1046, 29, 175DOTHIE : X-BAY ANALYSIS. 279show them to be different minerals. Quartz and chalcedony also give identicalpatterns.73 X-Ray and allied studies have shown boksputite to be a mixtureof bismutite and r n a s s i ~ o t , ~ ~ and berthonite to be identical with b ~ u r n o n i t e .~ ~The sensitivity of the method is greatly dependent on particularconditions, but in some cases it is not possible to detect constituents whichare present in a mixture to the extent of less than about 76 In thecase of the opium alkaloids, however, it is possible to detect as little as0.7 p.g.36X-Ray diffraction analysis has been applied to a wide variety of problems.Boiler- and turbine-scales have been studied,3141> 773 78 organic compoundsanalysed,79~ 80, 8l and new alkaline-earth tungstates identXedas2 Thedifferences in melting points of certain organic compounds which give thesame X-ray pattern have been shown to be due to irnpuritie~,~~ anddifferences in colour to be due to differences in particle size.The methodhas also been used for checking the constancy and purity of calciumpho~phates,~~ for investigating unreduced ferric oxide Fischer-Tropschhigh-alumina sIag,s6 chrome-steel slags,87 and nickel skeletoncatalystss8 It has revealed the presence of a- and @-cristobalite in opal,sgof spinel-type Fe2Ti04 in titaniferous iron ore:(' and of mercury containingfine particles of a-iron in iron amalgam,91 and a- and @-cobalt in cobaltamalgam,g2 and the relationship of three modifications of y-manganesedioxide to ramsdellite and pyrolusite.93 Other applications include theexamination of " oxine " pre~ipitates,~4 lead thioantimonates ini 3 J.Novttk, Ve'stnik Stat. Geol. Ostavu Rep. Ceskoslov., 1946, 21, 231.7 5 R. AT. Thompson, Univ. Toronto Studies, Geol. Ser., 1946, No. 51, 81.76 M. L. Fuller, Iron Age, 1942, 149, 65.7 7 P. E. Fitzgerald, Petroleum Engineer, 1940, 11, 161, 164; C. E. Imhoff and7 8 L. M. Clark and C. W. Bunn, J . Xoc. Chem. Id., 1940, 59, 155.79 W. G. Perdok, Pharm. Weekblad, 1946, 81, 194.8o H. G. Fletcher and C. S. Hudson, J . Amer. Chem. SOC., 1947, 69, 1146.X. S. Marsden, K. J. Mysels, and G. H. Smith, J . Colloid Xci., 1947,2, 265.82 H. P. Rooksby and E. G. Steward, Nature, 1946,157, 548.83 J . J . de Lange and J. P. W. Houtman, Rec. Trav. chim., 1946, 65, 891.E. W. Heinrich, Amer. Min., 1947, 32, 365.L. A4. Burkardt, Power, 1942, 86, 64.H.C. Hodge, M. L. Le Fhvre, and W. F. Bale, Ind. Eng. Chenz. A n d , 1938,8 5 L. J. E. Hofer, W. C. Peebles, and W. E. Dieter, J . Amer. Chem. SOC., 1946,8 6 D. S. Belyankin, V. V. Lapin, and Y . P. Simanov, Compt. rend. Acad. Sci.8 7 G. P. Chatterjee and S. S. Sidhu, J . AppZ. Physics, 1947, 18, 519.88 G. G. Urazov, L. M. Kefely, and S. L. Lel'chuk, Compt. rend. Acad. Xci. U.H.S.S.,89 V. Cirilli and A. Giannone, Rend. Accad. Sci. Napoli, 1940, 11.I?. Mogensen, Geol. Poren. B'orh., 1946, 68, 578.91 N. Katoh, J . Chem. Soc. Japan, 1043, 64, 1079.s2 Idem, ibid., p. 1211.93 W. F. Cole, A. D. Wadsley, and A. Walkley, Tvanu. Electrochem. SOC., 1947,92.R. C . Chirnside, C. F. Yritchard, and H. P. ICooksby, Analyst, 1941,66, 399.10, 156.68, 1953.U.R.S.X., 1946, 53, 649.1947, 55, 735280 ANALYTICAL OHEM1STK.Y.bo~langerite,~~ soil colloids,96, 979 98 clays,99 slates,lW iron ores,lOl lignites,1O2phosphors,lo3 nickel-tungsten and nickel-molybdenum catalysts,lO*thomsenolite and pachnolite,1O5 and cellulose in paper.40The method is of value in connection with pneumoconiosis, with regardnot only to dust analysis,106 but also to the presence of crystalline siliceousminerals in silicotic lungs.lo7 As little as 0.2% of d i c a has been determinedin dry lung tissue.lo8 Chemically extracted mineral residues of lung tissue,and tissue sections have also been successfully studied.1O6Recent applications include the analysis of condensation products fromarsenic vapour under different conditions,1og of the sulphur-rich residue afterthe chemical determination of sulphur in bronze,1l0 of bauxite ores ll1 andof acid-extracted non-metallic inclusions in steels.l12General reviews of qualitative and quantitative diffraction methods aregiven by W.P. Davey,la P. A. Thiessen,ll3 E. Brandenberger,l14 M. Patry,l15J. B. Nelson,llG J. S. Buhler,l17 I?. W. Ma,tthews 11* and Rooksby.' Furtherapplications 119-120 throw light on the constitution of bleaching powder,12fO 5 F. C. Foley, Microfilira Abs., h i 1 Arbor, 1943, 6, No. 2, 39.96 J. Shearer and W. F. Cole, J . Roy. SOC. TVcdern Australia, 193!1--40,26, 121, 133.97 J. S. Hosking, J . Counc. Sci. Ird. Res. Arrstrulk, 1940, 13, 206.ga E. Jung, Z . PJEanz., Diingung u. Boded., 1946, 37, 2.gg A.RiviBre, Conapt. rend., 1946, 222, 1446; G. Nagelschmidt, J . Sci. Instr., 1941,18, 100; 31. Rolla, Ind. cerana. e silicati, 1946, 1, 1 ; S. Yusjupove, Compt. rend. Acad.Sci. U.R.S.S., 1946, 51, 631 ; R. Michaud, It. Cerighelli, and G. Drouineau, Compt. rend.,1946, 222, 94; S. Oda, J . Chem. SOC. Japan, 1941, 62, 827.loo H W. Fairbairn, Anaer. Min., 1943, 28, 246.lol C. W. Correns, B'orschungen u. Portschr., 1947, 21-23, No. 416.lo2 C . Mahadevan, Proc. Indian Acad. Sci., 1946, 24, A , 216.lo3 R. Nagy and C. K. Lui, J . Opt. SOC. Amer., 1947, 37, 37.lo4 S. Tanida, Bull. Chem. SOC. Japan, 1943, 18, 30.lo5 R. B. Ferguson, Trans. Roy. SOC. Canada, 1946, 40, 1 1.lo6 L. H. Berkelhamer, J . I d . Hyg., 1941, 23, 163.lo7 H. C. Sweany, R. Klaas, and G.L. Clark, Radiology, 1938,31,299 ; C . 11. Jephcott,lo8 H. C. Sweany and R. Klrtas, J . Anaer. Med. ASSOC., 1939, 112, 610.lo9 I. N. Stranski and A. Korb, Naturwiss., 1946, 33, 220.110 L. SiIverman and W. B. Goodman, Chsir&t-Analyst, 1947, 36, 28.111 I. NBray-Szab6 and J. Neiigebauer, Tecknika, 1044, 25, 259 ; J. Il'eugehuer,112 G. Murfitt, J . Iron Steel Inst., 1947, 157, 96.113 2. EZektrochem., 1940, 46, 414.11* Tech. Id. Schweiz. Chem. Ztg., 1941, 24, 177.115 Chim. et Ind., 1941, 45, 259.1%'. M. Gray, andD. A. Irwin, Canadia,? Med. Assoc. J . , 1938,38, 209.Mwgyar Clrenz. Pol., 1944, 50, 102." Crystallographic Techniques in Chemical Analysis ", British Cod UtilisationResearch Association, Monthly Bulletin, (Sept.1946), Y, No. 9, 267.117 Metals and Alloys, 1944, 20, 1316.118 Canadian Chem. Process Inda., 1945, 29, 719.llg H. P. Rooksby, J . Sci. Instr., 1941, 18, 54.la0 Idem, J . Roy. SOC. Arts, 1940, 88, 308; A. J. Howard, Mfg. Chemist, 1942, 13,51; H. P. Rooksby, Elec. Times, 1942, 102, 116, 189, 360, 337, 347, 406, 476; J. A.Darbyshire, J . Sci. Instr., 1941, 18, 99.121 C. W. Bunn, ibid., p. 70DOTHIE : A--RAY ANALYSIS. %81electroplating,f22 refractories and steels,123 gla~ses,~2* interface compounds ofcoated filaments,125 and titanium enamels.126The most commonly used radiation hitherto has been Mo-Ka, but thereis a tendency to go over to Cu-Icy. as giving better dispersion, and chromiumtargets have been used in some cases.127 The question of optimum specimenthickness is dealt with by A.Taylor.12* B. E. Warren 129 discusses thedisplacement of the diffraction lines caused by absorption in cylindricalspecimens, and gives a correction factor proportional to the complement ofthe Bragg angle. The effect of particle size on intensities is considered byG. WT. Brindley.130 The construction and use of cameras are described,131and a camera has been designed for obtaining powder-type patterns fromsingle crystals up to 10 em. in diameter, or coarse aggregates, for identifyingThe method can be extended to low-temperature 133 and high-temperature 134 studies by the design of suitable cameras. Apparatus forthe accurate measurement of films is described by H. P. K1ug,1a5 and aphotometer by A.H. Jay.136 W, Hume-Rothery 137 describes an apparatusfor the preparation of metal filings in a vacuum or in an inert atmosphere.0. E. Brown 138 gives charts showing the relation between Bragg angle andintcrplaimr spacing for use with Cr, Pc, Co, Clu, and Mo targets. A rapidmethod of analysis has been used by A. T. M~Cord,l3~ in which the sample isformed into a rigid rod 3 mm. in diameter, and used as one of the definingedges for the collimating slit.Quantitative Analysis.-Quantitative X-ray diffraction methods can bedivided into two classes, according as (a) a shift in line position or ( b ) achange in line intensity is measured.In cases where there is formation of a solid solution or of a complex, aline may be shifted from the position it occupies when it arises from a purecomponent.140 The amount of the shift is dependent on the degree of solidsolution or complex formation.This method has been applied to the studylZ2 H. R. Isenburger, Proc. Awier. Electroplutcrs' Soc., June 1939, 77.lZ3 A. H. Jay, J . Sci. Instr., 1942, 18, 81.12* S. K. Majumdar and B. K. Bmerjee, X a / u r e , 1946, 158, 753.lZG H. P. Rooksby, ibicl., 1947, 159, 609.126 A . L. Friedberg, F. A. Petersen, and A. I. jlnclrews, J . A i i i c r . C'ercir,tic ~Soc., 1947,l Z i F. W. Matthews and J. H. Michell, Ind. E n y . Che7)L. A)~ul., 1946, 18, 661.lZ8 Phil. Mug., 1944, 35, 632. lZ9 J . Appl. Physics, 1945, 16, 614.Phil. Mag., 1945, 36, 347.131 &4. J. Bradley, H. Lipson, and H. J. Yetch, J . Sci. Instr., 1941, 18, 216.132 G.Switzer and R. J. Holmes, -47~er. Min., 1947, 32, 351.133 (Mrs.) I<. Lonsdale and H. Smith, J . S c i . Imtr., 1941, 18, 133.134 M. J. Buerger, N. W. Buerger. and F. G. Chesley, Amcr. Min., 1943, 28, 2 8 5 ;135 Ind. Eng. Chem. Anul., 1940, 12, 733.136 J . Sci. Instr., 1941, 18, 128.1 3 8 J . Appl. Physics, 1947, 18, 191.130 Itzd. Eng. Chem. Anul., 1942, 14, 793.140 R. Rigamonti, Gazzetta, 1946,76, 474 ; Atti R. Accad. Lincei, 1947, 2, 44G.30. 261.E. A. Owen, J . Sci. Instr., 1943, 20, 190.13' Ibid., 1947, 24, 75282 ANALYTICAL CHEMISTRY.of nickel-copper alloys,' and to lithium carbonate-barium carbonate mixtureson filaments.119 Changes in composition of 0*5y0 are detectable inmanganese orthosilicate-zinc orthosilicate mixtures in phosphors, but anaccuracy of 1-2y0 is normally obtainable.60The method of intensity measurement is of more general application.For this it is necessary to measure the relative intensities of certain diffractionlines and compare them with those given by a standard.There are twomethods available : (i) the direct comparison method, (ii) the internal-standard met hod.If the unknown substance contains not more than two or threecomponents, and if these can be identified, then the direct comparisonmethod may be used. A line due to each component is chosen, and theratio of their intensities is compared with that of the same lines given by amixture containing known amounts of the components. It is possible todetermine 0.1% of calcium oxide in magnesium oxide and 04% of zincoxide in zinc sulphide,141 and a method has been worked out for estimatingm~ntrnorillonite.~~~ The underlying theory of the method 143 and the choiceof the appropriate voltage 144 have been described.The internal-standard method has been used for the estimation ofquartz.145 Here, standard samples containing known- amounts of quartzare mixed with known amounts of calcium fluoride or nickel oxide as internalstandards.Intensity ratios of five internal standard lines and four quartzlines are determined, to give twenty analytical curves. These can then beused for comparison against similar ratios given by unknown samples. Thismethod is also described by S. T. Gross and D. E. Martin,146 who makegraphical corrections of the relative intensities for absorption and sampleshape.The estimation of quartz is also reported by similar methods.14'T. M. Durkan148 recommends concentration of the quartz by chemicalmethods, preliminary to X-ray study, in order to obviate lines due to otherminerals which may be superimposed on the quartz lines.I n ordinary case8 an accuracy of 1-5% can be expected,64 but accuraciesof better than 1% can be attained by careful working in favourable cases.'Quantitative methods have been applied to the determination ofm i n e r a l ~ , l ~ ~ of titanium nitride in ferro-alloys,lm and of aldehydes andketones as the 2 : 4-dinitrophenylhydrazones using sodium fluoride as141 H. P. Rooksby, Analyst, 1945, 70, 166.142 D. M.C. MacEwan, J. SOC. Chem. I n d . , 1946, 65, 298.143 K. Schiifer, 2. Krist.,1938, 99, 142.144 L. Rivoir and J. M. G. Barredo, And. Pis. Quim., 1941,37,48.145 J. W. Ballard and H. H. Schrenk, U.S. Bureau of Mines, Report of Investigations146 I n d . Eng. Chena. Anal., 1944, 16, 95.14' J. W. Ballard, H. I. Oshry, and H. H. Schrenk, U.S. Bureau of Mines, Report of148 J. I n d . Hyg., 1946, 28, 217.149 T. N. Agafonova, C'orwpt. Tend. Acad. Sci. U.R.X.S., 1937, 16, 367.160 L. Silverman, Iron Age, 1947, 159, 68, 163.3888, 1946.Investigations 3520, 1940; G. Venturello, Bass, med. ind., 1942,13, 273DOTHIE : X-RAY ANALYSIS. 283internal standard.151 The question of photometers is dealt with by a numberof a ~ t h 0 r s . l ~ ~The introduction of the Geiger-counter spectrometer 153 has constituteda great improvement in quantitative X-ray diffraction methods.This,more than any other single development, has increased both the speed andthc accuracy of quantitative determinations. In this instrument, theX-rays diffracted by the specimen, instead of being recorded on aphotographic film, are passed into a Geiger-Muller counter. The countercan be swung in a horizontal plane along an arc about the specimen, i t bposition being indicated by an accurate scale, and the X-ray energy itintercepts a t its various positions is thus converted, by suitable countingcircuits, into figures on an arbitrary scale. In this way both the position andthe intensity of the lines are measured directly.The Geiger-counter spectrometer has been applied to metallurgicalproblems,l= as, for example, cemented carbides in powder .metallurgy.155F.G. Firth 156 describes a recording instrument which is able to give thepattern of cc-Al,O, powder in 35 minutes. Another instrument is used inconjunction with a continuously balanced high-speed recording electronicp0tentiometer.1~' The use of the Geiger-counter spectrometer for back-reflection work is also described.158Alloys and Equilibrium Diagrams.-X-Ray methods have been usedextensively in the field of alloy studies, the usual procedure being to identifyconstituents by means of their powder diffraction patterns. The subject isreviewed by H. L i p ~ o n , l ~ ~ J. L. Abbott,l= L. Rivoir and A. andC. Schaub.161and deal with binary 1 6 * 7 lti5 and ternary alloys.164, 166It is possible to determine phase boundaries 7 5 Iti2 for transitionThe study of diffusion151 G.L. Clark, W. I. Kaye, and T. D. Parks, I n d . Eng. Chem. Anal., 1946,18, 310.152 J. W. Ballard, H. I. Oshry, and H. H. Schrenk, U.S. Bureau of Mines, Report ofInvestigations 3638, 1942 ; M. Spiegel-Adolf and R. H. Peckham, I n d . Eng. Cheni. Anal.,1940,12,182 ; E. E. Berkley and 0. C. Woodyard, ibid., 1938,30,451; H. R. Ronnebeck,J . Sci. Instr., 1943,20, 154; J . C. M. Brentano, Reu. Sci. Instr., 1945, 16, 309.lS3 H. Friedman, Electronics, 1945, 18, 132.154 Iron Age, 1947, 159, No. 7, 50, No. 8, 57, No. 9, 56.lS5 E. S. Kopecki, ibid., 1946, No. 9, 48.D. M. Considine and D. P. Eckman, J.Chenz. Educ., 1946,23,274.lS8 L. A. Carapella and H. F. Kaiser, Rev. Sci. Instr., 1945, 16, 214.lS9 Nature, 1940, 146, 798.161 I n g . Vetens. Akad., Stockholm, 1940, 161.lG2 W. Hume-Rothery and G. V. Raynor, J. Sci. Instr., 1941, 18, 74; Metal, I n d .(London), 1942,60, 412 ; V. Montoro and E. Hugony, Ric. sci., 1941,12, 1032.163 G. Borelius, T e k . Tid., 1942, 72 A, 500; K. G. Brummage, P. W. Cooke, andK. R. Gordon, Instr. Petrol. Rev., 1947, 1, 33, 65.164 A. J. Bradley, W. L. Bragg, and C. Sykes, J . Iron Steel Inst., 1940,141, 63.lG5 W. Trzebiatowski, H. Ploszek, and J. Lobzowski, I n d . Eng. Chem. Anal., 1947,19,93; N. V. Ageev andD. L. Ageeva, Bull. Acud. Sci. U.R.S.S., C1. Sci. Chim., 1946, 143.IG6 H. Lipson, Rep. Pmg. Physics, 1940, 6, 361; W.Guertler and G. Itassmam,Alelullw., 1943, 22, 1, 34, G6; W. Hofmann, Aluminium, 1938,20, 865; H. W. L.Phillips,J . Inst. Metals, 1946,72, 151 ; C. S. Barrett, J. Appl. Physics, 1941,12, 385.156 Colloid Chemistry, 1946, 6, 108.160 Anal. 3'3s. Quim., 1940, 36, 20284 ANALYTICAL CHEMISTRY.in alloys is described by A. H. S ~ 1 1 y . l ~ ~ 0. S. Edwards and H. Lipson Ici8discuss the experimental technique, choicc of radiation, and p-filterthicknesses.Closely akin to the subject of alloys is the study of the solubility ofhydrogen in palladi~rn,16~ and of gallium, germanium, and arsenic in copperand in ~ilver.1~0 Similar methods are used in investigations into equilibriumdiagrams, including the systems NiO-A1,0,,171 Fe,O,-BaCO, in presence ofoxygen,172 Bi20,-MOO,, Bi203-W03, PbO-Moo,, and PbO-W0,,173Mg0-Mg,P20,,174 TiC-WC,175 and carbides of tantalum, titanium,niobium, and zirc0nium.1~~ A new crystalline phase was found byexamining the Fe,O,-Cr,O, mixed gel and the phase compositionof calcined magnesite 178 and the reduction-equilibrium of ferric oxide bycarbon monoxide in presence of silica 179 and in presence of alumina,lsOhave been studied.(b) Spectroscopy.For the detection and estimation of small amounts of elements thespectroscopic method is becoming well established.Here the sample isplaced on the anticathode and the radiation excited by it is diffracted by acrystal and examined as a spectrum. The chief advantage of this over tlicoptical spectroscopic method is the simplicity of the X-ray spectra. Theseconsist of five lines in the K-series, as compared with the multiplicity of linespresent in optical emission spectra.l*lFor qualitative work it is possible to detect the elements from magnesiumto uranium, and the method has been applied to the study of minerals andrare elernents.182 Keys are given by P.A. Herrlin.l=Applications to quantitative work have been made, and progress in thisfield has been stimulated by Y. Cauchois, who describes a new method inwhich the sample and comparison sample are placed on the anticathode, andthe rays from each are separated by means of a crystal.ls4 The method is1 6 i J . Sci. Instr., 1945, 22, 244.l i 0 E. A. Owen and V. W. Rowlands, J . Inst. MetaZs, 1940, 66, 361.lil 11'.0. Milligan and L. Merten, J . Physical Chenz., 1946, 50, 466.l i 2 M. Erchak, I. Fankuchen, and H. Ward, J . Anher. Chevt. Soc., 1946,88, 2085.l i 3 L. G. Sillen and K. Lundborg, ArEiv Kern& Min. Geol., 1943, A, 17, No. 21.174 R. Jagitsch and G. Perlstrom, ibid., 1946, A , 22, No. 5.175 A. G. Metcalfe, J . Inst. Metals, 1947, 73, 591.l i G A. E. Koral'skii and Ya S. Umanskii, J . Phpical Cl~em. U.S.S.K., 1946, 20,177 W. 0. Milligan and L. Merten, J . Plqsical CIien2., 1947,51, 521.l i 8 V. T'. Goucharov, Compt. rend. Acad. S c i . U.R.S.S., 1947, 55, 743.17s V. Cirilli, Gazzetta, 1946, 76, 331.180 Idem, ibid., p. 339.181 H. Hirst, Chem. Eng. iMin. Rev., 1939, 31, 208.168 Ibid., 1941, 18, 131.D. P. Smith and C. S.Barrett, J . Anter. CJLem. Xoc., 1940, 62, 2565.769, 773.I. B. Borovskii and M. A. Blokhin, BUZZ. Acad. Sci. U.R.S.S., 1937, 929;31. A. Blokhin, Zavod. Lab., 1945, 11, 1069.ln3 Medd. Lunds Geo1.-Mineral Inst., 1941, A'o. 87, 16.lS4 Bull. Seci. sci. roumaine, 1942, 24, 479DOTTITE : -X-RAY ANALYSTS. 2%very sensitive both in mixtures and in the pure static, it being possible todetect 5 i(Methods of X-ray spectroscopy 186 are discussed by H. Hirst,I*l whogives the estimation of minute amounts of elements in metals and alloys.The accuracy obtainable depends on the atomic number of the clemc~nt, andfalls off for elements of lower atomic number than that of niagnesium.For other elements an amount of impurity as small as one part in lo5 partscan be detected and measured.When analysing alloys with large amountsof constituents the accuracy is about O.OSyo if the elements are close togetherin the periodic system, but if they are far apart the accuracy may fall to 1 yo.The method is therefore best suited to the estimation of minute amounts ofimpurities. Spectroscopic methods are also reviewed by Clark,64 whoconsiders their application to ceramics, by I. B. Borovskii 18' on the methodof Cauchois and Johann, by Vainshtein 63 and by 0. Alvfeldt.188 Estimationsof the rarer elements, using an optical wedge and of minuteamounts of nickel ancl cobalt,lW are also described. In the latter case anexposure time of 60 minutes was given, using a copper anticathode, a tungsten-filament cathode, ancl running at 18 kv.with an emission of 5 ma., and usinga calcite crystal.A vacuum spectrograph for use with light elements has bsendescribed ; lgl electrostatic shielding of the anticathode gives rapid andexact analysis,lg2 and ionic X-ray tubes have been deve10ped.l~~Y. Cauchois lg4 describes a spectrograph for use up to 20 A.The necessity for demounting the tube after every determination hasprevented the wide application of this method, but this difficulty can beavoided by placing the specimen outside the tube, and irradiating it with theprimary rays.64 The specimen then gives rise to secondary fluorescentradiation which may be diffracted by a crystal and thus formed into aspectrum. High-intensity tubes which produce a dosage of 5,500,000 r.perminute lg5 are particularly valuable for this technique. L. v. Ham05 lg6discusses the formation of true X-ray images by reflection from cylindricalcrystal surfaces, anti the determination of very small quantities ofs i i b ~ t a n c e s , ~ ~ ~ utilising the secondary X-radiation of an element.la5 Y. Canchois, J . Chini. physique, 1942, 39, 161.l B 6 I. B. Rorovskii and 31. A. Blokhin, Btill. -4cad. isci. lJ.R.s.S., S6r. phys., 194.1,g. of uranium in the pure state.185196.Trudy Vsesoyuz Ronferentsii, A?zaL. Khi?r/., dkad. Xutilu'., S.S.S.R., 1939, 1, 13.5.l S s Ing. I'efens. Akad., Niockholnz, 1943, 217.lS9 S. Sinoda, J . C'hem. SOC. Japan, 1941, 62, 629.lg0 I<. Rimura, M. Nrtkamura, and N. Tanaka, ibid., 1043, 63, 349.lgl N. D.Borisov and Ya. M. Fogel, J. Tech. Phys. U.S.S.K., 2938, 8, 1709.lg2 P. Brauer, 2. tech. Physik, 1938, 19, 232.IB3 G. F. Komovskii and Ya. Golovchiner, J . Twit. Phys. U.S.S.R., 1942, 12, 579;Ig4 J . P h p . Radium, 1945, 6, 89.lgB T. H. Rogers, Ind. Iludiograpliy, 1946, 4, 36, 61.Ig8 Arne?.. &!in., 1938, 23, 215; Z. Krisr., 1939, 101, 17.l e i ilrkiv Mat. A8tTOTL. Fysik, 1946, A , 31, NO. 25,Btcll. Acad. Sci. U.R.S.S., S6r. phys., 2941, 201286 ANALYTICAL CHEMISTRY.E. Abbolito lg8 gives details of the v. Hamos method, including the use ofa curved mica focusing crystal; the method is applicable to the detectionof those elements whose characterstic radiation lies in the wave-lengthregion between 0.7 and 2-7 A.( c ) Microradiogruphg.It is noteworthy that the absorption of X-rays by materials has beenused to advantage as an analytical tool, and by its means it is possible todistinguish phases.64, Ig9 A.Guinier 200 uses minute quantities of materialplaced on a photographic plate; this is irradiated and the absorptiondetermined by microscopic examination. It is possible to distinguishbetween the composition and diffraction effects.199 A. Engstrom m1 uses afine-grained calcium tungstate fluorescent screen in place of a photographicplate. A further advance 202 is the use of a fluorescent screen in conjunctionwith a photomultiplier tube, in which case the intensities are read as electriccurrents. In another method 203 the absorption coefficient is measured bycomparing the ionisation currents caused by the X-rays before and afterabsorption.The composition of binary compounds can be determined, and the methodhas been applied to the study of organic compounds.2m The absorptioncoefficients of hydrogen, carbon, nitrogen, and oxygen have been measuredrelative t o aluminium, and the additive law of absorption coefficients foundto be valid for liquid hydrocarbons.Developments along similar lines havebeen made in the field of mi~roradiography,~05 and the subject is reviewed byVain~htein.