摘要:

QUARTERLY REVIEWS VOL. IV 1950 Committee of Publication Chairman .- SIR CYRIL HINSRELWOOD M.A. Sc.D. D.Sc. F.R.S. SIR WALLACE Aroe~s C.B.E. B.A. R. P. BELL M.A. B.Sc. F.R.S. G. M. BENNETT C.B. M.A. Sc.D. F. BERGEL D.Phil.Nat. D.Sc. E. J. BOWEN M.A. D.Sc. F.R.S. H. BURTON Ph.D. D.Sc. F.R.I.C. A. H. COOK Ph.D. D.Sc. F.R.I.C. F. S. DAINTON M.A. Ph.D. C. W. DAVIES D.Sc. F.R.I.C. M. G. EVANS D.Sc. F.R.S. D LL. HAMMICIC M.A. D.Sc. R. D. HAWORTH D.Sc. Ph.D. F.R.S. D. H. HEY Ph.D. D.Sc. F.R.I.C. E. D. HUGHES D.Sc. F.R.S. R. P. L~STEAD C.B.E. M.A. D.Sc. H. W. MELVILLE Ph.D. D.Sc. F.R.S. L. N. OWEN Ph.D. D.Sc. F.R.I.C. D.Sc. F.R.I.C. F.R.S. F.R.I.C. F.R.S. S. PEAT Ph.D. D.Sc. F.R.S. S. G. P. PLANT D.Phil. M.A. B.Sc. E. HI. RIDE& F.R.S. M.B.E. M.A. D.Sc. J. M. ROBERTSON M.A. D.Sc. F. L. ROSE O.B.E.Ph.D. D.Sc. H.N. RYDON,D.SC. D.Phil.,F.R.I.C. C. W. SHOPPEE D.Sc. D.Phil. R. SPENPE Ph.D. D.Sc. F.R.I.C. D. W. G. STYLE Ph.D. A. R. TODD M.A. D.Sc. F.R.S. J. WALKER Ph.D. D.Phil. D.Sc. W. WARDLAW C.B.E. D.Sc. T. S. WHEELER Ph.D. D.Sc. F. G. YOUNG M.A. D.Sc. F.R.S. F.R.S. F.R.I.C. F.R.I.C. F.R.I.C. F.R.I.C. F.R.I.C. Editor R. S. CAHN M.A. D.Phil.Nat. F.R.I.C. Assistant Editors A. D. MITCHELL D.Sc. F.R.I.C. L. C. CROSS Ph.D. A.R.C.S. F.R.I.C. Indexer MARGARET LE PLA B.Sc. L O N D O N T H E C H E M I C A L S O C I E T Y CONTENTS PAUE THE EMISSION SPECTRA OF FLAMES. By A. G. GAYDON . 1 CHEMISTRY OF THE TRANSURANIC ELEMENTS. By M. W. LISTER . . 20 BIOGENETIC ORIGIIN OF THE PSRROLE PIGI~NTS. By P. MAITLAND . . 46 THE REDUCTION OF ORGANIC COMPOUNDS BY METAL-AMMONIA SOLUTIONS.By ARTHUR J. BIRCH. . 69 RELATION BETWEEN THE OXIDATION-REDUCTION POTENTIALS OF QUINONES AND THEIR CHEMICAL STRUCTURE. By M. G. EVANS and J. DE HEER . . 94 INTERHALOUEN C O M P O ~ S AND POLYHALIDES. By A. G. SHARPE . . 115 ROTATION SPECTRA. By D. H. WHIFFEN . 131 LIMIT~G DENSITIES. By R. WEYTLAW-GRAY . . 153 ISOTOPIC TRACER TECH*~IQUE. By H. R. V. ARNSTEIN and R. BENTLEY . . 172 So= ASPECTS OF FURAN PYRAN CHEMISTRY. By D. G. JONES and A. W. C. TAYLOR 195 ORGANOMETALLIC COMPOUNDS OF THE FIRST THREE PERIODIC LIGHT ABSORPTION AND PHOTOCHEMISTRY (including photo- polperisation and the effects of light on dyes). By E. 5. BOWEN . 236 SOME ORGANIC PEROXIDES AND THEIR REACTIONS. By E. G. E. HAWEINS . . 251 STRUCTURE AND ACTIVITY IN SYNTHETIC INSECTICIDES. By W. A. SEXTON . . 272 By G.M. BURNETT . . 292 THE CYANINE DYES. By F. M. HAMER . . 327 MELTING AND CRYSTAL STRUCTURE. By A. R. UBBELOHDE . 356 THE NITRATION OF HETEROCYCLIC NITROGEN COMPOUNDS. By K. SCHOFIELD . . 382 ANIONOTROPY. By E. A. BRATJDE . . 404 GROUPS. By G. E. COATES . . 217 RATE CONSTANTS IN RADICAL POLYMERISATION REACTIONS. QUARTERLY REVIEWS THE CHEMICAL SOCIETY PATRON HIS MAJESTY THE KING President E. K. RIDEAL M.B.E. M.A. D.Sc. F.R.S. Vice-Presidents who have filled the office of President F. G. DONNAN C.B.E. D.Sc. LL.D. SIR IAN HEILBRON D.S.O. D.Sc. SIR CYRIL HINSHELWOOD M.A. F.R.S. LL.D. F.R.S. Sc.D. F.R.S. W. H. MILLS M.A. Sc.D. F.R.S. SIR ROBERT ROBINSON O.M. D.Sc. N. V. SIDGWICK C.B.E. D.Sc. LL.D. F.R.S. LL.D. F.R.S. Vice-Presidents R. P. BELL M.A. B.Sc. F.R.S. G. M.BENNETT C.B. M.A. Sc.D. J. W. COOK D.Sc. F.R.I.C. F.R.S. F.R.S. R. P. LINSTEAD C.B.E. M.A. D.Sc. A. R. TODD M.A. D.Sc. F.R.S. W. WARDLAW C.B.E. D.Sc. F.R.S. F.R.I.C. Treasurer SIR WALLACE AKERS C.B.E. B.A. D.Sc. F.R.I.C. Secretaries D. H HEY Ph.D. D.Sc. F.R.I.C. I H. BURTON Ph.D. D.Sc. F.R.I.C. E. D. HUGHES D.Sc. F.R.S. Ordinary Members of Council J. S. ANDERSON M.Sc. Ph.D. G. BADDELEY M.Sc. Ph.D. C. E. H. BAWN B.Sc. Ph.D. L. L. BIRCUMSHAW M.A. D.Sc. G. R. CLEMO D.Phil. D.Sc. A. H. COOK Ph.D. D.Sc. F.R.I.C. L. HUNTER Ph.D. D.Sc. F.R.I.C. F. E. KING M.A. D.Phil. D.Sc. T. MALEIN Ph.D. D.Sc. F.R.I.C. L. N. OWEN Ph.D. D.Se. F.R.I.C. A.R.C.S. F.R.S. E. G. V. PERCIVAL Ph.D. D.Sc. J. D. ROSE M.A. B.Sc. R. SPENCE Ph.D. D.Sc. F.R.I.C. F. S. SPRING Ph.D. D.Sc. F.R.I.C. M. STACEY Ph.D. D.Sc. F.R.S. L. E. SUTTON M.A. D.Phil. F.R.S. A. I. VOGEL D.Sc. D.I.C. F.R.I.C. J. WALKER Ph.D. D.Phil. D.Sc. W. A. WATERS M.A. Sc.D. F.R.I.C. T. S. WHEELER Ph.V. D.Sc. F.R.I.C. GWYN WILLIAMS D.Sc. Ph.D. F.R.I.C. Ex-Officio Members of Council H. E. Cox D.Sc. Ph.D. F.R.I.C. (Chairman of the Joint Libra3 Committee). A. FINDLAY C.B.E. D.Sc. LL.D. F.R.I.C. (Chairman of the Chemical Council). L. H. LAPMPITT D.Sc. F.R.I.C. (Chairman of the Bureau of Abstracts). General Secretary J. R. RUCK KEENE M.B.E. B.A. Telephone Numbers Regent 1676/6 Librarian A. E. CUMMINS. Printed in Great Britain by Butler & Tanner Ltd. Frome and London

ISSN:0009-2681    

DOI:10.1039/QR95004FP001

出版商:RSC    

年代:1950

数据来源: RSC

摘要:

