摘要:

QUARTERLY REVIEWS THE CHEMICAL SOCIETY PATRON HER MAJESTY THE QUEEN President E. L. HIRST M.A. D.Sc. LL.D. F.R.S. Vice-Presidents who have filled the office of President SIR IAN HEILBRON D.S.O. D.Sc. W. H. MILLS M.A. Sc.D. F.R.S. SIR CYRIL HINSHELWOOD M.A. D.Sc. F.R.S. C.K. INGOLD,D.SC. F.R.I.C. F.R.S. F.R.I.C. LL.D. F.R.S. SIR ERIC RIDEAL M.B.E. M A . Sc.D. F.R.S. W. WARDLAW C.B.E. ([D.Sc. Vice-presidents WILSON BAKER M.A. D.Sc. F.R.S. M. STACEY Ph.D. D.Sc. F.R.S. R.D. HAWORTR D.Sc.,Ph.D.,F.R.S. L. E. SUTTON M.A. D.Phil. F.R.S. E. D. HUGHES D.Sc. F.R.I.C. SIR ALEXAXV~ER ToDD;%M;A. D.Sc. F.R.S. F.R.S. Honorary Treasurer M. W. PERRIN C.B.E. M.A. F.R.I.C. Honorary Secretaries F. BERGEL D.PhiI.Nat. D.Sc. J. CHATT M.A. Sc.D. F.R.I.C. F.R.I.C. M. J. S. DEWAR M.A. D.Phi1. Ordinary Members of Council D.W. ADAMSON M.Sc. D.Phil. R. G. R. BACON Ph.D. A.R.C.S. G. R. BARKER B.Sc. Ph.D. R. M. BARRER D.Sc. Sc.D. F.R.S. F. BELL D.Sc. F.R.I.C. F.R.S.E. A. J. BIRCH M.Sc. D.Phi1. V. M. CLARK M.A. Ph.D. A. G. EVANS Ph.D. D.Sc. F.R.I.C. A. HICKLING D.Sc. Ph.D. F.R.I.C. L. HUNTER Ph.D. D.Sc. F.R.I.C. A. W. JOHNSON M.A. Ph.D. J. D. LOUDON Ph.D. D.Sc. B. LYTHGOE M.A. Ph.D. F.R.I.C. A. MACCOLL M.Sc. Ph.D. R. S. NYHOLM M.Sc. D.Sc. F.R.I.C. F. H. POLLARD B.Sc. Ph.D. R. E. RICHARDS M.A. D.Phi1. L. A. K. STAVELEY M.A. J. C. TATLOW Ph.D. D.Sc. F.R.I.C. W. WILD B.Sc. Ph.D. A.R.I.C. A.R.I.C. A.R.C.S. G. T. YOUNG Ph.D. M.A. A.R.I.C. Generd Secretary J. R. RUCK KEENE M.B.E. T.D. M.A. Librarian Deputy Librarian R. G. GRIBFIN F.L.A. J. BIRD Telephone Numbers Regent 0675-6. Printed in Great Britain by Butler & Tanner Ltd.Frome and London QUARTERLY REVIEWS Publication Committee Chairman C. K. INGIOLD D.Sc. F.R.I.C. F.R.S. C. C. ADDISON,D.SC.,P~.D.,F.R.I.C. F. BERGEL D.Phil.Nat. D.Sc. E. BOYLAND D.Sc. Ph.D. N. CAMPBELL D.Sc. Ph.D. N. B. CHAPMAN M.A. Ph.D. J. CHATT M.A. Sc.D. F.R.I.C. P. B. D. DE LA MARE D.Sc. Ph.D. M. J. S. DEWAR M.A. D.Phi1. D. D. ELEY Sc.D. Ph.D. H. J. EMELEUS D.Sc. A.R.C.S. D. H. EVERETT M.B.E. M.A. D.Phi1. G. GEE Sc.D. A.R.I.C. F.R.S. T. G. HALSALL Ph.D. M.A. A.R.I.C. B. A. HEMS D.Sc. F.R.I.C. D. H. HEY D.Sc. F.R.I.C. F.R.S. E. L. HIRST C.B.E. D:Sc. LL.D. H. R. ING M.A. D.Phil. F.R.S. D. J. G. IVES D.Sc. A.R.C.S. F.R.I.C. F.R.S. F.R.S. F.R.I.C. E. R. H. JONES D.Sc. F.R.I.C. G. W. KENNER M.Sc. Ph.D. H. C. LONGUET-HIGGINS M.A.B. LYTHGOE M.A. Ph.D. F.R.I.C. R. A. MORTON D.Sc. Ph.D. F.R.S. A. NEUBERGER Ph.D. M.D. F.R.S. R. G. W. NORRISH Sc.D. F.R.I.C. H. T. OPENSHAW M.A. D.Phi1. M. W.PERRIN,C.B.E.,M.A.,F.R.I.C. V. PETROW Ph.D. D.Sc. F.R.I.C. H. M. POWELL M.A. B.Sc. F.R.S. P. L. ROBINSON D.Sc. F.R.I.C. K. SCHOFIELD Ph.D. D.Sc. F.R.I.C. J. C. SPEAKMAN M.Sc. Ph.D. D.Sc. H. W. THOMPSON,M.A. D.Sc. F.R.S. E. E. TURNER M.A. D.Sc. F.R.S. A. R. J. P. UBBELOHDE M.A. D.Sc. F.R.S. D.Phi1. F.R.S. F.R.S. Editor R. 5. CAEN M.A. D.Phil.Nat. F.R.I.C. Assistant Editors A. E. SOMERFIELD Ph.D. A. D. MITCHELL D.So. F.R.I.C. L. C. CROSS Ph.D. A.R.C.S. F.R.I.C. LONDON T H E CHEMIOAL S O C I E T Y CONTENTS PAGE QUANTITATIVE STUDY OF STERIC HINDRANCE. By C. K. Ingold 1 MESO-IONIC COIMPOUNDS. By Wilson Baker and W. D. Ollis 15 THE CHEMISTRY OF POLONIUM.By K. W. Bagnall . . 30 SOME GENERAL ASPECTS OF THE INORGANIC CHEMISTRY OF CARBOHYDRATE PHOSPHATES. By A. B. Foster and W. G. ENERGY TRANSFER IN GASEOUS COLLISIONS. FLVORINE. By A. G. Sharpe . . 49 Overend . . 61 and W. D. McGrath . . 87 HALOGEN COMPOUNDS. By I. T. Millar and H. Heaney . 109 By 5. C. McCoubrey GRIGNARD AND ORGANOLITHIUM REAGENTS DERIVED FROM DI- THE STRUCTURES OF ELECTRON-DEFICIENT MOLECULES. By ULTRASONIC ANALYSIS OF MOLECULAR RELAXATION PROCESSES NUCLEAR QUADRUPOLE @UPLING AND CHEMICAL BON~ING. By RECENT ADVANCES IN SESQUITERPENOID CHXMISTRY. By D. H. H. C. Longuet-Higgins . . 122 IN LIQTJIDS. By R. 0. Davies and J. Lamb . 134 W. J. Orville-Thomas . 162 R. Barton and P. de Mayo . 189 SEMICONDUCTIVITY AND CATALYSIS. By Peter J. Fensham . 227 THERMAL TRANSFORMATIONS IN SOLIDS. By A. R. Ubbelohde 246 THE MOLECULAR-ORBITAL AND EQUIVALENT-ORBITAL APPROACH TO MOLECULAR STRUCTURE. By J. A. Pople . . 273 ELECTRON CORRELATION AND CHEMICAL CONSEQUENCES. By P. G. Dickens and 5. W. Linnett . . 291 ELEMENTARY REACTIONS IN GAS-PHASE SLOW COMBUSTION. By C. F. H. Tipper . . 313 INORGANIC STEREOCHEMISTRY. By R. J. Gillespie and R. S . Nyholm . . 339 LIGAND-FIELD THEORY. By J. S. Griffith and L. E. Orgel . 381 CUMULATIVE INDEXES Vols. I-XI . 395 THE INOSITOLS. By S. J. Angyal . . 212

ISSN:0009-2681    

DOI:10.1039/QR95711FP001

出版商:RSC    

年代:1957

数据来源: RSC

摘要:

MESO-IONIC COMPOUNDS By WILSON BAKER &LA. D.Sc. X.R.S. and W. D. OLLIS PH.D. (DEPARTMENT OF ORGANIC C~MISTRY THE UNIVERSITY BRISTOL) IN 1949 the term meso-ionic was introduced to describe a class of novel heterocyclic compounds of which the sydnones are the most closely investi- gated members. Since the proposal was first made the wide generality of this structural type has been recognised and several new members have been discovered so that a review of this subject seems both opportune and desirable. Sydnones as Meso-ionic Compounds In 1935 Earl and Mackneyl showed that treatment of N-nitroso-N- phenylglycine (1 ; R = Ph R' = H) with warm acetic anhydride yielded a well-crystalline neutral anhydro-derivative which was given the fused- ring structure (2 ; R = Ph R' = €€). Later work showed that such dehydration is a quite general reaction.2 The exact nature of these anhydro- derivatives has aroused considerable interest and various structural proposals have been made.2 The name " sydnone " has been given to this class of compound because they were first studied at the University of Sydney and the anhydro-derivative of N-nitroso-N-phenylglycine was termed N - phenylsydnone.The sydnones are hydrolysed by hot aqueous sodium hydroxide with regeneration of the original nitroso-acid and by hot dilute acid to give an aryl- or alkyl-hydrazine (3) a carboxylic acid (formic acid in the case of N-phenylsydnone) and carbon dioxide.2 These facts made any lEarl and Mackney J. 1935 899. aEade and Earl J. 1946 591. ( a ) Baker and Ollis Nature 1946 158 703 ; (b) Kenner and Mackay ibid.p. 909 ; (c) Earl ibid. p. 910; ( d ) Baker Ollis Poole Barltrop Hill and Sutton ibid. 1947 160 366; ( e ) Earl Leake and Le Fbvre ibid. p. 366; (f) Eade and Earl J. 1948 2307; (9) Baker Ollis and Poole J. 1949 307; (h) idem J. 1950 1542 ; Crane Eastman Kodak Co. Org. Chem. Bull. 1950 22 No. 2 ; (i) Earl Chem. and Id. 1953 746 1284 ; ( j ) Haminick and Roe ibid. p. 900 ; (k) Orville Thomas &id. 1955 533 ; ( I ) Baker and Ollis ibid. p. 910 ; (m) Bieber $bid. p. 1055 ; (n) Earl Rec. Trav. chim. 1956 75 346; ( 0 ) Jennen IIIe Congr6s National des Sciences Brussels 1950 ; Chimie e t Industrie 1952 67 ; XXVIIIe Congr@s International de Chimie Industrielle Brussels 1954 622. 16 16 QO’ARVERLY REVIEWS molecular rearrangement during sydnone formation most unlikely and formed the basis of the original covalent structure (2).19 2 This fused-ring structure was considered unacceptable by Baker and Ollis 3a who suggested that the sydnones could be satisfactorily represented by a modification of the structure (2) which had been tentatively proposed by Earl and Mackney.In view of the impossibility of representing the sydnones by any even approximately satisfactory covalent structure the sydnones were regarded as resonance hybrids of a number of dipolar and tetrapolar forms of which twelve were shown in the original paper ; three of these are shown below for the case of N-phenylsydnone. CH=C-O- ,CH=C-O- CH-C-0’ P h - K N Ph*N I Ph.h4- 11 - \N = Ot \N -o+ When this proposal was made it was emphasised that the contribution of these canonical forms to the hybrid molecule would vary considerably and it was felt that the arbitrary selection of any one of them as a structural formula would be misleading.Clearly what was required was a symbol and a general adjectival term which would indicate that the sydnones had a mesomeric structure derived from a number of ionic in the sense of zwitterionic forms. The word meso-ionic was therefore introduced and the symbol & suggested by Simpson Hence for example N-phenylsydnone was referred to as a meso-ionic compound and it was represented by formula (4) in which all the atoms taking part in the hybrid structure were shown as linked by single bonds. was a t first accepted. ,CH-C-0 Ph*N 2 I “-0 (4) It was later found that the concept of molecules of this type had been anticipated by Schonberg in 1938 in the case of the “ endothiodihydro- thiodiazoles ” (see p.24) and the reagent “ nitron ” (see p. 26).5 Schon- berg indeed appears to have been the first to recognise the existence of compounds which cannot be represented satisfactorily by a covalent struc- ture but which can be properly regarded as a hybrid of electrically charged forms. The generality of this class of molecule was recognised only after the structure of the sydnones became known although the views of Schonberg had been expanded and more precisely formulated by Jensen and Friediger in 1943. The Term Meso-ionic and the Representation of Meso-ionic Compounds The use of the term meso-ionic and of the early symbolism shown in formula (4) requires careful examination. Neither is justified unless existing nomenclature and formula are inadequate.If the sydnones had been an isolated class of compound it is doubtful whether any such suggestions Simpson J. 1946 95. 6Schonberg J. 1938 824. 13 Jensen and Friediger Kgl. danske Videnskab. Selskab Jlat.-fys. Medd. 1943 20 1; Chem. Abs. 1945 39 2068. BAKER AND OLLIS MESO-IONIC COMPOUNDS 17 would have been necessary but as will be seen there are many known groups of compounds related to the sydnones which it is otherwise impossible to classify except as “ sydnone-like ’,. The scope of the word meso-ionic needs clear definition in view of the fact that inaccuracies in its application have appeared in the literature. These have been discussed by Katritzky7 who also raised objections to the word meso-ionic. We believe that a satisfactory definition of the word meso-ionic is now possible and that its retention is desirable but the special symbolism shown in formula (4) is no longer necessary because existing accepted symbolism widely adopted since the & sign was first put forward may now be used.The revised definition of the word meso-ionic and the use of an accepted instead of a special symbolism were advanced by the Reviewers in 1955,s2 who realised the advantage of discussing these compounds in terms of mole- cular orbital theory. Almost exactly similar proposals were put forward a few weeks later and independently by Bieber,3m the only difference being a very minor one of symbolism which is mentioned lielow. These new proposals emphasise the essentially aromatic character of tjhe sydnones and related compounds which was explicitly recognised in 1946.3a The essential feature of all aromatic compounds is a five- six- or seven- membered cyclic structure with a total of six n electrons associated with all the atoms of the ring. The ring must be planar or almost planar and it must possess a considerable resonance energy. These conditions are satisfied in the carbocyclic series in the case of benzene with its planar six- membered ring and six n electrons. In the case of the cyclopentadienyl anion each of the five CH groups contributes one electron and the sextet is made up by the gain of a further electron so that aromatic character is exhibited in the anion C,H,-. I n the seven-membered carbocyclic ring as in the tropylium cation C7H7+ each of the seven CH groups contributes one electron ; loss of an electron then gives the sextet which therefore becomes associated with a positive charge.The negative charge may be resident on an accompanying anion as in tropylium bromide C7H7 +Br- or on a covalently linkcd atom such as oxygen in tropone. The same conditions apply to the requirements for the development of aroniatic char- acter in heterocyclic compounds. In furan and pyrrole the heteroatoms each supply two electrons so that in these cases the five-membered rings become aromatic when neutral. In pyridine the nitrogen atom supplies one electron giving a neutral aromatic molecule with a six-membered ring. It is desirable to mention these facts in order to make clear the basis of the new formulation of the sydnones and related compounds. Reference may be made t o two recent reviews “Non-benzenoid Aromatic Com- pounds ” 8 and “ The Development of the Concept of Aromaticity ” where these matters are dealt with in much greater detail.Katritzky Chein. and I n d . 1955 521. 8 Baker and McOmie “ Progress in Organic Chemistry ” od. J. W. Cook Butter- Baker “ Perspectives in Organic Chemistry ” ed. Sir A. Todd Interscience worth London 1955 Vol. 111 pp. 44-50. Publ. 1956 pp. 28-67. B 18 QUARTERLY REVlEWS For N-phenylsydnone as a typical representative of the class it will be seen that before delocalisation there is a total of seven 2p8 electrons supplied by the atoms which make up the five-membered ring and one more such electron is available on the exocyclic oxygen atom ; the origins of these electrons are shown in formula (5) by the positions of the numerals representing their numbers.The lone pairs of electrons which are accom- modated in orbitals unsuitable €or overlap and which therefore are not involved in the delocalisation process are also shown. A sextet of n electrons may now be acquired in association with the ring if one of the seven electrons initially supplied by the five annular atoms is paired with the single electron provided by the exocyclic oxygen atom. The result is that the sydnone ring becomes both positively charged and aromatic. (7)- .. ( 5) (6) ,CH - C-0- ,CR'- 01 6- (9) &- Ph-N (+) I R.N 'N -0 N -a (8) The situation is very similar to that occurring in tropone lo which has been represented both by the covalent structure (6) and by the polar struc- ture (7) with its sextet of n electrons in association with a positive charge the sextet being represented by the large inscribed circle.This symbolism which is now widely accepted was first used by Doering and Knox.ll Formulae (6) and (7) are both acceptable and for this reason tropone and its derivatives are not regarded as meso-ionic and the definition given later does not include such compounds.* It is to be noted that formula (7) does not imply that a complete negative charge is resident upon the exo- cyclic oxygen atom. It does however emphasise the aromatic weakly ketonic and dipolar nature of tropone which has a considerably higher boiling point than its isomer benzaldehyde and is miscible with water. The sydnones may similarly be very satisfactorily represented by the structural formula (8) and they may be regarded as five-membered hetero- cyclic analogues of tropone.The large inscribed circle represents the six z electrons occupying molecular orbitals associated with all the annular atoms though this association will certainly be unequal ; it follows that the positive charge must also be regarded as unevenly distributed though it is probably mainly associated with the nitrogen atom to which the pheiiyl group is attached. First that Two points must be especially emphasised. lo Pauson Chem. Rev. 1955 55 9. 'lDoering and Knox J . Amer. Chem. Soc. 1952 74 5686. * In the Annual Reports on the Progress of Cl~ernisiry (1955 52 2.13) it is stated that the term meso-ionic should be applicable to tropone and t o the betaine (12) (p. 19). In its context the statement seems to imply that tjhis represents our view but we have definitely stated that we are of tIhe opposite opinion.3' We are informed by the Reporter Dr.W. Wilson that the statement in the Aian74al Repovt.9 represented solely hk own view. BARER AND OLLIS MESO-IONIC COMPOUNDS 19 no covalent structure for the sydnones can be written corresponding to the covalent structure (6) for tropone and secondly that the use of forniula (8) for the sydnones and formula (7) for tropone does not imply that unit positive and negative charges are associated with the ring structures and the exocyclic oxygen atoms respectively. The Reviewers prefer to use the simple formula (8) for the sydnones with the mental reservation that the charges are something less than unit charges i.e. the molecule will assume a state of compromise between the opposing tendencies towards the com- pletely polar aromatic form and towards the neutralisation of the opposite charges.Organic chemists are well used to such reservations in inter- preting for example the Kekul6 structures for benzene or the covalent structures usually written for the amides or the cyanides. The only differ- ence between the proposals now put forward and those of Bieber Qm is that the latter prefers to incorporate these reservations in the formula for the sydnones by means of a special symbol as shown in (9) which although fairly self-evident needs to be explained ; the lone pairs of electrons are shown by short lines. The representation of N-phenylsydnone by formula (8) stresses its aromatic character and its close similarity to y-pyrone (10) and to the y-pyridone (11).At first sight it may apparently be also very closely related to the betaine (12) but it is not intended that such a compound should be regarded as meso-ionic because it almost certainly possesses a high degree of charge fixation and it may be sntisjacforily represented by the dipolar structure (12).* Similarly the " enol-betaines " such as (13) are not to be regarded as meso-ionic although this description has been given to them.12 Examples of the various known types OE compound which are regarded as meso-ionic are described later and a definition of the word in as precise terms a.s possible must be attempted. I n its very nature it is as difficult to define as the word " aromatic " in view of the varying degrees of aroma- ticity which are found in passing from benzene a t one end of the scale to say furan towards the other end.Probably the best definition of an aromatic compound is that given by Dewar l3 who states that " an aromatic compound may be defined as a cyclic compound with a large resonance energy where all the annular atoms take part in a single conjugated system ". 12Stafford J. 1952 581. l 3 Dewar " The Electronic Theory of Organic! Chemistry " Oxford 1949 p. 160. * See footnote p. 18. 20 QUARTERLY REVIEWS The necessarily vague phrase here is “ with a large resonance energy ” and no attempt to define the value of “ large ” in kcal. per mole would be acceptable. It is now suggested that a compound may appropriately be called meso- ionic if it is a five- or possibly a six-membered heterocyclic compound which cannot be represented satisfactorily by any one co-valent or polar structure and possesses a sextet of electrons in association with all the atoms comprising the ring.The ring bears a fractional positive charge balanced by a corresponding negative charge located on a covalently attached atom or group of atoms. The inevitable ambiguity here is the word “ satisfactorily ” and chemists are not likely always to agree on what may or may not be a satisfactory constitutional formula for a given com- pound. Indeed different formule may rightly be used on different occasions for the same compound according to the structural feature which it is desired to emphasise e.g. the two representations of tropone (6) and (7) have already been mentioned. As a corollary to the definition it follows that in any particular polar structure which may be written for a meso-ionic compound the charges cannot wholly neutralise one another to give a covalent structure.The meso-ionic compounds described in this Review are all five-membered heterocyclic compounds. Although six-membered meso-ionic compounds might conceivably exist none has as yet been definitely prepared. The Chemistry and Physical Properties of the Sydnones The mechanism of the formation of N-phenylsydnone by the action of acetic anhydride on N-nitroso-N-phenylglycine was studied by Baker Ollis and Poole 3h who showed that the mixed anhydride (14) behaves as a true intermediate. The pure mixed anhydride was prepared by reaction of the potassium salt of N-nitroso-N-phenylglycine with acetyl chloride and when kept for a few days a t room temperature or more rapidly when 0 H ,CH2-t-oAc I P -OAc- ,ti~-cG CH-C-0 .- ph.N< I 2 Ph-N’ c;) I Ph*N t N - 0 ‘N-0 ONTO (14) 0 ,CHP,H ‘c=o ,Cti2-8pOAc ,CH,-c=O - N I t ‘%-0 H-N L*‘c HN R U R R Oxazolone heated in benzene solut.ion it was transformed into N-phenylsydnone.The reaction sequence may be represented as annexed and it will be seen that it is very closely analogous to the formation of oxazolones by dehydration of a-acylamino-acids. This mechanism is also compatible with the observa- tion that N-nitroso-N-phenylglycine yields N-phenylsydnone when treated either with thionyl chloride. or with trifluoroacetic anhydride which is BAKER AND OLLIS MESO-IONIC COMPOUNDS 21 known to form mixed anhydrides with carboxylic acids; l4 the second reaction proceeds instantaneously in ethereal solution at -5" in 93% yield.Many sydnones (15) are now known in which R may be an alkyl or aryl group [R cannot be a hydrogen atom otherwise rearrangement to the oxadiazoles (16) would be possible] and R' may be hydrogen or an alkyl or an aryl group. The existence of stable N-alkylsydnones such as N - methyl- N-n-butyl- N-cyclohexyl- and N-benzyl-sydnones demonstrates that conjugation of the sydnone ring with another aromatic system is not essential. Compounds e.g. (17) and (18) in which the sydnone ring forms part of a polycyclic system have also been prepared.15 N-3'-Pyridylsydnone (15 ; R = 3-pyridyl R' = H) is normally colourless but exposure to sun- light causes an almost instantaneous phototropic change to a deep blue modification which slowly reverts to the colourless form.16 The sydnones are stable and highly crystalline with the exception of a few N-alkyl sydnones,ls and most of them are fairly soluble in benzene.N-Phenylsydnone has m.p. 135" and sublimes unchanged a t l l O o / l mm. ; N-cyclohexylsydnone has m.p. 64" and N-methylsydnone has m.p. 36". Their lactonic character is revealed by reaction with various nucleophilic reagents but they are much more stable than normal y-lactones. Thus N-phenylsydnone may be crystallised unchanged from boiling water but is hydrolysed when heated with aqueous sodium hydroxide; it reacts with hot benzylamine yielding the benzylamide of N-nitroso-N-phenylglycine Ph*N(NO)*CH,*CO*NH*CH,Ph but it is unaffected by aniline a t 125". 3h The sydnones undergo an interesting reaction when heated with aqueous acid giving an alkyl- or aryl-hydrazine a carboxylic acid and carbon dioxide.lt 2 Compounds (17) and (18) cannot hydrolyse in this way ; (17) gives carbon dioxide and l-amino-1 2 3 4-tetrahydro-2-oxoquino- line.15 The probable mechanism of acid hydrolysis is shown below and is supported by the interesting observation that a benzene solution of N - phenylsydnone reacts rapidly with one molecular proportion of water and hydrogen chloride or bromide in ether giving N-formyl-N-phenylhydrazine and carbon dioxide.N-Phenylsydnone reacts rapidly with chlorine or bromine to give mono- halogen derivatives and the same bromo-derivative is obtained by reaction 14Bourne Stacey Tatlow and Tedder J. 1949 2976. l6Harnmick Roe and Voaden Chem. and Ind. 1954 251. l6 Fugger Tien and Hunsberger J .A ~ w . Chem. SOC. 1955 77 1843 ; Tien and This is the easiest route to a-acylhydrazines." HuILBberger ibid. p. 6604. 17Kenner and Mackay Nature 1947 160 465. 22 with N-bromosuccinimide in chloroform. In these reactions the hydrogen atom directly attached to the sydnone ring is replaced and no substitution in the phenyl group is observed. It is a,lso possible to nitrate N-phenyl- sydnone in concentrated sulphuric acid a t - lo" to give C-nitro-N-phenyl- sydn0ne.3~ These reactions demonstrate the aromatic character of the sydnone ring. The nucleophilic reactivity of sydnones is also involved in their recently discovered reaction with 1 4-quinones giving the complex heterocyclic quinones (19) and (20) and carbon dioxide.18 The stability of the sydnone nucleus is clearly demonstrated by the observation that N-phenylsydnone resists catalytic hydrogenation except in presence of highly active catalysts.It may be slowly reduced to the ammonium salt of N-phenylglycine with hydrogen and Adams's platinum oxide catalyst. 3g In an attempt to prepare a thiosydnone N-phenylsydnone was treated with phosphorus pentasulphide but the product proved unexpectedly to be 1 4-diphenyl-1 4-dihydrotetrazine (2l>.l9 ,CH=N PhN N*Ph N=CH' (2 0 Further evidence in support of the aromatic meso-ionic structure for the sydnones is provided by the ultraviolet absorption spectra of iV-cycZo- hexyl- and N-benzyl sydnones which both show a well-defined absorption band a t 292 m ~ . ~ ~ 2o The position and the intensity of this band are char- acteristic of an aromatic system and when further conjugation of the sydnone ring is possible as in N-phenyl- or NC-diphenyl-sydnone the expected shift to longer wavelength is observed.No detailed study of the infrared spectra of sydnones has been reported but the published results 16 2l show that the position and nature of the sydnone carbonyl absorption vary considerably with the structure of the sydnone and in some cases a double band in the carbonyl region is observed. The position of the carbonyl 18Hammick and Voaden Chern. atad Ind. 1956 739. 1g Baker Ollis and Poole J . 1950 3389. 2o Earl Le Fi.vre and Wilson J . 1949 S 103. alEarl Le FBvre Pulford and Walsh J. 1951 2207. BSKER AND OLLIS MESO-IONIC COMPOUNDS 23 band varies over the range 1720-1'770 cm.-l but the interpretation of this in terms of the degree of double-bond character is not possible because of the unique structural nature of the sydnones.It is however incompatible with the bicyclic structure (Z) as the @-lactonic carbonyl absorption is a t 1818 cm.-l for ,!?-butyrolactone.22 Of the various physical methods which are now available for the exam- ination of organic compounds it was recognised at an early stage that the measurement of their dipole moments WRS likely to be the most revealing. ,4n interpretation of the dipole moments of a large number of sydnones has been made by Hill and Sutton 2 3 ; C f - 3d and by Earl Leake and Le FBvre. 3e 24 N-cycZoHexylsydnone which is non-polar except for the sydnone nucleus has a moderately large dipole moment of 6.7 D in benzene. A comparison of the dipole moments of N-phenyl-(6.48 D) N-p-chlorophenyl- (5.01 D) and N-p-tolylsydnone (6.89 D) with those of chlorobenzene (1.55 u) and toluene (0.4 D) shows that the dipole of the sydnone structure has its negative pole directed towards the carbonyl-oxygen atom.Further analysis showed that the five-membered ring was almost certainly flat and this coupled with the magnitude and direction of the sydnone group moment provided strong support for their formulation as meso-ionic compounds. This very satisfactory agreement inade a more quantitative theoretical treatment of the sydnones very desirable. This was done and the formal charge distribution on the various atoms of the sydnone ring was calculated by the molecular-orbital method. The results olota'ined by Hill Sutton and Longuet-Higgins 25 are summarised in formula (22) and after some refine- ment the results given in formula (23) were obtained Iny Orgel Cottrell Dick and Sutton.26 Both calculations show that the ring bears an aggregate positive charge of the order 0.7-0.9 balanced by a negative charge on the exocyclic oxygen atom.These calculations indicate that there is a sub- stantial charge transfer from the sydnone ring and that the bonding of the carbonyl group has quite a high degree of single-bond character (the two values given for the calculated n bond order are 0.37 and 0.59). This is in complete agreement with the meso-ionic structure. It is important to recognise that a meso-ionic compound does not necessarily possess a large dipole moment,27 and that such a moment is not necessarily indicative of a meso-ionic structure. 2 2 Taufen and Murray J.Amer. Chem. Soc. 1945 67 754. 23Hill and Sutton J. 1949 746; 1953 1482. 2 4 Earl Leake and Le FBvre J. 1948 2269. a 5 Hill Sutton and Longuet-Higgins J. Chim. phys. 1949 46 244. z6 Orgel Cottroll Dick and Sutton Truns. Paraday SOC. 1961 47 113 27 Kaufmann Ernsberger and McEwan ibid. 1956 78 4197. 24 QUARTERLY REVIEWS Katritzky 7 has recommended that if a systematic name for the sydnones is required the nomenclature for betaines should be employed. Thus N-phenylsydnone becomes anhydro-5-hydroxy-3-phenyl-l-oxa-2 3-diazo- linium hydroxide. Survey of Known Meso-ionic Compounds As expected heterocyclic compounds with structures analogous to those of the sydnones can exist and in fact many such compounds are known but when they were first described they were often given either bridged-ring or other stereochemically impossible endo-types of structure.Since the generality of the meso-ionic type of structure was first recognised several new examples have been discovered. I n this survey of meso-ionic com- pounds it has been felt desirable to classify them by the trivial names under which many of them were first described but if necessary the betaine nomen- clature could be applied. Xydnone 1;mines.-Brookes and Walker * have found that various N-methylamino-N-nitroso-acetonitriles (A) react with acids to give salts (B) of sydnone imines. Thus the hydrochloride (B ; X = C1) is precipitated in high yield when the nitrosamine (A) is treated with ethereal hydrogen chloride and the nitrate (B ; X = NO,) is similarly formed when an equi- molecular proportion of concentrated nitric acid is used.This nitrate is dehydrated by acetic anhydride or concentrated sulphuric acid to the meso- ionic compound (C) in which the exocyclic electron-accepting nitramine . group is Under very mildly basic conditions the salts (B) do not yield either free sydnone imines or the sydnones but undergo hydrolysis to the open- chain nitroso-amides Me*N(NO)*CHR*CO*NH,. “ Endo-thiodihydrothiodiaxo1es.”-These compounds were first prepared in 1895 by Busch and his co-workers 28 who gave them the endo-structure (26) but in 1938 it was suggested by Schonberg that they should be represented by a hybrid structure involving charged forms. It is now clear that they are best represented by the meso-ionic structure (25). They were prepared by Busch by reaction of an acid chloride with the potassium salt of an N-aryl-N’-dithiocarboxyhydrazine (24) ; for the synthesis of compounds unsubstituted in position 5 (Le.25 where R’ = H) the potassium salts are treated with ethyl formimidate hydrochloride or more conveniently with sodium dithioformate in aqueous solution. 29 28 Busch and co-workers Ber. 1895 28,2635 ; J. prakt. Ohm. 1899 60,218 228 ; 1903 67 201 216 246 257. 2Q Baker Ollis Phillips and Strawford J. 1951 289. * P. Brookes and J. Walker (unpublished work) to whom we are indebted for this re-publication information. BAKER AND OLLIS MESO-IONIC COMPOUNDS 25 (26) These thiadiazoles (25) are bright yellow stable compounds with high melting points and they are sparingly soluble in the usual organic solvents. They cannot be dethionated with mercuric oxide even in boiling benzene and they react exothermally with methyl iodide to give products which were first given covalent structures but it is obvious from a consideration of their physical properties that they are salts (27) ; they behave as strong binary electrolytes in aqueous or alcoholic solution.The structural relation between these salts (27) and tropylium bromide (28) is very close in that in neither case does the covalent form exist owing to the stability of the cation with its associated six z electrons. The meso-ionic character of the “ endo-thiodihydrothiodiazoles ’’ is shown by their large dipole moments ; the diphenyl compound (25 ; R = R’ = Ph) has a dipole moment 6 of 8.8 D. The dipole moments of several members of this series have been measured by Edgerley and Sutton 3O and from the dipole moments of the N-phenyl (25 ; R = Ph R’ = H) N-p-chlorophenyl (25 ; R = p-Cl*C,H, R’ = H) and N-p-tolyl(25 ; R = p-Me*C6H, R‘ = H) derivatives which are 8-36’ 7.09 and 8.70 D respectively it is clear that there is a high degree of charge transfer from the five-membered ring to the exocyclic sulphur atom.‘ ‘ Endo- thiotriaxolines . ’ ’-The ‘ ‘ endo - thiodihydrot hiodiazoles ’ ’ react with primary amines giving substances which were originally formulated as in (29).28 It is now clear that they are meso-ionic compounds for which two isomeric structures are possible (30) or (31). These compounds may also be formed from acid chlorides and 1 4-diarylthiosemicarbazides and the tendency to form the aromatic system is so great that they are even formed from benzaldehyde and 1 4-diarylthiosemicarbazides.(30) (3 I> The dipole moment R = R” = Ph ‘‘ Endo-irnino- and Endoxy-triazo1ines.”-These compounds prepared of the compound (30 or 31 ; R‘ = Me) is 8.4 D. 30 Edgerley and Sutton personal communication. 26 QUARTERLY REVIEWS from substituted guanidines and acid chlorides (or where R2 = H by using formic acid) were originally given the structure (32) but this must now be replaced by the meso-ionic formula (33). 31 (3 2) (3 3) These compounds are yellow basic substances whose nitrates are usually very insoluble in water. The nitric acid precipitant “ nitron ” (dipole moment 32 7-2 D) is the triphenyl- derivative (33) (Rl = R3 = R4 = Ph R2 = H) and it was recognised by Schonberg as having a hybrid structure.It was originally given the “ endo-imino ” structure (32) and is unfortun- ately still usually given this sterically impossible formula. “ Endoxytriazolines ” (34) and (35) have been prepared by Busch and his co-workers 33 by the annexed routes. phCCI= N Ph ,CPh=NPh cot, ,CPh-NPh / CPh-0 Ph.N\ (,+,’i I Of Ph-N :+ I - \N‘-C-fiPh + - Ph-N N-C-O- (3 5) PhN H-N H NH2 . The 3-aryloxatriazoles (36) may be prepared by treating nitroform with diazonium and recently it has been shown 35 that N-alkylsemicarb- azides (37) and nitrous acid give the 3-alkyloxatriazoles (38). 3-Aryloxa- triazoles cannot be prepared by the latter reaction because the intermediate N-aryl-N-nitrososemicarbazides undergo loss of nitroxyl giving the aryl- azocarbamides. 36 N-C-0- Ar.Nl + HoC(NO~)~ -+ Are” $ + I “-0 (36) “ Tetraxo2es.”-Methylation of 5-amino-2-methyltetrazole with methyl benzenesulphonate yields a monomethyl derivative which has the meso- ionic structure (39).37; cf.27 The hydrochloride and hydrobromide of the 31 Busch et al. Ber. 1905 38 856 4049 ; J . prakt. Chem. 1906 74 501 533. 32 Warren J. 1938 1100. 33Busch et al. J . prakt. Chem. 1903 67 263; Ber. 1910 43 3008. 34 Ponzio Gaxxetta 1933 63 471. 35Boyer and Canter J . Amer. Chern. SOC. 1955 ‘77 1280. 36 Widman Be?. 1895 28 1925. 37 Brydon Henry Finnegan Boschan McEwan and Van Dolah J . dnaer. Chem. Boc. 1953 75 4863; Henry Finnegan and Lieber,.ibid. 1954 76 2894. RAKER AND OLLIS MESO-IONIC COMPOUNDS 27 tetrazole (39) are isoinorphous and it was possible to carry out an X-ray analysis of the compound without making any previous assumpt,ions con- N-NMe I lN=Y Ph.S02.0Me __p &” :*z; Me*N N= C-NH ‘NLC-QH (39) cerning its structure.The preliminary results show that the five-membered ring is planar and is definitely not bridged. Normal tetrazoles show only end absorption in the ultraviolet region but this hydrochloride shows aromatic-type absorption (Amax. 354 mp E = 2600 in H,O). Polycyclic Meso-ionic Compounds Several compounds are known in which a meso-ionic ring forms part of a polycyclic aromatic system. For example the nitrile (40) when treated with acetic anhydride gives a monoacetyl derivative which is basic and no longer contains a C1 =N group (infrared spectrum) ; it regenerates the nitrile on mild hydrolysis and forms a methiodide. A rneso-ionic structure was proposed for this and it may now be represented by formula (41).In the methiodide the methyl group is attached to the exocyclic nitrogen atom because hydrolysis with dilute sulphuric acid gives methyl- amine. Similar meso-ionic compounds in which the benzyl group is replaced by phenyl ethyl or various heterocyclic groups have been prepared. The acylation may also be effected by benzoyl chloride or benzenesulphonyl chloride to give the corresponding N-acyl derivatives. The coinpound (41) has a structure which is analogous to those discussed previously. Thus the atoms comprising the two rings of the bicyclic structure (41) have before delocalisation eleven electrons in their Zp orbitals so that t’he establishment of an aromatic system involving ten electrons (cf. naphthalene) requires the displacement of one of these electrons to the exocyclic acylamide grouping giving the structure (41 ).It has also been suggested that the pigment Besthorn’s Red has the meso-ionic structure (42).3j1 39 Substances no longer regarded as Meso-ionic In a few cases the meso-ionic structures which have been proposed for The (ary1azothio)acetic certain compounds have been replaced by others. 38 Bristow Charlton Peak and Short J. 1954 4748. 3B Krollpfeiffer and Schneider Annalen 1937 530 34 ; Httmmick and Brown Nature 1949 164 831. 28 QUARTERLY REVIEWS acids (43) give anhydro-compounds when treated with acetic anhydride and pyridine. These anhydro-compounds are weak bases stable to mineral acids and they react with electrophilic reagents in position 5. Thus direct bromination and nitration give the derivatives (45 ; X = Br and NO,) and arylation with diazonium salts in neutral or alkaline solution gives the 5-aryl derivatives.Originally these anhydro-compounds were regarded as hybrids derived from ionic forms,4o and were represented by a structure (46) which according to the current proposals for meso-ionic compounds would be formulated as in formula (47). Recently it has been suggested 41 that their formulation as (47) is unsatisfactory because they are soluble in non-polar solvents and react with electrophilic reagents in position 5. This observation we believe to be incorrect. Many meso-ionic compounds have large dipole moments and yet are quite readily soluble in benzene. Moreover reaction with electrophilic reagents does not require “ a degree of negativity on the 5 carbon atom” as suggested but it does demonstrate that the negative charge associated with the exocyclic oxygen atom can in fact be made available in this position to permit the generation of a transition state suit- able for substitution by electrophilic reagents.However there is another consideration which presumably excludes these compounds from being represented as meso-ionic. If dsp2 hybridisation of the sulphur atom occurs in these compounds 42 they may perhaps be regarded as satisfactorily represented by the covalent structures (44) and (45) and accordingly they would not be termed meso-ionic. It is recognised however that this exclusion is somewhat artificial because the substances are very closely related to the sydnones in that the annular atoms in formulze (44) and (45) have seven 2pz electrons and a sextet may be formed by electron- transfer to the oxygen atom.Statements which have appeared in the literature make it necessary to point out that the electron distribution in a molecule cannot be determined unequivocally by a study of its chemical reactions. Physical measurements are far more reliable. Dehydration of (2-pyridy1thio)acetic acid (48) with acetic anhydride 40Kendall and DufIin Congress Handbook XIVth Internat. Congr. Pure Appl. 41Duffin and Kendall J. 1956 3189. 42 Longuet-Higgins Trans. Faraday SOC. 1949 45 173 ; Craig Maccoll Nyholm Orgel and Sutton J. 1954 333. Chem. 1955 p. 320. BAKER AND OLLIS MESO-IONIC COMPOUNDS 29 gives a substance first formulated as a thiophen and later as a keten. A detailed investigation by Duffin and Kendall 43 showed that it was a bicyclic compound which they first represented as a hybrid molecule derived from a number of dipolar forms but later they preferred to represent it by formula (49).The structure is very similar to that of the anhydro-deriva- tives of the (ary1azothio)acetic acids so that their representation by the covalent structure (49) instead of as a meso-ionic compound may be justified although it should be emphasised that it is very closely similar to the anhydro-derivatives (41) as is shown by their aromatic character. These substances are yellow and their ultraviolet spectra have been investigated by K n ~ t t . ~ ~ They are fairly stable but hydrolysis with 50% aqueous sulphuric acid yields the parent acid. Previously it has been suggested that the compounds benzofuraznn (50 ; X = 0) piazthiole (50 ; X = S) and piaselenole (50 ; X = Se) should be regarded as having partially meso-ionic structure^.^^ We are now of the opinion however that this is undesirable because the o-quinonoid structures (50) are quite suitable for them.For piazthiole and piaselenole too formula (51) involving the higher valency states of sulphur and selenium can also be used. On the other hand the o-quinonoid structures (50) may be considered adequate for all these compounds because they react additively 45 with bromine to give tetrabromides (52). 43Duffin and Kendall J. 1951 734; 1956 361. 44Hnott J. 1955 918. 45 Hammick Edwardes and Steiner J. 1931 3308 ; Calcott-James De Witt and 0 1 lis unpublished results .