~~ Applications to metals and alloys are described by M. Paiq206G. L. Clark and W. M. Shafer,207 and Taylor,58 and to colloidal materials byG. L. Clark.208 Details of technique 209 and industrial applications 210 aregiven, and a stereoscopic camera is described.211 H.F. Sherwood212lg8 Ric. sci., 1940, 11, 856.leg R. Smoluchowski, C. M. Lucht, and J. M. Hlird, J. Appt. Physics, 104G,l?, 864.2oo Compt. Tend., 1943, 216, 48.202 H. A. Liebliafsky and E. H. Winslow, Gen, Elec. Review, 1945, 48, 36; 11. A.Liebhafsky, H. 31. Smith, H. E. Tanis, and E. H. W7inslow, I n d . Eng. Ghen2. A d . ,1947, 19, 861.201 Experientia, 1947, 3, 208.203 J. Devaux and A. Guinier, Compt. rend., 1944, 218, 318.204 Idem, ibid., 1945, 220, 44.205 G. L. Clark and 8. T. Gross, Ind. Eng. Chem. Anal., 1942, 14, 6 7 7 ; J. J. Trillat,Rev. aluminium, 1945, 22, 44; C. S. Barrett, Trans. Amer. Inst. Min., Met. E92yrs.Inst. Met. Div., 1945, Tech. Pub. No. 1865.206 Rev. mdt., 1944, 41, 169.207 Trans. Amer.SOC. Metals, 1941, 29, 732.208 J. Alexander, " Colloid Chemistry ", 1944, Vol. V, 146.sos G. L. Clark, Phototechnique, 1939, 1, (7), 19; Ind. Radiography, 1942, 1, 21;S. E. Maddigan, J. Appl. Physics, 1944,15, 43; J. J. Trillat, B d . soc. franc. elect., 1943,(6), 3, No. 25.S. T. Gross and G. L. Clark, Ind. E n g . Chem. Anal., 1942, 14, 676; G. L. Clarkand S. T. Gross, Iron A g e , 1943, 152, 44.211 G. L. Clark and R. W. Eyler, Rev. Sci. Instr., 1943, 14, 277.*12 Ibid., 1947, 18, 80SEXTON : OILS, FATS, AND SURFACE-ACTIVE AGENTS. 287describes an exposure holder suitable for the microradiography of thinspecimens such as metal sections, paper, and textiles. The good contactneeded to ensure maximum sharpness is obtained by means of a vacuumframe in which the apecimen i s covered with a film of vinylite.The questionof the accurate interpretation of radiographs is gone into by H. R. Clauser?l3together with the influence of film contrast and definition on sensitivity,film blemishes and viewing lamps. An interesting development is the useof a phosphor possessing X-ray storage properties, the energy being releasedon subsequent infra-red i r r a d i a t i ~ n . ~ l ~A. Engstrom 215 and his co-workers have developed a quantitative methodof microradiography suitable for the analysis of elements, of atomic numberabove 6, in extremely small quantities of biological tissues. It is capableof determining 10-lo-lO-ll g. of calcium or phosphorus with an error of 10%.H. J. D.4. OILS, FATS, AND SURFACE-ACTIVE AGENTS.The analytical description of natural fats may be based either onempirical " constants " of the fat as a whole (e.g., saponification or iodinevalues) or on its content of definite chemical substances or radicals (e.g.,arachidic acid in arachis oil, squalene in olive oil, -OH in castor oil).Although a complete description of the latter kind is the ideal, analysts are,at present, largely restricted in practice to terms of the former kind.It istherefore proposed in the present Report to review recent developments inthe technique of determination of empirical constants, followed by someindication of the trends of research which may develop into acceptableanalytical procedure for the determination of specific ingredients.Certaincases where the determination of these can already be regarded as analyticalpractice are considered rather more fully. Finally, methods for theexamination of substances derived from natural fats (mono- anddi-glycerides ; surface-active agents) and now important in industry, andtherefore in practical analysis, are reviewed.Empirical Constants.77nsaturation.-0. Freire recommends W. A. Alexander's oxidationvalue in a study of the possibility of determining it a t 100". G. Knowles,J. C. Lawson, and T. McQuillen3 treat an oil in acetic acid plus anemulsifying agent with excess of potassium permanganate for an hour at25", then titrate the excess. The results agree with I.V.s, and whereunsaturation is due to conjugated linkages the true I.V.is obtained from this213 Materials and Methods, 1945, 32, 1418.2 1 4 0. E. Berg and H. F. Kaiser, J . AppZ. Phgsics, 1947, 18, 343.215 A. Engstrom, Nature, 1946, 158, 664; idem, Acta Racliol. Suppl., 1946, 63;A. Engstrom and B. Lindstrom, Experientia, 1947, 3, 191 ; A. Engstrom and M. A.Jakus, Nature, 1948, 161, 168.Chem. Abs., 1947, 41, 1470.J . Oil Colour Chem. ASSOC., 1940, 23, 4.Analyst, 1939, 64, 157288 ANALYTTCA4L CIIEMTSTRY.oxidation value. The oxygen consumed is equivalent to the I.V. as ameasure of unsaturation but is of inore general value.G. K. Jones * and J. W. McCutcheon discuss the Wi& method, andP. Levy criticises this and other methods.investigated sample : reagent ratio in the Wijs method and suggest a rapidtest for conjugated systems.H. D. Hoffman and D. E. Green,8 by addingmercuric acetate to the reaction mixture in the Wijs method, reduced thetime required from 30 t o 3 mins. The same salt in the Hanus method alsoaccelerates the reaction but the rapid method is unsuitable for castor oil and“ conjugated ” fats because the I.V. varies with the excess of reagent used.P. S. Skell and S. B. Radlove,lo using the Wijs rapid method, first protect thehydroxyl groups in castor oil, etc., by propionylation. H. Jasperson l1used direct bromine addition (D.B.A.) with mercuric acetate catalyst toobtain the I.V. of hydrogenated fats by titrating with bromine in glacialacetic acid. G. W. Priest and J. D. von Mikusch,l2 using a large excess ofreagent in the Hanus method, obtained satisfactory results for castor oil(dehydrating) ; and Mikusch and C.FrazierY13 using a large excess of double-strength Hanus solution, obtained theoretical 1.V.s for “ conjugated ” fats.The same workers,l4 using this method and a short-time contact Wijssolution at 0--5”, determine conjugated or non-conjugated unsaturation offats.During the war, bromine reagents were much used for I.V.s, the pyridinesulphate bromide method being used in B.P. work. Two modifications ofH. P. Kaufmann’s method were described.l59 l6 Bromine methods seem tobe the most popular for microchemical work. K. Schmidt-Nielsen l7determines the I.V. of g. of oil by treating it with bromine and sodiumbromide in methyl alcohol and estimating the excess; and N.Kretchmer,R. T. Holman, and G. 0. Burr l8 use a modified Rosenmund-Kuhnhennmethod on 10-100 pg. of oil.Kass andhis co-workers conclude that former hexabromide numbers are too high anddescribe a more adequate procediire which gives trustworthy, if empirical,results.Although it has been shown 21, 22 that the addition of -SCN is neitherW. C. Forbes and H. A. NevilleTwo studies 1 9 7 2o of the polybromide number have been made.Paint Manuf., 1946, 16, 58.Chinr. peint., 1945, 8, 123.* Oil and Soap, 1939,16, 236.F. A. Norris and R. J. Buswell, Ind. Eng. C‘hew. Anal., 1943, 15, 238.Itid. Eng. C’l~em. Anal., 1940, 12, 265.Ind. Eng. Clwm. Anal., 19.10, 12, 72.lo Ibid., 1946, 18, 67.l1 J . SOC. C’hem. Id., 1942, 61, 116.Ind. Eng. Chenr.Anal., 1941, 13, 782.l 5 A. Muller and L. Feher, Fetle u. S e i f e n , 1944, 51, 171.l6 S. Korpacsy, Ind. corps gras, 1945, 1, 49.18 Arch. Biochena., 1946, 10, 101 ; Oil and Soap, 1946, 23, 266.2o J. P. Kass, W. R. Roy, and G . 0. Burr, Anal. C‘hem., 1947, 19, 21.21 J. P. Kass, 11. G. T,oeb, F. A. Norris. and G. 0. Burr, Oil and Soap, 1940, 17, 118.s2 Analyst, 1940, 65, 437.l2 I n d . Eng. Chetr,., 1940, 32, 1314.l4 Ibid., 1943, 15, 109.l7 Chent. Abs., 1946, 40, 2011.E. 0. Aeulle and M. C. Pineda, Ion, 1945, 5, 257 ; Cheni. Abs., 1945, 39, 5099SEXTON : OILS, FATS, AND SURFACE-ACTIVE AGENTS. 289quantitative nor independent of the concentration of -SCN reagent used,this has not made the method obsolete but it has made it necessary to replacethe theoretical Kaufmann values by values obtained under standardisedconditions. The new values have been adopted by the A.O.C.S.,= theA.O.A.C., and by T.P. Hilditch and his co-workers.B. A. Ellis and R. A. Jones’s maleic anhydride or diene value 24 has beeninvestigated by R. S. McKinney, N. J. Hslbrook, and W. G. whoshow that the actual values of conjugated acids, like the SCN value ofunsaturated acids, vary with the conditions of reaction.26 The sameworkers 25 use the diene value to detect the adulteration of tung oil.A specific titration method for oxirane (epoxy) oxygen in unsaturatedfatty materials, based on the opening of the oxirane ring by 0*2~-hydrogenchloride in anhydrous ether, is described by D. Swern, T. W. Findley,G.N. Billen, and J. T. S ~ a n I a n . ~ ~Saponi$cution Value and UnaaponiJiable iMatter.-E. Andre 28 has studiedS.V. methods and possible errors ; and W. Rieman’s methods 29 for determiningthe S.V. by potentiometric analysis 01‘ double indicator avoid “ blank ”determinations and are suitable for micro-work. The micro-procedure isdescribed30 for O*l--O-OOl-g. quantities of fat as well as a modified semi-micromethod.31 J. P. Wolff,32 using potentiometric methods to find thebest indicator for use in alcohol, concluded that thymolphthalein was bestfor fatty acids and rosin. Some years ago W. R. Street 33 proposed potassiumhydroxide in “ cellosolve ” for samples difficult to saponify ; B. H. Knight 34advises the addition of alcohol to this, while S.Rovira 36 saponifies “ difficult”samples with this hydroxide in benzyl alcohol, ethylene glycol, or glycerol.G. Kirsten,36 reporting on standard methods for unsaponifiable matter,preferred the Society of Public Analysts’ (S.P.A.) method. This is now“ official ” in the A.O.A.C. methods ; the F.A.C. method has been deleted.N. D. Sylvester, A. N. Ainsworth, and E. B. Hughes 37 improved the S.P.A.method by using adsorption. M. L. Karnovsky and W. S. Rapson38modify the S.P.A. method in analysing marine oils. They determine thea-glyceryI ether content of the isolated unsaponifiable matter by periodicn* Official and Tentative Methods of the A.O.C.S., 1946 ; A d y e t , 1947,73,167.er Ibid., 1936, 61, 812.e6 W. G. Rose and G. S. Jamieson, ibid., 1943, 20, 227.c 7 Anal.(%ern., 1947, 19, 414.bo W. Rieman and K. Marcali, ibid., 1946, 18, 144.*l D. Ketchurn, ibid., p. 273.Analyst, 1936, 61, 687.Ann. Chim., 1946, 20, 660.A d y e t , 1946, 70, 296.8b Oil and Soap, 1942, 19, 141.Olkagineux, 1946, 1, 12, 68.Ind. Eng. Chem. Anal., 1943,15, 325.I d . corps gras, 1945, 1, 36.a4 Anal. Chem., 1947, 19, 359.B6 J . Aseoc. Off. Agric. Chem., 1946, 29, 248.81 J . SOC. Chem. Id., 1947, 66, 95.REP.-VOL. XLIV. 290 ANALYTICAL CHEMISTRY.acid oxidation.39 Although some marine oils contain much, amongother oils only tung oil has any appreciable a-glyceryl ether content.40 Theyalso41 use J. Fitelson’s squalene method to obtain the squalene contentof marine oils ; this method for olive oil in mixtures is now ( ( official ” in theA.O.A.C. methods.The average squalene content of olive oil is 330, arachis27, and teaseed 12 mg./100 g. ofAcetyl Value.--In a modification 43 of the Roberts-Schuette method foracetyl value, the hydroxyl number does not vary with the quantity ofsample. The AndrB-Cook method for acetyl values requires a fairly complexequation ; this, however, is capable of a simple graphical solution, and threenomograms are given.4Deterioration.-C. H. Lea’s comprehensive report 45 is now, unfortunately,out of print. Most of the tests described in it, or modifications, are still inuse. There are also some new tests. Much work has been done on theestimation of peroxides in fats by iodometric methods. D. H. Wheeler’s 46cold method, using saturated potassium iodide solution for one minute, ispopular in America.A. Taffel and C. Revis 47 used 8olid barium iodide or50% potassium iodide in glacial acetic acid, but no chloroform. W. Frankeand D. Jerche14* and Franke and J. Monch49 use carbon tetrachloride andhydriodic acid and dilute acetic acid for one hour in diffused light. J. Gangland W. Rurnpel 5o determined the undecomposed iodide. Lea’s originalmethod was a hot method using solid potassium iodide. Later, N. N. Dasturand C . H. Lea 51 gave a modified method estimating the undecomposediodide as in Gangl and Rumpel’s method. Lea,62 following his work 53 onthe ferrometric procedure and de-aeration of reagents, showed that in theiodometric method also it is necessary to de-aerate the solvent beforedissolving the fat. Lea describes a piece of apparatus and a hot and a coldmethod of determining peroxide values-cold, one hour a t room temperature ;hot, boiling for two minutes.C. B.Stuffins and H. Weatherall 54 studied Lea’s and Wheeler’s methodsand proposed a cold method, using saturated potassium iodide solution andan inert gas. M. E. Stansby 55 uses a similar method for fish oils.K. Nozaki 56 uses sodium iodide and acetic anhydride in the cold whendetermining organic peroxides. J. H. Skellon and E. D. Wills 67 for benzoyl39 Ibid., 1946, 65, 138.4s K. Helrich and W. Rieman, Anal. Chem., 1947, 19, 691.44 T. C. Patton, J . Amer. Oil Chem. Soc., 1947, 24, 158.45 D.S.I.R. Special Report No. 46 : Rancidity in Edible Fats, 1938.40 Ibid., p.425.J . Assoc. Off. Agric. Chern., 1945, 28, 282.4 1 Ibid., 1947, 66, 124.Oil and Soap, 1932, 9, 89; A. E. King, H. L. Roschen, and W. H. Irwin, ibid.,Annalen, 1937, 533, 46.1933, 10, 105.4 7 J . SOC. Chem. Ind., 1931, 50, 87T.49 Ibid., 1944, 556, 200.51 Analyst, 1941, 66, 90.m Ibid., 1945, 64, 106; Analyst, 1945, 70, 306.b4 Ibid., p. 403.6b I d . E q . Chem. Anal., 1941,13,627.6 7 Analyst, 1948, 73, 78.bo 2. Untersuch. Lebensm., 1934,68,533.b2 J . SOC. Chem. Id., 1946, 65, 286.Ibid., 1946, 18, 683SEXTON : OILS, FATS, AND SURFACE-ACTIVE AGENTS. 291peroxide use a cold method with sodium hydrogen carbonate as a source ofgas. S. Siggia 58 uses an arsenious oxide method for benzoyl peroxide,where an iodometric method could not be employed.C. D. Wagner,R. H. Smith, and E. D. Peters 59 tested various methods and described theirown recommended procedure using sodium iodide and isopropyl alcohol.The ferrous thiocyanate colorimetric 60 and the ferrous-titanous procedurehave also been studied.The ferrometric method is based on the oxidation of ferrous to ferriciron by the peroxides present. The reagent is a dilute solution of ferrousammonium sulphate and ammonium thiocyanate in 96% acetone. Thecolour developed is measured by a spectrophotometer. The peroxide valuesare double the iodometric values. C. H. Lea showed that the ferrometricvalues were reduced by about 75% if the reagents were de-aerated.G. Hills-Loftus and C . C . miel63 modify the method by usingbenzene : methanol (7 : 3) as solvent with ferrous chloride.The Kreis test for acetals of epihydrinaldehyde has been investigated bymany w0rkers.M Perhaps the single-phase technique of W.P. Walters,M. M. Muers, and E. B. Anderson 66 or a modification 66 is the mostsatisfactory. 0. Frehden's diaminofluorene colour-test for peroxides 67 andJ. Stamm's diphenylcarbazide test 68 for hydroxy-aliphatic acids (modifiedby Frehden) 69 are still used. The salicylaldehyde test45 for ketonicrancidity was modified by N. N. Dastur and C. H. Lea.51 The Schibstedtest has been modified by W. R.The Schaal test by oven incubation a t 60" or 63" was used by someworkers,71 and Swift's stability test wag investigated by V. C. Mehlenba~her,'~who accelerates it by using 110" thus saving 60% in time : hours a t 110"multiplied by 2.5 give the 97.9" values.An all-glass improved apparatusin which one tube is required for each sample was devised for the Swifttest.73 E. W. Eckey's apparatus and procedure 74 for measuring the oxygenabsorption of fats records the time required for 1 g. of fat to absorb 3 ml. oioxygen. Another apparatus 75 shows the volume absorbed under constant6 8 Anal. Chem., 1947, 19, 872.6o C. D. Wagner, H. L. Clever, and E. D. Petors, ibid., p. 980.b 1 C. D. Wagner, R. H. Smith, and E. D. Peters, ibid., p. 976.62 A. Lips, R. A. Chapman, and W. D. McFarlane, Canadian J. Res., 1943,21B, 153 ;63 J . Dairy Res., 1946, 14, 340.b4 B. M. Watts and R. Major, Oil and Soap, 1046, 23, 222.g5 J .SOC. Chern. Ind., 1938, 57, 53.6 6 M. F. Pool and A. N. Prater, Oil and Soap, 1945, 22, 215.6 7 Analyst, 1938, 63, 536.'l N. T. Joyner and J. E. McIntyre, Oil and Soap, 1938, 15, 184; K. F. Mattil and72 Oil and Soap, 1942, 19, 137.7L Ibid., 1942, 23, 38.7 6 R. Gilmont, H. 8. Levenson, and L. W. Elder, ibid., 1046, 23, 248.59 Ibid., p. 976.Oil and Soap, 1943, 20, 240.Ibid., 1926, 51, 416.Mikrochim. Acta, 1937, 2, 214. 70 J . Dairy Res., 1947, 15, 55.H. C. Black, J. Amer. Oil Chem. SOC., 1947, 24, 325.R. W. Riernensehneider, J. Turer, and R. M. Speck, ibid., 1943, 20, 169292 ANALYTICAL CHEMISTRY.pressure ; the rate is plotted and the induction period is shown by a break inthe curve.There are two new colorimetric methods for a-dicarbonyl compounds.E.A. Bill 76 converts these into their oximes, forms the nickelous, cupric, orferrous derivative of these, and then extracts the characteristically-colouredcomplexes with benzene, finally measuring the colour. L. O’Daniel andL. B. Parsons 77 state that autoxidised fats treated with alcoholic potashgive colours due to quinonoid compounds formed by aldol condensation ofa-diketones in a manner analogous to the formation of p-xyloquinone fromdiacetyl, and describe a simple and rapid method of estimation.H. Jasperson, R. Jones, and J. W. Lord 78 have investigated both thesemethods. G. A. Grant and H. J. Lips,79 studying rancidity in lard, conaiderthat the determination of stable a-dicarbonyl compounds is the best forassessing deterioration ; and S.A. Kaloyereas 80 considers the Wheelerperoxide method the most reliable and the Kerr-Issoglio test of no value.W. H. White,81 F. C. Vibrans,82 and B. W. Beadle a3 discuss the various testsfor rancidity and their limitations.Miscellaneous Tests.-An accurate semimicro-method for determiningReichert-Meissl, Polenske, and Kirschner values on 1 g. of fat is given.84Methods for the determination of ash in oils, refining and bleaching tests arereported R. T. O’Connor, D. C. Heinzelman, and M. E. Jefferson 86describe an emission spectrographic method for traces of metals in oils (fewp.p.m. in 2.5 g. of oil). The detection of argemone oil in mustard oil isde~cribed.8~ The specific heats of vegetable oils over the range 0-280”were determined by P.E. Clark, C. R. Waldeland, and R. P. Cross.88K. A. Williams 89 modifies the method 90 for “ tristearin ” in lard. Thismethod is still “tentative ” in the A.O.A.C. Methods.s1 R. W. Sutton,A. Barraclough, R. Mallinder, and 0. Hitchen’s long and important paper 92on the adulteration of lard contains useful photomicrographs. T. Connorand G. F. Wright s3 describe a novel procedure for the analysis of mixtures ofgeometrical isomers, using methoxy-mercuration and taking advantage ofthe fact that cis-isomers react more quickly than trans-forms. F. A. Norrisand K. F. Mattil s4 used catalysed interesterification for a new approach toglyceride structure.76 Oil and Soap, 1942, 19, 107.78 J . SOC. Chem. Ind., 1945, 64, 143.82 Oil and Soap, 1941, 18, 109.** B.Dyer, G. Taylor, and J. Hamence, Analyst, 1941, 66, 355.7 7 Ibid., 1943, 20, 72.79 Canadian J . Res., 1946, 24F, 450.8 1 Canadian J . Res., 1941, 190, 278.83 Ibid., 1946, 23, 33.J . Amer. Oil Chem. SOC., 1947,24, 39.J . Amer. Oil Chem. SOC., 1947, 24, 76.Ibid., p. 185.Ind. Eng. Chem. Anal., 1946, 38, 350.A d y s t , 1940, 65, 596. 90 [bid., p. 508.91 ‘‘ Official and Tentative Methods of the A.O.A.C.”, 1945.Oe A d y e t , 1940, 65, 623.94 Oil and Soap, 1946, 23, 289.ST A. K. Sen, Chem. Abs., 1947, 41, 2261.J . Amer. Chem. SOC., 1946, 68, 256SEXTON t OILS, FATS, AND YURFAUE-ACTIVE AGENTS. 203U. T. Hill 95 describes a colorimetric method for fatty acids and estersbased on a ferric hydroxamate colour complex.The preparation of thehydrazides of n-aliphatic acids (Cl-C,,) from 20 mg. of their esters isdescribedg6 as a means of identification in mixtures from melting points;and F. L. Breusch and E. Ulusoy 97 isolate and identify fatty acids its theircrystalline ureides with bis - ( p -dimet nylarninopheny1)urea.After much collaborative work, an A.O.C.S. committee 98 recommend thegrading of the colour of oils by a photoelectric system. L. K. Whyte 99describes the photometric determination of the colour of fats by a methodwhich even a colour-blind person can use.G. Zeidler loo gives a simple test for tung oil in mixtures, and a staidardrapid-chilling technique for melting points of fats and waxes isrecommended.lol The aluminiurn nurnber,lo2 hydrogen-addition ~ i t l u e , ~ O ~and amide value lo4 methods are described.Assessments of Ingredients.1’. P.Hilditch’s revised monograph lo5 includes a chptw 011 tlicexperimental technique used by the Liverpool school. J. A. Lovern lo6describes the methods of analysis used by him, and the new methods fordetermining the composition of fatty acid mixtures have been described byJ. A. Boyle 10’ and B. W. Beadle.lO*The methods commonly used in determining the detailed composition offats are :(a) Separation of saturated and unsaturated acids by the lead-salt methodor by the lithium-salt method log followed by the lead-salt method. TheA.O.A.C. methods 91 retain the lead-saltether method ; the A.O.C.S.methods 23 adopt the better Twitchell alcohol method.For larger amountsof fats the method of T. P. Hilditch loci is preferable.( b ) Estimation of saturated acids by permanganate oxidation, either bya Bertram method 110 or by Hilditch and co-workers’ method of solution inacetone .111, 105’j Ind. Eng. Chem. Anal., 1946, 18, 317 ; ,4?tal. Chern., 1947, 19, 932.9 6 L. Kyame, G. S. Fisher, and W. G. Bickford, J . Amer. Oil Chena. Soc., 1947,24,332.9 7 Arch. Biochem., 1946, 11, 489; Analyst, 1947, 72, 364.9 8 Oil and Soap, 1946, 23, 292. J . Amer. Oil C‘hem. SOC., 1047, 24, 137.loo Chem. Zentr., 1944, 11, 378.l o ‘ D. M. Copley, J . Amer. Pharrrz. ASSOC., 1946, 35, 7s.I o 2 E. Eigenberger, Pette u. A’eifen, 1944, 51, 43, 87.lo3 H. P. Kaufmann and M. C. Keller, ibid., p.223.lU4 S. Olsen, Die Chemie, 1943, 56, 202.lo5 ‘‘ The Chemical Constitution of Natural Fats ”, h t l etltn., 194T.Io6 D.S.I.R. Food Investig. Special Report, No. 61.Io7 Manuf. Chem., 1946, 17, 282.Io8 B:W. Beadle, Oil and Soap, 1946, 23, 140 (Review).log T. P. Hilditcli and L. Maddison, J . SOC. Chem. Ind., 1942, 01, 169.K. A. Pelikan and J. D. von Mikusch, Oil and Soap, 1938,15, 149.ll1 T. P.. Hilditch and C. H. Lea, J., 1927, 3106.Composition of Dep6t Fats ofAquatic Animals, 1942.K 294 ANALYTIOAL OHEMISTRY.(c) Eatimation of unsaturated acids by isolation and analysis of theirbromo-compounds. Although this method is not quantitative on accountof mutual solubility effects, different behaviours of isomers, etc., it can bemade to yield trustworthy re~ults.1~~ 2O(d) Estimation of oleic, linoleic, and linolenic acids by H.P. Kaufmann’sthiocyanometric method. Although W. Kimura in 1929 had pointed outthe shortcomings of this method, these were not generally recognised until1939 and later.ll3, 114 Since 1940 Kaufmann’s theoretical values have beenreplaced by empirical figures for thiocyanogen ~alues.10~~ 23 The thiocyanu-metric method may soon be superseded by the following method.