CHEMISTRY OF THE TRANSURANIC ELEMENTS By M. W. LISTER M.A. D.PHIL. (CHEMISTRY DIVISION ATOMIC ENERUY RESEARCH ESTABLISHMENT HARWELL) THE elements which have now been discovered beyond uranium [atomic number (Z) = 921 are neptunium (Z = 93) plutonium (Z == 94) americium (Z = 95) and curium (Z = 96). Thus the last three periods of the Periodic Table start as follows Number of places be- yondinert gas . . 0 1 2 3 4 5 6 7 8 9 10 2ndlongperiod. . . Kr Rb Sr Y Zr Nb Mo Tc Ru Rh Pd 3rdlongperiod . . . Xe Cs Ba La Ce Pr Nd 61 Sm Eu Gd Lastperiod . . . . Rn Fr Ra Ao Th Pa U Np Pu Am Cm Written in this way the Periodic Table shows the contrast between the second and third long periods caused by the presence of the rare earths. The reason for this difference as is well known is that in the rare-earth series the fourth quantum shell is filled up from 18 at lanthanum to 32 at lutecium where it is complete whilst in the second long period the third quantum shell cannot expand beyond 18.The availability of the 4f orbits gives the rare earths their characteristic properties. In the last period a similar espansion of the fifth quantum group could take place; and the evidence is very strong that in fact 5f electrons occur in uranium and the succeeding elements. If no 5f electrons were present we should expect the elements neptunium plutonium americium and curium to be analogous to rhenium and the platinum metals. What is perhaps not so clear is the behaviour we should expect for elements containing 5f electrons. In the first place it by no means follows that because the first 4f electron appears in the fourth element beyond the inert gas (in cerium) the first 5f electron will appear in thorium.However we might reasonably expect that when 5f orbits were occupied the properties of the elements would deviate from the sequence found in the first and second long periods; and because an electron in a 5f orbit might to some extent be removed from the region of chemical attack as 4f electrons are that the deviations from first- and second-long-period behaviour would be in the direction of a series of elements of similar chemical properties. These remarks will be amplified later in the comments on the observed chemical behaviour of the transuranic elements. Since the rare-earth series starts in effect at lanthanum the chemistry of the elements from actinium onwards will have to be taken into account though this will be done very briefly for the elements before uranium.The resemblances of the chemistry of neptunium and plutonium to that of uranium are so extensive that a rather more extended account of uranium will have to be given. 20 LISTER CHEMISTRY OF THE TUNSURANIC ELEMENTS 21 Solution Chemistry All the elements from actinium to curium are base metals and with the possible exception of protoactinium form compounds which give simple hydrated ions in aqueous solution. In this it is at once seen that they resemble the rare earths whose most characteristic compounds are their tervalent salts which in solution give hydrated M3+ ions; the platinum metals and also tungsten and rhenium on the other hand give little indication of simple cations in solution.The simple ions of the heavy elements are _I u3 + AcS+ - - T h 4 + - u4+ Np4+ Pu4+ In addition the characteristic oxy-ions are known U022+ NpO,2+ PUO,%+ UO,+ Np02+ PuO,+ and there are compounds such as UOC1 and NpOC1 which possibly give quadrivalent oxy-ions in solution. Some of these ions are somewhat un- stable but where the stability is sufficient a series of salts can be prepared by the ordinary methods and the ions of any element can be converted into each other by suitable oxidising or reducing agents. In considering *the stability of these ions in aqueous solution we must take into con- sideration the following types of reaction which might remove the ion in question (i) oxidation or reduction by water or the associated anion (ii) disproportionation to a higher and lower valency state (iii) hydrolysis and (iv) formation of a covalent complex with the anion.(i) and (ii) can conveniently be considered together since they are both dependent on the oxidation-reduction potentials. All the compounds of actinium are tervalent,l and there can be little doubt that the hydrated Ac3+ ion with a rare-gas structure is present in solution. Thorium gives the well-known series of quadrivalent salts such as thorium(1V) nitrate Th(NO,),. Though tervalent and bivalent thorium compounds such as thorium tri-iodide can be obtained by dry methods these are decomposed by water to give quadrivalent thorium.2 The equilibrium Th3+(aq.) + H20 $ Th4+(aq.) + OH- + &H2 is evidently very much in favour of the right-hand side. In other words the oxidation-reduction potential of the Th(IIIJ1V) couple is very positive.In this thorium resembles hafnium as opposed to cerium. Little is known of protoactinium ions in solution ; the few protoactinium compounds that have been characterised are quinquevalent but it is very improbable that protoactinium forms a simple quinquevalent ion in solution. Recently indications of a lower valency state of protoactinium produced by reduction - - - - - - Am2+ - Np3+ Pu3 + Am3 + Cm3 + - - S. Fried and F. Hagemann AEXD 1891 (References to MDDC or AECD numbers * J. S. Anderson and R. W. M. D’Eye Chemical Society Symposium Oxford here and later are to American atomic energy declassified reports). April 1949; J . 1949. k244. 22 QUARTERLY REVIEWS with zinc amalgam have been obtained. In this state protoactinium gives an insoluble fluoride which is taken as an indication of ter- or quadri- valent protoactini~m.~ The formation of this compound might also explain the cathodic deposition of protoactinium when electrolysed in solutions containing fl~oride.~ Uranium forms two well-known series of salts the uranyl salts of U022+ and the uranous salts of U4+.Moderately strong reducing agents are needed to reduce uranyl to uranous compounds e.g. amalgamated zinc; and conversely most oxidising agents convert uranous into uranyl salts. The evidence that uranyl solutions do in fact contain UOa2+ presumably hydrated comes first from the formula of the salts which always contain a bivalent UO group e.g. U0,S04,3H20 NaUO,( OAc), and secondly from the vibrational fine structure of the spectrum of the solutions,5 which indicates a cation containing more than one atom that is unchanged by considerable variations of pH and thirdly from the electrochemistry of the solutions which is described below.The Raman spectrums can be explained in terms of a bent ion (04-O)++. If the uranyl solution is reduced electrolytically the first stage of the reduction involves a single electron transfer and occurs at a half-wave potential that is little affected by acidity 7 9 8 9 9 lo so that evidently this process is U0,,+ + e- -+ U0,f. This is confirmed by the diffusion constants of these ions calculated from the diffusion current at a dropping mercury electrode by the Ilkovic equa- tion id = 605nD$m*ta where id is the diffusion current per g.-mol. n is the number of charges transferred in the electrode process D is the dif- fusion constant m is the mercury flow rate and t the time of formation of the mercury drops.If n is assumed to be 1 the value of D becomes 0.65 x 10-5 cm.2/sec. whilst the value of D obtained from the conductance of UO2Cl solutions is 0.5 x The UO,+ ion readily dispro- portionates to sexi- and quadri-valent uranium. The rate is proportional to the square of the UO,+ concentration and to the H+ concentration. The rate constant is 130 (moles/l.)-l. sec.-l when the H+ activity is unity so that disproportionation is rapid at UO,+ concentrations above about ~/1000 though the stability increases in less acid solutions. H. G. Heal 7 calculates that at equilibrium in a M-SOhtiOn of UO,,+ and of U4+ N. with respect to H+ the concentration of UO,+ would be only 10-6.The polarogmphic reduction of UO,,+ gives a second wave which is a two-stage reduction uranium(V) to uranium(III) which shows signs of a kink at half its height. Before the kink which presumably corresponds to reduction to uranium(1V) the wave is irregular whilst its second half is cm.2/sec. 9 M. Haissinsky and G. Bouissi6res Compt. rend. 1947 226 573. 4 G. Bouissihres J . Phys. Radium 1941 [viii] 2 72. 6R. E. Connick M. Kasha W. H. McVey and G. E. Sheline MDDC 892. 6H. W. Crandall MDDC 1294. 7 Nature 1946 15'9 225 ; Tram. Faradag Soo. 1949 45 1. 8 I. M. Kolthoff and W. E. Harris J . Amer. Chem. SOC. 1945 67 1484 s D. M. H. Kern and E. F. Orlemann MDDC 1703. l o K. A. Kraus and F. Nelson AECD 2394. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 23 logarithmic Hence the reduction uranium(V) to uranium(1V) is not rever- sible at a dropping mercury electrode whilst the uranium(1V) to uranium(II1) stage is.This is consistent with the view that we have a change of ion type in passing from uranium(V) to uranium(IV) but not from uranium(1V) to uranium(III) i.e. U02+ + 4H+ + e- -+ U4+ + 2H20 u4+ + e- + u3+ This change is confirmed by the formulae of the quadrivalent salts which are not those of an oxy-ion and by the fact that the interchange of uranium between uranium( IV) and uranium(V1) compounds (e.g.,UCI and UO,CI,) occurs at a measurable rate.ll Further the U(VI/IV) couple is not rever- sible at a platinum electrode and so far as it can be observed appears to be strongly dependent on the acid concentration. The U(IV/III) couple is reversible and not acid dependent 7 10 l 2 at a mercury electrode.(A platinum electrode however takes up the potential of a hydrogen elec- trode.) Both the UO,+ and U3+ ions are very easily oxjdised for instance by air at room temperature; UO,+ can be titrated with ferric salts. Neptunium almost certainly gives the same series of ions as uranium namely NpO,,+ NpO,+ Np4+ and Np3+ (all hydrated) but their relative stabilities are altered.13 l4 In particular quinquevalent neptunium is stable in aqueous solution. Sexivalent neptunium requires more vigorous oxida- tion to prepare it than is necessary for sexivalent uranium but less than for sexivalent plutonium. Cold bromate solutions for instance oxidise neptunium(1V) solutions to neptunium(VI) the reaction passing through neptunium(V) and it is believed that it is the first stage that is the rate controlling step ; but the kinetics of the reaction are not simple.Ceric or argentic solutions will also oxidise it to neptunium(VI) as will potassium permanganate. Neptunium(V1) is reduced by stannous chloride rapidly to neptunium(V) and then more slowly to neptunium(1V). The same is true of reduction by hydrazine hydroxylamine or sulphur dioxide. Ferrous iron also reduces neptunium(V1) or neptunium(V) to neptunium(1V) at a rate proportional to the neptunium(V) concentration and to rather more than the first power of the hydrogen-ion concentration suggesting that the slow stage is Np02+ + Fea+ + H,O+ -+ Fe3+ + H20 + Np02H+ followed by a faster conversion into NpQ+. Hydrogen peroxide will reduce neptunium(V1) to neptunium(V) and sodium nitrite also effects reduction only as far as neptunium(V).Chlorine oxidises neptunium(1V) to nep- tunium(V) whilst chloride ion will slowly reduce neptuniurn(V1) to nep- tunium(V). Strong reduction (e.g. electrolytic) is required to produce neptunium(II1) solutions and they are oxidised by air. That sexivalent neptunium solutions do indeed contain NPO,~+ ions is shown by the isolation of NaNpO,(OAc), isomorphous with the corre- llE. Ron& AECD 1909. lS L. B. Magnusson J. C. Hindman and T. J. La Chapelle MDDC 1266 1267 l4 S. Fried and N. R. Davidson MDDC 1332. lnB. J. Fontana MDDC 1453. 1381; J. Amer. Chem. Xoc. 1949 71 687. 24 QUARTERLY REVIEWS sponding uranium compound and by the electrochemistry of the neptunium ions. Neptunium(V1) solutions on reduction with one equivalent of a reducing agent give solutions that are quite stable of a neptunium ion with a characteristic absorption spectrum.This is presumably the NpO,+ ion ; this conclusion is supported by the fact that the Np(VI/V) couple is reversible and is only slightly dependent on the hydrogen-ion concentra- tion (this apparent slight dependence may in any case be due to liquid- junction potentials). The absorption spectrum of the NpO,+ ion is very similar to that of the iso-electronic PuO,~+ ion. The Np(V/IV) couple on the other hand is not reversible at a platinum electrode and it has only been measured indirectly by means of the equilibrium NpO,+ + Faa+ + 4H+ f? Np4f + 2H,O + Fa3+ As with uranium the irreversibility of this couple is attributed to the slowness of removal of the covalently-bound oxygen atoms in the quinque- valent ion.The Np(IV/III) couple is reversible and acid independent so that the ions in these valency states are probably hydrated Np4+ and Np3+. The disproportionation of quinquevalent neptunium analogous to the rapid disproportionation of UO,+ does occur ; but in M-sulphuric acid the rate con- stant k (from d[NpO,+]/dt = k[Np0,+I2) = 5.3 x lo- (moles/l.)-l.min.-l at 25". For the reverse reaction the rate constant is 2-15 (moles/l.)-1 . min.-l. Hence in M-sulphuric acid the equilibrium constant of the reaction 2NpO,+ + 4H+ + NpOaa+ + Np4+ + 2Ha0 is K = [Np0,+]2/([Np0,2+][Np4+]) = 40. It is also found from measure- ments of the " reproportionation '' rate at two temperatures and from a study of the kinetics of oxidation of neptunium(1V) by bromate that the activation energy of the reaction Np(1V) + Np(V1) -+ 2Np(V) is 27 kcals./g.-mol.Plutonium in aqueous solution also gives a similar series of ions Pu022+ PuO,+ Pu*+ and Pus+. The tervalent ion is however much more stable than with uranium or neptunium; Pu02+ is intermediate in stability be- tween U02+ and NpO,+. Plutonium(1V) is probably the most stable valency state of plutonium; to obtain plutonium(V1) it is necessary to use hot bromate l 5 or permanganate l6 solution (though these will oxidise plutonium(1V) slowly in the cold) but ceric nitrate argentic ions hot perchloric acid,17 potassium dichromate,ls nitric acid l9 at moderate con- centrations or in fact any vigorous oxidising agent can be used. Conversely plutonium(V1) is reduced by a variety of reducing agents (e.g.ferrous ions hydroxylamine or sulphur dioxide) initially to plutonium(V) which dispro- portionates and is further reduced. The reduction of plutonium(1V) to plutonium( 111) is much easier than the corresponding process for uranium or neptunium and as will be seen is not much more difficult than the reduction of plutonium(V1). Sulphur dioxide hydrazine iodide ion or 15R. E. Connick and W. H. McVey MDDC 335. l* B. G. Harvey H. G. Heal A. G. Maddock and E. Rowley J. 1947 1010. I'M. Kahn MDDC 391. I s R . E. Connick W. H. McVey J. W. Gofman and G. E. Sheline MDDC 687. 19 R. E. Connick and W. H. McVey MDDC 337 ; K. A. Kraw MDDC 1378. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 25 hydrogen and a platinum catalyst will all give plutonium(II1) solutions. The oxidation of plutonium( 111) to plutonium(1V) needs a moderate oxidis- ing agent and is for instance not effected by air.20 There is no sign of a lower ion than Pu3+.That the plutonium(V1) solutions do in fact contain PUO,~+ ions is shown (i) by the formulae of their salts e.g. NaPuO,(OAc), isomorphous with the uranium and neptunium compounds 21 or the 8-hydroxyquinoline derivative Pu02(CoH6~O),,CoH,N0 ; l6 (ji) by the fact that the absorption spectrum shows vibrational fine structure in the same wave-length region and with nearly the same separation of the lines as does that of U022+ ; and (iii) by the electrochemistry of plutonium solutions. Electrolytic reduction of a plutonium(V1) solution leads in the first place to a solution with a different absorption spectrum from either that of plutonium(V1) or plutonium(IV) and this must be plutonium(V) since only one equivalent is needed to reduce plutonium(V1) to this state.Similarly it can be made under the right conditions by oxidation of plutonium(1V) 22 z3 [this generally leads directly to plutonium(VI)]. The plutonium(VI/V) couple is reversible and the potential is independent of the acid concentration,22 z3 24 which indicates that the quinquevalent ion is Pu0,f. It has been found that this ion disproportionates and no well-defined compound derived from it has been obtained (or at least described) though it is believed to be present in a complex carbonate precipitated from alkaline solution. The kinetics and equilibria involved in the disproportionation of plutonium( V) have been z 3 8 25 It is found that plutonium(V) is fairly stable at pH values from about 2 to 5 ; but a t all acidities it slowly disproportionates to plutonium(1V) and plutonium(V1).The concentrations of the various plutonium ions can be followed by their absorption spectra; the initial process in the disappearance of plutonium(V) appears to be 2PuO,+ + 4Hf + PuO,a+ + Pu4f + 2H20 . ' (1) at least in effect though presumably (as with neptunium) there is an inter- mediate stage involving an oxy-ion of plutonium(1V) (e.g. PuO,H+) which then reacts with more hydrogen ion. A faster equilibrium than the above reaction is then set up PUO," + Pu4* + PuO,2+ + Pu3+ . (2) As soon as appreciable amounts of Pu(II1) are present the reaction PuO,+ + Pu3+ + 4H+ + 2Pu4+ + 2H20 . . (3) occurs [again probably with some intermediate stage involving an oxy-ion of plutonium(IV)] and this reaction is believed to be in practice the most important one in removing plutonium(V).22 259 26 Thus the mechanism of disproportionation of plutonium(V) is more complicated than that of 2oR.E. Connick and W. H. McVey MDDC 338. 21 W. H. Zacharissen MDDC 67. aeR. E. Connick M. Kasha W. H. McVey and G E. Sheline MDDC 749. ei J. C. Hindman AECD 1893. 45M. Kasha MDDC 904. L. H. Gevantman and K. A. Kraus MDDC 1251. *sR. E. Connick MDDC 666. 26 QUARTERLY REVIEWS uranium( V) or neptunium(V) because of the production of plutonium(II1) as well as plutonium(1V) and plutonium(V1); and it is one of the main peculiarities of the plutonium ions in aqueous solution that the 3- 4- and 6-valency states can exist together in comparable concentrations in solu- tions of moderate acidity.Consequently the study of the mechanism of disproportionation of plutonium(V) has to be carried out in solutions con- taining more than negligible amounts of plutonium(III) (IV) and (VI) so that the precise elucidation of the mechanism is difficult. R. E. Connick 25 finds for the equilibrium constant of (2) above in O*5~-hydrochloric acid Kasha 26 finds H = 10-7 in 0-lM-perchloric acid. constant obtained for the disproportionation of Pu(1V) (see below) Combining this with the K = [Pu(III)]~[Pu(VI)]/[PU(IV)]~ = 0.05 we get for the disproportionation of plutonium(V) to plutonium(1V) and (VI) (in 0*5~-hydrochloric acid at 25"). This may be compared with the value of for uranium(V) and 40 for neptunium(V) (both in M-acid). Con- sequently in fairly acid solution very little plutonium(V) will be present at equilibrium but as can be seen from the reaction (1) above [which assumes that plutonium(V) is present as the oxy-ion PuO,+] the stability of plutonium(V) would be much favoured by higher pH.This is in fact found by L. H. Gevantman and K. A. K r a ~ s ~ who also found decreasing stability with rising temperature. The interpretation of these kinetic measurements is complicated by the reduction of plutonium(V1) by the products of the alpha-particle bombardment of the solution which destroys plutonium(V1) at the rate of 1-2% per day. Gevantman and Kraus attribute this reduction to hydrogen peroxide which is known to reduce plutonium(V1) ; plutonium(V) reacts with hydrogen peroxide much more Quadrivalent plutonium in suflticiently acid solution (more than about 0*2N.) is probably largely present as hydrated Pu4+.Thus the Pu(III/IV) but not the Pu(IV/V) or (IV/VI) couple is reversible and reasonably inde- pendent of acid concentration. Plutonium( 111) gives under these conditions the simple hydrated ion Pu3+. This is confirmed by the formulz of the salts of plutonium in these valeneies e.g. Pu(IO,), Pu2(C204),. As was mentioned above the plutonium ions are remarkable in that at moderate acidities the oxidation-reduction potentials of the Pu( III/IV) and (IV/VI) couples are not very different. Consequently all three ions can exist in solution simultaneously in equilibrium 3Pu*+ + 2H,O r? PUO,~+ + 4H+ + 2Pu8+ . ' (4) The equilibrium constant written as K4 = [Pu(III)]~[P~(VI)]/[P~(IV)] was found 26 to have the following values using plutonium concentrations about 0.001~.slowly. K4 252 40.2 0.195 0.0405 Molarity of HCIO 0.052 0-102 0.516 0.994 LISTER CHEMISTRY OF THB TRANSURANIC ELEISIENTS 27 K4 is of course dependent on the hydrogen ion concentration and equation (4) suggests that it should be inversely proportional to its fourth power ; in fact it is inversely proportional to the third power of the perchloric acid concentration but it must be remembered that no account has been taken of activity coeacients. However these results are more consistent with this equation involving only the simple hydrated ions than with those based on hydrolysed ions [e.g. in particular plutonium(1V) as PuOH3+]. It will be seen from these values of K4 that if the acidity falls below about 0 .2 ~ . considerable disproportionation of plutonium( IV) occurs. At low acidities plutonium(V) is also formed possibly by the reverse of equilibrium (2) above or possibly directly thus 2Pu4f + 2H20 + PuO,+ + Pu3+ 3. 4H+ The latter mechanism is supported by the observation that the rate of disproportionation of plutonium(1V) is proportional to [Pu(IV)I2 ; the rate constant is 0.053 (mole/l.)-l. min.-l a t 25" in O*48~-perchloric acid. The oxidation-reduction potentials of the uranium neptunium and plutonium ions have been measured in various solutions. The results in gome cases indicate considerable complex formation with the anion but as is usual the potentials in perchlorate solutions appear to give the most reliable figures for the simple hydrated cations ; the potentials in chloride solutions are not much different.The most thorough investigation of the plutonium redox potentials is that of Kraus,27 who has studied their depen- dence on hydrogen-ion concentration (cf. also ref. 28) ; the following table gives the potentials relative to the normal hydrogen electrode; a smaller negative value for the potential indicates that the oxidised state of the couple is relatively more stable. The uranium potentials are for M-hydro- chloric or -perchloric acid solutions ; somewhat different values have also been reported for uranium(IV/V) I Couple. U. Np (in N-HCI). Pu (in H-€IClO4). III/IV . . . + 0.63 - 0.14 - 0.96 I V / V . * . . - 0.55 - 0.74 - 1.20 V / V I . . . . - 0.06 - 1.14 - 0.93 Pu (in M-HCl). - 0.97 volts - 1.13 - 0.91 *7 K. A. Kraus MDDC 814. as B. J. Fontana NDDC 1603 ; K.A. Krrtus and G. E. Moore MDDC 906 ; and refs. (9) (12) (13) (22) and (24). 2s L. Brewer AECD 1899. **E. F. Westrum AECD 1903. CI 28 __ 1 Ionformed. M4+. . . . . - 23.6 M02+ . . . . + 12.8 MOe2+ . . . . + 9.6 I I QUARTERLY REVIEWS NP. Pu. _- - + 12-9 - 5.9 + 33.1 + 62.9 + 55-44 + 79.7 The lower the value of AH the more stable is the ion relative to ter- valent M3+. Neither americium nor curium forms the series of ions given by uranium neptunium or plutonium. Both elements are predominantly tervalent and there can be little doubt that in solution they give the ions Am3+ and Cm3+. Americium cannot be oxidised by argentic ions in B~-nitric acid nor by potassium permanganate or sodium b r ~ m a t e ~ ~ suggesting that its oxida- tion potential is more negative than - 2 v.(for the III/IV couple). I n alkaline solution it can be oxidised by strong oxidising agents such as sodium hypochlorite ; but the higher oxidation state has not been definitely characterised. Americium(II1) can be reduced by sodium amalgam but not by zinc amalgam.32 The product of the reduction is believed to be Am2+ as it can be co-precipitated with europous and samarous sulphates presumably as AmSO ; americium(II1) is not carried on these precipitates. Curium so far has been obtained only as tervalent compounds and is not affectgd by the reagents which oxidise or reduce americium. These oxidation-reduction potentials show an analogy with the behaviour of the rare-earth ions. If we consider the 3+ rare-earth ions starting with Ce3+ where the first 4f electron appears it becomes progressively more difficult with increasing atomic number (and in fact after praseodymium impossible) to remove a further 4f electron by chemical means.The rising nuclear charge holds the 4f electrons progressively more firmly though it is somewhat screened by the other 4f electrons. Eventually in samarium a point is reached where the electrons are so firmly held that the bivalent ion Sm2+ can be obtained in solution by strong reduction and in europium this reduction is easier. In gadolinium the trends of the redox potentials are sharply interrupted gadolinium is only tervalent and the next element terbium shows signs of quadrivalency. Thereafter the elements are only tervalent until ytterbium is reached which can be bivalent. Thus the trends of the first half of the rare-earth series are repeated.This break a t gadolinium is no doubt because in Gd3+ with seven 4f electrons another electron (to give the unknown Gd2+) would have to be paired with one of the previously-held electrons and it is known from the spectroscopic and magnetic properties of the rare-earth ions that this pairing involves a rela- tively higher energy i.e. a more.unstable ion. In the heavy elements more electrons can be involved in chemical reaction than in the rare earths ; that is to say the outermost electrons are not so firmly held as is generally the case with elements of high atomic number. As with the rare earths the tervalent ions become progressively more stable relative to the quadri- slB. B. Cunningham AECD 1879. 8. G. Thompson R. A. James and L. 0. Morgan AECD 1907.LISTER CHEMISTRY OF THE TRANSURANIO ELEMENTS 29 valent and further on the bivalent relative to the tervalent. This is also true of the M0,2+ ions relative to the M4+ ions the M(1V) becomes more stable relative to M(V1). The changes are more rapid than in the rare- earth series and it is to this that we owe the far less uniform chemistry of the heavy-element series. The 5f electrons seem to provide a less efficient screening of the nuclear charge than do the 4f electrons. Finally in Cm3+ a point is reached where the 5f shell is half full (assuming no 6d electrons) and the Cm2+ ion like the Gd2+ ion is unknown. It should also be mentioned at this point that the relative energy levels of 4f and 5d as compared with 5f and fid electrons are probably somewhat different the 6d-electron levels being relatively of lower energy.As will be seen later the ground state of the atom (un-ionised) of thorium is 6d27s2 ; and there is some not entirely conclusive magnetic evidence for 6d electrons in some uranous compounds. At present no very definite assignment of the un- shared electrons in heavy element compounds can be made in all cases and the position on this question appears to be as follows. It is still possible to maintain that all unshared electrons in compounds of the heavy elements beyond the radon core are in 5f orbits ; but it seems more probable that at the beginning of the series we have 6d orbits which become relatively less stable as we go to higher atomic numbers. By the time uranium is reached the 5f orbits are probably somewhat the more stable and beyond uranium there is no evidence of unshared electrons in 6d levels.Thus the only compounds likely to contain unshared 6d electrons are the lower valency compounds of thorium and protoactinium. Mention was made earlier that the heavy-element ions were probably of a simple hydrated type in acid solution. In fact of course an equilibrium of the type or is set up in solution for any n-valent ion. Investigations have been made of the equilibrium constants of these reactions for the heavy-metal ions by measurements of the pH of solutions of their salts when titrated with alkali,27 and by changes in the absorption spectra and redox potentials in solutions of various pH. The values of the hydrolytic constants so obtained241 2'1 33134135 are given in the table following where K = [H30+J.[MOH(n-l)+]/[Mn+] and pK = - log, K so that pK is equal to the pH at which 50% hydrolysis occurs. Mention3' may be made for comparison of the ceric ion which is largely hydrolysed to CeOH3+ and so is a much weaker base than Th*+ or Pu4+ and of the tervalent rare-earth ions where pK ranges from roughly 8 (in lanthanum) to 6. Plutonium tetrahydroxide is thus a base of very much the same strength as uranium tetrahydroxide. Plutonium( IV) also readily polymerises at pH values above about 1 so that in its solutions if the p H is raised by the Rii%+(aq.) + 2H,O + ICSOH(%-l)+(aq.) + H,Of M%+(aq.) + OH- + MOH@-l)+(aq.) K. A. Kraus and F. Nelson AECD 1864. ap Idem AECD 1888. 3s J. C. Hindman and D. P. Ames MDDC 1213. 30 QUARTERLY REVIEWS Ion. M 3 + . . . . . ~ 1 4 + . . . . .MO,+ . . . MOZ2+ . . . . U. - 1.44 1.15 (10) - 4.7 (36) NP. Pu. 6.95 (in M-c104-) (27) 7.1 (35) 7.2 (34) 1.53 (34) 1.4 (in M-GI-) 9.7 5.7 (Figures in parentheses are references.) addition of alkali there is a rapid initial change as the monomeric hydroxide complex is formed followed by a slow drift in pH to lower values as the polymer is formed. On acidification the polymer is only slowly destroyed though this can be hastened by heating the solution. The solution of the polymer has a characteristic absorption spectrum different from that of monomeric plutonium(1V). On further addition of alkali to a polymeric plutonium(1V) solution a polymeric hydroxide is precipitated different from that obtained by rapid addition of excess of alkali to monomeric plutonium(1V). The composition of these polymeric precipitates is often approximately (I%( OH)3.85X0.15)ra where X is the anion initially present.27* 34 Uraniuni(1V) also polymerises. It is not clear a t present whether the polymeric plutonium(1V) is simply a mixture of a number of ions contain- ing various numbers of Pu atoms combined by Pu-0-Pu links and with varying numbers of hydroxyl groups attached or whether it is a definite compound but in spite of the relative constancy of the amount of associated anion it is probably the former. Ions containing more than one metal atom occur also in somewhat basic uranyl and probably plutonyl solutions e.g. TJ2052+,xHz0. Analogous to the hydrolysis of the heavy-metal ions is their combina- tion with anions other than hydroxyl in the solution. Some evidence of such combination comes from the formation of double salts such as (NH,),Pu(NO,), but this is not by itself a proof of complexity as X-ray examination has shown many double salts e.g.RbUO,(NO,), not to con- tain complex anions. More definite evidence of complexity comes from electrical migration experiments and from observed changes in absorption spectra solubilities and cell e.m.f.s when various anions are added. Quali- tatively i t is found that sulphate acetate oxalate and probably fluoride combine strongly with Pu4+ the nitrate moderately and the chloride and perchlorate still less. 38 In perchloric acid solution plutonium(1V) and (VI) show no signs of migration as an anion even a t l0M-concentration. In hydrochloric acid plutonium(II1) migrates chiefly as a cation even in 86 H. Guiter Bull.SOC. chim. 1947 64. 37 M. S. Sherrill C. B. King and R. C. Spooner J. Amer. Chem. Soc. 1943 65 170. C. K. McLme J. S. Dixon and J. C. Hindma MDDC 1215. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 31 IOM-acid; plutonium(1V) begins to migrate chiefly to the anode when the acid concentration reaches about 5-6M. and the same is found for plutonium(V1). In nitric acid plutonium(1V) migrates as an anion a t concentrations above about 6~-acid and plutonium(V1) does so above about lOM-acid. In sulphuric acid plutonium(II1) migrates as an anion at concentrations above about 4M- plutoniurn(1V) above about O - ~ M - and plutonium(V1) above about M-acid. The behaviour of neptunium(V1) is very like that of plutonium(VI) though anionic complexes are slightly more easily formed. Acetate and oxalate both readily give anionic com- plexes with plutonium(IV) but fluoride does not do so even at 10M-con- centration in transference experiments although there is other evidence showing that a positively charged plutonium( IV) fluoride complex is formed.Since plutonium(II1) combines less readily with these anions than does plutonium(IV) the potential of the Pu(III/IV) couple should be lowered by complex formation and this i s found to occur. The extent of this effect is shown by the following values 39 E.m.f. v. - 0.966 - 0.953 - 0.92 - 0.74 - 0.50 Acid x. HCl HClO HNO H,SO HF It is interesting to note that both thorium and cerium(1V) have been shown to form complex anions with nitrate and this has been rarely found else- where. These results and the absorption 40 *l can be inter- preted by assuming that at least initially a complex of the general formula PuX3+ is formed by Pu(1V) with an anion X- and the value of its associa- tion constant K = [PuX3+]/([Pu4+].[X-I) is about 3 (mole/I.)-l for X = nitrate and about 0.2 for chloride. For sulphate the value is prob- ably about 2000 and for fluoride 42 6 x lo8 (mole/I.)-l. These figures apply only to the first complex formed by association with an anion; it was shown by the transference measurements described above that in many cases further combination occurs leading presumably to ions such as PU(NO,),~-. Compounds of the Transmanic Elements From the solutions of these ions of the transuranic elements various solid salts have been obtained by the usual methods of evaporation and precipitation. In certain cases solutions have been described (e.g.in work on absorption spectra) without an actual separation of a solid salt having been made the nature of the salt present being inferred from the method of preparation of the solution. In this section an account will be given of the compounds actually isolated from solution. In addition to preparation from solution many compounds have been obtained by dry methods and these will also be described here. The analogous thorium uranium or rare-earth compounds will be briefly noted. Metals.