ISSN:0069-3030    

DOI:10.1039/OC97572FX001

出版商:RSC    

年代:1975

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC97572BX003

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (ii) Nuclear Magnetic Resonance Spectroscopy By L. PHILLIPS Chemistry Department Imperial College of Science and Technology London SW7 2AY 1 Introduction This Report as last year is a highly selective review of areas of n.m.r. which are of continuing or growing importance to organic chemists. Inevitably therefore it concentrates upon applications of 13Cn.m.r. Fourier Transform technique selective T,measurements and high-field ’H n.m.r. Many important areas such as ‘other nuclei’ studies of molecules in liquid-crystaI solvents and structure determination by routine methods have been ignored although the author is not blind to their merits! 2 AppIications of ”C N.M.R. Relationships between Structure and Shielding.-These are fundamental to the application of the technique in many fields.In the first volume’ of the important new series ‘Topics in Carbon- 13 N.M.R. Spectroscopy’ there are excellent chapters covering the theory of 13Cchemical shifts and substituent effects. Maciel comments in Chapter 2 of this work,that he ‘hasheard talks introduced with a phrase equivalent to ‘now that I3Cchemical shifts are well understood. . .’ Such speakers have either grossly misjudged the situation or eise have been keeping one of the world’s best guarded secrets!’ The past year’s literature has done little to change this situation aIthough an empirical approach has often proved helpful. There is still widespread faith in a simple relationship between chemical shift and charge density.An examination* of allyl pentadienyl and arylmethyl carbanions suggests a linear relationship to .rr-electrondensity,of 160ppm. per electron. This agrees with an earlier value3 but is twice as large as a recent suggestion for non-ionic specie^,^ which lends weight to Maciel’s assertion that undue importance should not be placed on the values of such slopes.5 Substituent effects in 4-substituted phenylacetylenes,‘ isothiazoles,’ and couma-rim’ have all been examined in this light as have chemical shifts in ionic spe~ies.~”’ I ’Topics in Carbon-13N.M.R.Spectroscopy’ ed. G. C.Levy Wiley-Interscience New York 1974. D. H. O’Brien A. J. Hart and C. R.Russell J. Amer. Chern. Soc. 1975,97,4410. G. A. Olah and G. D. Mateescu J. Amer. Chem. Soc. 1970,92,1430.G. E.Maciel J. L. DalIos R.L. Elliott and H. C. Dorn J. Amer. Chern. Soc. 1973 95 5857. G. E. Maciel ref. 1 p. 74. D.A. Dawsoo and W. F. Reynolds Canad.J. Chem. 1975,53,373. ‘R.E.Wasylishen T.R.Clem and E.D.Becker Canad.J. Chcrn. 1975,53,596. 8 H. Giinther J. Prestien and P. Joseph-Nathan Org. Magn. Resonance 1975,7,339. G. A. OIah P.W.Westerrnan and D.A. Forsyth J. Amer. Chern. Soc. 1975,97,3419. lo E. Dradi and G. Gatti J. Amer. Chem. Soc. 1975 97. 5472. 10 Part (ii) Nuclear Magnetic Resonance Spectroscopy Martin et a/.'' have examined in more general terms the theoretical and empirical calculation of 13C chemical shifts in terms of electronic distribution. In an important paper Roberge and Fliszar" analyse the relationship between 13C chemical shifts and charge-density distributions in cyclohexane and methyl- substituted cyclohexanes.All observed effects are accommodated by the relation- ship 8 = -237.1qc+242.64 where qcis the net charge density (ab initio) on a particular carbon. It is not necessary to consider extra terms for 'sterically crowded' carbons such as the 3-carbon in axial methylcyclohexane. With cyclopropanes such a simple relationship does not hold. Particular attention has been given to the influence of substituents upon carbon shielding at y positions and the idea of a y gauche sterically induced high-field shift is of continued importance in conformational and assignment problems (e.g.ref. 13). It was pointed out last year14 that y truns effects were also important and often paralleled y gauche shifts casting some doubt on their steric origin.This is emphasized by work on 2-substituted bicyclo[3,3,l]nonan-9-0nes'~where y truns high-field shifts of a magnitude comparable with y gauche are observed. Eliel et have examined the universally upfield shifts caused by N 0,and F atoms in a y antiperiplanar relationship to the observed 13C nucleus and it always appears to be significant unless the substituent is at the bridgehead of a bicyclic compound. Elsewhere Eliel" points out an interesting parallel between substituent effects upon 'H and 13C in analogous y positions with respect to substituents. Usually they are interpreted in quite different terms but the implication is that they have a common origin. Batchelor'* points out (in agreement with the assessment in last year's Rep~rt'~) that the theory of the steric origin of y gauche high-field shifts cannot account for low-field S effects in sterically crowded situations.He suggests that in such close proximity the second-order electric field influence of fluctuating dipoles (i.e.van der Waals interactions) may be decisive. In keeping with his earlier assessment of the electric field origin of chemical shifts induced by remote dipolar substit~ents,'~ this same author further develops the theory2* and because of the orientation dependence of electric fields suggests an application to conformational analysis. He also applies these ideas to 13C protonation shifts in amines carboxylic acids and amino-acids.2' Conformational Analysis.-A novel method for observing n.m.r.spectra of high-energy conformations in systems with barriers to conformational interconversion as G. J. Martin M. L. Martin and S. Odiot Org. Mugn.Resonance 1975,7 2. l2 R. Roberge and S. Fliszar Cunud. J. Chem. 1975,53,2400. l3 Y. Senda J. Ishiyama and S. Imaizumi Tetruhedron 1975,31 1601. l4 R. B. Jones and L. Phillips Annual Reports (B) 1974,26. lS A. Heumann and H. Kolshorn Tetrahedron,1975,31 1571. l6 E. L. Eliel W. F. Bailey L. D. Kopp R. L. Willer D. M. Grant R. Bertrand K. A. Christensen,D. K. Dalling M. W. Duck E. Wenkert F. M. Schell and D. W. Cochran J. Amer. Chem. SOC.,1975,97,322. l7 E. L. Eliel V. S. Rao F. W. Vierhapper and G. Zuniga Juaristi Tezruhedron Letfers 1975 4339. J.G. Batchelor J. Mugn. Resonance 1975,18 212. l9 J. G. Batchelor R. J. Cushley and J. H. Prestegard J. Org. Chem. 1974,39 1698. 2o J. G. Batchelor J. Amer. Chem. Soc. 1975,97 3410. 21 J. G. Batchelor J. Feeney and G. C. K. Roberts J. Mugn. Resonance 1975 20 19. 