ISSN:0009-2681    

DOI:10.1039/QR9571100015

出版商:RSC    

年代:1957

数据来源: RSC

摘要:

THE CHEIVIfSTRY OF POLONIUM By K. W. BAGNALL B.Sc. PH.D. (ATOMIC ENERGY RESEARCH ESTABLISHMENT HARWELL NR. DIDCOT BERKS.) POLONIUM the heaviest member of the sulphur family (Group VIB of the Periodic Table) has hitherto been available only in less than microgram quantities derived from natural sources. This has limited the study of its chemistry to co-precipitation experiments from which little definite infornia- tion could be gathered Within the last few years however the situation has radically changed because the isotope 210Po once obtainable only as the penultimate member of the radium decay series can now be made in milligram amounts by the neutron-irradiation of bismuth. The natural and the artificial routes are shown for comparison 2AiPb (Ra-D) + B 'i:Bi(Ra-E) 2tiPo(Ra-B') '::Pb(Ra-G) 6 days 1384 days \ 209 83Bi By ordinary standards these quantities are small ; nevertheless by applying suitable experimental methods a quantitative study of compounds in visible a'niounts has been possible and as it is hoped to show great advances have been made in our knowledge of the element itself and of its reactions.Natural Occurrence and Discovery.-Polonium (namely 2lOPo) is in radio- active equilibrium with radium (226Ra) in all uranium minerals and pitch- blende (U,O,) contains approximately 0.1 mg. per ton. It was in this material that Mme. Curie1 discovered the element in 1898 being led to suspect the presence of a strongly radioactive substance from the fact that the activity of uranium minerals was always greater than would be expected of the uranium actually present.The story of the processing of a vast bulk of uranium ore on the lines of group analysis remarkable for the time at which it was done has been told and filmed. Here it is only necessary to mention that an extremely active material was precipitated with bismuth ; from this precipitate Mme. Curie was able to make a rough separation by fractional precipitation of the bismuth hydroxide or sublimation of the sulphides in a vacuum. Satisfied that it was a hitherto unknown element she named it after her native Poland.2 Although clearly a new element polonium was for a time known as " radioactivated bismuth 77,3 implying that it consisted of bismuth which 'M. Curie Compt. rend. 1598 126 1101. 2 P. Curie end M. Curie ibid. 1598 127 175. GieseI Ber. 1900 53 1666 30 BACNALL THE CIIEMISTRY OF POLONIUM 31 had acquired radioactivity by contact with another radioelement a view derived from the fact that bismuth became intensely a-active when immersed in solutions of radium salts.The activity was of course due to the electro- chemical replacement of bismuth by polonium. As polonium could be separated from the crude bismuth fraction by addition of stannous chloride and as this precipitate carried down a good deal of tellurium (an impurity in the uranium ore) the element received another temporary name " radio- tellurium ".* The various preparations displayed markedly different half- lives in their decay through contamination with various proportions of other a-emitters. Measurements of the half-life of later preparations of greater radioactive purity showed that the a-emitting constituents were identical and since the chemical properties of polonium as far as they were then ascertained resembled those of tellurium it seemed probable that polonium was the missing higher homologue of tellurium which it eventually proved to be.Isotopes.-There are 21 known isotopes of polonium of which the 138.4-day a-emitter of mass 210 is the one most commonly used. The longer-lived 3-year 208Po and the 100-year 209P~ would be better for chemical work because of their much lower activity. They can be produced but unfortunately only in relatively small quantities by the bombardment of lead or bism uth with high-energy a-particles protons or deuterons. z07Pb + 4€Ie + zOsPo + 3n 209Bi + lH --+ Zo*Po + 2n zOOBi + 2D -+- 209P~ + 2n The other isotopes are all short-lived.Hevesy and Guenther found no evidence of an inactive isotope but Hulubei and his co-workers claim to have detected an inactive or long- lived isotope in certain ores of tellurium ; it has not yet been assigned a mass number nor has its existence been confirmed. The separation of polonium The extraction of polonium from uranium is extremely tedious and the tracer amounts used in investigations before 1945 were usually obtained from aged radon ampoules ; after the radon (3-825-day 222Rn) has decayed they contain a mixture of radium-D -E -P and -a contaminated with some mercury and other impurities. Most of the early literature on the element is devoted to its separation from such il mixture and many of the methods then devised have since been applied to the purification of milligram amounts.Methods of Dealing with Mixtures of Radium-D -I# and -$'.-These can be conveniently considered whcn divided into four different groups according to the operations involved. In the first a large part of the lead Hevesy and Guenther Nature 1930 125 744. Hulubei and Cauchois Compt. rerid. 1940 210 761 ; 1947 $324 1265 ; Ripan * Marclrwald Ber. 1902 35 4239. Faladi and Hulubei Geneva Conference 1955 paper A/Conf. 8/P/1096. 32 QUARTERLY REVIEWS both radioactive (2lOPb) and stable is removed by ordinary chemical means ; in the second the polonium is precipitated from solution on a carrier ; in the third it is separated by solvent extraction ion exchange or paper chronmto- graphy methods which have however been applied to the recovery of tracer amounts only. The fourth group comprises the electrodeposition of the element on a suitable metal from which it can later be removed by chemical or pbysical means ; such depositions provide the most commonly used ways of purifying both tracer and milligram amounts.The groups of methods are described below in detail commensurate with their importance and interest. (i) Much of the lead in lead-rich polonium solutions is precipitated by the addition of concentrated nitric 7 or hydrochloric acid,* and this provides a useful preliminary concentration. From weakly acid or alkaline solution lead can be removed by dialysis since it alone migrates from the solution ; unfortunately a good deal of the polonium is adsorbed meanwhile on the semipermeable membrane.lO Neither of these methods takes the purifica- tion very far.(ii) Various carriers have been used in the precipitation of traces of polonium these include compounds of tellurium antimony bismuth and the rare earths. Tracer amounts are brought down with lead tellurate from dilute acid solution. The lead is eliminated by digestion with sulphuric acid tellur- ium after reduction to the quadrivalent state by boiling hydrochloric acid is removed as the element by treatment with sulphur dioxide leaving a relatively pure solution of polonium.ll Polonium and active bismuth (Ra-E) are precipitated together by O-5~-nitric acid on antimony or bismuth pyrogallate.12 The polonium formed in bismuth by neutron-irradiation can be separated from the latter by co-precipitation with elementary tellurium following reduction by stannous chloride.13" After removal of the tellurium it is often convenient to concentrate the poloniuni on a precipitate of lanthanum hydroxide brought down by making the solution alkaline.Further purifica- tion can then be achieved by dissolving the hydroxide in acid and precipitat- ing the sulphides insoluble in acid with hydrogen sulphide. The mixed sulphides when heated in a vacuum to 500° give a sublimate of metallic polonium and leave as a residue lead and other stable non-volatile sulphides .lac Over the last decade this mode of partition employing a variety of organic materials has been increasingly used. (iii) (a) Solvent extraction. I . Curie J. Chim. phys. 1925 22 471. * Debierne Compt. rend. 1904,139,281 ; Broda and Wright British report BR 641 1946. Paneth Sitzungsber. AIcad. Wiss. Wien Abt.IIa 1912 121 2193. lOHaissinsky J. Chim. p?~ys. 1932 29 453. l1 Karl Sitzungsber. Akad. Wises. Wien Abt. IIa 1931 140 199. l2 Guillot and Haissinsky Bull. SOC. chim. France 1935 2 239. l3 ( a ) Meinke American report AECD 2738 Sec. 84-1 1949 ; ( b ) Rollier Gazzetta 1954 84 658; (c) Bagnall and Robertson J. 1957 1044. BAGNALL THE CHEMISTRY OF POLONIUM 33 Tributyl phosphate (TBP) extracts polonium from aqueous hydrochloric acid ; l4 the amount taken up depends markedly on the acid concentration reaching a maximum when it is between 7~ and 9 ~ . Solubility studies 14a suggest that the complex formed is PoC14,2TBP. A little bismuth is extracted from even a GN-solution but most of this can be removed from the organic phase by backwashing with fresh 6~-hydrochloric acid.14 The polonium itself can be recovered from the organic extract by means of concentrated nitric a~id.13~ The extraction of high-level poloniuni sources with tributyl phosphate has not given entirely reproducible results probably because of radiolysis of the solvent.Dithizone dissolved in chloroform removes l5 traces of polonium from both nitric and hydrochloric acid a t pH 0.2-5. Milligram amounts are however readily hydrolysed at low acidities ; further the dithizone is rapidly decomposed by the cc-radiation. It seems probable that the red complex extracted by hydrochloric 140 or nitric acid16 is PoODz (Dz = dithizonate ion). The volatility of the complex 14a3 l7 makes it dificult to determine the polonium content with accuracy. " Thcnoyltrifluoroacetone " (2-yyy-tr~fluoroacetoacetylthiophen) (TTA) in benzene extracts the element from solutions at pH 0-2 and a reasonable separation from lead and bismuth is effected.ls With polonium in milligram amounts the high neutron emission from the a,n nuclear reaction with fluorine might make the use of the reagent a little hazardous.It has been stated that tracer polonium can be extracted from aqueous solution with diisopropyl ketone l9 or mesityl oxide. 2o Acetylacetone and isobutyl methyl ketone (hexone) remove milligram amounts of polonium from dilute hydrochloric acid allmost quantitatively the extraction probably depending on a condensation with the ketones analogous to that displayed by tellurium tetrachloride. (iii) (b) Ion exchange. When dissolved in dilute hydrochloric acid bismuth and poloniiim can be separated on Dowex 50 resin; the bismuth is removed by elution with 2~-nitric acid and the polonium with 2~-hydro- chloric acid.20a With Dowex 1X-4 resin the thrce heavier elements of Group VIB in I2N-hydrochloric acid can be separated from one another ; selenium is eluted by 6~-hydrochIoric acid tellurium by 2~-hydrochloric acid and polonium by N-nitric acid.Sulphur as sulphate is not adsorbed ijy the resin under these conditions.20b The presence of milligram amounts might introduce difficulties froni the effect of the These methods have been restricted to tracer studies. l4 Karracker and Templeton Phys. Rev. 1951 81 510. 14aBagnall and Robertson J. 1957 509. l5 Bouissihres and Ferradini Anal3t. China. A cta 1950 4 610. l6 Ishimori Bull. Chern. SOC. Japan 1954 27 520. l7 Kimura and Mabuchi ibid.1955 28 535. l8Wagemann J . Amer. Chem. Xoc. 1950 72 768. l9 Cairo Geneva Conference 1955 Paper A/Conf. 8/P/1028. 3o Marechal-Cornil arid Picciotto Bull. SOC. chirm. belges 1923 62 372. 20a Radhakrishna J . Chim. plhys. 1054 51 354. 2 Q b Sasaki Bull. Chem. SOC. Japan 1955 28 89. C 34 QUARTERLY REVIEWS ,x-radiation on the resin and solvent ; gas evolution from the latter would probably cause vapour-locks in the column. If this were the only difficulty it could be overcome by passing the solutions up the column or using it in a horizontal position. Paper chromatography does not appear to have been very much used as a means of separating tjhe element ; only one application of this technique to the separation of tracer polonium has been recorded. The most interesting procedures for the isolation of polonium utilise its spontaneous deposition on a less noble metal.The element when present in dilute hydrochloric acid solution is rapidly plated out on copper,21 and under reducing conditions on platinum 22 and palladium,23 but in all instances there is some contamination by bismuth when it is also present. From the same acidic medium polonium is deposited on gold by the intervention of thiourea and this procedure is said to give a good separation from The use of silver for the separation of polonium has the advantage of giving an almost complete separation from bismuth and massive amounts of bismuth do not interfere with the deposition.25 The conditions necessary to attain this are somewhat critical and the literature on the subject is rather conflicting.The best results are obtained from 0.5-2-O~-hydro- chloric acid a t 70-80" ; at this temperature the ozone formed by the or-bombardment of water is largely expelled from the solution before it can attack the silver surface.25 The deposition of polonium is inhibited by gold mercury platinum or tellurium and these impurities must first be removed by reduction with hydrazine. Even in the absence of impurities the presence of a reducing agent is advantageous particularly when dealing with milligram amounts of polonium. A little hydrocyanic acid is also beneficial when heavy deposits are being formed since it removes from the receiving surface much of the silver chloride which would be formed there by electrochemical replacement. By following the procedure described multi-curie sources of a density about 2 curies per square centimetre of foil surface can readily be prepared.These conditions of deposition do not prevent the formation of a black film presumably of silver oxide on the surface of the silver foil even when very small amounts of polonium are involved. The extraction of the polonium from this film can be extremely Generally the polonium is sublimed from the silver in a vacuum and if this is done immediately after the formation of the deposit the recovery is good but it falls off very markedly if the surface is allowed to remain in the plating solution or in air. The reason for this is unknown possibly a comparatively stable silver compound is formed as the result of oxidation or an oxide 21 Bates and Rogers Proc. Roy. SOC. 1924 A 185 360 ; Cook J .Chews. Educ 1934 11 313. 22Erbttcher 2. phys. Chem. 1931 156 A 142. 23 Kame Phys. Reu. 1937 52 380. 2 4 Erbacher Naturwiss. 1932 20 390. 2 5 Erbacher and Philipp Z. Physik 1928 51 309. 25aErbacher and Icading 2. phys. Chena. 1933 165 A 421. (iv) (a) Electrochemical replacement. BAGNALL TEE CHEMISTRY OF POLONIUM 35 film grows over the surface of the polonium or the element diffuses into the silver to some extent. Of course the polonium can always be recovered by dissolving the foil in nitric acid and precipitating the silver as chloride and provided the acidity is sufficient to prevent hydrolysis of the polonium chloride very little of it is adsorbed on the surface of the silver chloride. Metallic bismuth has afforded a very effective means of separating milli- gram amounts of polonium from quantities of irradiated bismuth.The irradiated material is converted into chlorides and the polonium separated from the solution on a few grams of bismuth powder ; by repeating this process a number of times with decreasing volumes of acid and amounts of metal the concentration of polonium relative to bismuth can be increased several thousandfold. 26 This obvious alternative has also been used. Thus milligram amounts of polonium can be easily electroplated on a platinum or gold electrode and the procedure is frequently used as a final stage in its purification.26 27 The pure metal is recovered from the cathodes by vacuum -sublimation. 2 7 As a method of obtaining tracer quantities of the element from mixtures of radium-D -E and -3’ it has probably little value as a primary separation ; certainly the published data on the subject are rather conflicting.(iv) (b) Electrodeposition. Handling of polonium Before describing the element and its chemistry in greater detail it is necessary to give some idea of the problems involved in handling the material in the laboratory. The first thing to note is that since polonium is almost a pure a-emitter radiation shielding is not required. The real difficulty arises because the maximum permissible tolerance for ingested 21OPo is as low as 0.02 microcurie that is 4-5 x g. so that one curie the amount normally used for preparative and analytical work a t Harwell represents no less than 5 x lo7 tolerances. I n order to safeguard the chemist these experiments must be carried out under the most stringent control.The chemical work is usually done in glore-boxes (also known as dry- boxes because they were earlier used for hygroscopic materials) which have Perspex windows and are fitted with shoulder-length rubber gloves. Boxes typical of those used for polonium are shown in Plates 1 and 2 they are constructed of Perspex sheet on a steel frame and are enclosed in an.outer shell of similar construction. The box itself and the enclosed space about it are both maintained a t a pressure less than that of the laboratory by means of air-ejectors. Thus in the event of a leak air flows from the laboratory into the box and prevents the exit therefrom of dangerous dust or vapour. The extracts from the box and shell are passed through a filter system to remove any contamination before being discharged into the extract ducts of the laboratory.The normal glove-boxes contain a wide range of equipment and reagents and have the ordinary laboratory services such as gas electricity etc. i 26 Burbage Record of Chem. Progr. 1953 14 157. 27 Bagnall D’Eye and Freeman J . 1955 3969. 36 QUARTERLY REVIEWS they are in fact miniature self-contained laboratories. Special services which include vacuum-systems and counting-equipment are available in separate glove-boxes connected to the working areas by trinnkiiig through which specimens or equipment can be conveyed on a trolley. Fresh reagents and equipment are introduced into the glove-box system through a double-transfer box which acts as an air-lock between the glove-box and the laboratory. Contaminated trash is brought out into a plastic bag attached to the box and this when full is sealed off by means of a radio- frequency heat-sealer.The operator working in this laboratory must wear surgical gloves in order to guard himself against skin contamination since the natural-rubber gloves fitted to the boxes are rapidly penetrated by polonium. Neoprene gloves are more impervious but are generally more clumsy to work in and tear more easily than those made of natural rubber. It goes without saying that the successful handling of small pieces of equipment such as for example X-ray capillaries with the hands so protected requires a good deal of practice. When milligram quantities of polonium are used the radiation effects are considerable in both a physical and a chemical sense. This is under- standable for the specific a-activity is 4.6 curies per milligram that is 1013 disintegrations per minute per milligram.Glassware is attacked by the a-bombardment and becomes crazed within a few days (cf. Plate 3) the change being attended by the separation of visible amounts of silica and a marked increase in fragility. X-Ray ca$pillaries containing anhydrous polonium compounds have a tendency to disintegrate round the areas in contact with the material. In some cases the capillaries explode owing to the formation of gas which may give rise to a pressure of six atmospheres in the course of a week. With hydrated compounds explosion usually occurs within a few hours of sealing ; this makes it impossible to obtain powder photographs of them. There is risk of contamination from such explosions though this can be considerably reduced by painting the capillaries with a suitable plastic immediately after sealing; the coating so formed is sometimes strong enough to withstand the explosion.28 An interesting effect is the degree of self-heating of the specimen resulting from the stoppage of the disintegration of a-particles within its boundaries.This is very considerable amounting to 27.4 calories per hour per curie of 210Po or about 140 watts per gram. As a consequence compounds cannot be accurately weighed and the polonium is assessed from the a-emission for which purpose the half-life must be accurately known. The rise in temperature does however afford a useful method for the rapid determina- tion of large polonium sources and a simple calorimeter for this purpose has recently been described.29 Another physical effect is the glow which surrounds the element and its compounds arising from the excitation of the surrounding gas ; this is quite bright with milligram amounts as may be gathered from Plate 4 which aaBapall and Froeman J . 1956 4379. as White J . Sci. Instr. 1966 33 230. BAGNALL THE CHEMISTRY OF POLONIUM 37 shows a specimen of the metal photographed in its own light. Incidentally the external temperature of the containing tube was 75". As might be expected such intense radiation induces a marked fluorescence in silica or glass. Turning to specifically chemical effects we have to note both decom- position and synthesis. The radiation-induced decomposition of solid polonium compounds is often extremely rapid so rapid indeed that it has not yet been possible to analyse the salts formed by organic acids the cyanide and similar compounds.In preparative experiments the effects may obscure the reactions taking place. Thus for example the radiolysis of the solvent in a 10-3~-polonium solution (Le. 1 curie per millilitre) causes a visible continuous evolution of gas 30 31 (cf. Plate 5). Work with precipitates cont'aining the element is complicated by scattering of the solid as a result oE radiolysis of the trnpped solvent. Further the intensely oxidising conditions resulting from the attack on water make the study of the element in its lower valency states very fa<r from easy. Another difficulty associated with high-level polonium work arises from the oxidation of nitrogen in the air ; this causes an exposed polonium compound to be rapidly converted into a white solid probably a basic nitrate.31 To avoid the trouble milligram amounts of the element or its compounds are usually handled in sealed systems generally under a vacuum.Many authors have reported the appearance of widespread contamination about open polonium sources and in the past this has been attributed to an aggregate recoil mechanism. 32 Observations on curie sources suggest however that the effect is mainly due to the volatility of the compound itself. For instance the difference in the spread of the contamination experienced after high-level spills of the involatile dioxide and volatile tetrachloride was particularly noticeable. With the former the activity showed no sign of spreading and air-monitoring gave no evidence of airborne activity but with the latter contamipation was widespread and appreciable amounts of the activity became airborne.Metallic polonium The metal is easily prepared by the vacuum-sublimation of the deposits obtained by electrodeposition on platinum 33a and gold,34 by spon- taneous deposition on silver and nickel 31 or by thermal decomposition of the sulphide or dioxide under a vacuuni. Thick layers (-1 c/cm.2) have a silvery metallic appearance whereas thinner layers (-10 mc/cm. 2 appear as a smoked film. The metal exists in at least two allotropic modifications a-polonium the low-temperature form with a simple cubic lattice and 18-polonium the high-temperature form with a simple rhombo- hedral lattice.32 33a2 The a-p-transformation ,takes place a t about 75" 30 Curio and Debierne Compt.rend. 1910 150 386. 3l Bagnall and D'Eye J. 1954 4295. 32 E.g. Lawson Sitzungsber. Akad. Wiss. Wien Abt. IIa 1915 124 509 637. 3 3 ( a ) Beamer and Maxwell J. Chem. Phys. 1946 14 569; (b) 1949 17 3203. 34Bagnall D'Eye and Freeman J. 1955 2320. 38 QUARTERLY REVIEWS and is said to be accompanied by a sniall increase in volume ; 35 however the X-ray data show that the p-form has a higher density. Freshly prepared specimens of the meta.1 always consist of the p-form owing to the heating effects of the a-radiation. The sample cools as the polonium decays and after a few days the a-form appears. Lead formed in the decay of the polonium seems 33b to form a solid solution with polonium up to about 50 atoms yo. The physical properties of polonium metal summarised in Table 1 resemble those of thallium lead and bismuth its neighbours in the Periodic Table rather than those of tellurium its lower homologue.TABLE 1 u-1'0 Cell parameter33b . . a = 3.345 A Calc. density (g./c.c.) . 9.32 Space group . 0 Resistivity ohm em. at 0") 35 . . 42 f 10 Atomic diameter 33b . M . P . ~ ~ . B . P . ~ ~ . V . P . ~ ~ log p = - 5377-8/27 + 7.2345 (at 435-745") (kcal./mole) 36 . B-PO a = 3.359 A fx = 98" 13' 9-5 1 44 f 10 DL 3.255 a 254" 962" 24.597 The first studies of its electrochemistry were made on such extremely dilute solutions that it remained uncertain whether deductions based on the ordinary electrochemical laws could be made. The normal electrode potential a t dilutions of 10-8-10-9~-polonium could be obtained only by an extrapolation of the critical decomposition potential determined by measur- ing the rate of deposition of the element a t different cathode potentials.The mean value 37 resulting from this approach was E,H P0,Po4+ = + 0.77 volt. Recently 38 the electrode potential has been measured directly by using a gold wire coated with 0.2 mg. of polonium as the polonium electrode; the result + 0.76 volt is in good agreement with that from the tracer studies. The potentials of the polonium-polonium chloride electrode were also investigated but the ionic species involved are uncertain. An att'empt to measure directly the Po-Po2+ potential was unsuccessful owing to oxidation brought about by the high a-particle flux amounting to 1011 a-particles per cm.2 per sec. across the electrode layer. Chemistry of polonium The account given below presents in some detail current knowledge uf the chemistry of the element.As has been indicated the earlier work restricted to tracer quantities has been greatly extended and amplified as the result of experiments made with milligram amounts. Since the later work which afforded a sight of a number of compounds is likely to be 35Maxwell J . Chem. Phys. 1049 17 1255. 36 Brooks J . Rmer. Chem. SOC. 1955 77 3211. 3 7 IIaissinsky Comit6 intern. Thermodynam. et CinBt. electrochim. Compt. rend. RBunion (1951) 1952 214. 