(e) The spectrophotometric method of J. H. Mitchell, H. R. Kraybill,and F. P. Zscheile 115, lo* which directly estimates the proportions of linoleicand linolenic acids after alkali-isomerisation of these to conjugated acids.T. P. Hilditch, R. A. Morton, and J. P. Riley 116 confimed these findings andextended the method to the determination of these acids in the presence ofelaeostearic acid.l17 Spectrophotometric methods for a-elzeostearic acid 11*and a-, p-, and total elaeostearic acids 119 in tung oil are described. Thespectrophotometric method 115 is modified by using nitrogen to protect bothsamples and reagent during isomerisat ion.l20Although the thiocyanometric and spectrophotometric methods arenotable advances, there are indications that they need to be furtherinvestigated. R. T. Milner, reporting on collaborative work on SCNvalues,121 states that the results obtained gave compositions for the oilsstudied different from those obtained by the spectrophotometric method.T. P. Hilditch, M. L. Meara, and J. Holmberg 122 state that “ it has recentlybeen shown 123 that the spectrophotometric determination of linolenic acidmay proably give somewhat higher figures than the true values when theproportion of the latter acid is not large ”.(f) Separation of mixed fatty acids or glycerides by fractionalcrystallisation from solvents a t low temperatures, introduced by J.B. Brownand his c o - ~ o r k e r s , l ~ ~ ~ 125 which bids fair to oust the lead-salt method ofseparation 126s 127 and is the only available method for separating the mixedlla J . Soc. Chem. Ind. Japan, 1929, 32, 138B.113 R. W. Riemenschneider and D. H. Wheeler, Oil and Soap, 1939, 16, 219.114 T. P. Hilditoh and K. S . Murti, Analyst, 1940, 65, 437.115 Ind. Eng. Chem. Anal., 1943, 15, 1.117 T. P. Hilditch and J.P. Riley, J . SOC. C h m . Id., 1946, 65, 74.118 R. T. O’Connor, D. C. Heinzelman, A. F. Freeman, and F. C . Pack, I n d . Eng.1ls R. T. O’Connor, D. C. Heinzelman, and R. S. McKinney, J . Amer. Oil Chem. SOC.,lao R. T. O’Connor, D. C. Heinzelman, and F. G . Dollem, OiE and Smp, 1945,22,257.124 Ibid., p. 321.123 T. P. Hilditch and R. K. Shrivastava, Analyst, 1947, 72 (h the press).124 J. B. Brown and G. C. Stoner, J . Amr. Chern. SOC., 1937, 59, 3.125 J. B. Brown, Ohm. Reviews, 1941, 89, 533.126 T. P. Hilditch and J. P. Riley, J . SOC. Chem. Ind., 1945, 64, 204.127 F. A. Smith and J. B. Brown, Oil and Soap, 1946, 23, 321; 1946,23, 9.116 Araalyst, 1946, 70, 67.Chem. Anal., 1945,17,467.1947, 24, 212.J . Amer. Oil Chem. SOC., 1947, 24, 78SEXTON : OILS, FATS, AND SURFACE-ACTIVE AGENTS.295triglycerides of a fat. Incidentally, fractional crystallisation is nowcommercial practice.128 R. G. de Gray and A. W. de Moise 129 recommendthis method for separating fatty acids in analysis, and F. R. Earle andR. T. Milner 130 use it for the quantitative separation of the saturated acids ih5 g. of soya-bean oil fatty acids. F. E. Luddy and R. W. Riemenschneider 131prefer the crystallisation method in determining trisaturated constituents inedible oils. D. S. Anthony, F. W. Quackenbush, and H. Steenbock 132 alsofavour the technique for the analysis of 1 g . of oil. For the rapid estimationof saturated glycerides in edible fats, C. A. Coffey and H. T. Spannuth usecrystallisation .I33(9) Some form of distillation-by steam or by fractional distillation in avacuum, of the esters of acids, or molecular distillation.105 The first twomethods are in common use, the last has been somewhat disappointing.A.W. Weitkamp 134 found the amplified distillation of fatty acid methylesters satisfactory but not that of the acids themselves because of theformation of azeotropes with the hydrocarbon component. I n theester-fractionation procedure for the component acid analysis of fats thecompositions of the fractions are calculated from their saponificationequivalents and 1.V.s. With marine animal oils these calculations can bevery laborious, YO W. S. Rapson, H. M. Schwartz, and N. J. Van Rensburg 135describe and supply definite computation forms.Using a Valentineimproved precision refractometer, P. M. Althouse, G. W. Hunter, andH. 0. Triebold 136 determined the refractive indices of methyl, propyl, andisopropyl esters of the C6-C,, saturated fatty acids between 20" and 45".(h) Hydrogenation, either total or partial, in stages has been used withsuccess .lo5(i) Chromatographic methods. S. Claesson 137 has developed a flowingchromatographic method for the separation of fatty acids, using activatedsilica and a non-polar solvent. The members of a homologous series canbe separated in a similar manner by using activated carbon.122H. J. Dutton's 138 method for colourless compounds uses R. I. measurementof the percolate during continuous flowing. K. A. Williams 139 reviewed theuse of chromatography in fat analysis.A recent paper by the Liverpool school 122 shows how these methods wereused in determining the glyceride structure of soya-bean oil.Low-temperature crystallisation from solvents, the spectrophotometric method,fractional distillation, and adsorption methods were pressed into service.The Evers-Bellier test is discussed by C. M. Desai and A. H. Patel 140R. E. Kistler, V. J. Bluckerheide, and L. D. illeyers, Oil and Soap, l!kiG, 23, 146.lZD I d . Eng. Chent. Anal., 1941, 13, 22.131 Ibid., 1946, 23, 385.134 J . Amer. Oil Chem. SOC., 1947, 24, 236.135 Ibid., p. 84.13' Arkiv Kenzi, Min. Geol., 1946, 23A, No. 1 ; Rec. Trav. chim., 1946, 65, 571.138 J . Physical Chem., 1944, 48, 179.13@ Analyst, 1946, 71, 259.140 C.M. Desai and A. H. Patel, Curr. Sci., 1945, 14, 130; 1947, 16, 92.130 Oil and Soap, 1940, 17, 106.132 Ibid., 1943, 20, 53. 133 Ibid., 1940, 17, 216.136 Ibid., p. 267296 ANALYTICAL CHEMISTRY.and by 8. Naraya11ier.l~~ 5:. ‘l’. Voorhies and 8. 1’. Bauer 142 consider themodified Renard and Kerr tests for the determination of arachis oil unreliable.Despite this, the A.O.A.C. retain the method although it is not now consideredto be strictly quantitative.F. H. Smith’s two spectrophotometric methods 143 for gossypol in crudccottonseed oils require less than 2 hours compared with the 5 days of thegravimetric method. The A.O.C.S. gossypol committee 144 reported 011gravimetric and spectrophotometric methods for the determination ofMethods for the analysis of lecithin are given 85 and for lipids in feediiigstuffs by R.R e i ~ e r . 1 ~ ~ G. Gorbach 146 gives details of micro-methods forphosphatides in fats. Recent cases of poisoning lend interest toP. Malangeau’s method 14’ for tricresyl (tritolyl) phosphate in vegetable oils.gossypol.Mono- and Di-glycerides.These are rarely purc products-they are usually mixtures of all theetypes of glyceride with one type preponderating. For inst’ance, commercialglyceryl monostearate contains free glycerol, and mono-, di-, a,nd tri-stearinas well as stearic acid soaps.S. Kawai and S. Yamamoto,1*8 investigating the production of 1110110-glycerides from tea-seed oil by inter-esterification, determined the acid,saponification, and hydroxyl values at intervals and thence calculated themono-, di-, and tri-glyceride contents.K. S. Markley 149 states that thethree types of glyceride may be separated by fractionation from alcohol.J. H. Newburger 1.50 determines monostearate in a sunburn creamcontaining lanolin, by chloroform extraction, determination of free itndcombined glycerol by I. Shupes’s periodate method,156 of unsaponifiahlcmatter, fatty acids, and their equivalent weight, and then caIculatioii of theinonoglyceride content. A. Troy and A. C. Bell 151 use a somewhat similarmethod for cosmetics.E. Handschumaker 152 and his co-workers detect and estimate diglyceridesin hydrogenated oils by using the principles of Hilditch’s crystallisation fromacetone. N. Ivanoff,ls in a new method for monoglycerides in fats, oxidisesin alcohol with standard periodate and back-titrates with sodium arsenite.The hydroxyl groups give 2 mols. of corresponding aldehydes.W. D. Pohle,Io1 Curr. Xci., 1945, 14, 177.lo3 F. H. Smith, Ind. Eng. C’henb. Anal., 1!146, 18, 41, 658.146 t’ette u. Seife?), 1944, 51, 53; Che??~. Abs., 1947, 41, 1469.” 7 Ann. Phurnt. frunq., 1944, 2, 102; Chent. Abs., 1946, 40, 4900.148 J . SOC. Chem. Ind. Jupam, 1940, 43, 219.log ‘‘ Fatty Acids ”, p. 306.150 J . Assoc. Off. Agric. Chem., 1947, 30, 683.l 5 I Amer. Perfumer, 1946, 48, 54; Chem. Abs., 1946, 40, 6667.152 E. Handschumaker, S. W. Thompson, and J. E. McIntyre, Oil u i ~ d Soap, 1943,l m Chem. Abe., 1946, 40, 6361.142 Oil and Soup, 1943, 20, 175.J. .41ucr.Oil Chenb. Soc., 1947, 24, 369. l i t 5 Ibid., p. 199.20, 133V. 0. Mehlenbacbher, aiitl J. H . Cook IM determine inonoglywride by periodic.oxidation ; di- and tri-glycerides do not interfere. R. 0. F e ~ g e , ~ ~ ~ analysingpurified mono- and di-glycerides prepared by himself, from total combinedglycerol content by the A.O.C.S. clichromnte method, monoglyceridecontent,la free fatty acid content, and mean molecular weight of the fattyacids, calculated the mono-, di-, and tri-glyceride composition of the products.E. Handschumaker and L. Linteris 230 modify the periodate method,lM byusing an inert solvent. 'Phis avoids heat-induced secondary oxidat ioiire;tctions and the time required is reduced from 30 to 2 minutes.Surface-crct iue A gmts IThese fall into three main classes : anionic, cationic, an(\ non-ionic types(a general account with classification is to be found in works by H.K. Dean,and by C. B. Young and I<. W. C O O ~ ~ S , ~ ~ ~ and articles by C. G r a n a ~ h e r , ~ ~ ~J. A. Hill,159 R. Ackley,160 I. Hollenberg,lG1 J. Ripert,162 andJ. C. L. Resuggan 163). They are used either alone or with soaps, inorganicsalts, cellulose derivatives, etc., so their examination calls for all the ingenuityand skill of the chemist and the response to the challenge is to be observed inthe large number of papers published in the past few years.Evaluation and Cor,&parison.-This is generally done by wetting tests,surface and interfacial measurements, and detergency tests. The wettingtest is usually C.Z. Draves and R. G. Clarkson's sinking-time test or somemodification of it.lG4 I. J. Gruntfest, 0. B. Hager, and H. B. Walker 165criticise the test and propose it hydrometer modification. The German testis Surface and interfacial-tension measurements are made bysome convenient rneth0d.1~~6 A. E. Alexander and J. H. Schulman167determined benzene-water interfacial tensions in the presence of surface-active agents, and R. 0. Feuge155 measured the interfacial tension ofoil-water systems containing mono- and di-glycerides. As inorganic saltsare often present in large amounts in surface-active agents,l68 surface-tensionmeasurements are not of much value for comparison purposes.The detergency test is carried out by washing soiled material underIb4 Oil a d Soap, 1945, 22, 115.l x J . Awtcr. Oil Cheiti. Soc.., 1947, 24, 19..I. A4ssoc. OJ. A g r i c . P/wm., 1913, 26, 249; S. H. Sewburger an(l ('. F. Hriirning,15' H. K. Dean, " Utilisation of' Fnts ", 1938; ('. H. Young and K . IT, C'oon\,158 ('iba Review, 1945, 56, 2039.lsS J . SOP. Dyers Col., 1947, 63, 319.lb1 Soap, Perfumery, and C'osmetics, 1947, 20, 56.'.1 6 2 Ibid., 1945, 18, 885; 1946, 19, 552.ls3 Food Manzrf., 1947, 22, 163, 203, 299, 363.l b 4 A-l)wr. Dyestiif Rep., 1931, 20, 301 ; 1939, 28, 425.l C 5 Ibid., 1947, 36, 325.IfiQ I\'. Baird, C. P. Brown, and C . R. Purdue, J . SOP. Dyers Pol., 19-16, 62, 323.I G 7l f i 8 L. 11. Flett, C'heni. Enq. S e w s , 1942, 20, 1 3 ; J. A. Hill and C. L. Hunter, Xnttwe,ibid., 1947,30, 651." Surface Active Agents ".160 Boap clnd Snn.C ' h e t t i . , 1917, 23, 39.'I'mns. Faraday Soc., 1940, 36, 960.1946, 158, 585208 ANALYTICAL CHEMISTRY,standard reproducible conditions in a " launderometer ", in which 20 samplesof soiled cloth can be washed simultaneously in separate containers, and thencomparing the washed cloths either visually or by reflectance measurements.S. F. S y I ~ e s t e r , ~ ~ ~ instead of the Atlas " launderometer ", used a " detergencycomparator '' to compare synthetic detergents with soap, as regards scouringefficiency. W. G. Tiedeman l70 reviews the evaluation of some dish-washingdetergents, and a performance test for these is given by E. H. Mann andC. C. Ruchhoft.I7l A simple laboratory method of comparing detergents isdescribed by A.J. Kelly and D. H. G ~ n t h e r . l ~ ~ Using a " launderometer ",A. K. Epstein 173 and his co-workers determined the reflectance of the washedcloths with a photovolt reflectometer. The preparation of standard soiledmaterial and the construction of a soiling machine are described byB. S. Van Zile.174 Studies in soiling and detergency, standard " soils ", andwaahing procedure were made by J. R. Clark and V. B. H01land.l~~J. P. Sisley discusses the determination of the industrial value ofdetergents.228 The many methods for comparison of detergents aredescribed.176 R. B. Whitehead177 writes on the evaluation of wettingagents and criticises the tests. Information on washing tests is given byM.L. H ~ r w i t z , l ~ ~ 0. Bac0n,1~~ and E. Kornreich.lsoA colorimetric method for evaluating dispersing agents is described byG. C. Tesoro, W. T. Donahue, and J. A. Casey.ls1 The testing compoundwas Hansa-yellow YT-445D which is neither surface-active nor easilydispersed. The degree of solubilisation of water-insoluble dyes by soapsand detergents was measured by J. W. McBain and A. M. Green.182M. Z. Poliakoff describes a simple and well-tested method of evaluatingdetergent efficiency, using dispersion cylinders.la G. Davis, S. J. Ward,and P. D. Liddiard lE4 have constructed an instrument for measuring thestrength of detergents; and F. W. Gilcreas and J. E. O'Brien ls5 andR. C. Hughes and R. Bernstein ls6 describe photoelectric methods ofmeasuring detergent efficiency.E. L. Pouts and T. R. Freeman 187 describea simple apparatus for the same purpose.AnaZysis.-The analysis of surface-active agents is conveniently dividedinto (a) analysis of surface-active agents and ( b ) detection and determinationof these.169 Amer. Dyestu, Rep., 1947, 36, 91. 170 Soap and Sun. Chem., 1947,23, 48, 102.1 7 1 Pub. Health Repts., 1946, 61, 877. 172 Anaer. Dyestuff Rep., 1947, 36, 455.173 A. K. Epstein, B. R. Harris, M. Katzman, and S. Epsteifi, OiZ and Soap, 1943,20, 171.Ibid., p. 55. 175 Amer. Dyestuff Rep., 1947, 36, 734.178 Amer. Dyestuff Rep., 1946, 35, 83.180 Text. Manuf., 1946, 72, 271.l T G A.S.T.M. Bulletin, 1946, No. 140, 78; No. 141, 49; J. C. Harris.l i 7 Ciba Review, 1945, 49, 1789.l i 9 Ibid., 1945, 34, 556.Rubber A g e , 1946, 60, 319.lB2 J .Amer. Chem. SOC., 1946,68, 1731 ; J . Physical Cliem., 1947,51, 286.183 Anal. Chem., 1947, 19, 140.lE4 Abstr. Proc. Xoc. Agric. Bact., 1944, 53.Amer. J . Pub. Health, 1941, 31, 143.1e6 Ind. Eng. Chem., 1945, 37, 170. lB7 *J. Dairy Sci., 1947, 30, 61SEXTON : OILS, FATS, AND SURFACE-ACTIVE AQENTS. 299(a) The A.O.C.S. methods23 include a section (F) on the analysis ofsulphonated and sulphated oils, and D. Burton and G. F. Robertshaw’spublication 18* remains indispensable. I n further work 189 on thedetermination of free and uncombined unsaponifiable matter in oils, waxes,and sulphated products, Burton and Robertshaw investigated the S .P.A.,I.C.S.F., and Wizoeff methods and recommend the first for most oils as wellas describing procedures for sulphated oils and alcohols and petroleumsulphonic acids. D.Burton and L. F. Byrne,lgo~ l 9 1 on the constitution ofsulphated oils, give methods for determining the carboxyl, sulphato-, andsulphonic groups and their salts. S. L. Glicher Ig2 describes the tests used inanalysing sulphated oils, and much useful information can be found inarticles by M. G. de Navarre.l93 An early method for aryl alkyl sulphatesin solution was the benzidine method of W. Kling and F. P~schel.19~ Thishas been used by A. Brunzelllg5 in determining dodecyl sulphate in thepresence of sodium sulphate and soap. Dodecyl sulphate was determinedby titration of the acid liberated by acid hydrolysis.The Kling-Puschelmethod was used by D. A. Shiraeff Ig6 in the quantitative analysis ofIgepon T. T. V. Marron and J. Schifferlei lg7a describe a direct volumetricdetermination of the organic sulphate content of synthetic detergents, whichinvolves reaction of p-toluidine with sulphonates, extraction of the complexinto carbon tetrachloride, and subsequent titration. A reference sample isanalysed by the “ difference ” method of D. Berkowitz and R. Bernstein,lg8who separate “ active ” ingredients by 50% alcohol, determine soap, “ fat ”,and chloride in the alcoholic solution, and calculate synthetic detergent as thedifference between total alcohol-soluble matter and the sum of soap, “ fat ”,and chloride. Oil-soluble petroleum sulphonates are analysed by extractionwith chloroform, potentiometric titration, and adsorption on Attapulgus~lay.1~9Themethods of determination can be used for detection and vice versa Whensurface-active agents are to be detected or determined it is usually firstnecessary to extract them from the material in which they are contained bymeans of some suitable organic solvent, immiscible or otherwise.Eachsample has to be treated on its merits so as to obtain the surface-active agentin as pure and concentrated form as possible.2m, 201“ Sulphated Oils and Allied Products : Chemistry and Analysis ”, 1939.J . Inter. SOC. Leather Trades’ Chem., 1946, 30, 279.(b) Many methods are now in use or have been prop0sed.1~~6lgo lbid., p. 306. lgl Ibid., 1947, 31, 100.lg3 Soap, Perfumery, and Cosmetics, 1946-47.lg5 Svensk Parm.Tid., 1947, 51, 101 ; through Chem. Abs., 1947, 41, 3641.lQ6 Amer. Dyestuff Rep., 1947, 36, 313.l g 7 0 I n d . Eng. Chem. Anal., 1946,18, 49.19”, C. J. Pederson, Amer. Dyestuff Rep., 1935, 24, 137; F. M. Biffen and F. D. Snell,lg8 Ibid., 1944,16, 239.lQ9 F. Brooks, E. D. Peters, and L. Lykken, ibid., 1946, 18, 544; Ana7yd, 1946,2oo J . Amer. Oil Chem. SOC., 1947, 24, 54.201 Dr. Wurzschmidt, Chimie anal., 1947, 29, 44.lg2 Petroleum, 1945, 8, 130, 232.lQ4 Melliand. Textilber., 1934,15,21.Ind. Eng. Chem. Anal., 1935, 7, 234; J. C. Harris, ibid., 15, 254.71, 5933 0 ANATdYTTC-4Td ORRRITSTRY.Methods for the estimation of quaternary ammoninm compounds arereviewed by A. S. DuBois,202 who gives a titration met’hod 203 using 0.01%bromophtnol-blue and 0.04:/, sodium dodecyl sulphat e , and anargentometric 204 inethod with eosin or dichlorofluorescein indicator.M.E. Auerbach’s method205 consists in treatment of 2 mols. of thequaternary salt with 1 mol. of bromophenol-blue t,o form a blue dye, which isthen extracted with ethylene dichloride and examined colorimetrically ; hisown modified method 206 use8 benzene.avoids the extraction. T. H. Harris 208 estimates quaternary ammoniumcompounds in fruit juices by Auerbach’s method, the method of measurementbeing as described by J. B. Wil~on,~O~ who also describes two methods forthese compounds in foods. The first is a modified Auerbach method ; in thesecond the quaternary compound is precipitated as the ferricyanic acid salt,the unused ferricyanide being determined by titration. The ferricyanidemethod is described elsewhere.210 0. Hager, E. Young, T. Flanagan, andH. Walker 211 describe two qualitative and three quantitative methods forquaternary ammonium compounds based on the insolubility of theirtri-iodides in water. Determination by precipitation with anionic dyeswas proposed by G . S. Hartley and I>. F. Runnicles 212 and by A. Krog andC. G. Mar~hall.~l~ The determination of the concentration of quaternaryammonium solutions and their detection in milk are described.229 Thesolubilities of such compounds in organic solvents have been determined.214Methods for the estimation of small quantities of sulphonated or sulphatedsurface-active agents have been offered by F. M. Scales,215 J. C. Harris,216H. H. Jones, 217 and L. F. H0yt.~18 Jones’s method is based on the fact thatsulphonated surface-active compounds (colourless anion) formed colouredchloroform-soluble salts with methylene-blue (coloured cation). Thecoloured chloroform solution is read in a spectrophotometer : 1.0 mg. ofanhydrous methylene-blue chloride = 3.13 x equiv. of ‘‘ sulphonate ”.This method is also useful as a rapid qualitative test. Hoyt’s methoddetects surface-active agents by their solubilising action on the oil-solubleNational Brilliant-Blue B.M.A. The surface active agent, after isolation, isdissolved in water. The dye in 2% dilution in sodium chloride is added,and a blue solution is obtained in the presence of a surface-activeE. L. Colichman’s modification202 Amer. Dyestuff Rep., 1915, 34, 245. 203 Soap and Saii. C h e w . , 1926, 22, 12.5.204 I d . Eng. Clzem. Anctl., 1945, 17, 744. 205 Ibid., 1943, 15, 492.2oc lbid., 1944, 16, 739. 2oi Anal. Chein., 1947, 19, 430.408 J . Assoc. Off. Agric. Chem., 1946, 29, 310. ?09 Ibid., p. 311.210 “ New and Non-official Remedies ”, 1946, p. 165 (ferricyanide method).2 1 1 Anal. Chent., 1947, 19, 886.213 Anter. J . Pub. Health, 1940, 30, 341.214 R. S. Shelton, J . Anter. Chem. Soc., 1946, 68, 753; I?. A. Reck, H. J . Hnrwood,and A. W. Ralston, J . Orq. Cheni., 1947,12, 517.2 1 5 Proc. Inter. Assor.. Milk Dealers, 1939, 31, 197.2 1 2 Proc. Ro!J. Sor., 1938, A , 168, 424.I n d . Eng. CJLeitz. Anal., 1043, 15, 234.J . Assoc. Off. Agric. Chew?., 1945, 28, 399.t J . Anier. Oil Chem. SIoc., 1947, 24, 54SEXTON OTT,S, FATS, ANn SURFACE-ACTTVR AGENTS. 301caonipouncl. The method is suitable for the anionic, cationic, and non-ionic:types.Certain cationic surface-active agents form st,oicheiometric salts withanionic types. This fact has been used as the basis of t,wo titrimetricmethods 212j 219 which, according to S. R. Epton,220 are not entirely satis-factory. He titrates the alkyl sulphate in water-chloroform mixture withcetylpyridinium bromide solution using a methylene-blue indicator solution ;when the colour in both layers is of the same intensity the equivalence pointhas been reached. T. Barr, J. Oliver, and W. V. Stubbing< 221 confirmEpton's findings and claim that their own method is an improvement on thetnethylene-blue method.The estimation of mono- and di-alkyl phosphates and free dodecyl alcoholin the presence of free acid is described.222 A Hintermaier 223 givesqualitative tests for detergent mixtures, and K. M. Linsenmeyer's scheme 224separates wetting agents into eight classes. H. B. Goldstein 225 describes thequalitative analysis of surface-active agents, and A. Parisot 226 gives indetail the analysis of some wetting agents. A. Steigmann227 gives twocolour tests for anionic wetting agents. G. E. W. S.H. J. DOTHIE.J. R. NICHOLLS.6. E. W. SEXTON.I<. (:. MTOOI,." I y 6. M. Preston, J . SOC. 1)yer.s Vd., 1045, 61, 163.220 Nature, 1947,160, 795.2"3 Fette u. Seifen, 1945, 51, 10.225 Amer. Dyestug Rep., 1947, 36, 629.22i J . Sor. Chenz. Id., 1947, 66, 356.s29 W. J. Harper, P. 13. Elliker, and W. I<. Moseley. J . Dairy Sci., 1047,30, 536.621 {bid., p. 909.134 Melliand. l'extilber., 1940, 21, 468.226 Corps gras et savons, 1943, 1, 11.428 Anzer. Dyestuff Rep., 1947, 36, 457.S. B. McFarlane, jiinr., Oil and ~Tonp, 1946, 23, 337..I. -4fner. Oil Chemz. h'oc., 1947, 24, 14.3