-Neptunium and plutonium metal have both been prepared by methods which show that these elements like uranium and unlike the 39 J. J. Howland J. C. Hindman and K. A. Kraus MDDC 1260. 40 J. C. Hindman MDDC 1256. 4% C. K. McLane MDDC 1147. 41 Idem MDDC 1257.32 QUARTERLY REVIEWS platinum metals are base metals and vigorous methods have to be used for their isolation. Neptunium l4 is prepared by the reduction of the fluoride by barium vapour at 1200". Plutonium uranium and americium 43 can be obtained similarly. The heats of formation (given in the table below in kcals./g.-mol.) of the ions of these elements from the metal 29 also show that we are not dealing with noble metals [compare e.g. Pt + 2C1 + PtCI (solid) - 56 kcals./g.-mol.] Ion formed. Th. U. _________ M3+ . . . . - - 123.6 - 159.8 M4+ . . . . - 185.5 - 147.2 - 165.7 Pu. - 141.9 - 129.0 I I Curium metal has not been described. The density of americium metal is given as 10-11 which makes the atomic volumes in the series roughly Pu Am - 22-24 Th Pa U NP 20.9 - 12.8 13.5 Ce Pr Nd - Sm Eu 20.6 20.8 20.6 - 21.7 29.0 It is interesting to notice that a sudden increase occurs a t europium and (presumably) americium an increase which is attributed in the case of europium to packing of essentially Eu2+ with two valency electrons as compared with say Ce3+ with three such electrons.Thorium does not fit the expected trend but this may be due to electrons in 6d orbits. Oxides.-The transuranic elements like uranium form a number of oxides though it has not always proved possible to obtain all the oxides corresponding to all the valency states known in solution. If we exclude peroxides the following oxides have been described The oxides UO NpO and PuO have been obtained usually in relatively small amounts by vigorous reduction of the higher oxides-for example when traces of oxygen are present as an impurity during reduction of the fluoride to meta1,44 or by reactions such as U + TJO -+ 2UO a t tempera- tures above 2000".Uranium mono-oxide is a brittle high-melting substance with a metallic appearance ; the monoxides of neptunium and plutonium are apparently-similar. They all have a crystal structure of the sodium chloride type. These oxides correspond to valency states that are not known in solution ; they are presumably semi-metallic compounds. Americium monoxide is obtained from the dioxide and hydrogen a t 800" ; 43 S . Fried AECD 1930. 4 4 R. C. L. Mooney and W. H. Zachariasen AECD 1787. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 33 it can be sublimed to give black crystals isomorphous with uranium or plutonium mono-oxide and is probably a normal oxide though it has not been obtained directly from the americious salts.The cornpourid Pu,O was obtained by reduction of the dioxide by atomic hydrogen or by heating the dioxide to 1700° It forms body- centred cubic crystals isomorphous with the C modification of the rare- earth sesquioxides. The lattice constant is somewhat variable in different preparations and this is attributed to variable composition over the range P U O ~ . ~ to P U O ~ . ~ ~ but the system does not seem to have been examined in detail. Its direct preparation from tervalent plutonium solutions has not been reported presumably because plutonium trihydroxide is too readily oxidised to be dehydrated to the sesquioxide Pu,O The same applies to the preparation of sesquioxides from uranium(II1) or neptunium( 111) solutions.It is however remarkable that americium trihydroxide on ignition in air gives americium dioxide and this on reduction in hydrogen gives americium monoxide and not the sesquioxide. Curium so far as is known forms only the sesquioxide Cm,O,. The dioxides Tho, UO, NpO, PuO, and AmO all have the fluorite- type structure with lattice constants (A,) as follows PUO Amo ::% 5.386 5-372 Tho uos 5.586 6.457 All except uranium dioxide are the normal oxides formed by ignition of their other oxides or decomposable salts such as nitrates in air at not too high a temperature. Plutonium dioxide is the highest plutonium oxide 45 known and attempts to oxidise it further by nitrogen dioxide or atomic oxygen were unsuccessful. Neptunium dioxide can however be oxidised under these conditions to give a compound of composition about NpO,.,, presumably Np,O with a slight deficiency of oxygen.-It is isomorphous with the uranium analogue U,08. Uranium is remarkable for the range of oxides intermediate between UO and UO that it forms.4* Triuranium octaoxide U,O is of course the oxide formed by heating other oxides in air but this can be converted into uranium trioxide UO by heating it in oxygen under pressure. Low-temperature oxidation of uranium dioxide goes about as far as UO,. with small change in the crystal structure and magnetic measurements 47 show that the U(1V) oxidised in this range becomes sexivalent uranium. From U,O to UO we have another range of stability with progressive change of crystal structure and magnetic measurements can best be interpreted in terms of quinquevalent uranium being p r e ~ e n t .~ ~ ~ 48 Hydroxides.-These are formed by the addition of aqueous ammonia or other alkali to solutions of the transuranic elements. Tri- and tetra- hydroxides of plutonium neptunium tetrahydroxide and americium tri- raD. M. amen and J. J. Katz AECD 1892. 46 E.g. K. B. Alberman and J. S. Anderson Chemical Society Symposium Oxford 47 J. K. Dawson and M. W. Lister unpublished. 48 H. Haraldsen and R. Bakken Natzlr&s. 1940 28 127. April 1949; J. 1949 s303. 34 QUARTERLY REVIEWS hydroxide are all obtained as insoluble precipitates redissolving in acids to give the corresponding salts and insoluble in excess of aqueous ammonia. There is no sign of ammine formation. The trihydroxides of the elements before plutonium are too easily oxidised to be isolated ; Pu(OH) is easily oxidised whilst americium trihydroxide is quite stable.The latter is a pink gelatinous material. Plutonium tetrahydroxide has been examined in some detail by K r a ~ s * ~ who finds that the dark-brown precipitate formed by addition of alkali to aqueous plutonium tetranitrate contains after thorough washing nitrate in the proportion Pu(OH),.~~(NO~)~.~~. It will be remembered that polymeric plutonium(1V) precipitates contain anions in roughly this proportion so that polymerisation is presumably occurring. Ksaus by following the pH changes on precipitation and washing also obtained evidence of basic nitrates. In its sexivalent state plutonium like uranium has acidic properties. Barium hydroxide precipitates a compound of composition about BaPu30, -at least this is the Ba Pu ratio.27 This is no doubt a polyplutonate analogous to the polyuranates.A similar precipitate can be obtained with sodium hydroxide which is considerably more soluble ; the precise com- position is uncertain. There is evidence from the pH titration curves of M0,2+ solutions with alkali where M is uranium neptunium or plutonium that polymerisation of all these ions occurs in slightly alkaline solution and on addition of acid again depolymerisation occurs only slowly. Peroxides.-Various peroxides may be mentioned. Uranyl solutions with hydrogen peroxide precipitake a uranium(V1) peroxide hydrated UO,. Plutonyl solutions on the other hand are reduced by hydrogen peroxide rapidly to plutonium(V) and then more slowly to plutonium(IV).50 Plu- tonium(1V) with amounts of hydrogen peroxide comparable to the plutonium present gives two soluble peroxido-complexes which can be distinguished by their absorption spectra.The brown complex which is formed first contains two plutonium atoms and one peroxido-group -0-O- per molecule; the red compound contains one more peroxido-group. It can be shown that the dissociation constant of the brown compound K = [brown compound]/([Pu*+]~ [H,02]) = 7 x lo7 (moles/l.)-l in 0 . 5 ~ - hydrochloric acid at 25" whilst for the red compound the constant K = [red compound]/([brown compound]. [H202]) = 145 (moles/l.)-l. It is thus evident that most of the plutonium in these solutions will be com- bined with the hydrogen peroxide. The structure of these complexes has not been elucidated in detail.If an excess of hydrogen peroxide is added a green precipitate is obtained 5 1 9 52 which contains some of the anion present particularly if this is sulphate. Its composition varies somewhat owing to decomposition but approximates to Pu207,xH,0 or Pu,06,S0,,xH,0 ; somewhat different forms are precipitated depending on the relative amounts of plutonium and hydrogen peroxide. These compounds con- 4* K. A. Kraus MDDC 1377. E. Connick and W. H. McVey MDDC 619. 61 E. I). Koshland J. C. Kromer and L. Spector MDDC 1263. 62H. H. Hopkins MDDC 1334. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 35 tain quadrivalent plutonium so we must write formuls for them such as O\ I Pu-0-0-Pu / O 1 . They have been examined by X-ray diffraction 44 l o OH o/ I OH and shown in one case to resemble closely thorium peroxide which forms a compound of empirical formula Th,O,,SO ; but detailed structures have not been determined.Salts,-Hatides and oxy-htides. The following simple halides of the heavy elements have been described (in this table X = any halogen) (PuF,) - NpF6 - NpF, NpCI NpBr, PuF NPX PuX Valency. - - I - - - - AmX CmX 6 . . . 6 . . . 4 . . . 3 . . . 2 . . Th. j u _. ThX ThI ThI Ny. 1 Pu. 1 Am. 1 Cm. 1 The volatile easily hydrolysed uranium hexafluoride has long been known; it is made from uranium tetrafluoride and fluorine. Neptunium trifluoride with fluorine a t red heat gives neptunium hexafluoride which melts at 53" and is easily volatile; this is isomorphous with uranium hexafluoride and is a white solid easily hydrolysed; its stability is less than that of uranium hexafluoride.Uranium hexachloride made by the reaction ZUCI -+ UCI + UCI, is much less stable than the hexafluoride ; as would be expected therefore neptunium hexachloride is unknown. Plutonium hexafluoride is not known for certain though traces of it may have been obtained. The uranyl halides are well-known stable com- pounds UO,X,. The corresponding neptunyl and plutonyl fluorides chlorides and bromides must all have been obtained in solution; iodide reduces these cations. PuO,F,,xH,O is a white fairly soluble solid. Quinquevalent uranium fluoride and chloride are known and U2F9 but no corresponding transuranic compounds. Quinquevalent salts of the type Np0,Cl must occur in solution but the solids have not been described. Neptunium tetrafluoride has been made as a light-green solid on the micro-scale by the reaction 4NpF3 + 0 + 4HF -+ 4NpF4 + 2H,O at about 500".Neptunium tetra- chloride and tetrabromide can be obtained by interaction of the dioxide with carbon tetrachloride and aluminium tribromide respectively. The tetrachloride is a yellow solid volatile at high temperatures ; the tetra- bromide is a reddish-brown solid volatile a t about 500". No tetraiodide could be made. Plutonium tetrafluoride is the only tetrahalide of plutonium that can be isolated though the tetrachloride must exist in solution but attempts to separate it have led only to the trichloride. Plutonium tri- The tetrahalides of uranium are all stable. m S. Fried and H R. Davidson J . Amer. Chem. SOC. 1948 70 3539 ; MDDC 1332. 36 QUARTERLY REVIEWS chloride does not react with chlorine at 170°.54 The hydrate PuF4,2H,0 is precipitated from aqueous solution; 55 the tetrafluorides of all of this group of elements are insoluble but the other halides are soluble.No tetrahalides of americium are known so that we have a regular decrease in the stability of the tetrahalides in passing from uranium to americium. The oxyhalides UOCI and NpOC1 are known. The series of the trihalides of these elements is known more or less completely except of course with thorium. They are obtained in the earlier elements (uranium and nep- tunium) by heating the higher halides in hydrogen or in the later elements by heating the oxides with an aluminium or carbon halide. Neptunium trifluoride has been made by heating the dioxide with hydrogen and hydrogen fluoride and americium trifluoride has similarly been made by heating the trihydroxide in gaseous hydrogen fluoride.Plutonium tri- fluoride can be precipitated from aqueous solution. The fluorides are in general insoluble but the other halides dissolve to give M3+ solutions. Their relative stability like that of the 3 + ions rises in passing from uranium to americium and curium. It is interesting to note 56 that although plutonium tetrachloride cannot be obtained the tetrafluoride can be made by use of the equilibrium QPUF $0 + BPUF +PuO Plutonium trichloride with 6 3 or 1 molecule of water of crystallisation can be obtained from aqueous solution. On heating it gives the oxy- chloride PuOC1 not the anhydrous trichloride. The oxybromide can similarly be prepared from the tribromide hexahydrate or by the following reaction at high temperatures 57 PuO + #Ha + HBr + PuOBr + H,O The equilibria PuX3 + H80 + PuOX + 2HX (where X = C1 or Br) have been measured a t 500-700".A number of complex halides 59 has been prepared from solution. These consist of a variety of fluorides and one series of double chlorides ; the fluorides are as follows The oxyiodide behaves ~imilarly.~8 Complex halides. C,H,NH,UO,F,,H,O C,H,NH,PuO,F ,H,O Cs,( Pu0,),F8,28H,0 M,PuF6 (M = K or NH,) KPu,F ; CsPu,Fg,3H,0 NaPuF KThE' KUF MPuF (M = Na K or Rb) K2UF6 KNPZF9 KTh,F KU,F9 Other complex thorium and uranium fluorides are known but the table shows only those analogous to the transuranic compounds. It is uncertain whether these plutonyl fluorides contain true complex ions ; and the same is true of the lower complex fluorides since though combination of plu- tonium and fluoride certainly must occur in solution as was mentioned (NaLaF is known) 64 B.M. Abraham MDDC 1574. H. H. Anderson MDDC 1130. 56 S. Fried and N. R. Davidson MDDC 1250. 68 I. Sheft and N. R. Davidson MDDC 1712 1713. N. R. Davidson MDDC 1578. El[. H. Anderson MDDC 1129 1130 1362. ** E. S. Maxwell AECD 2134. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 37 above there is no evidence from electric migration experiments of complex anions. A small number of complex chlorides has been prepared of the general formula M,PuCl, where M was casium tetramethylammonium pyridinium or quinolinium (cf. Cs2ThC1,,8H,0 and Cs,UC1,). No double chlorides could be isolated with potassium rubidium or zinc. The complex anion Puc162- has been shown to be present in the crystal by X-ray diffraction.Transuranic sulphides have been prepared by dry methods ; they are all lower-valency compounds The compounds KMF and KM,F form isomorphous series.,l Xulphides. ThS us (PUS) NPaSa NpOS Triuranium octaoxide when heated in hydrogen sulphide at 1300-1400" gives uranium disulphide US, and some of the sesquisulphide U2S3. The disulphides ThS and US are normal covalent compounds but the sesqui- sulphides Th,S and U2S3 are semi-metallic. 639 64 Neptunium dioxide on heating to 1000" in hydrogen sulphide gives first an oxysulphide NpOS and a t 1200" a sesquisulphide Np2S3 which is isomorphous with U,S and also apparently semi-metallic. Plutonium dioxide and hydrogen sulphide at 1300" give a compound Pu,O,S with a metallic lustre.On further treat- ment a t 1340" a black compound with a composition intermediate between Pu,S and Pu,S is obtained which gives a different X-ray difiaction pat- tern from the sesquisulphide obtained from plutonium trichloride and hydrogen sulphide at 800-1000". Plutonium sesquisulphide is not semi- metallic in character so that as usual we have a progressive increase in the stability of the lower valencies in passing from uranium to plutonium. There are some indications of a lower sulphide probably PUS obtained when plutonium trifluoride and calcium vapour react in a barium sulphide crucible.65 Nitrates. A nitrate Pu(NO,),,xH,O has been prepared 66 as light- green crystals. No double salts could be obtained with nickel cobalt or manganese nitrates but the salt (NH4),Pu(N03) has been prepared,40 isomorphous with the corresponding thorium and ceric compounds.Ths compounds M,Pu(NO,) are also known where M is Cs Rb T1 K or quinolinium. These probably contain the complex anion PU(NO,),~- as is shown by the uniformity of their formula by the electric-migration experiments and by analogy with the corresponding thorium compounds Rb,Th(NO ,) and Cs,Th( NO ,) whose diamagnetic susceptibilities are much less than the sum of those of their components suggesting that new bonds are formed in the double salts. $1 W. 33. Zachariasen J. Amer. C h m . Soc. 1948 70 2147. esE. F. Strotzer and M. Zumbusch 2. anorg. Chem. 1941 247 215. **E. D. Eastman MDDC 193. *sB. M. Abraham N. R. Davidson and E. F. Westrum AECD 1788. 66 H. H. Anderson MDDC 1130. *' C. Braselitin Cbmpt.r e d . 1941 212 193. 38 QUARTERLY REVIEWS Sulphates. Quadrivalent plutonium gives the reddish-brown sulphate Pu(SO4),,4H,O which on heating loses water to 3H20. H. H. Anderson 68 could not obtain the anhydrous salt without decomposition. Uranium disulphate also gives a tetrahydrate which loses water on heating to give a hemihydrate which cannot be completely dehydrated without hydrolysis. Plutonium gives a greyish-green basic sulphate Pu,0(S0,),,8H20. Double sulphates M,Pu(SO,) + 1 or 2H20 with M = NH, K or Rb have been prepared and there are thorium and uranium salts of the same composi- tion. The electric-migration experiments make it probable that these are true complex salts. Tervalent plutonium gives light-blue crystals of composition Pu,(SO,),,xH,O. A number of double sulphates are known MPu(S0,),,4H20 where M is TI Na Rb Cs or "H,; potassium gives a pentahydrate.Double salts K,Pu(SO,) and T1,Pu(S04) can be made but no compounds of the type M,Pu(SO,) known. The rare earths of course give numerous double sulphates of the type M(R.E.)(SO,), but of somewhat variable hydration. Iodates. The light-brown iodate plutonium tri-iodate and the light-pink tetraiodate are both insoluble. Plutonyl iodate is somewhat more soluble,~Q Oxuhtes. Diplutonium trioxalate is a slightly soluble salt,70 and the compound Pu(C204),,6H,0 is also insoluble (about 10-4 g.-mol./l. at 25"). 71 With excess of oxalate it gives a more soluble complex ion Pu(C,O,),~- and it is found that the constant of the equilibrium Pu(C~O,) 3- H2c204 + Pu(C,O4),'- + 2H+ g.-mols./l.). Thorium oxalate is similarly soluble in excess of oxalate.Neptunium dioxalate is also Acetates. The sexivalent ions of uranium neptunium and plutonium form isomorphous easily-crystallised compounds NaM02( OAc) ,. This is a relatively insoluble salt of these ions whose compounds are generally easily soluble. The solubility of sodium plutonyl acetate is 19.5 g./L in water at 25" and is less in the presence of excess of sodium acetate.60 The tetra-acetylacetonate of plutonium has been pre- pared and is isomorphous with the thorium compound. It is soluble in benzene or chloroform and can be sublimed under reduced pressure.72 The plutonyl oxine compound PuO,(oxine),,H(oxine) analogous to the uranyl compound,16 and the dark- red Pu(oxine) are Plutonyl nitrate gives a reddish-brown precipitate with potassium ferricyanide probably (PUO,),[F~(CN)~],,~H,O.Potassium ferrocyanide reduces plutonium(V1) rapidly but reduces plu- Acetyhcetonutes. S - ~ ~ d r o x y q ~ ~ n o Z ~ n e (oxine) derivatives. Terri- and ferro-cyanides.74 $8 H. H. Anderson MDDC 1127. loD. F. Maatick and A. C. Wahl MDDC 1761. 'a J. S. Dixon and C. Smith MDDC 1205. 7 s R. L. Patton MDDC 1386. ** Idem MDDC 1407. 71 W. H. Reas MDDC 1218. H. H. Anderson MDDC 1434. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 39 tonium( IV) only very slowly. Aqueous plutonium(1V) and potassium ferricyanide give a greyish-brown precipitate Pu3[ Fe( CN),], 15H,O. Plu- tonium( IV) and potassium ferrocyanide or plutonium(II1) and potassium ferricyanide give black precipitates of apparently different solubility and water content ; they are both PuFe(CN),,xH,O.The individuality of these two compounds is said to be uncertain and indeed it would seem probable that they are the same compound with the resonance forms PU(III)Fe(III)(CN) and Pu(IV)Fe(II)(CN), analogous to the Prussian blues NaFe(II)Fe(III)(CN),. This is supported by the black colour of the compound. Plutonium( 111) and potassium ferrocyanide gave a pre- cipitate from acid solution of HPuE'e(CN),. Hydrides.-Uranium and plutonium metal both combine with hydrogen to give solid hydrides whose formule approximate to 'U-H and PuH,. The hydrogen content is frequently lower than that required by these formule but there is no evidence of a definite lower hydride. The absorp- tion isotherms and kinetics of the reaction 2Pu + 3H2 -+ 2PuH3 have been examined.75~ 7 It is remarkable that the decomposition pressure of plu- tonium(II1) deuteride may be 1.4 to 1.5 times that of the hydride at cer- tain temperatures.The heat of reaction calculated from the pressure- temperature curve is 4.4 kcals./Pu atom at moderate temperatures. The structure of uranium(II1) hydride has been examined by X-ray diffraction ; the uranium atoms have a cubic (@-tungsten) arrangement ; the hydrogen atoms cannot of course be located directly. R. E. Rundle '7 believes that U-H-U bridges occur with one pair of valency electrons available in each bridge i.e. to the two U-H bonds. This conclusion is supported by L. Pauling and F. J. Ewing '* who calculate that such a structure would agree with the observed cell dimensions. Nitrides.-Plutonium nitride PUN can be made by the action of ammonia on the trichloride trihydride or metal at high te~nperatures.~~ Under these conditions no other nitride is formed.gives a nitride UN and also U,N3 and UN,. Carbides.-Carbides PuC and UC are known. All these mono-nitrides carbides and oxides have the sodium chloride type of structure 43 81 with the following lattice dimensions (in A.) Uranium ..~___..____ _____._ MC . . . . MN . . . . MO . . . . U. NP. Pu. Am. 4.951 - 4.910 - 4.880 - 4.895 - 4.92 5-00 4.948 4.95 _ _ ~ _ _ ___ - 751. B. Johns MDDC 717. 77 J . Amer. Chem. SOC. 1947 69 1719. 79 B. M. Abraham N. R. Davidson and E. F. Westrum MDDC 1640. 76 J. E. Burke .4ECD 2124. 78iZbid. 1948 70 1660. R. E. Rundle N. C. Baenziger and A. S. Wilson J . Amer. Chem. Soc. 1948 W. H. Zachariasen AECD 2196.70 3299. 40 QUARTERLY REVIEWS Borohydrides.-Aluminium borohydride reacts with heavy-metal tetra- halides to give volatile borohydrides of which the following have been identified These borohydrides are stable in the cold and in air but are hydrolysed by water with evolution of hydrogen When heated they decompose to give borides. Their vapour pressures are of the order of 0.1 mm. Hg at room temperature. The composition of the plutonium compound is un- certain ; it was prepared from plutonium tetrafluoride and aluminium borohydride but its formula has not been definitely established. Structure of the Heavy-metal Atoms As was mentioned in the introduction the heavy elements from actinium onwards might follow the sequence of the second long period owing to filling of 6d orbits or the sequence of the third long period (rare earths) owing to filling of the 5f shell or some modification of the sequence of the third long period owing to the filling of the 5f shell starting at some rela- tively later element.In the chemistry of these elements it is evident that thorium behaves as a group 4 element protoactinium (probably) as a group 5 element and uranium predominantly as a member of group 6. After this the sequence differs entirely from the second long period and neptunium to curium are not analogues of rhenium and the platinum metals but instead resemble uranium and to some extent the rare earths. There is a strong similarity between these elements when they are in the same valency state ; thus uranium(VI) neptunium(VI) and plutonium( VI) are similar ; so are thorium(IV) uranium(IV) neptunium(IV) and pluton- ium(1V) ; and actiniurn(III) plutoniumfIII) americium(III) curium(III) and to a lesser extent the easily oxidised uranium(II1) and neptunium(II1).Thus the properties of for instance uranium(IV) apart from its oxidation to wcanium(VI) closely resemble those of thorium(IV) and are not very like those of tungsten(1V). We have good chemical evidence for the presence of 5f electrons in uranium and the succeeding elements. The oxidation-reduction relations as was explained above are also consistent with the presence of 5f electrons if these are assumed to be less firmly held than 4f electrons (at least at first) and to provide relatively less screening of the nuclear charge so that the oxidation-reduction relations alter more rapidly along the series.Finally we may review briefly the physical evidence that bears on this point. The atomic spectra of thorium and uranium have been examined. Thorium s2 has its four valency electrons in 6d27s2 ; uranium 83 has its six valency electrons in 5f36d17s2. Thus in uranium and presumably in suc- ceeding elements 5f levels are in fact occupied. The fact that uranium 82 W. F. Meggers Science 1947 105 514 ; quoting P. Schuurman Thesis Amster- dam 1946. 8a 0. C. Kiess C. J. Humphreys and D. D. Law J . Res. hTat. Bur. Stand. 1946 37 57. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 41 has three 5f electrons suggests that the starting place of the series is two places earlier namely at thorium ; but this is largely an artificial point of view since it assumes a regularity that need not and in fact does not exist.Further evidence for 5f structures comes from the absorption spectra of the heavy-element compounds and particularly from their resemblances therein to the rare earths. It is well known that the colours of the ter- valent rare-earth ions are due to transitions amongst 4f levels; this is shown by the great sharpness of the absorption bands since the 4f levels are shielded by the 5s and 5p electrons from disturbance by the fields of surrounding molecules ; and by their relatively low intensity having regard to the narrowness of the bands since these are " forbidden " transitions in the sense that the 1 quantum numbers do not change. The absorption spectra of the heavy-element ions also give narrow absorption bands which are to be interpreted as transitions between 5f levels.(See for instance plut~nium,~ neptunium,13 or americium spectra. 31) The spectra of the tervalent ions in some cases somewhat resemble those of the " correspond- ing " rare-earth ions i.e. uranium(II1) and neodymium(II1) ; plutonium(II1) and samarium(II1) ; and particularly americium(II1) and europium(III).84 The resemblance of the spectra of americium and europium trichloride which were examined in the crystal is evidence of six 5f electrons in the former but no detailed analysis of the spectra has yet been published. The ions of the heavy elements like those of the rare earths are fre- quently paramagneti~.~~~ 8 6 ~ 8' Thorium(1V) ions having a rare-gas struc- ture are of course diamagnetic and the uranyl ion has a small temperature- independent paramagnetism.As a result of measurements in solution the following values of the magnetic moments in Bohr rnagnetons were obtained Np0,2+ f f 1 NpO,+ . . u4+ * . . I No. of Ion. I electrons ~ Moment. above Rn core. ~~ Ion. .__ 2.40 u3+ . . 3 3.20 3-03 3.086 Pu4+ . 4 1.85 2.95 0.90 2.91 Am3+. . . 6 0-8 6 I above En core. These results are mostly from measurements at room temperature only and the calculated values of the moment assume that A in the Weiss- Curie law is zero. Analogous measurements on the rare-earth ions show 8c S. Fried and F. J. Leitz AECD 1890. 86 J. J. Howland and M. Calvin AECD 1895. 86 C. A. Hutchison and N. Elliot AECD 1896. 87 R. W. Lawrence J . Am?. Chem. Soc. 1934 S6 776. 42 QUARTERLY REVIEWS that A may be appreciable even in magnetically-dilute materials so that the values of some of these moments may need some modification prob- ably upwards.The general trend of these values closely follows that of the rare-earth ions Ion (all 3 f ) ce Pr Nd - Sm Eu Electrons above xenon cor0 1 2 3 4 6 6 Moment 2.39 3.47 3.52 - 1.58 3-54 In addition to these results in solution various solid compounds have been measured e.g. uranous oxalate trihydrate 88 3-66 ; uranous sulphate 86 3.46 ; uranous acetylacetonate 86 3.39 ; UF4 89 3.30 ; UO 47 3-19. These moments are a11 given in Bohr magnetons; the susceptibilities were measured over a range of temperature and obeyed the Weiss-Curie law x(T + A) = C where x is the magnetic susceptibility. The moments of the rare-earth ions have been well explained by H. J. Van Vleck90 on the assumption that all electrons above the inert-gas core are in 4j orbits and that the spin-orbital coupling is not disturbed.The agreement of the moments of the ions Np02,+ and Ce3+ makes it probable that neptunium here has one 5f electron (ground state 2P5,2). The moments of the U4+ NpO,+ and PuO,~+ compounds differ somewhat but in general they are lower than that of Pr3+ compounds. This may be due to the strong interaction of neighbouring atoms suppressing the contribution of the orbital momentum so that only the spin is effective. In such a case an atom containing n unpaired electrons will have a moment of dn(n + 2) which is 2-83 in these ions and the moments of various uranium(IV) nep- tunium(V) and plutonium(V1) compounds are not much above this value. However such interaction would be more probable for 6d than for 5f elec- trons and these low values provide some support therefore for 6d structures.On the other hand if the uranous ion had a 6d2 structure in which L S coupling were preserved ground state 3F2 the calculated moment would be 1.63 much lower than any of the observed values. The observed values are indeed usually somewhat higher particularly for the uranous com- pounds than the " spin only " moment ; and also the A values where these are known are large and positive so that unless this constant is also measured the observed moments will really be too low. Moments of uranium tetrafluoride and dioxide are undoubtedly nearer the spin-only value but these are of course the most magnetically concentrated substances. The uranous sulphate and oxalate moments are in agreement with a 5f2 structure.The values for the Np*+ and U3+ ions are also lower than that calculated for three 5f electrons and L-S coupling ground state 419,2 namely 3.62 ; and here the spin-only formula gives a higher value of 3.87 whilst structures involving 6d electrons would give values much lower than those observed. The values for Pu3+ and Am3+ ions fall much below those of Sm3+ and Eu3+; but it will be This is also true of the Pu4+ ion. 88 C. A. Hutchison and N. Elliot. Php. Reviews 1948 73 1229. a@ N. Elliot &id. 1949 '76 431. $0 '' Theory of Electric and Magnetic Susceptibilities " Oxford 1932. LISTER CHEMISTRY OF THE TRANSURANIC ELEMENTS 43 remembered that Van Vleck and Frank in their calculation of the moments of latter ions had to assume that the multiplet intervals were comparable with kT so that states above the ground state are appreciably contribut- ing.The other moments are calculated assuming multiplet inteivals large compared with k17 this would lead to a value of 0434 for Sm3+ and 0.0 for Eu3+. Consequently the moment of Pu3+ agrees with a 5f5 structure (ground state 6H5,z) with wider multiplet spacing ; and the value for Am3+ is probably also best explained as a 5fs structure (ground state 'FO) with multiplet intervals somewhat wider than those of the europium ion; but detailed calculations have not yet been published. Thus the magnetic evidence taken as a whole undoubtedly supports the 5f structures for the transuranic compounds. The crystal structures of a number of series of analogous heavy-element compounds have been determined by X-ray diffraction and from these radii for the heavy-element ions have been deduced assuming values for the radii of the associated ions.21v 91 The series most fully investigated are the trifluorides trichlorides tribromides and dioxides.The radii (A.) so obtained are as follows 3+ ion . . Pu. Am. __ _-_____ M-0 distance in MO . . . La. Ce. Pr. Nd. - I sm. Ell. 1.04 1.02 1.00 0.99 - 1 0.98 0.97 l ipp -~~~~ Whilst these absolute radii depend on the values chosen for the radii of the halide ions their relative values are unambiguously determined by the X-ray data. It will be seen that a steady fall takes place with rising atomic number and this of course parallels the behaviour of the rare-earth compounds. Corresponding figures for the rare-earth 3+ ions using the same halide radii are In addition the cell dimensions have been found to show a similar contraction in other series of heavy-metal compounds such as NaM02( OAc), KM2Fs where M is the heavy element ; and indeed this contraction seems to be quite general.The cause of this phenomenon is no doubt the same as in the rare-earth group vix. that the ionic size is determined by the quantum numbers of the outermost electrons and by the effective nuclear charge (ie. the nuclear charge minus the screening effect of the other @1 W. H. Zachariasen MDDC 1572. D 44 QUARTERLY REVIEWS electrons) in which they are held. In the heavy-metal ions if we assume that their structure is similar to that of the rare-earth ions the outermost electrons are always in the completed 6p sub-shell and the effective nuclear charge rises with the atomic number since the screening effect of the extra electrons in the 5f shell does not entirely compensate for the increased nuclear charge.Hence this contraction is in fact evidence for the 5f theory of the structure of the heavy-metal compounds. It will also be seen that the contraction is somewhat more rapid in the heavy metals than in the rare earths which is at least consistent with the more rapid alteration of the oxidation-reduction potentials. The author thanks the Director Atomic Energy Research Establish- ment for permission to publish this review.