38Bagnall and Freeman J. 1956 2770. BAGNALL THE CBEMISTRY O F POLONIUM 39 of special interest in this Review it has been dealt with first instead of adopting a chronological order. The upshot of all the investigations has been to show that polonium behaves chemically very much as might be expected from its position in the Periodic Table although as has been mentioned its metallic properties Group I V V VI C N 0 Si P S Ge As s e Sn Sb Te Pb Bi Po are more akin to those of bismuth and lend.The " inert-pair " effect likely to be more marked in polonium than tellurium is very little in evidence for there is but slight resemblance to the chemistry of lead which this would imply. By analogy with tellurium the element should show valencies of 2 4 and 6. The bivalent state has been well established by tJhe characterisation of the halides and the quadrivalent equally well by the characterisation of the dioxide halides and other compounds. The evidence for the sexavalent state rests partly on the behaviour of the anodic deposit of tracer polonium from acid solution.39 This deposit is of unknown com- position but the fact that it dissolves in hydrogen peroxide 4O suggests it may be a higher oxide.Other evidence for sexavalency is based on observations of the co-precipitation of tracer polonium with tellurates,41 but these could also be explained by the formation of a polonium tellurate. A stable and probably volatile hexafluoride is the most likely compound of this valency but such a compound has not yet been prepared. There does not seem to be any conclusive evidence for the tervalent state (shown so markedly by bismuth) deduced by many authors from tracer electro- chemical and co-precipitation experiments. The well-known acidic character of the sulphur sub-group is vestigially present in polonium (witness the format.ion of polonides and a hydride) but it is so weakened with increase in atomic weight that even tellurium exhibits feebly basic properties forming a tartrate and some basic salts such as a nitrate and sulphate.As would be expected polonium dioxide and hydroxide are even less acidic than their tellurium analogues ; this is demonstrated by the ease with which they react with weak acids such as acetic and o x a l i ~ . ~ l ~ Polonium in contradistinction to tellurium also forms a well-defined disulphate and its dihalides are much more stable than the corresponding tellurium compounds which disproportionate rather readily. Studies of the solubilities of the sulphate,28 nitrate,42 acetate and oxalate 41a in their respective acids show extensive complex-formation in 39 Hevesy and Paneth Sitzungsber. Akad.Wiss. Wien Abt. IIa 1914 123 1619 ; Monatsh. 1915 36 46. 40 Haissinsky and Cottin Gompt. rend. 1947 224 467. 41 Samartzewa Cowipt. rend. Acad. Xci. U.R.S.S. 1841 33 498. 41u Bagriall and Freeman unpublished results. 4 2 Orban American report MLM-973 1954. 40 QUARTERLY REVIEWS solution; indeed the chemistry of polonium has been described a-s a chemistry of complexes. Po1onides.-Lead and mercuric polonides 43 have recently been prepared from the elements a t 325-350" ; both are black and have a simple cubic (NaC1) lattice with cell edge 6,590 A for PhPo and 6.250 A for HgPo. The calculated densities are 9.6 and 11.1 g./c.c. respectively. No chemical propertlies have been recorded for either compound. Tracer experiments suggest that sodium polonide results from tlhe reduction by sodium dithionite of polonium in alkaline solution under an atmosphere of hydrogen.44c4 5 Hydri.de.-This has been prepared on a tracer scale in poor yield by the action of dilute hydrochloric acid on magnesium foil upon which pglonium had been deposited chemically or electr~lytically,~~~ OF by the addition of magnesium powder to a solution of tracer polonium in dilute hydrochloric a ~ i d . ~ 6 It is not formed from the elements on a milligram scale. 26 Polonium hydride appears to be even less stable than bismuth hydride and is said to be rapidly decomposed by most drying agents.45$ 47 A number of its physical properties have been estimated by extrapolation ; the probable melting and boiling points a're 237.0" and 308.5" K respecti~ely.~~ Halides.-These like the tellurium halides are covalent volatile readily hydrolysed compounds of which the quadrivalent are rather less and the bivalent much more stable than their tellurium analogues.Complex salts of the form M,PoX,(IV) (X = C1 Br I) have been prepared from the quadrivalent halides and closely resemble the corresponding tellurium derivatives with which they are isomorphous. Of the univalent metals caesium gives the least soluble complex salt in every instance. There is no record of the making of a fluoride on the milligram scale though an unsuccessful attempt to prepare a volatile one has been reported. 26 Incidentally such compounds might be rather hazardous to handle because of the high neutron emission from the a-11 reaction with fluorine. (i) The tetrachloride is a bright yellow monoclinic or triclinic solid which melts in chlorine a t about 300°.349 49 The molten salt is straw-coloured below 350" and scarlet a t higher temperatures possibly through decomposition to the dichloride.The liquid boils a t 390" giving a purple-brown vapour which becomes blue-green above 500".34 The com- pound is formed from the elements a t 200" or when the dioxide is heated in the vapour of carbon tetrachloride in hydrogen chloride or in thimyl chloride or with phosphorus pentachloride.26s 349 49 It is hygroscopic arid 4 3 Wittemann Giorgi and Vier America,n report LA-1890 1955. 4 4 (a) Chlopin and Samartzewa Compt. rend. Acad. Sci. U.R.S.S. 1934 4 433 ; ( b ) Samartzewa Trav. Inst. &tat Radium [J.B.S.R. 1938 4 253. 4 5 E.g. Paneth Sitzwaysber. Akad. Wiss. IVien ,4bt. IIa 1918 127 1729. 46 Paneth Johanscn and Matthies Rer.1022 55 769. 4 7 ildler Sitzungsber. Akad. Wiss. Wien Abt. T l a 1938 147 197 ; Paneth and 48 Pearson and Robinson J . 1934 736. 49 Joy American report M-4123 1947. (1) Fluorides. ( 2 ) Chlorides. Rabinowitsch Ber. 1025 58 1138. PLATES 1 & 3 Boxes used in handling polonium. PLATE 2 PLATE 2 PLATE 5 Gas evolution from 1 O-3~-polonium tetrachloride solution (ca. 1 c/ml.). BAGNALL THE CHEMISTRY OF POLONITJM 41 readily hydrolysed to a white solid of indefinite composition; there is no certain evidence for a basic chloride such as PoOC1,. The tetrachloride dissolves in hydrochloric acid in thionyl chloride and with slow hydrolysis in water. It is moderately soluble in ethyl alcohol acetone and some other ketones the solubility in ketones being probably due to compound formation.Solutions in all these solvents are bright yellow and the presence of complex ions in hydrochloric acid is shown by an immediate precipitation of greenish-yellow cEsium hexa- chloropolonite cs~Poc~~(Iv)~34y 50 on addition of an alcoholic solution of cmium chloride. PO^+ + 6C1- $ Poc1,2- has been calculated from electrochemical data 38 to be about 1014. The tetrachloride may form an ammine with gaseous ammonia at a low temperature but decomposition with the formation of the metal occurs on storage in excess of the gas at the ordinary temperature; an ammine of the dichloride may also be formed.34 These observations are probably best explained as reduction effects due to the atomic hydrogen resulting from irradiation of the ammonia.(ii) The dichloride is a dark ruby-red solid which melts above 355" and sublimes a t 190°,49 and may be orthorhombic or possibly monoclinic or tri~linic.3~ It is prepared by the thermal degradation of the tetrachloride in a vacuum at 200°,341 49 and by the reduction of that salt in hydrogen49 at ZOO" in hydrogen sulphide or carbon monoxide at 150°,34 or in sulphur dioxide at room temperature. Continued heating in hydrogen or hydrogen sulphide takes reduction as far as the metal. Solutions of the dichloride are obtained by reducing the tetrachloride in hydrochloric acid with sulphur dioxide or hydrazine in the cold or with arsenious oxide on warming. Neither hydroxylamine nor oxalic acid reduces a solution in this acid possibly because of the stability of the chloride c0mplex.3~ The dichloride dissolves in dilute hydrochloric acid to give a pink solution which is oxidised to the quadrivalent state rapidly by the products of the radiolysis and immediately by chlorine water or hydrogen peroxide.34 The oxidation induced by its own radiation has been used to obtain a value for the redox potential.The trichloride may be formed in the course of this oxidation. Migration experiments indicate that the dichloride forms complexes in hydrochloric acid.3s An ammine is formed by interaction of the dichloride and ammonia at 200". (i) The tetrabromide is a bright-red probably face- centred cubic solid which melts about 300°.279 51 The liquid boils 51 at 360"/200 mm. It can be obtained by heating the metal to 250" in bromine at 200 mm. pressure for 1 hour 26 and more rapidly by heating it in a stream of bromine vapour carried by nitrogen ; by dissolving the metal or dioxide in hydrobromic acid and evaporating the solution to dryness ; or by heating the dioxide in hydrogen bromide.Polonium does not react readily with bromine in the The equilibrium constant for t,he reaction (3) Bromides. Staritzky American report LA-1286 1951. 5l Joy Chem. Eng. N e w 1954 32 3848. 42 QUARTERLY REVIEWS This compound is hygroscopic and easily hydrolysed. It dissolves in hydrobromic acid giving a solution which is orange-red at 0.0O1M-PoBr4 and carniine-red a t 0 . 0 2 5 ~ ~ and contains some complex ions since aqueous cmium bromide precipitates dark-red czsium hexabromopolonite Cs,PoBr,(Iv). When the hydrobromic acid solution itself is cooled to -30" the complex acid separates a,s a blackish-brown solid.The tetra- bromide is insoluble in benzene chloroform and carbon tetrachloride sparingly soluble in bromine and quite soluble in ethyl alcohol acetone and other ketones. With ammonia a t room temperature it forms an unstable yellow ammine and gives some indications of a volatile colourless 0118.27 (ii) A dibromide is formed by thermal degradation of the tetrabromide in a vacuum at about 250" or by its reduction by hydrogen sulphide in the cold. This purple-brown solid sublimes with slight decomposition a t 1 lO0/3Op and appears to disproportionate a t 270-280"/1 atm. In hyerobromic acid and a number of ketones it gives purple solutions in which the polonium is rapidly oxidised to the quadrivalent state. Solutions of the dibromide in hydrobromic acid can be obtained by methods similar to those used for the corresponding chloride.There is no evidence how- ever of an intermediate tribromide in the course of the autoxidation from bi- to quadri-valency.27 The only iodide known this is a black solid which sublimes with partial decomposition to the metal at 200" in nitrogen. It may be prepared by heating the elements to 40"/1 mm. ; by allowing the " hydroxide " or dioxide to react with 0-1N-hydriodic acid ; by pre- cipitation from an acid solution of the tetrachloride with O.1N-hydriodic acid; or by sublimation from the dioxide in a stream of hydrogen iodide at ZOO". I n the cold the dioxide and hydrogen iodide appear to form a black addition compound. The tetraiodide is insoluble in 2~-hydrochloric acid N- and 2~-nitric acid acetic acid chloroform and other organic solvents and slightly soluble in acetone and ethyl alcohol.It is slowly hydrolysed by water and is oxidised by acidified potassium nitrite and other oxidising agents. Studies of the solubility of the tetraiodide in aqueous hydriodic acid indicate the formation of the complex ions POI,- and PoI,2- (4) Tetraiodide. POI + I- + POI,- K = 6.7 x lo- at 22" POI + 21- + Po12,- K = 5.9 x at 22' and black caesium hexaiodopolonite is precipitated from solutions in 2~-hydriodic acid on the addition of czsium iodide. It is reduced to the metal by hydrogen sulphide without evidence of an intermediate di-iodide.52 Polonium dichlorodibromide is formed as a salmon pink solid by the reaction of bromine with polonium dichloride.27 Polonium dichloride and dibromide may form black unstable interhalogen compounds with iodine by reaction with solutions of iodine in carbon tetrachloride 5 2 The tetraiodide does not seem to react with ammonia.(5) Interhalogen compounds. 52B~gnaII D'Eye and Frceman J. 1956 3385. BAGNALL THE CHEMISTRY OF POLONIUM 43 ( 6 ) Hexahnlogenopolonites. Tracer co-precipitation studies had indicated the presence of hexachloropolonite ion in hydrochloric solution 53 but the valency of the polonium was uncertain. The preparation of the caesium salt has already been described ; the rubidium potassium ammonium and tetramethylammonium compounds are formed by evaporating a hydro- chloric acid solution of the two con~tituents.~O The ammonium salt can be made by heating the two halides together. The tetramethylammonium salt is rapidly discoloured by autoirradiation.Caesium hexabromo- and hexaiodo-polonite are prepared by precipitation and ammonium hexa- bromopolonite by heating the two bromides together. All the compounds are brightly coloured ; the chlorides are greenish-yellow the bromides dark red and the iodide black they are isomorphous with their tellurium analogues. The czesium salts decompose into their components when heated but amrnoniuni hexabromopolonite blackens and explodes a t about 300" possibly owing to the formation of an unstable nitride. This may be formed by the anodic deposition of tracer polonium from acid solution 39 but no analytical data are available ; it has not been prepared on the milligram scale. If it exists it should be acidic. Dioxide. The solid has two crystal 54 tetragonal (apparently red) and face-centred cubic (yellow).The latter is the low-temperature modification and is a U0,-type oxide with variable oxygen content; the cell edge 31 varies from 5-626 to 5-687 A. The radius of the Po4+ ion deduced from the X-ray data is 1.02 64 or 1.04 and the calcula,ted density about 9 g./c.c. It is formed from the elements a t about 250" and becomes progressively darker when heated having a chocolate colour a t 885" the sublimation temperature under 1 atmosphere. The colour changes are reversible. Polonium dioxide decomposes to the metal a t 500" under a va~uum.~1 The corresponding hydroxide or hydrated oxide is obtained as a pale-yellow flocculent precipitate on the addition of aqueous ammonia or alkali hydroxide to acid solutions of polonium salts ; it is sparingly soluble in alkali,34 and its composition is unknown.As with tellurium these com- pounds should show some acidic character but it is not well marked. The black solid is produced in the spontaneous decomposition of polonium sulphotrioxide or selenotrioxide. 28 The corresponding hydrated oxide or hydroxide is formed as a dark-brown precipitate on addition of alkali to solutions of the dihalides in acid. It is rapidly autoxidised to the quadrivalent state. 34 The white solid results from treating polonium tetrachloride or " hydroxide " with 0.5-5.0~- sulphuric acid. It suffers dehydration when kept or heated becoming pink a t 200" and deep purple a t 380" and can also be dehydrated by washing it with anhydrous ether. The purple anhydrous salt stable up to over 400" decomposes to the dioxide at about 550".The disulphates are insoluble in acetone and ethyl alcohol but may be hydrolysed by the latter. 53 Guillot J . Chim. phys. 1931 28 107. 5 4 Martin J . Phys. Chem. 1954 58 911. Oxides and Hydroxides.-TTrioxide. Monoxide. Sulphates and Se1enate.-Hydruted disdphute. 44 QUARTERLY REVtEWS They are very soluble in dilute hydrochloric acid. On the other hand the solubility in dilute sulphuric acid is remarkably low only 420 pg. of the anhydrous salt per 1. of 0 . 5 ~ sulphuric acid ; an increase in solubility with acid concentration suggests complex-ion formation. 28 This is also a white solid though yellow above 250" and may be made in the same way as the disulphate by using more dilute (0.02-0.25~) sulphuric acid. The compound appears to be ZPoO,,SO, analogous to tellurium sulphate and is stable up to over 400" ; decomposition takes place a t about 550".It is more soluble in dilute sulphuric acid than the disulphate ; solubility studies indicate that the basic sulphate is metastable. 28 The reduction of suspensions of the disulphate in boiling ~-2~-sulphuric acid with hydroxylamine 28 probably yields a solution of the bivalent sulphate. Ea'rlier tracer observations had sug gested that reduction occurred under these ~onditions.55~9 ' The polonium is re-oxictised to the quadrivalent state on cooling and the disulphate is reprecipitated even in the presence of an excess of hydroxylamine.28 The white solid made by treating polonium tetrachloride or hydroxide with 0.0 15-5.0~-selenic acid has the composition represented by 2Po0,,Se03.It becomes deep yellow above 250" and appears to be stable to temperatures over 400". It is very soluble in dilut'e hydrochloric acid and studies made of its solubility in selenic acid suggest complex formation. This is formed as a black precipitate by the action of hydrogen sulphide on solutions of polonium dichloride or tetrachloride in dilute hydrochloric acid ; 13c it decomposes to the metal when heated under a vacuum (cf. polonium dioxide) and slowly dissolves in hydrochloric acid probably owing to the chlorine liberated by the a-bonibardment. The solubility product is about 5 x Workers using tracer amounts of polonium believed the compound to be the sesquisulphide,53 a description which was also applied to the material formed by the slow decomposition of polonium NN-diethyldithiocarbamate in 57 Polonium metal is vigorously attacked by concentrated nitric acid giving a solution yellow when l O V 5 ~ in respect of polonium and becoming colourless on dilution 31 ; evaporation of either solution yields a white solid of uncertain composition.The solubility of a polonium nitrate in nitric acid has been determined over a wide range of concentration and temperature. The method used consisted in finding the polonium content of the solution in equilibrium with a deposit of the metal on platinum.42 The nature of the nitrate formed in this way is uncertain but since the observed solubilities were extremely low of the same order as that of barium sulphate in water it 66 ( a ) Guillot and Haissinsky Compt. rend. 1034 198 1911 ; ( b ) Haissinsky and Guillot J .Phys. Radium 1934 5 419. 6 6 Guillot J . Chim. phys. 1931 28 14. 6 7 Idem Compt. rend. 1930 190 127 1553. Basic poZonium(1v) sulphate. Polonium(~~) suZphute. Basic pobnizcm(Iv) selenate. A diseleiiate has not been prepared.28 Other Compounds.-Monosulphide. Nitrate. BAGNALL THE CHEMISTRY OF POLONIUM 45 seems probable that a basic nitrate is involved. Complex ions such as Po(NO,),- may be present but definite information is not yet available on this point. Oxides of nitrogen derived from the a-bombardment of air react slowly with polonium and many of its compounds coating them with what appears to be a white basic nitrate. A similar material is also formed by the action of dilute nitric acid on polonium halides. Acetylacetone CompZexes. A mixture of ter- and quadri-valent acetylace- tone complexes is said to be formed by the action of acetylacetone on tracer quantities of polonium " hydroxide ".58 The valencies were deduced from co-crystallisation studies with thorium aluminium and scandium acetylace- tone complexes.The compound (or mixture) appeared to distil with partial decomposition a t 230"/10 mm. By contrast milligram amounts of the acetylacetone complexes seem to be much more volatile and two series of compounds have been obtained one containing two atoms of halogen the other none. It seems likely that the products of the reaction of acetylace- tone with the polonium di- and tetra-halides are cyclic formed by condensa- tion of the polonium halide across the terminal methyl groups of the diketone in a way analogous to the behaviour of tell~rium.~g If this view of the structures is correct then the co-crystallisation data are valueless.It is interesting that similar compounds are formed with monolretones and in every case there appears to be one form with two atoms of halogen per polonium atom and another without any halogen at a11.60 Investigation of these compounds is hindered by rapid charring due to the a-bombardment ; deterniination of the carbon would be facilitated by labelling the acetylacetone with 14C. Alcoholic camphoric acid is said to react with alkaline suspensions of tracer polonium and about half of the product is then extracted by benzene and is soluble in chloroform. Its composition is unknown. Tracer amounts of dimethylpolonium can be prepared in about 10% yield by the action of dimethyl sulphate on mixtures of the polonide and telluride of sodium in water saturated with hydrogen.44b It is possibly formed 62 in the decay of tetramethylradiolead ( 210Pb).Dibenzylpolonium is stated to be produced when benzyldimethyl- phenylainmonium chloride acts on a mixture of sodium polonide and telluride in ~ a t e r . 4 4 ~ ~ NN-L)iethyZdithiocarbamate. Tracer polonium is precipitated from weakly alkaline solution in about 87 % yield by sodium NN-diethyldithio- carbamate ; the product is soluble in chloroform and co-crystallisation studies are said to indicate that the polonium is here t e r ~ a l e n t . ~ ~ ~ 57 Solvent-extraction work on tracer amounts of polonium in Camphorate. Dimethyl and dibenxyl derivatives. These compounds have not been amlysed. Dithizonate. 58Servigne Compt.rend. 1933 196 264; J. Chim. phys. 1934 31 47. 5Q Morgan and Drew J . 1925 127 531. 6o Bagnall Freeman and Robertson unpiiblished results. 61Servigno Compt. rend. 1934 198 731. 6 2 Morteiisen and Leighton J . -4mer. Chern. Soc. 1934 56 2397. 46 QUARTERLY REVIEWS nitric acid 16 and milligram amounts in hydrochloric acid 14a point to the formation of a compound which is probably PoODz (Dz = dithizonate ion). Tracer Solution Chemistry.-There is an extensive literature on tracer experiments carried out with extremely dilute solutions of polonium but largely owing to the unavoidable absence of analytical data the inferences drawn from these are somewhat speculative. A good deal of the work seems to have been concerned with seeking what have proved to be very tenuous similarities between polonium and bismuth its neighbour in the Periodic Table.The much. closer relationship of its chemistry to that of its honiologue tellurium was rather overlooked. A number of comprehensive reviews of the tracer work have been p ~ b l i s h e d ~ ~ and for the convenience of the reader the results obtained are summarised under the individual reagents studied. Hydrochloric acid. The electrodeposition of polonium from hydro- chloric acid is principally anodic even in an @2N-~olution.~~ Diffusion and ion-mobility studies in more dilute acid indicate the presence of bivalent cations ; 65 the species involved is probably a partially ionised or hydro- lysed form of polonium tetrachloride P o C ~ ~ + or Po0 ,+. Solvent-extraction data obtained with dithizone suggest the latter.A soluble basic chloride has been thought to be present in ~-3~-hydrochloric acid,53 and hydrolysis to the hydroxide in very dilute acid has been postulated. But this is not in agreement with results on a milligram scale which indicate some complex- ion formation even in N-acid. Tracer co-precipitation work has shown that very little polonium is carried down on silver chloride a t high concentrations of acid or chloride,66 and that it is not co-precipitated with lead chloride 53 or mercurous chloride.67 Studies of the diffusion of tracer polonium in these acids 6* and measurements of its deposition in neutral sodium nitrate or potassium sulphate solution 69 indicate the formation of complex ions. Results from co-crystallisation with lanthanum and other rare-earth oxalates are said to indicate ter~alcncy.~~ 70 It was thought 71 that oxalic acid reduced solutions of polonium to a lower valency state but the electrochemical data on which this idea was based might also be tasken to indicate complex formation.55b Stannous chloride precipitates polonium from solution This sublimes l7 a t 12Q0/1 atm. Nitric oxalic and sulphuric acid. Reducing agents. 63 Gmelin " Handbuch der anorganischen Chemie " System nr. 12 Verlag Chemie Berlin 1941 ; Haissinsky " Le Polonium " Act. Sci. 517 Hermann et Cie. Paris 1937 ; idem " Electrochimie des Substances Radioactives " Act. Sci. 1009 Hermann et Cie. Paris 1946. 6 4 Paneth and Benjamin 2. EZectrochem. 1925 31 572. 6 5 Hevesy Phil. Mag. 1914 27 666. 6 6 Escher-Desrivi+res Ann. Chim. (France) 1926 5 251. 67 Brennan ibid.1925 3 390. 68Servigne J. Chim phys. 1934 31 147 211. 70Servigne ibid. p. 41. Guillot and Haissinsky Compt. rend. 1934 198 1758 ; Haissinsky &id. 1933 195 131. 71 Joliot J . Chim. phys. 1930 27 119. BAGNALL THE CHEMISTRY OF POLONIUM 47 probably as the metal.4 57 Sulphurous acid reduces it to the bivalent state,34 but in the presence of selenium some precipitation of polonium may occur,72 7 3 possibly through its adsorption on the ~elenium.7~ Polonium selenide might also be formed under these conditions. Sulphur dioxide inhibits the electrodeposition of tracer polonium from sulphuric acid solution,71 owing probably to a reduction of the sulphite to dithionite which might well precipitate the polonium as metal.12 Hydrazine reduces solutions to the bivalent state,34 55b but the further reduction to metal does not occur 7 2 even at 100".In alkaline solution the metal is said to be precipitated in the co1d,l2 but the precipitate may consist of the bivalent hydroxide. Although sodium nitrite has been described 5ja as precipitating tracer polonium from solution this does not appear to occur with milligram amounts of polonium. 5 2 Ferrous sulphate,75 formic acid and formaldehyde do not effect its reduction in acid but formaldehyde is said to precipitate the metal from an alkaline solution.l2 55a Hydrolysis in Aqueous Solution.-A large number of papers deal with the precipitation of tracer quantities from neutral or weakly acidic solutions and the ease with which tracer polonium can be centrifuged from such solutions suggested that the polonium is present as a genuine suspension.But the solubility products of the compounds concerned are so small that this explanation seems rather unlikely; it is more probable that the impurities present act as centres of adsorption for the material.76 and Godlewski 7 7 have shown that solutions of tracer polonium under these conditions do exhibit colloidal properties but it is uiicertain whether the polonium is present as a genuine colloid or is adsorbed on another colloid also present. Further work using larger amounts will be necessary in order to clarify the position. Paneth Uses Polonium has been mainly used for the preparation of neutron sources which are virtually free from y-radiation. These are made by mixing or alloying polonium with other elements such as beryllium possessing a high K n cross-section.Attempts have been made to use it in the manufacture of " static eliminators " for. the removal of static charges which are troublesome in certain industries. These eliminators were found to be unsafe owing to the leakage of polonium from them ; 78 but with improved design directed to overcoming this trouble such a use might very well become considerable. The incorporation of polonium in alloys for the electrodes of sparking 73Mar~k~a1d Ber. 1905 38 591. 73Reymontl and da Tchang Tcheng Compt. rend. 1931 192 1723. 7 4 Haissinsky J. Chim. pliys. 1937 34 94. 7511evesy and Guenther Z. anory. Chem. 1930 194 162. '13 Paneth " Radioelements as Indicators " McGraw-Hill Book Co. Inc. New York 1928 p. 55. 7 7 Godlewski Kolloid. Z. 1914 14 229. 78 Bryan and Silverman American report AECU-343 (UCLA-18) 1949 ; Silverman and Bryan American report UCLA-84 1951.48 QUARTERLY REVIEWS plugs in internal combustion engines has the effect of reducing the break- down voltage across the gap. An engine fitted with such plugs is said to be more easily started from the cold than one with the usual variety. When however the engine reached its normal working temperature the polonium would be rapidly vaporised from the points and would in certain circumstances introduce an undesirable hazard to health. One of the most interesting applications of polonium is to analysis though this requires comparatively large sources of about 160 millicuries. For e~ample,'~ small amounts of fluorine can be determined by counting the positron emission from the 2.6-year 22Na formed in the reaction I9F( cc ,n) 2Na. Odsblad Acta Rdiol. 1954 42 391.