12 L.Phillips small as 30 kJ mol-’ has been described.22 A high-temperature equilibrium in which high-energy conformations become significantly populated is set up and then frozen by cryogenic deposition under high vacuum. The power of the method is illustrated by the direct observation using i.r. techniques of the twist-boat confor- mation of cyclohexane; the n.m.r. study of this system is presently under way.23 A limitation on the use of 13C n.m.r. as a tool for studying conformational rate processes at low temperatures is the absence of a suitable ‘Chemical Shift Ther- mometer’ as widely used in ‘H n.m.r.Two answers to this problem have now appeared. One makes use of the great linewidth variation (in the range 0-80 “C) in the 13Cspectrum of furfural due to the conformational rotation about the ring- aldehydic bond;24 the other ulitizes the temperature dependence (in the range -80 to +40 “C) of the pseudo-contact-shifted 13C carbonyl resonance of acetone in the presence of the Yb(f0d)3 shift reagent.25 When a conformational equilibrium may be ‘frozen out’ at low temperatures 13C n.m.r. offers a very powerful tool for estimating free-energy differences. This has been exploited by Booth for example with some N-substituted decahydro-quinolines..26In such circumstances spectral assignment is often straightforward and the free-energy difference may be obtained directly by integration of the relevant signals.In an averaging situation the observed spectral parameters must be dissected into different contributions from the constituents of the equilibrium and it is necessary to characterize properties which are ‘conformationally dependent’. Much use is made of high-field y gauche effects as mentioned above; for example in six-membered cyclic sulphoxides with the oxygen atom axial the 3-carbon resonance is 7.5 p.p.m. to high field of the analogous equatorial situation.*’ In these compounds the 2-carbon (p to 0)also shows a high-field shift for the same structural change of 5.5 p.p.m.; this is rationalized in terms of intramolecular electric field effects.The same properties of the sulphoxide group have been used to show that conversion of penicillins into their sulphoxides produces a conformational change.28 Pearson believes that the upfield shift in the I3CH3 resonance of toluenes on ortho-methylation is a classical y-gauche (in this case actually syn) effect. Further alkylation of the substituent sometimes increases and sometimes decreases the shielding due to the ‘steric’ origin of the ‘6 effect’ which is to low field; by balancing the two together the conformational behaviour of the u-alkyl substituent may be deduced. 29 Traditionally coupling constants have given the most useful conformational information; one- two- and three-bond couplings between ‘H and 13Chave all been used in this way.Cantacuzene et al.have reported the stereochemical dependence of ‘J(CH) in a-halogen~-ketones,~’ while two papers demonstrate the importance of 22 F. A. L. Anet and M. Squillacote J. Amer. Chem. SOC.,1975,97,3243. 23 M. Squillacote R. S. Sheridan 0.L. Chapman and F. A. L. Anet J. Amer. Chem. SOC.,1975,97,3245. 24 S. Combrisson and T. Prange J. Magn. Resonance 1975 19 108. *5 H. J. Schneider W. Freitag and M. Schommer J.Magn. Resonance 1975,18 393. H. Booth and D. Vaughan Griffiths J.C.S. Chem. Comm. 1975 111. 27 G. W. Buchanan and T. Durst Tetrahedron Letters 1975,1683. 28 K. Tori T. Tsushima Y. Tamura H. Shigemoto T. Tsuji H. Ishiboti and H. Tanida Tetrahedron Letters 1975 3307. 29 H.Pearson J.C.S. Chem. Comm. 1975 912. 30 J. Cantacuzene R. Jantzen M. Tordeaux and C. Chachaty Org. Magn. Resonance 1975,7,407. Part (ii) Nuclear Magnetic Resonance Spectroscopy 13 variation in ,J(C,H) as a conformational The sign of 2J(C,H) may be either positive or negative under different circumstances depending for example upon orientation of the coupled ‘H to an oxygen attached to the 13C; 0 anti to H gives a positive contribution to 2J(C,H) while 0gauche gives a negative contribu- ti~n.~~ This work suggests that 2J(C,H) is a ‘more definitive type of stereochemical descriptor than ,J(C,H)’ but this may not be generally so since two papers show that the more useful parameter for studies on peptides is 3J(C,H).33,34 In 13C-enriched materials 2J(C,C) and 3J(C,C) may be observed in addition to the more obvious ‘J(C,C).Barfield et al. have examined the theory of these3’ by the finite perturbation formulation in the INDO approximation and show that 3J(C,C) shows a strong dihedral angle dependence with 3J(C,C) (cis)apparently larger than 3J(C,C) (trans). This parameter has been used in studies of I3C-enriched amino- Coupling to ‘other nuclei’ also shows stereochemical dependence and 2J(P,C) 3711J(P,C) +2J(P,C)1,38 3J(C,14N),39 and 3J(C,199Hg)40 have all been used as conf ormational probes. Lanthanide shift reagents continue to play their part although their use has been much more limited than in recent years. Their value is shown for example in the conformational study of the valinomycin backbone in CDCI and in the investigation of nicotinamide mononucleotide in aqueous Physical Organic Chemistry.-Donor-acceptor equilibria may be conveniently studied by 13C n.m.r.Forskn et al. have pointed out that on adduct formation ‘H n.m.r. spectra of donor molecules show downfield shifts; 13C resonances may move downfield or upfield in spite of the accompanying electron ~ithdrawal.~~ A report that AsCl is a convenient solvent for 13C n.m.r. studies ‘unless the solute contains OH or NH when the AsCI acts as a shift reagent’ is best considered as an example of donor-acceptor c~mplexation.~~ Similarly the shifts induced by TiCI on the 13C n.m.r. spectra of carbonyl should not be confused with the shifts induced by lanthanide shift The charge-transfer complexes of nitroben-zene with various electron-rich aromatic donors have been examined and association constants and 1 1 complexation shifts evaluated.46 MacNico14’ has made very elegant use of the ability of the cyclodextrins to complex hydrocarbons into their voids; the complexation results in a ‘spreading out’ of the hydrocarbon n.m.r.31 J. A. Schwartz N. Cyr and A. S. Perlin Canad. J. Chem. 1975 53 1872. 32 T. Schaeffer K. Chum D. McKinnon and M. S. Chauhan Canad. J. Chem. 1975,53,2734. 33 P. E. Hansen J. Feeney and G. C. K. Roberts J. Magn. Resonance 1975,17,249. 34 V. F. Bystrov Ya. D. Gavrilov andV. N. Solka J. Magn. Resonance 1975,19 123. 35 M. Barfield I. Burfitt and D. Doddrell J. Amer. Chem. SOC.,1975,97 2631. 36 S. Tran-Dinh S. Fermandjian E.Sala R. Mermet-Bouvier and.P. Frornageot J. Amer. Gem. Soc. 1975,97,1267. 37 J. P. Dutasta and J. B. Robert J.C.S. Chem. Comm. 1975 747. 38 R. K. Harris E. M. McVicker and M. Field J.C.S. Chem. Comm. 1975 886. 39 R. DiBlasi and K. D. Kopple J.C.S. Chem. Comm. 1975 33. 40 W. Kitching D. Praeger D. Doddrell F. A. L. Anet and J. Krane Tetrahedron,1975,31 759. 41 K. L. Servis and D. J. Patel Tetrahedron,1975,31 1359. 42 B. Birdsall N. J. M. Birdsall J. Feeney and J. Thornton J. Amer. Chem. SOC.,1975,97,2845. 43 J. S. Hartman P. Stilbs and S. ForsCn Tetrahedron Letters 1975 3497. 44 A. K. Bose M. Suguira and P. R. Srinivasan Teirahedron Letters 1975 125 1. 45 A. K. Bose and P. R. Srinivasan Tetrahedron Letters 1975 1571. 