ISSN:0009-2681    

DOI:10.1039/QR9500400020

出版商:RSC    

年代:1950

数据来源: RSC

摘要:

BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS By P. MAITLAND M.B.E. B.Sc. PH.D. F.R.I.C. (UNIVERSITY LECTURER IN ORGANIC CHEMISTRY CAMBRIDGE) THE whole subject of the metabolic pathways adopted by living cells in the synthesis of their multitudinous and often exceedingly complex products is bound up with the most =cult and recondite problems in the fields of biochemistry and physiology. In every case most of the essential informa- tion and especially the final proof can come only from biochemical studies by the application of their typical techniques but the purely organic chemist has already made and can still make an important contribution. The distinctive methods used in the biochemical approach have been well described by M. Thomas 1 and involve the search for intermediate metabolites fixation of intermediates by chemical combination with added reagents differential inhibition or activation of enzymes and feeding and privative experiments.The introduction of isotopic tracers during the last few years has completely altered the whole picture and great advances have been made. There is no doubt also that if the special technique developed by T. Caspersson for identifying nucleic acids and proteins in the actual living cell by microspectrography could be extended to other simpler cell substances results of very great importance would follow. The organic approach has so far been confined mainly to the field of plant products and to the work of two authors. in England from 1917 to the present day has made outstanding contributions to the whole field and C. Schopf in Germany since 1932 to the alkaloid field in particular.Two distinct methods have been developed. The first method initiated during 1900-10 by some early ideas of Pictet Willstatter and Winterstein and Trier on alkaloids was widely elaborated and extended with impressive results by Robinson over the whole field. The method entails first a careful examination of the main architectural framework of the individual members of each class such as for example sugars fats anthocyanins steroids alkaloids ; then by dissecting the molecules and applying a wide knowledge of organic reactions and common cell metabolites the detection of a repeating feature which occurs intact in more than one form of combination and is so prominent that it justifies valid deduction as a building unit. The second method initiated by Robinson with his elegant synthesis of tropinone in 1917 and widely developed by Schopf in a striking and very successful R.Robinson ’‘ Plant Physiology ” 3rd Edn. J. & A. Churchill London 1947 pp. 213-219 ; for a review of the biochemical approach to the particular problem of alkaloid biogenesis see R. F. Dawson Adv. Enzymol. 1948 8 203. a Symposia of the Society for Experimental Biology I 1947 p. 127. a (a) J. 1917 111 762 ; (b) ibid. p. 876 ; (c) Madrid Lecture IX Congreso Inter- national de Qulmica Pura y Aplicada 1934 ; ( d ) J. 1936 1079 ; (e) J. Roy. SOC. Arts 1948 Q6 795. 4 (a) Angew. Chem. 1937 50 779 797 ; (b) FIAT Review of German Science 1939-1946 Preparative Organic Chemistry Part 11 p. 117. 45 46 QUARTERLY REVIEWS manner has come to be known as synthesis under physiological or cell-possible conditions.The starting materials used are reactive substances which are either known (or presumed) to be plant-cell intermediates ; the reactions are carried out in aqueous solution at room temperature the reagents used must be mild (Robinson) and the pH conditions especially must be carefully controlled (Schopf). From the biogenetic point of view the general methods of organic chemistry are much too drastic to be of assistance and there is no doubt that a broad development of this type of synthesis under physiological conditions would be of great value both for the contribution it would make to general synthetic methods and for the bearing it would have on problems of biogenesis. Although the biochemical approach will always be the more important the chemical approach is considered to be necessary since the two are complementary information gained from the one side suggesting new approaches from the other.The Review which follows has been confined to the one topic of the origin of the pyrrole pigments.* After a detailed account of the evidence which has accumulated from biochemical inTestigations on both plant and animal pyrrole pigments the chemical methods of synthesis are considered in juxtaposition in order to see whether any clues may be obtained from this side and finally the review is summarised and some conclusions are drawn and speculations made. General.-The basic skeleton of the pyrrole pigments is formed from four pyrrole nuclei joined together by four methene bridge carbon atoms as shown (I) to give a large inner ring of sixteen atoms.The molecule is flat and its great stability and aromatic character show that it must be stabilised by resonance. Only one of the many possible arrangements of the double bonds is shown in (I). The nomenclature in the series is in an unsatisfactory state.6 The parent substance (I) is called porphin but the derivatives are called either porphins or porphyrins. These derivatives are often found free in small amount in living material but when they are co-ordinated with a metal such as iron or magnesium and combined with a protein they become substances of outstanding physiological importance. Thus the chlorophylls the green colouring matters of plants are protein-magnesium dihydroporphyrins con- taining an extra ring; hmmoglobin the red pigment in blood cells is an iron porphyrin combined with the protein globin ; and the enzymes peroxi- dase catalase and the widely-occurring cytochromes are essentially of the same type as hmmoglobin.It should be noted that in all the naturally occurring porphyrin deriva- A. D. Mitchell “ British Chemical Nomenclature ” Ed. Arnold London 1948 pp. 124 131. * Since the present review was completed the problem has been discussed by R. Bentley (Ann. Reports 1948 45 253). There is some overlap in the references quoted but Bentley’s article was of much wider scope and his treatment of the present subject was necessarily much briefer. The problem has also been briefly considered by C. Rimington in “ Haemoglobin ” (Symposium) Butterworth’s Scientific Publica- tions London 1949 p. 241. MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 47 tives there are no ring-carbon atoms carrying hydrogens ; * all axe sub- stituted or involved in ring formation.The predominating side-chains found are CH, *CH:CH, *CH,*CH2*C0,H and less often *C,H, *CHO *CH,*CO,H the groups *CO*CH and *CH(SR)*GH (= vinyl + RSH) occur once only.6 One of the most widely distributed porphyrins is protoporphyrin 9 (IT) which contains methyl vinyl and propionic acid groups. Co-ordination of this porphyrin with iron gives hiemin the prosthetic group of htx?moglobin ; co-ordination with magnesium addition of two hydrogen atoms formation of an additional &membered ring with one of the propionic acid residues and esterification of one carboxylic acid group with methyl alcohol and the other with phytyl alcohol give one of the protein-free chlorophylls (111).The attack on the intricate problem of the biosynthetic origin of the pyrrole pigments has been in progress for a great many years. The end is not yet in sight but great advances have been made. The problem has been approached from both the plant- and the blood-pigment side with the latter greatly predominating. There is as yet no evidence that both the plant and the animal cells adopt the same mechanism for synthesising the porphyrin nucleus ; but to take one example only in view of the fact that 6 S. Granick and H. Gilder Adv. Enzymot. 1947 7 305. * Unless the ring is reduced &s in (111). 48 QUARTERLY REVIEWS the porphyrin-containing cytochromes have been shown by D. Keilin 7 to occur in such a very wide variety of living cells it would not be unreasonable to assume that the route employed is essentially the same.Information from the Plant Side.-The information from the plant side will be considered first. In 1915 and 1920 B. Odd0 and G. Pollaccis con- ducted experiments with seedlings which showed that chlorophyll formation could take place in the absence of iron salts but only if the nutrient media contained an assimilable pyrrole derivative. If no pyrrole deriva.tive was present iron was an indispensable element. The conclusion was therefore drawn that iron was concerned only in the formation of the pyrrole nucleus and that it played no further part in the synthesis of chlorophyll. This result has been questioned by other workers who while recognising that absence of iron always causes chlorophyll deficiency (chlorosis) do not agree that it can be cured by addition of pyrrole derivative^.^ Although Oddo’s results were confirmed by A.Lodoletti lo in 1938 the most recent work summarised by H. Burstrom,ll indicates that the whole problem of chlorosis is much more complex than was at first thought. Thus the ability of the plant cell to build up chlorophyll from a nutrient containing preformed pyrrole units is still an open question. In 1929 H. Emde l2 reviewed the constitution of hsmin which had just been synthesised by H. Fischer and K. Zeile,13 and considered the question of its biogenesis. Assuming the origin of the vinyl groups to be by loss of carbon dioxide from an acid Emde suggested that the main structure of hzmin could be dissected into four normal hexose chains and four triose chains thus requiring originally six hexose molecules.He suggested that the pyrrole nuclei arose by substitution of oxygen by nitrogen in original furan rings. It must be pointed out that on chemical grounds the latter suggestion is very improbable because the conversion of furan into pyrrole derivatives requires vigorous conditions. l 4 No further suggestions regarding the biosynthesis of chlorophyll were made until 1940 when the subject was reviewed by G. Mackinney.15 This author refers to the great difficulty of chlorophyll investigations owing to the ease with which chlorophyll can be formed in the leaf from colourless precursors and the speed with which it can disappear in dying leaves. He is of opinion that it is somewhat unimaginative to assume that proline (IV) hydroxyproline (V) or a pyrrole derivative is the probable precursor in the living leaf and mentions the very important fact that at no stage have the presence of dipyrrylmethenes (VI) or bilin (VII) pigments been detected in higher plants.1947 pp. 112 et seq. 7 See E. Baldwin “ Dynamic Aspects of Biochemistry ” Cambridge Univ. Press 8 Atti R. Accad. Lincei 1915 [v] 24 ii 37 ; Gazzetta 1920 50 i 54. 9 (a) G. Mackinney Ann. Rev. Biochem. 1940 9 470 ; ( b ) H. H. Strain ibid. 1944 10 Boll. Chim. farm. 1938 77 609 ; Chem. Abstr. 1939 33 7843. l1 Ann. Rev. Biochem. 1948 17 593. la Pharm. Acta Helvet. 1929 4 121. 14L. N. Owen Ann. Reports 1945 42 169. 13 598. lS Annalen 1929 488 114. l6 Ref. 9 (a), MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 49 In fact nothing is known either about the route taken in chlorophyll destruction or about the fragments resulting,ls so that no clue concerning the reverse process the biosynthesis has yet been obtained from this direction.No light on the biosynthesis of chlorophyll has resulted from the large number of investigations carried out on the supposed chlorophyll precursor known as protochlorophyll which has been isolated from plants grown in the dark. A description of the confusing results obtained has been given by E. I. Rabinowitch (1945) in his comprehensive book on photosynthesis,17 and the conclusion reached by this author after careful survey of all the evidence is that the whole problem of chlorophyll development in seedlings is greatly in need of further study. The most important chemical evidence is that of H.Fischer et aZ.,l* who in 1939 identified a product from proto- chlorophyll which supported the view that protochlorophyll itself was simply chlorophyll less the two hydrogen atoms on ring IV. If proto- H,C\ ,CH*CO,H H2CMCH- CozH NH NX N H0'HF-?H2 H C-Hz I 1 chlorophyll is the true precursor of chlorophyll the final stage produced by the action of light is therefore a reduction. This observation if correct would dispose of all theories based on the final reaction being an oxidation. Some evidence that this final stage is more than a simple photochemical transformation has recently been obtained by J. H. C. Smith.19 A different type of approach to the whole problem and one which takes us to what must be the final stages of the biosynthesis was started in 1948 by S.Granick.20 An X-ray-induced mutant of ChloreZZa was found to produce instead of the normal green cells brown cells which on extraction gave only protoporphyrin 9 (11). Thus the mutant appeared to have lost the power to complete the synthesis of the chlorophyll molecule (111). A mutant was also obtained which produced only magnesium proto- porphyrin 9 thus suggesting that introduction of magnesium is the next stage. This leaves the final stages of suitable oxidation reduction ring closure and esterification to be completed. Earlier S. Granick and 16 Confirmed also by K. Egle Bot. Arch. 1944 45 93. 17 " Photosynthesis " Interscience New York 1945 Vol. I pp. 404 431 445. 1* H. Fischer H. Mittenzwei and A. Oestreicher 2. physiob Chem. 1939 257 IV. 19 J . Amer. Chem. SOC. 1947 69 1492 ; Arch.Biochem. 1948 19 449 ; see also 2o J . Biol. Chem. 1948 172 717 ; 1948 175 333. V. M. Koski and J. H. C . Smith J . Amer. Chem. SOC. 1948 70 3558. 50 QUARTERLY REVIEWS H. Gilder 21 had shown that in the analogous case of the biological intro- duction of iron into a porphyrin the presence of the vinyl side-chain was essential. Information from the Bbod-pigment Side.-Work from the blood-pig- ment side was summarised in 1940 in two valuable reviews by K. Dobriner and C. P. Rhoads 22 and by W. J. Turner.23 In order to appreciate these contributions it will be necessary to mention first the reference substances the ztioporphyrins used by Hans Fischer in his outstanding investigations in this field.24 If a fully substituted porphyrin be built up with a methyl and an ethyl group in each ring only four combinations are theoretically possible.These are given below an abbreviated formula being used for simplicity. Et Me E t E t M e 7 T E k Me,? ?,Me Me/ \Et Me/ \Me EL\ I /Me M e b ' p e M e A a / M e Et\=/Et M e E t E t M e Me None of these aetioporphyrins (1-IV) occurs in Nature but all four were prepared synthetically by Fischer . Any porphyrin under investigation could then be converted by suitable methods into an ztioporphyrin and the type thus determined by comparison with the four standard Btiopor- phyrins of known constitution. The important discovery was made that all naturally occurring porphyrins are derived from atioporphyrins I or 111 the chlorophylls from type I11 only but the blood pigments from both types ; and the existence of these two types in Nature was referred to by Fischer as the dualism of the p~rphyrins.~~ Inspection of the two formula concerned reveals that I11 could be derived from I simply by the reversal of one pyrrole nucleus.The significance of this will be discussed later. The Theory of Dobriner and Rhoads.-Dobriner and Rhoads have put forward a theory to account for the formation in Nature of both type-I and type-I11 pigments as illustrated by coproporphyrin I and haemin.* They postulate the formation of the tetrapyrrole by the linking together through two carbon atoms of unspecified origin of two planar dipyrrylmethene building units A and B as shown in formuh on facing page. If two A's unite type-I porphyrins result (the discrepancy here will be J. &en. Physiot. 1946 30 1. 21 Physiol.Rev. 1940 20 416. a8 J . Lab. Clin. Z e d . 1940 26 323. H. Fischer and H. Orth " Die Chemie des Pyrrols " Akademische Verlagsgesell- schaft Leipzig 1934 1937 1940. * 6 Ref. 24 Band 11 1 507 ; the dualism of the blood hamins reported by H. Fischer 2. physiol. Chem. 1939 259 1 was later withdrawn by H. Fischer and C. G. Schrijder Annalen 1939 541 196; see C. Rimington Ann. Rev. Biochern. 1943 12 442. * A theory on the same general lines was suggested independently by C. Rimington but as it was published in relatively inaccessible journals and inadequately abstracted it is not generally known; see Onderstepoort J . Vet. Xci. Animal Ind. 1936 7 567; Compt. rend. Trau. Lab. Carlsberg Sir chim. 1938 22 454, MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 51 discussed later).For formation of coproporphyrin I on this theory the vinyl groups after linking up become *CH,*CH,*CO,H. If A unites with B a type-I11 porphyrin is formed ; and if two B’s unite a type41 compound results. The latter has not been found in Nature. The medical evidence obtained by studying normal and pakhological body conditions indicates that normally type-I11 porphyrin formation greatly predominates over that of type I and abnormally the reverse.Z8 It will be seen that this theory of Dobriner and Rhoads requiring as it does the final linking of two dipyrrylmethenes is based on Fischer’s successful synthetic methods which started from such units. It must be stressed that there is practically no experimental evidence for or against the theory. Me - 7 Y v ‘\I /Me Me I ”\ Me /Me V Me P Coproporphyrin I !Y V Ma V Me ___) m Me/ \V - - - - - - - - ---- Me\ /Me B Me\ P P /Me P P P P Me/ \Me II Me\ /Me P P Not found in nature V = CH:CH P = CH,*CH,*CO,H Only one claim has been made in connection with the isolation of a dipyrryl- methene from a natural This concerns the substance known as porphobilinogen which occurs in the urine of certain porphyria cases and is thought to be a mixture of two dipyrrylmethenecarboxylic acids.The evidence presented so far however is not sufhient to characterise the substance definitely. It has been obtained only in aqueous solution and the molecular weight of about 350 was found by a diffusion method. The colourless aqueous solution on storage or when boiled with hydrochloric acid gives probably two porphyrins one of which was identified through its methyl ester as uroporphyrin I11 (abbreviated formula below).Since 26D. L. Drabkin Ann. Rev. Biochem. 1942 11 532; see also ref. 33 and R.R.MeSwiney R.E.H. Nicholas and F. T. G. Prunty Biochem. J. 1949 44 xx. 27 J. Waldenstrorn and B. Vahlquist 2. phpiol. Cbm. 1939 260 189 ; eee also F. T. G. Prunty Biochern. J. 1945 39 446, 52 QUARTERLY REVIEWS uroporphyrin I11 requires a condensation of the A-B type porphobilinogen is thought to be a mixture of two methenes. The Theories of Turner.-The second review mentioned above by Turner,23 will now be discussed in detail as it is considered to be a very stimulating contribution to the main problem Turner commences his analysis by drawing attention to the fact that any complete theory of V Me Me/ \P p \ /Me Me V Protoporphyrin 2 ( Type 1) "\ /Me Me p Me Me\ /Me P P Protoporphyrin 9 ( Type m P Me Me/ \P Me\ dMe Coproporphyrin I Coproporphyrin P A P A A/ \P A / \P p\ /" A P "\ /A P P Uroporphyrin 1 Uroporphyrin m P= CH,-CH,*CO,H A = CH,* CO H V = CH:C H porphyrinogenesis in animals must explain the following experimental observations (a) the occurrence of the following porphyrins protopor- phyrins 2 and 9 coproporphyrins I and 111 uroporphyrins I and 111; ( b ) the normally great predominance of protoporphyrin 9 ; (c) the normal appearance of small and equal amounts of the two coproporphyrin isomers ; and (d) the extremely rare occurrence of the uroporphyrin isomers.Although the protoporphyrins are numbered 2 and 9 after Fischer to distinguish them from the numerous other isomers it will be seen that lika MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 53 the two coproporphyrins and the two uroporphyrins they are derived from the basic type aetioporphyrins I and 111.On careful examination of these six formuh Turner detects that they can all be built up by suitable choice from three primary units pyrroles 1 2 and 3. A P 8-/i NH Me P 0 NH Mi3 NH PyrroJe I Pyrrole 2 Pyrrole 3 A = CH;CO,H P=CV,*CH,*CO,H V = CHZCH It is obvious that pyrrole 2 could be derived from pyrrole 1 by decarboxylation of the acetic acid residue and pyrrole 3 from pyrrole 2 by dehydrogenation and decarboxylation. Although Turner states that these are well-known biological reactions he must be speaking generally because while the analogy of the well-known succinic + fumaric acid dehydrogenation would apply to the first stage biological decarboxyla- tion has so far only been demonstrated in the systems *CO-CO,H *CO*CH,*CO,H and *CH(NH,)*CO,H.On the other hand H. Kscher et d2* have stated that the few acetic pyrroles known are chemically unstable and lose carbon dioxide readily. Turner therefore puts forward pyrrole 1 as the primary building stone of the proto- copro- and uro-porphyrins. In order to show how these arise from pyrrole 1 he assumes the formation of a dipyrrylmethene through the usual aldehyde synthesis that is introduction of an aldehyde group into one pyrrole nizcleus and condensation with another in presence of acid to give the dipyrrylmethene normally isolated as a salt ; but A. H. Corwin et have shown that this type of synthesis is not so simple or straightforward as was at first thought but proceeds through the intermediate formation of a tripyrrylmethane which then undergoes fission a t points a or b as shown and when the units involved are dissimilar gives rise to several dipyrrylmethenes.In the case of pyrrole 1 only one nucleus is involved and according to Turner only two dipyrrylmethenes (a and b below) result. This statement however is correct only if certain assump- tions are made namely that in both the condensations necessary to give the tripyrrylmethane the linking takes place under the A (acetic acid) group and not under the P (propionic acid) group. Since pyrrole 1 itself has not yet been synthesised the preferred point of attachment is still in doubt. Support for the tripyrrylmethane mechanism operating in Nature comes from one source only-the isolation from Bacillus prodigiostcs by 28 H.Fischer and H.-J. Hofmann 2. physiol. Chem. 1937,246,23 ; H. Fischer and A. Muller ibid. p. 31 ; see also H. Fischer and E. Elhardt ibid. 1938-39 257 61 ; H. Fischer W. Neumann and J. Hirschbeck ibid. 1943 279 I . 29A. H. Corwin and J. S. Andrews J . Amer. Chem. SOC. 1936 58 1086; 1937 59 1973 ; J. Paden A. H. Corwin and W. A. Bailey ibid. 1940 62 418. 54 QUARTERLY REVIEWS F. Wrede et uZ.,~O of the red pigment prodigiosin which has been shown to be a tripyrrylmethene derivative. If tetrapyrroles are now made as shown by combining the planar dipyrrylmethene units a + a b + by a + b through two carbon atoms of unspecified origin uroporphyrins I 11 and I11 result. A = CHiC0,H a 9 c A P A P P A A P P = CH,*CH,*CO,H Uroporphyrin I Uroporphyrin a Uroporphyrin m By a similar process but using pyrrole 2 in place of pyrrole 1 Turner derives coproporphyrin I 11 and I11 (above formulz with Me replacing A throughout).For protoporphyrins 2 and 9 the initial units must be two of pyrrole 3 and one of pyrrole 2 and (again not stated by Turner) condensation under the Me groups must be assumed. In the case of the methyl pyrrole propionic 3O For refs. see ref. 24 Band 11 1 153 ; see also H. Fischer and W. Siedel FIAT Review of German Science 1939-46 Biochemistry Part I p. 116. 31 The purpose of the asterisk on the formulae is to aid identification of the particular type when compared with the four standard atioporphyrins. When turned round in the plane of paper on the marked group so that this group becomes the top left-hand corner Me of the mtioporphyrin comparison should be assisted.MAITLAND BIOCENETIG ORIGIN OF THE PYRROLE PIGMENTS 55 acid it is known that condensation does actually take place preferentially under the methy1,32 but for the methyl-vinyl derivatives no experimental evidence exists t o indicate how the condensation would proceed. V Me Me/ \p p\ Me /M8 V h + a ) Protoporphyrin 2 ( Type 1) Additional possibilities V Me* Me/ \p Me\ /p V Me ”\ /p Me Me p\ /” Me Me V Me Me/ \P ”\ / p *Me Me (a + 6) Protoporphyrin 9 ( Type III) Me p \ /” *Me Me The error mentioned in discussing Dobriner and Rhoads’s review and repeated by D. L. Drabkin,26 is also made by Turner. In none of these reviews is attention drawn to the fact that in the case of the combination sa A.H. Corwin Gilman’s “ Organic Chemistry ” John Wiley & Sons New York 1943 Vol. 11 1275. 56 QUARTERLY REVIEWS through two carbon atoms of unknown origin of two dipyrrylmethene mts containing unlike first and fourth groups a second porphyrin can result by reversal of one of the dipyrrylmethene units. Thus in the case of proto- porphyrin there are three additional possibilities-types IV 11 and I11 as shown-and in the case of uroporphyrin and coproporphyrin one additional possibility each-type IV-by reversal of one of the units in the a + a combination (see p. 55). To explain the normally great predominance of protoporphyrin 9 Turner supposes that this is due to the production of pyrrole 3 in excess for a reason unknown but perhaps because of its greater stability compared with the other two.The normal appearance of small and equal amounts of the two coproporphyrin isomers would require pyrrole 2 to be next in stability and the extremely rare occurrence of the uroporphyrin isomers would be caused by the normally great instability of pyrrole 1 an observation which receives experimental support as regards the *CH,*CO,H group from the chemical investigation by Fischer. 28 On examination of Turner’s contribution as a whole it is considered that within the limitations indicated it offers a very reasonable explanation of the experimental facts. It also has the great merit that it suggests new experimental approaches such as a further search for dipyrrylmethene intermediates and for types-I1 and -1V isomers and also biological investiga- tions using pyrroles 1 2 and 3 and dipyrrylmethenes preferably all marked isotopically in feeding experiments.* In the latest contribution from the medical side C.J. Watson and E. A. Larson,33 in a comprehensive review mainly of the urinary copro- porphyrins in health and disease state that the production of uroporphyrin I appears to be characteristic of the metabolic error known as porphyria but that the position of uroporphyrin I11 is less understood. On paper the interconversion of the uro- and copro-porphyrins appears to be simple involving as it does the gain or loss of two carbon dioxide molecules but there is no proof that these interconversions take place in the body. In spite of all the careful investigations which have been carried out the authors’ final conclusion is that the site mode of formation and physio- logical role of the coproporphyrins still remain in doubt.Recent work with Tracers.-Turning now to the consideration of the most recent work in the general field we find very important results achieved from 1945 onwards by the use of isotopic tracers. K. Bloch and D. Ritten- 33 Phgsiol. Rev. 1947 27 478. * Added in Proof. An impressive new theory of porphyrinogenesis has been put forward by R. Lemberg and J. W. Legge “ Hematin Compounds and Bile Pigments ” Interscience New York December 1949 pp. 632-645. It is postulated that from simple cell constituents such as a-ketoglutaric acid and ammonia a pyrrole precursor is given similar to that proposed by Turner containing acetic and propionic acid residues but with the significant addition of cr-carbon substituent.This unit is held to produce fwe dipyrrolic precursors only which give uroporphyrins I and 111 coproporphyrins I and 111 and protoporphyrin 9 (type 111). The non-occurrence of type-I1 porphyrins is accounted for and finally it is shown mathematically that the new theory can be used to predict correctly the ratio of the coproporphyrin isomerides I and 111 produced under various pathological conditions. MAITLAND BIOUENETIC ORIGIN OF THE PYRROLE PIGMENTS 67 berg 34 administered deuteroacetate orally to rats and found deuterium in the hBmin isolated from the blood. They drew attention to the possible significance of this in view of the known biological conversion of acetate into ,acetoacetate 35 and the well-known &orr synthesis of pyrroles from acetoacetic ester (and compounds of similar type) and ammonia.36 This was followed by some results of outstanding importance obtained by D.Shemin and D. Rittenberg.37 They fed a man and also rats with glycine labelled with 15N and proved that this glycine-nitrogen was the precursor of the nitrogen in the protoporphyrin of hamoglobin in the man and the rat. (The utilisation was later 38 proved to be very rapid in the case of man.) They also fed labelled glutamic acid (VIII) proline (IX) leucine (X) and ammonia (as ammonium citrate) to rats. The choice of H,C-CH - I J H27-fH2 OC\ ,CH.CO,H Ho2C /CH.C*2 N H N H2 c H I H,N * CH-C02H these particular substances was significant. Proline already possesses the pyrrole structure and glutamic acid can obtain it by dehydration and both of these substances have often been suggested as precursors ; leucine was chosen as a representative amino-acid which with its branched chain was most unlikely to take part in pyrrole ring formation; and ammonia was selected in case the nitrogen source was simply ammonia obtained by deamination of any amino-acid.The results were conclusive. The isotopic nitrogen of glycine appeared in such concentrations in the hmnin as to suggest direct utilisation of glyeine in the synthesis while all the other compounds gave concentrations of only one-thirteenth to one-Hth of the glycine value which supported an indirect route. Although this result J . Biol. Chem. 1945 159 45 (footnote) ; L. Ponticorvo D. Rittenberg and K. Bloch ibid. 1949 179 839. s6E. Stotz Adu. Enzymol. 1945 5 149. 86 A. A. Morton " The Chemistry of Heterocyclic Compounds " McGraw-Hill Book J .Biol. Chem. 1945 159 567 ; ibid. 1946 166 621 627 ; summarised by E. ssI. M. London D. Shemin R. West and D. Rittenberg J. Biol. Chem. 1949 Co. New York and London 1946 p. 57. Lederer Ann Rev. Biochem. 1948 17 496. 1'79 463. 58 QUARTERLY REVIE Ws only supports the direct use of the nitrogen of the glycine molecule Shemin and Rittenberg suggested that perhaps the two carbon atoms mere also involved. In support of this they drew attention to the purely chemical experiment reported by H. Fischer and E. Fink 39 in 1944. This consisted of mixing aqueous solutions of formylacetone (in the form of its sodium salt or its acetal) and glycine a t room temperature and pH 8 and after a short time obtaining a positive Ehrlich test for the presence of a pyrrole.It must be emphasised that the theory which follows is built up on the chemical side on this colour test alone for no solid was isolated and the work which was to be continued was interrupted by Fischer’s death. Since the Ehrlich test usually indicates a free a-position although some pyrroles with only a free /?-position respond to it,40 the condensation could have proceeded as shown (XI XII). Condensation with the formylacetone in the reverse position would give a pyrrole with both a-positions substituted. Fischer and Fink suggested that this type of mild condensation might be the method employed in Nature for the synthesis of pyrrole derivatives. Consideration of this work in conjunction with the results obtained with 16N and 1 with deuterium led Shemin and Rittenberg to suggest that the pyrrole nuclei in porphyrins might originate from the nitrogen and a-carbon atom of glycine and some carbon unit derived from acetate ; but since all naturally occurring metallic porphyrin derivatives contain completely substituted pyrrole rings the deuterohaemin in the first experiments must have the deuterium in the side chains or on the methene bridge carbons and therefore no real clue concerning the source of the remaining three carbon atoms of the ring can be obtained from deuterium experiments.Further work on blood obtained from human subjects suffering from sickle- cell anaemia on isolated duck’s and on dog’s blood 42 confirmed the synthesis of hzmin from glycine labelled with 16N. The discovery involving isolated duck’s blood is of special interest and importance since it provides a readily accessible biological system for further study in vitro.The next step was to test Shemin and Rittenberg’s theory that in addition to the nitrogen both carbon atoms of glycine were involved in haemin synthesis. The experiments to determine the position of the a-carbon were carried out by K. I. Altman et aE.43 who fed rats with glycine saZ. physiol. Chern. 1944 280 123. 41 D. Shemin I. M. London and D. Rittenberg J . BioZ. Chern. 1948,173 797 799. 43 M. Grinstein M. D. Kamen and G. V. Moore J . Lab. Clin. Med, 1948 33 1478. 43K. I. Altman G. W. Casarett R. E. Masters T. R. Noonan and K. Salomon Fed. Proc. 1948,7,2 ; J . BioZ. Chern. 1948,178,319 ; see also K. I. Altman K. Salomon T. R. Noonan ibid. 1949 177 489. 4 40 Ref. 24 Band I 66. MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 59 labelled on the methylene carbon atom and obtained results which indicated that this carbon atom was incorporated into hamin.The exact point is still to be determined by degradative experiments but it is reasonable from all the other evidence to suggest that it appears in the pyrrole nuclei. The fate of the carboxyl carbon atom of glycine was examined by M. Grinstein M. I). Kamen and C. V. Moore 44 by giving glycine labelled on the carboxyl- carbon atom to a dog and a rat and isolating crystalline protoporphyrin methyl ester and globin from the blood. Their results showed that the carboxyl carbon atom was not utilised in porphyrin formation but appeared in the globin. Thait glycine is incorporated into both types of substituted pyrrole found in protoporphyrin 9 (XIII) (namely the methyl-vinyl- and the methyl- propionic acid substituted nuclei) was then shown by J.Wittenberg and D. Shemin.45 Hi~min isolated from the blood of ducks and also from a man after they had been fed with 16N-labelled glycine was chemically Me I Me. I JT:H-oMe NH / MeO-CH Me I Y C H M ~ ~ ~ M ~ ( =..> Me i P Y - Me\ /Me Me\ P P /Me P P ( =.) (xms o ~ = ~ ~ NH V = CH:CH P = CH,. CH *CO,H treated to convert the vinyl groups into *CHMe*OMe thus giving hamatoporphyrin dimethyl ether (XIV) which was then oxidised. The 16N concentrations found in the porphyrin and the resulting two malein- imides (XV and XVI) were all equal thus proving that glycine was the precursor for both types of pyrroles. Although it is not mentioned by Wittenberg and Shemin this result would seem to support the view of Turner described above that the pyrrole building units originate &om a common pyrrole precursor.The most recent work with 16N-glycine on a human mbject 46 suggests that coproporphyrin 1 uroporphyrin 1 proto- porphyrin 9 from hamin and stercobilin (an open-chain tetrapyrrole) all derive from a common pyrrole precursor. Since the work of Escher and Fink described above on a mild method 44 J . Biol. Chem. 1948 174 767 ; 1949 179 359. 461bid. 1949 178 47; the same conclusion was reached independently by H. M. Muir and A. Neuberger using a similar isolation procedure ; Biochem. J. 1948 43 lx; 1949 45 163. 46M. Grinstein R. A. Aldrich V. Hawkinson and C. J. Watson J. Biol. Chem. 1949 179 984; see also C. H. Gray and A. Neuberger Biochem.J. 1949 44 xlv. E 60 QUARTERLY REVIEWS of forming the pyrrole nucleus two further contributions have been made. M. Errera and J. P. Greenstein 47 examined the effect of pH on the ultra- violet absorption of pyruvoylglycine. At pH < 10 two characteristic maxima were obtained but these disappeared irreversibly at pH > 10. From this evidence and from the fact that the ionisation constant of the crude material obtained was similar to that of the known pyrrolidone- carboxylic acid the authors tentatively suggest that a pyrrolidone derivative (XVII) is formed from pyruvoylglycine at pH > 10. A. M. Kuzin and A. R. G~seva,~* from the condensation of glycine and pyruvic acid a t pH 5-6 have isolated as a calcium salt a compound thought to be the pyrrolidine derivative (XVIII) containing only the glycine-nitrogen in the ring but the evidence produced so far is anything but conclusive.?O*NH*CH; CO,H &O*NH*CH; C0,H (=I The Contribution of Granick and Gilder.-In 1947 a very valuable contribution to the whole subject was made in a review by S. Granick and H. Gilder.6 This review forms a very comprehensive background to the whole question of the biosynthesis for it deals with the distribution struc- ture and function of the naturally occurring tetrapyrroles (porphyrins) the functions of the porphyrin side-chains porphyrin synthesis decomposition of the porphyrins and iron porphyrins and the physical properties of the tetrapyrroles. The section on porphyrin synthesis is very brief and refers simply to the reviews by Dobriner and Rhoads and by Turner already discussed above but one point of interest is made.They draw attention to the fact that the reduced ring IV in chlorophyll and baeteriochlorophyll is usually thought of as having arisen by addition of two hydrogen atoms to the pyrrole ring IV; but they suggest that in fact the pyrrole rings in porphyriils might originate from dihydro- or even tetrahydro-pyrroles by oxidation. In this connection the recent demonstration by C. Schopf 49 of the great reactivity of the CN=N linking in the dihydropyridine ring of some compounds in tetrahydropyridine itself (Al-piperideine) and in the *? Arch. Biockern. 1947 14 477 ; 15 445 ; J . Nal. Cancer Inst. 1947 8 39. 48 Biochimia 1948 13 27. dB FIAT Review of German Science 1939-46 Preparative Organic Chemistry Part 11 p. 117 ; see also E.Herzog Chimia 1948 2 206. MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 61 newly isolated but insufficiently characterised Al-pyrroline may be of importance in the linking of the pyrrole units in the a-position to give the porphyrins although so far the reactions studied with Al-pyrroline involve the addition of a further ring across the CH=N linking embracing the nitrogen a,s well as the a-carbon atom.490 Robinson’s Theory.-Robinson has applied his method (cf. p. 45) to the problem of the pyrrole pigments.60 To simplify the discussion he deals with Fischer’s four standard etioporphyrin types (I-IV) b a a / I \b \a a> \b \ C l b\ /a a\”/“ “\m/a b\=/b a b b b b b a a The methyl and ethyl groups or their equivalents are represented by a and b. The problem is to find an explanation of the occurrence of the natural pigments in two types only I and 111 instead of the four theoretically possible.Robinson refers to Fischer’s surprising discovery of the “ dual- ism” of the natural porphyrins in which the two types produced are so closely similar except for the reversal of one pyrrole nucleus. As already mentioned Robinson’s approach is to search for an intact unit which occurs linked in more than one way. If this can be detected it is a very strong argument that the whole unit itself’ is used in the biosynthesis. In the above case the complete reversal of a pyrrole nucleus identifies it immedi- ately as a structural unit. On this evidence a reasonable dissection of the porphyrin molecule is into four pyrrole nuclei joined by four carbon atoms of unknown origin.In the condensations necessary to build up the ring the linkings C-ab and C-ba will not be accomplished with equal ease. Robinson selects the union C-clb as the favoured combination although the argument would apply equally well to C-ba. The four types could then result as shown below. It will be seen that the exact stage at which the C atoms are added is very important and where necessary each C atom is therefore numbered to indicate this sequence. Starting with four preformed C-ct-b units condensation can only lead to the formation of type I. Starting with two b-a-G-a-b units formation of type I1 only is possible. Regular cyclic condensation starting with four a-b units and four C atoms with the stipulation of preferred condensation of C under a whenever possible gives type 111.Less regular cyclic condensation starting as in type 111 but adding the last unit to the starting end and then completing the ring with the fourth C gives type IV. **O Cf. E. b e t G. K. Hughes and E. Ritchie Nature 1949 163 289 and 164 501 who have shown that the open-chain 3-methylaminobutyraldehyde and also 4-amino- and 4-methylamino-valeraldehyde condense with acetoacetic acid or acetone- dicarboxy lic acid at mild pH to give na turally-occurring 2-substituted pyrrolidine and piperidine compounds. so Ref. 3 (e) p. 799. 62 QUARTERLY REVIEWS The important conclusion reached by Robinson is that the formation of type I would result from the presence of an excess of the preformed unit C-a-b while in the absence of such an excess regular cyclic condensation of the independent units a-b and C as indicated would give type 111.Two b-a- C - a - b And two c Four a - b and four c I 2 3 b-ya- C-a-b- C-a-b-C-aTb *__.- -. .-.c.--*- -. -- Four ff-b and four c I 2 b-a-C-a-b-C-a-b 3 4 Chemical Methods of Synthesis.-The chemicd methods of synthesis of the porphyrin ring system will now be considered in order to see whether they can throw any light on the mode of biosynthesis. During evolution and development of these syntheses this biochemical aspect appears not to have received attention and purely chemical considerations have pre- MAITLAND BIOGENETIC ORIGIN OF THE PYRROLE PIGMENTS 63 vailed throughout. The methods employed have been discussed fully by Fischer and Orth in their b00k,5l and the most widely used procedures have been summarised by Morton.52 They consist essentially of joining two suitably substituted dipyrrylmethanes or the unsaturated dipyrrylmethenes (as salts) under drastic conditions such as treatment with concentrated sulphuric acid or boiling formic acid or heating with a reducing organic acid melt at 180-190".One example illustrates the method (XIX -+ XX). E t \ /Me Me E t These unusual synthetic methods which have yielded such fruitful and far-reaching results in the porphyrin field were discovered quite accidentally by Fischer when he was trying to proceed from one dipyrrylmethene (or methane) to another. With different substituents filling the vacant posi- tions in the pyrrole nuclei and in the vigorous conditions of the condensa- tions many isomers result and the yields are normally poor ; it was only by prodigious efforts that Fischer and his collaborators were able to isolate pure products at all.Fischer discovered a milder method for performing this type of con- densation but used it only occasionally. This consisted of dissolving a dipyrrylmethane in 90% formic acid and a t room temperature or 40" drawing air through the solution for several days.53 The condensation of one dipyrrylmethane with two Eree a-positions with another dipyrrylmethane containing two aldehyde groups a synthesis which at first sight would appear to offer the advantage of milder reaction conditions was tried once by Fischer 54 with little success and does not seem to have been pursued further. The preparation of a porphyrin by step-wise addition of each pyrrole nucleus and final closure of the resulting linear tetrapyrrole has many attractions from the constitutional point of view.Fischer although he made several of these linear tetrapyrr~les,~~ appears not to have examined this route but A. If. Corwin and S. R. B u c ~ ~ after some preliminary experi- ments have been able to delimit the conditions necessary for success. The synthesis of porphyrins starting with a single-nucleus pyrrole derivative was used by Fischer only on rare occasions owing to its obvious 61Ref. 24 Band 11 1 pp. 160-173. 53 H Fischer and H. Andersag Annulen 1926 450 217 ; H. Fischer P. Halbig 64 H. Fischer and P. Halbig ibid. 1926 447 128. 65 Ref. 24 Band 11 1 p. 619. 69 Ref. 36 p. 86. and €3. Walach ibid. 1927 452 284. seJ. Amy. Ohm. Sm. 1944 $6 1161. 64 QUARTERLY REVIEWS limitation to the simplest symmetrical compo~nds.~~ With a pure synthetic pyrrole derivative treatment with formic acid at 100" gave no porphyrin and heating in a sealed tube to 160" was necessary.This was explained by postulating that a source of hydrogen was necessary and that this hydrogen was obtained at the higher temperature by decomposition of the formic acid. By direct addition of a hydrogen donor such as formaldehyde to the formic acid the porphyrin was obtained at 100". The simple pyrrole derivatives isolated by degradation of porphyrins usually contained impurities which acted as hydrogen donors and the porphyrin reaction with derivatives of such origin proceeded at Other conditions used were treatment of a pyrrole with glyoxal tetramethyl acetal and concentrated hydrochloric acid at loo" or with di(chloromethy1) ether in ethereal solution a t room temperature.59 The most recent synthesis of this single-nucleus type was discovered by W. Siedel and F. Winkler 6o while examining the properties of the pyrrole derivative (XXII) prepared by oxidation of (XXI) with lead tetra-acetate. A mixture of stioporphyrins I and 11 probably formed through their reduced (porphyrinogen) forms was obtained from this single-nucleus carbinol by heating it alone at 160-170" (49% yield) by boiling its solution in methyl-alcoholic hydrobromic acid in a stream of air (36.4% yield) or simply by setting it aside in methyl alcohol alone for several days exposed to air (yield less than above). The last method in particular is very sur- prising and demonstrates the great tendency for the large stable 16-mem- bered porphyrin ring to be formed.This tendency is connected with the 67 Ref. 24 Band 11 1 p. 165. 6* H. Fischer E. Sturm and H. Friedrich Annalen 1928 461 247 ; H. Fischer and 6* Ref. 24 Band 11 1 192. A. Treibs ibid. 1926 450 144. 6o Annakn 1943 554 165 186. MAITLAND BIOaENETIC ORIGIN OF THE PYRROLE PIUMENTS 65 presence of substituent groups in the /?-positions. Removal of one or both substituents produced a carbinol-acid which gave no porphyrin even when heated with reagents in a sealed tube. An entirely new method of joining two dipyrrylmethenes together to give the open-chain bilin derivative (XXIII) in 60-66y0 yield has been described by W. Siedel and E. Grams.61 The reagent was lead tetra- acetate and the conditions were very slow addition of the oxidising agent in the cold to the substance dissolved in acetic acid followed by a final warming on the water-bath.It is possible that this method could be extended to the preparation of a porphyrin by oxidising a dipyrrylmethene or even a single nucleus pyrrole containing two or-methyl groups. This oxidation would probably require a reagent other than lead tetra-acetate which with some porphyrins has already been shown by Pischer 62 to give xanthopor- phinogens (porphyrins + 4 oxygen atoms of unknown constitution) and would have more force if it succeeded with a biological oxidising agent. R R R R R R R R R R R k ( =.) [ m.1 The parent substance of the porphyrins porphin (XXIV ; R = H) and symmetrical porphins containing substituents on the methene-bridge carbon atoms only (XXIV ; R = alkyl or aryl) were made by P.Rothemund 6a by treating various aldehydes with pyrrole itself in presence of basic cata- lysts; but although over 25 aldehydes are stated to have given porphins (presumably identified spectroscopically) experimental details and analysis have been given only for porphin itself and for tetraphenylporphin and for their metallic salts [together with some evidence for the existence of " iso- porphins " which are very probably dihydroporphins (chlorins) J .64 Thus pyrrole with formaldehyde in methyl alcohol in presence of pyridine in a sealed tube a t 90--95" gave in 30 hours porphin in O.lyo yield. Rothemund states that these condensations proceed at room temperature during several weeks but no details are given and in the latest preparation of the deep-blue crystalline tetraphenylporphin obtained in about 10% yield 2.physiol. Chem. 1940 267 49. J . Amer. Chem. SOC. 1935 57 2010 ; 1936 58 625 ; 1939 61 2912 ; P. Rothe- mund and A. R. Menotti ibid. 1941 63 267 ; 1948 70 1808. 64 S. Aronoff and M. Calvin J . Org. Chem. 1943 8 205 ; M. Calvin R. H. Ball S . Aronoff J . Amer. Chem. SOC. 1943 65 2259; R. H. Ball G;. D. Dorough and M. Calvin ibid. 1946 88 2278. 62 Ref. 24 Band 11 2 p. 423. 66 QUARTERLY REVIEWS from bemaldehyde and pyrrole in presence of pyridine the conditions involved heating in a sealed tube for 48 hours at 220". Porphin itself was also synthesised by H. Fischer and W. Gleim 65 in about 0.1 yo yield contemporaneously with Rothemund but the method used by them was to heat pyrrole-2-aldehyde in alcohol and formic acid for 36 hours.Brief consideration will now be given to the properties and conditions necessary for the formation of the partially reduced porphyrins known as porphyrinogens (porphinogens) (XXV). Fischer prepared some of these (XXV; R = H and ring positions substituted) by mild reduction of the corresponding porphyrins 66 and showed that they were colourless crystal- line substances which when impure were re-oxidised in air quantitatively in one day to the original porphyrin but when pure were stable in air for several weeks. A. Vannotti 67 has summarised the few experimentally observed colour changes which have suggested the natural formation in certain body conditions of porphyrins through the porphyrinogen forms. In the new synthesis of ztioporphyrins I and I1 mentioned above,60 Siedel and Winkler postulated the mixed aetioporphyrinogens as intermediates in the condensation and after shorter treatment of the pyrrylcarbinol with boiling methyl-alcoholic hydrobromic acid actually isolated crystalline porphyrinogens.On long storage in air the colourless crystals gradually gave the mixed porphyrins. Several stable porphyrinogens (XXV ; R = alkyl) with fully substituted methylene-bridge carbon atoms have been made by condensing some aliphatic ketones with pyrrole.68 For example when acetone and pyrrole in alcohol are warmed with a trace of concentrated hydrochloric acid a vigorous reaction takes place and the colourless crystal- line octamethylporphyrinogen is soon deposited in good yield. A small yield was also obtained G9 from a homogeneous solution of pyrrole excess of acetone and water in presence of a trace of hydrochloric acid added at room temperature.The solution became warm (to 37") during the reaction. Porphyrinogens with two aryl groups on the methylene bridges or with only one hydrogen on the bridges substituted by any type of group are unknown. These colourless porphyrinogens are of fundamentally different character from the coloured porphyrins. Those containing unsubstituted methylene bridges are unstable and this must be caused primarily by the impossibility of resonance between the p-yrrole nuclei. Stability can be achieved either by loss of hydrogen to give the corresponding porphyrins or by substitution of all the methylene hydrogen atoms by alkyl groups. Summary Conclusions and Some Speculations.-With so much chloro- phyll being synthesised and degraded every year in re'adily accessible leaves of all types it seems strange that no clue at all to the biosynthesis of the main structure itself has yet been obtained from this source.By the application of the newer and more delicate techniques of chromatography $6 Annalen 1935 521 157. 67 " Porphyrin und Porphyrinkrankheiten," Springer Berlin 1937 p. 20. 68Ref. 24 B&nd I pp. 393-395. 69 V. V. Tschelincev and B. V. Tronov J . Russian Phys. Chem. Soc. 1916 48 105. 66Ref. 24 Band 11 2 p. 420. MAITLAND BIOUENETIC ORIGIN OF THE PYRROLE PIGMENTS 67 and partition chromatography and by further development of tracer experi- ments with plants it is probable that the great difficulties encountered from this side will soon be overcome. The success so far achieved regarding the final stages of the chlorophyll biosyntheses by the method of approach using X-ray induced mutants of plant cells is encouraging and valuable advances may be obtained by extension of this method.The experimental observations from the medical side are being added to rapidly. The theory of the formation of the porphyrin ring by condensa- tion of dipyrrylmethene units is an ingenious interpretation of the experi- mental facts. Its weakness lies in the fact that many more types could result than are actually observed although this could be explained by enzymic direction along the correct channels. The work with tracers has only just begun and the results of outstanding importance already obtained with glycine augur well for the future develop- ment of this fundamental method.Several lines of investigation have converged to indicate that the four pyrrole nuclei are all derived from a common pyrrole precursor and therefore that in the biosynthesis they are added as complete units. With regard to the chemical methods of synthesis of the porphyrin skeleton the general impression obtained is one of very drastic typically organic methods relieved by glimpses of very mild methods which might well have biological importance. The great tendency for the large ring to be formed from a well-substituted reactive single nucleus pyrrole simply by storage in a solvent with access to air and the joining together of two dipyrrylmethene molecules admittedly only at one end so far by oxidation of the two a-methyl groups may be of great significance biologically.The formation of the final aromatic ring system via the partly reduced por- phyrinogen forms is quite possible since these forms are chemically unstable and change into the stable aromatic form even on storage in air. In connection with the possible formation by way of the completely reduced system there is no evidence here to act as a guide since such a substance has not yet been prepared. Preliminary condensation of partly reduced pyrrole units such as the reactive Al-pyrrolines to form the large 16-membered ring with later aromatisation should also receive consideration. With regard to the side-chains it would be unlikely from a chemical standpoint for these to be added after completion of the main skeleton. No suggestion appears yet to have been entertained that the final ring system is formed by the collapse of a 20-membered ring containing 8 CO groups suitably placed for conversion into pyrrole rings by treatment with ammonia on the lines of the well-known synthesis of 2 5-dimethylpyrrole from acetonylacetone.On the present evidence such a route is unlikely. The final picture which emerges from all the evidence is of a common preformed pyrrole precursor for all the rings built up from the glycine- nitrogen and probably the %-carbon atom the side-chains in the two @-positions being possibly *CH2*C02H and *CH,*CH,*CO,H ; this pyrrole derivative then condenses with adjustment of the side chains at some stage, 68 QUARTERLY REVIEWS by means of four carbon atoms whose origin is yet to be discovered,* in a manner which leads on the chlorophyll side to a type-I11 protoporphyrin with subsequent formation of the additional ring and on the blood-pigment side to both type-I and type-I11 pigments. Thus although there are many important gaps to be filled the successes achieved up to the present offer much encouragement for the prosecution of further studies and the final solution of the problem seems to be approaching within reach. * Possibly the methylene carbon atom of glycine. See H. 35. Muir and A. Neuberger Biochem. J. 1949 45 xxxiv.