ISSN:0365-6217    

DOI:10.1039/AR9474400264

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

INDEX OF AUTHORS’ NAMES.Abbolito, E., 286.Abbott, J. L., 285.Abel, E., 78, 80.Abelson, P. H., 57.Abrams, R., 229.Ackley, R., 297.Adam, N. K., 13.Adam, W. B., 265.A d a m , R., 173.Adamson, P. S., 155.Adler, H., 277.Aelony, D., 99, 107.Aeulle, E. O., 288.Agafonova, T. N., 282.Agar, J. N., 5, 6, 23, 25, 31.Ageev, N. V., 283.Ageeva, D. L., 283.Ahlborg, K., 224.Ainsworth, A. N., 289.Aladjalova, N., 21, 28.Albu, H. W., 69, 70.Alcock, T. C., 277.Alder, K., 157.Alderson, T., 116.Alexander, A. E., 297.Alexander, E. R., 142.Alexander, H. E., 262.Alexander, J., 286.Alexander, W. A., 287.Allison, F. E., 235.Althouse, P. M., 295.Altschul, A. M., 229, 231.Alvfeldt, O., 285.Alyea, H., 69.American Oil Chemists’Society, 289, 293, 297.Ames, S.R., 243.Amiard, G., 245.Anderson, D., 135.Anderson, E., 251.Anderson, E. B., 291.Anderson, E. H., 262.Anderson, G. W., 247.Anderson, H. C., 278.Anderson, T. F., 53, 262.Andr6, E., 289.Andrews, A. I., 281.Andrussow, L., 68.Angeli, A., 68.Angliker, E., 189.Angus, W. R., 73.Anner, G., 170, 177, 199,201, 202, 203, 204.Anson, M. L., 227, 233.Anthony, D. S., 295.Antopol, W., 237.Antweiler, H. J., 14.Apfelbaum, P. M., 146.Ara, A., 283.Archbold, H. K., 222.Arends, B., 78.Argument, C., 80.Ark, P. A., 263.Armstrong, G., 11.Arnold, H., 162. 163, 164:Arpagaus, (Miss) T., 163.Aschner, M., 221.Assoc. of Official Agric.Chemists, 292, 293.Aston, J. G., 37.Astwood, E. B., 247, 248,252, 263, 254.Audubert, R., 20, 30.Audureau, A., 261.Auerbach, C., 260.Auerbach, M.E., 300.Austin, A. E., 277.Aveniri-Shapiro, S., 221.Avery, W. H., 68.Avramenko, L., 65.,4xelrod, H. E., 238.Baars, E., 11.Babcock, J. H., 101.Bach, S. J., 228.Bachelet, M., 57.Bachman, G. B., 100.Bachmann, P., 148.Bachmann, W. E., 132, 177,179, 183, 193, 199, 203.Backus, M. P., 259.Bacon, O., 298.Baddiley, J., 240.Badger, G. M., 132.Badger, R. M., 135.Biickstrom, H. L. J., 69, 70.Baeyer, A., 63.Bagotsky, 25.Bailey, D. L., 231.Baird, W., 297.Baker, L. D., 237.Baker, W., 120, 130, 162.Bale, W. F., 277, 279.Balla, G., 156.Ballard, J. W., 282, 283.Ballou, N. E.; 57.Balz, G., 73, 107.Bancroft, W. D., 29.Bandes, H., 12.Banerjee, B.K., 281.Banga, I., 231.Barbier, P., 184.Barclay, I. M., 16.Barker, C. C., 224.Barker, G. C., 26.165.302Barker, H. A., 217, 220,Barnard, G. A., 266.Barnes, R. B., 190.Barr, T., 171, 301.Barraclough, A., 292.Barredo, J. M. G., 282.Barrer, R. M., 28.Barrett, C. S., 278, 283, 284,Barrett, R. L., 275.Bartlett, M. D., 229.Bartlett, M. S., 271.Barton, M. N., 246.Bassett, H., 48.Bastian, H., 124.Bastiansen, O., 123.Bastron, H., 37.Basu, V. P., 188.Bates, J. R., 62.Batty, J. W., 149.Batuecas, T., 62.Baubigny, H., 70.Bauer, C. D., 175.Bauer, S. H., 54, 135.Bauer, S. T., 296.Baxendale, J. H., 63, 67.Baxter, G. P., 51.Baxter, R. A., 143.Beach, J. Y., 54.Beadle, B. W., 292, 293.Beadle, G.W., 254, 255,Beakbane, A. B., 230.Bean, W. B., 237.Beanblossom, W. S., 99,Bear, R. S., 226.Beck, G., 56.Beck, L. W., 183.Becker, E., 255.Beerstecher, E., 260.Beiler, J. M., 247.Bell, A. C., 296.Bell, D. J., 222, 225, 226.Bell, R., 277.Bell, R. P., 18, 53, 55.Bellamy, W. D., 240, 241,Bolmore, E. A., 116.Belyankin, D. S., 277, 279.Benedetti-Pichler, A. A.,Bengston, B., 277.Bennett, G. M., 74, 75.Benning, A. F., 87.Berg, 0. E., 287.Berger, H., 124.221.286.256, 258.101.242, 245.59INDEX OF AUTHORS’ NAMES. 303Berger, K., 73, 74.Bergmann, W., 175.Berkelharner, L. H., 280.Berkley, E. E., 283.Berkowitz, D., 299.Berkson, J., 272.Berl, E., 68.Berliner, E., 41, 126.Bernal, J. D., 50.Bernert, T., 51.Bernfeld, P., 223.Bernstein, J., 95.Bernstein, R., 298, 299.Berwald, E., 227.Bhagvat, K., 231.Bhatacharyya, B.K., 169.Bickford, W. G., 293.Bide, A. E., 174.Biffen, F. M., 299.Bigeleisen, J., 78.Bigelow, L. A., 88, 89, 92,Bikerman, J. J., 14.Billen, G. N., 289.Billetkr, J. R., 174, 192, 204,Binder, O., 278.Bindsich, A. W., 178.Birkenbach, L., 79.Bissell, A., 248, 252.Bixby, E. M., 114.Black, H. C., 291.Blass, L., 143.Blaxter, D. K. L., 265.Blewett, M., 255.Bliss, C. I., 272, 273.Bloch, E., 181.Block, I., 89.Block, K., 232.Blokhin, M. A., 284, 285.Blumann, A., 160.Bockemuller, W., 88, 107.Bockris, J. O’M., 25, 28, 29,Bodenstein, M., 62, 64, 68.Bohme, H., 152.Bogert, M. T., 146.Bogue, R. H., 277.Bohle, K., 189.Boivin, A., 262.Boldyrev, A.K., 276.Bolt, R. O., 94, 112, 118.Bombinska, J., 118.Bond, R. L., 98.Bondhus, F. J., 41.Bonhoeffer, K. F., 11, 65.Bonner, D., 255, 256, 257,Bonner, J. F., 277.Booth, H. S., 99, 114.Boppel, H., 224.Borei, H., 228.Borelius, G., 283.Borisov, N. D., 285.Borissova, T., 6.Borovskii, I. B., 284, 285.97.206.30.258, 259.Borsche, W., 137.Borsook, H., 259.Bose, A., 154.Bourne, E. J., 222, 223.Bourquin, J. P., 144, 146.Bowden, F. P., 5, 6, 11, 12,Bowden, K., 32.Bowen, E. J., 32, 64.Box, G. E. P., 273.Boyce, J. C., 32.Boychenko, E. A., 233.Boyle, J. A., 293.Bradley, A. J., 281, 283.Bradlow, H. L., 142.Bradshaw, B. C., 68.Bradsher, C. K., 126.Bragg, W. L., 283.Braida, A., 101.Brand, J.C. D., 74, 75.Brandegee, M. &I., 87.Brandenberger, E., 278,280.Brattain, R. B., 37.Braude, E. A., 32.Brauer, P., 285.Braun, J. von, 133.Braun, W., 261.Brauner, B., 87.Brauns, D. H., 109.Braunstein, A. E., 243,Bray, G. T., 265.Bray, W. C., 63, 79.Breitner, S., 177.Breitschneider, O., 114.Brentano, J. C. M., 283.Breusch, F. L., 293.Breyer, B., 7, 10.Brice, J. J., 114.Brickwedde, F. G., 37.Bridgeman, W. B., 225.Briggs, L. H., 152.Brindley, G. W., 281.Brink, N. G., 388.Brockway, L. O., 55, 108,Brode, W. R., 114.Brooks, F., 299.Broom, W. A., 272.Brown, A. H., 231.Brown, C. P., 297.Brown, F., 223.Brown, H. C., 55, 97.Brown, J. B., 294.Brown, 0. E., 281.Brownlee, K.A., 266.Bruce, W. F., 245, 246.Bruening, C. F., 297.Brugger, W., 147, 148.Brummage, K. G., 283.Bruns, B., 14, 27.Brunzell, A., 299.Bryant, P. M., 29.Buben, N. Y., 31.Buckley, G. D., 99.Buchi, G., 186.23, 30.244.126, 130.Buerger, M. J., 281.Buerger, N. W., 281.Buhler, J. S., 280.Buisman, J. A. K., 174.Bune, N., 27.Bunn, C. W., 278, 279, 280.Burawoy, A., 53, 55, 149.BurcMeld, P. E., 99, 114.Burg, A. B., 49, 114.Burgers, W. G., 278.Burkmdt, L. A., 277, 279.Burr, G. O., 44, 288.Burris, R. H., 234.Burton, D., 299.Buswell, R. J., 288.Butenandt, A., 180, 192,196, 214, 255.Butler, B., 242.Butler, J. A. V., 5, 11, 14,Butz, L. W., 37.Byrne, L. F., 299.Bywater, W. G., 247.Cady, G. H., 89, 95, 96.Cagle, F.W., 277.Calcott, W. S., 109.Calfee, J. D., 88.Calvin, M., 34.Cambi, L., 68.Cameron, J. L. M., 133.Campbell, N., 127.Campbell, W. P., 151.Cantarow, A., 251.Capato, E., 153.Carapella, L. A., 283.Carlin, R. B., 246.Carpenter, L. E., 238.Carr, E. P., 35.Carr, J. G., 260, 263.Carr, N. E., 28.Carter, A. H., 70.Carter, F. D., 150.Cartmight, G. E., 238.Casey, J. A., 298.Cason, J., 109.Caspari, E., 255.Castor, J. G. B., 227.Cattle, M., 224.Cauchois, Y., 284, 285.Cecil, R., 225.Cerighelli, R., 280.Chaikoff, I. L., 248, 251.Chakravarti, R. N., 154.Chakrevarty, S. K., 277.Challinor, S. W., 231.Chambion, J., 152.Champetier, G., 20.Chandler, C. A., 262.Chantrenne, H., 229.Chapman, D. L., 14.Chapman, R.A., 291.Chareffer, H. A., 252.Chargaff, E., 225.Charkey, L. W., 245.Charonnat, R., 188.16, 17, 18, 19, 20, 26301 INDEX OF AUTHORS' NAMES('haterjee, N. N., 154.Chatterjee, G. P., 279.ChBdin, J., 74, 76.Chesley, F. G., 281.thirnside, R. C., 279.Chistyakov, F., 25.Choppin, A. R., 28.Christian, S. M., 6.Christiansen, J. A., 77.Christopers, H. J., 96.Chuoke, R. L., 41.Churchman, C. W., 467Chute, W. J., 142.Chilli, V., 279, 284.Claesson, S., 295.Clancey, V. J., 274.Clar, G., 151.Clark, D. M., 188.Clark, G. L., 277, 278, 280,283, 286.Clark, I., 246.Clark, J. R., 298.Clark, L. M., 279.Clark, P. E., 292.Clark, R. E. D., 12.Clarkson, R. G., 297.Clayton, J. O., 277.Clemo, G. R., 144.Clever, H. L., 291.Cline, J.E., 68.Clisby, K. H., 247.Coates, G. E., 29.Cochran, W. G., 274.Cocker, W., 144.Coffey, C. A., 295.Cohen, A., 215, 236.Cohen, J. A., 219.Cohen, P. P., 269.Cole, A. G., 127.Cole, W., 193.Cole, W. F., 279, 280.Colichman, E. L., 300.Colonge, J., 146, 153.Colowick, S., 219, 220.Comar, C. L., 233.Common, R. H., 230.Connor, T., 292.Considine, D. M., 283.Conway, B. E., 25.Cook, E. S., 229.Cook, G. A., 62.Cook, J. H., 297.Cook, J. W., 120, 131, 13.2,133, 137, 138.Cooke, P. W., 283.Coolidge, A. S., 15.Coolidge, T. B., 228.Coons, K. W., 297.Cooper, M., 101.Coover, H. W., 246.('ope, A. C., 121.Copley, D. M., 293.Copp, F. C., 150, 155.Cori, C. F., 219, 226.Cori, G. T., 225, 226.Cornforth, J.W., 170, 171.('omens, C . W., 180.Corson, D. R., 51.Corvalen, M. I., 58.Coryell, C. D., 57.Coulson, Cj. A.. 36, 45, 126,Coulson, E. A., 132.Courrier, R., 204.Cowdrey, W. A., 140.Craxford, S. R., 13, 14.Croland, R., 261.Crosbie, G. W., 132.Cross, R. P., 292.Cruess, W. V., 231.Cullumbine, H., 273.Cunningham, B. B., 59.Cunningham, E., 242.Dadieu, A., 135.Dainton, F. S., 68.Daker, W. D., 221.Daly, J. F., 270.Damiens, A., 87.Damkohler, G., 65.Dane, E., 178.Daniel, L. J., 246.Darbyshire, J. A., 280.Darral, R. A., 117.Dasler, W., 176.Dastur, N. N., 290, 291.Davey, W. P., 376, 280.Davidson, N. R., 55.navies, D., 99.lhvies, 0. L., 265, 270,273.Davis, G., 298.Davis, R. E., 37.Davis, S. B., 131.Dawes, E.A., 258.Dawsey, L. H., 66.Dawson, J., 258.Dean, H. K., 297.Deb, S., 277.De Bethune, ,4. J., 24.Deborin, G., 26.De Gray, R. G., 295.De La Mare, P. B. D., 41.De Lange, J. J., 279.Delaunay, A., 262.Delbruick, M., 262.Demerec, M., 259, 262, 263.De Moise, A. W., 295.Dempsey, E. W., 250.De Navarre, M. G., 299.Derjugin, W. von, 255.De Robertis, E., 251, 253.Desai, C. M., 295.Deshapande, S. S., 15G.Devaux, J., 286.Dewar, M. J. S., 53.Dick, J. A., 99.Dieter, W. E., 279.Dijk, J. van, 129.Discherl, W., 175. 180.Dittman, A. L., 116.Dixon, M., 228.Djerassi, C., 177. 178, 186.127.Dobriner, R., 190.Doehlemann, E., 71.Doering, W. E., 131.noisy, E. A., 190, 191, 192.Dolin, P., 6, 9, 20.Dollear, F. G., 294.Donahue, W. T., 298.Dore, W.H., 217, 220.Doudoroff, M., 217, 220.Doyle, A. M., 237.Drake, N. L., 138.Draves, C. Z., 297.Drouineau, G., 233, 280.Dubinina, V. N., 276.Dubnoff, J. W., 259.DuBois, A. S., 300.Duchesne, J., 43.Dufrenoy, J., 273.Dumont, L., 146.Duncan, A. B. I?., 44, 48.Dunitz, J. D., 36,Dunning, N. J., 277.Dunstan, S., 223.Dupont, R., 160.Durkan, T. M., 282.Dushman, S., 78.Dutta, C. P., 153.Dutton, H. J., 296.Dwyer, R. J., 66.Dyer, B., 292.Earle, F. R., 295.Eckey, E. W., 291.Eckman, D. P., 283.Edgerton, R. O., 132.Edse, R., 65.Edwards, 0. S., 284.Egerton, (Sir) A., 62.Ehmann, L., 185, 202.Ehrenfeld, R. L., 116.Eigenberger, E., 293.Elder, L. W., 291.Elliker, P. R., 301.Elliott, M. A., 29.Ellis, B. A., 289.Elmore, W., 11 1.Elsey, H.M., 99.Eltenton, G. C., 63.Elvehjem, C. A., 227, 243,Emeldus, H. J., 87.Kmmens, C. W., 272.Engstrom, A., 286, 287.Ephrussi, B., 254.Epprecht, W., 277.Epstein, A. K., 298.Epstein, S., 298.Epton, S. R., 301.Erchak, M., 284.Erdey-Gruz, T., 12, 77.Erkama, J., 231.Ershler, B., 6, 9, 20, 26.Nssin, O., 17.Etzler, D. H., 277.Euler, H. von, 74, 227, 233,EIIW, .J. 173, 183.256IXDEX OF AUTHORS’ NAMES. 305Ihttiis, .Id. K., 160.Evans, M. G., 67.Xvans, R. D., 248.Evans, T. H., 221.Evans, U. R., 50.Eversole, W. G., 14.Eyler, R. W., 286.Kyring, H., 18, 19.Pairbairn, H. W., 280.Jl’ajkos, J., 165.Walk, G., 7.F’ankuchen, I., 124, 284.Fano, U., 262.Faraday Society, 5.PBher, F., 76.Peher, L., 288.Feller, D.D., 248.Ferguson, A. L., 12.Ferguson, R. B., 277, 280.Fernholz, E., 175.Perrebee, J. W., 237.Beuge, R. O., 297.Fieller, E. C., 270, 272.Vieser, L. F., 109, 127, 190,Findley, T. W., 289.Finger, G. C., 107.Fink, H., 227.Finney, D. J., 266, 271, 272,273, 275.E’irmenich, G., 147.Firth, F. G., 278, 283.Fischer, H., 226.Fischer, J., 93.Fischer, W. H., 174.Fisher, A., 242, 243, 246.Fisher, G. S., 293.Fisher, R. A., 265.Fishgold, H., 68.Bitelson, J., 290.Fittig, A., 137.Fitzgerald, G., 237.Pitzgerald, P. E., 273.Flanagan, J. V., 103.Flanagan, T., 300.Fletcher, H. G., 279.Flett, L. H., 297.Fluegge, S., 50, 51Eogel, Y. M., 286.Foley, F. C., 280.Folkers, K., 239, 241, 246.T’onteyne, K., 77, 78.Poose, R.31., 277.Forbes, G. S., 68.Forbes, W. C., 2138.Forrest, J., 125.Foster, J. W., 246.Foster, L. S., 57.Foust, C. E., 241.Fouts, E. L., 298.Fowler, R. D., 87, 90, 96.Foy, (Mrs.) RI., 142.Fraenkel, G., 255.France, H., 125.Franck, J., 69.215.Frank-Kamenetsky, D., 31.Franke, W., 290.Franklin, A. L., 251.Frantz, A. M., 237.Frazier, C., 288.Freeman, A. F., 294.Freeman, T. R., 298.Frehden, O., 291.Freire, O., 287.French, C. S., 233.Freudenberg, K., 224.Frevel. L. K., 275, 276, 378.Frey, H., 176, 184, 186.Friedberg. -4. L.. 281.Friedman, H., 283.Fries, K., 124, 131.Friess, (Miss) E., 164.Fromherz, H., 71, 72, 7s.Froning,.J. F., 87.Frost, B., 137.l-c’rumkin, A., 6, 7, 8, 9, 11,12, 13, 14, 15, 16, 17,18, 19, 20, 21, 24, 25, 26,27, 28.E’ruton, J.S., 260.Fuehs, H. G., 187.Fuchs, W., 139, 140.Furst, A., 153, 154, 163,164, 165, 166, 173.Fukuhara, N., 88, 89, 97.Fukushima, D. K., 173.Fuld, M., 226.Fuller, M. L., 279.FUOSS, R. M., 29.Furchgott, R. F., 190.Gaddum, J. H., 270.Gale, E. F., 240, 243.Gallagher, T. I?., 184.Galston, A. W., 233.Gangl, J., 290.Garrod, A. E., 254.Gassmann, A., 15 I .Gates, M. G., 109.Gatty, O., 13.Gauthier, B., 188.Gavin, G., 238.Gaydon, A. G., 44.Gaylor, RI. L. V., 277.Geffner, J., 273.Geib, K. H., 61.Geissman, T. A., 14 1.Ghiorso, A., 59.Giacomello, G., 174.Giannone, A,, 279.Giese, M., 94.Gilcreas, F. W., 298.Gilder, H., 226.Giles, C.H., 273.Gillam, A. E., 147, 155, 160.Gillespie, R. J., 75.Gilman, A., 260.Gilman, H., 107, 135.Gilmont, R., 291.Ginsburg, N., 40.Girard, A., 193.Glassner, A., 19.Glasstone, S., 6, 18, 19, 29.Glendenin, L. E., 57.Glicher, S. L., 299.Glick, D., 254.Goddard, D. R., 230, 231.Goddard, R., 75.Gold, V., 5.Qoldberg, M. W., 178, 189.Goldfinger, P., 68, 70, 80.Goldman, A., 137.Goldschmidt, B. L., 67.Goldschmidt, V. M., GO.Goldschmiedt, G., 132.Goldsmith, E. D., 252.Goldstein, H. B., 301.Goldwasser, S., 120.Golovchiner, Y., 2135.Goncalves, I. If., 261.Goodman, D., 275.Goodman, W. B., 280.Goodway, N. F., 157.Goodwin, R. H., 230.Gorbach, G., 296.Gordon, A. S., 252.Gordon, ill., 252.Gordon, It.K., 283.Gordon, W. E., 7.3.Gordy, W., 46, 135.Gorodetskaya, A., 12, 17.GOSS, H., 244.Goubeau, J., 79.Goucharov, V. V., 284.Gouny, P., 233.Gouy, G., 14.Goyan, F. M., 273.Graebe, C., 132.Graf von Schweinitz, H. D.,Graham, J., 76.Graham, W., 133.Grahame, D. C., 6, 13, 14,Granacher, C., 297.Granick, S., 226, 233.Grant, G. A., 292.Gray, C. H., 259.Gray, P. P., 227.Gray, W. M., 280.Grebinskij, S. 0.. 930.Green, A. M., 298.(ireen, D. E., 242, 288.