46 R. C. Griflith D.M. Grant and J. D. Roberts J. Org. Chem. 1975 40,3726. 47 D. D. MacNicol Tetrahedron Letters 1975 3325. 14 L.Phillips spectrum. Although this has sofar been used only for ‘H n.m.r. the extension to 13C studies is obvious. The co-ordination of organic molecules to metal ions in solutions may be observed. Following the assignment of the I3Cn.m.r. spectrum of tetra~ycline,~’ the complexation with metals has been studied and the binding site analy~ed.~~ The complexation between Co”’ and dimethylglyoxime has been studied.” Some molecules have the ability to form adducts with both cations and anions; valinomycin has been examined in this way,s1 as have the nucleosides cytidine and guanosine.52 I3CN.m.r. may be used to study chemical exchange processes.Grant et al. have looked at tautomerism in purine^.^^*'^ A set of 13Cn.m.r. parameters from studies on model compounds having been the tautomeric populations in purine adenine hypoxanthine 6-rnercaptopurine7 and others were quantitatively e~timated.~~ Prototropic tautomerism in the imidazole ring was examined together with lactam-lactim or thione-thiol tautomerism in the pyrimidine ring. Prototropic rearrangements in azoles have also been studied by Russian ~orkers.~~,~~ The importance of competing interactions with solvents is highlighted by the slow reaction of benzimidazole derivatives with acetone which affects the tautomeric eq~ilibriurn.~~ Tourwe et al. have made direct I3C n.m.r. observations upon the tautomeric equilibrium involving enamines and enamino-ketones; they were able to deduce the preferred conformation of the cyclohexanone enamine ta~tomer.~~ The more widely studied keto-enol equilibrium involving p -diketones has also received further at ten tion.’* A different sort of exchange namely fluxion in co-ordination compounds may be usefully studied by 13Ctechniques. Thus Howell et uLS9have examined isocyanide derivatives of tetracarbonylbis-(q-cyclopentadieny1)di-iron and were able to differentiate between derivatives which show fluxion and those which do not. They also demonstrated clear differences between CNR ligands which are bridging or terminally bonded. Studies of stable ionic species continue to be of importance. These are typified by Olah’s and references therein.By this technique Olah has been able to establish the non-classical nature of the secondary and tertiary 7-norbornenyl cations,60 and the technique is described in his recent book.6‘ Other relevant work 48 G. L. Asleson and C. W. Frank J. Amer. Chem. SOC.,1975,97,6246. 4p J. Gulbis and G. W. Everett J. Amer. Chem. SOC.,1975 97 6248. 50 C.Bied-Charreton B. Septe and A. Gaudemar Org. Mugn. Resonance 1975,7 116. 51 D. G. Davis and D. C. Tosteson Biochemistry 1975,14,3962. 52 T.Yokono,S. Shimokawa and J. Sohma J. Amer. Chern. SOC.,1975,97,827. 53 M.T. Chenon R. J. Pugmire D. M. Grant R. P. Panzcia and L. B. Townsend J. Amer. Chem. Soc. 1975,97,4627. 54 M. T. Chenon R. J. Pugmire D. M. Grant R. P. Panzcia and L. B. Townsend J.Amer. Chem. Soc. 1975,97,4636. 55 A. N. Nesmeyanov E. B. Zavelovich V. N. Babin N. S. Kochetkova andE. I. Fedin Tetrahedron,1975 31,1461. 56 A. N. Nesmeyanov E. B. Zavelovich V. N. Babin N. S. Kochetkova and E. I. Fedin Tetruhedron,1975 31,1463. s7 D. Tourwe,G. Van Binst S. A. G. de Graaf and U. K. Pandit Og. Mugn. Resonance 1975,7,433. 58 N. N. Shapet’ko S. S. Berestova G. M. Lukovkin and Yu. S. Bogachev Org.Magn. Resonance 1975,7 237. 59 J. A. S.Howell T. W. Matheson and M. J. Mays J.C.S. Gem. Comm. 1975,865. 6O G.A.Olah and G. Liang J. Amer. Chem. SOC.,1975,% 6803. 61 G. A. Olah ‘Halonium Ions’ Wiley New York 1975. Part (ii) Nuclear Magnetic Resonance Spectroscopy 15 includes studies of cyclopropenylium ions,62 xanthylium ions,l0 and uronium thiouronium and guanidinium The mutarotation of hexoses has been studied by examining the 13C n.m.r.spectrum of a-glucopyranose in D,O solution as a function of the concentration of added potassium hydroxide.& The titration shifts suggest that the results cannot be explained in terms of a simple ionization and a rapid equilibration between cyclic and acyclic ionized species is suggested (Scheme 1). The experiment shows clearly that the rate-determining step for the mutarotation is rotation around the C(H0H)-C(0)R bond in the acyclic form. OH OH CH20H HOo-Scheme 1 The use of 13C labels in arder to give mechanistic information is well established. Rees et al.65have used this technique to investigate the pyrolysis of 1,4-and 1,5- diphenyl-1,2,3-triazoles.Similarly the mechanism of formation of azepines from the reaction of dimethyl ace tylenedicarboxylate with 2-methylquinolines has been elucidated.66A 13C label arising from the methyl group of 2-methylquinoline or its 6-bromo-derivative is found at pgsition 10 or 11 of the azepino[ 1,2-a]quinolines formed in the reaction.This excludes a reaction pathway involving an ester shift but is entirely consistent with a route involving a spiro intermediate. Rummens et aZ.67have compared the utility of 13C and radioactive I4C labels as quantitative probes in scrambling studies. They examined 1,2-phenyl shifts in the reaction between labelled triphenylvinyl bromide and silver acetate. Both techni- ques proved useful but the radiotracer method gives greater precision.In a similar study Oka and Lee68 have used the 13C scrambling label technique for the acetolysis and trifluoroacetolysis of triani~yl[2-~~C]vinyl bromide. The modification of horse-heart cytochrome c by carboxymethylation has been studied using [2-13C]bromacetate. The 13C n.m.r. spectrum clearly reveals that the protein is much more extensively changed than previously In a some- what more detailed study amino-acid side-chains have been derivatized with a 62 E. V. Dehmlow R. Zeisberg and S. S. Dehmlow Org. Magn. Resonance 1975,7,418. H. 0.Kalinowski and H. Kessler Org. Magn. Resonance 1975,7 128. 64 G. de Wit A. P. G. Kieboom and H. van Bekkum Tetrahedron Letters 1975,3943. 65 T. L. Gilchrist C. W. Rees and C.Thomas J.C.S. Perkin I 1975,8. 66 R. M. Acheson and R. F. Flowerday J.C.S. Perkin I 1975 394. 67 F. H. A. Rurnmens R. D. Green A. J. Cessna M. Oka and C. C. Lee Canad.J. Chem.,1975,53,214. 68 M. Oka and C. C. Lee Canad. J. Chem. 1975,53,320. 69 R. T. Eakin L. 0.Morgan and N. A. Matwiyoff Biochemistry 1975,144538. 