ISSN:0009-2681    

DOI:10.1039/QR9500400045

出版商:RSC    

年代:1950

数据来源: RSC

摘要:

THE REDUCTION OF ORGANIC COMPOUNDS BY METAL-AMMONIA SOLUTIONS By ARTHUR J. BIRCH M.Sc. D.PHIL. (SMITHSON RESEARCH FELLOW OF THE ROYAL SOCIETY CAMBRIDGE) Introduction THE aims of this Review are to present a picture of the process of reduction especially as observed in metal-ammonia solutions and to survey some of the advantages and limitations of these reagents in synthesis and degrada- tion. Several excellent reviews 1 exist of various aspects of metal-ammonia solutions but they are chiefly concerned with reactions rather than with mechanisms. The theory of the process of reduction itself is very well set out by L. Michaelis and M. P. Schubert.2 In the present Review no attempt is made to present a complete literature summary ; work is included which has a pertinent bearing on the more fundamental aspects of the subject.Other reduction processes are mentioned where it is considered necessary for an understanding of reaction mechanisms. It is hoped to state the problems raised by the subject if not always to solve them in detail. To make the following sections comprehensible it is necessary first to consider briefly the most probable mechanism of reduction by chemical agents. The essential step is the addition of one electron to a molecule to give an anion-radical or an anion and a radical or of two electrons to give a di-anion or two anions. The charged molecules are associated with positive ions usually derived from a metal supplying the electrons so ionised salts may be considered to act as intermediates. Sometimes these salts even of anion-radicals (e.g. ketyls) can be isolated as stable com- pounds; in other cases they may exist only momentarily as part of a transition complex.In the following sections the reductions are usually represented in terms of the ions rather than the un-ionised salts which may be in equilibrium with them because the ions are the active agents and because there is considerable uncertainty with some of the mesomeric systems as to where the cations are attached. The cation in most cases mentioned here is that of sodium. Two types of reaction may be distinguished * the fission of a molecule X-Y+e-+X*+Y-orX-Y+2e-+X-+Y-; andtheopeningofa multiple bond X=Y + e -+ X-Y X-Y or X=Y + 2e -+ X-Y. These both involve the breaking of a bond (albeit of different types) and the production of charged centres so they can be treated on similar lines.The See e.g. C. A. Kraus Chem. Reviews 1931 8 251 ; C. B. Wooster ibid. 1932 11 1 ; W. C. Fernelius and G. W. Watt ibid. 1937,20,216 ; B. K. and K. N. Campbell ibid. 1942 31 78. Frequent reviews also appear in the J . Chem. Educ. e.g. G. W. Watt and W. B. Leslie 1941 18 210. - - * - - * Y Chem. Reviews 1938 22 437. *An asterisk is used to denote the odd electron in a free radical. 69 70 QUARTERLY REVIEWS fission type is somewhat simpler because the fragments are free to move apart and can usually be examined separately. It is important to distinguish between one-electron and two-electron addition as the rate-determining step. Often the uptake of the first electron is the potential-determining stage although. a second electron is then taken up and the products are those derived from the anion rather than from the radical.The polarographic reduction of polycyclic hydrocarbons shows this ~learly.~ This mechanism is very common because the radical initially formed is usually more readily reduced than the starting material and is reduced before it can undergo other reactions e.g. dimerisation. In some cases it seems that the initial stage demands the addition of two electrons at once. Section I is chiefly con- cerned with a discussion of such problems. Section XI treats the subsequent stages of the process the reactions of the charged centres. Protons may be added e.g. Ph*CH=CH*Ph-+ This is not always easy. Td?x? Ph*eH-GH*Ph -+ Ph*CH,*CH,*Ph ; * CH&H*CH,*OH -+ CH2-CH-CH -+ CH,*CHSH ; an anion-radical may dimerise with the addition of protons 2Ph2C=0 -+ 2PhC-0 -+ Ph2C(OH)*CPh,(OH),B or a radical may dimerise as in the Ullmann reaction 2PhBr (+ 2Cu) -+ 2Ph* -+ Ph-Ph.Much the same dimeric products can however result from a purely ionic mechanism through the action of an anion on the starting material e.g. Ph,C=CH + 2e -+ Ph2C-CH (+ Ph2C-rCH2) + Ph26*CE12*CH2*GPh2 -+ Ph,CH*CH,*CH,*CHPh,. It is important if possible to distinguish between radical and ionic processes but the controversy between W. Schlenk and E. Bergmann 4.8 on one hand and I(. Ziegler and his co-workers 7 s 9 on the other illustrates some of the difliculties. Purely chemical methods alone are usually inconclusive.3 Polymeric materials are sometimes obtained by repetition of the addition of ions to the starting material and there is good evidence lo that in the production of Buna rubber ions not radicals are involved.The processes are often carried out at the surface of a metal dissolving with evolution of hydrogen gas in an excess of an " acid " (including in that tern solvents like alcohol or even ammonia) or at the surface of an electrode in a similar solution. H. Burton and C. K. Ingold l1 have postulated that the primary reaction under such conditions is the polarisation of the molecule # - - - The investigation of mechanisms for many reductions is not easy 3 S . Wawzonek and H. A. Laitinen J . Amer. Chem. Soc. 1942 64 1767 2365 ; 4 W. Schlenk and E. Bergmann Annalen 1928 463 114. 6E. Chablay Ann. Chim. 1917 8 145. 6W. E. Bachrnann J . Amer. Chem. Xoc. 1930 52 2823. 7 K. Ziegler and 0. Schiifer Anden 1930 479 160.*K. Ziegler H. Colonius and 0. Schiifer {bid. 1929 473 36. 10 W. Kern FIAT Review Preparative Organic Chemistry Part 111 1948 179. l1 J. 1929 2022. S . Wawzonek and J. W. Fan ibid. 1946 68 2541. Ibid. p. 78. BIRCH THE REDUCTION OF ORQANIC COMPOUNDS 71 at the surface and the addition of a proton followed by two electrons ; e.g. C=C-C=C -+ C-C-C-C--H -+ C-G-C-C-H. This sequence of events seems unlikely in any but a fairly strongly acid solution,12 but as will be seen later the theory now outlined gives rise to the same kind of intermediate by a slightly different route. Many reactions can be carried out in homogeneous solution in liquid ammonia because it dissolves many organic compounds and most of the alkali and alkaline-earth metals. A theory of the constitution of such metal-ammonia solutions has been put forward e1~ewhere.l~ Because of the low acidity of ammonia (pK about 34) 1* intermediate organo-metallic salts are often stable enough to be examined particularly at the low tem- peratures used (ammonia b.p.- 33" m.p. - SO"). The availability of protons can be regulated by the addition of " acids " like alcohols or ammonium salts. Furthermore the dipolar and associated character of ammonia makes it a very favourable solvent for the production of salts of very weak acids whether these are derived from the acids by the action of bases or in the course of reduction reactions. The differences between ammonia and other solvents are usually differences in degree due to the differences in solvation energies of ions rather than differences in kind.16 For example the same dihydroanisoles are obtained from anisoles either with potassium and ethanol or with sodium and ethanol in ammonia although much more readily with the latter reagent.One divergence in the course of reduction has been observed by D. B. Clayson,l* which must be due to a difference in the primary reduction stage - + H+ - 2e - I. Electron-addition Stage Fission Reactions.-The reductive fission of unsaturaited ethers or alcohols is possible where one charge is stabilised by the wnsaturation and the other by the electron-affinity of the oxygen e.g. Ph-0-Ph-+ -X?-z? Ph- + PhO- ; l7 Com- pounds producing very stable anions e.g. C1- are reduced more readily,ls but the effects of altered substitution on reaction rates are not so easiry observed for that very reason. More side-reactions also occur owing to the CH&H*CH,*OH -+ CHs-CH-CH2 + OH-.5 -* la J.W. Baker W. C. Davies and M. L. Hemming J. 1940 692. lsA. J. Birch and D. K. C. MacDonald Oscford Science 1948 2 1. lP S. Makishima J. Pac. Eng. Tokyo Imp. Univ. 1938 21 No. 3 116. 16A. J. Birch Nature 1946 158 686. 18 J. 1949 2016. 17P. Shorygin and S. A. Skoblinskayra Compt. rend. A d . Sci. U.R.S.S. 1937 14 606. P. M. Dean and a. Berchet J. Amer. Chem. Soc. 1930 52 2823. 72 QUARTERLY REVIEWS attack of the carbon-anion on the starting material for example in the Wurtz-Fittig reaction. In order to distinguish between the production of radicals and anions in the rate-determining stage it is necessary to study the effect on reaction rates of altering the substitution of the system being reduced.It is not sufficient merely to study the products which may correspond to the forma- tion of anions merely because the primarily formed radicals are more easily reduced than the starting material. With readily reduced substances anions or radicals may be detectable according to the relative concentration of reducing agent and substance; it is clear that in such cases the rate- determining step is radical formation. An example is the reduction of esters with sodium in liquid ammonia.19 With one atomic proportion of sodium the ester R*C02R' produces 8 high proportion of the diketone R*CO*CO*R. With two atomic proportions the ketol R*CO*CH(OH)*R is formed together with the aldehyde RGHO in some cases e.g. R = CMe or Ph. The aldehyde is formed through the sodium derivative R*C(Na)=O because the action of an alkyl halide on the solution leads to the alkyl ketone e.g.Ph*CO,Et -+ Ph-C(Na)=O -+ Ph*COEt. The evidence favours the occurrence of the reactions a R*C=O 2R*CO,Et + 2Na -+ 2R*8=O + 2NaOEt $ I R*C==O + 2NaOEt 2R*CHO y,. 12.. &. 2R*C(Na)=O + R*C--ONa NH R-C-OH 2R*COEt R*C--OX'a c R*C-OH + 2NaNH 4 li 7- It / /2EtBr The reversibility of a b and c was demonstrated by acting on the ketol or diketone with sodium ethoxide and sodium amide in ammonia. Alterations in reaction rate caused by alterations in substitution can be qualitatively predicted by considering the energies of formation of anions and radicals in similar systems. From acidity measurements,20 it is clear that a negative charge requires an increasing energy of formation as hydrogen atoms are successively replaced by electron-repelling groups like alkyl or methoxyl.Evidence for radicals is more scanty but indicates that almost any type of substituent in place of hydrogen stabilises the amphoteric unpaired electron.21 Therefore if the rate of reduction in a fission reaction is decreased by increasing the degree of alkylation of the system upon which the charge resides then the potential-determining stage involves anions provided that in the transition state the two fragments can be treated separately. This last assumption would appear to be justified when one fragment (e.g. OH C1) has a much higher electron-affinity than the other. l9M. S. Kharasch E. Sternfeld and F. R. Mayo J . Org. Chem. 1940 5 362. zoA. J. Birch Paraday SOC. Discussion 1947 2 246. 21 H. S. Taylor and J. 0.Smith J . Chem. Physics 1940 8 543 ; A. J. Birch Faraday Xoc. Discussion 1947 2 262; M. S. Kharasch H. C . McBay and W. H. Urry J . Amer. Chem. SOC. 1948 70 1269; C. E. H. Bawn J. 1949 1042. BIRCH THE REDUCTION OF ORaANIC COMPOUNDS 73 On this basis the reactions of the alcohols and ethers to be considered below involve the addition of two electrons as the primary process. Another fact in favour of this assumption is that dimeric products are not detectable. The production of dimeric products is not an argument in favour of radical-intermediates because sufficiently reactive anions can attack the starting material but its absence is somewhat better evidence against the formation of radicals. The eqerimental methods so far employed to test the effects of sub- stitution in this series have been comparative rather than absolute.Such methods provide quickly a mass of data from which a general picture can be built up but direct measurements of velocities and of reduction potentials by polarographic methods will be necessary before quantitative calculations can be made. Quantitative measurements have hardly begun although it is already clear that polarographic methods can be used in ammonia and that the homogeneity of many reacting systems in ammonia obviates the difficulties encountered in measuring velocities in poly-phase systems. Comparison has been made of the extent of reduction of compounds in a series compared with a standard competing reaction e.g. the dealkylation of aryl alkyl ethers by alkali metals in ammonia in competition with the reaction of metal and ammonia to give hydrogen gas.22 The extent of reduction of a standard group compared with groups of varying substitution is another method which has been used.23 For example there are two com- peting reactions in the reduction of Ph*CRZ=CHGMe(OH)*R (R = H Me) the formation of Ph*CH,*CH,*CMe( OH)*R and hydrogenolysis to the hydro- - carbon Ph*CH,.CH-(?Me*R by way of the anion Ph*CHzCHzCMe-R.When R = H the hydrocarbon predominates but when R = Me the chief product is the dihydro-alcohol. It is evident that the extra methyl group (R = Me) can only have a second-order effect on the double-bond reduction but that it has a first-order (destabilising) effect on the mesomeric anion. Another comparative method employs a molecule which is symmetrical apart from the substituents to be studied e.g.unsymmetrically substituted diphenyl ethers.2* Information is then obtained from the direction of fission. The use of a limited amount of reducing agent on a mixture of two substances can give an idea of the relative ease of reduction; e.g. a mixture of benzyl alcohol Ph*CH,*OH and phenyldimethylcarbinol Ph*CMe,*OH with a limited amount of sodium in ammonia gives toluene not isopropylbenzene (p. 75).23 In the fission of ethers R-0-R‘ + 2e -+ (R- + R’O-) or (R’- + RO-) + 2H+ + RH + R’*OH or R’H + R*OH the direction is decided by which transition state has the lower energy. From the fact that RH (pK about 37-40) is a much weaker ‘‘ acid ” than R*OH (pK about 16-18) it is clear that the greater part of the energy will be required to form the carbon A. Sartoretto and F.J. Sow& J . Amer. Chem. SOC. 1937 59 603; A. L. Kranzenfelder J. J. Verbance and F. J. Sow& ibid. p. 1488; F. C. Weber and F. J. Sow& ibid. 1938 60 94. 22A. J. Birch J. 1947 102. 231dem J. 1945 809. 74 QUARTERLY REVIEWS anion R- or R'- Le. that the greater part of the energy of the transition state will be consumed by the carbon system. Furthermore substituents should produce greater effects on this system since they are directly attached to the atom bearing the charge. In a particular series therefore the R-group containing less electron-repelling groups or more electron-attracting groups should appear as RH if anions are intermediates. In practice this is found to be 50.26 The simplest case is the reduction of propylene oxide to isopropyl the high strain-energy of the three-membered ring evidently assisting a process which is impossible with ordinary saturated ethers.The transition state which is chosen contains CH,- rather than CH- CH2-CH-CH3 + 2e -+ ?lH2-h€-CH3 + CH,*CH(OH)*CH,. More ex- tensile evidence is provided by the fission of aryl ethem24 The following examples are typical 0- /O\ p-MeO*C,H4--O-c,H -+. p-MeO*C,H,*OH p-H02C*C,H4-O-C,H6 -+ pHO,C*C,H,(reduced) + HO*C,H 0 -MeO°C,H4-O-C,H,*Oib -p + HO-C,H,*OMe -p p-C,H4M-O-C,H -j. p-C,H,Me*OH (76%) + HO*C,$& (26%) Usually the phenolic products were the only ones examined. The one substituent group so far examined which does not show an immediately obvious re1a;tiomhip between its known electronic character and its influence on reductive fission is the methoxyl group. Its influence on the foregoing diphenyl ether fissions and on those of the aryl alkyl ethers and benzyl alcohols (below) depends on its position.An o-methoxyl is activating (ke. charge-stabilising relative to hydrogen) and a p-methoxyl is strongly deactivating. The dual effect may be related to the known dual electronic character of the group but this would mean that in an 0-position the inductive effect C -+ OMe must predominate but in a p-position the mesomeric effect C-OMe. There are no obvious reasons why this should be so. A more likely explanation is that in the o-position there occurs a hyperconjugation which stabilises the charge by transferring it &,!HZ a o c H z partially to the carbon of the methoxyl group as shown in the inset. The o-methyl is found to be less deactivating than the p-methyl which may be due to a small stabilising contribution of the same kind.It is noteworthy that anisoles are invariably metallated ortho- to the methoxyl. 28 The same effects of substituents including methoxyl are shown in the fission of aryl alkyl ethers to give phenols a reaction which is much less %&A. J. Birch J . Proc. Roy. SOC. N.S.W. in the press. 86 G. Wittig and U. Pockels Ber. 1939 72 89 ; G. Wittig and G. Fuhrmann ibid. 1940 78 1179 ; H. Gilman W. Langhstm and A. L. Jecoby J . Arner. Chem. Xoc. 1939 81 216. .t\ - BIRCH THE REDUCTION OF ORGANIC COMPOUNDS 75 readily performed because one of the groups is saturated In this case the relevant charge appears not on carbon but on oxygen. The demethylation of some anisole derivatives with sodium in ammonia under standard con- ditions gives the following yields of the phenol 22 anisole 27% ; o-Me 17%; m-Me 9%; p-Me 4%; o-OMe 89%; m-OMe 71%; p-OMe 2.5% ; 3 4-dimethoxytoluene gives 3-hydroxy-4-methoxytoluene.Altera- tion of the alkyl group confirms that a methyl ether is more readily cleaved than for example an isopropyl ether (I) giving rise to (11). Another interesting transformation involves the direct removal of oxygen from a benzene ring e.g. (I11 ; R = Me) gives (IV) while (I11 ; R = C02H) gives (V).22 Here as expected the oxygen meta to the electron-repelling methyl but para to the electron-attracting carboxyl is the one removed. In the hydrogenolysis of benzyl or allyl alcohol the standard group OH- is split off in each case so that only the substitution of the benzyl or allyl system need be considered.The results again agree with the anion hypothesis the same dual effect of methoxyl also being observed.25 In some cases the relative energies of the anions can be estimated from " acidity " measurements e.g. the '' acidity " of isopropylbenzene is much less than of toluene,27 which agrees with the fact that benzyl alcohol is reduced in preference to phenyldimethylcarbinol. It may be pointed out that with these weak " acids " the effects of substituents on energies seem to be so great that variations due to probability e.g. to the number of replaceable hydrogen atoms are negligible. The o- or m-methoxyphenylcarbinols (o- or m-MeO*C,H,*CRR'*OH ; R = R' = H or Me) behave in the same manner as compounds lacking the methoxyl group and give rise to the o- or m-alkylanisole (o- or m-MeO*C,H,*CHRR').The p-methoxyphenyl- carbinols (VI ; R = R' = H or Me) are reduced instead in the ring to 4-methoxy-2 5-dihydrophenylcarbinols (VII ; R = R' = H or Me) hydrolysed and dehydrated by mineral acid to the 4-alkylidenecyclohexe- nones 26 (VIII ; R R' = H Me). There is no appreciable difference in the ease of the ring-reduction of m- and p-tolyl methyl ether so the conclusion must be dram that the p-methoxyl raises the energy of the charge in the transition state of hydro- genolysis to a prohibitive level. The presence of a hetero-atom with readily 87 A. A. Morton J. T. Massengale aad M. L. Brown J. Amer. Chem. Xoc. 1945 67 1260; H. Gilman and L. Tolrnan ibu. 1946 68 522. F 76 QUARTERLY REVIEWS available p-electrons engaged in the aromatic resonance of a heterocycle has a similar deactivating effect relative to the corresponding benzene derivative e.g.furylbutylcarbinol is little hydrogenolysed under vigorous conditions. 23 Little evidence is available from acidity measurements on methoxylated systems but the isomerisation of (IX) to (X) shows clearly that an anion is more readily formed by loss of a proton from a methylene group in the m- rather than the p-position to methoxyl.28 2 5-Dihydro- anisoles have a comparatively acidic 2-position ortho- to the methoxyl. 2s The allyl alcohol reductions are very sensitive to changes in the substitu- tion of the allyl system. Examples of the reaction are the conversions of geraniol C,H,,*CMe:CH*CH,*OH and linalool C6Hll*CMe( OH)*CH:CH, into the same hydrocarbon methylgeraniolene C,H,,*CMe:CH*CH,.5 3O The identity of the products in this case and the bond-shifts which occur in other cases (p. 84) are clear indications that mesomeric systems are involved in the transition ; in this case as inset. There are no dimerisation products obtained which is some evidence against the ,-z-* formation of radicals. The experimental evidence c,H,,. C M X C H - C H 2 shows that reduction occurs if a CH or a CHPh group is at one or other end of the mesomeric system ; which end seems to matter little. The hydroxyl can be directly attached to this group as in geraniol or Ph*CH(OH)*CH:CMe, or at the other end as in linalool or Ph*CH:CH*CMe,*OH presumably because the energy level of the ion is high compared to the difference in energies of the isomeric alcohols. It is clear also from simple theoretical considera- tions that the substitution of both ends of the mesomeric system must be taken into account in arriving at an estimate of the ease of producing it.The effect of an alkyl group can be seen by comparing (XI ; R = H) with (XI ; R = Bun) ; the former is reduced to ethylidenecyclohexane the latter is not reduced. The alcohol CHMe:CH*CHBun*OH does give a small amount of an octene under rather vigorous conditions so the alkylation of both ends of the system is not completely prohibitive. If mesomeric radicals were the potential-determining intermediates increased alkylation would probably tend to make reduction easier as has been pointed out (p. 72). The effect of phenyl groups is no evidence either way although it is possible that substituted aryl groups might provide valuable information.The experimental evidence available from ‘‘ acidity ” z8C. T. Beer D. Phil. Thesis Oxford 1948. %*A. J. Birch J. 1947 1642. 10 G. Dupont R. Dulou and V. Desreux Bull. SOC. chim. 1939 6 83 ; J. Deuvre ibid. 1939 6 882. BIRCH THE REDUCTION OF OBGANIC COMPOUNDS 77 measurements can be correlated with the anion hypothesis. The position from which a proton is removed in the “metallation” of hydrocarbons confirms that increased alkylation of either end of the potential mesomeric anion lowers the “ acidity ”,20 and the isomerisation of unsaturated hydro- carbons with sodium or potassium amide in ammonia is an illustration of the same rule. These isomerisations proceed via the metal salts which in some cases are present in high concentration 2Q (p.85). An example of the process is The critical stage with 1 5-dienes is obviously the first bond-shift since the acidity is greatly increased in the 2 5-dienes by increased resonance in the ion. It is found that no isorherisation takes place unless the first poten- tial anion has a CH or a CHPh group in the system. Furthermore the reduction of 1 5-dienes with calcium hexammoniate or sodium in ammonia must be preceded by isomerisation to conjugated dienes and is not observed unless the same conditions are A discussion of other relations between structure acidity and ease of reduction particularly of hetero- systems will be found elsewhere. 2o The reductive fission of allyl or benzyl alcohols can be prohibited by placing a negative chaxge on the oxygen through salt formation.This explains Chablay’s observation 5 that only half the allyl alcohol is reduced by sodium in liquid ammonia unless ethanol is present. The equilibrium RONa + EtOH + ROH + EtONa is evidently set up allowing the (irreversible) reduction of ROH to proceed. Use can be made of the observation to protect hydroxyl groups in such systems while reducing other groups. It has already been pointed out for example (see p. 73) that Ph*CH:CH*CMe,*OH is reduced in part on the double bond and in part to lose the hydroxyl. The sodium salt with sodium in ammonia gives only the dihydro-alcohol with retention of the hydr0xyl.~5 A more complicated case is the reduction of cotarnine (XI). With sodium in liquid ammonia in the presence of ammonium chloride (an “ acid ” of the ammonia system) the hydroxyl group is lost and the compound (XIII) formed.If the ammonium chloride is replaced by sodium hydroxide the hydroxyl group is retained and the product can be converted into the metho-salt (XIV).lS I n the second case there seems no doubt that the protection is afforded by formation of the sodium salt of the carbinol. Alteration of the connecting atom can also change the ease of fission. From the order of acidities SH > OH > NH (dependent chiefly on decreas- ing nuclear charge) it appears that the fission of sulphur compounds should be easier and of nitrogen compounds more difEcult than that of the corres- ponding oxygen compounds. This expectation is borne out in practice. 31 31A. J. Birch J. 1946 693. 78 QUARTERLY REVIEWS Unlike saturated ethers dialkyl sulphides are reduced readily with sodium in ammonia e.g.C,H,.X*C,H + 2Na + NH,+C,H,*SNa + C3H + NaNH,.3X Very few amines undergo fission except under drastic condition^.^^ D. B. Clayson 34 has observed the fission of the tetrahydroisoquinoline ring of Me '' MeO OH OMe Iaudanosine with potassium in liquid ammonia at room-temperature and G. R. Clem0 and T. J. Kings5 have observed an allylamine fission in strychnine derivatives. The necessity for forming a nitrogen anion in the reaction is avoided by using a quaternary ammonium salt in which fission is found to occur readily with the production of an electrically neutral amine,l6* 25 e.g. Ph-NMe -+ PhH + NMe ; Ph*CH,*NMe -+ Ph-CH + NMe,. The presence of ethanol in this reaction is beneficial in preventing side-reactions due to the strongly basic amide anion.It is a powerful variant of the well-known Emde reduction using sodium amalgam.36 The evidence thus indicates that the potential-determiniag stage is the addition of two electrons. An examination of the reduction of triarylmethyl radicals with sodium amalgams 37 shows that the free-energy change (- AF) is much the same for all of them (about 17-20 kcals.) ; the resonance energies of a single electron and an electron-pair in the same system are therefore about the same. A slight increase (1-5 kcals.) is observed for the electron pair as the resonance possibilities increase in number. The presence of polarisable groups in the system may however alter the picture considerably. A pmethoxyl group as in diphenyl(methoxyphenyl)rnethyl shifts the fkee energy change to more positive values and although tri- (methoxypheny1)methyl chloride is readily reduced to the radical the radical itself is not reduced with sodium amalgam.The presence of the methoxyl group thus makes a considerable difference between the resonance energies of the radical and anion. Two electrons carry twice as much energy as does one electron so in f + 32F. E. Williams and E. Gebauer-Fdlnegg J. Amer. Chem. Soc. 1931 53 362. 33 E. Stoelzel Ber. 1941 74 982. *' Private communication. a6E.g. H. Emde and H. Kull Arch. Pha~m. 1934 272 469. J. 1948 1661. H. E. Bent et al. J . Amer. Chem. Soc. 1930 52 1498 ; 1931 53 1789 ; 1932 54 1393; 1935 57 1242 1452; 1936 58 1228. BIRCH THE RERUCTION OF ORGANIC COMPOUNDS 79 the absence of high interaction energies (such as may occur when two adja- cent negative charges are formed in the reduction of an unsaturated system) and special resonance effects such as above the addition of two electrons in one stage would appear to be favoured.There are no kinetic difficulties about this since the reactions occur at a conducting metal surface or in a conducting ammonia solution. The lower the energy associated with the metal electrons the more is the likelihood of the production of radicals if the reaction can proceed at all. For example the Ullmann reaction 2RX + 2Cu -+ R-R + 2CuX requires considerable heat energy and probably goes via radicals whereas the Wurtz-Fittig reaction 2RX + 2Na -+ R-R + 2NaX is carried out at low temperatures under the driving energy associated with the metal and goes via ions. The Reduction of Unsaturated Sgstems.-The isolated carbon-carbon double bond does not undergo reduction with chemical agents,s 38 presum- ably because the intermediate electron-addition products would require an energy which the ordinary reagents cannot reach.It is noteworthy that ethylene reacts with cssium to give Cs*CH,*CH,*Cs decomposed by proton- donors to give ethane.S9 The simplest double bond which does undergo reduction is that between carbon and oxygen the energy of formation of the charged inter- mediates being lower than in a carbon system because oxygen has a greater electron-affinity than has carbon. One or two electrons can be added depending on concentration factors i.e. the potential-determining stage is the addition of the first electron. The addition of one atom of sodium in an inert solvent (ether or ammonia) to an aromatic or non-enolisable aliphatic ketone gives rise to a compound R,C*ONa called a ketyl.*O The ketyls were formulated as free radicals by W.Schlenk and his co-workers 4 1 because of physical and chemical similarities to the triarylmethyls and they are paramagnetic.4 Electrical conductivity measurements show that quite a complex series of equilibria exist in the soluti0ns,4~ and these are confirmed by other methods.441 45 * The equilibria +- Phz8*ONa + Ph,CO + Na+ . * (1) 2Phz&ONa + Ph,C( ONa)*CPh,( ON&) . ' (2) Ph,&ONe + Ph,% + Pk,C(ONa)*CPh,(O-) . * (4) Ph,C( ONa)*CPh,( ONa) + Na+ + Ph,C( ONa)*CPh,( 0-) . * (3) all exist in solutions of the benzophenone ketyl. Bachmann 44 showed that 38P. Lebeau and M. Picon Compt. vend. 1914 159 70.sBL. Haekspill and R. Rohmer ibid. 1943 217 152. ** E. Beckmann and T. Paul AnnuZen 1891 266 1 ; A. E. Favorskii and I. N. 41Ber. 1911 44 1182; 1913 46 2840. 42 S. Sugden Trans. Paraday SOC. 1934 30 23. 43 C. B. Wooster J. Amer. Chena. SOC. 1937 59 377 44W. E. Bachmann ibid. 1933 55 1179. 4s C. B. Wooster ibicl. 1934 66 2436. Nazarov Bull. Acad. Sci. U.R.S.S. 1933 1309. 80 QUARTERLY REVIEWS (2) exists in ether and Wooster 45 showed that in liquid Smmonia it lies about 85% in favour of the monomeric products. The action of acids gives rise to the pinac01,~~ e.g. Ph,C*ONa -+ Ph,C(OH)*CPh,(OH). The further equilibrium 2R2C*ONa + R,C=O + R,C(Na)*ONa was shown not to exist by Wooster,45 46 because benzyl alcohol has little action on the ammonia solution of the ketyl but reacts rapidly with R,C(Na)*ONa formed by further action of sodium.Absorption spectra confirm this conclusion.47 However the equilibrium Ph,C*ONa + Ph3C* + Ph2C=0 + Ph,CNa does exist,48 and is an important demonstration of the comparative stability of the ketyl radical and also of the reversibility of the electron (i.e. metal) addition. A considerable body of evidence is available that the addition of both the first and the second electron can be reversed. For example mercury acts upon Ph,C(Na)*ONa to form Ph,C*ONa and sodium amalgam,49 and the reaction can be reversed if sufficiently concentrated amalgam is used.50 The treatment of R,C(Na)*ONa with R,C=O may lead to 2R2C*ONa,50 and the action of R,C*ONa on R',C=O can in some cases give R',C*ONa and R,C=0.51 A similar reversibility is found with the sodium addition compounds formed by many hydrocarbons e.g.Ph*CHNa*CHNaPh acts as an electron-source by producing a Wurtz product R-R with an alkyl halide R-X together with the original unsaturated hydrocarbon e.g. Ph*CEE:CHPh.52 Compounds of this type have even been used as catalysts for the Wurtz reaction.K3 Many sodium-addition compounds can carry 6ut isomerisations characteristic of radicals not ions e.g. of cis- to trans- ~ t i l b e n e . ~ ~ K. Ziegler and H. Wollschitt have also observed the transfer of sodium from one olefin to an0ther.~6 Finally the polarographic method 3 shows that the potential-determining step for many carbonyl and hydro- carbon reductions is the reversible addition of the first electron. The reduction of carbon-carbon unsaturated systems is possible when the multiple bonds are conjugated because the charges are stabilised by resonance.Isoprene CH,:CMe*CH:CH, is reduced by sodium in ammonia through the di-anion 56 .n * * * * * - CH2-CMe-CH-CH2 -4 CH,. CMe:CH.CH Y 46 J . Amer. Chem. Soc. 1929 51 1858. 47 H. E. Bent and A. J. Harrison ibid. 1944 66 969. 4aC. B. Wooster and J. G. Dean ibid. 1935 5'4 112. 