(frew. K. E., 11, 23, 30.Gridgeman, N. T., 266, 270.Griesbach, W. E., 247.Griffith, R. O., 79.Gross, S. T., 277, 282, 286.Grosse, A. V., 87,95,96,104.Gruntfest, I. J., 297.Guertler, W., 283.Guichard, M., 51.Guinier, A., 278, 286.Guirard, B. M., 238, 345.Gunness, M., 242.Gunsalus, I.C., 240, 241,242, 243, 244, 245, 268.70, 230.16, 18306 INDEX OF AUTHORS’ NAMES.Gunther, D. H., 298.Gunther, G., 227.Gupta, P., 188.Gutfreund, H., 225.Gutmann, F., 7, 10.Gutowsky, H. S., 55.Gutsche, C. D., 182.Gyorffy, B., 231.Haagea-Smit, A. J., 167,255, 257.Haagman, P. W., 128.Haas, E., 234.Haber, F., 61, 63, 65, 67,Haberlmd, G., 214.Hadley, E. H., 88.Haeckl, F. W., 110.Hager, G. P., 173Hager, 0. B., 297, 300.Hahn, O., 59.Haissinsky, M., 29.Halberstadt, E. S., 74.Halbrook, N. J., 289.Hale, F., 242.Hall, M. B., 41.Halsall, T. G., 223, 224.Halverstadt, I. F., 247.Hambly, E. J., 77.Hamence, J., 292.Hamilton, T. S., 245.Hammett, L. P., 142.Hamos, L. von, 285.Hanawalt, J.D., 276.Hand, D. B., 229.Handschumaker, E., 296,Hanes, C. S., 224.Hanford, W. E., 115.Hantzsch, A., 74, 75, 134.Hanusch, F., 180.Happold, F. C., 258.Harcourt, G. A., 276.Harington, C. R., 250.Hariton, L. B., 173.Harper, S. H., 149, 265.Harper, W. J., 301.Harris, B. R., 298.Harris, J. C., 298, 299, 300.Harris, 8. A., 239, 241, 245.Harris, T. H., 300.Harris, W. E., 70.Hart, B. F., 237.Hart, R. T., 138.Harteck, P., 61, 69.Hartley, G. S., 136, 300.Hartree, E. F., 228.Harvey, B. G., 59.Harwood, H. J., 300.Haslewood, G. A. D., 190.Ham, H. B., 99, 111, 114.Hassid, W. Z., 217, 220,221, 222, 223, 225.Hauptmann, H., 189.Hausch, W. R., 113.Hawkins, G. I?., 107.69, 70.297.Hawkins, W. L., 221.Haworth, R.D., 137, 192,Haworth, W. N., 222, 223,Hayano, M., 259.Heal, H. G., 59, 71.Heath, R. L., 223.Heckert, L. C., 135.HedBn, G. G., 260.Heer, J., 177, 179, 191,192, 194, 196, 198, 202,206.Hegner, P., 185.Hehre, E. J., 221.Heide, J. D., 269.Heidelberger, M., 120.Heilbron, (Sir) I. M., 149,Heilbronner, E., 165, 166,Heinrich, E. W., 279.Heinzelman, D. C., 292,Hellerbach, J., 154.Hellriegel, W., 160.Hellstroem, H., 227.Helrich, K., 290.Henbest, H. B., 174.Henne, A. L., 95, 100, 103,105, 106, 109, 110, 111,112, 113, 114, 115, 116,117, 119.236.226.171.169.294.Henry, D. C., 14.Herman, D. F., 97, 99.Herrlin, P. A., 284.Herschberg, E. B., 215.Herzfeld, K. F., 41.Hess, K., 223.Hestrin, S., 221.Heuser, G.F., 245.Heusler, F., 107.Heusser, H., 182, 188, 189.Hewett, C. L., 131, 132,Hey, G. B., 274.Heyl, D., 239, 241.Heyrovsky, J., 5, 10.Hibbert, H., 221.Hickling, A., 9, 11, 12, 21,26, 28, 29.Hicks, D., 278.Higgins, G. M., 237.Hilbert, G. E., 224.Hildebrand, J. H., 87.Hildebrandt, F., 177, 182.Hilditch, T. P., 293, 294.Hill, B. R., 190.Hill, J. A., 297.Hill, R., 230, 231, 232, 233.Hill, S., 29.Hill, U. T., 293.Hills-Loftus, G., 291.Hinshelwood, C. N., 50, 61,Hinfermaier, A,, 301.137.65, 71, 79, 140, 262.Hippchen, H., 104.Hirota, K., 20.Hirst, E. L., 222, 223, 224,Hirst, H., 278, 284.Hitchen, O., 292.Hixson, A. W., 31.Hocart, R., 277.Hodge, H. C., 277, 279.Hodgson, H. H., 134, 136.Hodnett, E. M., 99.Hoehn, W.M., 185.Honigschmid, O., 51,Hoss, O., 178.Hofer, L. J. E., 277, 279.Hoff, H. E., 252.Hoffman, H. D., 288.Hofmann, W., 283.Hogg, J. A,, 211.Hogness, T. R., 229.Hohlweg, W., 191.Holdsworth, R. S., 44.Holland, V. B., 298.Hollander, V. P., 184.Hollenberg, I., 297.Holman, R. T., 288.Holmberg, J., 294.Holmes, R. J., 281.Holt, A. S., 233.Holt, E. K., 78.Hoover, S. R., 238.Hopff, H., 124.Hopkins, B. S., 56.Hopkins, R. H., 224, 238.Horeau, A., 204.Horiuti, J., 18, 19, 20, 21.Horn, F. H., 277.Horowitz, N. H., 258, 260.Horton, W. J., 183.Hosking, J. S., 280.Hotelling, H., 267.Houlahan, M. B., 258.Houtman, J. P. W., 279.Howard, A. J., 280.Howard, P. L., 31.Howell, S. F., 230.Hoyt, L. F., 300.Huang-Minlon, 143.Huber, K., 156.Hudson, C.S., 220, 279.Huckel, W., 144.Hiiter, F., 162, 163, 164.Huff, J. W., 238, 245, 257.Hughes, A. M., 248, 252.Hughes, E. B., 289.Hughes, E. D., 74, 76.Hughes, R. C., 298.Hugony, E., 283.Hume-Rothery, W., 281,Humiston, B., 87.Humphreys, S., 238.Hundiecker, C., 188.Hungate, M. G., 260.Hunsdiecker, H., 188.Hunt, H., 94.226.283INDEX OF AUTHORS’ NAMES. 307Hunter, C . L., 297.Hunter, G. W., 295.Hunter, J. H., 204, 211.Hurd, J. M., 286.Hurwitz, M. L., 298.Huszak, I., 229.Hutchison, C. A., 62.Hutchison, D. A., 52.Ikusima, M., 19.Ilkovic, D., 18.Imhoff, C. E., 277, 279.Imperial Chemical Indus.tries, Ltd., 277.Inghram, M. G., 51.Ingold, C. K., 74, 75, 95.Ingold, E.H., 95.Inhoffan, H. H., 177, 178,Ipatiev, W., 131.Irwin, C. F., 91.Irwin, D. A., 280.Irwin, J. O., 272.Irwin, W. H., 290.Isenburger, H. R., 281.Isherwood, F. A., 226.Ivanoff, N., 296.Jacobi, R., 184.Jacobs, S. E., 273.Jacobsen, R. P., 183, 184,Jacques, J., 204.J a c q u k , R., 157.Jagitsch, R., 277, 284.Jakovlev, W., 131.Jakus, M. A., 287.James, R. A., 69.James, W. O., 231, 232.Jamieson, G. S., 289.Jamison, (Miss), M. M., 34.Jasperson, H., 286, 292.Jay, A. H., 281.Jeanloz, R., 172.Jefferson, M. E., 292.Jeger, O., 189.Jenesel, N. D., 247.Jephcott, C . M., 380.Jerchel, D., 290.Jirasek, K., 163, 166.Jofa, S., 11, 13, 17, 24, 25.Joff6, V. S., 28.Johnson, B. C., 245.Johnson, M. J . , 259.Johnson, P., 225.Johnson, T. L., 183.Johnson, W.S., 137, 138,153, 165, 182.Johnston, H. L., 52.Jones, ,4. R., 138, 153.Jones, E. R. H., 32, 171,Jones, G., 6.Jones, G. K., 288.Jones, H. H., 300.Jones, J. K. N., 223, 224.191.189.174.Jones, M. J., 261.Jones, P., 288.Jones, R., 292.Jones, R. A., 289.Jones, R. C., 112.Jones, R. G., 107.Jones, R. N., 32, 190.Jones, W. E., 149.Jorma, J., 234.Joslyn, M. A., 227, 231.Joyce, R. M., 115.Joyner, N. T., 291.Judrt, W., 15.Jung, E., 280.Jung, F., 246.Junqueira, L. C., 254.Kabanov, B., 11, 25, 29.Kaimm, S., 277.Kaiser, H. F., 283, 287.Kalckar, H. M., 220.Kaloyereas, S. A., 292.Kamm, O., 190.Kandler, L., 26.Kaplan, N., 220.Karabinos, J. V., 143.Karan, M.L., 231.Karasch, M. S., 142.Karlik, B., 51.Karnovsky, M. L., 289.Karrer, P., 169, 241, 243.Kasha, M., 35, 40.Kass, J. P., 288.Kassatochkin, W., 63.Katoh, N., 279.Katzman, M., 298.Kaufman, H. S., 124.Kaufmann, A., 146.Kaufmann, H. P., 288, 293,Kawai, S., 296.Kaye, W. I., 283.Keating, F. R., 245.Kefely, L. M., 279.Keilin, D., 227, 228, 230,231, 232, 234, 235.Keim, R., 87, 100.Keller, M, C., 293.Kelly, A. J., 298.Kench, T. E., 232.Kennedy, J. W., 57, 58.Kennedy, T. H., 247.Kenney, E. F., 266.Ketchum, D., 289.Ketelaar, J. A. A., 130.Kharasch, M. S., 74, 97.Khunyants, I. L., 118.Kilby, B. A., 148.Kilham, J. K., 67.Kimball, G. E., 19, 20, 24.Kimball, R. H., 94.Kimmelman, L. J., 202.Kimura, K., 285.Kimura, T., 185.Kimura, W., 294.Kindler, K., 143.294.King, A.E.; 290.King, C. V., 31.Kipping, F. B., 148, 156.Kirk, P. L., 59.Kirsteq G., 289.Kir’yalov, N. P., 168.Kishen, K., 268.Kistler, R. E., 295.Klaas, R., 280,Klaui, H., 159, 161.Klein, M., 262.Klevens, H. B., 32, 42, 44.Kling, W., 299.Klingman, W. O., 237.Klinkenberg, L. J., 73.Klug, H. P., 281.Knell, M., 107,Knight, B. H., 289.Knorr, C . A., 26.Knowles, G., 287.Koechlin, B., 188.Koenig, K. O., 13.Koster, H., 148.Kohlrausch, K. W. I?., 136.Kolotyrkin, Y., 27.Kolthoff, I. M., 5, 70.Kolychev, A., 24,Komovskii, G. I?., 285.Komppa, G., 144, 152.Koolhaas, D., 153.Kooyman, E. C., 130.Kopecki, E. B., 283.Korb, A., 2&0.Korman, J., 204.Kornfeld, G., 66.Kornreicb, E, 298.Korpacsy, S., 288.Kossiakoff, A., 127.Kotov, W., 03.Kovalev, G.A., 276.Koval’skii, A. E., 284.Kovner, M., 113.Krajnc, B., 223.Kraybill, H. R., 294.Krehl, W. A., 256.Kreke, C. W., 229.Kretchmer, N., 288.Kritzmann, M. G., 243.Krjukova, T., 14.Krog, A., 300.Kromrey, G., 12.Krossing, G., 233.Kriiger, F., 10.Krueger, J., 185.Kriiger, I?., 146.Bruyt, H. R., 14.Ksenofontov, A., 17.Kubo, H., 234.Kuchinski, E., 25.Kuhn, M., 145.Krthn, R., 236.Kurbatov, J. D., 57.Kushner, S., 177, 199.KUSS~FOW, G. W., 159.Kwok, D., 143.Klyne, w., 182, 190308 INDEX OF AUTHORS' NAMES.Kyaine, L., 293.Lachmann, A., 142.La Forge, F. B., 220.Laidler, K. J., 18, 19.Laine, T., 234.Lampen, J.O., 261.fianda*u, R., 87.Landis, Q., 224.Lang, R., 77.Lange, E., 7.Langseth, A., 123.Langston, J. W., 104.Laning, S. H., 277. .Lapin, V. V., 277, 279.Lapina, R. A., 214.Lardon, A., 172.Larson, R. A., 248.L a t h e r , W. M., 5, 87.Lauritsen, M., 238.Lawrence, C. A., 131.Lawrence, W. J. C., 264.Lawson, A., 254.Lawson, E. J., 190.Lawson, J. C., 287.Lawson, M., 44.Lea, C. H., 290, 291, 293.Le Barron, I. M., 28.Lebeau, P., 87, 101.Leblond, C. P., 252.Leckie, A. H., 73.Lederberg, J. S., 259, 260.Le FBvre, M. L., 279.Le Fbvre, R. J. W., 135.Legran, A., 20, 28.Lehmann, G., 65.L e h m m , H., 232.Lehoult, Y., 262.Leicester, H. M., 112.Leidy, G., 262.Lel'chuk, S. L., 279.Leloir, L. F.. 242.Lemay, L., 167.Lepkovsky, S., 238, 257.Lerner, S.R., 251.Lesslie, (Miss) M. S., 34.Levenson, H. S., 291.Levi, I., 221.Levich, B., 14, 31.Levina, S., 20, 24, 28, 30.Levine, A. A., 127.Levine, P., 131.Levitas, N., 267.Levy, P., 288.Ilewin, L., 191.Tdowin, S., 63.I>ewis, C. J . , 99.Lewis, G. N., 34, 36, 40.Ley, H., 78.Libby, R. L., 259.Lichstein, H. C., 242.Liddiard, P. D., 298.Lieberman, S., 173, 190.Liebhefsky, H. A., 80, 286.Liggett, W. B., 102.'IA~vY, H., 184.Lili, K.-H., 71.Lindegren, C. C., 264, 261Linder, T. van der, 93.Lindgren, V. V., 102.Lindstrom, B., 287.Lingane, J. J., 5.Lingfelter, E. C., 96.Linkola, H., 234.Linn, C. B., 96, 104.Linsenmeyer, K. M., 301.Linsk, J., 185.Linstead, R. P., 131, 136Linteris, L., 297.Lippincott, E.It., 123.Lips, A., 291.Lips, H. J., 292.Lipson, H., 281, 283, 284.Little, H. N., 234.Litvan, F., 191.Llopis, J., 24, 26.Lobzowaki, J., 283.Lock, G., 132, 143.Locke, E. G., 114.Locquin, It., 184.Loeb, H. G., 288.Logemann, W., 180.Long, L. H., 47.Longuet-Higgins, H. C., 5354, 55, 127.Lonsdale, (Mrs.) K., 281.Lord, J. W., 292.Lord, K. A., 265.Lord, R. C., 123.Lothrop, W. C., 127.Lovern, J. A., 293.Low, E. M., 175.Lucas, E. H., 231.Luddy, F. E., 295.Ludwig, C. A., 235.Ludwig, W., 250.Luoht, C. M., 108.Luft, F., 93.Lui, C. K., 280.Lukovtsev, P., 20, 28.Lundborg, K., 284.Lunge, G., 69.Luria, S. E., 254, 262.;u Valle, J. E., 63.,woff, A., 261.,ykken, L., 299.Jyman, C.IT., 841.,ynas-Gray, J. I., 155.,yne, R. R., 222.h 4 r d l e , B., 237.dcArthur, R. E., 98.dcBain, J. W., 298.dcBee, E. T., 94, 99, 100,101, 102, 103, 109, 111,112, 113, 114, 118.263.153.Lucht, C. M., 286.dcBryde, A., 237.dcCarty, M., 262.dcCasland, G. E., 246.Maccoll, A., 123.MacColl, H. G., 269.McCollum, E. V., 237,McCombie, H., 99.McConnell, W. T., 237.McCord, A. T., 281.MacCorquodale, D. W., 190,RIcCready, R., 223, 226.McCutcheon, J. W., 288.Macdonald, D. C., 57.McElroy, L. W., 244.BIcElvain, S. M., 104.MacEwan, D. M. C., 283.Macey, A., 223.McFarlane, S. B., jun., 301.McFarlane, W. D., 291.McGinnis, N. A., 131.McGinty, D. A., 247.McGrath, J., 230.McHenry, E. W., 238.Machlis, L., 230,McIlwain, A.J., 237.RlcIntosh, A. O., 27s.McIntyre, J. E., 291, 296.McKay, H. A., 13.McKee, R. H., 142.3IcKelvey, J. B., 114.McKenna, F. E., 95.Blackenzie, C. G., 247.Mackenzie, J. B., 247.Mackenzie, K. R., 51.McKeown, A., 79.McKinley, J. B., 277.McKinney, R. S., 289, 294.McLeish, N., 127.McMillan, E. M., 57.McMurry, H. L., 44.McQueen, J. H., 62.McQuillen, T., 287.Maddigan, S. E., 286.Maddison, L., 293.Maddock, A. G., 59.Magyar, G., 167.Mahadevan, C., 280.Maidanowskaja, L., 27.Mailhder, E., 73.Maitland, P., 125.Major, F., 265.Major, R., 291.Majumdar, S. K., 281.Malangeau, P., 296.Mallinder, R., 293.Ualmgren, B., 260.Manchot, W., 65, 69.\landel, J., 268.\I-, E. H., 298.\lam, T., 230.Marcali, K., 289.Karcuse, S., 269.Marinsky, J.A., 57.Ilark, H., 124.Uarker, R. E., 185, 190,Markley, K. S., 396.Sarkov, B., 17.191.194li?bE% OF AtJTEORS’ NAMES. 309Marks, H. l’., 272.Xarkus, R., 152.Marlow, A. M., 155.Marrian, G. F., 185, 190.Marron, T. V., 299.Marsden, E., 136.Narsden, S. S., 279.Marsh, J. K., 56.Marsh, P. B., 231.Marshall, C. G., 300.Martin, D. E., 282.Martin, D. W., 237.Martin, E. L., 142.Martin, G. J., 247.Marvel, C. S., 132.Mashentoev, A. I., 98, 107.Mason, H. L., 186.Masson, I., 80.Matsen, F. A., 40, 41.Xat’tauch, J., 50, 51.Matthews, F. W., 278, 280,MattiI, K. F., 291, 292.Maxfield, J. R., 237.Rfayer, E. W., 159.Meara, M. L., 294.Medwedowsky, W., 14.Me,gaw, H. D., 277.Nehlenbacher, V. C., 291,Mehmel, M., 276.Meier, K., 182.Melson, J.A. van, 159.Menke, W., 233.Menschik, W., 78.Rlentzer, C., 214.Menzel, W., 101.Merian, E., 163.Merling, G., 147.Merritt, H. H., 237.Merry, J., 231.Merten, L., 284.Rfeslans, 31. N., 87.Metcalfe, A. G., 284.Metzendorf, W., 143.Meunier, P., 175, 187.Jleyer, K., 190.Xeyer, K. H., 223, 225.Meyers, L. D., 295.Meystre, C., 175, 184, 185,Rlichaelis, K. 0. A., 153.Michaud, R., 280.Michel-LBvy, A., 277.AGchel-Levy, M., 277.Michell, J. H., 281.iMidgley, T., 109, 113.Miemher, K., 170, 174,175, 177, 179, 180, 184,185, 186, 188, 191, 192,193, 194, 196, 198, 199,201, 202, 203, 204, 206,215.281.297.186.Mikander, L., 162.Mikheev, V. I., 276.Mikusch, J.D. von, 288,293.Alilazzo, G., 38.Millen# D. J., 75.Miller, J. F., 94.Miller, W7. H., 247.Miller, W, Ldg 10, 88; 91.Blilligan, W. O., 284,Mills, W. H., 127.Milner, R. T., 294, 296.JIinkoff, G. J., 63.Minor, F. W., 235.Xirsky, A. E., 227.Mitchell, G. J., 237.Mitchell, H. H., 245.Mitchell, H. K., 256, 257,Mitchell, J., 131.Mitchell, J. A., 269.Mitchell, J. H., 294.Mituya, A., 23.Moller, E. F., 246.Moeller, T., 57.Moffet, R. B., 185.Mogensen, F., 279.Moissan, H., 87.Molko, D., 214.Moll, T., 246.Monch, J., 290.Monod, J., 261.Montgomery, E. M., 224.Montoro, V., 283.Moore, D. H., 225.Moran, R. F., 268.Morgan, A. F., 238.Morgan, F., 57.Morgan, L. O., 59.Rforgeli, E., 194.Morse, C. W., 68.Morton, M.E., 251.Morton, R. A,, 294.Moseley, O., 242.Moseley, W. K.; 30 1.Mothes, K., 234.Muckerheide, V. J., 395.Miiller, 0. H., 5.Muller, P., 178, 194.Mciller, P. H., 144, 153.Muers, M. M., 291Mukhcrjee, S. M., 151.Blnller, A., 288.Mulliken, R. S., 32, 33, 35,39, 40, 44, 46, 49.ntummery, W. R., 291.Mllrfitt, Q., 280.Murray, R. L., 99.Jlurti, K. S., 294.hhshett, C. W., 246.Musseron, M., 157.Mutzenbecher, P. von, 330.Myrbiick, K., 224.Mysels, K. J., 279.Nagelschmidt, G., 278, 280Nagy, R., 280.Nahm, H., 175.Nakamura, N., 285.95, 98, 116.268.KLiray-Szeib6, 1.; ?SO.Narayanier, S., 296.Naves, Y. It., 148, 156, 156,158; 162, 168, 169.Nettle, S. M., 16.Nbetlhatn, D. M:, 819.N6her; R:, 175, 186, lsYi,Neisch, A, C,, 2133;Nelson, J.Bd9 280’:Nelson, R. E., 111,Nernst, W., 30.Nesty, G. A., 132.Neuberger, A., 264.Neugebauer, J., 280.Neuman, E. W., 62.Neumann, W., 189.Neville, H. A., 288.Newbery, E., 11.Newburgor, S. H., 296, 397.Newkirk, A. E., 104.Newman, M. S., 116, 117,Newton, It. G., 269.Xey, F. P., 52.Nicholls, M. J., 222.Nichols, M. L., 68.Nickels, J. E., 277.Nicol, A., 277.Nigrell, R. F., 252.Nishida, K., 152.Nixon, I. G., 127.Nocito, V., 242.Nordheim, G., 39.Norris, F. A., 288, 296.Norris, F. W., 238.Norris, L. C., 245.Norrish, R. G. W., 47.Norton, a., 64.Norymberski, J ., 189.Novak, J., 279.Novick, A., 77.Novoselski, I. S., 30.Nowinski, W. W., 253.Noyes, A. A., 79.Noyes, R.M., 277.Nozaki, K., 290.Nuffield, E. W., 277.Nye, J. F., 266, 257.Nygren, C. A., 273.Nyman, G. A., 152.Oakberg, E., 362.Oakwood, T. S., 190.Oberst, I?. W., 277.O’Rrien, J. E., 298.O’Brien, J. R. P., 237.O’Connor, I%. T., 292, 294.Oda, S., 280.O’Daniel, L., 292.Oertel, A. C., 273.Ortenblad, B., 224.Ogston, A. G., 225.Ohlinger, H., 124.Okami, K., 167.Okamoto, G., 20, 21.215:138310 JNDlaX OF AUTHOBS' NAMES.O'Ksne, D. E., 243, 244.Oldenberg, O., 65.Oliver, J., 301.Olsen, S., 293.Onslow, M. W., 231.Oostermrtnn, J., 14.Opemhaw, H. T., 236.Oppenheimer, C., 69.Orchard, W. M., 142.Orchin, M., 124, 125.Orth, H., 226.Orton, K. J. P., 134.Osborne, S. G., 87.Oshry, H.J., 282, 283.Ott, W. H., 246.Overbeek, J.T. G., 14.Owen, E. A., 281, 284.Owen, L. N., 144.Owen, M. D., 158.Pabst, A., 277.Pack, F. C., 294.Yaic, M., 286.Palmer, K. J., 36.Palmer, W. G., 126.Paneth, F. A., 50.Papazian, G., 158.Parisot, A., 301.Park, G. S., 67.Park, J. D., 