16 L.Phillips variety of 13C-labelled ele~trophiles,~" namely acrylonitrile 3-bromopropionic acid acrylamide iodoacetic acid and methyl iodide. The technique involves blocking the N-terminus as a t-butoxycarbonyl derivative and the C-terminus by esterification; the side-chain is then electrophilically labelled. With the amino-acids cysteine lyseine histidine and serine there are sufficient differences in the chemical shifts of any one of these labels that they may be used as probes for these acids in enzyme active sites.13 C N.m.r. is a very convenient method of locating deuterium labels since replacement of 'H by 2Hconsiderably increases the spin-lattice relaxation time (Tl) of a bonded I3Cnucleus and reduces the nuclear Overhauser enhancement (NOE) obtained on 'H spin decoupling. This effectively removes the 13Cresonance line from the spectrum under normal conditions. In this way Hanson and Siverns71 have located the site of deuteriation in the aromatization reaction used to synthesize methyloestratrienes. This has enabled a differentiation between two possible reac- tion pathways. Biosynthesis.-The incorporation of I3C labels during biosynthesis continues to be an area of great importance.There have been many studies utilizing singly labelled precursors. For example acetate (labelled 1 or 2) has been used to elucidate the biosynthesis of fusi~occin,~~ aflatoxin B,73leucomycin A3,74 and sterigrnat~cystin.~~ [1-13C]-Pr~pionate and -butyrate have been incorporated into leucomycin A3,74 and [4-'3C]mevalonate has proved a useful precursor for oleanene and ursene-type triterpene~.~~ has been incorporated into chl~ramphenicol~~ [6-13C]-~-GI~~~~e and streptomycin.78 The major development in this field has been the increased use of doubly-labelled precursors including [1,2-13C2]acetate,73*74*7y-87 and [1,3-13C2]phenylalanine,88.89 [1,4-13C2]succinate.76 Last year's Report emphasized that doubly-labelled tracer studies could be difficult to interpret quantitatively because I3C-l3C dipolar relaxa- tion could be important for quaternary carbonsgo and cause intensity anomalies.70 I. J. G. Clunie D. A. Evans and M. Akhtar J.C.S. Chem. Comm. 1975 160. 71 J. R. Hanson and M. Siverns J.C.S. Perkin I 1975 11 10. 72 K. D. Barrow R. B. Jones P. W. Pemberton and L. Phillips J.C.S. Perkin I 1975 1405. 73 P. S. Steyn R. Vieggaar P. L. Wessels and D. B. Scott J.C.S. Chem. Comm. 1975 193. 74 S. Omura A. Nakagawa H. Fakeshima K. Atusmi J. Myazawa F. Pirion and G. Lukacs J. Amer. Chem. Soc. 1975,97,6601. 75 K. G. R. Pachler P. S. Steyn R. Vleggaar and P. L. Wessells J.C.S. Chem. Cornm. 1975 355. 76 S. Seo Y. Tomita and K. Tori J.C.S. Chem. Comm. 1975 270. 77 M. H. G. Munro M. Taniguchi K.L. Rinehart and D. Gottlieb Tetrahedron Letters 1975,2659. 78 M. H. G. Munro M. Taniguchi and K. L. Rinehart J. Amer. Chem. SOC.,1975,97,4784. 79 R. C. Paulick M. L. Casey D. F. Helenbrand and H. W. Whitlock J. Amer. Chem. SOC. 1975,97,5303. 8o A. G. McInnes D. G. Smith J. A. Waiter L. C. Vining and J. L. C. Wright J.C.S.Chem. Comm. 1975 66. 81 T. J. Simpson and J. S. E. Holker Tetrahedron Letters 1975,4693. 82 F. C. Baker C. J. W. Brooks and S. A. Hutchinson J.C.S. Chem. Comm. 1975 293. 83 S. Seo Y. Tomita and K. Tori J.C.S. Chem. Comm. 1975 954. 84 J. Bolonsky G. Lukacs N. Cagnoli-Bellavita and P. CeccherelIi Tetrahedron Letters 1975,481. 85 J. S. E. Holker and K. Young J.C.S. Chem. Comm. 1975 525. 86 A. J. Birch T. J. Simpson and P. W. Westerman Tetrahedron Letters 1975 4173.87 R. E. London N. A. Matwiyoff V. H. Kollman and D. D. Mueller J. Magn. Resonance 1975,18,557. E. Leete N. Kowanko R. A. Newmark L. C. Vining A. G. McInnes and J. L. C. Wright Tetrahedron Letters 1975 4103. 89 E. Leete N. Kowanko and R. A. Newmark J. Amer. Chem. SOC. 1975,97,6826. 90 C. G. Mcxeiand and F. I. Carroll J. Magn. Resonance 1974 15 596. Part (ii) Nuclear Magnetic Resonance Spectroscopy 17 Additionally if the C-resonances are close together the tightly coupled spin system also causes intensity errors to arise in F.T. spectra." Matwiyoff et alqg7 have recently pointed out that singlet (ie. non-coupled) and multiplet resonances will have differentNOE's which can also lead to incorrect enrichment values if the effect is not taken into account.These same workers have made a thorough investigation into the anomalies caused by the ~plittings.~~ They point out also that 13C-13C coupling extends the value of 13C enrichment as a biosynthetic tool in several ways namely (i) as an aid to spectral assignment (ii) as an indicator of dilution of the labelled substrate by unlabelled material (iii) by giving information about intermediate steps in the biosynthesis from the 13C-13Cspin-spin multiplet pattern (iv) where equivalent carbons occur giving rise to a single resonance they may not be labelled equivalently by a biological system; the differential labelling may be studied by observing splitting of adjacent carbon resonances. These aspects are illustrated using labelled carbohydrates to study glycolysis.In contrast in a study of the biosynthesis of bikaverin it was necessary to remove the '3C-*3Csplitting by homonuclear spin decoupling." This overcame the difficulties caused by low 13C incorporation of [1,2-'3CJacetate and enabled the assembly pattern of the precur- sor units in the metabolite to be established In an attempt to ensure equal relaxation rates of 13C coupled and non-coupled resonances Paulick et al.79have used the so-called 'shiftless relaxation reagent' Cr(acac) in their study of the biosynthesis of islandicin from [1,2-'3CJacetate. They were able to differentiate successfully between two alternative pathways by this technique. Following their earlier study of incorporation of [4-13C]mevalonate into oleanene and ursene-type triterpenes (in which they were able to verify Ruzicka's hypothesis for cyclization of squalene-2,3-oxide as the mechanism for formation of the pen- tacyclic triterpene~),~~ Seo at al.have used [1,2-"C;]acetate to elucidate the biosynthesis of ring E in these compounds. The difficult assignment of the relevant spectra was carried out with the aid of lanthanide-induced shifts and this paper corrects an earlier as~ignment.~~ Usually in a double-labelling study it is an alI-or-nothing situation. The directly bonded 13C-13C coupling from the precursor is either retained in the metabolite or is lost. Simpson and Holker however observe the 2J(C,C)values which arise from cleavage and re-assimilation of the fragments of [1,2-13CJacetate in the biosynthesis of a pyrone metabolite of Aspergillus melleus.This is mechanisti- cally useful and is the first example of detection of such a coupling from biosynthetic rearrangement of a doubly labelled precursor. 2J(C,C)is a parameter which has sometimes been observed due to high incorporation of [1-13C]acetate(e.g.ref. 94) and has been seen as a result of an intramolecular rearrangement of [2,11- 13 CJporphobilinogen during protoporphyrin bio~ynthesis.~~ A neat reversal of this occurs when labels in a 1,3 configuration are rearranged during biosynthesis to a 1,2 relationship. The unmistakable directly bonded cou- pling appears in the metabolite and demonstrates a point of mechanism. Leete et al. S. Schaublin A. Hohener and R.R. Ernst J. Magn. Resonance 1974,13 196. q2 R. E. London V. H. KoIlman and N. A. Matwiyoff J. Amer. Chem. Soc. 1975,97,3565. 