ISSN:0009-2681    

DOI:10.1039/QR9571100030

出版商:RSC    

年代:1957

数据来源: RSC

摘要:

SOME GENERAL ASPECTS OF THE INORGANIC CHEMISTRY OF FLU0RI"E By A. G. SHARPE M.A. Ph.D. (UNIVERSITY CHEMICALABORATORY CAMBRIDGE) RECENT advances in the descriptive inorganic chemistry of fluorine and its compounds have been the subject of several reviews,l but their correlation and interpretation in terms of measurable physical properties have rarely been discussed. The aim of this Review is to describe briefly some of the principal properties of the fluorine molecule the fluorine atom and the fluoride ion and to show how a knowledge of these properties can help in the understanding of the chemistry of fluorine and its relationship to the other halogens. The Physical Properties of Fluorhe.-Interatomic Distance. The values obtained by the electron diffraction and the Raman spectroscopic method (1.435 and 1.418 A respectively) are in good agreement and the covalent radius of fluorine (the bond being assumed to be of unit order-see p.50) may be taken as 0.71 A. Since the corresponding radii for chlorine bromine and iodine are 0.99 1.14 and 1-33 8 the volume of a fluorine atom in the combined state is only one-third of that of a chlorine atom and less than one-sixth of that of an atom of iodine. Dissociation Energy. This quantity (the energy absorbed when a gaseous molecule is converted into two atoms in the ground state) has been the subject of much controversy. Fluorine does not show banded absorp- tion in the visible or ultraviolet region (presumably because of the instability of the excited state) and spectroscopic determination of D(F2) is therefore impossible. Older values for the dissociation energy were usually based explicitly or implicitly on extrapolation of those for chlorine bromine and iodine (58.0 46.1 and 36-1 kcal.respectively) and were of the order of 60-70 kcal. In 1950 however Evans Warhurst and Whittle,4 on the basis of recent work on the thermochemistry and absorption spcctrum of chlorine monofluoride suggested that the true value was 37 & 8 kcal. Most later investigations support this lower figure ; the following deter- minations may be taken as representative. ( a ) Simons Editor " Fluorine Chemistry " Academic Press Inc. New York Vol. I 1950 ; Vol. 11 1954 ; ( b ) Haszeldine and Sharpe " Fluorine and its Com- pounds " Methuen and Co. Ltd. London 1951 ; (c) Gutmanil Angew. Ckevn,. 1950 62 312; ( d ) Sharpe Quart. Rev.1950 4 115; (e) Leech Research 1952 5 lOS 449 ; (f) EmelBus J. 1954 2979 ; ( 9 ) Klemm Angew. Chein. 1954 66 470 ; ( h ) Rudge Chem. and Ind. 1956 504 ; (i) Mellor " A Comprehensive Treatise on Inorganic and Theoretical Chemistry " Suppl. 11 Part I Longmans Green and Co. Ltd. London 1956. 2 Rogers Schomaker and Stevenson J . AnTer. Ch,em. SOC. 1941 63 2610. 3 Andrychuk Canad. J . Phys. 1951 29 151. 4 Evans Warhurst and Whittle J. 1050 1524. D 49 50 QUARTERLY REVIEWS (i) Doescher 5 studied the pressure-temperature relationship for fluorine in a ire-treated nickel vessel over the temperature range 759-1115' K by comparing the pressure with that of nitrogen a t the same temperature using a differential manometer containing a fluorocarbon oil. His results indicate a value for D(F,) a t 25" of 37.4 & 0.4 kcal.(ii) From observation of the rate of effusion of fluorine a t low pressures through a small hole (a method which permitted the use of relatively low temperatures 500-650" K) Wise 6 found D(F,) = 39.9 5 0.8 kcal. determined the dissociation energies of the potassium rubidium and caesium halides spectroscopically and combined their results with independently obtained thermochemical data for these substances and the alkali metals (iii) Barrow and Caunt iD(F2) = D(MF) + L(MP) - L(M) - &(MF) where &(MF) is the heat of formation of a solid fluoride MF from solid M and gaseous F, and L(MF) and L(M) are the heats of sublimation of the fluoride and of the alkali metal respectively. They obtained B(F2) = 37.6 5 3.5 kcal. I n this Review the dissociation energy is henceforth taken to be 38 kcal.This low value is generally ascribed to the repulsion of non-bonding electrons in the F molecule but it has also been suggested that for chlorine bromine and iodine hydridisation of p - and d-valence shell orbitals strengthens the b0nding.~9 8 The nice distinction between the bond in fluorine being abnormally weak and the bonds in the other halogens being abnormally strong is essentially a theoretical matter. It should however be pointed out that the N-N and 0-0 bond energies (21 and 35 kcal. in N,H4 and H,O respectively g are also low and that here too repulsion of non-bonding electrons of small atoms may well be the cause. The usual thermodynamic functions for atomic and molecular fluorine have been calculated lo from the interatomic distance,2 the fundamental vibration frequencyY3 and Doescher's value for D(F,).First fluorine is dis- sociated into atoms to a greater extent than chlorine a t the same tempera- ture and since reactions of atomic fluorine are strongly exothermic the great reactivity of the element may be attributed to the weakness of the bond in the F molecule. Secondly since the standard entropies of mole- cular and atomic fluorine (48.6 cal. mole-1 deg.-l and 37.9 cal. g.-atom-l deg.-l) differ but little from those of molecular and atomic chlorine (53.3 and 39.5 entropy units 11) differences between the two halogens are due to heat effects (e.g. the strengths of bonds) rather than to entropy effects. This generalisation holds in fact for all the halogens. The energy required for removal of an electron Thermodynamic Properties.Two important points may be noted. Ionisation PotentiaZ. Doescher J. Ghem. Phys. 1952 20 330. Mulliken J . Amer. C'hem. SOC. 1955 77 884. Cottrell " The Strengths of Chemical Bonds " Rut,terworths Scientific Publications Wise ibid. p. 927. ' Barrow and Caunt Proc. Roy. Soc. 1963 A 219 120. London 1954. lo Cole Farber and Elverurn J. Chem. Phys. 1952 20 586. l1Nat. Bur. Stand. Tables Circular No. 500. SHARPE THE INORGANIC CHEMISTRY OF FLUORINE 51 from atomic fluorine is 401 kcal./g.-atom.12 This figure combined with that for D(F,) leads to a standard heat of formation of the gaseous B'+ ion of 420 lrcal./g.-ion. Such a high value (those for C1+ Br+ and I+ are 327 301 and 268 kcal. respectively 11) suggests that even solvated fluoro- ilium ions are unlikely to be encountered in chemical investigations ; there is in fact a t the present time no evidence of any kind for the existence of " positive fluorine ".Electron Aflnity. The classical method for determining the heat liber- ated E when gaseous halogen atoms combine with electrons giving gaseous halide ions is by the Born cycle where I ( M ) is the first ionisation potential of the alkali metal M and U(MX) the lattice energy of the solid halide MX (the heat liberated when one formula weight is produced from gaseous M+ and X- ions). U may be calculated from the interionic distance T in solid MX (determined by X-ray analysis) and the compressibility of the solid by an expression of the type U = NMz,x2e2 (1 - l / n ) / r where M the Madelung constant is a geometrical constant for a particular type of structure x1 and x2 are the charges on the ions e the electronic charge N the Avogadro number and n a constant (about 9) which takes account of interionic repulsion arising from the finite size of the ions.This method when applied to fluorine yields E(F) = 84 & 2 kcal./g.- atom,13 a value intermediate between those for chlorine and bromine (88 and 82 kcal./g.-atom respectively). This somewhat surprising result is as was first pointed out by Evans Warhurst and Whittle,* an inescapable conse- quence of the low value of D(F,) ; it must however be remembered that additional factors are always involved in determining the stability of com- pounds containing fluoride ions. The Valency of Fluorine.-The electronic configuration of the fluorine atom is ls22s22p5 and expansion of the valency shell beyond 2s22p6 is impossible.It is known from the atomic spectrum of fluorine that pro- motion of an electron to the 38 3p7 or 3d level is a highly endothermic pro- cess ; this of course provides no direct evidence concerning the possibility of promotion in a stable molecule but comparison with other first-row elements strongly suggests that fluorine should be exclusively univalent .14 With the possible exception of the difluorides and trifluorides of the alkali metals l5 (e.g. RbF, obtained by the action of fluorine on rubidium chloride a t 150') this generalisation seems valid for all fluorine compounds. Rubi- dium trifluoride must obviously contain multivalent rubidium or multivalent fluorine ; the structure Rb3+F is inadmissible on energy considerations but a decision between structures such as Rb+F,- and Rb+(RbF,)- is a t present impossible E(X) = &(MX) + L(M) + I(M) + W(XJ - U(MX) l2 Nat.Bur. Stand. Tables Circular No. 467. l3 Pritchard Chem. Rev. 1953 52 529. l4 Gillespie J . 1952 1002. l5 Bode and Klesper 2. anorg. Chem. 1951,267,97. For a discussion of the structure of RbF see also Sharpe Ref. l(a) Vol. I1 p. 2. 52 QUARTERLY REMEWS The Physical Properties of the Fluoride Ion.-Ionic Radius. X-Ray structure determinations yield information about atomic positions and for the division of interionic distances into ionic radii the introduction of certain hypotheses is necessary. The simplest of these is that in the lithium halides the anions are in contact; this and a variety of other more elaborate methods l6 lead to the values I? 1.36 ; C1- 1-81 ; Br- 1.95 ; I- 2.16 8.The fluoride and oxide ions are of almost identical size [ r ( 0 2 - ) = 1-40 A] and thence arises the similarity in structure which is often found between oxides and fluorides of the same formula type (e.g. MgO and NaF) ; fluorides and chlorides of the same metals however often have quite different struc- tures (e.g. CdF and HgF both crystallise with the fluorite structure but CdC1 has a layer lattice in which the Cd2f ion has co-ordination number six and HgCl has a molecular lattice). The crystal chemistry of both simple and complex fluorides is admirably discussed by We1ls.l' When an ionic crystal dissolves in water the sum of the heats of hydration of the ions must equal the lattice energy of the solid plus the heat of solution.Two principal difficulties attend the assignment of individual heats of hydration uncertainty over the values for ionic radii in solution [which would enable approximate values to be calculated from Born's expression Ne2(1 - l / D ) / 2 r where D is the dielectric constant of the medium] and the absence of any precise knowledge of the structure of hydrated ions. Differences in heats of hydration how- ever are not subject to the same uncertainty e.g. the heats of solution of sodium fluoride and sodium chloride are both very small and since their lattice energies a t 25" are 215.4 and 183.5 kcal. respectively the heat of hydration of F- must be 32 kcal. greater than that of C1-. The absolute values are estimated l8 to be P- 123 ; C1- 89 kcal. ; these lead to standard heats of formation of the hydrated ions of 188 and 148 kcal.* A similar position exists with regard to entropies of hydration which have to be obtained from entropies of solid salts entropy changes attending dissolution and entropies of gaseous ions calculated by statistical mechanics ; the estimated values l8 for fluoride and chloride ions (I? -29 ; C1- -15 cal.g.-ion-l deg.-l) are however so similar that (as with molecules and atoms) entropy changes in fluoride-chlorine substitutions may almost be neglected in comparison with the big difference in heats of hydration the standard free energies of hydration are F- -114 ; C1- -84 kcal. The Standard Potential of the Fluorine-Fluoride Ion E1e~trode.l~ An Heat and Entropy of Hydration. l6 Pauling " The Nature of the Chemical Bond " 2nd edn.Cornell Univ. Press 17 Wells " Structural Inorganic Chemistry " 2nd edn. Oxford Univ. Press 1950 ; Ithace New Pork 1940. Quart. Rev. 1954 8 380. Latimer Fitzer and Blansky J. C'hent. Phys. 1939 7 108. lQ Latimer " The Oxidation States of the Elements and their Potentials in Aqueous Solutions " 2nd edn. Prentice-Hall Inc. New York 1952. * It should be noted that these are absolute values ; the National Bureau of Standards values l1 are based on a standard heat of formation of the hydrated hydrogen ion of zero. This practice is more coiivenieiit in thermochemistry because of the uncertainty in the magnitude of the hydration energy of the proton SI'IARPE THE INORGANIC CHEMISTRY OF FLUORINE 53 indirect calculation of Eo for the $l?2/F-(aq) electrode from related thermo- chemical data leads to a value of +2.S v (relative to Eo for the +H2/H+(,q) electrode as zero).The figure for fluorine expresses the fact that it is the most powerful oxidising agent known and explains why the element can be prepared only by thermal decomposition of a few higher fluorides (such as cobalt trifluoride) or by electrolysis of solutions of fluorides in media (such as hydrogen fluoride) in which no other anion is present. The factors which determine the oxidation potential of a halogen may be seen by considering the following sequence The first stage involves absorption of energy equal to one-half of the dis- sociation energy the second stage the liberation of the electron affinity and the third stage the liberation of the hydration energy. Although therefore the electron affinity of fluorine is lower than that of chlorine the weaker bond in the F molecule and the higher hydration energy of the smaller fluoride ion make fluorine the more powerful oxidising agent.The Electronegativity of Fluorine.163 20-A11 of the quantities mentioned hitherto however difficult their measurenient may be are easily defined. The concept of electronegativity however calls for some comment. The strength of trifluoroacetic acid the absence of basic properties in the fully fluorinated amine (CF,),N and the retardation of attack by electrophilic reagents in aromatic substitution when the CW group of toluene is replaced by CF, all suggest that fluorine in such molecules attracts electrons. This " power of an atom in a molecule to attract electrons to itself'' l6 is what most chemists mean by electronegativity but unfortunately this quantity is not susceptible to direct.experimental measurement. (It is indeed an assumption that each element has a numerically expressible electronega- tivity which remains constant through its compounds.) Three principal methods for the assessment of electronegativity have been suggested. Mulliken proposed taking the mean of ionisation potential and electron affinity ; in this context however it is the ionisation potential of the element in its valency state (which has to be estimated) that is required. Malone related electronegativity to dipole moments ; unfortunately bond dipole moments (as distinct from molecular moments) are not in general measurable since the effect of unshared pairs of electrons on the moment is considerable.This is clearly illustrated by the fact that nitrogen trifluoride although having a pyramidal structure with LFNF = 102" and N-F = 1.37 A has a dipole moment of only 0.2 D. Pauling's scale rests on a number of unproven assumptions but does have the advantage of being related to molecular properties. The energy of a normal single covalent bond between two elements A and B (e.g. H and F,) is taken to be the mean of the Fond energies in A and B,. The difference in electro- negativity of A and B xA - xB is then taken as The corresponding value for chlorine is + l a 3 6 v. QX,(g) -+ X(g) -+ X-M + X-(aq) XA - XB = 0*208[EA - (EAA + EBB)/2]' 2o Pritohard and Skinner CiLern. Rev. 1965 55 745. 54 QUARTERLY REVIEWS where E is the actual bond energy in AB (in kcal.) and the expression in square brackets is regarded as " extra " bond energy arising from the partial ionic nature of the A-B bond.This relationship does lead to a fairly self- consistent set of electronegativities and if xH is arbitrarily taken to be 2.1 (in order to make all values of x positive) xp is found to be 4.0 making fluorine easily the most electronegative element. Bond energies in fluorine compounds are discussed again later. Some Properties of Inorganic Fluorine Compounds The Dissociation of Hydrogen Fluoride in Aqueous Solution.-The large dipole moment of hydrogen fluoride (1-9 D at pressures so low that associa- tion is negligible 21) shows the bond in this compound to be strongly polar and the chain structure in the solid 22 (the other hydrogen halides have close-packed structures) arises from dipole-dipole interaction.I n dilute aqueous solution however hydrogen fluoride is a much weaker acid than the other hydrogen halides. This fact when considered in conjunction with the well-known increase in dissociation constant along the series CH,*CO,H CH,I*CO,H CH,Br*CO,H CH,C1*C02H and CH,F*CO,H a t first seems surprising ; in the carboxylic acids however ionisation always involves the breaking of the same bond whereas in the hydrogen halides the bonds to be broken are all different. The general process of ionisation may be represented as taking place in the following stages 23 24 HX(aq) + HXW -+ H a ( ) + X.(,) + H+(g) + X-(g) The stages involving the conversion of a hydrogen atom into a solvated proton are the same for all acids and only four variables have to be con- sidered the energy of solution of the undissociated molecule the dissocia- tion energy of the H-X bond the electron affinity of X and the solvation energy of X-.The first factor is approximately the same for all of the halides the electron affinity of fluorine lies between those of chlorine and bromine and the hydration energy of the F- ion is much larger than those of other halide ions. The decisive factor must therefore be the strength of the bond in hydrogen fluoride (Bond energies HF 135; HCl 103; HBr 8 7 ; HI 71 kcal.). I n more concentrated solutions (5-15~) ionisation into H,O+ and HI?,- H2F3- and H3F4- takes place and hydrogen fluoride becomes a strong acid.25 The formation of these stable acid anions in liquid hydrogen fluoride accounts for the great proton- donating (i.e.acidic) properties of this solvent. Hydrogen Bonding in Fluorine Compounds.-As the most electronegative element fluorine would be expected to take part in hydrogen bond forma- tion and some of the best known instances of this phenomenon do in fact -+ H+laq) + X-(aq) 21 Oriani and Smyth J . Amer. Chem. SOC. 1948 70 125. 22Atmoji and Lipscomb Acta Cryst. 1954 7 173. 23 Bell " Acids and Bases )) Methuen and Co. Ltd. London 1952. 24McCoubrey Trans. Paraday SOC. 1955 51 743. 26 BelI Bascombe and McCoubrey J. 1956 1286. SHARPE THE INORGANIC CHEMISTRY OF FLUORINE 55 involve covalently bonded fluorine or the fluoride ion. The structural difference between hydrogen fluoride and other hydrogen halides has already been mentioned ; the strength of the bonding in the KF,- ion is also remark- able.The fluorine-fluorine distance in this ion is only 2.26 8 and a neutron- diffraction study 26 of potassium hydrogen difluoride shows that the hydrogen is (to within 0-1 8) in the middle of the linear ion. The structure of ammonium fluoride differs completely from those of the other ammonium halides (which crystallise with the sodium chloride or czesium chloride structure) ; in this salt (which has the wurtzite structure) each nitrogen atom forms four N-I€-F bonds of length 2.69 A to the four fluoride ions arranged tetrahedrally around it. 27 The N-H vibration frequency is lowered from its normal value of about 3300 cm.-l to 2820 cm.-l; rather surprisingly nuclear magnetic resonance studies 28 indicate that this reduction in the N-H vibration frequency is not acconipanied by any considerable stretch- ing of the N-H bond (length in NH,F 1.04; in NH,Cl 1.038 A).In hydrnzinium fluoride however (the structure of which is also determined by hydrogen bonding) a slightly greater N-H distance of 1.075 A is reported.29 It should not be thought that all ammonium salts of fluoro-acids exhibit strong hydrogen bonding. In salts of complex acids this is certainly not so ; a wide variety of evidence (X-ray s t ~ d i e s ~ O - ~ ~ infrared spectra,32 33 and nuclear-resonance spectra 34) suggests that in salts such as NH4Bl? and (NH4),TiF there can be no more than very weak hydrogen bonding. This somewhat unexpected conclusion shows that the participation of fluorine in hydrogen-bond formation is not nearly so general as that of nitrogen or oxygen.No satisfactory explantion of this fact has yet been put forward and the recent discovery 35 of the HC1,- ion indicates that it may soon be necessary to modify present ideas about hydrogen bonding and 'its relation to the electronegativities of the halogens. Fluorides of Non-metals Bond Energies and Bond Lengths.-Fluorine often invokes highest covalencies (e.g. in SF, IF,) and although steric factors must be of some importance in this connection a satisfactory dis- cussion of this topic must involve consideration of the energy changes involved. The formation of sulphur hexafluoride may be represented as taking place in the following rdages S (solid) --+ S (gas ; ground state 3523~3~) --+ S (gas ; valency state 3s13p33d2) 3F2 (gas) ________+ 6F (gas) + SF (gas) 26Peterson and Levy J.Chem,. Phys. 1952 20 704. 27 Plumb and Hornig ibid. 1955 23 947. 28Drain Discuss. Faraday Soc. 1955 19 200. 2g Deeley and Richards Trans. Faraday SOC. 1954 50 560. 30 Hoard and Blair J . Amer. Chem. XOG. 1935 57 1985. alCox and Sharpe J. 1953 1783. 321dem J. 1954 1798. 33Cot6 and Thompson Proc. Boy. SOC. 1951 A 210 217. a4Pend.red and Richards Trans. Faraduy SOC. 1955 51 468. 36Herbrandson Dickerson and Weinstein J . Amer. Chem. SOG. 1954 76 4046. 56 QUARTERLY REVIEWS In considering why sulphur forms a hexafluoride but not a hexahydride or a hexachloride the fundamental question to be answered is will the energy liberated by bond formation in the compound compensate for the energy required to raise the sulphur atmom from its ground state to its valency state and to effect dissociation of the halogen (or hydrogen) molecules ? In general (molecular fluorine constitutes an exception and is discussed again below) smaller atoms form stronger bonds a fact which is simply accounted for on modern valency theory by the greater overlapping of orbitals of low principal quantum number.Equally important however is the dissociation energy of the halogen (or hydrogen) and the low value for fluorine (F, 38 ; Cl, 58 ; H, 104 kcal.) is probably the most important factor in this case. Because of the weakness of the bond in molecular fluorine most fluorine compounds are strongly exothermic (this term it will be remembered refers to heats of formation from elements in their standard states) ; conversely because of the strength of the bond in molecular nitrogen (225 kcaL36) most nitrogen compounds containing a high proportion of the element are endothermic.The widely quoted fact that nitrogen trifluoride is an exothermic compound (Qf = +26 kca'1.j whilst the trichloride is endo- thermic (Qf = -55 kcal.) thus represents a case essentially similar to the existence of SF but not of SC16 or SH,. In discussing electronegativity it was mentioned that bonds involving fluorine are usually much stronger than would be expected on the basis of an " arithmetic mean " rule. They are also much shorter than values calculated by adding standard covalent radii the universally accepted carbon-carbon single bond length for example is 1.54 8 and F-F in F is 1.42 8 ; C-F in CF, however is only 1.32 A.m Similarly unexpectedly short bonds have also been found in fluorides of silicon nitrogen phosphorus arsenic oxygen and sulphur.For first-row elements such as carbon multiple bond formation appears to be impossible in these compounds and a suggestion which has met with much favour is that the observed bond length should be less than the sum of the covalent radii by an amount proportional to the difference between the Pauling electronegativity co- efficients of the elements concerned the actual length being given by the empirical Schomaker-Stevenson equation 38 TAB = rA rB - o'Og(x xg) The general applicability of this relation has been severely criticised by Wells 39 but the qualitative conclusion that bonds between fluorine (and to a smaller extent oxygen nitrogen and chlorine) and less electronegative elements are shorter than expected on the basis of a simple additivity rule is unchallenged.These generalisations about the energies and lengths of bonds involving fluorine suggest that perhaps it is once again a property of the reference 36McDoweII PTOC. Roy. SOC. 1956 A 236 278. 37Hoffman and Livingston J . Chem. Phys. 1953 21 565. 3sSchomaker and Stevenson J . Amer. Chem. SOC. 1941 63 37. a9 Wells J . 1949 55 ; ref. 17 p. 56. SHARPE THE INOR(XAN1C CHEMISTRY OF FLUORINE 57 standard (the F molecule) which lies a t the root of the matter. If the weak bond in the fluorine molecule is due to repulsion of non-bonding electrons i t seems not unreasonable that as the molecule is split into atoms which then combine with elements to form compounds in which there are few or no unshared electrons on the central atom (e.g.CP, SF,) such repulsion should disappear. This it is suggested may be the reason for the " abnor- mal " strength and shortness of bonds in other compounds formed between elements of widely differing electronegativities (e.g. C and 0 P and 0 Si and F). The stability of non-metal fluorides (especially of CF and SFJ is often cited as a remarkable feature of fluorine chemistry and it is not always realised that these compounds are not thermodynamically particularly stable The free energies of the following hydrolytic reactions (neither of which proceeds a t a detectable rate under ordinary experimental conditions) have been calculated from standard thermochemical data 11 3ga CF,(g) + 2H,O(,) = CO,(g) + 4HF(,) SF,(,) + 3H,0(g) = SO,(g) + 6HF(,) AGO = - 36 kcal. AGO = - 72 kcal.They show that the inertness of the fluorides must be due to activation- energy considerations ; these may well involve the failure of a water mole- cule to co-ordinate on to a combined fluorine atom (because of the octet restriction) but it cannot be said that a convincing explanation has yet been given. Fluorides of Metals.-Two general features stand out in the chemistry of metal fluorides first many metals show their highest oxidation states attained in salts in their fluorides (e.g. Co in COP, Ag in AgF, Bi in BiF5 Tb in TbF, Rh in RhF,) ; secondly many fluorides of high oxidation states are salt-like in properties where the corresponding chlorides are not (e.g. AuF3 PbF, TlF3). (The highest fluorides of many transition metals e.g. MoF, UF, OsF8 are volatile and generally resemble the fluorides of non-metallic elements.) Both of these generalisations are illuminated by consideration of a modified Born cycle.Suppose for example the possi- bility of a metal's forming a saline tetrahalide is examined by analysing the stages involved In this context the latent heat of sublimation of the metal will be relatively small ; for all of the halogens the sum of E - D/2 which represents the net energy change in forming a gram-ion of halide ions from half a gram- molecule of molecules is about 60 kcal. The essential question is then will 4(E - D/2) plus the lattice energy of MX compensate for the energy required to remove four electrons from the metal atoms ? I n the absence of a knowledge of the structure (and thence the lattice energy if the calculation 39. Kirkbride and Davidson Nature 1954 174 79.58 QUARTERLY REVIEWS is simple enough) of the halide no precise answer to this question can be given ; but since the lattice energy will depend inversely on the interionic separation it will clearly be a maximum when for a given cation the radius of tJhe anion is a minimum. This condition is fulfilled by the anion’s being fluoride. The other common anion of similar size ( 0 2 - ) involves the absorption of a large amount of energy when it is formed from molecular oxygen ; this is however largely compensated for by the double charge and the conse- quent increase in the electrostatic lattice energy. It is not therefore sur- prising that ionic oxidation states in oxides are often as high as or even higher than those in fluorides (e.g. MnO, Ago Pro,) or that manysalt- like fluorides (e.g.AuF, PbF, COP,) are hydrolysed by water with the formation of very insoluble oxides and fluoride ions ; the high hydration energy of the fluoride ion is also an important factor in bringing about hydrolysis. One further argument which may be developed from the simple electro- static treatment concerns the use of alkali-metal fluorides as halogen- exchange reagents in organic chemistry. If we consider the replacement \ \ / / -C-Cl + MF + -C-F + MC1 where M = Na or K the driving force of the reaction will depend on the free-energy difference (or fairly accurately the difference in lattice energy) between sodium fluoride and sodium chloride on the one hand and potassium fluoride and potassium chloride on the other. Lattice energy being inversely proportional to interionic distance the increase in free energy when sodium chloride is formed from the fluoride will be proportional to and it is easily seen that for a larger cation the amount of free energy which has to be supplied by the C-Cl-+ C-B’ change is less.Pluorine-exchanging ability therefore increases steadily with increasing ionic size among fluorides of metals which form isomorphous compounds.40 In the special case of the use of silver fluoride it is easily shown from inde- pendent thermochemical data that the difference in lattice energy between silver fluoride and silver chloride is very small (owing to the contribution of non-ionic bonding in solid silver chloride) ; hence arises the especial power of silver fluoride as a halogen-exchange reagent. Complex Fluorides and Fluoro-acids.-The factors which govern the stability of complex fluoro-ions will be similar to those concerned with the stabilities of simple fluorides.Among complex fluorides the relatively small size of the anions (thus leading to increased lattice energy) will play an important part; and within recent years especially by the use of ele- mental fluorine a t medium temperature^,^^ and of bromine trifluoride as a 40 Woyski J. Amer. Chem. Xoc. 1950 72 919. 41 Klemm and HUSS 2. anorg. Chem. 1949 258 221 and later papers by Klemm and his co-workers. SHARPE THE INORGANIC CHEMISTRY O F FLUORINE 59 non-aqueous solvent and fluorinating 43 many new complexes of unusual oxidation states have been obtained (e.g. Cs,CoF, K,NiF, K,CuP, K,RhF, KIrF6 AgAuF,). Most of these compounds are hydrolysed to oxides by water.Although for base metals fluorides are the most stable complex halide ions in solution the reverse is true for noble metals such as platinum and gold.44 This is often interpreted as being due to n-bond formation between the noble metal and chlorine bromine or iodine d-electrons of the metal being used for this purpose.45 Fluorine would not be able to accept more electrons and the bonds in complex fluorides would therefore necessarily be devoid of multiple character with its consequent strengthening effect. It must however be pointed out that this is not the only factor involved in an equilibrium such as PtFO2- + 6CI- + YCC1,2- + 6F- and that the larger solvation energy of the fluoride ion must also play a n important part in influencing the stability of the complex.All complex fluoro-acids (and indeed complex halogeno-acids in general) are extremely strong. The univalency of fluorine provides a simple and convincing explanation of this fact in a case such as fluoroboric acid where the formulation of the undissociated molecule HBF is impossible without invoking quinquevalent boron or bivalent fluorine. A study of the HF-BF system has shown the non-existence of a 1 1 compound ; only if a molecule such as NH, H,O or a second molecule of HF is available to combine with the proton (giving NH,+BF4- H,O+BF,- or H,F+BF,-) will the com- pounds combine. Reasonable formulae for other undissociated molecules such as HPF, H,SiP, and H,PtCl (none of which is known in the free state) are also impossible. Because of the impossibility of a fluoroborate's having a covalent struc- ture this ion is very useful in studies in which it is desirable t o be sure of the ionic nature of bonding e.g.in the interaction of silver salts and aromatic hydrocarbons 46 (AgBF is soluble in and forms stable complexes with these substances) and in the investigation of the spectra of organic cations 47 (e.g. Ph,C+ in Ph,C+BF,-). A mixture of hydrogen fluoride and boron trifluoride is indeed the most acidic solvent known and in it even so weak a base as hexamethylbenzene is largely converted into the salt [C6(CH3),H] +BF4-.489 49 Conclusion.-The principal properties which confer on fluorine its remark- able chemical behaviour are the-smallness of the fluorine atom and the fluorine ion the restriction to an octet of electrons and the weakness of 4 2 Sharpe J.1949 2901 and later papers. 43 Hepworth Robinson and Westland J. 1954 4268. 4 4 Sharpe J. 1950 3444 ; Carleson and Irving J. 1954 4390. 45See e.g. Chatt and Leden J. 1955 2936. 46 Sharp and Sharpe J. 1956 1855. 4 7 Sharp and Sheppard J. in press. 48 McCaulay and Lien J . Amer. Chem. Soc. 1951 73 2013. 49 Kilpatrick and Luborsky ibid. 1953 75 577. 60 QUARTERLY REVIEWS the bond in the F molecule. It would be entirely misleading to suggest that our understanding of the chemistry of the element is yet complete but with the aid of physical methods of investigation a deeper insight into its properties is rapidly becoming possible.