109.Parks, T. D., 283.Parrish, W., 278.Parsons, L. B., 292.Pascher, F., 157.Paschkis, K. E., 251.Pataki, J., 182, 187.Patel, A. H., 295.Paterson, J. Y. F., 190.Patry, M., 280.Patton, T. C., 290.Pauling, L., 34, 36, 54, 88Peacock, M. A., 277, 278.Peacock, W., 248.Pearl, I. A., 142.Pearlman, W. H., 180, 181Pearlson, W. H., 99, 114.Pearson, E. S., 270.Pearson, J. D., 11, 26.Pearson, P. B., 238, 257.Pearson, T. G., 65.Peat, S., 221, 22'2, 223.Pecherskaya, A. G., 29.Yeckham, R.H., 283.Pederson, C. J., 299.Peebles, W. C,, 277, 279.Peeling, E. K . A., 75.Peevers, K. IV., 174.Peiser, H. S., 277.Pelikan, K. A., 293.Penfold, A. R., 165.Pennington, H. J., 238.Perdoli, W. G., 279.Yerisutti, G., 229.Perlmun, I., 57, 58.96, 108, 123, 126.185.Perlstrom, G., 284.Perlzweig, W. A., 238, 24EPerrier, C., 61.Perrottet, E., 152, 156, 15€Petch, H. J., 281.Peters, E. D., 291, 299.Peters, J. B., 252.Petorsen, F. A., 381.Petersen, J. W., 182.Peyronel, G., 277.Pfeiffer, M., 147, 148.Phaff, H. J., 227.Philippot, E., 231.Philips, F. S., ?60.Phillips, H. W. L., 283.Philpot, J. StL., 13, 16.Picha, G. M., 184, 189.Pickett, A. N., 237.Pierce, 0. R., 94, 100, 118,Pieser, (Miss) E., 118.Pietz, J., 234.Piggott, H.A., 99.Pillarsky, R., 107.Pineda, M. G., 288.Pink, R. C., 124.Pinkney, P. S., 132.Pitt-Rivers, R. V., 250.Pitzer, K. S., 49, 63, 55.Platt, J. R., 32, 42, 44.Plattner, P. A., 144, 151152, 163, 154, 156, 157159, 161, 163, 164, 165166, 167, 169, 173, 182187, 189.257.169.Platz, B. R., 238.Pleskov, V., 30.Ploszek, H., 283.Plueddeman, E. P., 106.Pohle, W. D., 296, 297.Polanyi, M., 18.Poliakoff, M. Z . , 298.Pool, M. F., 291.Pool, M. L., 57.Poole, H. G., 75.Popp, w. c., 237.Porret, D., 67.Porter, C. C., 246.Powell, R. D., 233.Prahl, W., 139.Prater, A. N., 291.Pratt, R., 213.Prelog, V., 173, 176, 189.Preobrajenski, N. *4., 214.Preston, J. M., 301.Preston, R. W. G., 137.Prey, V., 193.Price, C.C., 74, 119.Price, J. R., 254.Price, W. C., 32, 34, 36, 37,38, 39, 48.?rice, W. H., 220.'rier, F., 164.'riest, G. W., 288.'riest, H. F., 87.Prili, E. A., 292.Prins, D. A., 172.Pritchard, C. F., 279.Prober, M., 116.Proskurnin, M., 6, 7, 9, 14,Pullman, A., 41.Purdue, G. R., 297.Purves, H. D., 247.Puschol, F., 299.Pyzhev, V., 21.Quackenbush, F. W., 285.Quill, L. L., 57, 117.Rabidean, G. S., 233.Rabinoviteh, E., 72.Rabinowitch, I. E., 233.Rabinowitz, J. B., 238, 243,Radcliffe, C. B., 152, 156.Rudlove, S. B., 288.Hukitin, L., 131.Ralston, A. We, 300.Kamage, G. It., 157.Ramler, E. O., 117.Randles, J. E. B., 6, 9.Rannefeld, A. N., 239.Rao, B. S., 160.Rapson, W. S., 289, 298.Raschig, F., 68, 139.Rasmussen, R.S., 37.Rassmann, G., 283.Ilath, E., 133.Ratner, S., 269.Rault, C., 263.Rawson, R. W., 248.Raynor, G. V., 283.Reck, It. A., 300.Reddelien, G., 127.Rcdfern, S., 224.Redlich, O., 78.Reed, R. I., 74.Keggel, L., 124, 125.Rehbinder, P., 13.Reich, H., 170.Reichhardt, H., 65.Heichstain, T., 170, 182,Reid, E., 219.Reid, J. C., 116.tteinhardt, W. O., 251.Reiser, R., 296.Ltenoll, M. W., 105, 109.ttoppe, J. W., 120.Resuggan, J. C'. L., 297.Kovis, C., 290.Rhoads, C. P., 190.Rice, F. O . , 66.Rice, 0. K., 94.Richter, C. P., 247.%ideal, E. K., 11.tiegel, B., 173.tieke, C. A., 32, 39.tieke, F. F., 65.17.244.Rae, c. s., 78.185, 187, 188, 189INDEX OF AUTHORS’ NAMES. 31 1Kiemaii, W., 289, 290.Riemenschneider, R .W.291, 294, 295.Rigamonti, R., 281.Riley, J. P., 294,Rimington, C., 232, 254.Rinck, E., 50.Rinn, H. W., 276, 278.Ripert, J., 297.Risse, F., 159.Rittenberg, D., 232.Rius, A., 24.RiviBre, A,, 280.Rivoir, L., 282, 283.Robert, H., 189.Roberts, J. K., 21.Robertshaw, GI. F., 299.Robertson, J. E., 237.Robertson, J. M., 36, 126.Robertson, P. W., 41.ttobertson, W. W., 40.Robinson, (Mrs.) A. M ., 132,Robinson, G. M., 264.Robinson, J., 257.Robinson, (Sir) R., 170, 171,Roblin, R. O., 247.Roboz, E., 257.Robson, J. M., 260.Roe, A., 107.Roebuck, J. R., 80.Roepke, R. R., 259, 261.Rothlitsberger, A., 144.Rogers, A. O., 111.Rogers, T. H., 285.Rolla, M., 280.Romanoff, L., 189.Romburgh, P.van, 153,Rometsch, R., 201.Roniger, H., 163, 164.Ronnebeck, H. R., 283.Rooksby, H. P., 276, 279,Roothaan, C. C. J., 35.Roschen, H. L., 290.Rose, W. G., 289.Rosebrugh, T. R., 10.Rosen, F., 238, 257.Rosen, R., 87.Rosenkrantz, H., 190.Rosenthal, K., 9.Roudier, A., 224.Rouve, A,, 149.Rovira, S., 289.Rowlands, V. W., 284.Rowley, (Mi=) E. L., 59.Roy, W. R., 288.Royals, E. E., 150.Ruchhoft, C. C., 298.Ruckstuhl, H., 169.Ruff, O., 87, 98, 94, 100,Ruh, R. P., 115.Ruigh, W. H., 175.Rumpel, W., 290.138.177, 191, 198, 254.280, 281,282.101, 114.Rundle, H. E., 53, 56.Runnicles, D. F., 300.Rupe, H., 151.Rusoff, I. I., 44.Rust, F. E., 111.Ruzicka, L., 123, 144, 146,147, 148, 151, 153, 156,157, 159, 167, 183, 187,189, 194.Ryan, F.J., 261.Rydon, H. N., 156.Sabetay, S., 168.Sachsse, H., 63.Saenger, H. H., 68.St. Pfau, A., 144, 161, 163,St. Thugutt, J., 278.Salley, D. I., 62.Salmi, E., 145.Salt, F. W., 12, 21, 28.Sandrin, R., 163.Sandulesco, Q., 193,Sarinsky, V., 24.Sarma, P. S., 243, 256.Sattler, L., 220.Saunders, B. C., 99.Savage, J., 135.Sawin, P. B., 264.Sawyer, R. A., 32.Scales, F. M., 300.Scanlan, J. T., 289.Scarisbrick, R., 232, 233.Schachner, H., 261.Schhfer, K., 282.Schaeffer, G. W., 42, 56.Schappi, G., 145, 148.Schenck, P. W., 62, 64.Schemer, W., 147.Schiemann, G., 107.Schifferlei, J., 299.Schilling, K., 131.Schintz, A., 157.Schinz, H., 144, 145, 146,Schlenk, F., 220, 242, 243.Schlesinger, H.I., 55, 114.Schlicting, O., 184.Schluchterer, E., 221.Schmid, H., 164.Schmidlin, J., 185.Schmidt, J., 163, 178.Schmidt-Nielson, K,., 288.Schneider, H., 238.Schneider, P. H., 28.Schneider, W. P., 137.Schoenbach, E. B., 262.Scholz, C. It., 186.Schomaker, V., 48.Schotland, C. E., 237.Schramm, G., 214.Schrenk, H. H., 282, 288.Schtschukina, N. N., 214.Schiibh, W., 107.Schulman, J. H., 297.Schulz, L., 160.169.147, 148, 149, 153.Schulze, 0. W., 134.Schwartz, H. M., 295.Schwartzmm, a., 246.Schweigert, B. S., 238, 267.Schwenk, E., 174, 177, 181,Schwitzer, C., 26.Scott, M. L., 245.Scott, w. o., 79.Scott-Moncrieff, R., 254.Scudi, J. V., 241.Seaborg, G. T., 67, 58, 69,Secrist, J. H., 108.Seeler, A.O., 246.Segr6, F., 51, 57, 58.Seidel, C. F., 144, 146, 147,Semmler, F. W., 159.Sen, A. K.$ 292.Serini, A., 180.Shafer, W. M., 286.Shakespeare, N., 246.Shearer, J., 280,Sheldrick, G., 137.Shelton, R. S., 300.Shemin, D., 232.Sheppard, H., 136.Sherk, K. W., 143, 195.Sherman, J., 123.Sherwood, H. F., 286.Shiraeff, D. A., 299.Shive, W., 200.Shoppee, C. W., 171, 172,Shorr, E., 190.Short, W. F., 124, 152, 156.Shrivastava, R. K., 294.Shtifman, L., 24.Shupes, I., 296.Sice, J., 189.Sidgwiok, N. V., 127.Sidhu, S. 8., 277, 279.Siebenschein, R., 78.Siegel, J. M., 51.Siggia, S., 291.Silber, R. H., 246.Silberfarb, M., 30.Silbeman, H., 188.Silberman-Martyncewa, S.,Silbiger, G., 54.Sillh, L.G., 284.Silverman, L., 280, 282.Siiaanov, Y. P., 277, 279.Simmonds, S., 260.Simon, A,, 76, 78.Simon, H. L., 146.Simonenko, D. L., 56.Simons, J. H., 89, 97, 98,99, 114, 117.Simonsen, J. L., 144, 150,156, 167.Sinoda, 8., 285.Sisler, E. B., 229.Sisley, J. P., 298.182.60.148.179, 180, 190, 197.188312 JNDEX OF AUTHORS' NAMES.Sjodh, A., 228.Skell, P. S., 288.Skellon, J. H., 290.Sklar, A. L., 40, 41.Slein, M. W., 219.Slender, V. V., 29.Slygin, A., 14, 26.Small, M. H., 259.Smallwood, H. M., 68.Smelt, M. A., 229.Smith, C. S., 275.Smith, D. P., 284.Smith, E. S., 126.Smith, F., 89, 93, 94, 116,Smith, F. A., 294.Smith, F. H., 296.Smith, G. H., 279.Smith, H., 281.Smith, H. M., 286.Smith, J. C., 142.Smith, J.D., 235.Smith, J. W., 5, 50.Smith, K. W., 272.Smith, L. I., 120.Smith, R. H., 210, 291.Smith, S. G., 237.Smoluchowski, R., 286.Smyth, H. D., 58.Snell, E. E., 238, 239, 242,243, 244, 245.Snell, F. D., 299.Soffer, M. B., 143, 195.Soffer, M. D., 143, 151, 156,Soldate, A. M., 277.Somers, G. F., 229.Sorm, F., 165.Spannuth, H. T., 295.Speck, R. M., 291.Speiser, P., 182, 189.Spiegel-Adolf, M., 283.Spiegelman, S., 262.Spies, T. D., 237.Spinks, J. W. T., 75.Sponer, H., 32, 39, 40, 41.Spornitz, K. E., 159.Spring, F. S., 143, 171.Springall, H. D., 36, 127.Sproull, W. T., 278.Srb, A. M., 258.Stace, H. C. T., 273.Stacey, M., 221, 222.Stach, K., 143.Stackellberg, M. von. 14.Stafford, J. E., 185.Stahmann, M.A., 260.Stainforth, R. A., 117.Stallcup, M. J., 41.Stanley, M. M., 253.Stansby, M. E., 290.Stauffer, J. F., 259, 260.Stebbins, M. E., 152.Stebbins, R. B., 246.Stecher, O., 55.Steenbock, H., 238, 295.117.195.Stefanoskii, Y. F., $5.St>eigmann, A., 301.Stein, G., 68.Steiner, E. H., 265.Steinhardt, C., 152.Stephenson, O., 135.Stern, O., 14.Sternbach, L., 15 1.Stevens, W., 174.Stevenson, A. C., 157, 199.Stevenson, D. P., 48.Stevenson, J. K., 103.Steward, E. G., 279.Stier, T. J. B., 227.Stiles, W., 232.Stiller, E. T., 246.Stilmar, F. B., 93, 101.Stitt, F., 53.Stix, W., 139.Stobbe, H., 136, 137.Stockmayer, W., 72.Stormer, I., 180.Stokes, J. L., 242, 246.Stoll, M., 147, 149.Stone, I., 227.Stoner, G.C., 294.Stout, H. P., 28, 29, 30.Strait, L. A., 273.Stranski, I. N., 280.Strassman, F., 59.Street, W. R., 289.Stromberg, H., 124.Strong, F. M., 238.Strong, L. C., 263.Struve, W. S., 91, 93, 101.Stubbings, W. V., 301.Stucklen, H., 40.Studer, A., 164, 166.Studer, S., 156.Stuffins, C. B., 290.Stull, D. R., 50.Sturdivant, J. H., 56.Subramaniam, K. S., 160.Sudo, T., 277.Sugden, T. M., 32, 37.Sugg, G. Y., 221.Sugihara, J., 231.Sugiyama, G., 185.Sully, A. H., 284.Sumner, J. B., 229, 230.Sustendal, G. F., 237.Suter, M. St. A., 229.Sutherland, G. B. B. N.,Sutton, L. E., 126.Sutton, R. W., 292.Swanson, M. A., 896.Swarts, F., 95, 96, 99, 103,108, 109, 110, 112, 117,118.136.Sweany, H. C., 280.Swedin, B., 231.Swern, D., 289.Swientoslawski, W., 118.Switzer, G., 281.Sykes, C., 283.Siylvel.iter, N.B., 289.Sylvester, S. F., 298.SZHSZ, G., 37.Szent-Gyorgyi, A., 231.Szpilfogel, S., 173, 189.Tabor, D., 12.Taffel, A., 290.Takvorian, S., 5'7.Tanaka, N., 285.Tanida, S., 280.Tanis, H. E., 286.Tarbell, D. S., 246.Tarrant, P., 92.Tatum, E. L., 255, 256,Taube, H.. 63.Taurog, A., 348.Tavel, C., 148.Taylor, A,, 278, 281, 286.Taylor, D., 36.Taylor, E. S., 240.Taylor, G., 292.Taylor, H. S., 61, 120.Taylor, T. W. J., 126, 130.Taylor, W. I., 162.Teller, E., 32, 39.Temkin, M., 21.Tepley, L. J., 266.Terenin, A., 64.Tesoro, G. C., 298.Teston, R., 95.Thayer, S. A., 190, 191.Theorell, H., 226, 231.Thibaudet, G., 175.Thiel, C.C., 291.Thiessen, P. A., 280.Thomas, S. L. S., 153.Thompson, H., 192.Thompson, R. J., 48.Thompson, R. M., 277, 279.Thompson, R. Y., 92.Thompson, S. W., 296.Thompson, W. R., 272.Thomson, A. F., 120.Thornton, H. G., 235.Thornton, (Miss) N. V.,Thorpe, T. E., 77.Tiedeman, W. G., 298.Tiemann, F., 146.Tillson, E. K., 251.Tinker, J. M., 109.Toland, W. G., 114.Tomlinson, H. M. R., 243.Trabaud, L., 168.Traube, W., 62, 118.Treibs, A., 227.Treibs, W., 156, 160, 161.Tresadern, F. H., 265.Triebold, H. O., 295.Trillat, J. J., 286.Trott, P., 116.Troy, A., 296.Truchen, A., 114.Trzebiatowski, W., 283.258, 259, 260, 261.114INDEX OF’ AUTHORS’ NAMES. 3 1 3‘I’schesehe, R., 189.Tschopp, E., 201.Tschung, W.W., 193.Tucker, S. H., 125.Tiifts, L. E., 94.Tnkey, J. W., 269.Tunnicliff, D. D., 37.Turer, J., 291.Turner, E. E., 34.Turner, G., 152.Turner, R. B., 174.Ubbelohde, A. R., 124.Uhlig, H. H., 28.Umanskii, Y. S., 284.Umbreit, W. W., 340, 241,Unna, K., 246.Uota, H., 152.Urazov, G. G., 279.Urban, F., 14.Urey, H. C., 50, 66.Ussanovitch, M., 74.Vainshtein, E. E., 278.Vanderlaan, J. E., 248,Vanderlaan, W. P., 248,Van der RIeulen, P. A.,I‘ander Werf, C. A., 142.Van Rensburg, N. J., 295.Van Zile, B. S., 298.Vaughan, W. E., 1 I 1.Veen, A. G., van, 153.Velluz, L., 246.Vendrely, R., 262.Venturello, G., 282.Verdier, E. T., 30.Verley, A., 147.Veselovsky, V. I., 14.Vibrans, F. C., 292.Vickerstaff, T., 273.Vieweg, W., 137.Villar, G.E., 60.Villiger, V., 63.Vilter, R. W., 237.Vincent, J. R., 120.Vine, H., 135.Virtanen, A. I., 234, 2%.Viscontini, M., 241, 243.Vliet, J. van de, 174.j’oorhiers, S. T.. 296.Vorsina, M., 7, 13, 17.Waalkes, T. F., 106.Wackher, R. C., 96.\Yadsley, A. D.. 279.Wagner, C., 77.Wagner, C. D., 291.LVagner-Jaiuegg. T., 163\Vahl, A. C., 57, 58.ITlusoy, E., 2983.242, 244, 258.249.249.277.164.\Vald, A., 266.FValdeland, C. It., 292.Walden, P., 74.Waldvogel, M. J., 220.Walker, H., 300.Walker, H. B., 295.Walker, J., 177, 198.Walker, 0. J., 67.Walkley, A,, 279.Wallace, W. N. W., 269.Wallach, O., 107.Wallis, E. S., 188.Walls, H. ,J., 72.Walsh, A. D., 32, 34, 35,37, 38, 39, 40, 42.43, 44,45, 46, 49, 53.Walter, E., 132.Walkers, W. P., 291.Wang, Y. L., 334, 235.Wansbrough-Jones, 0. H.,Ward, R., 284.Ward, S. J., 298.Warren, B. E., 281.Warren, F. L., 215.Waser, E., 120.Waters, W. A,, 60, 135.Watson, W. G., 119.Watts, B. M., 291.Weakley, F. B., 224.Wealt, W. M., 116.Weatherall, H., 290.Weber, P., 111.Weichert, R., 255.Weidel, W., 255.Weidlich, H. A., 191, 198.Weil, R., 277.Weil-Malherbe, H., 64, 69.Weinglass, A. R., 252.Weinmayr, V., 109.Weinstein, B. B., 237.Weinstein, C., 189.M7eiss, J., 20, 61, 62, 63,64, 67, 68, 69, 70, 76, 78,80, 142.70.Weissberger, A., 63.Weitkamp, A. W., 295.Welch, A. J. E., 49, 99.Welde, R., 147.Wells, J. J., 237.Wendt, G., 236.\Yenstrom, E.. 13.Werner, L., 157.Werner, L. B., 59.Wernimont, G., 269.Wertheim, M., 223.West, T. F., 147, 157.Westheimer, F. H., 71, ’77.Westphal, K., 236.Westphal, O., 236.Westphal, I T . , 180.Wettstein, A., 175, 184, 1%Whaley, A. M., 103, 111.Wheeler, D. H., 290, 294.\%eland, G. W.. 127.Whelton, R., 227.187.Whetstone, It. K., 131.White, H. L., 14.White, J. G., 126.White, L., 94.White, W. H., 292.Whitehead, R. B., 298.Whitman, B., 174, 181,Whitney, R. B., 13, 14.Whyte, L. K., 293.Whytlaw-Gray, R., 51.Wibaut, J. P., 128. 129.Wiberg, E., 55.Wick, H., 27.Wieland, H., 184.\Vieland, K., 166.Wieland, P., 175, 188.Wilds, A. L., 177, 178, 183,Wiles, A. E., 124.Wiley, R. H., 132.Wilke-Dorfurt, E., 73.Wilkinson, P. A., 174.Wilkinson, T. F., 232.Willenberg, W., 94.Williams, A. H., 64.Williams, D., 52, 135.Williams, G., 74, 75.Williams, H. O., 150.Williams, K. A., 292, 295.Williams, R. H., 252.Williams, R. J., 238.IVilliams, V. Z., 190.Wills, E. D., 290.Willstaedt, H., 169.\Villstiitter, R., 62, 120, 230.Wilson, A. J. C., 276.Wilson, J. B., 300.Wilson, J. M. G., 254.Wind, A. H., 153.IVinn, A. G., 79.Winnacker, K., 68.Winslow, E. H., 286.IVinstein, S., 173.Winternitz, F., 157.Wintersteiner, 0.. 180, 181,Wintrobe, M. M., 238.M7irth, W. V., 93, 101.Wiseman, P. A, 100.Wittle, E. L., 190.Wohl, Z., 237.Wojcik, B. H., 99, 101, 116.Wolff, J. P., 289.\Volfrom, 11. L., 143.IVollman, E., 262.\Vollman, S. H., 40.Wood, E. C., 270, 271, 273.Wood, S.. 242.Wood, W. A., 244, 258.Woodward, C. R., 245.Woodyard, 0. C., 2883.Woolley, D. W., 256.Woolley. H. W., 37.IVoroshtzow, N. N., 139,182.193, 203.182.140314Wreath, A. R., 277.Wright, B., 260.Wright, G. F., 142, 292.Wright, S., 254. wu, c. s., 57.Wurzschmidt, 299.Wuthier, H., 188.Wyart, J., 277.Wysa, J., 163.Yamamoto, S., 296.INDEX OF AUTHORS’ NAMES.Yates, F., 267.Youden, W. J., 274.Young, C. B., 297.Young, D. S., 88, 97.Young, E., 300.Young, F. G., 219.Young, G. T., 224.Yusjupova, S., 280.Yuster, P., 52.Znnko, A. M., 77.Zbinden, E., 169.Zeidler, G., 293.Zenitz, B. L., 173.Zerban, F. W., 220.Zerfas, L. G., 228.Ziegler, W. T., 277.Zima, O., 246.Zimmerschied, W. J., 100,Zscheile, F. P., 294.119