93 S.Seo Y.Tomita and K. Tori Tetrahedron Letters 1975,7. D. P.H.Hsieh J. N. Seiber C. A. Reece D. L. Fitzell S. L. Yang J. I. Dalezios G. N.La Ma,D. L. Budd and E. Motell Tetruhedron 1975,31,661. 95 A. R. Battersby E. Hunt and E. McDonald J.C.S. Chem. Cornrn. 1973,442. 18 L. Phillips have used [1,3-13CJphenylalanine to demonstrate such a rearrangement in the biosynthesis of tenellins* and tropic acid.89 The determination of relative signs of 'J(CC) in doubly labelled compounds is of some consequence and has been demonstrated by Hansen et ~1.~~ Selective TIMeasurements.-13C Spin relaxation is the subject of Chapter 3 in ref.1. This provides an excellent background to both theory and practice and is mainly concerned with longitudinal or spin-lattice relaxation characterized by the time constant Tl. Levy and Peat have considered the experimental aspects of Tl measurement for 13C nuclei in some detail.97 They compare and contrast the saturation recovery inversion recovery and partial saturation techniques. In addi- tion they provide a useful discussion about the influence of sample geometry sample state transmitter r.f. pulse power computer and data-processing characteristics instrument gain and stability and magnetic field homogeneity. An earlier paper by the same considers the different experimental approaches in greater detail and describes a technique which greatly shortens the length of time required for measurements by the inversion recovery technique.This 'Fast Inversion Recovery Fourier Transform' method (FIRFT) uses the conventional [180"-~-90"-(FID)-T] sequence but with an arbitrary short interval Tbetween the sequences. Normally T is 5( Tlma)and is a limitation of the usefulness of the method; with a much smaller T (which is nevertheless long enough to allow the decay of tranverse magnetization before application of the next 180" pulse) the speed of the other methods may be achieved. In the same context a fast non-linear least-squares method for calculating TIhas been described.99 This also uses short repetition times T,and since it obviates the necessity for determining S (the intensity of lines in a fully relaxed spectrum) it offers considerable savings of time.Perhaps the most widespread use of 13C Tl measurements is in the study of mobility in large molecules particularly in alicyclic species. loo An examination of n-alkyltrimethylammonium halides with polar substituents in the chain demon- strates that molecular motion is reduced in the region of the substituent.lol A study of NOE and Tl values in zinc and nickel insulin as well as in the metal-free system has been carried out using 90% 13C-enriched carbonyl groups attached to A1 glycine B1 phenylalanine and B29 lysine. The state of aggregation of the molecules is revealed by the correlation times for overall tumbling while the correlation times for internal rotation of the carbonyl functions indicate the relative mobilities of their local environments.lo' Deslauriers et al. have examined the conformational properties of cyclic dipep- tides,lo3 the octapeptide hormone [5-isoleucine]angiotensinII,l@' and the conforma- tional flexibility of luteinizing-hormone-releasinghormone (LH-RH) lo' in aqueous 96 P. E. Hansen 0.K. Poulsen and A. Berg Org. Magn. Resonance 1975,7,405. 97 G. C. Levy and I. R.Peat J. Magn. Resonance 1975,18,500. 9a D. Cault G. C. Levy and I. R.Peat J. Magn. Resonance 1975,18 199. 99 D. L.De Fontaine D. K. Ross,and B. Ternai J. Magn. Resonance 1975,18 276. 100 G. C.Levy,R.A. Komoroski and R.E. Echols Org. Magn. Resonance 1975,7,172. 101 J. M.Brown and J. D. Schofield J.C.S. Chem. Cbmm. 1975,434. 102 J. J. Led D. M.Grant W. J. Horton,F. Sundby and K. Vilhelmsen J. Amer. Chem. SOC.,1975,97,5997. 103 R.Deslauriers Z.Gozonka K. Schaumberg T. Shiba and R.Walter J. Amer. Gem. SOC.,1975,97 5093. 104 R.Deslauriers A.C. M. Paiva K. Schaumberg and I. C. P. Smith Biochemistry 1975,14,878. 105 R.Deslauriers G. C. Levy W. H. McGregor D. Sarantakis and I. C. P. Smith Biochemistry 1975,14 4335. Part (ii) Nuclear Magnetic Resonance Spectroscopy 19 solution at various pH values. In this latter work Ti's are evaluated for all hydrogen-bearing carbons at both 25.2 and 67.9 MHz. LH-RH is shown to be a flexible molecule in solution with segmental motion along the backbone as well as in the non-aromatic side-chain. This is one of the rare determinations of 13C Tl's at 67.9 MHz and in another paper Levy sounds a note of caution concerning interpre- tation of such data for unsaturated carbons not bonded to hydrogen.lM At such high field-strength the chemical shift anisotropy mechanism for relaxation becomes import ant .Adenosylcobalamin and alkylcorrinoids selectively enriched with 13C have been examined.lo7 The Tl values of the CH2 carbons of [5-13C]adenosylcobalaminand [2-'3C]carboxymethylcobalamin are similar to that of the methine bridge carbon (C-10) of the corrin ring indicating severely restricted rotation around the C-Co bond. The rotation about the Co-Co bond of methylcobalamin appears to be rapid however. The motional properties of biological macromolecules are conveniently studied by the Tl method. By using 13C enrichment of the oleic acid chains in whole virions it has been possible to investigate their mobility directly.lo8 Examination of the temperature dependence of Tl for 13C nuclei in some fractionated membrane^'^^ has enabled activation energies (-15-24 kJ mol-') for the C-C bond rotations to be evaluated. The details of segmental motion of the chains in these membranes have been elucidated.lW Lyerla and Torchia have studied molecular mobility in elastin' lo and collagen molecules. '11 The determination of the anisotropy in the motion of a molecule in solution gives useful structural information. Roberts et al. have described a computer program to calculate the rotational diffusion tensor for anisotropic motion from 13C T1data."' They show an application to methyl-substituted cycloalkanes and conclude that the degree of anisotropic motion decreases with increasing ring size.A similar study on androstane and cholestane confirms that the preferred axis of rotation in the anisotropic tumbling of these molecules in solution is the 'long' steroid This is shown by the fact that all CH and CH2 carbons except C-3 which is on the axis have the same Tl within experimental error. The correlation times for internal rotation of the C-18 and C-19 methyl groups depend upon the number of 1,3- diaxial methyl-H interactions and so C-19 has a longer Tl than C-18 in androstane. In trans-cholestanol C-19 has a longer TI than in either cis-cholestanol or choles- ter01.l~~ In an important and elegant piece of work Freeman et al.'14 have used motional anisotropy as a probe for transient complex formation in solution.They point out that even transient association alters the degree of motional anisotropy of a molecule by a significant amount. The tumbling rate of an associated pair of molecules is loci G. C. Levy and U. Edlund J. Amer. Chem. Soc. 1975,97,5031. lo' H.P.C. Hogenkamp R. D. Tkachuch M. E. Grant R. Fuentis and N. A. Matwiyoff Biochemistry, 1975,14,3707. lo8 W.Stoffel and K. Bister Biochemistry 1975,14 2841. log R.E.London V. H. Kollman and N. A. Matwiyoff Biochemistry 1975,14,5492. 