ISSN:0009-2681    

DOI:10.1039/QR9571100049

出版商:RSC    

年代:1957

数据来源: RSC

摘要:

CARBOHYDRATE PHOSPHATES By A. B. FOSTER YH.D. (UNIVERSITY OF BIRMINGHAM) and W. G. OVEREND D.Sc. (BIRKBECK COLLEGE UNIVERSITY OF LONDON) IN their classical studies of the effect of inorganic phosphate on cell-free sugar (glucose) fermentation Harden and Young showed that carbohydrate phosphate is formed in addition to alcohol and carbon dioxide according to the equation 2 Glucose + 2 Phosphate = 1 Hexose &phosphate + 2 Alcohol + 2 Carbon dioxide . - (1) The phosphoric ester which accumulates is fructose 1 6-diphosphate fre- quently termed the Harden-Young ester. These observations led to other important investigations for example the isolation of glucose monophos- phates by Robison and Embden studies of glycolysis in muscle extracts by Meyerhof and Lohmann and Lundsgaard's observations on the chemical events which accompany the alactacid muscle contraction.This work clearly indicated that phosphoric esters play a central part in the biological world by linking processes of respiration and fermentation with other essential cellular reactions. Quite a large number of esters of this class are now known and the group is still growing as further compounds are isolated. Amongst these phosphoric esters those of the carbohydrates form a principal class and are known to function as intermediates in the network of enzymic reactions associated with the breakdown and interconversion of carbo- hydrates in plants and animals. Consequently it is not surprising that this class of compound has attracted widespread interest and there is a flood of papers annually on their biological function.Although strictly chemical studies are less numerous all facets of the subject could not be condensed adequately into a Review of the present type so we propose to emphasise chemical synthesis isola.tion and reactions of sugar phosphates and to mention only briefly their biological r81e. For more detailed account's reference should be made to recent re~iews.l-~ Detection and Estimation Both in the intact cell and in the isolated enzyme systems in which biological reactions are studied phosphoric esters usually occur as mix- tures. Colour reactions are used to identify the sugar component of carbo- hydrate phosphates ; e.g. the reaction with resorcinol permits the estimation Leloir Portschr. Chem. org. Naturstoffe 1951 8 47. 2Foster Overend and Stacey Die Starke 1953 11 285.Benson " Phosphorylated Sugars " in " Moderne Methoden der Pflanzenanalyse " 1'01. 11 Springer-Verleg Berlin 1955. 61 62 QUARTERLY REVIEWS of ketose esters,4 and pentose esters are detected with orcinol. The rate of colour development with the latter reagent serves to differentiate ribose 3- and 5-phosphate,5 * and also compounds containing phosphoribose residues (and possibly related pentose phosphates). (The method is rapid and can be used on as little as 10 i ~ g . of phosphate ester. It cannot be used precisely on crude plant and bacterial extracts containing polysac- charides since these alter the rate of colour development.) As in other branches of carbohydrate chemistry paper chromatography provides a valuable micromethod for identification. Removal of inter- fering ions by ion-exchange resins from hydrolysates of hexosephosphates improves the chromatograms.6 Hanes and Isherwood 7 demonstrated that it is €easible to separate phosphoric esters including compounds of very similar constitution on a filter-paper chromatogram and to detect them by spraying the papers with an acid molybdate solution and then heating thein under conditions which hydrolyse the esters without unduly decom- posing the paper.The orthophosphoric acid produced fornis a phospho- molybdate complex and this is reduced to an intensely blue compound on exposure to hydrogen sulphide. Various solvent mixtures have been detailed for the chromatographic separation,8 and lists of R values for sugar phosphates have been published. Addition of boric acid to the solvents helps to separate esters with cis-hydroxyl groups from esters in which this grouping is absent .Q The unidimensional chromatography described by Hanes and Isherwood does not always adequately resolve the complex mixtures obtained from some plant materials (cf.Mortimer 8) and so two-dimensional chromato- graphy with successive development in an acid and in a basic solvent has been worked out.1° I n addition? modifications of the original Hanes- Isherwood method have been described. It is claimed that by upward migration at 4" on acid-washed paper with appropriate solvents it is possible to adopt shorter running times and achieve higher R values. This method gives more discrete spots than the two-dimensional procedure and these spots are detected by dipping rather than spraying the papers.11 Irradia- tion with ultraviolet light resulting in colour differences,1° has been used to differentiate between organic compounds containing bound phosphorus and those containing inorganic phosphate.Two drawbacks to the widely used Hanes-Isherwood method are that 6Albaum and Umbreit ibid. 1947 167 369. Roe J . Biol. Chern. 1934 107 15. Dulberg Roessler Sanders and Brewer ibid. 1952 194 199. Hanes and Isherwood Nature 1949 164 1107. Mortimer Canad. J . Chem. 1952 30 653 ; see also Wright and Khorana J . Amer. Chem. SOC. 1956 '78 811 and Loring Levy and Moss Analyt. Chem. 1956 28 539. Scott and Cohen J . Riol. Chem. 1951 188 509 ; Science 1950 111 543. lo Bandurski and Axelrod J . Biol. Chem. 1951 193 405. l1 Burrows Grylls and Harrison Nature 1952 1'70 800. * In this Review nomenclature of the type ribose 5-phosphate is used as customary when it is not desired t o specify whether the compound is present as free acid R*O.PO,H or as salt.For part'icular derivatives the Anglo-American agreed nomenclature is used [see J. 1952 51 11 rule 1 l(d)] e.g. cr-D-ribose &(barium phosphate). FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 63 the prolonged initial " digestion " necessary to break down the more resistant esters often leaves the paper in a fragile state and that further analyses cannot be carried out on the spot after the detection treafment. To overcome the former difficulty Fletcher and Malpress 1 2 used an enzyme (alkaline phosphomonoesterase) to break down the esters resolved on the chromatogram. To counteract the latter a method has been used depend- ing on fixation of ferric ions by the esters and reaction of the free ferric ion with " salicylsulphonic acid ".13 The phosphates appear as white spots on a pale mauve background orthophosphoric acid having a band of deeper mauve surrounding it.Other spot indicators of ferric ions also have given good results but in some cases the colours fade in light. In experiments with diphenylphosphoric esters ultraviolet contact prints have been used to find the position of the spots on a chromstogram,l4 and radiograms of sugar phosphates labelled with 32P have been examined by Calvin and his colleagues 15 during their work on photosynthesis. Ion-exchange resin chromatography has been used to separate mixtures of sugar phosphates ; e.g. Horecker and Smyrniotis 16 used Dowex-1 formate for the separation of pentose phosphates formed from 6-phospho- gluconate by yeast enzyme.Separations have also been achieved by ion- exchange with the aid of the borate c0mplex,~75 l8 and by ionophoresis l4 in borate buffer a t pH 10 and in acetate buffer at pH 5 at 800 v. Different phosphate esters have been separated by counter-current distribution the solubility in the organic phase was increased by addition of long-chain amines.lg Procedures other than chromatography have also been used to estimate sugar phosphates. A method described by Slater 2o depends on enzymic conversion of these compounds into dihydroxyacetone phosphate which subsequently reacts with reduced diphosphopyridine nucleotide (DPN) in the presence of glycerol phosphate dehydrogenase. The amount of reduced nucleotide undergoing reaction is determined spectrophotometrically.The method is highly sensitive-0.05 millimole of phosphorylated sugar can be measured with an accuracy of a few per cent. Methods for the estimation of fructose diphosphate 21 and glucose 6-phosphate 22 have been outlined and very small amounts of glucose diphosphate can be estimated by taking advantage of its coenzyme activity for phosphoglucomi~tase. 23 A method l2 Fletcher and Malpress Nature. 1953 1'71 838. l3 Wade and Morgan ibid. p. 529. l4 Matthews and Overend unpublished results. l5 Benson Bassham Calvin Goodale Haas and Stepka J . Amer. Chem. Xoc. 1950 l6 Horecker and Smyrniotis Arch. Biochem. Biophys. 1950 29 232. l7 Khym and Cohn J . Amer. Chem. SOC. 1953 75 1153. l8 Khym Doherty Volkin and Cohn ibid. p.1262. Plaut Kuby and Lardy J. Biol. Chem. 1950 184 243. 2o Slater Biochem. J. 1953 53 157. 21 Meyerhof and Wilson Arch. Biochem. Biophys. 1948 17 153. 2 2 Haas J . Biol. Chem. 1944 155 333. 23 Carclini Yaladini Caputto Leloir and Trucco Arch. Biochenz.. Biophys. 1949 72 1710. 22. 87. 64 QUARTERLY REVIEWS proposed for the estimation of fructose diphosphate is based on the deter- mination of the phosphate groups liberated during osazone formation. 24 Differences in the rate of hydrolysis of various sugar phosphates provide in some cases a method for their estimation in simple mixtures. Optical rotation has been used for distinguishing between ribose 3- and 5-phosphate and other pentose phosphates. Isolation from Natural Sources and Preparation by Enzymic Methods The pioneer investigations of Harden and his colleagues stimulated work on the isolation of sugar phosphates from natural sources.In addition to the changes formulated in equation (1) (the Harden-Young equation) it is possible under different conditions to obtain by the use of dried yeast or yeast- juice fermentations hexose monophosphate in amounts varying from 20 to 50% or more. The diphosphates can be separated from the monophosphates 25 and can be further differentiated by fractional crystal- lisation of their brucine salts.26 I n 1937 Cori Colowick and Cori 27 showed that a-D-glucose 1-phosphate (Cori ester) is formed when a solution of glycogen inorganic phosphate and adenylic acid is incubated with a dialysed muscle extract. Phosphorylase is now known to be widespread in Nature. The reverse of this reaction namely the enzymic conversion of the Cori ester into 1 4-a-glucosans is well known (cf.equation 2) and a recent review in this series by Barker and Bourne 28 on the enzymic synthesis of polysaccharides includes a full dis- cussion of the formation of amylose and glycogen from glucose 1-phosphate. (CgH1005)n + nK2HPOd + nC,H,1O,.OPO,K2 . - (2) 1 4-a-Glucosan K salt of Cori ester At equilibrium the ratio of total inorganic phosphate to total glucose 1-phosphate depends on the pH value of the system but the ratio of the bivalent ions [HP0,]2-/[C,H,,0,~O*P03] 2- is independent of pH and is always constant 299 30 a t 2.2. Hence the conversion of an unbranched 1 4-a-glucosan into a-glucose ]-phosphate can be carried to virtual com- pletion if the polysaccharide is treated with phosphorylase in the presence of a sufficiently large excess of inorganic phosphate to ensure that the equilibrium ratio of the bivalent ions is not attained before all the poly- saccharide is degraded.31-33 Since the enzymic degradation of amylose is so effective and easy to control the preparation of a-glucose 1-phosphate by this method is popular. Glucose 1-phosphate can be rearranged by 2 4 Deuticke and Hollman Z. physiol. Chem,. 1939 258 160. 25Robison and Morgan Bioc1io.m. J. 1930 24 119. 26 Robison and King ibid. 1931 25 323. 2 7 Cori Colowick and Cori J . Biol. Clhem. 1935 123 375 381. 28 Barker and Bourne Quart. Rezj. 1953 7 56. 29 Hanes Nature 1940 145 348 ; Proc. Boy. Soc. 1940 By 128 421 ; 129 174. 3O Trevelyan Mann and Harrison Arch. Rioclbetn. Biophys. 1952 39 419 440.31 Swanson J . Biol. C'h,ena. 1948 172 805 825. 32Bourne Sitch mid Peat J. 1949 1448. 33 Hestrin J . Biol. Ch,ern. 1949. 179 943. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 65 phosphoglucornutase to glucose 6-phosphate,34 which can also be obtained in good yield directly frpm starch by using phosphorylase and phospho- glucomutase in conjunction. 35 In Escherichia coli a biosynthesis has been detected in which a tmnsphosphorylation between two glucose 1 -phosphate molecules gives glucose 1 6-diphosphate and free glucose.36 Glucose 1 6-diphosphate has been isolated in small amount from crude fructose diphosphate preparations 37 obtained by fermentation procedures the diphosphates being separated by destroying the fructose ester with alkali which leaves the glucose analogue unchanged.Hydrolysis of fructose 1 6-diphosphate with phosphatase splits off both phosphate residues at the same rate and thus half of the monophosphate formed is fructose l-phos- hate.^^ It is not advisable to use highly purified phosphatase since the crude enzyme also changes fructose 6-phosphate into glucose 6-phosphate. The glucose derivative can be oxidised to 6-phosphogluconic acid and separ- ated as its insoluble barium salt. Consequently less fructose 6-phoaphate remains to be separated from the l-isomer than is the case if purified enzyme is used. Fructose l-phosphate was later obtained by an aldolase-induced condensation of phosphodihydroxyacetone and D-glyceraldehyde. 39 If DL-glyceraldehyde is used the products are fructose 1 -phosphate and sorbosc l-phosphate.39 To cite one example fructose 6-phosphate is formed when fructose and adenosine triphosphate are incubated with yeast hexokinase.40 41 This ester is also produced by the action of a specific enzyme (phosphomannose isomerase) on mannose 6-phosphate itself obtained by phosphorylation of mannosc with hexokinase. There are many references to the enzymic preparation of other hexose phosphates but the products have not in all cases been fully purified or satisfactorily characterised. Kalckar 42 observed that enzymic phosphorolysis of some ribonucleosides (inosine guanosine) leads to the formation of a pentose phosphate considered to be D-ribofuranose l-phosphate. The yield is very low possibly owing Inosine + Phosphate T Ribose l-phosphate + Hypoxanthine . (3) to losses by acid hydrolysis t o specific and non-specific contaminant phos- phatase action during the incubation with the enzyme and to retention on the bulky barium phosphate precipitate during working-up.Moreover in reaction (3) the equilibrium favours formation of the nucleoside rather a4 Colowick and Sutherland J . Biol. Chem. 1942 144 423 ; Sutherland Colowick and Cori ibid. 1941 140 309. 36 Swanson ibid. 1950 184 647. 36 Lelok Trucco Cardini Paladini and Caputto Arch. Biochem. Biophys. 1949 37 Idem ibid. 1948 19 339; 1949 22 87. 38MacLeod and Robison Biochem. J . 1933 27 286. 39Meyerhof Lohmann and Schuster Biochem. Z. 1936 286 301 319. 40 Kunitz and McDonald J . Gem. Physiol. 1946 20 393. 4lBerger Slein Colowick and Cori ibid. p. 379. r a Kalckar J. Biol. Chem. 1946,158,723 ; 1947 167,477 ; Fed.Proc. 1946,4,248 ; The action of kinases on the sugars is well established. 24 65. Symp. Boo. Expt. Biol. 1947 1 38. XI 66 QUARTERLY REVIEWS than of the pentose phosphate. Addition of xanthine-oxidase to the system leads t o the removal of hypoxanthine by conversion into xanthine and uric acid the pentose phosphate is then isolable as its barium salt Naturally occurring nucleosides are derivatives of P-ribofuranose 43 and apparently nucleoside phosphorylase produces inversion and this ribose 1 -phosphate has been shown to have the or-c~nfiguration.~~~ Synthetic ribopyranose l-phosphate 45 will not serve as substrate for the enzyme producing nucleo- sides a result which suggests that the pentose phosphate produced according to equation (3) is of the furanose type. This has been confirmed by the chemical synthesis of or-D-ribofuranose 1 -phosphate 44b which was found to be identical with enzymically prepared samples and to be fully active as a substrate for the fish-muscle purine-nucleoside phosphorylase.Phosphorolysis of deoxyribonucleosides has also been achieved. Enzyme preparations from calf-thymus gland and rat liver act on hypoxanthine deoxyriboside to give an acid-stable phosphate ester ; this is 2-deoxyribose 5-phosphate and is formed from deoxyribose 1 -phosphate by mutase action.46 From the enzymic phosphorolysis product of guanine deoxy-D- riboside Friedkin 47 isolated %deoxy-~-ribose 1 -phosphate as the crystalline cyclohexylamine salt. Recently a simplified procedure for the isolation of deoxyribose 1 -phosphate has been developed it involves phosphorolysis of thymidine in the presence of ammonium dicycEohexy1 hydrogen phosphate followed by a fractionation with butan-1 -01-diethyl ether which yields crystalline dicyclohexylammonium deoxyribose 1 -phosphate after a single filtrati0n.4~ This ester is even more unstable than ribose l-phosphate and is hydrolysed by the acid used in methods for phosphate estimation it therefore appears in analyses as “ inorganic phosphate ”.By mutase action ribose l-phosphate can be converted into ribose 5-phosphate. Klenow and Larsen 4s have shown that phosphoglucomutase acting with glucose 1 6-diphosphate (and probably ribose 1 5-diphosphate) as coenzyme will bring about this change. Preparations from liver also contain a mutase capable of transforming ribose l-phosphate into the 5-is0mer.~~ Levene et aL51 claimed to have prepared ribose 3-phosphate from nucleo- tides (xanthylic and yeast adenylic gcid) but more recent work has shown that they were handling mixtures.In the light of present knowledge con- cerning the migrations of phosphate esters it is obvious that the experimental conditions employed by the Levene school could not have resulted in the retention of isomeric integrity in the compounds studied but would lead 43Davol1 Lythgoe and Todd J. 1946 833. 4 4 (a) Wright and Khorana J . Amer. Chem. Xoc. 1956 78 811 ; ( b ) Tener Wright 4 5 Kalckar Biochim. Biophys. Acta 1950 4 232. ‘6Manson and Lampen J . Biol. Chem. 1951 191 95. 4 7 Friedkin ibid. 1950 184 449. 481i.riedkin and Roberts ibid. 1954 207 257. 49 Klenow and Larsen Arch. Biochem. Biophys.1952 37 488. bo Wajzer and Baron Bull. SOC. Chim. biol. 1949 31 750. 61 Levene and Harris J . Biol. Chenz. 1932 95 755 ; 98 9 ; 1933 101 419. and Khorana ibid. p. 506. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 67 to mixtures. Ribose phosphates have been obtained in ingenious fashion by Khym et al.18 Hydrolysis of the glycosylamine nitrogen-carbon linkage in adenylic acid " a " and " b " was achieved with the hydrogen form of a polystyrenesulphonic acid resin at a rate comparable with the rate of isomerisation. The ribose phosphates were released from the resin at the moment of formation (in contrast to adenine and most of the adenylic acid) and little or no isomerisation takes place subsequent to their formation. In this way ribose 2-phosphate was obtained from adenylic acid " a " and ribose 3-phosphate from adenylic acid " b ".Subsequently the method was developed to obtain pure ribose 2- and 3-phosphate by hydrolysis of adenylic acids with a polystyrenesulphonic acid cation-exchange resin. The mixture of phosphate esters was separated by ion-exchange chromato- graphy with borate complex-formation. Khym et al. also prepared ribose 5-phosphate by treating adenosine-5' phosphate with resin [Dowex-SO(H+)] at 100" for 4 minutes. This ester had been obtained by Levene and Jacobs 62 by subjecting the barium salt of inosinic acid to acidic hydrolysis thereby cleaving the sugar-base linkage. An improved method for the preparation from muscle of inosinic acid and then of ribose 5-phosphate has been de- scribed recently. Optimum conditions were determined for the hydrolysis.53 This ester is also obtainable by acidic hydrolysis of cozymase 64 and it can be prepared in a high degree of purity from adenosine triphosphate by ion-exchange.55 A fraction containing 70-80y0 of ribose 5-phosphate is afforded when xylose and adenosine triphosphate are incubated with a pentose phosphate isomerase from extracts of Lactobacillus pent0sus.56~ The enzymic conversion of 6-phosphogluconic acid into ribulose 5-phosphate and then ribose 5-phosphate is now well established.In the past to obtain ribose phosphates from ribonucleotides it has been necessary to work with purine nucleotides but very recently Cohn and Doherty 56b have developed a method for obtaining ribose from pyrimidine nucleosides and ribose phosphates from pyrimidine nucleotides. The accessibility of sugars (and derivatives) of pyrimidine nucleosides and nucleotides is severely limited by the resistance of the glycosylamine link- age to acid hydrolysis.It has long been known that this stability is depend- ent on the ethylenic unsaturation between the adjacent carbon atoms in the ring and that reduction or bromination of the 4 5-double bond renders the glycosylamine linkage susceptible to acid hydrolysis. Cohn and Doherty completely hydrogenated pyrimidine ribonucleotides under mild conditions with a rhodium catalyst and cleaved the product by dilute alkali a t room temperature to the phosphate of /?-ribosylureidopropionic acid. Dilute acid 'at room temperature hydrolyses this substance to ribose phos- phate and @-ureidopropionic acid without appreciable isomerisation of the 62Levene and Jacobs Ber.1908 41 2703; 1911 44 746. 53Marmur Schlenk and Overland Arch. Biochem. Biophys. 1951 34 209. 54Schlenk J . Biol. Chem. 1942 146 619. 5 5 Groth Mueller and LePage ibid. 1952 199 389. 66 (a) Lampen ibid. 1953 203 999 ; ( b ) Cohn and Doherty J . Amer. Chm. SOC. 1956 78 2863 ; (c) Bergmann and Burke Angew. Chem. 1955 67 127. 68 QUARTERLY REVIEWS phosphate group thus making available the sugar phosphates of pyrimidine nucleotides. No previous isolation of a sugar phosphate from a pyrimidine nucleotide had been reported and even the reduction of such substances to achieve labilisation of the glycosylamine linkage has been achieved only rarely. The sodium-ethanol-liquid ammonia procedure so effective with nucleosides is seemingly ineffective with n ~ c l e o t i d e s .~ ~ ~ From uridylic acids " a " and " b " ribose 2- and 3-phosphate respectively were obtained thus confirming the identity of the pyrimidine nucleotide isomers. The method is also applicable to deoxyribonucleotides and has been used with deoxycytidylic and thymidylic acid Evidence has been presented to show that xylose is phosphorylated a t the expense of adenosine triphosphate by extracts of Pseudomonas Chemical Syntheses Intrigued by the problems presented and no doubt stimulated by the biological implications of sugar phosphates organic chemists have developed chemical syntheses for many members of this class. I n early experiments it was usual to phosphorylate unprotected sugars and the products were probably mixtures. As far as we can trace the first phosphorylation of a carbohydrate was carried out in 1858 by Berthelot,58 who treated glucose with syrupy phosphoric acid a t 140".I n the past the most widely used reagent in synthesis of sugar phosphates was phosphoryl chloride. It was used by Neuberg and Pollak 59a to prepare sucroseand dextrose phosphates by Fischer 6o to obtain a phosphoric ester of methyl glucoside and by Helferich et aL61 to phosphorylate an unprotected disaccharide (trehalose). Neuberg and Pollak attempted to control the reaction by adding alkali to absorb the hydrogen chloride formed. Substances which have been added by others for the same reason include sodium hydroxide magnesium oxide anhydrous pyridine and quinoline. Inconsistencies have been noted and it has been reported that phosphorylation of glucose was unsuccessful when barium or calcium hydroxide was replaced by calcium carbonate as the added base.59b 62 More examples need to be studied before all the incon- sistencies can be satisfactorily explained.Many phosphorylations have been carried out with suitably protected sugars. The following are a few representative examples reaction between methyl 2 3-O-isopropylidene-~-ribofuranoside and phosphoryl chloride in pyridine a t -40° followed by hydrolysis of the isopropylidene and glycoside residues yielded ribose 5-phosphate ; 63 arabinose 5-phosphate has also been prepared ; 64 phosphorylation of 1 2-5 6-di-O-isopropylideneglucose hydrop h i h .57 67 Hochster and Watson Nature 1952 170 357. 