ISSN:0365-6217    

DOI:10.1039/AR9474400302

出版商:RSC    

年代:1947

数据来源: RSC

摘要:

INDEX OF SUBJECTS.ATP. See Adenosine triphosphate.Absorptiometer, Hilger photo-electric, 274.Absorption coefficients, measurement of,Acetaldehyde, spectrum of, far ultra-Acetamide, fluoro-derivatives, 11 5.Acetic acid, chlorodifluoro-, and difluoro-,286.violet, 44.117.trifluoro-, preparation of, 109, 116.Acetoacetic acid, trifluoro-, ethyl ester,Acetofluoro-sugars, 109.Acetone, fluorination of, 88.Acetone, trifluoro-, 117.Acetophenone, fluorination of, 97.Acetophenone, o-difluoro-, 97.trifluoro-, 11 7.Acetyl chloride, trifluoro-, 11 7.Acetyl value, 290.Acetylacetone, tri- and hem-fluoro-, 117.Acetylation in steroids, 173.N-Acetyl-DL-di-iodotyrosylglutamic acid,Acetylene, catalytic polymerisation of, 120.spectrum of, vacuum ultra-violet, 35.Acetylenes, hydrogen fluoride addition to,N-Acetyl-DL-thyroxylglutamic acid, 250.y - Acid.See %Naphthol- 6-sulphonic acid,2-amino-.Acids, fatty, and their esters, detn. of, 293.identification of, as hydrazides andureides, 293.metabolism of, 238.separation of, 295.spectra of, ultra-violet, 44.hydrogen overpotential in, 24.44.irradiation, 68.117.260.104.Acraldehyde, spectrum of, far ultra-violet,Acrylonitrile, polymerisation, initiated byActinium-K, 5 1.Actinons, 56, 59.Acyl fluorides from acid anhydrides, 98.Adenine, biosynthesis of, 258.Adenosine triphosphate, phosphorylationof sugars with, 219.Adipic acid, peduoro-, 119.Adiponitrile, pet-fluoro-, reduction of, 119.Adrenaline, effect of, on sugar phosphoryl-Atio- 5-aZZocholanic acids, 189.Alanine, pyridoxine synthesis from, 236.Alcaptonuria, amino-acid catabolism in,Aldehydes, detn.of, 282.Alkaline-earth tungstates, X-ray detectionation, 219.254.of, 279.Alkaloids, effect of, on hydrogen over-opium, X-ray detection of, 277, 279.,41kyl phosphates, detn. of, 301.Alloys, microradiography of, 286.X-ray analysis of, 283, 285.by powder diffraction, 278.~ - A l l u l ~ ~ e , 220.D-Altroheptulose, 220.Aluminium alkyls, dimeric structure of,potential, 25.55.alloys, 277.borohydride, 54.hydride, 55.number, 293.Americium, 59.Americium hydroxide, 59.Amide value, 293.Amines, enzymes producing, from amino-Amino-acids, decarboxylation of, byacids, 240.bacterial enzymes, 240.catalysts, 68.of, 300.synthesis of, by bacteria, 242.spectrum of, ultra-violet, 48.Ammonia, oxidation of, on platinumAmmonium compounds, quaternary, detn.Amylopectins, 222, 223.sources of, 223.Amylose in starch, 222.synthesis of, 217.Anaemia due to pyridoxine deficiency, 237.a- and B-pyracins in prevention of, 245.Analysis, 264.biological, dose metameter in, 270.errors in, 273.microbiological, procedure in, 272.probit, 272.X-ray, 276.by powder diffraction, 276.microradiographic, 286.qualitative, 276.quantitative, 28 1.spectroscopic, 284.replication in, 268.spectrochemical, of cations, 273.Androsterone, mol.rotation of, 180.Aniline, spectrum of, far ultra-violet, 40.Anodes, iridium, palladium, and platinumelectrodeposition of azides on, 30.platinum, electrodeposition of oxygenon, 29.Anthocyanins, synthesis of, in flowers, 254.Anthracene, hydrogenation of, 84, 130.Anthrapinacol, 142.Anthrone, Clemmensen reduction of, 142.Antimony fluorides, as fliiorinating agen t,s,100.31316 INDEX OF SUBJECTS.Antithyroid drugs, 245..4poenzymes from deca.rboxylases, 240.Apple rootstocks, haematin in, 230.IA-Arabinose, condensation of, witha-glucose- 1 -phosphate, 220.Arachis oil, detn.in, of squulene, 290.Argemone oil, detection of, in mustard oil,Arginine, biosynthesis of, 258, 261.~--4rginine, decarbosylation of, I )y~-Arginine decarboxylase, 240.Aromadendrene, structure of, 165.Aromatic compounds, 120.Arsenic, solubility of, in copper and silver,vapour, X-ray analysis of productsArsenious acid, oxidation of, by iodine, 80.Artemisia ketone, 84, 146.Aryl fluorides, preparation of, 107.Aspartic-alanine transaminase, 244.Aspergillus funaigatus mut.helvola, 176.Aspergillus oryzoe, amylase from, 224.Astatine, 51.Atomic weights, 51, 52.Autoxidation, ozone in, 64.Azides, electrodeposition of, on iridium,Azide ions, electrodeposition of, 5.Azulenes, 85, 162.assay of, 252.detn. of, 296.292.enzymes, 240.284.from, 280.palladium, and platinum anodes, 30.radical, 69.Bacteria, mutation in, 259.Bacteriophage, miitants resistant to, 262.Barium silicate, 277.Barley roots, polysaccharide from, 222.Bauxite ores, X-ray analysis of, 280.Beans, broad, leares, haemochromogens in,Beetroots, sugar, haernatin in, 230.Renzaldehyde, Cannizzaro reaction with,232.142.spectrum of, far ultra-violet, 44.Benzaldehyde, 2-chloro-, reduction of, 143.1 : 2-Benzanthrene, synthesis of, 138.Benzene, derivatives, ozonolysis of, 127.fluorination of, 93.spectrum of, far ultra-violet, and of it4Benzene, chloro-, and fluoro-, spectra of,derivatives, 39, 40.far ultra-violet, 40.hezuchloro-, fluorination of, 88, 101.perfluoro-, 101.iodo-, difluoride, as fluorination agent,107.Renzenediazocyanide, 4-bromo-, and2 : 4 : Wribromo-, vibration spectraof, 136.ethyl sucoinate, 137.sen rediictiori of, 142.Benzoic acid, fluorination of, 102.Benzophenone, condensation of, withBenzophenone, 4 : 4’-dichloro-, Clemmen-13enzopin a ~ o l , /druchl or0 - ~ 1 18.Benzotrifluoride, 99.Renzoyl peroxide, detn. of, in hits andBenzoylmalonic acid, ethyl ester, catalyticBenzyl fluoride, 107.Benzylidene difluoride, catalytic hydro-genation of, 110.(4 )-7-Benzylmarrianolic acid, 191.Benzyltrimethylammoninm fluorido, de-composition of, 107.Herthonite, identity of, with bournonite,279.Beryllium borohydride, 54.Betabacteriunt vermifornae’, dextran forni-Betacoccus arabinosus, dextran formationBile acids, side-chain degradation of, 184.Biological tissues, microradiography of,Biotin, biosynthesis of, 259.Bisdehydrodoisynolic acids, 180, 194, 197,catalytic hydrogenation of, 110.oils, 291.reduction of, 143.ation by, 221.by, 221.steroid synthesis from, 85.287.206.estrus threshold values for, 201.a-Bisdehydrodoisynolic acid, 86, 191.Risdehydromarrianolic acid, oestriis thrcs-Bisdehydromarrianolic acids, 197.($-)-Bisdehydromarrianolic acid, 193.Bisdehydro-estrolic acid, and its lac.tone,Bistrifluoromethylbenzenes, 99.2 : 4-Bistrifluoromethylbenzene, I -chloro-.Bistrifluoromethylpyridines, 99.Bleaching powder, constitution of, 280.Blue acid, decomposition of, 68.Boksputite, X-ray analysis of, 279.Bond strength in relation to polarity, 46.Borazole, ultra-violet absorption spectriimBoron, at.wt. of, 52.Roulangerite, lead thiomtimonates in, -380.Brancium, 51.Brassicasterol, 175.Hromination of fluorinated compoiinds,Bromine cation, 79.Bromine, reaction of, with hydrogen per-oxide, 79.Bromine trifliioride as fluorinating agent,100, 101.Bronze, detn.in, of sulphur, X-rayRiicherer reaction, 84. 138.Butadiene, spectrum of, far ultra-violet,, 37.Biitadiene, perfluoro-, 114.Riitane, l-chloro-2 : Tdifluoro-, chlorin-hold value for, 201.1 84.fluorination of, 92.and structure of, 42.114.analysis of residues from, 280.ation of, 112.2 : 2-difluoro-, chlorination of, 112.2 : 2-di- and 1 : 1 : 1-fri-fluoro-, chlorin-ation of, 1 1 1INDEX OF BTTBJECTS. 31 7cycZoButene, perfluoro-, 116,trum-But-2-ene, spectrum of, far ultra-teri. -Butylbenzene, spectrum of, nearButyric acid, afi-difluoro-, 97.Cadalene, synthesis of, 138, 153.Cadalene, 5-hydroxy-, 167.Cadinene, structure of, 151.Citdinene hydrocarbons, 81.Cadinol, 152.Calciferol, isomerisation of, 175.(’alciferol, iodo-, 178.Calcite, X-ray analysis of, 278.Chlcinm, at.wt. of, 52.Calcium oxide. detn. of, in magnesiumviolet, 33.ultra-violet, 41.detn. of, in tissues, 287.oxide, 282.phosphates, purity of, 279.stereoscopic, for X-ray microradio-Calmeon, 153.Cameras, X-ray, 281.Cannizzaro reaction, 84, 141.Carbides, equilibria of mixtures of, 284.Carbonyl compounds, catalytic reductionof, 143.ionisation potentials and ultra-violetabsorpt.ion spectra of, 44.Carboxyl groups, reduction of, 189.Carcinogenics, hydrocarbon, mutation in-duced by, 262.Caryophyllene, structure of, 85.C‘aryophyllenes, structure of, 156.Caryophyllene oxide, 156.Caryophyllenic acid, structure of, 158.Casein, incubation of, with iodine, 250.Catalase in chloroplasts, 233.yeast, 229.Catalysts, iron oxide and nickel, X-raynickel-mol ybdenuxn and nickel-tungsten ,Catalytic reduction, 142, 143.Cathodes, iron, hydrogen overpotential on.nickel, hydrogen overpotential on, -38,palladium, hydrogen overpotential on,tliallium, hydrogen overpotential on, 28.Cedtwwood oil, American red.See Jrrn iper( ‘edrene, striicture and properties of, 158,a- and p-Cedrenes, 159.( ledrenedicasboxylic acid, 159.Cedrenene, 160.Cedrenol, 160.(ledrenone, 159.(Jedrtss atlantica, leaf oil of, 153.(~ellulose, diffraction data for, 277.Cellulose felrafluoroethyl ether, 116.Ceric ions, effect of irradiation on, 67.Ceriiim tptrafliioride, fluorination with, 91.graphy, 286.analysis of, 279.X-ray analysis of, 280.28.30.28.virginiuna.161.(‘\uLlcedony, X-ray analysis of, 279.Chalinasterol, 175.Chamosite, 277.Charcoal surfaces, adsorption at, 14.Cheilosis, treatment of, with pyridoxine,Chlorofluoro-hydrocarbons, preparation of,Chloroplasts, 233.Chloroprene, spectrum of, far 1111 rti-violet, 37.5-aZZoCholanic acid, 188.degradation of, 185.5-aZZoCholanic acid, 3(fl)-hydrouy-, rle-gradation of, 185.Choleglobin, 234.i-Cholest-6-ene, 173.Cholest-4-en-S-one, 85.Cholesterol, ( f )-cestrone synthesis from.237.106.reactivity of chlorine in, 11 3.177.fl-orientation oi hydroxyl in, 171.oxidation of, by chromium trioxide, 171.structure of, 85.Cholesteryl acetate, brominrttion of, 174.i-Cholesteryl acetate, 173.Cholic acid, pregnan-20-one from, 185.Choline, biosynthesis of, 258.Chromatography in fat analysis, 295.Chromic acid, oxidation by, in solution, 77.Citrals, 144.Clays, X-ray analysis of, 280.Clemmensen reduction, 142.Clionasterol, 175.Clove oil, caryophyllene oxide from, 166.Cobalt, detn.of, 285.Cobalt alloys with mercury, X-ray analysisof, 279.carbide, 277.trifluoride, fluorination with, 90.Cobaltic ions, oxygen formation by, i npresence of water, 67.Codecarboxylase, interconversion of, withpyridoxine derivatives, 242.Codecarboxylase activity, testing for, 240.Colorimeter, Duboscq-type, 274.Columbium hydrazides, 277.Copaene, structure of, 152.Copper, K , radiation from, 281.germanium, 284.Copper alloys, 277.Coproporphyrin, synthesis of, by yeiist,232.Corrosion, 50.Cosmetics, detn.of monostearate in, 296.(lottonseed oil, detn. in, of gossypol, 296.(‘reams, sunburn, detn. of monosteamte in,(:resols, trifluoro-, stability of, 1 12.C’ristobalites in opal, 279.Crotonaldehyde, far ultra-violet spwtriitnCrystallisation, fractional, 295.Cirrc/rt)?a nronmticn, oil from. 1.50.solubility in, of arsenic, gallium ant1with nickel, X-ray analysis of, 282.296.of, 44318 TNDEX OF SUBJEOTS.Curcuma longa, oil from, 151.Curcumene, 150.a-Curcumene, synthesis of, 150.I - U - and -/?-Curcumenes, 160.Curium, 59.Cyanogen halides, spectra of, vacuumultra-violet, 35.Cyclodehydrogenation, 124.Cymenesulphonic acid, sodium salt, ashydrotropic agent in Cannizzaro re-action, 142.Cytochrome b,, 228.Cytochrome c in yeast, 228.Cytochrome c peroxidase, 229.Cytochrome f, 233.Cytochromes in plants, 23 1.in tissues, 226.nomenclature of, 23 5.yeast, 227.DDT, diffraction data for, 277.Aa -Decahydropyrene, 133.Decarboxylases, amino-acid, 240.inhibition of, by keto-fixatives, 240.Dehydronorcedrenedicarboxylic acid, 1 60.Delafossite, 277.Demjanov rearrangement, 164.7-Deoxybisdehydrodoi~yn0lic acid, 2 10.Deoxycholic acid, and its methyl ester,degradation of, 185.preparation of, and separation fromcholic acid, 188.11 -Deoxycorticosterone acetate and 2 1 -methyl ether, 187.17-Deoxyoestrone, 180.Deoxypyridoxine, 246.Detergency comparator, 298.Detergents, detn.in, of organic sulphates,tests, 297.299.dish-washing, evaluation of, 298.solubilisation of dyes by, 298.Deuteracetone, spectrum of, far ultra-Deuterium, electrodeposition and adsorp-Deuterium peroxide, Raman spectrum of,N-Deuteropyrrole, ultra-violet spectrumDextrans, bacterial, 221.Diacetylene, vacuum ultra-violet spectrumDiazocyanides, structure of, 84, 134.Diazoethane, trifluoro-, 118.Diazonium borofluorides, decomposition of,Diazosulphonates, isomerism of, 136.Uihenzanthracene, mutation induced by,1 : 2 : 6 : 6-Dibenzanthracene, bondlengthsDiborane, spectra of, 48, 53.violet, 44.tion of, 27.76.of, 38.synthesis of, 217.of, 35.107.263.in, 84.structure of, 126.structure of, 52.a-Dicazbonyl compounds, detn.of, 292.Dichlorine heptoxide, structure of, 78.Diene value, 289.Diethylbenzenes, fluoro-derivatives, 99.a/3-Diethylstilbenecarboxylic acids, 2 15.Diethylstilbaestrol, estrus threshold valueDiffusion in electrolysis, 30.Difluoro-acids, 119.Diginane, 190.Diginigenin, 190.Diglycerides, 296.Dihydroequilin, 181.Dihydroeremophilone, hydroxy-, struct lireDihydroguaiene, 167.Dihydroguaiols, 167.Dihydropyrene, structure of, 132.Dihydro -6 - vetivol, 1 6 9.7 : 12-Diketocholanic acid, 3-iodo-, asopaque substance for gall-bladderX-ray diagnosis, 189.Dimethylaminodihydrocaryophyllene,oxidation of, 157.5 -Dimethylaminonaphthalene- 1 -sulphonicacid, kinetics of hydrolysis of, 140.1 : 4-l>imethylazulene, 167./3y-Dimethylbutadiene, spectrum of, farultra-violet, 37.Dimethyldiacetylene, spectrum of, vacuumultra-violet, 36.Dimethyldiborane, 55.1 : 2 : 4 : 5-Dimethylenecyclohexa-2 : 5-Dimethylethylallenolic acid, 86, 204, 21 6.Dimethylgallium borohydride, 55.1 : 3-DimethylcycZohexane, perfluoro-, 91.1 : 2-DimethylcycZohexylacetic acid, 155.Dimethylnaphthalenes, ozonolysis pro-2 : 3-Dimethylnaphthalene, ozonisation of,1 : 4-Dimethylphenanthrene, synthesis of,1 : 4-Dimethyl-7-isopropylazulene, 156,aa-Dimethyltricarballylic acid, 161.Dinitrogen tetroxide, hydrolysis of, 76.Diphenyl ether, fluorination of, 94.yy-Diphenylbutyrolactone, 137.24 : 24-Diphenylchola-20 : 23-diene,bromination of, 186.24 : 24-Diphenyl-5-aZZochol-23-ene, 22-bromo- 3(/?) -hydroxy-, 3( 8) - acety 1 tle-rivative, oxidation of, 188.Diphenylenephenanthrone, 142.1 : l-Diphenylethane, 1 : 2-difluoro-, 97.Diphenylmethane, 4 : 4’-diamino-, goitro-genic activity of, 247.Diphenylsulphone-NN’-didextrose, pp’-diamino-, sodium sdphonate. SeePromin.for, 201.detn.of, in hydrogenated oils, 290.of, 154.diene, 123.ducts from, 129.83.138.168.2 : 2-Diphenylvinylacetic acid, 138.Dispersing agents, evaluation of, 298.Distillation of fatty acids and esters, 295INDEX OF SUBJEUTS. 31 9Divinylacetylene, spectrum of, far ultra-violet, 37.o-Divinylbenzene, relation of, to naphth-alene, 124.Dodecyl alcohol, detn. of, 301.Dodecyl sulphate, detn.of, 299.Doisynolic acid, 19 1.estrus threshold value for, 201.structure of, 85.( +)-Doisynolic acid, estrogenic action of,Dose metameter, 270.Drosophila, mutation induced in, 260.Drosophila melamqwter, mutation in,Drugs, anti-thyroid, 247.resistance to, mechanism of, 262.Dyes, detn. of strength of solutions of,solubilisation of, by detergents and193.254.assay of, 252.274.soaps, 298.Earths, rare, 56.Eleostearic acids, det". of, in tung oil, 294.Elder leaves, hsmochromogen from, 233.Electric current, alternating, use of, inelectrode processes, 6, 9.Electrode processes, kinetics of, 5.Electrodes, amalgam, deposition of metal-lic ions at, 10.capacity measurements of, 16.convective diffusion at, 31.differential capacity of, 13.lead, hydrogen overpotential on, 27.mercury, 7.platinum, 9.hydrogen deposition at, 23.overpotential decay at, 11.hydrogen deposition at, 26.hydrogen or oxygen deposition on, 11,hydrogen overpotential at, 29.Electrolytes, adsorbed, on surfaces, 17.Electrolytic double layer, 12.Electroplating, X-ray analysis in, 281.Element 61, 57.Elements, new, naming of, 50.rare, X-ray analysis of, 284, 285.Enamels, titanium, X-ray analysis of,281.Enzymes, producing ainines from amino-acids, 240.respiratory, effect of yeast extracts onaction of, 229.Ephestia kuhniella, eyes, brown pigmentin, 255.Epihydrinaldehyde acetals, Kreis test for,291.Equation, Lippman, for polarisable elec-trodes, 13.a- and p-Equilenanes, 183.Equileqin, and its isomers, structure andsynthesis of, 182.(+ )-Equilenin, structure of, 180.Equilenins, structure of, 197.synthesis of, 86.Equilibrium potential in relation tohydrogen adsorbed, 9.Equilin, structure of, 180.Eremophila mitchelli, ketones from, 154.Eremophilone, structure of, 85, 154.Eremophilone, hydroxy-, structure of, 154.Ergosterol, and its derivatives, 175.neoErgostero1, 175.Ergothioneine, anti-thyroid action of,Escherichia coli, mutants of, bacterio-254.phage-resistant, 262.mutation induced in, 260.tryptophan decomposition by, 258.Ethane, fluorination of, 89, 97.Ethane, pentachloro-, fluorination of, 104.hexachloro-, fluorination of, 88.1 : l-dichloro-2 : 2-difluoro-, reaction of,with phenylmagnesium bromide, 1 12.s-tetrachlorodifluoro-, 88.1 : 2-difluoro-, instability of, 109.2 : 2-difluoro-, 106.difluoro-, 109.iodide, fluoro-, 107.sulphides, 2-chloro-, mutation inducedEthanol. See Ethyl alcohol.Ethyl alcohol, mono- and hi-fluoro-, 118.Ethyl chloride, fluorination of, 88.by, 260.Ethylamine, trifluoro-, 117.structure of, 118.Ethylamines, 2-chloro-, mutation inducedby, 260.Ethylbenzene, spectrum of, near ultra-violet, 41.Ethylene, spectrum of, far ultra-violet, 33.Ethylene, trans-dz'bromo -, -dichloro -, and-diiodo-, heights of triplet states for,35.tetrafluoro-, 114.halogeno-derivatives, spectra of,vacuum ultra-violet, 42.Eudalene, synthesis of, 154.Eudesmol, structure of, 153.Euonymus, leaves, haemochromogen in,Explosives, diffraction data for, 277.Fats, analysis of, 287, 293.chromatographic, 295.colour of, detn.of, 293.deterioration of, 290.detn. in, of monoglycerides, 296.of peroxides, 290.of phosphatides, 296.edible, detn. in, of saturat(ed glycerides,295.iodine value of, 288.m. p. of, 293.oxygen absorption of, 291.saponification of, 289.232.Fatty materials, detn. of oxirane oxygenFenton's reagent, 67.Ferrous salts, reaction of, with hydrogenperoxide, 65.in, 289320 INDEX O F SUBJECTS.Ferula pyra?ti&tn, shairol from, 168.Fig trees, peroxidase in sap of, 230.Fluoranthene, synthesis of, 125.Ihorene, 142.Fluorenone, Clemmensen reduction of, 142.Fluorescence, quenching of, 69.Fluorides, inorganic, as fluorinating agents,l’luorinated compounds, partly-, pro-1-’luorinating agents, 98, 100.I*’luorination of hydrocarbons, 82, S7.l’luorine, at.wt. of, 52.synthesis of, 125.by molecular oxygen, 64.98.perties of, 108.vapour-phase, 88.handling of, 87.supply of, 86.Fluorine organic compounds, 86, 96.Fluorocarbons, 82, 87.properties of, 94.Fluoroform, 11 7.Fluoronitriles, 11 8.Fluoro-olehs, 114.Food problems, application of statistics to,9-Formylanthracene, reduction of, 143.4-l~’ormyl-2-methyl-5-hydroxymethyl-pyridine, 3-hydroxy-, 339.Frohbergite, 277.Fructose, phosphorylation of, 219.Fruit juices, detn. in, of, quaternaryFliran, spectrum of, vacuum nltra-violet,Furfuraldehyde, spectrum of, far ultra -properties of, 115.265.ammonium compounds, 300.38.violet, 44.Gallium, solubility of, in copper and silver,Gallium hydride, 55.Gases, spectra of, absorption, 48.Gastropods, sterol content of, 175.Germanium, solubility of, in copper andsilver, 284.Ginger oil, African, 162.Glaucodot, 277.Glucose, phosphorylation of, 219.separation of, from fructose, 222.C:lucose-6 phosphate from ribose- 1 phos-a-Glucose-1 phosphate, action of plant284.phate, 220.phosphorylases on, 223.%a-D-Glucosido-L-arabinose, 220.1,-Qlutamic acid, decarboxylation of, 1)y12-Clntamic acid decarboxylase, 240.C lilt amic-aspartic transaminase, pyriclosa 1phosphate as coenzyme of, 242.condensation of, with L-arabinose, 220.enzymes, 240.resolution of, 243.C:lutaric acid, perfiuoro-, 119.Glyceryl monostearate, constitiientfi of.Glycine, hiospnthesis of, 261.and its detn., 296.Cilycogen, 2%.Glycosides, cardiac, structure of, 85.alloGlycosides, structure of, 85.Glycosidic derivatives, natural, enzymicGlyoxal, spectrum of, far ultra-violet, 44.Goitres, toxic, proteolytic activity of, 253,Goitrogenic agents, 247.Gossypol, detn.of, in cottonseed oiI, 296.Grasses, levan in, 222.Grignard reagents, action of, on cliiwn-cyanides, 134.Guaiazulene, structure of, 85.Guaiol, structure of, 85, 167.Guanine, biosynthesis of, 261.Guanosine, synthesis of, 217, 320.Hzmatins in plants, 226, 230.Haemochromogens in leaves, 232.Haemoglobin, root-nodule, 334.HEmoproteins, 226.Halogen ions, complexes of, with cations,Hansa-yellow YT-445D, 298.Heat of activation in electrode reactions,Heazlewoodite, 27 7.n-Heptane, perfluoro-, 82, 89.Heptanes, chlorofliioro-, fluorination of,Hercynite, 277.Heterocyclic compounds, fluoro-, 93.wHexadecane, fluorination of, 97.Hexadecyl sulphides, 277.cjjcZoHexadiene, spectrum of, vacuiims- and as-Hexahydropyrenes, striictrire of,c!/cZoHexane, fluorination of, 97.cycloHexane, perfluoro-, 82, 89.crystallography of, 96.Hexatriene, spectrum of, far ultra-violet,37.(XycZoHexene, 1 : 2-dichloroperfluoro-, 200.Hexokinases, catalysis of sugar phos-phosphorylation with, inhibition of, 2 19.cycloHexy1 ether, peifluoro-, 04.1,- Histidine, decarboxylation of, hyenzymes, 340.Hofer-Moest reaction, eqiiil i hrir in1potential of, 5 .D-Homoandrost-4-ene-3 : 17a-dione, 189.Homocadalene, 84.D-Homotestosterone, synthesis of, 189.Horse-radish roots, hzcmatins in, 2.30.Hutchinsonite, 277.Hydrindanones, substituted, addition ofdiazomethane to, 165.tJydrindanylmethylizmines, substitute(\,llemjanov rearrangement of, 164.Hytlroborons, structure of, 63.Hydrocarbons, aromatic non-benzenoirl,127.c*nrcinogenic, rniit8ation induced hp, 932.syntheses of, 217.yeast, 227.71.23.101.ultra-violet, 38.132.phorylation by, 219INDEX OF SUBJECTS.32 1Hydrogen, adsorption of, 011 metals, 21.atoms, bond energy of, 64.electrodeposition of, from aqueous solu-on mercury and platinum, 5, 7, 9.overpotential, 5.a t high current densities, 28.in acids, 24.in alkalis, 25.i n non-aqueous solvents, 30.on iron cathodes, 28.on lead cathodes, 27.on nickel cathodes, 28, 30.on palladium cathodes, 28.on platinum cathodes, 26, 29.on thallium cathodes, 28.theories of, 18.with oxygen, 65.tions, 23.reaction of, with nitric oxide, 68, 69.solubility of, in palladium, 284.Hydrogen-addition value, 293.Hydrogen cyanide, spectrum of, vacuumfluoride, addition of, to unsaturatedproside, photochemical and thermalultra-violet, 35.hydrocarbons, 104.reactions of, 63.reaction of, with bromine, 79.with ferrous salts, 65.state of, in solution, 76.violet, 48.violet, 48.selenide, spectrum of, vacuum ultra-t,elluride, spectrum of, vacuum ultra-Hydrophenanthryl-l-acetic acids, 191.Hydroxyl radical, 65.a-Hyodeoxycholic acid, degradation of,Hypobromic acid in solutions, 79.Hypoiodous acid in solutions, 79.Tgepon T, analysis of, 299.Illinium, 57.Indane, structure of, 126.Indaiies, substituted, addition of ethyldiazoacetate to, 163.Indium hydride, 55.Infra-red absorption with diazocyanides,Inorganic reactions, intermediate com-Xnosine, synthesis of, 217, 220.Insulin, effect of, on sugar phosphorylation,Zodic acid, ions in solutions of, 78.Iodicle ions, retlction of, with IiydrogeiiI odination in benzene nucleus, agent for, 80.Iodine, concentration of, by thyroid, 248.detn. of, in thyroid, 252.treatment with, in thyrotoxicosis, 253.Iodine pentufluoride as fluorinating agent,perchlorate, YO.Iodine cation, 79.value, 287.185.135.pounds in, 60.218.peroxide, 76.100.Ionisation poteiitials and ultra-violetspectra, 37.molecular, 32.of carbonyl compouiids, 44.