110 J. R.Lyerla and D. A. Torchia Biochemistry 1975,14 5175. D.A. Torchia J. R. Lyerla and A. J. Quattrone Biochemistry 1975 14 887. 11* S.Berger F.R. Kreissl D. M. Grant and J.D. RobertsJ. Amer. Chem. Soc. 1975,97,1805. 113 J. W.Apsimon H. Beierbeck and J. K. Saunders Canud. J.Gem. 1975,53 338. 114 I. D.Campbell R. Freeman and D. L. Turner J. Mugn. Resonance 1975,20,172. 20 L. Phillips slower than that of the discrete species about an axis perpendicular to the direction of the 'bond' between them. The change in the rotational diffusion tensor may be conveniently followed by 13C Tl measurements. Transient complexes whose lifetimes exceed the correlation time for end-over-end rotation (typically lo-'' s) may be observed in this way. The approach is illustrated for hydrogen-bond formation in a molecule which does not self-associate but forms a hydrogen bond with a second species and thereby acquires anisotropic motion.Changes in the ratio of the Tl values of the carbons in this molecule (termed a 'Motional Anisotropy Probe') give a sensitive test for the size and shape of the complex. A good example is pyridine in which C-2 C-3 and C-4 all have equal Tl values in the neat liquid or in CCI solution. Addition of a hydroxyl-containing compound causes the axis of fastest rotation to be coincident with the N * H-0 bond direction and C-2 and C-3 retain equal Tl while that of C-4 is shortened. The spin-lattice relaxation of protons has been used to study fast proton exchange in aqueous ~olution~,"~ but its main use to date appears to be as a conformational mobility probe. A study of thermally unfolded ribonucIease A' l6 concentrates upon the four histidine residues.Two of these are exposed to solvent interactions [His-48 and (tentatively) His-1051 while two remain in regions of residual (ie. folded) structure [His-12 and (tentatively) His-1191. Rowan and Sykes'l7 have examined the conformational behaviour and flexibility of the polyene chains in retinals using this technique and other workers have studied the conformational dynamics of nicotinamide adenine dinucleotide and nicotinamide mononucleotide.' '* The effect upon 'H Tl values of replacing neighbouring protons by *H1 and thereby removing the dominating dipolar-relaxation mechanism from the system has been put to good use. Akasaka et a[. have christened this technique DESERT (DEuterium Substitution Effect on Relaxation Times) and have used it to estimate inter-hydrogen distances in 2',3'-isopropylidene-3,5'-cycloguanosine whose con- formation is fixed and to study syn-anti conformational equilibria in 2',3'- isopropylidene-adenosine adenosine and 5'-adenosine m~nophosphate."~ Specifically deuteriated L-malate has been used in a study of the aspartate trans- carbamylase catalytic site.'20 Spin-lattice relaxation in the presence of paramagnetic ions has received some attention.The use of Cr(acac) to ensure equal relaxation times of all carbons in a complex molecule (e.g. ref. 79) is not without its difficulties. Levy and Edlund'*' have pointed out that the highly efficient directly bonded 13C-'H dipole-dipole relaxation mechanism can compete successfully with the electron-nuclear spin relaxation due to the paramagnetic CrI'I.The suppression of the NOE in the 'H decoupled spectrum may be incomplete and variable and the spectrum may actually degrade as a result. This work examines the 13C Tl values of cholesteryl chloride at 67.5 MHz and shows that as much as 60% of the relaxation of C-5 (non-hydrogen 115 S. Waelder L. Lee and A G. Redfield J. Amer. Chem. Soc. 1975,97,2927. 116 C. R. Matthews and D. G. Westmoreland Biochemistry 1975,14 4532. 117 R. Rowan and B. D. Sykes J. Amer. Chem. SOC. 1975,97,1023. 118 A. P. Zens T. J. Williams J. C. Wisowaty R. R. Fisher R. B. Dunlop T. A. Bryson and P. D. Ellis J. Amer. Chem. Soc. 1975,97,2850. 119 K. Akasaka T. Imoto S. Shibata and.H. Hatano J. Magn. Resonance 1975,18,328. H. I. Mosberg P. G. Schmidt and S. S.Seaver J. Magn. Resonance 1975,20,82. 121 G. C. Levy and U. Edlund J. Amer. Gem. SOC.,1975,97,4482. Part (ii) Nuclear Magnetic Resonance Spectroscopy 21 bearing olefinic carbon) arises from the chemical shift anisotropy mechanism. 12' In another paper'22 these workers suggest that Cr(dpm) is a more suitable TI-equalizing reagent than Cr(acac),. It is more intert towards organic substrates and produces no observable contact shifts. Cr(acac) actually causes shifts as large as 0.64 p.p.m. for CDC13 and up to 0.4 p.p.m. with nitrogen-containing aromatic From an examination of Tl for 13C nuclei in histidine complexed to paramagnetic Mn" it has been possible to calculate the precise distances between the metal and the carbon atoms in the ligand. These correspond closely to the distances determined in the X-ray crystal structure of the analogous Ni" complex and it is claimed that the structural parameters are comparable in accuracy to X-ray data.124 It has been possible to locate the Ca2' ion binding site in bovine a-and p-trypsin using the relaxation effects of Gd3+ as a probe in metal-inhibitor-trypsin ternary complexes.It is established that Ca2' and Gd3' compete for the same It should not be imagined that paramagnetic species are able to shorten TIof all nuclei. Because of the overwhelming importance of quadrupolar as opposed to dipolar relaxation for 2H a concentration of a paramagnetic species which reduces Tl of 'H in 'H20 by a factor of CQ. 400 will only shorten Tl of 2H,0 by a factor of 3 High-field N.M.R.Studies of 'H Resonance One of the major limitations upon the usefulness of 'H n.m.r. in biological systems has been the narrow range of chemical shifts. This leads to overlapping lines and tightly-coupled spin systems which do not yield easily to analysis. The use of high fields from superconducting magnets has overcome some of these difficulties and although the studies may be of a somewhat routine spectroscopic nature they are important in terms of the results that are now achievable. The 'H n.m.r. spectrum of bovine pancreatic trypsin inhibitor has been examined at 250MHz and all proton resonances of the aromatic rings of the four tyrosine residues have been located and assigned.127 pH titration enables the pK of each of the tyrosines to be measured and a similarly successful study was carried out with mono- and di-nitrated derivatives.The polypeptide antibiotic N-methyl-leucine gramicidin-S dihydrochloride has been examined at 220 MHz and all resonances have been assigned to the specific hydrogens of the constituent amino-acid frag- ments. ,J(H,H) (across C-N bonds) and chemical shifts give conformational information.12' The ability of high fields to spread out 'H n.m.r. spectra makes available new conformational information. Thus fragments from the anticadon loop of baker's yeast phenylalanine transfer ribonucleic acid have been examined in this way.'29 The 270 MHz spectrum of Histone H2A shows variations with ionic strength and pH lz2 G. C. Levy,U. Edlund and J. G. Hexem J.Magn. Resonance 1975,19,259. lz3 P. M. Henricks and S. Gross J. Magn. Resonance 1975,17 399. lZ4 J. J. Led and D. M. Grant J. Amer. Chem. SOC.,1975,97,6962. F. Abbott J. E. Gomez E. R. Birnbaum and D. W. Darnall Biochemistry 1975,14,4935. 