49 W. E. Bachmann ibid. 1933 55 1183. S O H . E. Bsnt and W. B. Keevil ibid. 1936 58 1367. 61 W. Schlenk and A. Thal Ber. 1913 46 2840. 6aW. Schlenk and E. Bergmann Annalen 1928 463 1. 63 0. L. Talmud Acta Physicochim. U.R.S.S. 1938 8 27. 64 Annalen 1930 479 130. 5 6 " Handbuch der Katalyse " Bd. VI Ed. G.-M. Schwab Springer Verlag Vienna 66T. Midgley and A. L Heme J . A ~ w . Chem. SOC. 1929 51 1293. 1943 p. 109. BIRCH THE REDUCTION OF ORGANIC COMPOUNDS 81 Conjugation with aromatic systems has the same stabilising effect e.g.Ph.CH:CHPh + Ph*CH*CH*Ph -+ Ph*CH,*CH,*Ph.4 Aromatic rings in polycyclic systems are reduced by sodium in ammonia to give dihydro- derivatives as the initial products e.g. naphthalene and diphenyl. This happens despite the high resonance stabilisation of the aromatic system because of the large number of resonance possibilities in the electron- addition products. 'Unless there are electron-stabilising groups present like carboxyl,57 the mono-benzenoid compounds are not reduced except under special conditions to be considered later. The high resonance energy due to the special configuration of six electrons is not compensated in such cases by any correspondzngly high resonance energy in the electron-addition product.The presence in the ring of a hetero-atom in place of carbon e.g. nitrogen which can provide a more stabilising site for a negative charge assists the reduction process. For example pyridines are readily reduced even with sodium and alcohol. 58 The evidence from polarographic reduc- tion 3* 59 and equilibria with amalgams 37 shows that for polycylic systems including polycyclic ethylenes the potential-determining stage is the addition of the first electron although the products in most cases are derived by the addition of another electron. The acetylene triple bond is reducible,GO the products from dialkylacetyl- enes being the trans-ethylenes -C=C- -+ -Cud- -+ -CH=CH-. That this reduction takes place and that the reduction of a double bond does not is probably to be explained on the basis of the greater free-energy change in passing from a triple to a double bond than in passing from a double to a single bond.Furthermore there is a greater stabilisation of an electron in the more electron-deficient system. This may be correlated with the known acidity C=CH > CH.20 Sodium acetylides are not reduced presumably because of the negative charge.61 The effects of altering the solvent in the reduction of naphthalene by sodium are of great interest. N. D. Scott J. F. Walker and V. L. Hansley 6s found that naphthalene in ethylene glycol dimethyl ether or in dimethyl ether itself reacts with sodium to take up one atom per molecule and form a ketyl-like compound (also observed in diethyl ether with anthracene 5O).Dilution of the solution with &ethyl ether causes the deposition of sodium metal and naphthalene is left in solution. In liquid ammonia naphthalene readily fakes up two atoms of an alkali metal per m0lecule.~3 The reducing power of the sodium therefore varies with the ability of the solvent to stabilise the electron-addition products by solvation the higher its polarity the further to the right is the equilibrium Cl0H + 2e + C1,H,*- + e + clOHs-. a7A. J. Birch J. in the press. 6a I. M. Kolthoff and J. J. Lingane " Polarography " Interscience N. Y. 1941 e°K. N. Campbell and L. T. Eby J. Amer. Chem. SOC. 1941 63 216 2683; slA. L. Henne and K. W. Greenlee ibid. 1943 65 2020. 63W HuckeF an4 H. Bretschneider Annulen 1937 540 157 - _ . - - asB. D. Shaw J. 1937 300. Part v. K. W. Greenlee and W.C. Fernelius ibid. 1942 64 2506. Ibid. 1936 58 2442. 82 QUARTERLY REVIEWS This equilibrium is also illustrated by the fact that the mono-sodium compound behaves chemically as the di-sodium compound. The effects of substitution on the reduction of an unsaturated system are somewhat more complicated than with the fission reactions already considered because the two charged atoms remain attached to each other. It is evident however that substituents should affect the bivalent anions in a similar way to the univalent anions with an additional factor due to charge interaction. Even with the addition of one electron to give an anion-radical it is clear that the essential step is the addition of a negative charge so the ease of reduction should be affected by substituents in the same way.Moreover the reduction of radicals 37 shows that the resonance effects of a system are more pronounced on a negative charge than on a radical even when it is a hydrocarbon system and with the introduction of more readily polarisable groups like methoxyl the difference between negative charge and radical is even more pronounced. Electrochemical reductions provide direct evidence on the point; e.g. the potential for styrene Ph*CH:CH, is - 2.343 v. and for methylstyrene Ph.CH:CHMe under the same conditions it is - 2.537 v . ~ Similar differences are noted in the reduction of p-substituted benzaldehydes. l2 The electron-addition step has been treated so far as if it were completely divorced from the proton-addition step. In many cases this treatment appears to be justified in others it is not.The reduction potential of the carbonyl group is known to be greatly influenced by pH,S9 but in this and similar cases it is probably the cation formed by the addition of a proton rather than the substance itself which is reduced. At the dropping- mercury electrode the potentials of hydrocarbons are not affected by pH a t least on the alkaline side,3 and W. C. E. Higginson in preliminary experi- ments has also observed that the reduction potential of anthracene in liquid ammonia is unaffected by the presence of alcohol.6* The presence of alcohols in ammonia solutions does however exercise a profound influence on the course of reduction of monocyclic benzene derivatives. In its absence sodium does not reduce benzene hydrocarbons noticeably and it dealkylates phenyl ethers.22 66 Wooster 66 found that in presence of water or alcohols reduction takes place ; e.g.benzene gives 1 4-dihydrobenzene. From the fact that the hydrogen gas given off is less by about two atoms per molecule of substances like toluene or anisole he concluded that they also give 1 4-dihydro-derivatives. It was later shown by A. J. Birch 6 5 that the reaction leads to 2 5-dihydro-derivatives e.g. 2 5-dihydroanisole from anisole. The reasons for this profound influence of water or alcohols are still not completely clear but it is evident from the identity of products obtained when a reduction is carried out by electron-addition followed by proton-addition (where this is possible) or by simultaneous addition that no fundamentally new mechanism is involved 64 Private communication.6 5 A. J. Birch J . 1944 430. *6 C. B. Wooster and K. L. Godfrey J. Amer. Chem. Soc. 1937 59 586; C. B. Woostar U.S.P. 1939 2,182,242. BIRCH TIfE REDUCTION OF ORQANIC COMPOUNDS 83 for the latter process. For example it is unlikely that atomic hydrogen or metal hydrides intervene. The most likely explanation is that the equilibrium X + 2e + X*- + e -= X- is present but is far to the left because of high resonance energy in the benzene ring and the small number of resonance possibilities in the charged products together with the high charge-interaction energy in the di-anion. It is known that sodium reacts surprisingly slowly with alcohol in ammonia to give hydrogen but that anions react very rapidly so it is possible that the reaction is forced to the right by removal of the ions as the conjugate " acid," even though the instantaneous concentration of ions is small.Another explanation somewhat similar to the last is that the exothermic proton addition and endothermic electron addition may occur in one stage the energy of the former amisting the latter. How- ever if this were true compounds which can be reduced by a two-stage mechanism might be expected to take an easier path in presence of alcohol and be reduced at a (numerically) lower potential. Higginson's preliminary results 64 indicate that this is not so but a further examination of mono- benzenoid compounds is necessary. Other observations 7 are important in demonstrating the r61e of an " acid '' in ammonia solutions. 1 1-Diphenylethylene is reduced by sodium in ammonia to tetraphenylbutane evidently by the route Ph,C:CH + 2e -+ Ph,C-CH (+ Ph,C:CH,) -+ Ph2&CH,*CH,*6Ph (+ 2H+) -+ Ph,CH*CH,*CH,*CHPh,.In the presence of indene (an " acid ") a different course is taken Ph,C-GH (+ 2H+) -+ Ph,CH*CH,. Indene itself is almost unaffected by sodium in ammonia so its r61e must be confined to that of a supplier of protons to the primary anion which i t must do more rapidly than the anion can add to another molecule. Hydrogen from the indene cannot accept an electron before reduction occurs ; Le. atomic hydrogen or some equivalent cannot be involved. Moreover no di-indenyl .is formed so hydrogen is not abstracted from it &s the atom. - - - - 11. Nature of the Products The products are determined not only by the position of the electron- addition equilibrium but ako by the rates of secondary rmctions e.g.proton additions or dimerisation and by secondary equilibria e.g. between monomeric and dimeric ions X = Y 7 - X - H-Y- X - X -Y- H e e H-X-Y-H / -YH The proton-additions can be either reversible or irreversible according to the conditions (see Section 111) ; the primary products are those of irreversible addition. Addition to anions uni- or bi-vdent Beems to be 84 QUARTERLY REVIEWS more rapid than to anion-radicals presumably because resonance stabilisa- tion of the latter increases the acidity of the conjugate “acid” X-Y-H [compare the slow and incomplete action of benzyl alcohol on Ph,C*ONa with its rapid action on Ph,C(Na)*ONa 46]. Therefore if the di-anion is present in the equilibrium to any appreciable extent the products might be expected to result principally by addition of protons to its two charges.Two problems remain to be solved if the products of reduction are to be explained on the basis of proton addition to mesomeric anions. It is necessary to determine the effects of structure on the position in the meso- meric system taken up by a proton; and to see whether two protons are added simultaneously or successively to a bivalent anion. The experimental evidence with mesomeric carbon-anions shows that proton-addition occurs at the point of highest charge-density ; 205 22 e.g. li_ R . C M e s C H ~ ~ ~ 2 + R . C M ~ = C H . C H ~ The conversion of sabinol (xv) into a-thujene (XW) and of (XVII) into (XVIII) are other examples whereaddit- ion occurs to the least alkylated end of the ion. The conversions show that * * addition occurs adjacent to the charge-stabilising phenyl group.With hetero-enoid systems e.g. c - 0 the charge is chiefly concentrated on the hetero-atom because of its greater electron-affinity but it is often difficult to find conditions where proton-addition is truly irreversible. When this can be done e.g. by the use of very low temperatures the enols result. d Ic-)c”? It hliLs been pointed out elsewhere 2o that the reaction of an addendum with the point of highest charge-density is to be expected only if it requires little activation energy-as apparently does the proton reaction-and if it is irreversible. The products of reversible addition are governed by an equilibrium dependent on the free energies of the possible products not on the rates of addition at the various positions carrying a free charge.20- 67 The equilibrium is AH + A B + BH where A and B are the canonical forms representing the resonating ion.The following examples 6‘ are of considerable importance to an understanding of the nature of the primary reduction products of benzene rings and also the secondary products con- @? P. B. D. de kt Mase E D. Hughes and C. K. Ingold J. 1948 17. - - - - L-.z BIRCH THE REDUCTION OF ORGANIC COMPOUNDS 85 To avoid confusion in these and subsequent sidered in the next section. formula only the relevant hydrogen atoms are shown. 0 Me OMe ;6H H H t xxn.) (mrms If a small molecular proportion of potassium amide in ammonia acts upon the unconjugated 2 5-dihydroanisole (XIX) the potassium salt (XX) acts merely as a turntable to set up the equilibrium and the conjugated (lower-energy) 2 3-dihydroanisole (XXI) results.The conditions are those of reversible proton addition. If a large relative amount of potassium amide is used the potassium salt (XX) is the preponderating substance present and if protons are added to it by the rapid action (irreversible) of alcohol or ammonium chloride the unconjugated (XIX) results. This is true whether the salt is made from (XIX) or (XXI). The proton is added most rapidly at the 2-position which should be the position of greatest charge-density since it is in the middle of the mesomeric system and ortho to the methoxyl group. A similar conversion of 3 4-dihydro-l-naphthoic acid (XXII) into 1 4-dihydro-l-naphthoic acid (XXIII) can be produced through the &potassium salt in ammonia.Again addition occurs to the point of highest density in the middle of the system and adjacent to the charge-stabilising CO,K group. Whatever the theoretical interpretation of these results they are experimental facts which must be accepted. The production of ions of this type in a reduction reaction would obvi- ously lead to the ad-dihydro-derivatives (unconjugated) encountered in practice if protons can be added irreversibly. This is undoubtedly possible if an '' acid " strong compared with the hydrocarbon " acid " formed in the reduction is present. Alcohols (pK about 16-18) Mfill this condition but ammonia itself (pK about 34) does not. origin all^,^^ it had been assumed that protons are added simultaneously to a bivalent mesomeric anion formed by the addition of two electrons to a benzene ring in order to explain by mutual charge repulsion the a$-positions taken up by the protons.If one proton comes from the ammonia and one fiom the alcohol this would not be improbable from a kinetic point of view but the results above make it unnecessary. Examples of successive addition are to be found in reactions like Ph2Cz--CH2 -+ Ph2C-CH -+ P h 2 6 4 H (compare Wooster's " benzhydryl rule ' ' ) 6 ~ where the unstabilised charge 6sC. B. Wooster and N. W. Mitchell J . Amer. Ghem Soc. 1930 62 688 i C. B Wooster and J. F. Ryan ibid. 1932 54 2419 - 86 QUARTERLY REVIEWS corresponding to the weakest " acid " is the first to abstract a proton from the solvent. From this and on general grounds it seems likely that if two charges are present in a molecule the one which reacts first will be that corresponding to the weakest " acid " Le.the one whose reaction produces the greatest free-energy change. This assumes that purely steric effects are negligible which appears to be true for the systems considered. In fact using the results already arrived at it is possible to predict with considerable detail the products obtained by the reduction of substituted benzenes. This is strong support for the whole theory. The rule of addition of hydrogen atoms to a benzene ring based on the experimental evidence is as follows 65 the atoms are added in positions ad-to each other avoiding carbon atoms carrying electron-repelling groups in the order NMe,,OMe > alkyl and being attracted to carboxyl groups. The last influence outweighs all others so far investigated presumably because it acts by a mesomeric mechtjnism which can stabilise the charge on an oxygen while the others act by a mere electron-repelling tendency.In the last section it was shown that even if the potential-determining stage is the addition of one electron the products will almost certainly correspond to the addition of two electrons. Two-electron addition may even be obligatory for monobenzenoid compounds. The products are there- fore discussed on the assumption that they are determined by addition in successive stages of two protons to bivalent mesomeric anions of which (XXIV 0; and b) are canonical forms. OMe OMe OMe OMe In such a mesomeric anion the electron-distribution can be estimated qualitatively without much difliculty. The two charges cannot reside on the same carbon atom without violating the octet rule or on carbon atoms me& to each other without introducing very improbable ions containing three-membered rings.They must therefore be disposed among alternate carbon atoms as in (XXV) one charge to each set of three carbons.* The truth of this can easily be confirmed by writing out the various canonical forms. The effects of substituents are best illustrated by examples. Two electrons added to o-methylanisole will be distributed one between the 1 3 5- and the other between the 2 4 6-positions (XXVI). Both *The complete charge is distributed between the carbon atoxnh at t,he corners of the triangle. BIRCH THE REDUCTION OF ORGANIC COMPOUNDS 87 substituents raise the energy of the system to which they are attached but the effect is greater in the 1 3 5-system because of the greater electron- repulsive power of the methoxyl group.In addition the 2 4 %charge will be stabilised by the ortho-infiuence of the methoxyl group (p. 74). The 1 3 5-charge must therefore react first and its point of highest charge-density will be at the unsubstituted 3- or 5-position. Neither of these carries a substituent but they are not equivalent because of the effect produced by charge-repulsion in the 2 4 6-system. In the latter the charge-density is evidently higher in the 6- than in the %position because of the methyl group. This means that the 3-position will carry the greater charge but since the effect is a second-order one the difference between the 3- and the 5-position is probably not very pronounced.The expectation is therefore that addition will be initiated chiefly in the 3-position to give (XXVII) and to a lesser extent in the 5-position to give (XXVIII). These will then react according to the experimental results above to give respec- tively (XXIX) and (XXX). These two substances are in fact with a preponderance of (XXIX). 0 Me OMe An alkyl group in a m-position e.g. with m-tolyl methyl ether (XXXI) exercises a primary influence on the addition of the first proton since it is directly attached to the 1 3 5-system. Accordingly only one product is to be expected in this case 2 5-dihydro-m-tolyl methyl ether. A particu- larly interesting case is that of 5-methoxy-1 2 3 44etrahydronaphthalene (XXXIII) for which there was originally no basis on which the course of the reaction could be p r e d i ~ t e d .~ ~ It is now clear that the product should be (XXXIV) obtained experimentally. Where addition of the second proton must take place in a position occupied by an alkyl group (or a saturated carbon atom) in order to give acheduction some &-reduction to give a conjugated diene might be expected as well. 5-Methoxytetralin (XXXIII) is a good test-case and in fact the further reduction products of the expected conjugated diene (XXXV)- 9 10-octalin (XXXVI) and (after acid hydrolysis) 1-ketodecalin corres- ponding to (XXXVI1)-could be detected in the crude product of reduction by sodium and ethanol in amm0nia.6~ With anisole itself only a trace of methoxycyclohexene accompanies the methoxycycbhexadiene formed in this process. A. J. Birch unpublished work.88 QUARTERLY REVIEWS In the reduction of benzene rings containing electron-attracting groups like carboxyl the di-anion has a high electron concentration in the vicinity of the C0,Na group due to its ability to stabilise the negative charge by the resonance C-C(ONa)=O C=C( 0Na)-0. This concentration repels the other (less stabilised) charge to the p-position which accordingly forms - - - the seat of initial reaction. The product on this basis should be the experi- mentally found 1 4-dihydrobenzoic acid.67 Other electron-attracting groups like carbonyl are usually reduced in preference to the ring. Where the effect of carboxyl would require a negative charge to occupy a position on a carbon bearing methoxyl this is eliminated as an anion presumably because of the greater electron affinity of oxygen than of carbon.The product is the reduced benzoic acid.69 The elimination of methoxyl observed below in the reduction of 2 3-dihydroanisoles (e,g. XXI) is probably for the same reason. III. Secondary Processes What may for convenience be termed primary reduction products are those obtained under conditions of irreversible proton addition whereas secondary products are those obtained when proton addition is reversible. To illustrate the difference we may take the example of naphthalene. In the reduction of naphthalene with sodium in ammonia at the boiling point,70 it was found that four atoms of sodium are taken up per molecule the eventual product being 1 2 3 44etrahydronaphthalene. It was assumed that a tetrasodium addition product was formed.Later,63 it was shown that the initially-formed disodium addition product abstracts protons from the ammonia to give 1 4-dihydronaphthalene (XXXVIII) which is I-.) (=.) isomerised by the sodium amide formed in the process to the conjugated 1 2-dihydronaphthalene (XXXIX) through the sodium salt. The 1 2- di-hydronaphthalene is then reduced further by two more sodium atoms to tetrahydronaphthalene. The conjugated isomer is formed because the conditions favour reversible proton-addition and it is then reducible because of the conjugation. 'OC. B. Wooster and F. B Smith J . Amer. Chew. SOC. 1931 53 179. BIRCH THE REDUCTION OF ORGANIC COMPOUNDS 89 Reversible proton-addition can occur only if the initial reduction product is an “ acid ” comparable in strength with the strongest “ acid ” present in the solution-in this case ammonia itself.If a stronger acid is present e.g. ethylaniline the primary reduction product is obtained and if the product is the strongest “ acid ” in the solution it is again unchanged because it is protected as its sodium salt until the reaction mixture is worked up. An example of the latter is the reduction of 2-naphthol to 2-tetralone in up to SOY0 yield by sodium and alcohol in amm0nia.~67 69 It may seem sur- prising that a ketone can escape reduction under such vigorous conditions but it is evidently protected by the negative charge on the enolate ion. The enol forms of the ketones are probably fairly stable at the low tempera- tures used and unlike the keto-forms their acidity must be quite high (of the order pK 10).Even nitroparaffins are not reduced by sodium and ammonium bromide in ammonia presumably because they form stable ammonium salts of the mi-form.71 Another good example of the stabilisa- tion of an unsaturated compound by salt formation can be seen in the contrast between the following reactions (ammonium chloride is an ‘‘ acid ” on the ammonia scale) 72 +Na-NH3 Na-NH3* - N H4CL ( X = 0 s ) The presence of ammonium salts may assist reactions by removing the strongly basic compounds (sodium hydroxide or amide) formed. For example nitroguanidine goes smoothly to aminoguanidine in the presence of ammonium bromide but not in its absence.?3 The production of tetrahydrobenzenes from benzenes by the action of calcium hexammine Ca(NH,), observed by Kazanskii and his co-workers,7* is to be explained on the basis of secondary reductions.The primary products are undoubtedly the same as those obtained from the sodium- dcohol-ammonia reduction-unconjugated dihydrobenzenes-and these are then conjugated probably by the influence of calcium amide and then further reduced. The original discoverers of the reaction 75 in fact obtained from benzene the 1 4-dihydrobenzene although later workers presumably using slightly different conditions were unable to repeat the preparation. Anisole derivatives often give rise chiefly to di- rather than tetra-hydro-deriva- t i ~ e s . ~ ~ 3 l The reaction can be imitated by using sodium-ammonia solutions in several stages.2B The first stage is with sodium-alcohol-ammonia to form 71G. W. Watt and C. M. Knowles J . Org. Chem. 1943 8 540. 73 L.P. Fuller E. Lieber and G. B. L. Smith J . Amer. Chem. Soc. 1937 59 1150. 74 B. A. Kazanskii and N. F. Glushnev J . Qen. Chem. Russia 1938 8 642 ; Bull. Acad. Sci. U.R.S.S. 1938 1061 1065; B. A. Kazanskii and N. V. Smirnova ibid. 1937 647. 76 A. V. Dumanskii and A V. Zvyereva J . Russ. Phys. Chem. Soc. 1916 48 994. C. M. Knowles and G. W. Watt {bid. 1942 7 60 90 QUARTERLY REVIEWS the unconjugated dihydro-derivative. This can then be reduced to tetra- hydrobenzenes by the action of sodium in ammonia the sodium amide formed in the reaction acting as the conjugating agent. Alternatively the unconjugated dihydrobenzene can be conjugated first by the ttction of metal amide in ammonia and then reduced by sodium in ammonia. An example is p-tolyl methyl ether the principal stages being 0 M e i - rnethy!clr/ohexene + 3- methylcycfohexene Me Me Me Me 4- methylcyclohexene Phenols may be obtained by the Kazanskii method from phenol ethers which are difficult to reduce e.g.2 6-dimethylanisole but owing to the complex mixture of products the reactions are not of much value. Good yields of 1 -methoxycycZohexenes can be obtained from resorcinol dimethyl ethers,Gg and benzsuberan has been reduced to its tetrahydro-derivative as a preparative method.76 W. Applications in Synthesis and Degradation From the reactions already mentioned it is clear that the reagents are likely to have many applications. Work up to the present has however been concerned mainly with an exploration of properties and mechanisms Applications may be based on such properties as lack of steric hindrance ; 77 the formation of trans-ethylenes from acetylenes (catalytic methods give chiefly cis-); but above all on their combination of great power with structure-specificity.The formation of ad-dihydrobenzenes shows that the sodium-alcohol-ammonia reagent is powerful enough to reduce a benzene ring but specific enough to add only two hydrogens. The dihydrobenzenes are intrinsically interesting and can also be converted into compounds inaccessible by other methods. For example the dihydroanisoles are the en01 methyl ethers of ketones and can be converted by acid hydrolysis first into the Py- and then into the a/?-unsaturated ketones.% 31 This method was the chief one used to identify the products of such reductions. Anisole itself gives 2 5-dihydroanisole (XL) which is hydrolysed first to cycbhex-3- enone (XLI) and this is converted into cyclohex-2-enone (XLII).The syntheses of the sesquiterpenes a- B- and y-curcurnene (XLIII) (XLIV) and (XLV) illustrate some important characteristics of the 76 P. A. Plattner Helv. Chim. Acta 1944 27 808. 77 N. L. Lochte J. Horeczy P. L. Pickard and A. D. Barton J . Aww. Chern. Soc. 1948 70 2012. BIRCH TRE REDUCTION OF ORGANIC] COMPOUNDS 91 reagent.78 The production of a-curcumene (XLIII) shows that a benzyl alcohol can be hydrogenolysed without noticeable reduction of the ring but that the ring can be reduced (production of XLIV) by sufficient reagent. The p-methoxy-compound employed in the synthesis of y-curcumene (XLV) cannot be hydrogenolysed directly but after dehydration the double bond can be hydrogenated because of its conjugation with the ring.In none of these compounds is the isolated double bond in the side chain affected. CO R QgBr ,I! CMe If CMe eMe CMe One of the greatest di-fliculties encountered in synthesis is that many compounds are but little soluble in ammonia particularly if their molecular weight is greater than about 150. Several methods can be applied to over- come the difficulty at least in part. Rise in temperature greatly increases solubility as can be seen from the example of cholesterol 79 (mg./100 c.c.) - 38" 0.00 ; O" 6.16 ; 49" 545.0. To utilise this requires however work under pressure with considerable mechanical difficulty. A more practical method which can be used with phenol ethers is to use side chains containing hydroxyl groups which render the molecule s0luble.~8? ** Hydrolysis of the reduced material gives a ketone with removal of the side chain so that its nature does not matter.The following syntheses have been accomplished thymyl 2-hydroxyethyl ether (XLVI) to piperitone (XLVII) ; a-oestradiol 1 -glyceryl ether (XLVIII) in several stages to nortestosterone (XLIX) and hexastrol bis-(2-hydroxyethyl) ether (L) to (LI) and (LII). A further advantage of such side chains is that the products are readily separated from any unchanged starting material by distillation or chromatography. According to G. IF. Pope,81 it is necessary to have about 10% of alcohol in 78 A. J. Birch and S. XI. Mukherji J. 1949 2531 ; A. J. Birch J . 1950 367. 7eR. G. Gustrtvson and J. B. Goodman J . Amer. Chm. Soc. 1927 49 2526. *OA. J. Birch and 8.M. Mukherji Nature 1949 163 766. 81 Private communicakion. a 92 QUARTERLY REVIEWS the ammonia to ensure reduction with the hexoestrol derivative. The use of mixed solvents merits further investigation. Another useful property of the solutions is that they can be used with sulphur compounds which poison metallic catalysts. Amino-acids contain- ing thiol groups are readily prepared by the reduction of benzylthio-deriva- tives.S2 Penicillamine (LIII) and some of its N-alkyl derivatives (LIV) have been similarly ~repared.~3 Another sulphur compound conveniently prepared is B.A.L. (British Anti-Lewisite) (LV),S* 2 3-dimercaptopropanol. An outstanding problem for synthetic work is the protection of reducible groups while others are undergoing reduction. The carbonyl group can often be protected by conversion into an acetal or an enol ether e.g.(LVI) can be converted into (LVII) the benzene ring reduced and the carbonyl Me,C.CH( NH,)*CO,H -+ Me,C.CH(NH,)-CO,H 1 SH I S*CH2 Ph ( m.) Me,C-CH * C0,H CH,. S CHiSH 1 ,CHPh -3 -. ,NH SH NH-CHRR' CH-S CH-sH R+(R I - I 1 I CH; OH ( LIP.) CH,* OH Me2r-jH.Co2H ( LY..) group recovered by the action of acid to give (LVIII).s5 An aryl ketone cannot usually be so protected because the acetal undergoes hydrogenolysis and an aj5-unsaturated ketone cannot be protected as its enol ether because this contains conjugated bonds capable of reduction. Fortunately a complementary method can often be employed in such cases because the 82 V. du Vigneaud et al. J. Bid. Chem. 1935 108 753 ; 109 97 ; 112 149 ; etc. 8 r L . A. Stocken J.1947 593. 86A. J. Birch and S. M. Mukherji unpublished. " The Chemistry of Penicillin " Princeton Univ. Press 1949 16 460. BIRCH THE REDUCTION OF ORGANIC COMPOUNDS 93 en01 salts of unsaturated ketones unlike the saturated ones are often stable enough in ammonia to protect the group even when the reduction demands the presence of an alcohol.69 The general problem is still under investigation but the principles are clear the unsaturated group must be converted (reversibly) into a saturated one or into one containing only an isolated carbon-carbon double bond or eke it must be charged negatively by salt formation. Few uses have been made of the reagents for the investigation of natural products although their properties suggest a number of possible applications. The fission of aryl or benzyl ethers has been tentatively applied in the investigation of lignin.86 I(.Freudenberg and his co-workers found that aryl- but not alkyl- glucosides are split By potassium in ammonia and from the fact that lignin is almost entirely removed from intact wood they conclude that any links between lignin and carbohydrate are of the aryl- glucoside type. Other workerss7 obtained about 80% of products of low molecular weight from a similar lignin treatment which confirms that most of the linkages between units are through oxygen rather than carbon A determination of the nature of the products may give further information on the structure of lignin. Methylated acacia tannin also gives a proportion of products of lower molecular weight.8s The fission of quaternary ammonium salts (Emde reaction type) may well prove useful tool in alkaloid investigations.16 Ammonia is cheap and the mechanical d2Eculties encountered when working at atmospheric pressure are small because the latent heat of vaporisation is large and the boiling point not unduly low. Ordinary apparatus can be used with or without “ dry-ice” baths and condensers. Dewar flasks are useful but not essential; the chief requisite is a good fume-chamber. Excess of sodium can be destroyed catalytically by a trace of ferric nitrate 68 or chemically by sodium 11itrate.8~ 71 1810; K. Freudenberg W. Lautsch and G. Piazolo ibid. 1941 74 1879. N. Shorygina and T. Y. Kefeli J. CTen. Chem. U.S.S.R. 1947 17 2058. 8 6 K. Freudenberg K. Engler E. Flickinger A. Sobek and F. Klink Bey. 1938 88A. J. Birch and A. M. Stephen unpublished work. 88 N. 0. Kappel and W. C. Fernelius J. Org. Chem. 1940 5 40.