$-Ionone, cyclisation of, 150.Ionones, 144.Ions from cation-anion complexes.7 1.Irene, structure of, 146.Iron alloys, detn. in, of titaniion nitride,with mercury, X-ray analysis of,cathodes, hydrogen overpotential 011,25.lron chlorides, ionic coinpleses of, i i isolution, 72.Jron ores, lY-ray analysis of, 280.titaniferous, X-ray analysis of, 279.hone, structure and synthesis of, 84, 146.a-Irone, synthesis of, 148.a-, /3-? and y-Irones, odour of, 148.Irradiation, reactions initiated hy, 67,Isomorphous substances, diffraction M I -Isoprene, spectrum of, far ultra-violet,Isotopes, concentration and separation of,Juniper virginiana, oil from, 159.3-Ketocholesta-1 : 4-diene, preparationKetones, aliphatic, spectra of, ultra-violet,ijromtttic, Clemmensen reduction of,tletn.of, 282.from reaction of oxy-acids with hydrogenions, 72.282.279.68.alysis of, 278.37.60.and isomerisation of, 178.44.142.9-Keto-as-octahydroanthracenes, 13 1 .1 -Keto-3-phenylindene-2-acetic acid, 1 J 7.1 l-Ketoprogesterone, 187.Ketosteroids, bromination of, 186.Kinetics of electrode processes, 5.Kok-saghyz plants, rubber content ofKolbe reaction, equilibrium potential of,Kynurenine, 355.Lactarazulene, 169.Lactarius deliciosus, lnutaroviolin from,I,actaroviolin, 169.1,actic dehydrogeiiasa of yeast, lianiatiiiLanthanons, 56.Lanthanum, preparation of, 56.Lard, adulteration of, 292.detn. in, of tristearin, 292.rancidity in, 292.Launderometer, 298.Lavrtndulol, 84, 144.Z-Lavandulol, 144.boLavtmdulo1, structure of, 146.roots of, 230.5.169.compound with, 228322 INDEX OF SUBJECJTS.Lavender oil, French, terpenes from, 144.Lead cathodes.See Lead electrodes.electrodes, hydrogen overpotential oil,Lead halides, spectra of, in dilute solution,lavandulol from, 84.27.71.oxide, 277.silicates, 277.Leaves, chloroplasts from, 233.haematin compounds in, 232.Lecithin, analysis of, 296.Ledene, 156.Ledol, 156.Legumes, nitrogen-fixing, red pigment inLemon oil, Javanese, 152.Leuconostoc dextranicune and mesen-Levans, bacterial, 221.synthesis of, 217.Levan-sucrase, 222.Light, inactivation by, of pyridoxineLignites, X-ray analysis of, 280.Linolenic acid, detn.of, in fats, 294.Lipids, analysis of, in feeding-stuffs, 296.Lipprnan equation for poIarisabIe elec-trodes, 13.Lithium borohydride, 54.silicate, 277.Lithocholic acid, degradation of, 185.from cholic acid, 188.Lublinite, X-ray analysis of, 278.Lubricating oils, fluorination of, 91.I,umiandrosterone, mol. rottition of, 180.Lumidoisynolic acid, estrus threshold( +)-Lumidoisynolic acid, 196.(+)-Lumimarrianolic acid, 196.Lummatrone, mol. rotation of, 180.Lungs, silicotic, detection of silica in, 280.L-Lysine, decarboxylation of, by enzymes,L-Lysine decarboxylase, 240.Magnesium oxide, detn.in, of calciumMaize starch. See under Starch.Maleic anhydride, adducts of caryo-Manganese trifluoride, fluorination with,Xanganosite, 277.Mannose, phosphorylation of, 219.Marrianolic acid, 85, 191.( +)-Marrianolic acid, estrus thresholdMasurium, 51.Materials, X-ray absorption by, 286.Medicine, pyriaoxine in, 237.Mercuric fluoride, fluorination with, 113.Mercury alloys with cobalt and with iron,root-nodules of, 234.teroides, dextran formation by, 22 1.derivatives, 342.value for, 201.240.oxide, 282.tungstates, 277.phyllene with, 157.91.value for, 201.X-ray analysis of, 279.cathodes. Bee Mercury electrodes.Mercury electrodes, 7.capacity of, IS.hydrogen deposition at, 5, 23.overpotential decay at, 11.violet, 44.Mesityl oxide, spectrum of, far ultra-Mesitylene, nonafluoro-, 99.Metabolism, effect of gene mutation on,fatty acid, pyridoxine relation to, 238.Metals, electrodeposition of, a t amalgamequilibrium of, with fused salts, 50.hydrogen adsorption on, 2 1.microradiography of, 286.potential difference between solutionsand, 14.X-ray analysis of, 285.Metal filings, preparation of, vacuum,apparatus for, 281.surfaces, electrokinetic8 of, 14.Metallic fluorides as fluorination agents, 90.Metallography, X-ray diffraction analysisMethaemoglobin in root nodules, 234.Methane, fluorination of, 88, 97.Methane, chlorodifluoro-, reaction of,Methanesulphonic acid, amino-, sodiumMethionine, biosynthesis of, 258, 261.4-Methylacetophenone, reduction of, 143.Methylacetylene, spectrum of, vacuuniultra-violet, 35.2-Methyl-4-aminomethyl-5-hydroxy-rnethylpyridine, 3-hydroxy-, 239.Nethylazulenes, 165, 166.7-Methylbisdehydrodoisynolic acids, 2 11.estrus threshold values for, 201.5-Methyl-2 : 6-bishydroxymethylpy-imidine, 4-hydroxy-, hydrochloride,246.7-Methyldoisynolic acids, 199, 212.astrus threshold values for, 201.Methyl ~-9-fluorenyl-/3-methyl-n-pmpylketone, 125.Methylcycbhexane, perfluoro-, 83, 91.7-Methyl- 1 : 2-cychhexanobisdehydro -doisynolic acids, 202, 212.2-Methy1-6-hydroxymethylpyrimidine,4-hydroxy-, hydrochloride, 246.6-Methylionone, 147.7 -Methyl -1umidoisynol ic mi ti, ccs trusthreshold value for, 201.l-Methyl-lO-norcholesta- 1 : 3 : 5-trieno,3-hydroxy-, 178.7-Methyl- 1 : 2-cyclopentanobisdehydro -doisynolic acids, 202, 212.O4-Methy1pyridoxine, 246.N-Methylpyrrole, spectrum of, ultra-Micro-organisms, action of, on sucrose, 221.Microradiography, 286.Milk, detection in, of quaternaryMinerals, detn.of, 282.254.electrodes, 10.in, 278.with hexachloropropylene, 106.salt, 139.violet, 38.ammonium compounds, 300INDEX OF SUBJECTS. 323Minerals, diffraction data for, 276.Molasses, cane, D-allulose from, 220.Molecules, electron-deficient, 52.Molybdenum, K , radiation from, 28 1.Monodehydrodoisynolic acids, 2 10.Rlonoglycerides, 296.Rlontbrayite, 277.Montmorillonite, detn. of, 282.Moraxella lwofl, mutation in, 261.Moths, flour.See Ephestia Buhniella.Moulds, mutation in, 256.Muscle, polysaccharide synthesis in, 223.Mustard oil, detection in, of argemone oil,Mutation, biochemical effects of, 254.X-ray analysis of, 284. .detn. of, in fats, 296.892.in bacteria, 259.in moulds, 256.Naphthalene, origin of, in coal tar, 124.Naphthalene, perfluoro-, 82.Naphthalene- 1 -sulphonic mid, 5-amino -,Niyhthionic acid, kinetics of hydrolysis of,Naphthionic acid, sodium salt, action ofNaphthols, conversion of, into naphthyl-8-Naphthol-6-sulphonic acid, 2-amino-,National Brilliant-Blue B.M.A., 300.Nausea, effect of pyridoxine on, 237.Neptunium, 67.Neurospora, mutation in, 265, 260.Neurospora sitophila, microbiologicalassays with, 238.Nickel, detn.of, 285.Nickel alloys with copper, X-ray analysisof, 282.Nickel cathodes, hydrogen overpotentialon, 28, 30.Nicotinic acid, and its amide, for Neuro-spora mutants, 256.structure of, 130.kinetics of hydrolysis of, 140.140.bisulphites on, 84, 140.amines, 139.manufacture of, 139.precursors of, 257.Nitracidium ion, 74.perchlorates, 74.Nitric acid, mixtures of, with sulphuricNitric oxide, react,ion of, with hydrogen,Nitrogen, anodic evolution of, from liquidfixation of, by root-nodules of legumes,Nitrogen pentoxide, Raman spectrum of,Nitronium ion, 74.perchlorate, 75.Nitrosonium perchlorate, 75.Xitrosyl borofluoride, 73.ion, 73.perchlorate, 73.sulphate, 73.acid, 74.68, 69.ammonia, 30.234.75, 76.Nitrous acid, decomposition of, in aqueousNitroxides, 69.n-Nonane, 2 : 2-difluoro-, 106.C-Norbisdehydrodoisyolic acids, 203,2 13.Norcedrenedicarboxylic acid, 159.B-Normonodehydrodoisynolic acid, 204,Nuclear chemistry, 50.Nricleotides, synthesis of, 220.Kiltrition, pyridoxine in, 237.bicycZo[4 : 2 : OIOctane, 7 : 8-dichloro-, and7 : 8-dihydroxy-, 122.cycZoOctatetraene, 83, 120.bicyclo[4 : 2 : OIOcta-2 : 4 : y-triene,isomer of cyctooctatetraene, 122.a-Gktradiol, estrus threshold value for,201.synthesis of, 85, 177.CEstrolic acid, and its derivatives, 183.(-t )-(Estrone, mol.rotation of, 180.mstrus threshold value for, 201.structure of, 85.synthesis of, 170.CEstrus threshold values, 20 1.Oils, analysis of, 287.colour grading of, 293.deterioration of, 290.detn.in, of ash, 292.of peroxides, 290.of tracea of metals, 292.edible, detn. of trisaturated constituentsin, 295.hydrogenated, detn. in, of &glycerides,296.iodine value of, 288.marine, analysis of, 289.oxidation value of, 287.saponification of, 289.sulphated and sulphonated, analysis of,vegetable, detn. in, of tritolyl phosphate,hydrogen fluoride addition to, 104.solutions, 73.213.299.296.Olcfins, fluorine addition to, 106.Oleic acid, detn. of, in fats, 394.Olive oil, detn. in, of squalene, 290.Opal, cristobalites in, 279.Opium alkaloids, diffraction data for, 277.X-ray detection of, 279.Organic compounds, fluorination of, 82.L-Ornithine, decarboxylation of, byL-Ornithine decarboxylase, 240.Orris root, perfume from, 84.Oscillograph, cathode-ray, potciitiitlmeasurements with, 11.Ostrsasterol, 175.Dverpotential, activation, concentratioii,and resistance, 6.decay of, on mercury electrodes, 11.in acids, 24.in alkalis, 26.enzymes, 240.decay of, 10.hydrogen, 5324 INDEX OEOverpotential, hydrogen, on lead elec-trodes, 27.on platinum, 26.theories of, 18.solvents, 30.hydrogen and oxygen, in non-aqueousOvervoltage.See Overpotentid.Oxidases in plants, 232.Oxidation, 50.anodic, hydrogen peroxide theory of, 29.Oxidation value, 287.Oxides, equilibria of mixtures of, 984.Oxy-acids, reaction of, with hydrogenOxygen, electrodeposition of, on platinumions, 72.anodes, 29.molecular, electron affinity of, 64.inhibition of reactions by, 63.reaction of, with potassium, 63.reactions of, in solution, 63.overpotential in non-aqueous solvonts,30.photochemical formation of, 233.reaction of, with hydrogen, 65.reaction of, with potassium hydroxide,spectrum of, absorption, 63.Ozone in autoxidation, 64.63.Ozonolysis of aromatic compounds, 127.Pachnolite, X-ray analysis of, 280.Palladium, solubility of hydrogen in, 284.Palladium cathodes, hydrogen over-Paper, detection of cellulose in, 280.Pelecypods, sterol content of, 175.Pellagra, treatment of cheilosis in, 237.(1-Pelletierine, cyclooctatetraene from, 1 SO.Penicillium mutants, 269.Penicillium notaturn, mutation induced in,cyrZoPentadiene, spectrum of, vacuumqcZoPentene, octachloro-, fluorination of,potential on, 28.260.ultra-violet, 38.101.dichloroperfiuoro-, 100.perfluoro-, 116.Pentoic acid, ochfluoro-, 119.Perchloric acid, ions in solutions of, 77.Perfluoro-acids, 116.Perhydroanthracene, 131.Perhydrophenanthrene, 132.Periodic acid, ions in solutions of, 73.Periplogenin, degradation of, 189.rrlloPeriplogenin, degradation of, 189.l’ermanganates, ions in acid solutions of,Peroxidases, horse-radish, separation of,Peroxide acidium ion, 76.Peroxide value, 290,Petroleum sulphonates, oil-soluble,analysis of, 299.Phenanthrene, hydrogenation of, 132, 484.Phenol, spectrum of, far ultra-violet, 40.77.231.in plants, 230.9 UBJECTG.Phenylalanine, biochemical coii\wsion of,Pheoylalanine, dihydroxy -, oxidation of,2-Phenylazulene, 164.Phenylglyoxylic acid, catalytic reduction1 -Phenyl-2-naph thoic acid, 4 -hydrox y -,Phenylthiourea, goitrogenic effect of, 147.Phosphatides, detn.of, in fats, 296.Phosphors, X-ray analysis of, 280, 282.Phosphorus, detn. of, in tissues, 187.Phosphorylases, muscle and plant, 326.Photometers, 283.Photosynthesis, catalase in, 233.haernatin compounds in, 232.Plant materials, peroxidatic activitj- of, inPlants, cytochromes in, 231.flowering, chlorophyll and iron in, 232.hematins in, 226, 230.oxidase systems in, 232.I’lminodiurn lophurce, effect of pyridoxineon growth of, 246.Platinum electrodes, 9.hydrogen deposition at, 5, 26.hydrogen or oxygen deposition on, 1 1.hydrogen overpotential on, 29.oxygen deposition on, 29.into tyrosine, 260.by tyrosinme, 234.of, 143.137.X-ray-storing, 287.sucrose synthesis hy, 250.relation to food, 23 1 .nomenclature of, 235.surfaces, adsorption at, 14.Plutonium, 57.Pneumoconiosis, X-ray analysis in, 280.Poisons, catalase, effect of, on photo-Polarity, relation of, to bond stre~igtli,Polybromido number, 288.Polyhydrodoisynolic acids, 206.Polyhydromarrianolic acids, 20G.Polymerisation, chain, initiation of, byPolyperAuorovinyl chloride, 1 15.Polysaccharides, production of, 221.synthesis, 233.46.Fenton’s reagent, 67.synthesis of, from fructose and glucose,217.in muscle, 223.Polytetrafluoroethylenc, 1 15.Porifermterol, 175.Potassium, at.wt.of, 51.Potassium hydroxido, reaction of, withozone, 63.telraoxide, 62.Potential, diffuse doulde Iayer. effect of,on hydrogen deposition, 22.See also Overpotential.Pregnancy, effect of pyridoxine on sick-ness of, 237.Pregnanes, epimeric, 190.Proline, biosynthesis of, 261.Promin, toxicity of, counteracted bypyridoxine, 237.Propme, fluorination of, 104INDEX OF SUBJECTS. 325isoPropyl alcohol, oxidation of, in acidisoPropyl alcohol, fluoro-, 118.isoPropylbenzene, spectrum of, nearPropylene, spectrum of, far ultra-violet, 33.Propylene, hezachloro-, reaction of, with6-n-Propyl-2- thiouracil, goi trogen icPseudomoms saccharophila, phosphorylasea- and /3-Pyracins, 245, 246.Pyrene, bond lengths in, 84.Pyrethrin I, detn.of, 265.Pyridine, spectrum of, far ultra-violet, 40.Pyridine, 2- and 3-fluoro-, 107,3-hydroxy-, synthesis of, 236.Pyridoxal, microbiological assay of, 238.phosphorylation of, 241.preparation and growth activity of, 239.Pyridoxal phosphate, 240.reactivation of apoenzymes by, 244.Pyridoxamine, antibacterial properties of,microbiological assay of, 238.preparation and growth activity of, 239.solution, 77.ultra-violet, 41.chlorodifluoromethane, 106.activity of, 247.from, 220.hydrogenation of, 84, 132, 133.structure of, 126.246.Pyridoxamine phosphate, 243.4-Pyridoxic acid, 245.5-Pyridoxic acid, 245.Pyridoxine, and its derivatives, rBle of, inin amino-acid synthesis, 242.deficiency symptoms from, in animals,derivatives in transamination, 242.in treatment of diseases, 237.microbiological assay of, 238.oxidation of, 239.structure and synthesis of, 236.synthesis of, microbiological, 244.amino-acid breakdown, 240.2.17.Pyridoxine phosphate, 241.+-Pyridoxine, 238.Pyrochroite, 277.Pyrolusite, relation of, to y-manganesedioxide, 279.Pyrrole, hzm synthesis from, in mammals,233.spectrum of, vacuum ultra-violet, 38.Quartz, detn.of, 282.X-ray analysis of, 279.Radiation sickness, treatment of, withRadical, HO,, 61.Radical ion UO,, 70.Radicals, free, 61.Radiographs, interpretation of, 287.Radium, at. wt. of, 51.Rmmelsbergite, 277.pyridoxine, 237.NOH, 68.SH, 68.Ramsdellite, relation of, to y-manganeseRancidity, tests for, 292.Rape seed, goitrogenic effect of, in diet,247.X-Rays, analysis with, 275.by powder diffraction, 276.microradiographic, 286.qualitative, 276.quantitative, 2 8 1.spectroscopic, 284.dioxide, 279.diffraction index for, 276.diffraction of, 278.Reactions, inorganic, intermediate com-pounds in, 60.Reduction, 142, 143.Refractories, X-ray analysis of, 281.Resonance theory, 126.D-Ribose, biological origin of, 220.Ribose- 1 phosphate, constitution of, 220.Rice starch.See under Starch.Ring enlargement, 163.Root nodules, pigments in, 234.Salts, fused, equilibrium of, with metals,Sampling, sequential, 266.t,b-Santonin, 144, 154.Saponification value, 289.Scale, boiler and turbine, X-ray analysisScreens, fluorescent, for X-ray absorption,Sedum, ~-altroheptulose from, 220.Sesquiterpenes, 84.Shairol, 168.Shakosterol, 175.Silica, detn.of, in lungs. 280.Silicon, at. wt. of, 52.Silver, at. wt. of, 51.50.technique and methods of, 266.of, 279.286.solubility in, of arsenic, gallium, m dsurfaces, adsorption at, 14.Slags, alumina and chrome-steel, X-raySlates, X-ray analysis of, 280.Soaps, solubilisation of dyes by, 298.Sodium vapour, reaction of, with oxygen,Sodium sulphamate, 277.Soils, colloids in, X-ray analysis of, 280.Solvents, non-aqueous, overpotential in,Soya-bean oil, glyceride structure of, 295.Spectra, absorption, of irone, and itsgermanium, 284.analysis of, 279.63.30.separation of fatty acids of, 295.derivatives, 147.far ultra-violet, 32.X-ray, 284.Spectrochemical analysis of cations, 273.Spectrograph, vacuum, 285.Spectrometers, Geiger-counter, 283.Spectrophotometer, Hilger-Nutting, 274., Spectroscopy, X-ray, 284.I Sprue, treatment of cheilosis in. 237326 INDEX OF SUBJECTS.Squalene, detn. of, in oils, 290.Stannous halides, extinction curves of, inStarch, 222.presence of alkali halides, 72.maize, structure of, 224.rice, structure of, 224.Statistics, application of, to analysis, 264.Stearic acid, fluoro-, 109.Steel, X-ray analysis of, 280, 281.Steroids, 170.9 : 10-difluoro-, 97.acetylation of hydroxyl groups in, 173.elimination of keto-groups from, 189.introduction of radioactive carbon into,saturated and unsaturated, substitution174.in, 172.Sterols, marine, chemistry of, 175.Stigmastanol, 175.Stilpnomelane, 277.Stobbe reaction, 84, 136.Streptococcus fmulis, microbiological assayswith, 238.Succinic acid, diethyl ester, condensationof, with aromatic ketones, 136.Succinic acid, perfluoro-, 119.Succinic dehydrogenase of heart muscle,Succinimide, N-bromo-, bromination with,Sucrose, synthesis of, 217.cytochrome b with, 228.174, 186.by bacterial phosphorylase, 220.transglycosidation with, without phos-phate, 221.Sulphaguanidine, goitrogenic action of,247.5-Sulphanilylthiazole, 2-amino-, goitro-genic activity of, 248.Sulphites, oxidation of, in solution, 69.Sulphuric acid, mixtures of, with nitricacid, 74.Suprarenal bodies, haemochromogen andperoxidase in, 229.Surface-active agents, 29 7.analysis of, 298.sulphated or sulphonated, detn.of,300.Sweat, pyridoxine and its derivativesfrom, 245.Tafel relation, 8, 23.Tantalite, 277.Tantalum, 277.Tantalum nitride, 277.Teaseed oil, detn. in, of squalene, 290.glycerides from, 296.Technetium, 6 1.Terpenes, 84, 144.Terphenyls, polychloro-, chlorofluoro-oilsfrom, 101.Tetrahydrocaryophyllenol, 156.Tetrahydroionone, 146.Tetrahydroirone, 146.Tetrahydrolavandulol, 144.Tetrahydropyrene, structure of, 132.Tetrahydro-8-vetivol, 1 i9.Tetramethylethylene, spectrum of, farultra-violet, 33.Tetramethylplatinum, tetrameric struc-ture of, 56.Tetrapyrroles, 226.Thallium cathodes, hydrogen overpotentialThallium hydride, 55.Thionic acid radical, 69.Thiophen, spectrum of, vacuum ultra-Thiouracil, effect of, on thyroid, 249.Thomsenolite, X-ray analysis of, 280.Thyroid, detn. in, of iodine, 252.drugs affecting growth of, 247.iodine concentration by, 248.response of, to thiouracil dosage, 249.Thyroxine, biogenesis of, 250.Titanium nitride, detn.of, in iron alloys,282.Toluene, spectrum of, far ultra-violet, 40.near ultra-violet, 41.Toluene, perfluoro-, 102.Torreya mucifera, torreyol from, 152.Torreyol, 152.Torulopsis utilis, hzematin in, 227.Transamination, biological, 242.Transglycasidation, 21 7.without phosphate, 22 1.Trans-uranium elements, 56.1 : 2 : 4-Trimothylbenzene, ozonolysis of,1 : 3 : 5-Trimethylbenzene, spectrum of,2 : 2 : 4-Trimethyl-1 : 2-dihydrofluor-Trimethylethylene, spectrum of, far ultra-Trimethylcyclohexane, perfluoro-, 9 1.2 : 2 : 4-Trimethyl-1 : 2 : 3 : 4-tetrahydro-1 : 3 : 5-Triphenylbenzene, propeller shapeTristearin, detn.of, in lard, 292.2 : 4 : 6-Tristrichloromethyl-1 : 3 : 5-tri-1 : 3 : 5-Tristrifluoromethylbenzene, 99.Tristrifluoromethyltriazine, 11 8.1 : 3 : 5-Tristrifluoromethyl-2 : 4 : 6-tri-Tritolyl phosphate, detn. of, in vegetableTryptophan, biosynthesis of, 261.on, 28.violet, 38.inhibition by, of casein iodination, 251.128.near ultra-violet, 41.anthrene, 125.violet, 33.fluoranthene, 126.of, 34.azine, 99.azine, fluorination of, 94.oils, 296.conversion of, into kynurenine, 255.degradation of, to indole by Escherichiasynthesis of, by Lactobacillus arabinosusin presence of pyridoxine, 244.coli, 258.in Neurospora, 258.Tryptophanase, 244, 258.Tung oil, adulteration of, 289.Tungsten, at. wt. of, 52.Turmerone, 15 1.detection of, 293.detn. in, of elaeostearic acids, 594INDEX OF SUBJECTS. 327Tyrosine, biochemical formation of, fromTyrosine, diiodo-, thyroxine from, 250.L-Tyrosine, decarboxylation of, byTyrosine decarboxylase, formation of, byL-Tyrosine decarboxylase, 240.phenylalanine, 260.enzymes, 240.Streptococcus f m x d i s , 240.Unsaponifiable matter, detn. of, 289.Unsaturation of fats and oils, 287.Urane, 190.Uranium minerals, separation of, 57.Uranyl salts, fluorescence quenching of, 70.Urine, pyridoxine and its derivatives from,uZZoUzarigenin, synthesis of, 189.245.Vapour pressure of inorganic compounds,Vetivazulene, 165, 168.Vetiver oil, 168.Vetivone, 168.structure of, 85.a- and fl-vetivones, 169.Vinyl fluoride, 104.Vitamin-B,, complex nature of, 244.50.structure of, 85.polymerisation of, 116.group in natural tissues, 239.Vitamin-D, and -D3, relative potencies of,Vomiting, effect of pyridoxine on, 237.Vredenburgite, 277.Water, effect of irradiation on, 67.Waxes, m. p. of, 293.Weighing of small objects, 267.Wetting agents, analysis and classification266.of, 301.evaluation of, 298.Wetting tests, 297.Wheat germ, cytochrome c in, 231.Wolff-Kishner reduction, 143.o-Xylene, ozonisation of, 83, 127.p-Xylene from dehydrogenation of cyclo-octane, 123.Yeast, catalase in, 229.classification of, 227.coproporphyrin synthesis by, 232.cytochromes in, 227.enzymes of, 229.hcematin in, 227.microbiological assays with, 238.Zinc sulphide, detn. in, of zinc oxide, 282.Zingiber zerumbet, sequiterpene ketonefrom, 153.isozingiberene, 152

ISSN:0365-6217    

DOI:10.1039/AR9474400315

出版商:RSC    

年代:1947

数据来源: RSC