5BBerthelot Ann. Chim. (France) 1858 54 81. 59Neuberg and Pollak (a) Biochem. Z .1910 23 515; 26 514; ( b ) Ber. 1910 61 Helferich Lowa Nippe and Riedel 2. physio2. Chem. 1923 128 141. 6 2 Fawaz and Zeile ibid. 1940 263 176. 63Levene and Stiller J. Bid. Chern. 1934 104 299. srLevene and Christman ibid. 1938 123 607. 43 2060. 6o Fischer Ber. 1914 47 3193. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 69 and 1 2 3 6-tetra-O-acetylglucose and subsequent removal of the pro- tecting groups afforded glucose 3- G 5 66 and 4-phosphate 67 respectively. Another reagent which has been used to some extent is phosphoric oxide. Di-0-isopropylidene-D-fructopyranose was phosphorylated with phosphoric oxide in ether and the intermediate product presumably a mixture of tri- di- and mono-0-isopropylidenefructose 1 -phosphate was subjected to hydrolysis fructose 1-phosphate was isolated as the cyclo- hexylammonium salt.68 Although it is usual and frequently necessary to use protected sugars in phosphorylations selective reaction of free sugars can be achieved in some instances. After the conversion of glucose into glucose 6-phosphate 69 by metaphosphoric acid Percival and Anderson 70a directly phosphorylated glucosamine at position 6 with metaphosphoric acid in the presence of acetonitrile. Phosphate residues on other positions were removed by hydrolysis of the crude product with N-hydrochloric acid at 100". (A purer product has since been prepared by these workers by an alternative route ; 70b cf. Maley and Lardy.70c) Amino-sugar phosphate esters had previously only been obtained enzymically . In addition to working with protected sugars nowadays it is usual to use protected phosphorylating agents to eliminate undesirable side reactions.The value of such reagents was realised many years ago since Langheld 7 l in 1910 used ethyl metaphosphate in chloroform. To prevent the formation of di- and tri-esters it has become customary to use a disubstituted phos- phoryl monochloride usually in pyridine as the phosphorylating agent. It is essential of course that the protecting groups should be removed easily under mild conditions. Compounds which have been suggested as useful include phosphorochloridic dianilide the catechol ester of phos- phorochloridic acid and dibenzyl and diphenyl phosphorochloridate. The first-named compound was used for the phosphorylation of a series of com- pounds including a sugar ; 7 2 the aniline residues were removed as acetanilide by hydrolysis with acetic acid.It is claimed that catechol can be eliminated from the catechol ester of phosphorochloridic acid merely by treatment with water.73 The most useful and widely used phosphorylating agents are dibenzyl and diphenyl phosphorochloridate. The benzyl or phenyl groups can be readily cleaved by hydrogenolysis. The diphenyl derivative which is a stable liquid (for preparative details see Brigl and Muller 7 4 6 5 Nodzu J . Biochem. (Japan) 1926 6 31 ; Chem. Abs. 1927 21 924. 66 Levene and Raymond J . Biol. Chem. ( a ) 1928 79 621 ; ( b ) 1929 83 619; 6 7 Raymond ibid. 1936 113 375. 68Pogell ibid. 1953 201 645. 69 Viscontini and Olivier Heh. Chim. Acta 1953 36 466. 70 (a) Percival and Anderson Chenz,. and Id. 1954 1018 ; ( b ) Anderson and Percival J .1956 814; (c) Maley and Lardy J . Amer. Chem. SOC. 1956 78 1393. 'lLangheld Ber. 1910 43 1857. 7 2 Zetzsche and Buttiker Ber. 1940 B 73 47. 73Reich Nature 1946 157 133. 7 4 Brigl and Muller Ber. 1939 73 2121. (c) 1930 89 479. 70 QUARTERLY REVIEWS or Baer 75) has been used for the synthesis of monophosphates of ald0-,7~ 77 keto-,66b 74 78 2-deoxy-,79 and 2-amino-2-deoxy-hexoses,7~b~ and of pen- toses 809 81 and 2-deo~ypentoses.~~ In addition it has been used to prepare some aZdehydo-sugar phosphates.83 The initial reaction between the pro- tected sugar and the phosphorylating agent proceeds in good yield and the products are frequently crystalline. The phenyl residues can be removed not only by hydrogen and a catalyst but also by dilute sodium hydroxide and in some cases by sodium in liquid ammonia.Illustrative of the use of this reagent are the following phosphorylation of benzyl 3 4 6-tri-O- acetyl-P-D-glucoside yielded the 2-(diphenyl phosphate) which was treated with hydrogen over Adams catalyst to afford hexahydrobenzyl 3 4 6-tri- O-acetyl-P-D-ghcoside 2-phosphate from which the free glycoside phosphate was obtained by deacetylation.77 Similar phosphorylation of 1 3 4 6- tetra-0-acetyl-P-D-glucose followed by treatment of the product with potassium methoxide in methanol yielded glucose 2-( dipotassium phosphate). 1 2-O-koPropylidene-~-xylose when phosphorylated in anhydrous 2 6- lutidine at - 20" with diphenyl phosphorochloridate afforded pure crystalline 1 2-O-~sopropylidene-~-xylofuranose 5-(diphenyl phosphate) ; hydrogeno- lysis in glacial acetic acid over Adams catalyst then quantitatively removed the phenyl groups ; mild hydrolysis in acetic acid cleaved the isopropylidene grouping and D-xylofuranose 5-phosphate was obtained in 72% yield from D-xylose.81 Phosphorylation of 2 3 4 5-tetra-O-acetyl-~-galactose di- ethyl mercaptal with diphenyl phosphorochloridate in pyridine proceeded readily at Oo yielding crystalline 2 3 4 5-tetra-O-acetyl-~-galactose diethyl mercaptal6- (diphenyl phosphate) which on scission of the ethylthio- residues afforded 2 3 4 5-tetra-O-aCetyl-Uldehydo-D-galaCtOSe 6-(diphenyl phosphate).A similar reaction sequence was successfully completed with the 2-deoxygalactose anal0gue.8~ 1 3 4-Tri-O-acetyl-N-acetyl-P-~-gluco- samine with the reagent yielded the 6- (diphenyl phosphate) which after hydrogenolysis and acidic hydrolysis of the acetyl groups afforded crystalline D-glucosamine 6-phosphate 70b (cf.ref. 70c). Diphenyl phosphorochloridate was used in the nucleotide field by Bredereck and his collaborator^.^^ Monophenyl 85 phosphorochloridate (and phosphorochloridic monoanilide 7 2 has been used for the production of phosphate esters but shows no advantage over the corresponding disubstituted derivative. Although Zervas 86 mentioned the use of dibenzyl phosphorochloridate ' 5 Baer " Biochemical Preparations " Wiley and Sons New York 1949 Vol. I p. 51. 76 Reithel and Claycomb J. Amer. Chern. SOC. 1949 71 3669. 7 7 Farrar J. 1949 3131. 78Mann and Lardy J. Biol. Chern. 1950 187 339. 79Foster Overend and Stacey J. 1951 980. 8o Parker Ph.D.Thesis Birmingham 1952. Barnwell Saunders and Watson Chem. and Ind. 1955 173 ; Canad. J. Chem. 1955 33 711. 8zAllerton Overend and Stacey Chem. and Id. 1952 952. 83 Barclay Foster and Overend J. 1955 2505. 8 4 Bredereck Berger and Ehrenberg Bey. 1940 73 269. 8 5 Gulland and Hobday J. 1940 746. Se Zervas Naturwks. 1939 27 317. FOSTER AND OVEREND CARBOHYDR-4TE PHOSPHATES 71 he considered it too unstable to be of practical value. The reagent has been developed by Todd and his co-workers and is used extensively by them. If the sole purpose is the preparation of monoesters then possibly the more stable diphenyl analogue is more convenient but the use of dibenzyl phosphorochloridate is not limited to the preparation of simple phosphoric esters and can be applied to the preparation of esters of pyrophosphoric acid and triphosphoric acid (see p.76). A synthesis of ribose 5-phosphate provides an example of the use of this reagent. Methyl 2 3-O-isopropyli- dene-D-ribofuranoside with this phosphorylating agent in pyridine a t low temperature affords methyl 2 3-O-isopropylidene-~-ribofuranoside 5-(di- benzyl phosphate) from which protecting groups were removed by the usual methods to give ribose 5-phosphate in high yieldqs7 In the nucleotide field thymidine-3' phosphate was synthesised by the phosphorylation of 5'-triphenylmethylthymidine with this reagent and subsequent elimination of the triphenylrnethyl and benzyl residues.*8 Some sugar phosphates have been prepared by phosphorylation a t one site the ester grouping being then caused to migrate to another.Levene and Raymond 89 tried to prepare xylose 3-phosphate by phosphorylation of 5-O-benzoyl-1 2-O-isopropylidenexylose but the product was xylose 5-phosphate. Likewise phosphorylation of 5-O-benzyloxycarbonyl- or 5-O-acetyl- 1 2-O-isopropylidenexylose also yielded xylose &phosphate after removal with mineral acid of the acyl and isopropylidene groups and obviously a phosphate migration had occurred. Recently it was claimed by Watson and Barnwell 90a; that migration in the reverse direction (i.e. from position 5 to position 3) afforded xylose 3-phosphate xylose 5-phos- phate was merely heated in water a t pH 6.4 a t 50" for 2 hours. This claim was soon shown to be incorrect by Moffatt and K h ~ r a n a ~ ~ who successfully prepared and fully characterised D-xylose 3-phosphate.Crystalline 1 2-0- isopropylidene-D-xylofuranose 5-(diphenyl phosphate) was converted by alkali into the 1 2-O-isopropylidenexylofuranose 3 5-( cyclic phosphate) which was hydrolysed quantitatively to a mixture of 1 2-O-isopropylidene xylose 3- and 5-phosphate from which the isopropylidene groups were readily cleaved by the aqueous acids a t 100' for 10 minutes a t their own pH. The xylose 3- and 5-phosphates were separated satisfactorily on a Dowex- 2(formate) resin column and the products differentiated structurally by standard carbohydrate reactions. The 3-isomer was obtained in 15 yo yield. The nature of the reaction responsible for the change in the optical rotation of a solution of D-XylOSe 5-phosphate was re-investigated because the properties of the sample of D-xylose 3-phosphate prepared as described above were completely different from those of solutions of D-xylose 5-phos- phate treated according to Watson and Barnwell's procedure.90a Moreover a migration under neutral conditions as postulated by Watson and Barnwell Levene and Raymond J .Biol. Chem. 1934 107 75 ; cf. ibid. 1933 102 317 331 347. O0 ( a ) Watson and Barnwell Chem. and Ind. 1955 1089 ; ( b ) Moffatt and Khorana J . Amer. Chem. SOC. 1956 78 883 ; (c) Axelrod and Jang J . Biol. Chem. 1954 209 847. 87 Michelson and Todd J. 1949 2476. BBIdern J. 1953 951. 72 QUARTERLY REVIEWS seemed highly improbable. The change was found to be really due to the formation of xylulose 5-phosphate from xylose 5-phosphate a transformation analogous to that previously observed by Axelrod and Jang,s*c who reported that ribose &(barium phosphate) can be partially converted a t room temperature into a ribulose-containing compound.When ribose 2- or 3-phosphate is heated for 2 hours with Dowex 50(H+) resin or for 45 minutes with 0-1N-sulphuric acid it forms ribose 4-phosphate in low yield. A method of preparing phosphoric esters which might be further exploited in carbohydrate chemistry is that employing ethylene oxide derivatives of sugars as initial materials. Lampson and Lardy 91 treated 5 6-anhydro- 1 2-O-~sopropy~idene-~-g~ucofuranose in water with dipotassium or disodium hydrogen phosphate and cleaved the anhydro-ring. The phosphate residue was located at the terminal carbon atom of the sugar molecule and by removal of the isopropylidene group glucose 6-phosphate was obtained.Although the yield was lower than by other methods the authors recommend this procedure in the special case when it is desired to introduce labelled phosphate because it avoids the use of special phosphorylating agents. Todd and his co-workers s2 studied the action of dibenzyl hydrogen phosphate on mcthyl 2 3-anhydro-4 6-O-benzylidene-a-~-alloside (I). The product was a mixture of methyl benzylidenehexoside dibenzyl phosphates. After elimination of the benzyl and benzylidene residues this mixture was separ- ated into methyl or-D-altropyranoside 2-phosphate (II),* which was the main product and methyl or-D-glucopyranoside 3-phosphate (III).* The Me (II) (I) R PO,H general conclusion drawn by Todd and his colleagues was that the epoxide route is feasible for carbohydrate esters of phosphoric acid and compounds of the nucleotide type but is limited in its application.The limitations were considered to be inaccessibility of appropriate anhydro-compounds and the tendency to formation of more than one product from other than 5 6-anhydro-sugar derivatives. The method probably warrants further study however especially in the light of the newer methods available for the separation of sugar phosphates. Although the preparation of sugar phosphate esters with the substituent located at the glycosidic centre of the sugar is frequently achieved by en- zymic methods chemical syntheses have been developed. The reaction glLampson and Lardy J . Biol. Chem. 1949 181 693. B2Harvey Michelksi and Todd J. 1951 2271. * Depiction of this and other sugar phosphates as free acids does not imply that they were always isolated as such.FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 73 between the acetobromo-sugar and sodium or (more usually) silver phos- phate or silver diphenyl or dibenzyl phosphate is frequently employed. Depending on the experimental conditions and reagent either the a- or the @-derivative is formed. The a-form of glucose 1 -phosphate was successfully obtained by treating trisilver phosphate with acetobromoglucose in ben- ~ e n e . ~ ~ 9 93 The initial product tris(tetra-0-acetylglucose-1) phosphate was hydrolysed by acid in methanol until about 20% of the organic phosphate was liberated and deacetylation was completed with alkali. The method has been described in detail by Krahl and CorL9* In like fashion a-gal- actose l - p h ~ s p h a t e ~ ~ xylose l-pho~phate,~O and maltose 1 -phosphate Q8 have been prepared.Usually a-acetobromoglucose reacts with inversion of configuration at the glycosidic centre and in this respect the preparation of a-glucose 1-phosphate is anomalous. Posternak 97 treated acetobromo-aldoses with silver diphenyl phosphate and cleaved the phenyl groups from the product by hydrogenolysis. Treat- ment with alkali resulted in deacetylation and the glycoside phosphate was isolated. a-Glucose 1 -phosphate and cc-galactose 1 -phosphate were synthe- sised in this way and the yields are reported to be five times those obtained by the trisilver phosphate procedure. In similar fashion a-D-glucose 1 6-diphosphate was prepared from 2 3 4-tri-O-acetyl-l-bromo-l-deoxy- a-D-glucose 6- (diphenyl phosphate) .989 99 Other compounds prepared by this route include a-D-mannose l-phosphate and 1 6-diphosphate and a-lactose l-phosphate.If a-acetobromo-D-glucose (IV) is treated with silver dibenzyl phosphate reaction occurs with inversion of configuration and after elimination of protecting groups ,!%D-glucose l-phosphate (VII) can be isolated.86 loo The compound is formed via the intermediates (V) and (VI). O 3 Cori Colowick and Cori J . Biol. Chem. 1937 121 465. 9 4 Krahl and Cori '' Biochemical Preparations " Wiley and Sons New York 1949 95Colowick J. Biol. Chem. 1938 124 557. Q6Meagher and Hassid J . Arner. Chern. SOC. 1946 68 2135. " Posternak ibid. 1950 72 4824. "Posternnk J. Bid. Chem. 1949 180 1269. O9 See also Leloir Repetto Cardini Paladini and Caputto Andes Asoc.quim. loo Wolfroin Smith Pleteher and Brown J . Amer. Chem. SOC. 1942 64 23. VOl. I p. 33. argentim 1949 37 187. E" 74 QUARTERLY REVIEWS P-D-Galactose 1 -phosphate can also be obtained by this procedure,lo1 but a-D-mannose 1 -phosphate is formed when acetochloromannose is treated with silver diphenyl phosphate or silver dibenzyl phosphate with subsequent removal of protecting groups. loZu Likewise acetobromo-D- xylose affords finally a-D-XylOSe 1 -phosphate when treated with either silver diphenyl or dibenzyl phosphate. loZb Khorana and his colleagues have successfully synthesised both a- and P-D-ribofuranose 1 -pho~phate.lo~~? 2 3 Ei-Tri-O-benzoyl-~-~-ribose was converted into the corresponding ribofuranose l-bromide ( V I I I ) to which the P-configuration has been assigned.At low temperature this compound underwent some reaction with silver dibenzyl phosphate in a medium of chloroform and methylene dichloride and chromatography of the product after hydrogenation showed the presence of a fast-moving labile phosphate but much inorganic phosphate was also present. After debenzoylation only very small yields of ribofuranose l-phosphate were obtained. To reduce losses a much shorter reaction period appeared advisable and to achieve this advantage was taken of the high solubility in benzene of tri- ethylammonium dibenzyl phosphate. When a cooled benzene solution of this salt was added to a precooled solution of compound (VIII) a rapid reaction ensued. As expected the product (IX) was extremely labile and direct hydrogenation appeared desirable in order to secure some stabilisation of the ester by the creation of phosphoryl dissociation.This viewpoint was borne out by experiment and after removal of the benzoyl groups a considerably improved yield of P-ribofuranose 1 -phosphate (X) was obtained. (The P-configuration was based on enzymic studies and methods described later.) In this case we have the formation of a 0-glycose l-phosphate from a /3-glycose l-halide on reaction with a salt of dibenzyl phosphoric acid. The importance of " neighbouring group ' ' participation in the synthesis of purine nucleosides is well known and the configuration at appears to depend on the position of the 2-hydroxyl substituent in that in all known cases the base is on the opposite side of the ring from this 2-substituent regardless of the relative configuration at positions 1 and 2 in the original halogeno-sugar (see Baker et ~ 1 .l ~ ~ ~ for a fuller discussion of this point). lolReithel J . Amer. Chem Soc. 1945 67 1056. lo2 (a) Posternak and Rosselet Helv. Chim. Acta 1953 36 1614 ; (b) Antia and Wataon Chem. and Ind. 1956 1143. Io3 (a) Tener Wright and Khorana J . Amer. Chem. SOC. 1956 78,506 ; (b) Wright and Khorana ibid. 1955 77 3423 ; 1966 78 811 ; ( c ) cf. Baker Joseph Schaub and Williams J . Org. Chem. 1954 19 1786 ; ( d ) Maley Maley and Lardy J. Amer. (Ihern. SOC.. 1956. 78 6303. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 75 An analogous explanation can be entertained for the nature of the products formed when salts of dibenzyl phosphoric acid are treated with acylglycose 1-halides. To prepare the other form of the anomeric pair of phosphates the blocking group a t should not exercise the important neighbouring- group influence in the replacement reaction a t position 1 and in addition should be readily removed at a later stage in the synthesis.cc-D-Ribo- furanose 1 -phosphate was synthesised by taking account of these require- ments. Methyl 5-O-benzyl-~-ribofuranoside 2 3-carbonate (XI) was con- verted by hydrogen bromide in acetic acid into an oily bromide which was directly treated in benzene with one equivalent of triethylammonium dibenzyl phosphate. Hydrogenation of the product followed by mild alkaline treatment afforded a-D-ribofuranose 1 -phosphate (XII). The use of triethylammonium dibenzyl phosphate appears to be most promising for the synthesis of labile glycosidic phosphates.Lardy and his co-workers have recently prepared a-D -glucosamine 1 -phosphate (and its N-acetyl derivative) by treating acetobromoglucosamine hydrobromide with the triethylamine salt of diphenyl phosphoric acid and subsequent removal of the protecting groups.10M Reactions of acetohalogeno-sugars with monosilver phosphate (for pre- paration see Lipmann and Tuttle lo4) usually proceed with inversion and lead to the formation of p-glycosides. After removal of the protecting groups from the product of reaction of acetobromogalactose and monosilver phosphate p-D-galactose 1-phosphate was obtained.lol Methyl 2 3 4-tri- O-acetyl- 1 - bromoglucuronate with monosilver phosphate gave finally /I-glucuronic acid 1 -phosphate 105 (see also Pippen and McCready 106 for other attempts to prepare hexuronic acids with 1 -phosphate substituents).A thorough study of the reactions for the preparation of aldose l-phosphates would provide useful information. Although the nature of the products formed from acylglycosyl halides and salts of dibenzylphosphoric acid can be explained the reactions with salts of diphenylphosphoric acid appear anomalous. Likewise configurational assignments are demonstrated only for the aldose l-phosphates finally isolated and not on the initial pro- ducts of reaction of the acylglycosyl halides and phosphoric acid diester salts. * lo4Lipmann and Tuttle J . Biol. Chem. 1944 153 571. 105Touster and Reynolds ibid. 1952 19’7 863. lo6Pippen and McCready J . Org. Chem. 1951 16 262. * The reaction between the silver salt of these phosphoric acids and a halogeno-sugar in which the halogen grouping is located at positions other than 1 has apparently not been used to give simple sugar phosphates but has been used for nucleotides.Uridine-5’ phosphate was prepared by reaction of silver dibenzyl phosphate and 5’-deoxy-5’-iodo- 2’ 3’-O-isopropylideneuidine with subsequent debenzylation. The method is not 76 QUARTERLY REVIEWS In general for the various syntheses described the site of the phosphoryl residue in the sugar molecule has been confirmed by the classical methods of carbohydrate chemistry involving inter abia glycosidisation methylation periodate oxidation optical rotation and ion-exchange in the presence and absence of borate and differences in the decomposition rates in alkali. Work on the synthesis of esters of pyrophosphoric and triphosphoric acids has been limited to preparations of the nucleotides.Although in these compounds it is the sugar portion of the molecule which is esterified this work will be described only briefly as it is more appropriately included in a review of nucleotides. Methods have been developed which render it possible to eliminate selectively only one of the benzyl residues from the dibenzyl phosphate esters of sugars and nucleotides. If an alcohol of the general formula (XIII) is allowed to react with dibenzyl phosphorochloridate it affords the ester (XIV) which on hydrogenolysis yields a monoester (XV). Selective de- benzylation of compounds of type (XIV) can be accomplished by “ quaterni- sation”-a process depending on the transfer of a benzyl residue from oxygen to nitrogen with formation of a quaternary salt.A strong tertiary base such as 4-methylmorpholine 1O7 is satisfactory but the method has been extended to include all classes of amines. Debenzylation can also be brought about by a base hydrochloride. l08 Lithium chloride in 2-ethoxyethanol proved most efficient and was recommended for the preparation of mono- benzyl esters of the general formula (XVI). An equilibrium is set up between the triester and lithium chloride on the one hand and the lithium salt of the diester and benzyl chloride on the other. Precipitation of this lithium salt from the solution leads to quantitative reaction. In both methods of debenzylation the monobenzyl ester is produced as an anion and therefore a second debenzylation which would produce a doubly charged anion is not favoured.Treatment of the silver salt of the mono- benzyl ester (XVI) with dibenzyl phosphorochloridate gives the tribenzyl ester (XVII) and subsequently by hydrogenolysis the diphosphate (XVIII). Repetition of this sequence of reactions commencing with compound (XVII) yields the tetrabenzyl ester (XXI) and thence the triphosphate (XXII). generally applicable because of the difficulties encountered in the preparation of halogeno-sugar moieties owing to formation of cyclonucleoside salts. An unsymmetrical djester of phosphoric acid [a diribonucleoside phosphate (A)] has been synthesised by this reaction sequence. The silver salt of 2’ 3’-O-isopropylideneadenosine-5’ benzyl phosphate was treated in boiling toluene with 5’-deoxy-5’-iodo-2’ 3’-O-isopropylidene- uridine t o give after removal of the protecting groups adenosine-5’ uridine-5’ phosphate (Elmore and Todd J.1952 3681). lo7 Baddiley Clark Michalski and Todd J. 1949 815. losClark and Todd J . 