ISSN:0009-2681    

DOI:10.1039/QR9500400069

出版商:RSC    

年代:1950

数据来源: RSC

摘要:

RELATION BETWEEN THE OXIDATION-REDUCTION PO!I!ENTIALS OF QUINONES AND ‘J!HEm CHE”cAL STauCTuRlE By M. G. EVANS (PROFESSOR UNJYERSITY OF MANCHESTER) and J. DE HEER (RAMSAY MEMORIAL FELLOW OF THE NETHERLANDS) General Introduction THE problem of relating the oxidation-reduction potentials of quinones to their chemical structure can be divided into the following two parts (a) A study of the factors which influence the potentials of the unsubstituted quinones. In such a discussion we shall be concerned with the nature of the quinonoid ring and the structure of the aromatic system(s) attached to this ring. ( b ) An investigation of the influence of substituents on the potential of one particular parent quinone. This study includes a con- sideration of the nature the number and the position of the substituent groups.It is interesting in this introduction to trace the development of ideas in the above connections. Before oxidation-reduction potentials of quinones were known the effect of structure on their “ oxidising strength ” or their “stability” had already been discussed by organic chemists. The first “ theory ’’ was put forward by 2’. Kehrmann in 1898 ‘‘ The oxidising strength of quinones decreases as the molecular weight increases and as there are more negative substituents in the molecule.” No clear indication of what was meant by “ negative substituents ” was given ; the first part of the statement was based on the well-known sequence (I) (11) (111) in 0 0 0 (1.) (11.) (111.) W.) which the stability increases from left to right typical quinone properties being nearly absent in anthraquinone.R. Willstiitter and J. Parnas in 1907,2 however pointed out that the problem could not be quite so simple ; for example ampirzinaphthaquinone (IV) is extremely unstable although it has of course exactly the same molecular weight as the isomeric a- and p-naphthaquinone. Willstatter and Parnas then suggested that it is not so much the simple increase in molecular weight that is decisive but rather the stabilisation of the quinonoid system by linking an aromatic ring to its olefinic bonds. It was shown that even the extremely unstable amphi- 1 Ber. 1898 31 979. a Ibid. 1907 40 1406. 94 EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF Q’UINONES 95 naphthaquinone could be stabilised in this way as one could prepare “ amphichrysoquinone ” (V),3 “ anthanthrone ” (VI),* and “ amphi-iso- puvranthrone ” (VII),6 the stability again increasing from left to right.This (V.1 (VI4 (VII.) rule of Willstatter and Parnas has guided organic chemists for many years. The influence of substituents on the stability and oxidising power of quinones was even in this qualitative way less clearly delineated. Some general indications were apparent such as that by Kehrmann referred to above. 0. Dimroth and V. Hilcken in 1921 showed that the position of a substituent was as important as its nature. Real progress could only be made when qualitative considerations on oxidising power and stability could be replaced by quantitative determina- tions of oxidation-reduction potentials. Although F. Haber and R. Russ determined the potential of p-benzoquinone as early as in 1904,’ it was not until about 1920 that better and easier experimental techniques were developed (W.M. Clark E. Biilmann S. P. L. Sgrensen). This allowed a systematic investigation on a large scale. Between 1920 and 1935 Fieser and his collaborators at Harvard prepared a very large number of quinones and quinols and determined their potentials.8 Although other measure- ments Q had been reported and particular quinones had aroused interest in connection with special applications (as indicators dyes etc.) an entirely new point of view was stressed by Fieser and his collaborators. They clearly recognised how our understanding of the particular problems might be of great importance for other and more general problems in organic chemistry. To quote J. B. Conant and L.F. Fieser lo “The measurement of reduction potentials affords a new method of studying quantitatively the free energy of an addition reaction which can be brought about with a series of related substances. By such quantitative studies the differences caused by substitution and by structural changes can be discovered and when sufficient data have been obtained it should be possible to make many interesting and important generalisations in regard 3E. Beschke and F. Diehm AnnaZen 1911 384 173. 4L. Kalb Ber. 1914 47 1724. R. Scholl and C. TZinzer Annalen 1923 433 163. Ber. 1921 54 3050. 2. physikal. Chem. 1904 47 257. 8 See also refs. (10) and (1 1); full references given in subsequent paragraphs. For 8 survey of this work see also L. F. Fieser and M. Fieser “ Organic Chemistry ” Boston Heath 1944.See e.g. V. K. LaMer and L. E. Baker J . Amer. Chem. Soc. 1922 44 1954. lo Ibid. 1923 46 2194. 96 QUARTERLY REVIEWS to the driving force of a given organic reaction and the structure of the organic compound concerned.” However the important generalisations which were hoped for were not immediately apparent in terms of classical organic chemical ideas. In particular the problem of the influence of substituents appeared to be very complicated and even a comparison of the potentials of the unsubstituted “ parent quinones ” did not immediately yield results. Although the Willstatter-Parnas rule appeared to be of some guidance one observed great irregularities. Clearly as already pointed out by Conant and E’ieser in 1924,11 this is not surprising as an adequate interpretation of the facts should not only take into account the stability of the quinone (to be denoted by Q) but also that stability of the quinol (to be denoted by QH,) formed on reduction.From the theoretical point of view the first important step forward was not made until 1941. Then G. E. K. Branch and M. Calvin l2 put forward the hypothesis that in a reaction of the type Q + H --+ QH, e.g. 0 OH the driving force should be the gain in resonance energy of the aromatic QH,-system over that of the quinonoid &-molecule. The difficulty in testing this hypothesis was to evaluate R,,* and R, the two resonance energies concerned. For the unsubstituted quinones methods of approxi- mating these quantities have been developed by Branch and Calvin themselvesY12 by M. G. Evans,13 by M.Diatkina and J. Syrkin,l4 and recently with somewhat greater precision by M. G. Evans J. Gergely and J. de Heer.l5 As a result of these quantum-mechanical calculations we can now conclude that for a certain series of unsubstituted quinones the hypothesis of Branch and Calvin has been proved to be correct. A linear relationship is found between the oxidation-reduction potential EO and the difference in resonance energy of Q and QH, i.e. R,, - R,. The present state of our quantum-mechanical methods does not allow us to calculate resonance energies of substituted quinols and quinones with any accuracy. However for a number of compounds E. Berliner16 estimated these quantities from experimentally known heats of combustion and apparently proved that the resonance hypothesis can be extrapolated to substituted quinones.We will show in a subsequent paragraph that Berliner’s ideas can be criticised and might lead to confusion as to the nature l1 J . Amer. Chern. Soc. 1924 46 1858. l2 “ The Theory of Organic Chemistry ” New York Prsntice Hall 1941. l 3 Trans. Farachy Soc. 1946 42 113. l4 Acta Physicochim. U.R.S.S. 1946 21 921. l6Trans. Faraday Soc. 1949 45 312. l6 J. Amer Chem. Soc. 1946 68 49. EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINONES 97 of the resonance phenomena. As it is our conviction that here as in other parts of organic chemistry the resonance phenomenon is sometimes intro- duced too uncritically we will confine part of this Review to elaborating some fundamental notions and definitions which are involved. After that it will be clear that other intramoleciilar energetic factors will co-operate (or counteract) in the resonance stabilisation.In addition intermolecular and entropy influences will be involved in determining the free-energy change of the oxidation-reduction reaction under consideration and it is this total free-energy change that determines the potential. The entire problem is therefore seen to be a very complex one. The recognition of this fact in itself is of great advantage as it now becomes clear that simple theories should not be expected to cover all facts. Our task will be to analyse this complex problem into its different aspects and then to discuss several special topics within the framework thus outlined. 1. Experimental Data In the scope of this paper it is not our intention to give any details about experimental methods.The only idea underlying the inclusion of this section is to mention the sources of the experimental data and to comment on their exact meaning in connection with their comparison with theory. Q (solid) + H (gas 1 atm.) -+ QH (solid) . (1) We can consider three different reactions Q (in solution) + H {gas 1 atm.) + QH {in solution) . (2) Q (gas 1 atm.) + H (gas 1 atm.) -+ QH (gas 1 atm.) . (3) If we divide the free-energy changes AGs AGl and AGg accompanying these reactions by 2 F ( F = Faraday’s constant) we obtain the oxidation-reduction potentials referring to the solid solvated and gaseous state respectively. These three quantities all of which are mentioned in the literature we denote by Eg E i and E i ; each of these terms is a function of the tempera- ture.E; and EL can be determined directly by means of the usual electro- chemical methods.17 E can only be obtained indirectly and only if (i) Eg is known (ii) PQ and PQa, the vapour pressures of the quinone and quinol at the temperature concerned are known and (iii) the quinone and quinol vapours behave as ideal gases or have approximately the same activity coefficients at that temperature. We then obtain E i from 17e The free-energy change expressed by Eg will be dependent on the lattice energies of Q and QH in their respective crystals. As theoretical work is 1 7 (a) J. B. Conant H. M. Kahn L. F. Fieser and S. S. Kurtz Jr. J . Amer. Chern. Soc. 1922 44 1382; (b) J. B. Conant and L. F. Fieser ibid. p. 2480; (c) idem ibid. 1923 45 2194 ; ( d ) idem ibid. 1924 46 1858 ; ( e ) J.B. Conant,ibid, 1927 49 293 ; (f) L. F. Fieser ibid. 1928 50 439 ; (9) idem ibid. 1929 51 3101 ; ,(h) idem ibid. 1930 52 4916; (i) idem ibid. p. 6204; ( j ) L. F. Fieser and M. A. Peters ibid. 1931 53 793; (k) L. F. Fieser and M. Fieser ilvid. 1934 56 1666 ; ( E ) idem ibid. 1935 57 491. 98 QUmTERLY REVIEWS usually performed on isohted molecules and the lattice energies concerned are unknown Ei is of little use to us. It is evident that E would be very suitable but unfortunately the data required to determine this quantity with any accuracy are seldom available. So one usually considers EE only ; in the rest of this paper we will refer to this quantity as Eo. The dis- advantage remains that in correlating Eo with theoretical data solvation and association phenomena may interfere ; in other words we may expect EO to be dependent on the choice of the solvent.As the usual electro- chemical determinations must be made in polar conducting solvents it became a matter of interest to find a method to determine EO in a non-polar solvent. This problem was solved by Kvalnes l8 who developed an optical method essentially based on the equilibrium set up in a system containing the Q-QH pair to be investigated and a standard optically active &'-&Hi pair. In a dissociating solvent Eo is usually defined by the expression where [TI represents the total concentration of the reduced quinone In this reduced form the quinone may exist as undissociated molecules QH, in the first ionised state QH- and a,s fully ionised Q=. Thus where K and K represent respectively the first and the second dissociation constant of the quinol.Few second dissociation constants of quinoIs have been measured but K and K are usually of the order to 10-9 and 10-11 to 10-13 respectively. Hence at a hydrogen-ion activity of 10-1 which is the standard at which Eo is defined the last two terms in the above expression are negligible compared with unity and Eo measures effectively the free-energy change involved in the reaction Q + H -+ QH,. It would be of considerable theoretical interest if the free-energy change of the reaction Q + 2e -+ Q= could be measured and compared with that for hydrogenation. Unfortunately as mentioned above values of K and K which would be required for this measurement are rarely available and direct measurements in alkaline solution are nearly always impossible.The accuracy of the Eo determinations differs somewhat for different quinones according to the specific experimental difficulties encountered. Fortunately nearly all data which are important to us have been obtained by the same school l7 and should be very reliable for mutual comparison in which we are interested in the first place. In 1900 A. Valeur l9 deter- mined thermochemically the heats of reduction of several quinones. His results could be compared with the EL'S and Eg's obtained electrochemically as one also knew the temperature coefficients of the last two quantities. E. Biilmann 20 and Conant and Eeser 17b*e thus found "fairly concordant l8 W. H. Hunter and D. E.'Kvalnes J . Anher. Chem. Soc. 1932 54 2869 ; D. E. Kvalnes ibid. 1934 56 676 670 2478 2487.Is Ann. Chim. 1900 21 470. aoIbki'. 1921 15 109. EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINONES 99 results " and discrepancies have to be ascribed very probably to the uncer- tainties and approximations involved in the thermochemical method. An uncertainty in EO amounting to 10 mv. (which according to Fieser et al. is exceptionally high) would mean an uncertainty in free-energy change of about 0.5 k.-cal. As the accuracy of our theoretically obtained data will certainly not be of a smaller order these divergencies need not worry us. Finally one can say that very few of the values reported by Fieser et d. have been criticised (see however K. Wallenfels and W. Mohle 21 for & critical discussion of some data). Summarising we may conclude that the data communicated by Fieser et a2.seem to offer an adequate basis for comparison with our theoretical ideas. 2. An AnaJysis of the Factors Influencing Eo As stated in the previous section E* will be a measure of thefree-energy chnge AG1 accompanying reaction (2) as it occurs in solution. In analysing the various factors which contribute to this free-energy change it will be useful to relate AG1 to A@ the free-energy change of reaction (3) under ideal conditions in the gas phase. where AQsolv* is the free-energy change accompanying the solvation process of the species Q and QH,. The free-energy change in the ideal gas phase can be expressed by Q, is the free energy of a molecule of hydrogen under the ideal standard conditions chosen and will be a constant term throughout any sequence of quinones we consider.On the basis of the above analysis we can construct the following table in which H denotes heat content and S entropy Thus AG1 = AGg + A@$:; - A@$""* AGg = GQH - GQ - GH EO I 1-AGI---- 1 1 I I I AGg I AGCg; - 1 1- I a& - G8 I AHso'v' I- QH - I ASQB;; J J a l v J S o l V . - Q I '-?Ha &$ I--' -s& I r BQH - (Intra)rnolecular Environment (intermolecular) properties. properties. A slight simplification can be made by noting that h& will d8er very little from S& because these molecules differ little in mass and moments of inertia and internal vibrations will contribute little to the entropy. On the other hand the term AP$Z; - APG'v. may not always be negligible and will be Ber. 1943 78 924. 100 QUARTERLY REVIEWS dependent on the nature of the solvent.In fact Conant and Eeser’s observations 17b show that the temperature coefficients in aqueous and alcoholic media are different which emphasises this point. It is reasonable to suppose however that in a sequence of quinones containing the same number of polar groupings of the same configuration solvation effects influencing both AHsolv. and ASs01v- will remain consta.nt throughout the series if all EO’s are measured in the same solution. We can however not expect this simplification always to hold and especially will it fail in a sequence in which the number and nature of substituents are changed appreciably. This complication as we will see will make it difficult to analyse the effect of substituents on the intramolecular properties. Summarising the position we would say that in a series of closely related quinones the environmental energy and entropy terms while not being entirely negligible may reasonably be expected to remain coristant.This together with the slight simplification with regard to the intramolecular entropy change (see above) justifies us in attempting to relate the changes in free energy and hence the changes in Eo to the changes in intramolecular energy of such related compounds. It is necessary therefore to analyse the various molecular factors influencing HQHI and H (the superscripts g now having been dropped). (a) A framework of atomic nuclei. ( b ) A number of electrons not involved in chemical bonding Le. inner-shell electrons and those valence-shell electrons that are localised at particular nuclei. (c) The so-called “ a-electrons ” which in pairs form localised ‘‘ cr-bonds ” between two particular centres each centre consisting of an atomic nucleus plus a number of electrons of type (6).(d) A system of “ unsaturation-” “ conjugation-” “ mobile-” or ‘‘z ”-elec- trons being capable of moving through a larger part (“ unsaturation- ” or “ conjugation-path ’7 of the molecule. This division is more or less artificial and interaction between Merent types of electrons might very well occur. Usually we are incapable of considering this interaction in any detail. In fact in most cases only the energies of the n-electrons can be estimated quantitatively ; here two approximation methods are available (i) the “ valence bond ” approach ; (ii) the “ molecular orbital ” approach. In this survey we do not want to discuss the criticism to which both these two methods are open or to analyse their merits relative to each other.However we do want to stress that although inner-shell electrons may possibly not interfere with chemical phenomena this is certainly not the case with a-electrons. In other words in discussing the energetic aspects of an unsaturated molecule o-bond energies must be taken into account. In this connection it is very unfortunate that we usually have to confine ourselves to some qualitative remarks here as our present-day quantum-mechanical theories are inadequate to deal quantitatively with the characteristics of a-electrons and a-bonds. I n an unsaturated molecule we have to distinguish : EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINONES 101 The total n-electronic energy which thus can be calculated with the aid of one of the two approximation methods mentioned above is closely connected to the ‘‘ resonance-energy ” or ‘( delocalisation-energy ” of the molecule under consideration.However the two are not identical as the resonance or delocalisation energy is equal to the total n-electronic energy minus the sum of the energies of these n-electrons in a hypothetical localised bond-structure. Whether a difference in total n-electronic energy of two molecules (e.g. Q and QH,) is accurately resected by their difference in resonance energies is a question which cannot be answered in general but has to be considered in every particular case. Finally the energy of an isolated molecule may still be influenced by factors which are usually described under the heading “ ortho- effects ”.In a molecule of the type (VIIT) where X and Y may be complicated groups interactions between X and Y may give rise to special energetic terms (e.g. stabilisation through hydrogen- bridge formation). of atoms constituting X and Y often participate here. Again the ortho-effects are in many cases not tractable quantitatively and even their nature is not always completely clear. Here too we usually have to make rather rough guesses. Summarising the important part of the intramolecular energy of an unsaturated molecule has been sub-divided as is indicated below This is true of both methods (i) and (ii) above. 0 Electrons (‘ localised ’’ in the valence shells (VIII.) Intramolecular energy I I Energy of o-bonds (and localised electrons) I Special contributions hydrogen -bonding ) I Energy of the system of n-electrons con- (ortho-efSects e.g.nected with resonance energy We want to stress that this sub-division is not at all of a fundamental or of a more or less “unique ’’ character as is the main division given at the beginning of this section. On the contrary it is immediately con- nected with the quantum-mechanical approximation methods which are available at present for determining the energy of an unsaturated molecule. 3. Detailed Discussion of o- and p-Unsubstituted Quinones In this section we wish to discuss the changes in oxidation-reduction potential EO measured in a particular solvent in a series of related com- pounds in terms of the behaviour of the electronic energies of the molecules concerned. -We again emphasise that changes in solvation energy and entropy changes will be very closely the same throughout such a series.Fieser and Conant 176 have shown that the temperature coefficient of the E* is in aqueous solution of the order of 0.7 mv. per degree for a number of substituted and unsubstituted quinones. This value corresponds to an entropy change accompanying the reaction of about - 32 cals. per degree a change which 102 QUARTERLY REVIEWS corresponds roughly to the entropy of hydrogen under the standard con- ditions of pressure and temperature. According to the arguments given in section 2 this is what we should expect on theoretical grounds. We are aware that there are small but significant differences in this entropy change for the same reaction in different solvents but these are small compared with the energy changes that we shall have to discuss.Indeed the infiuence of environment on the total free-energy change which as we pointed out may include solvation association $alt-effects etc. is small compared with the value of the internal (intramolecular) free-energy change. It may however be of the same order as the differences between one quinone and another in which we are interested. Therefore we feel it important that any comparisons which are to be discussed in terms of electronic energy should be made between systems measured under the same environmental conditions and in as dilute a solution as possible. It seems to us that the equilibrium we are discussing which for a compound such as p-benzoquinone can be measured with great accuracy affords a very good system in which to make an extensive systematic study on the influence of intermolecular factors on a simple well-defined chemical process.For comparison with theoretical work we have chosen the EO’s in alcoholic solution since these are the most adequate for our purpose. The above arguments make it plausible that we may find a relation between EO and the intramolecular energy of unsubstituted 0- and p-quinones and if such a relation exists it wiU provide the best justification for this procedure. We now have to consider the electronic energies in the molecules Q and QH (cf. section 2). As an example take 0 OH Following Evans Gergely and de Heer,f6 we can analyse the energy El of Q + H, apart from the energy of inner-shell electrons into the following terms where all D’s refer to a-bond energies between the atoms indicated in the subscripts.Fig. la shows diagrammatically the assignment of p-electrons to the carbon-oxygen skeleton. On each of the oxygens there is a doubly occupied py orbital whose symmetry-axis is in the plane of the ring. The energy of an electron in such an orbital is denoted by Epo. The energy of the system of 8 mobile electrons originating from p orbitals is denoted Similarly the relevant part of the energy of the quinol E, can be El = ~Dc#-c + ~DC~-C* + ~DC-EI + 2D0-0 + DH-H + + Esn (1) by E&z* expressed EMJ Eg = 2Dbs-c + 4Db,-u + ~ I - F I + SDko + 2D0-73 + Elon (2) EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINONES 103 where the D”s have the same significance as the D’s in equation (l) and reference to Pig.l b shows that we now have to consider the energy of 10 mobile electrons Elon originating from 8 pz orbitals. FIG la Thus for the energy-change in the reaction p-benzoquinone + H -+ quinol we have where AD denotes the total change in o-bond energy resulting from the changes in the bond lengths concerned. Strictly speaking AD may be different for different quinones (in the reduction of naphthaquinones for example changes in ten not six C-C o-bonds are involved). However in the reduction of 0- and punsubstituted quinones we may assume the changes in bond lengths as essentially taking place in the “ quinonoid nucleus ” only and consequently the change in energy AD may be taken as a constant throughout a series of quinones. Thus if we change from one quinone to another the energy change AE in equation (3) will be governed by changes in E - El = AE = AD - D H - E + 2Do-E - 4EPo + Elon - Ean .(3) FIG. l b (El, - E,,) the difference between the total binding energy of 10 and 8 mobile n-electrons in QH and Q respectively. Now if we wish we can replace (El - Eh) by (RQa - BQ) the differ- 104 QUARTERLY REVIEWS ence in resonance energy of the compounds concerned. This is allowed here because one takes as datum line for the definition of resonance energy (essentially delocalisation energy) the total energy ,?ZiOc. of the n-electrons in hypothetical localised bond structures of the type (IX) and (X). I :OH 0 ~ 0 Then Thus RQH = Eion - and RQ = EsX - E:,. 0.1 0.3 0.5 0.7 0.9 €0. volt. FIG. 2 As the last term is the same throughout a series of unsubstituted 0- and p-quinones we can essentially deal with RQHI - R,.By molecular-orbital calculations Evans Gergely and de Heer l5 have shown that RQHz and R can be expressed adequately by means of certain additivity rules the value of which will be further discussed by Coulson Evans and de Heer (in preparation). These calculations follow the earlier crude approximations EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINOXES 105 made by Branch and Calvin 12 [see also ref. (22)] Evans,13 and Diatkina and Syrkin,l* approximations which can be severely criticised.16 In Fig. 2 we show the linear relationship obtained by plotting the EO’s of a series of unsubstituted o- and p-quinones against (RQri - RQ) expressed in units of /3 (the “ resonance integral ” in benzene) and only known apart from an additive constant (a; - b)/P as reported by Evans Gergely and de Heer.These values have been corrected empirically for the hydrogen-bonding in the o-dihydroxy-compounds which will stabilise these by an amount 0.128 (& 2.4 k. cals.). Any other small differences between o- and p-compounds [e.g. in DO-= see equations (2) and (3) above] might be included in this correction term but the hydrogen-bonding will probably be the largest specific ortho-effect. As a result of these recent investigations the resonance theory is well established for the compounds under consideration. In the light of the analysis of section 2 and this section this can only mean that several other factors have the same influence throughout this series of quinones or cancel out by coincidence.We should not be surprised therefore if the situation with substituted quinones turns out not to be so simple. 4. The Influence of Substituents (a) Influence of Entropy and Environment.-E’rom the evidence reported by Conant and Fieser quoted several times in this Review we again seem to be justified in assuming that the entropy change is of the order of 30 entropy units and will be constant in a series of substituted quinones provided the measurements are made in the same solvent. However no very extensive experimental study of this subject has been made and we understand from Dr. Guptar 23 that in certain solvents A 8 may be very different from the above value. As we pointed out in section 2 the energetic considerations of isolated molecules really apply to the gaseous state and whereas in the case of unsubstituted quinones the same polar groups are present throughout the series this is no longer true if we consider now a series based on the same parent quinone but involving a change in the number or/and nature of substituents.This effect is amply illustrated in Fig. 3 in which we show the effect of chlorine substituents; on the Eo of p-benzoquin~ne.~~~~ el l8 It is seen that whereas in the gaseous state the free-energy change increases progressively and regularly with the number of chlorine atoms yet in alco- holic and benzene solutions EO shows variations which can only be due to specific environmental effects. The difference of the trend in alcoholic solution and’in benzene would indicate that the influence of solvent is very sensitive to its polarity and approaches closest to the ideal gaseous state in the non-polar solvent benzene.As far as we know this is the only series in which it has been shown definitely by comparison of the AG’s in the gaseous state and in a solvent that the environment gives rise to such aaP. G. Carter Trans. Faraday SOC. 1949 45 697. 23 Imperial Chemical Industries Limited Laboratories Blackley ; private corn- munication. 106 QUARTERLY REVIEWS important changes as to obscure the intrinsic intramolecular variation. This alone however illustrates how careful one must be in drawing conclu- sions on the influence of substituents in terms of intramolecular electronic considerations. (b) Infiuence on Intemoleculitr Energies Inductive and Conjugation Etpects.-If 8 substituent X is linked to an aromatic molecule (Eg.4) in general the entire electronic structure will change. As mentioned before * e ccp 0690 0.6 70 0450 0.630 0.610 0.590 0.570 I I I I 0 2 3 4 Number OF Cl-substibenhs in p -~enzo~uinon~ FIG. 3 the present quantum-mechanical treatment of such molecules does not allow us to treat these electronic changes as a whole but in accordance with the considerations of section 2 we have to analyse the influence of a substituent into the following effects (i) As the group X will in general not have the same electronegativity as the centre A to which it is linked a polar A-X o-bond will be formed. This bond in turn will polarise adjacent o-bonds in the aromatic molecule and so the effect is passed on becoming smaller and smaller the greater the distance from the bond A-X.This effect is usually called the " inductive effect " although in our opinion " inductive effect on the o-electrons" would indicate more explicitly what it amounts to. As mentioned in section 2 it is impossible at present to treat any effect on a-bonds and o-electrons quantitatively and we have to limit the discussion to qualitative considerations. (ii) As the " o-framework " (nuclei inner-shell and o-electrons) of the XVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINONES 107 original aromatic molecule has been distorted by the effect mentioned under (i) the field in which the mobile n-electrons move will change also. Consequently all the n-electronic energies (and hence the resonance energy) will change. We suggest calling this effect the " inductive effect on the n-electrons ',.(iii) The substituent X may provide a p,-orbital (Fig 4) which will extend the conjugation path (unsaturation path) of the n-electrons of the aromatic molecule. As this p,,-orbital will in general be occupied by one or two electrons the number of n-electrons is also increased by this substitution. Resulting chnges in crt-electronic energies charge shifts etc. will be denoted by tlhe term " conjugation effects ". These effects together with the one mentioned under (ii) can in principle be taken into account quantitatively by introducing the 7 Y Fra. 4 appropriate parameters in the secular equations concerned. How- ever the choice of such parameters is very ambiguous and if we are not dealing with the simplest kind of substituted molecule calcula- tions become very laborious.So here too one often has to fall back on qualitative considerations. (iv) The substituent X may be in the o-position to a group already present in the aromatic molecule. This may give rise to effects which may be of different origin but which we group together under "ortho- effects ". To mention a few examples -OH -0AJky1 halogens and -NH all provide if linked to an aromatic molecule a doubly occupied p,-orbital. With slightly more complicated substituents the situation is completely analogous; e.g. if we link a carboxyl group then the carbon and the two oxygen atoms each provide a p orbital thus extending the conjugated system while together they contribute four n-electrons. The same (three extra orbitals four extra electrons) holds for -NO,. In all these examples all the effects mentioned under (i) (5) and (iii) are present.With sub- stituents such as -NIE,+ and -CH only the inductive effects are effective unless we take into account '' hyperconjugation ",24 which allows for all the 2*R. S. Mulliken C . A. Rieke and W. G. Brown J . Amer. Cheni SOC. 1941,63 41 I f 108 QUARTERLY REVIEWS conjugation effects mentioned above although compared with '' ordinary " conjugation these are of a smaller order. As for the ortho-effects it is clear that e.g. in (XI) hydrogen bridges will be formed in both the quinone and the quinol while in compounds such as (XI) there can only be a (weak) hydrogen bond in the quinol. o-Substituted groups may also through steric effects affect the conjugation.26 0 + 9 + 23(1) 4- 30(3) + 28 + 49 ::I 0 (XII.) C0,Me .COPh . CN . . NO,. . This long theoretical introduction was necessary to show clearly the complexity of the situation. In fact " simple theories covering all experi- mental results " must always be looked upon with great suspicion. With this in mind we now direct attention to Tables I and 11 which reproduce some of the results obtained by Fieser and Fieser 1-7g*z [see also (12)]. - 252 - 210 - 198 - 181 (aqueous) - 133 TABLE I Eflect. of substituents in the 1- or 3-position on the EO of 9 lO-pbmnthraquinone (alcoholic solution) OMe . . OH . . CH . . NHAc . CHPh . Substituent. NH,. . :2 OCH . AEO (mv.). - 98 - 64 - 50(1) - 53(3) - 39 Substituent. OAc. . Br . S0,H . CoSG AEO (mv.). 1 I Suttstitueiit. II ________ AEO (mv.). + 58 + 59 + 76 + 91 ____- TABLE I1 E&ct of substituents in the %position on the Eo of 1 ; 4-mphthaquinone (alcoholic solution) Substituent AEO (mv.).11 Substituent. AEO (mv.). - 131 - 128 - 76 - 67 - 51 Substituent. C6H6 . . C0,Me. . c1 . . SO,*C6H,MO S0,Na. AE@ (mv.). - 32 9 + 24 + 69 + 121 - Summarising their work Fieser and Fieser 8 remark that '' although there are minor irregularities in the order it is seen that the groups that lower the potential of a quinone facilitate substitution in the benzene ring whereas the groups that increase the potential retard benzene substitutions ". Thus p6 See e.g. B. M. Webster and P. E. Verkade Rec. Tmv. chim. 1948 67 411. EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUlNONES 109 there apparently is a correlation between the influence of substituents on different properties of the same molecules (see also section c below) but this correlation does not offer us an explanation for e.g.benzene substitution constitutes a very complex problem itself. Branch and Calvin l2 conclude that “ those substituents which through either resonance or induction can assist the ring to accommodate a positive charge will stabilize the quinone while reducing the stability of the hydro- quinone and thus reduce EO. Similarly those groups which can assist in the accommodation of negative charge will raise the potential.” M. J. S. Dewar 26 says something similar “ Since a quinone is a cationoid ring system passing over into the anionoid hydroquinone by the uptake of two electrons it will be stabilized more by negative substituents than will be its reduction product while positive substituents will stabilize the reduction product more than the quinone.” But surely the uptake of two electrons is not a simple electrostatic process but is essentially the adding of two electrons to an available mole- cular cn-orbital.Moreover this only constitutes the first part of the reaction Q + 2e + 2H+ -+ QH, as it will be followed immediately by the association of two protons (two OH a-bonds being formed) as the reduction is nearly always carried out in an acid medium (compare section 2). Inductive and conjugation effects most certainly both play their part and it is difficult to understand the overall result theoretically. In some cases we can come to a better understanding for evidently one or the other effect predominates. A good test for tracing conjugation effects is given by changing the position of a substituent group in the molecule.If we do this and thus vary its distance from the essential group(s) in the aromatic compound (“ essential ” with respect to the property we are studying) then the inductive effect on the a-electrons should decrease with this distance while conjugation effects (together with the inductive effect on z-electrons) very often alternate (compare the o-p-actiyation of benzene substitutions). Such an alternation effect was reported by Fieser 17g for the EO’s of several substituted 9 10-phenanthraquinones. This effect was most pronounced with OH substituents ; the results reproduced in Table 111 TABLE 111 &fect of the position of the OH group o l y ~ the EO of 9 10-phemnthraquins AE0 (mv.) (relative to imply that for the 1- and 3-substituted compounds there must be a stabilisa- tion of the quinone which (to the same extent) has no analogy in the case a6 “ The Eleotronic Theory of Organio Chemistry ” Oxford Univ.Pres8 1949. 110 QUARTERLY REVIEWS of the corresponding dihydric phenol. Fieser himself pointed out that this is a resonance (conjugation) phenomena. The extra conjugation stabilisa- tion can be expressed qualitatively by the inclusion of canonical structures such as (XIII) and (XIV). Similar structures cannot be written for the (XIII.) 0 2- and 4-substituted molecules unless we break the benzenoid configuration of every nucleus as e.g. in (XV) and hence these canonical forms do not contribute much to the stability of these compounds. The fact that the influence of an OH group in the 2- or 4-position is practically nil must be ascribed to a small inductive effect (on the a-electrons) of the OH group.It is clear from this discussion that the OH group affects Eo by the stabilisation of the quinone owing to this conjugation effect. We might now enquire what other groups we should expect on this basis to exert a similar influence. Such will be -NH, acting in a way illustrated in (XVI) OAlkyl acting in a way similar to OH by virtue of its O-2pZ-electrons halogens and finally CH by virtue of its hyperc~njugation.~~ The sequence of the stabilisation of the quinone would be given by the degree of conjugation which in its turn will be dependent on two factors (a) the electronegativity of the attached centre and (b) the magnitude of the resonance integral between the ppz orbital on this centre and the corresponding orbital of the carbon atom to which this centre is attached.Little is known about the values of these quantities [organic chemists often entirely neglect the factor mentioned under (b) in qualitative discus- sions] and it is difficult therefore to arrange these groups in order. We would however suggest tentatively the following sequence Stabilisation of the quinol on the other hand d l be given by groups AB which can contribute canonical forms of the type (XVII) and (XT7111). EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUlNONES 111 Such groups are CO C02H CN NO,. Here again the question of sequence depends upon factors of which we have no precise knowledge. Comparing our expectations on the basis of this discussion with the numerical results listed in Tables I and 11 we note that there are two important discrepancies namely that the apparent conjugation effect of CH is much greater than what one would expect on the basis of hyper- conjugation whereas with C1 and Br the results are in complete disaccordance with our ideas.These discrepancies only emphasise the point that we have already made namely that inductive effects operating on the o-bonds must be taken into consideration in any complete theoretical treatment. In general in organic chemistry opposite inffuences of CH and halogens as they often occur have been ascribed to inductive effects and we feel that a quantitative treatment of this phenomena is one of the greatest needs of molecular electronic theory at present. OH (XVII.) I OH (XVIII.) lo_l( - 1 (XIX.) Two remaining points appear from Tables I and I1 (1) We cannot always speak of the influence of a substituent group on the EO as this influence may depend upon the structure of the parent quinone to which it is attached.This is most marked in .the exceptional case of the carbomethoxy-group which causes a slight increase in the potential of 9 10-phenanthraquinone but lowers that of 1 4-naphthaquinone. (2) In general the influence on Eo is more pronounced in the case of naphthaquinone. We can understand this for (i) inductive effects on the a-electrons will be greater (shorter distances to the important groups) and (ii) conjugation-stabilisation which is reflected by the consideration of structures such as (XIX) need not break the benzenoid structure of any nucleus.ortho-Effects will certainly play their part in determining the Eo of many of the quinones of Tables I and 11 but it is d s c u l t to separate their influence from other factors. Prelog et aZ.,27 however have shown that ortho-effects are predominant in determining differences in EO between quinones of the type (XX) n varying from 9 to 19. For large values of n the potential CCHaIn - 3 (XX.) 27 V. Prelog 0. Hiifliger and K. Wiesner Helv. Chim. Acta 1948 31 878 ; V. Prelog K. TNiesner W. Ingold and 0. Hsfliger ibid. p. 1326 ; see also J. 1950 420. 112 QUARTERLY REVIEWS approaches that for 2 6-dimethyl(or diethy1)-p-benzoquinone but from n = 13 the potential rapidly decreases with a further decrease in n. By a careful analysis Prelog et al. conclude that the lowering of the potential has to be ascribed to hydrogen-bridge formation between the methylene groups and the oxygen atom.Evidently this will stabilise the quinone more than the corresponding quinol as the oxygen atom is more negative in the former case. It is admitted that the tension caused by the quinonoid or benzenoid ring system by the smaller polymethylene rings might also be of importance. In this connection we refer to the work of R. T. Arnold and H. E. Zaug,zs who showed that the potential of indane-4 7-quinone (XXI) is much larger than that of 2 3-dimethylbenzoquinone (XXII) or 5 6 7 8-tetrahydro- naphtha-1 4-quinone (XXIII) the last two compounds differing but little in 0 0 ~ 0 (XXI.) (641 mv.) 0 (XXII.) (588 mv.) (XXIII.) (585 mv.) potential. Hydrogen bridges will not be of much influence in (XXI) so the tension caused by the presence of the five-membered ring which accord- ing to Arnold and Zaug will reduce the stability of the quinone more than that of the more flexible quinol system must be the predominant factor.We might consider these experiments as a support to Prelog’s hydrogen- bond theory though strictly speaking the two cases cannot be compared directly. (c) The Inffuence of Substituents and Hammett’s a-Constants.-P. G. Carter 29 has discovered a linear relationship between the Eo of many substi- tuted quinones and the a,-constants used by L. P. Hammett.30 Admittedly there are exceptions and the linearity is often approximate but there appears to exist an underlying relationship. We find this relationship surprising in its simplicity for the following reasons (i) Hammett’s a-constants have been applied with great success to the reactivity of single groups attached 0 0 0 (XXIV.) (XXV.) (XXVI.) e8 J . Amer. Chem. SOC. 1941 63 1317. 3o See e.g. ‘‘ Physical Organic Chemistry ” New York McGrnw-Rill 1940. I.C.I. Laboratories Blackley ; private coxnmuniccttion. EVANS AND DE HEER OXIDATION-REDUCTION POTENTIALS OF QUINONES 113 to the benzenoid ring. Here we are considering however the quinonoid nucleus and moreover the 30’s are related to the behaviour of two centres. (ii) Only in 3-substituted phenanthraquinones is the substituent in the p-position (or in a position equivalent to that) to one of the two important centres and at the same time it is so far away from the other that it might have no influence ; but in all other cases mentioned by Carter the situation is ambiguous ; e.g.in (XXIV) we would expect a relation between Eo and the average of 0;n and op and not with ap as such while in (XXV) and (XXVI) the linear relationship is even more surprising as R is in an m-position to one important group and in an o-position to the other. We would conclude from these remarks that Carter’s relationship simple though it appears cannot have the same weight as the o-constant relationship has in the systems to which Hammett originally applied his ideas. 5. Special Topics (a) Berliner’s Empirical Relation between Resonance Energies and the Oxidation-Reduction Potentials.-Berliner16 has obtained by subtracting from the known heats of combustion a standard energy based on a set of standard bond energies what he called “ empirical resonance energies ” for a number of very different types of quinones and dihydric phenols.He found a linear relationship between (RQHp - RQ) thus determined and EO. That such a relationship was obtained for a series of such different com- pounds including substituted quinones is entirely understandable since apart from a constant term Berliner’s (RIQH - R,) measures the difference in total electronic energy. His “ resonance energy ” is Werent therefore from that defined by us in this Review. We have confined it to the “ de- localisation energy ” of the mobile system of melectrons whereas Berliner’s method must include as well the differences in energy of certain cr-bonds expressed in terms of ionic-homopolar resonance in these particular bonds.We would suggest that in speaking of resonance energy one should be careful to define exactly what one means and if possible to confine Oneself to one type of electronic system. Neglecting entropy solvation and ortho-effects it would have been strange had Berliner not obtained a linear relationship and it seems to us that while we have shown that the n-electronic system is of predominant importance in the case of certain unsubstituted quinones Berliner’s treatment does not bring us any further in understanding the EO’s of more complicated systems. (b) Pullman’s QuinoWethane Treatment for Unsubstituteif Quinones.- A. Pullman G. Rerthier and B. Pullman 31 have recently made an extensive study of the n-electronic structure of several quinodimethanes such as p-benzoquinodimethane (XXVII).One has often considered these mole- cules as prototypes for q ~ i n o n e s ~ ~ as it is easier in theoretical work to 31 Bull. SOC. chim. 1948 15 460. 32 C. A. Coulson D. P. Craig A. Maccoll and Mme. A. Pullman “ The Labile Molecule ” Faraday SOC. L)iScussiom 1947 36 ; Diatkina and Syrkin loc. cit. ref. (14) ; &L Diatkina A. J. Namiot and J . Syrkin Compt. rend. Acad. Sci. U.R.S.S. 1946 48 233 ; M. G. Evans J. Cergely and J. de Hew Proc. Physical SOC. 1949 62 A 505. 114 QUARTERLY REVIEWS perform calculations on the former type of molecule. Pullman et al. have calculated the “ free valencies ” 33 of the end carbon atoms (equivalent to the oxygen atoms in the corresponding quinones) and the C H 2 ) = C H 9 “ bond-orders ” of the C=CH2 bond (equivalent to the C===O bond).Obviously both quantities are inter- dependent ; the greater the free valency of the carbon atoms concerned the smaller the double-bond character in those bonds. Pullman et nl. discovered a linear relationship between the bond orders in the CI-CH bonds and the Eo of the corresponding unsubstituted quinone. It is difficult to see what meaning is to be attached to these results for certainly the EO’s should be determined by the structure of the quinols formed on reduction as well as by the structure and reactivity of the quinones. We believe that both in equilibrium and reactivity problems it is necessary to consider not only the initial state of the system involved but dso the structure which is being formed. As Pullman’s method is just another way of dealing approximately with n-electronic systems it can add no more to our understanding of the influence of aubstituents than we have been able to discuss in the foregoing pages. 93 For a definition of these quantities see e.g. C. A. Coulson “The Labile Molecule” Paraday SOC. Discussion 1947 9. (xxvll’)