126 J. Wooten G. B. Savitzky and J. Jacobus J. Amer. Chem. SOC. 1975,97 5027. G. H. Snyder R. Rowan S. Karplus and B. D. Sykes Biochemistry 1975,14,3765. N. G. Kiemar N. Izumiya N. Miyoshi H. Sugano and D. W. Urry Biochemistry 1975,14,2197. lz9 L. S. Kau P. 0.P. Ts'o F. von der Haar M. Sprinzl and F. Crarner Biochemistry 1975,14,3278. 22 L.Phillips which suggest that an equilibrium exists between largely unstructured coiled molecules and fully structured aggregated molecules. 13* Similar studies of histone IV and some fragments derived by cyanogen bromide cleavage have been reported.l3','32 Markley has used difference spectra at both 100 and 250 MHz to reveal a pH-dependent conformational change in ribonuclease A which affects only the chemical shift of a single tyrosine residue.133 This conformational change is absent in ribonuclease S and is changed in ribonuclease A by the presence of either acetate or cytidine 3'-monophosphate. Prior to this investigation it was necessary to reassign the 'H n.m.r. spectrum of the histidine residues in the ribonuclea~e;'~~ Bradbury and Seng Teh have independently arrived at the same conclusion.'35 Thermally induced conformational transitions have been monitored by the high- field 'Hn.m.r. method. By examining the 300MHz spectrum of the non-exchangeable purine and pyrimidine resonances together with the sugar resonances in a D20 solution of d-ApTpGpCpApT the helix-coil transition has been observed.136 The sequential thermal unfolding of valine transfer RNA has similarly been st~died.'~' The ability of this technique to elucidate minute details of structure is well illustrated by the binding of ethidium bromide to yeast tRNAPhe.At 300 MHz it is possible to observe that just two ring NH protons have moved on complexation; this uniquely determines the binding site as located between the base pairs AU6 and AU of the amino-acid receptor Application and Development of the FTTechnique Perhaps the most remarkable development has been that of 'Zeugmatographic High Resolution N.M.R.Spectroscopy'. 139-141 N.m.r. signals arising from samples subject to magnetic field gradients may be used to produce two- and three- dimensional images of the object from which they arise. The technique has recently been extended by Lauterbur et~Z.'~* and by Ernst A magnetic field gradient is imposed on the sample during a radiofrequency pulse causing resonance to occur only in a limited region. The gradient is then removed and the FID of the remaining transverse magnetization in the selectively excited region is Fourier-transformed. Repetition of this sequence with a slight change in the magnetic field or radiofre- quency gives information from other sections of the sample. The information may then be assembled to give one- two- or three-dimensional images of the distribution of resonating material in the sample.Chemically shifted species may be brought into 130 E. M. Bradbury P. D. Cary C. Crane-Robinson H. W. E. Rattle M. Boublik and P. Sautiere Biochemistry 1975,14 1876. 131 A. E. Pekary H. J. Li S. I. Chan C. J. Hsu and T. E. Wagner Biochemistry 1975,14 1177. 13* A. E. Pekary H. J. Li S. I. Chan C. J. Hsu and T.E. Wagner Biochemistry 1975,14 1184. 133 J. L. Markley Biochemistry 1975,14 3554. 134 J. L. Markley Biochemistry 1975,14,3546. 135 J. H. Bradbury and J. Seng Teh J.C.S. Chern. Comm. 1975,936. 136 D. J. Patel Biochemisrry 1975,14 3984. 137 R. V.Kastrup and P. G. Schmidt Biochemistry 1975,14,3612. 138 C. R. Jones and D. R. Kearns Biochemisfry,1975,14,2660. 139 P.C. Lauterbur Nature 1973.242 190. 140 P. C. Lauterbur PureAppl. Chem. 1974,40 149. 141 W. S. Hinshaw Phys. Letters (A) 1974,48 87. 142 P. C. Lauterbur D. M. Kramer W. V.House and C.-N. Chen. J. Amer. Chem. Soc. 1975,97,6866. 143 A. Kumar D. Welti. and R. R. Ernst J. Magn. Resonance 1975,18 69. Part (ii) Nuclear Magnetic Resonance Spectroscopy 23 resonance individually and the distributions of different materials in an object may be separately examined. It is hoped that there will be useful biological applications such as the differentiation between fat and other tissues in organisms'42 or the examination of the binding of water in biological systems and the differentiation of malignant and normal cells.'43 An exciting development has been the combination of stopped-flow techniques with FT n.m.r.to give spectra of intermediates in moderately fast chemical reactions (half-life greater than ca. 0.15 s typically of the order of seconds). Grimaldi and Sykes have Fourier difference spectro~copy'~~ to detect the weak resonances of the intermediate species in the presence of strong unwanted resonances. They describe a variety of pulse techniques for obtaining stopped-flow FT spectra and discuss in some depth the capabilities of the method. The technique has been applied to the observation of transient intermediates in the tricyanovinylation of NN-dimeth~laniline,'~~ and in the reaction between tris(pentane-2,4-dionato)Co1"and N-chlorosuccinimide.'47 By a somewhat related method Fyfe et al. have directly studied chemical reactions in flowing liquids.14* They have obtained information on intermediates in the reaction between methoxide and l-X-3,5-dinitrobenzenes (X= CN CF, C02Me or C0,Et). The development of double-resonance methods in FT n.m.r. continues. An improved method of completely decoupling ['aspins from I3C has been described,'49 which is claimed to be much more effective than random-noise decoupling giving signal :noise improvements by a factor of two or more. Phase modulation of the decoupler carrier wave with a 50% duty-cycle square wave brings about the bandwidth necessary for broad-band coupling. The combination of double irradiation and a simple two-pulse spin-echo sequence is a powerful method for detection of homonuclear decoupling in complex spectra.150 A 90°-r-1 80"sequence refocuses phase loss due to inhomogeneity and forms an echo at a time 27after the 90"pulse; data are then acquired. Non-selective pulses affect all spins equally and dephasing due to spin-spin coupling is not refocused and the phase loss follows a precise pattern e.g. at a time 1/Ja fist-order doublet of separation J Hz is inverted. Singlets and the central components of triplets do not change phase but outer components are inverted at time 1/2J. If selective double irradiation is applied during the period between the 90" pulse and the start of data acquisition the multiplicity and hence the phase of coupled resonances changes and gives a sensitive method of detection of the phen~rnenon.'