1950 2023 2030. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 77 By such methods Todd and his co-workers log synthesised adenosine di- phosphate (ADP) and adenosine triphosphate (ATP). It might be expected that a mixture of isomers would be obtained from the monodebenzylation. 3 9 R-OH + ~ph~CH~62pOCI - R+P(0.CHph)2 - R-O*P(0H2 (XIII) R; N ow I LlCl ( XV) r R O ~ - ~ - ~ . O . C H p t l (XVII) Phn-0 O*CH,Ph 1 I k . R-08-Of-OH R-08-0- 0 P-OCH2h and R-0.P-0 O Q - P-OCH,Ph H6'- OH HC) b€H2Ph PhCHsd OH ' 9 0 9 % 9,O.P (OCH2P h) R-0.7- 0 -b- 0-7 *O*CH,Ph R-0-P Ph.CH2.0 OCH2Ph (OCHfhL 4 CHph (XXI) I R-O('-O-f-O-F.OH Q O (XXIII) O Q/ & O H ) HO OH OH (XXII) \ t R-0-P 0g(W2 -.\ .A ' $,OH ?/Om 10 (xx I V) R-O-b ox<*.o(xv) For example the substance (XVII) could yield the triester (XIX) or (XX) Whereas further reaction of compound (XX) with dibenzyl phosphoro- chloridate would lead finally to the " unbranched " triphosphate (XXII) the isomer (XIX) would be expected to afford finally the " branched " substance (XXIV). If in compounds (XIX) and (XX) R were adenosine esterified a t position 5' then (XXII) would be natural ATP and (XXIV) an isomer of it. that the disilver salt of adenosine-5' phosphate reacts with an excess of dibenzyl phosphorochloridate to give after debenzylation natural ATP in far better yield than is obtained by the original alternative procedure.log 0 bviously a rearrangement is involved and probably compound (XXIV) is converted into ATP (XXII) via a cyclic intermediate (XXV).(At temperatures of 50" or above benzyl pyrophosphates are rapidly debenzylated by phenol with the production of nuclear-benzylated phenols.ll1 Practically it has been shown lo9Todd and co-workers J . 1947 648; 1949 582. 110 Michelson and Todd J. 1949 2487. ll1 Quoted by Christie Kenner and Todd J. 1954 46. 78 QUARTERLY REVIEWS This is an acid-catalysed reaction whereas anionic debenzylation occurs under neutral or alkaline conditions it is an alternative to hydrogenolysis as a method of debenzylation.) Other methods for the preparation of pyrophosphoric and triphosphoric esters have also been developed. Syntheses of ribonucleoside-5’ phosphites have been achieved.l12 Chlorination of phosphites can be effected with N-chlorosuccinimide and the chloro-derivative is a valuable intermediate for further stages in the synthesis of ribonucleotides.N 2 4-Trichloro- acetanilide can also be used to chlorinate the phosphites and although it is less reactive it might be a useful reagent for the preparation of water- soluble phosphates and pyrophosphates from phosphites since both N 2 4- trichloroacetanilide and 2 4-dichloroacetanilide produced from it are virtually insoluble in water and can be readily separated from the desired reaction products. Uridine-5’ pyrophosphate has been syrithesised in this way as shown in Scheme I. R is uracil and the reagents are (B) 2’ 3’-O-isopropylidene- uridine in acetonitrile containing 2 6-lutidine (C) N-chlorosuccinimide (D) triethylammonium dibenzyl phosphate and (E) lithium chloride hydrogenation and hydrolysis.B s CHjDVH I CH~O~-O-~.OCrCph 1 9 9 CHiO-?-O-?*OH I OCH2Ph OCH2Ph PhCHiO O€H2Ph HO OH Scheme I Esters of pyrophosphoric and triphosphoric acid can be synthesised by reactions of the following types 8 9 9 9 (a) R-CHd + Acf{-O.r-O-P.O.CH,Ph - R-CHiOf)-O-rOCH2Ph PhCHiO OCH,Ph PhCHiO OCH,Ph O Q - R-cH~o-P-o-~ OH HO OH 112 Corby Kenner and Todd J . 1952 3669; Kenner Todd and Weymouth J. 1952 3675. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 79 Again the methods have been developed for use in nucleotide syntheses. In reactions of type (a) with a variety of carbohydrate derivatives in which the substituent to be replaced is on the terminal carbon atom it was found that derivatives of open- chain aldehyde-sugars always react readily whereas those containing a lactol ring (e.g.methyl ribofuranoside derivatives) were so sluggish in reaction that they were of little preparative value. Alternative methods of preparing these esters have also been developed. Adenosine monophosphate has been treated with phosphoric acid in the presence of dicyclohexylcarbodi-imide to afford the di- and tri-phosphates 113 the use of protected intermediates is avoided. Employment of carbodi- imides as reagents has proved remarkably effective for the synthesis of symmetrical pyrophosphates and to a smaller degree of unsymmetrical pyrophosphates to which class most of the natural coenzymes belong. Although the method has been applied to the synthesis of inter alia uridine- diphosphate-glucose and the 5'-triphosphates of adenosine and uridine the unsymmetrical esters are always produced as components of complex mixtures with the corresponding symmetrical pyrophosphates.Recently attempts have been made to overcome this difficulty by the use of imidoyl phosphates,l14 which are analogous in structure to the hypothetical inter- mediates in the synthesis of pyrophosphates by use of carbodi-imides and consequently undergo phosphorolysis with the production of pyrophos- phates e.g. (R R' R1 R2 R3 and R4 are suitable protecting residues) No doubt this method will be further exploited. Exchange reactions with trifiuoroacetic anhydride can be used for pyrophosphate syntheses and fully esterified pyrophosphates can also be prepared by exchange reactions between diesters of phosphoric acid and a suitably reactive pyrophosphate.Exchange reactions with nucleosides were less successful than those with simple model compounds. Although cyclic esters of phosphoric acid have been made from glycols and their existence has been postulated as intermediates in various re- arrangements not much work has been done on the synthesis of such esters from simple sugars. Again examples generally must be drawn from nucleo- tide chemistry. Sometimes direct phosphorylation of the sugar moiety leads to a cyclic ester. For example treatment of riboflavin with phos- phoryl chloride in pyridine containing a small amount of water yields a cyclic 4' 5'-phosphate.lf5 An attempt 116 to synthesise a monobenzyl ester of flavin-adenine-dinucleotide consisted in bringing about an exchange llSKhorana J .Amer. Chem. Soc. 1954 76 3517. 114Atherton Morrison Cremlyn Kenner Todd and Webb Chem. and Id. 1955 115Forest and Todd J. 1950 3295. 116 Forest Mason and Todd J. 1952 2630 1183. 80 QUARTERLY REVIEWS reaction between riboflavin-5’ phosphate and 2’ 3’-O-isopropylidene adeno- sine-5’ (benzyl diphenyl pyrophosphate) e.g. (Ad = adenosine residue used as 2’ 3’-O-isopropylidene derivative ; F1 = riboflavin residue.) Prom many reactions in all cases the product was riboflavin-4’ 5‘ cyclic phosphate a compound which could also be obtained by treating ribo- flavin-5’ phosphate with tetraphenyl or tetrabenzyl pyrophosphate in the presence of bases. It may be reasonably assumed that in these reactions the desired exchange did in fact occur and that the pyrophosphate of ribo- flavin initially produced then behaved in the presence of a base as a phos- phorylating agent towards the adjacent hydroxyl group of the riboflavin residue.Riboflavin-5’ phosphate and trifluoroacetic anhydride afford 3 2’ 3’-tristrifluoroacetylriboflavin-4’ 5’ cyclic phosphate.l16 Uridine-diphosphate-glucose on treatment with alkali yields glucose 1 2-(hydrogen phosphate) as a cleavage product.l17 The cyclic 2’ 3’- phosphates derivable from the “ a ” and the “ b ” type of ribonucleotides have been well studied. The cyclic phosphates of this type were prepared by Brown et d118 from adenosine cytidine and uridine. The “ a ” and ‘‘ b ” nucleotides were treated with excess of trifluoroacetic anhydride followed by ethanolic ammonia to remove the trifluoroacetyl residues.There is no doubt that intramolecular reaction occurs as intermolecular reaction would have given diadenosine pyrophosphate. Reaction proceeds by the initial formation of a mixed anhydride of the phosphate with trifluoro- acetic acid and the mixed anhydride can react in intramolecular reaction as a phosphorylating agent towards the adjacent hydroxyl group. Adenylic acid “ a ” or “ b ” with dicyclohexylcarbodi-imide yields the cyclic phos- phate although subsequent opening of the ring may occur in further reactions.ll9 Recently the synthesis was reported of six-membered cyclic phosphates derived from sugars.120 Methyl a-D-ghcoside and phenyl phosphorodi- chloridate afforded a crystalline neutral ester (XXVI) in l0-20% yield O-H& 0 -H2C PhO-9-0 I 0 Me HO-P-0 I QOMr (XXVI) 0 OH 0 OH u<XVlD from which a phenyl group was removed by hydrogenolysis thereby afford- ing methyl ct-D-glucoside 4 &(hydrogen phosphate) (XXVII).From phenyl p-D-glucoside a better yield (40%)) of phenyl P-D-glucoside 4 6-(phenyl 117 Paladini and Leloir Biochem. J. 1952 51 426. 118Brown Magrath and Todd J. 1952 270s. l19Dekker and Khorana J . L4mer. Chern. SOC. 1954 76 3522. 120 Baddiley Ruchanan and Szabb J. 1964 3826. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 81 phosphate) was obtained which on hydrogenolysis afforded mainly glucose 4 6-(hydrogen phosphate). Properties and Reactions According to Leloir sugar monophosphates are stronger acids than free phosphoric acid and both pK and pK have smaller values. (Por a dis- cussion of this point see Kumler and Eiler.121) Aldose l-phosphates are very sensitive t o acid and in this respect resemble the glycosides and glycosylamines.Further like the glycosides the p-anomers are usually more acid labile than the or-forms (e.g. in comparative experiments hydrolysis constants for the a- and the @-form of glucose l-phosphate are 5 x and 15 x respectively.loO) Reasons for this difference are probably the same as those put forward for differences in hydrolysis rates of anomeric glycosides.122 The rate of hydrolysis of the glycosidic phosphate residue in a-glucose 1 -phosphate is greater than in cc-glucose 1 6-dipho~phate.~~ The phosphate substituent at C(s) reduces the rate of hydrolysis again probably for the same reasons as in Eydroly- sis of methyl a-D-glucoside methyl 6-deoxy-a-~-glucoside and methyl cc-D-xyloside (XXVIII ; R = CH,*OH Me and H respectively) where the rate increases as the bulk of R diminishes.lz2 Ribose 1 -phosphate is sufficiently acid-labile to undergo hydrolysis at the acidity employed in estimation of phos- phate.The ester is somewhat more acid-labile than The pyranose form of ribose l-phosphate is more stable towards acid than the furanose f0rm.lO3~ %Deoxy-~-ribose 1 -phos- phate is even more acid-labile than the ribose analogue. The mechanism of hydrolysis of aldose l-phosphate has been studied by various workers. The curve of first-order rate coefficient against acidity for the hydrolysis of a-D-glUCOSe l-phosphate is quite different from that obtained for a simple phosphate such as methyl phosphate. At 72.9" and in the range pH 1-4 the logarithm of the rate coefficient is proportional to the pH of the medium.At higher acidities the rate increases more rapidly than the stoicheiometric acidity and at 25" in aqueous perchloric acid the logarithm of the rate coefficient is accurately proportional to Hammett's acidity function H,. Isotope experiments at about pH 4 and in strong perchloric acid showed fission of the carbon-oxygen bond.123 These results are consistent with a single unimolecular mechanism operative over the whole range of acidities studied. The first step must be a rapid and reversible proton-transfer to the a-D-glucose 1 -phosphate followed by a slow reaction not involving a water molecule. There are two possible formulations one of which involves an opening of the hexose ring e.g. sequences (A) and (B).The two mechanisms possibly have different Me phosphocreatine but less so than acetyl phosphate. UXVl II) 121Kumler and Eiler J . Arner. Chem. SOC. 1943 65 2355. 122Foster and Overend Chem. and Id. 1955 566. 123 Barnard Bunton Llewellyn Oldham Silver and Vernon ibid. 1955 760 ; cf. Cohn J . Biol. Chem. 1949 180 771. a2 QUARTERLY REVIEWS stereochemical consequences mechanism (B) necessarily involves the production under kinetic control of the equilibrium mixture of a- and ,&glucose but for mechanism (A) this is not necessarily so. Further informa- tion on this point would be desirable. Since under the experimental con- ditions the mutarotation of glucose to produce the equilibrium mixture is extremely rapid this possible stereochemical distinction has no diagnostic value.In methanol however where the methyl glucosides produced are stable under the experimental conditions study of the steric course of the reaction may throw considerable light on the mechanism. To achieve acidic hydrolysis of the phosphate ester resulting from the esterification of the primary hydroxyl group in a sugar fairly drastic treat- ment is required which may lead to some decomposition of the sugar. Levene and Stiller 63 demonstrated that a pentose esterified at C(3) is hydrolysed more rapidly than the C(5 )-isomer. Thus hydrolysis of 5-0- methyl- 1 2-O-isopropylidenexylose 3-phosphate is many times faster than that of xylose 5-phosphate. Ribose 3-phosphate is hydrolysed 5-9 times faster than the 5-phosphate and 3-phosphoribonic acid is hydrolysed about twice as rapidly as 5-phosphoribonic acid.51 This rate difference has been used to determine whether substances containing a ribose phosphate moiety have the phosphate residue a t position 3 or 5.For the reasons given on p. 66 reservations must be made regarding the rates reported for the ribose phosphates obtained by Levene and his co-workers. An examination 124 of the hydrolysis of fructose 6-phosphate revealed that the hydrolysis is markedly slower than that of the l-phosphate and indeed it is possible to obtain a good yield of fructose 6-phosphate by hydrolysis of the 1 6-diphosphate 125 with hydrochloric or hydrobrornic acid a t 35" under special conditions. Comparison of the rate constants for hydrolysis of fructose 6-phosphate7 -pyrophosphate and -hiphosphate has shown that cleavage of t'he phosphate entity in the first subst'ance is slower by a factor of lo2-lo3 than is hydrolytic cleavage of a single phosphate group from either of the other two compounds.The hydrolysis of hexahydrobenzyl b-glucoside 2-phosphate by O*lN-sulphuric acid a t 100" was followed and it was found that k calculated for a unimolecular reaction increased from 2-9 x 10-5 after 30 minutes to 6.1 x 10-5 after 540 minutes. It might be inferred that the glycoside phosphate is more slowly hydrolysed l Z 4 Friess J . Amer. Chem. Soc. 1952 74 6521. Neuberg Lustig and Rothenberg Arch. Biochem. Biop?tgs. 1943 8 33. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 83 than glucose 2-phosphate (k = 8.4 x t o which it will give rise on cleavage of the glycosidic substituent. Glucose 2-phosphate is far less acid-labile than methyl 3 5 6-tri-0-methylglucoside 2-phosphate which is probably at least 80% hydrolysed by O-lN-sulphuric acid after one hour at 100".This difference is probably accounted for at least partly by the difference in lactol-ring forms in the two compounds because generally sugar phosphates without a glycosidic substituent and with a 2-phosphate group are more readily hydrolysed. It has been suggested that this is possibly due to migration of the phosphate residue from position 2 to position 1 but proof has not been presented. Rates of hydrolysis of esters of 2-deoxygalactose have been compared with those for analogous derivatives of galactose.126 Hydrolysis is faster in the 2-deoxy-series. The rates of hydrolysis (N-hydrochloric acid a t 100") of the phosphate groups in glucose 6-phosphate and glucosamine 6-phosphate were compared by Anderson and Per~ival.7~~ Whereas glucosamine 6-phosphate was only 50% hydrolysed during 73 hours glucose 6-phosphate was hydrolysed to the same extent in only 23 hours.A list of acid-hydrolysis constants for some carbohydrate phosphates can be found in the review by Le1oir.l For example D-ribofuranose l-phosphate is completely stable to 06~-sodiurn hydroxide at 80" for one hour.103 On the other hand other sugar phosphates are rapidly changed glucose 2-phosphate is 50% hydrolysed in 97 minutes by 0-1N-alkali at loo" and glucose 6-phosphate is 60% hydrolysed by O.2~-alkali a t 100" in 3 minutes. In the ribose series the decreasing order of stability towards alkali (0.OlN-sodium hydroxide at 22") is ribose 2-phosphate (which is scarcely attacked) 3-phosphate and 5-phosphate.It is reported 127 that phosphate residues are removed with greater difficulty than are sulphate residues in corresponding compounds. Robinson 128 initially suggested that hydrolysis of phosphoric esters is accompanied by Walden inversion and that D-galaCtOSe and D-ribose might arise in hydrolysates from natural products by decomposition of glucose 4-phosphate and xylose 3-phosphate. The alkaline hydrolysis of methyl a-D-glucoside 6-( barium phosphate) methyl D-glucofuranoside 3-(barium phosphate) and isopropylidene-D-glucose 3- and 6-( barium phosphate) was studied by Percival and Percival127 and in no case was any evidence found to support Walden inversion or anhydride formation. Levene et ~ 1 . however have claimed that treatment of fructose 3-phosphate with phenyl- hydrazine in acetic acid results in cleavage of the phosphate group with inversion since the final product is 3 6-anhydroallosazone.Further it is stated 66b that glucose 3-phosphate on treatment with phenylhydrazine also gives this anhydro-compound. On the other hand hydrolysis of glucose 3-phosphate with phosphatase and subsequent osazone formation afforded glucosazone and not allosazone. Sugar 1 -phosphates are resistant to alkali. 126 Foster Overend and Stacey J. 1951 987. 12' Percival and Percival J. 1945 874. 128Robinson Nature 1927 120 44 656. lZB Levene Raymond a d Walti J. Biol. Chrn. 1929 82 191, 84 QUARTERLY REVIEWS Only very brief mention can be made of the effect of phosphatases on glycose phosphates.Using 180 Cohn 123 demonstrated that intestinal alkaline phosphatase ruptures the oxygen-phosphorus bond a change apparently analogous to non-enzymic alkaline hydrolysis of sugar phosphates generally. Likewise prostate acid phosphatase cleaves the same bond. Phosphorylases have been used in experiments designed to determine the anomeric configuration of glycosyl phosphates but care must be exercised in interpreting the results. Changes in optical rotation have also been studied with this end in view (cf. Wolfrom et aZ.100 and Wright and Khorana it appears that assignment of anomeric configuration can be based on Hudson’s rules. A direct approach to this problem was sug- gested by the work of Dekker and Khorana 119 on the reactions of phosphate esters bearing an adjacent cis-hydroxyl function e.g.(XXIX) with dicycb- hexylcarbodi-imide. It was established that these esters give first the cyclic phosphates (XXX) which then form the phosphorylureas (XXXI). This reaction sequence may be followed readily by paper chromatography in suitable solvent systems the mobilities of the reaction products following the order (XXIX) > (XXX) > (XXXI) (examples drawn from the ribo- furanose series). Owing to the more or less planar nature of the furanose ring only the a-phosphate (XXIX) of the two anomeric ribofuranose l-phosphates is able to form a 5-membered cyclic ester and subsequently give rise to (XXXI). The anomeric configurations of synthetic /3- lo3 and enzymically produced a-ribofuranose 1 -phosphate can be assigned on the basis of these reactions. The phosphorylurea (XXXI) was much more stable than either of the samples of ribofuranose l-phosphate.It is likely that the method developed by Smith and his colleagues130 to determine the anomeric configuration of alkyl glycosides would be equally applicable for assignment of configuration in the glycose 1 -phosphate series. Properties of phosphate esters have been exploited in attempts to elucidate structural problems among natural products. To mention one example Brown et aZ. ,131 in experiments directed towards the determination of nucleotide sequence in polyribonucleotides made use of the fact that phosphates of P-aldehydo- and /3-keto-alcohols undergo elimination reactions with alkali. Reference has already been made to migration of phosphate groups and there are several observations in the literature concerning this.Tank6 and Robison 132 suggested that this might explain certain changes in optical 13O Abdel-Akher Cadotte Montgomery Smith Van Cleve and Lewis Nature 1953 131Brown Fried and Todd Chem. and Id. 1953 352; J . 1955 2206 132Tank6 and Robison Biochem. J. 1935 29 961. 171 474. FOSTER AND OVEREND CARBOHYDRATE PHOSPHATES 85 rotation of samples of fructose 6-phosphate which had been subjected to various treatments. Indirect evidence was obtained of phosphoryl migration during mild acid hydrolysis of trehalose phosphate. I n the migrations observed with glycerophosphates 133 and the " a " and " b " purine 134 and pyrimidine l35 nucleotides it is clear that the migration occurs via an inter- mediate cyclic ester. That interaction between neighbouring hydroxyl and phosphoryl groups takes place has been stressed by Kumler and Eiler,l21 who have shown that the polyol and sugar phosphates are abnormally strong acids in comparison with the monoalkyl phosphates.The difference in stability of ribo- and deoxyribo-nucleic acids towards alkali depends on the fact that only the former substance can form an internal cyclic triester. of the rates of oxidation of xylose 5- and 3-phosphate by periodic acid (and the readion of these compounds with dicyclohexyl- carbodi-imide) have led to the conclusion that xylose 3-phosphate exists in solution in the pyranose form (CI conformation) a conclusion which necessitates a re-interpretation of some of Levene and Raymond's s9 results. Marked differences have been observed in the rates of periodate oxidation of some cyclic phosphates methyl cc-D-glucoside 4 6-(phenyl phosphate) is unaffected even by prolonged treatment with periodate and methyl cc-D-glucoside 4 6-(hydrogen phosphate) is oxidised rather slowly but the rate of oxidation is greater for glucose 4 6-(hydrogen phosphate).120 The periodate oxidation of sugar phosphates has been discussed recently by Loring et ~ 1 .1 3 5 ~ A detailed description of the manifold enzymic reactions in which carbo- hydrate phosphates function as substrates is beyond the scope of this Review and only brief mention will be made of a few selected examples. Extensive investigations have established the importance of phosphate esters in carbohydrate metabolism both a t the pentose and hexose level and with the higher saccharides and polysaccharides.A recent development is the presentation of evidence that phosphoric esters of glucosamine and N-acetylglucosamine are concerned in the biosynthesis of mucopolysac- charides.136 As well as this substrate function some sugar phosphates have coenzyme activity e.g. glucose 1 6-diphosphate is a coenzyme for phosphoglucomutase and no interconversion of glucose 1 - and 6-phosphate is effected by this enzyme if the diphosphate is absent from the reaction medium. The r81e of phosphoglycosyl compounds in the biosynthesis of nucleosides and nucleotides has been reviewed by Ka1~kar.l~' Studies 133Verkade Stoppelenburg and Cohen Rec. Trm. chim. 1940 59 886. 134Brown and Todd J. 1952 52. 136 (a) Cohn J . Amer. Chem. Soc. 1950 72 2811 ; ( b ) Loring Levy Moss and las Glaser and Brown Proc. Nat. A d . Sci. U.S.A. 1955 41 253. 13' Kalckar Biochim. Biophys. Acta 1963 12 250. l'loeser J . Arner. Chem. Soc. 1956 78 3724.