ISSN:0009-2681    

DOI:10.1039/QR9500400094

出版商:RSC    

年代:1950

数据来源: RSC

摘要:

Authors of articles :- Arnstein H. R. V. and Bentley R. isotopic tracer technique 172 Birch A. J. the reduction of organic compounds by metal-ammonia solutions 69 Bowen E. J. light absorption and photochemistry 23 6 Braude E. A. anionotropy 404 Burnett G. M. rate constants in radical polymerisation reactions 292 Coates G. E. organometallic compounds of the first three periodic groups 217 Evans M. G. and De Heer J. relation between the oxidation-reduction potentials of quinones and their chemical structure 94 Gaydon A. G. the emission spectra of flames 1 Hamer F. M. the cyanine dyes 327 Hawkins E. G. E. some organic peroxides and their reactions 251 Jones D. G. and Taylor A. W. C. some aspects of furan and pyrarz chemistry 195 Lister M. W. chemistry of the trans- uranic elements 20 Haitland P.biogenetic origin of the pyrrole pigments 45 Schofield K. the nitration of hetero- cyclic nitrogen compounds 382 Sexton W. A, structure and activity in synthetic insecticides 272 Sharpe A. G. interhalogen compounds and polyhalides 115 Ubbelohde A. R. melting and crystal structure 356 Whiffen D. H. rotation spectra 131 Whytlaw-Gray R. limiting densities 153 iicetic acid vinyl ester polymerisation of 299 At:rylic acid butyl and methyl esters oolymerisation of 304 305 Adsorbed layers melting in 369 Btioporphyrins 50 Af3ni.n as synergist 289 Alcohols unsaturated reduction of 71 Alkali organic compounds 218 Alkenyl peroxides 259 Alkyl hydroperoxides 251 Alkylidene peroxides 258 Ally1 alcohols rearrangements of 407 esters rearrangements of 41 7 halides rearrangements of 419 Aluminium organic compound8 228 INDEX 1950 427 Americium 20 metallic 32 solution chemistry of 28 heptad 424 pentad 422 triad 407 Anionotropy d i d 404 Anisole reduction of 90 Anthracene orbitals of 241 Antimony bromo-octafluoride 123 Aralkyl hydroperoxides 268 peroxides 269 Asymmetry isotopic 191 Azacyanines 346 B.A.L.preparation of 92 Beckmann rearrangement 405 Benzene orbitals of 239 240 Benzophenone relaxation times of 151 Beryllium organic compounds 223 Bicyclic compounds nitration of 388 Bisdimethylaminophosphonous anhydride Bishydroxyalkyl peroxides 257 Blood pigments 50 Bond lengths and moments of inertia 133 Boron organic compounds 227 Burners for low-pressure flames 13 14 tert.-Butyl nitrite photolysis of 429 N-isoButylwdecenamide as synergist 286 289 Cadmium organic compounds 225 Carbon atomic weight of 169 isotopes analysis of 174 monoxide flame spectrum of 5 12 oxysulphide Stark effect with 136 Cationotropy 404 Chemiluminescence in flames 18 Chlordane 285 286 Chlorine monofluoride absorption spec- Chlorophyll biosynthesis of 48 Chromic complexes absorption spectra of Citric acid relation of to tricarboxylic Cobalt salts absorption spectra of 244 Compressibility and limiting density 159 Conductivity and melting 373 374 Copolymerisation 3 15 Copper organic compounds 221 Coproporphyrins 52 Crystal structure melting and 366 Crystals liquid 375 376 trum of 125 244 cycle 193 relaxation times of 149 428 INDEX a- 8- and y-Curcumenes synthesis of 90 Curium 20 Cyanamide synthesis 186 Cyanine 327 &oCyanine 327 Cyanines chain-substituted 343 nomenclature of 330 trinuclear 349 meroCyanines 349 Cyanine dyes 327 354 p-Qmene dipole moment of 145 DDT 281 Debye formula 143 Density limiting 153 Deuterium analysis of 173 syntheses with 187 Dialkyl peroxides 254 Diamagnetic susceptibility and melting 373 Dielectric constant and melting 372 Difluorobromonium stannate 123 Dihydrofurans 204 Dihydropyrans 204 2 3-Dihydro-4-pyran 195 Dimethylamino acetoxyphosphonous acid ethyl ester 286 Dimethylberyllium 224 Dimethylborinic acid 228 Dimethyldeuteramine density of 170 Dinitro-o-cresol as insecticide 291 Diphenyl series nitration in 400 1 1-Diphenylethylene reduction of 83 Dyes cyanine 327 photochemistry of on fabrics 244 E.600 287 E.605 287 Elements transuranic atomic structure of 40 chemistry of 20 compounds of 31 halides 35 oxides 32 Entropy changes in on fusion 356 Ether peroxides 258 Ethers unsaturated reduction of 71 Ethyldeuteramine density of 170 Ethylene light absorption by 238 2-Ethylfuran 198 2 -E thylte trahydrofuran 1 9 7 Fabrics photochemistry of dyes on 244 Ferric ion complexes absorption spectra Films surface on liquids melting of 370 Flame fronts reactions in 13 Flames atomic 9 carbon monoxide 5 12 cool 8 emission spectra of 1 excitation in 18 flat diffusion spectra of 14 15 hydrogen 4 9 of 243 Flames of gases at low pressures 13 Fluorobisdimethylaminophosphine oxide Freezing point effect of pressure on 367 Furans chemistry of 195 hydrogenation of 196 oxidation of 200 Furfuraldehyde autoxidation of 201 Furfuryl alcohol 197 Gallium organic compounds 232 Gases density and compressibility of 156 rotation spectra of 132 Glucose degradation of 177 Glyoxdines nitration of 384 Gold organic compounds 222 woGuanine lSN- 178 organic 6 oxygen 9 286 Hamin constitution of 48 Halogen fluorides 1 16 Hept amethinc yanines 3 3 6 Herculin as synergist 289 Heterocyclic compounds nitration of 382 Hydrocarbon flames 6.Hydrocarbons chlorinated as insecticides Hydrogen atoms and molecules light peroxides 270 281 absorption by 237 flames band spectrum of 4 peroxide photolysis of 249 H yd rox yalky 1 h ydroperoxides 2 5 4 Hydroxydialkyl peroxides 257 2-( 3-Hydroxypropyl)furan 197 Indium organic compounds 234 Indoles nitration. of 391 Insecticides synthetic 272 Interhalogen compounds 115 Iodine bromide 11 7 Isoprene reduction of 80 Isotopes malysis of 173 as tracers 56 172 Isotopic masses 134 Keto-acids reduction of 180 Kinetics of melting 369 Labelled compounds 175 Light absorption of 236 scattering of and melting 372 Liquids relaxation times of 150 structure and properties of near melting Lithium organic compounds 219 Magnesium organic compounds 224 2 -Mercaptobenz thiazole as insecticide 2 80 Mercury organic compowds 226 Melting entropy of 356 grain-boundary 370 chlorides 11 6 point 363 370 INDEX 429 Melting theories of 376 Mesomorphic states 375 Metals melting parameters of 357 Metal-ammonia solutions reduction by 69 Methacrylic acid methyl ester copoly- Methanesulphonyl fluoride as insecticide Methincyanines 331 p-Methoxystyrene polymerisation of 304 Methyl alcohol flame 9 Methylboronic acid 228 Methylcopper 222 2-Methylfuran 198 2-Methyltetrahydrofuran 199 Microbalance silica-fibre 166 Molecules linear rotation spectra of 132 Moments nuclear quadrupole 139 Monomer reactivity ratios 316 thermodynamics of 356 merisation of styrene with 323 polymerisation of 302 290 non-linear rotation spectra of 134 of inertia 133 Naphthacene structure of 239 Naphthalene reduction of 81 88 Neocyanine 349 Neptunium 20 metallic 31 solution chemistry of 23 sulphides 37 tetrahalides 35 Nicotine alkaloids as insecticides 276 Nitration aromatic 382 Nitric oxide reaction of with atomic Nitrobenzene molecular radius of 151 Nitrogen compounds heterocyclic nitra- oxygen 12 photolysis of 249 heavy syntheses with 186 isotopes analysis of 174 tion of 382 Octadecane molar specific heat of 366 Olefin peroxides 259 cycZoOlefin peroxides 264 Organic compounds reduction of by Organometallic compounds of Groups I Oscillators monochromatic Klystron 13 1 Oxidation-reduction potentials of Oxotropy three-carbon 407 Oxygen atomic reaction of with nitric compressibility of 160 density of 153 158 flame atomic 9 isotopes analysis of 175 rotation spectrum of 143 metal-ammonia solutions 69 11 and 111 217 quinones 94 oxide 12 cycZoP&ra& peroxides 262 Parathion 287 Penicillamine preparation of 92 Penicillin 35,SS-radioactive 179 Pentamethincyanines 335 Pentane-1 4-dio1 200 Pentme-1 5-diol 199 Peroxides organic 251 Phenothiazine insecticidal toxicity of Phosphorus organic compounds as iwecti- Photochemistry in relation to textiles 244 Photographic sensi tisation 32 7 352 Phthalimide Gabriel synthesis with 186 Pigments pyrrole biogenetic origin of 45 Pinacol-pinacone rearrangement 405 Pinacyanol 328 Plants,.pigment synthesis in 48 Plutonium 20 carbide hydrides and nitride 39 iodates 38 metallic 32 organic compounds 38 oxides 33 solution chemistry of 24 sulphides 37 tetrafluoride 35 tetrahydroxide 34 Polyhalides 1 15 11 8 Polymerisat ion pho tosen si tised 24 8 Polymers relaxation times of 150 Polymethincyanines 338 Polymethylene compounds convergence freezing points of 360 Polyolefin peroxides 261 Polyvinyl acetate and chloride relaxation times of 150 Porphin 46 Porphobilinogen 51 Porphyrinogens 66 Porphyriw 46 synthesis of 62 Premelting 364 Pressure limiting 166 Prodigiosin 54 Propargyl alcohols rearrangements of Propylene oxide reduction of 74 Protochlorophyll 49 Protoporphyrin 9 47 Protoporphyrins 52 Pyrans chemistry of 195 Pyrazoles nitration of 385 Pyrethrins 275 synergists for 288 Pyridines nitration of 386 Pyrrole pigments biogenetic origin of 45 series nitration in 383 Quinodimethanes structure of 113 Quinoline series nitration in 393 Quinones oxidation-reduction potentials 280 cides 286 supersensitisation 353 radical reactions in 292 416 and structure of 94 430 INDEX Radicals inorganic in flames 10 Rate constants for copolymerisation 325 Reactions radical 292 Reduction by met al-ammonia solutions Relaxation times 145 Resonance energy and oxidation-reduction Rubber solutions photo-oxidation of 249 Rubber-like solids crystallisation of 376 Sessmin as synergist 289 Silicon atomic weight of 157 Silver organic compounds 222 Solids amorphous relaxation times of 148 structure and properties of near melting point 370 Spectra band in flames 4 continuous 11 electron transfer 243 emission of flames 1 inversion 141 rotation 131 Spectrum-line reversal 16 Stark effect 135 2-Stilbazole nitration of 402 Styrene copolymerisation of methyl Sugars l*C-labelled 178 reactions with 292 for polymerisation 296 69 potentials 113 methacrylate with 323 polymerisation of 301 310 311 Temperature electronic excitation of measurements in flames 15 Tetraethyl pyrophosphate 287 Tetrahydrofwans 214 Tetrahydropyrans 214 Tetraphenylporphin 65 Textiles photochemistry in relation to 244 Thallium organic compounds 234 Thermochemistry of interhalogen com- Thermodynamics of melting 356 Th ioc y anat es aliphatic as insecticides 2 7 8 Toluene relaxation and viscous flow of 151 Toxaphene 285 286 Trie t hylthallium 2 3 5 Trimethincyanines 334 Trimethylaluminium 229 Trimethylgold 222 Unsaturated compounds reduction of 79 Uranium carbide hydrides and nitrides 39 flames 16 pounds 124 compounds 22 metallic 32 Uroporphyrins 52 Vinylidene chloride polymerisation of 310 Volume changes in on fusion 361 Water relaxation time of 152 Zinc organic compounds 225 tetraphenylporphin 249

ISSN:0009-2681    

DOI:10.1039/QR9500400427

出版商:RSC    

年代:1950

数据来源: RSC