ISSN:0009-2681    

DOI:10.1039/QR9571100061

出版商:RSC    

年代:1957

数据来源: RSC

摘要:

ERRATUM 1957 Vol. 11 No. 1 * From bottom of ma.in tsxt.

ISSN:0009-2681    

DOI:10.1039/QR9571100394

出版商:RSC    

年代:1957

数据来源: RSC

摘要:

CUMULATIVE INDEXES VOLUMES I-XI (1947-1957) CUMULATIVE INDEX O F Abrahams S. C. 10 407 Abrikosova I. I. 10 295 Addison C. C. 9 115 Albert A. 6 197 Allen G. ’7 255 Amphlett C. B. 8 219 Anderson J. S. 1 331 Angyal S. J. 11 212 Arnstein H. R. V. 4 172 Atherton F. R. 3 146 Avison A. W. D. 5 171 Bacon R. G. R. 9 287 Baddeley G . 8 355 Badger G. M. 5 147 Bagnall K. W. 11 30 Baker W. 11 15. Baltazzi E. 9 150 Barker S. A. 7 58 Barnartt S. 7 84 Barrer R. M. 3 293 Barton D. H. R. 3 36; Bassett H. 1 247 Bateman L. 8 147 Baughan E. C. 7 103 Bayliss N. S. 6 319 Bell R. P. 1 113 ; 2 132 Bentley R. 4 172 Bergel F. 2 349 Bevington J. C. 6 141 Birch A. J. 4 69 Bircumshaw L. L. 6 157 Bockris J. O’M. 3 173 Bolland J. L. 3 1 Bond G. C. 8 279 Bourne E. J. 7 58 Bowen E. J. 1 1 ; 4 236 Bradley R. S. 5 315 Rraude E.A. 4 404 Bremner J. G. M. 2 1 Brown B. R. 5 131 Brown R. D. 6 63 Bu’Lock J. D. 10 371 Burkin A. R. 5 1 Burnett G. M. 4 292 Burton H. 6 302 Cadogan J. I. G. 8 308 Caldin E. F. 7 255 Challenger F. 9 255 Coates G. E. 4 217 Collinson E. 9 311 Cook A. H. 2 203 Cook J. W. 5 99 Cookson R. C. 10 44 Cottrell T. L. 2 260 Coulson C. A. 1 144 Cowdrey U’. A. 6 358 10 44 ; 11 189 Cox E. G . 7,335 Crawford V. 9. 3 236 Crombie L. 6 101 Cruickshank D. W. J.. 7 Curran S. C. 7 1 Dalgliesh C. E. 5 227 navies A. G. 9 203 Davies D. S. 6 358 Davies M. 8 250 Davies R. O. 11 134 Dawton R. H. J7. M. 9 1 De Heer J. 4 94 de la Mare P. B. D. 3 126 de Mayo 11 189 Derjaguin B. V. 10 295 Dickens P. G. 11 291 Dubinin 31 M. 9 101 Duncan J. F. 2 307 Dunning W. J. 9 23 Eley D. D. 3 181 Emelhus H. J. 2 132 Evans R4.G. 4 94 ; 6 335 186 Fensham P. J. 11 227 Foster A B. 11 61 Freidlina R. Kh. 10 330 Gascoigne R. M. 9 328 Gaydon -4. G. 4 1 Gee G. 1 265 Gent W. L. Q. 2 383 Gibson D. T. 3 263 Gillespie R. J. 2 277 ; 8 Glenn A. L. 8 192 Goehring M. 10 437 Gold V. 9 51 Gray P. 9 362 Greenwood N. N. 8 1 Griffith J. S. 11 381 Gunstone F. D. 7 175 Gutmann V. 10 451 40; 11 339 Halpern J. 10 463 Hamer. F. M. 4 327 Hardy D. V. N. 2 25 Harris M. M. 1 299 Hartley G. S. 2 154 Hassel O. 7 221 Hawkins E. G. E. 4 251 Hawkins J. D. 5 171 Haynes L. J. 2 46 Heaney H. 11 109 Hey D. H. 8 308 Hickling A. 3 95 396 AUTHO R.S Hughes E. D. 2 107 ; 5 245 ; 6 34 Hush N. S. 6 186 Ingold C. I<. 6 34 ; 11 1 Irving H. M. 5 200 Jacobs P. W. )I. 6 236 Jain A. C. 10 169 Janz G. J. 9 229 Jeffrey G. A. 7 335 Jenkins E.N. 10 83 Jones D. G. 4 195 Kapustinskii A. F. 10 283 Katritzky A. R. 10 396 Kenyon J . 9 203 Khorana H. G. 6 340 Kipling J. J. 5 60 ; 10 1 Lamb J. 11 134 Lamberton A. H. 5 75 Law IT. D. 10 230 Lea F. M. 3 82 Leech H. R. 3 22 Leisten J. A. 8 40 Levy N. 1 358 Lewis J. 9 115 Lifshjtz E. &I. 10 295 Linnett J. W. 1 ‘73; 11 Lister B. A. J. 2 307 Lister M. W. 4 20 Long L. H. 7 134 Longuet-Higgins H. C. 11 Loudon J. D. 5 99 Lythgoe B. 3 181 31accol1 A. 1 16 McCoubrey J. C. 5 364; MacDiarmid A. G. 10 208 McGrath W. D. 11 87 McKennrt J. 7 231 Maddock A. G. 5 270 Maitland P. 4 45 Manners D. J. 9 73 Marsh J. I<. 1 126 Martin R. L. 8 1 Megson N. J. L. 2 23 Millar I. T. 11 109 Millen D. J. 2 277 Morgan R. J. 8 123 Morrison A. L. 2 349 Musgrave W. K. R. 8 331. 291 121 11 87 Nesmeyanov A.N. 10,330 Norrish R. G. W. 10 149 CUMULATIVE INDEX 307 Nyholm R. S. 3 321 ; 7 377 ; 11 339 Ollis W. D. 11 16 Orgel L. E. 8,422 ; 11,381 Orville-Thomas W. J. 11 Overend W. G. 11 61 Owston P. G. 5 344 Page. J. E. 6 262 Paneth F. A. 2 93 Pauson P. L. 9 391 Pepper D. C. 8 88 Percival E. G. V. 3 369 Phillips F. C. 1 91 Pople J. A. 11 273 Praill P. F. G. 6 302 Richards R. E. 10 480 Riddiford A. C. 6 157 Riley H. L. 1 59 ; 3 160 Rose J. D. 1 358 Rowlinson J. S. 8 168 Satchell D. P. N. 9 51 Saxton J. E. 10 108 162 Schofield K. 4 383 Seshadri T. R. 10 169 Sexton MT. A. 4 272 Sharp@ A. G. 4,115 ; 11,49 Shchukina L. A. 10 261 Shemyakin M. M. 10 261 Sheppard N. 6 1 ; 7 19 Simes J. J. H. 9 328 Simpson D. M. 6 1 ; 7 19 Smales A. A. 10 83 Smith J . A. S. 7 279 Smith M. L.. 9 1 Springall 13.D. 10 230 Stacey M. 1 179 213 Stavoley L. A. K. 3 65 Stern E. S. 5 405 Stone F. G. A.. 9 174 Sutton L. E. 2 260 Swallow A. J. 9 311 Synge R. L. M. 3 215 Szwarc M. 5 22 Taylor A. W. C. 4 195 Thomas. S. L. 7 407 Thomson R. H. 10 27 Thrush R. A. 10 149 Tipper C. F. H. 11 313 Tomkins F. C. 6 238 Topley B. 3 345 Trapndl E. M. %'. 8 404 Trotinan -Dj ckenson A. F. Truter E. V. 5 390 Turner E. E. 1 299 Turner H. S. 7 407 Ubhelohde A. R. 4 356; Uri N. 6 186 7 198 5 364 ; 11 246 Walsh A. D. 2 73 Warburton W. K. 8 67 Warhurst E. 5 44 Weedon E. C. I,. 6 390 Wells A. F. 2 185 8 380 Wells R. A. 7 307 Whjffen D. H. 4 131 Whytlaw-Gray R. 4 153 TF7ilson H. N. 2 1 Woodward L. A. 10 186 Yoffe A. D. 9 362 Zakharkin L. I. 10 330 CUMULATIVE INDEX OF TITLES Acetylenes infrared and Ramaii spectra Carbon-carbon bonds oxidative-hydro- lytic splitting of in organic molecules Acetylenic compounds as naturaI pro- 10 261 Carbon-carbon double bonds geometrical Acid use of the term 1 113 Acids carboxylic anodic syntheses with Carbon-hydrogen bond polarity of 2 383 6 380 Carbonitrides carbides and nitrides of Adsorption of non-electrolytes from solu - Carbons active study of porous structure Age geological determination of by raciio- adsorbent properties and nature of Aldehydes polymerisation of 6 141 Aliphatic nitro-compounds 1 358 Alkaloids ergot 8 192 of 6 1 ducts 10 371 isomerism about 6 101 association of 7 255 tion 5 60 iron 3 160 of by a variety of methods 9 101 activity 7 1 10 1 Carbonyls metal chemistry of 1 331 Catalysis by metals specificity in 8 404 Catalysis hydrogen mechanisms of 3,209 Catalysis and semiconductivity 11 227 nine 10 108 Catalysts redox initiation of polymer- isation processes by 9 287 Cations organic reactions of 6 302 Charcoals active study of porous struc- ture of by a variety of methods 9 101 inclole excluding harmine and strych- steroidal 7 231 Alkanes tetra- and tri- and related coni- Analgesics synthetic 2 349 extraction to 5 200 pounds 10 330 Analysis inorganic applications of solvent Chromatography inorganic 7 307 Collisions in gases energy transfer in 11 Colloida.1 electrolytes state of solution of Colour and constitution 1 16 Combustions slow in the gas phase ele- mentary reactions in 11 313 Complex compounds stabilities of 5 1 Conductance ionic in solid salts 6 238 Configuration of flexible organic molecules Conformational analysis principles of 10 Base use of the term 1 113 Conjugated cornpouiids free -electron Biological degradation of tryptophan 5 Anionotropy 4 404 Anodic syntheses with carboxylic acids 6 3 80 Aqueous solutions mechanism of electrode processes in 3 95 Aromatic bond 5 147 87 2 154 nitration 2 277 rearrangements 6 34 Association of carboxylic acids 7 253 Attraction molecular direct measurement of between solids separated by w 5 364 narrow gap 10 295 44 approximation for 8 319 Constitution and colour 1 16 227 methylation 9 225 Co-ordination compounds of boron tri- reactions role of phosphoric esters i n fluoride 8 1 5 171 Crystal structure and melting 4 3.56 Crystal structures of salt hydrates and Crystals ionic lattice energy of 10 283 location of hydrogen atoms in 10 480 Cyanine dyes 4 327 Bong{ aromatic 5 147 dissociation energies 5 22 properties interpretation of 2 260 complex halides 8 380 Bonding chemical and nuclear quadru- Boron hydrides and related compounds 2 pole coupling 11 162 132 Decarboxylation thermal mechanism of chemistry of 9 174 8 1 5 131 trifluoride co-ordination compounds of Densities limiting 4 153 Dielectric absorption 8 250 Dihalogen compounds Grignard and or- Carbides nitrides and carbonitrides of ganolithium compounds derived from Carbohydrate phosphates 11 61 Disproportionation in inorganic com- Carbohydrate sulphates 3 369 pounds 2 1 Carbon amorphous and graphite 1 59 iron 8 160 11 109 Diterpenoids chemistry of 3 36 398 C ZTMULATIVE I'NDEX 399 Dyes cyanine 4 327 effects of light on 4 236 organic and their constitution 1 16 Electrode processes in aqueous solutions Electrolytes colloidal state of solution of and electrolytic processes effects of Electromagnetic separation of stable Electron correlation and chemical conse- Electrons structures of molecules deficient Elements heavy radioactivity of 5 270 mechanism of 3 95 2 154 ultrasonic waves on 7 84 isotopes 9 1 quences 11 291 in 11 121 of Group VIII recent stereochemistry of Groups IVB and IV comments on of the rare-earth series separation of 1 terrestrial distribution of 3 263 transuranic chemistry of 4 30 of 3 321 the thermochemistry of 7 103 126 Emission spectra of flames 4 1 Energy transfer of in gaseous collisions Enzymic degradation of polysaccharides 11 87 9 73 synthesis of polysaccharides 7 58 Equivalent-orbital approach to molecular Ergot alkaloids structure of 8 192 Esters carboxylic and related com- pounds alkyl-oxygen heterolysis in 9 203 Exchange reactions of hydrogen isotopes in solution principles of 9 51 structure 11 273 Fatty acids straight-chain recent developments in the preparation of natural and synthetic 7 175 Ferrocene and related compounds 9 391 Flames emission spectra of 4 1 Flash photolysis and kinetic spectroscopy Flavones and related compounds nuclear isoFlavones 8 67 Fluorescence and fluorescence quenching Fluorine and its compounds laboratory and technical production of 3 2.2 compounds organic reactions of 8 331 general aspects of the inorganic chem- istry of 11 49 10 149 methylation of 10 169 1 1 Force constants 1 73 Free-electron approximation for con j u - Frce-radical addition reactions of olefinic FriedelLCrafts reaction modern aspects gated compounds 6 319 systems 8 308 of 8 355 Furan and pyran chemistry some aspects of 4 195 Gases elementary reactions in slow com- energy transfer in collisions in 11 87 Geological age determination of by radio- Graphite and aniorphous carbon 1 59 Grignard reagents derived from dihalogen bustions in 11 313 acti~it~y 7 1 compounds 11 109 Halides reactions of in solution 5 245 complex crystal structures of 8 380 Halogens kinetics of thermal addition of to olefinic compounds 3 126 Heats of formation of simple inorganic compounds 7 134 Heterocyclic nitrogen compounds nitrw- tion of 4 382 Heterogeneous reactions transport control in 6 157 Heterolysis nlkyl-oxygen in carboxylic esters and related compounds 9 203 cycZoHexane stereochemistry of 7 221 Hydrocarbons infrared and Raman spectra of.Part I. Acetylenes and olefins 6 1. Part 11. Paraffins 7 19 Hydrogen molecular homogeneous re- actions of in solution 10 463 Hydrogen atoms location of in crystals 10 480 catalysis mechanisms of 3 209 isotope exchange reactions in solution principles of 9 51 peroxide its radicals and its ions energetics of reactions involving 6 186 Hydrogenation catalytic and related re- actions mechanism of $ 279 Hyperconjugation 3 226 Ice structure of 5 344 Immunochemistry aspects of 1 179 213 Indole alkaloids excluding harmine and strychnine 10 108 Jnduction asymmetric and asymmetric transformation 1 299 Infrared and Raman spectra of hydro- carbons. Part I. Acetylenes and olefins 6 1. Part 11. Paraffins 7 19 Inorganic analysis applications of solvent extraction to 5 200 chemistry and magnetism 7 377 chromatography 7 307 compounds disproportionation in 2 1 Raman spectra of 10 185 simple heats of formation of 7 134 iodine compounds inorganic some re- actions of 8 123 stereochemistry 11 339 Inositols 11 212 Insecticides synthetic structure and activity in 4 272 400 CUMULATIVE INDEX Interhalogen compounds and polyhalides Intermolecular forces and some properties Iodine compounds inorganic some re- Ion exchange 2 307 Ionic conductance in solid salts 6 238 solvation 3 173 Ionisation potentials and far ultra- violet spectra their significance in chemistry 2 73 Iron carbides nitrides and carbonitrides of 3 160 Isomerism geometrical about carbon- carbon double bonds 6 101 Is0 topes stable electromagnetic separa - tion of 9 1 Isotopic exchange between different oxida- tion states in aqueous solution 8 219 Isotopically labelled organic compounds 4 115 of matter 8 168.actions of 8 123 tracer techniques 4 172 synthesis of 7 407 Lactones physiologically active unsatur- Lanthanons separation of 1 126 Lattice energy of ionic crystals 10 283 Ligand-field theory 11 38 1 Light absorption and photochemistry 4 Liquids ultrasonic analysis of relaxation Liquids and solids transitions in 3 65 Magnetic resonance absorption nuclear Magnetism and inorganic chemistry 7,377 Mass spectrometry application to chemi- Melting and crystal structure 4 356 Meso-ionic compounds 11 15 Metal carbonyls chemistry of 1 331 Metal-ammonia solutions reduction of Metals specificity in catalysis by 8 404 Methyl radicals reactions of 7 198 Methylation biological 9 255 ated 2 46 236 processes in 11 134 7 279 cal problems 9 23 oxides structure of 2 185 organic compounds by 4 69 nuclear of fiavones and related com- pounds 10 169 Molecular interpretation of thermodynamic properties of high polymers 1 265 structure determination by X-my crystal analysis modern methods and their accuracy 7 335 molecular-orbital and equivalent-or- bital approach t'o 11 273 Molecular-orbital approach to molecular Molecular-sieve action of solids 3 293 Molecules electron-deficient structures of simple representation by molecular structure 11 273 11,121 orbitals 1 144 Morphine synthetic approaches to struc- ture o€ 5 405 as 10 371 of 5 75 Natural products acetylenic compounds Nitramines some aspects of the chemiqtry Nitration aromatic 2 277 of heterocyclic nitrogen compounds 4 Nitrides carbides and carbonitrides of Nitro-compounds aliphatic 1 358 Nitrogen dioxide-dinitrogen tetroxide system structure and reactivity of 9 362 Nitrosyl group chemistry of 9 115 Non -electrolytes adsorption of from sol ci- Nuclear magnetic resonance absorption Nuclear quadrupole coupling and chemi- Nucleation in phase changes 5 315 Oceanic salt deposits 1 91 Olefinic systems free-radical addition reactions of 5 308 Olefins infrared and Raman spectra of 3 82 iron 3 160 tion 5 60 7 279 cal bonding 11 162 6 1 kinetics of oxidation of 3 1 kinetics of thermal addition of halogens oxidation of 8 147 to 3 126 6 63 1 144 Orbitals molecular and organic reactions representation of simple molecules by Organic cations reactions of 6 302 chemistry of derivatives of phosphorus compounds action of ionisinq radiations oxyacids 3 146 on 9 311 behaviour in sulphuric acid 8 40 estimation of thermodynamic proper- isotopically labelled synthesis of 7 polarography of 6 262 reduction of by metal-ammonia solu- fluorine compounds reactions of 8 331 molecules flexible configuration of 5 oxidative-hydrolytic splitting of car- ties for 9 229 40 7 tions 4 69 364 bon-carbon bonds in 10 261 peroxides and their reactions 4 251 reactions and molecular orbitals 6 34 Organolithium reagents derived from di- Organometallic compounds of the first 5-Oxazolones chemistry of 9 150 Oxidation of olefns 8 147 halogen compounds l l 109 three periodic groups 4 217 kinetics of 3 1 CUMUL4TIVE INDEX 401 Osidation-reduction potential of quin- ones relation to chemical structure 4 94 istry of 10 395 Oxides metallic structures of 2 185 X-Oxides aromatic heterocyclic chem- Paraffins infrared and Raniaii spectra of Penkillins chemistry of 2 203 Peptides methods of synthesis and 7 19 terniinal-residue studies of 10 230 naturally occurring 3 245 arid proteins structural investigation Feroxides orgmic and their reactions 4 Phase changes nucleation in 5 315 Phenols tautonierism of 10 27 Phosphates condensed 3 345 Phosphates of carbohydrates 11 61 Phosphoric esters role in biological re- actions 5.171 Phosphorus oxyacids some aspects of the organic chemistry of derivatives of 3 146 Photochemistry and light absorption 4,236 Photography cyanine dyes in 4 327 Photopolymerisation 4 236 Yo1arit:y of the carbon-hydrogen bond Polarography of organic ConipouCds 6 Foloniuni chemistry of 11 30 lolyhalides and interhalogen compounds Polymerisation initiation of by redox of 6 340 251 2 383 262 4,115 catalysts 9 287 ionic 8 88 of aldehydes 6 141 reactions radical rate constants in 4 292 Polymers high thermodynamic properties of and their molecular interpretation 1 265 9 73 silicon chemistry of 2 25 Polysaccharides enzymic degradation of enzymic synthesis of 7 58 Portlarid cement constitution of 3 S2 Properties of matter and intermolecular Proteins and peptides structural investi- Pteridines 6 197 Purine and pyrimidine chemistry some Pyran and furan chemistry some aspects Pyrimidine and purine chemistry some Pjrrrole pigments biogcnetic origin of 4,45 Quadrupole coupling zuclear and chemi- forces 8 168 gation of 6 340 aspects of 3 181 of 4 195 aspects of 3 181 cal bonding 11 102 Quenching of fluorescence 1 1 Quinones relation between the oxidation- reduction potential and chemical structure of 4 94 compounds 9 311 Radiations ionising action of on organic Radioactivation analysis 10 83 Radioactive tracers preparation of 2 93 Radioactivity determination of geological age by 7 1 of the heavy elements 5 270 Raman and infrared spectra of hydro- carbons.Part I. Acetylenes and olefins 6 1. Part 11. Paraffins 7,19 Ranian spectra of inorganic compounds 10 185 Rare-earth elements separation of 1 126 Reactions chemical estimation of ther- modyna,mic properties for 9 229 Rearrangements aromatic 6 34 Redox catalysts initiation of polymeri- sation processes by 9 287 potentials of quinones relation to chemi- cal structure 4 94 Reduction of organic compounds by metal-ammonia solutions 4 69 Relaxation processes molecular in liquids ultrasonic analysis of 11 134 Rotation spectra 4 131 Salt deposits oceanic 1 91 hydrates crystal structures of 8 380 Salts basic structure of 1 247 solid ionic conductance in 6 238 Sandmeyer and related reactions 6 358 Semiconductivity and catalysis 11 227 Sesquiterpenoids recent advances in chemistry of 11 189 Silicon polymers chemistry of 2 25 Silyl corypounds 10 208 Sodium Solids molecular-sieve action of 3 293 flame ” reactions 5 44 and liquids transitions in 3 65 separated by a narrow gap direct measurement of molecular attraction between 10 295 thermal transformations in 11 246 Solvation ionic 3 173 Solvent extraction and its applications to Solvents ionising non-aqueous reactions Specificity in catalysis by metals 8 404 Spectra charge-transfer and some related inorganic analysis 5 200 in 10 461 phenomena 8 422 emission of flames 4 1 far ultraviolet ionisation potentials and their significance in chemistry 2 73 infrared and Raman of hydrocarbons.Part I. Acetylenes and olefins 6 1. Part 11. Paraffins 7 19 Raman of inorganic compounds 10 185 rotation 4 131 402 CUMULATIVE INDEX Spectroscopy kinetic and flash photolysis St'abilities of complex compounds 5 1 Stereochemistry inorganic 11 339 Stereochemistry of cyclohexctrie 7 221 10 149 of Sub-grow VIB of the Periodic Table 10,467 of the Group VIII elements 3. 321 Steric hindmrke 3 107 Steric hindrance quantitative study of Steroidal alkaloids 7 231 Sub-group VIB stereochemistry of 10 Sulphur nitride and its derivatives 10 Sulphuric acid behaviour of organic Sydnones 11 15 Tautomerism of phenols 10 27 Terrestrial distribution of the elements 3 263 Thermochemistry of the elements of Groups IVB and IV comments on 7.103 11 1 40 7 43 7 compounds in 8 40 Thermodynamic properties of high poly- mers and their molecular interpret8a- tion 1 265 Tracers radioactive preparation of 2 93 Transformation asymmetric and mym- metric induction 1 299 Transformations thermal in solids 11 246 Transitions in solids and liquids 3 65 Transport control in heterogeneous re- Transuranic elements chemistry of 4 Triterpenes tetracyclic 9 328 Tropolones 5 99 Tryptophan biological degradation of 5 actions 6 157 20 327 Ultrasonic analysis of molecular relaxa- tion processes in liquids 11 132 Vltrasonic waves effects on electrolytes and electrolytic processes 7 84 Wool wax constitution of 5 390 - 3 Thermodynamic properties estimation of for organic compounds and chemical rcactions 9 239 X-Ray crystal analysis modern methods of molecular structure determination by and their accuracy 7 335

ISSN:0009-2681    

DOI:10.1039/QR9571100395

出版商:RSC    

年代:1957

数据来源: RSC