~~ This technique is related to methods described earlier for the detection of coupling by 'FTINDOR-like' experi- ments (e.g.refs. 151-153) which have recently found application^."^'^^ 144 J. J. Grimaldi and B. D. Sykes J. Amer. C'hem. Soc.,1975,97 273. 145 R. R. Erst J. Map. Resonance 1971,4,280. 146 M. J. T. Robinson and S. M. Rosenfeld Tetrahedron Letters 1975 1431. D. A.Couch 0.W. Howarth and P. More J.C.S. Chem. Cumm. 1975,822. 14* C. A.Fyfe M. Cocivera and S. W. H. Damji J. Amer. Chem. Soc. 1975,97,5707. 149 J. B.Grutzner and R. E. Santine J. Magn. Resonance 1975,19 173. I5O I. D.Campbell and C. M. Dobson J.C.S. Chem. Comm. 1975,750. J. Feeney and P. Partington J.C.S. Chem. Comm. 1973,611. 152 K. G. R. Pachler and P. L. Wessels J.C.S. Chem. Comm. 1974 1038.Is3 Refs. 156-162 of ref. 14. 154 G. Massiot S. K. Kan P. Gouord and C. Duet J. Amer. Chem. Soc. 1975,97 3277. 155 T.Bungaard and H. J. Jakobsen J. Magn. Resonance 1975,18,209. Is6 K.Kushida K. Aoki and S. Satoh J. Amer. Chem. Soc. 1975,97,443. 14'

ISSN:0069-3030    

DOI:10.1039/OC9757200010

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

2 Physical Methods Part (iii)X-ray Crystallography By M. B. HURSTHOUSE ChemistryDepartment Queen Mary College Mile End Road London El 4NS S. NEIDLE BiophysicsDepartment King’s College 2629Drury Lane London WC2B5RL Since the end of 1973 over 2000 organic structural papers have appeared. Some of these structures are described in other chapters of this and the 1974 Report; references to virtually all structures published can be found in ‘Molecular Structures by Diffraction Methods’’ and ‘Molecular Structures and Dimensions’.2 It is therefore our intention in this short contribution to report on recent developments in the processes of structure determination by X-ray methods and also on work which can best be described as ‘applied structure analysis’ i.e.use of crystal structure data for purposes other than molecular structure identification. One development which has arisen out of the availability of accurate X-ray data is the study of electron-density distributions in molecules. Coppens has outlined3 the implication of combined X-ray and neutron diffraction studies of bonding and lone-pair electron distributions and the results of such a study have been described for the molecule 1,3,5tria~etylbenzene,~ and compared with charge populations determined from semi-empirical calculations. Suitable modifications to the struc- ture refinement process can lead to the same information just with the use of X-ray data as has been shown for 3,6-dimethyl-S-thioformyl pyrrolo[:,l-b ]thiazole+ and tetracyanocyclobutane;b in the latter the polarities of the C-H bond and C=N group have been determined.The development of direct methods of structure analysis in which the phases needed for the correct synthesis of the crystal structure image are determined by building up relationships between them so that assignment of a few key phases leads to estimates for many has been of great importance for organic structures almost eliminating the need to make heavy-atom derivatives. ‘Molecular Structures By Diffraction Methods’ ed. L. E. Sutton and G. A. Sim (Specialist Periodical Reports),The Chemical Society London,1975 Vol. 3. ‘Molecular Structures and Dimensions’ Crystallographic Data Centre Cambridge University. 3 P.Coppens Acta Cryst. 1974 B30,255. B. H. O’Connor and E.N. Maslen Am Cryst. 1974 B30,383. A. Sharrna and R.C. G. Killean Acca *st 1974 B30,2869. 6 M. Hare1 and F.L. Hirshfield Actu Cryst. 1975 B31 162. 24 Part (iii) X-Ray Crystallography The solution of small and medium-sized (i.e.up to 50 atoms per asymmetric unit) ‘equal-atom’ (i-e. atoms of similar atomic number) crystal structures by well-established direct methods is now often a routine procedure. Indeed the ‘symbolic- addition’ method of phase determination which can be applied without the use of a computer has had some remarkable successesin the hands of skilled practitioners; for example the analysis’ of the cyclic dodecadepsipeptide valinomycin involved 156independent non-hydrogen atoms and is probably the largest structure solved by direct methods to date.However many structure analyses still pose problems and improvements and new developments are still being sought. Hauptmann,’ Schenk,’ and others have evolved a promising approach based on quartets of related reflec- tions rather than the triplets of ‘classical’ direct methods. Quartets seem to be a more reliable means of phase determination judging from the few applications which have been made so far. They have also been shown to be especially useful when in the form of negative quartets,” in which very weak reflections are utilized being particularly powerful in discriminating between correct and incorrect phase sek1 Woolfson and his collaborators have recently developed the concept of ‘magic integers’12” by means of which several unknown phases may be represented by a single symbol thus enabling a large number of phase sets to be developed.This technique has been successfully employed in the analysis12b of cephalotaxine which had previously resisted attempts at solution by conventional direct methods. Over the past few years an increasing amount of attention has been paid to the idea ofstructure-solving via crystal-packing considerations. In part these techniques have been developed as alternatives to direct methods and have been particularly useful in cases where special features of the molecular geometry have upset the phasing processes in the direct method approach. In addition however the depen- dence of these techniques on calculations of lattice energies using semi-empirical potential energy functions for the various ‘non-bonded’ interatomic interactions present has also led to the development of methods applicable to the calculation of conformations of individual molecules.For example in the structure analysis of guanosine- 3’,5’-cytidine monophosphate the most probable molecular conf orma- tion was first computed and then used as the basis for the packing search. This was also restricted by known constraints from the X-ray data (e.g. unit cell parameters space group position of the phosphorus atom orientations of the bases) and by inclusion of a geometric function which imposed Watson-Crick base-pairing. During the caIculations an interactive computer graphics system was used for visualizing the calculated structures.The structure of the rigid molecule spirodienone (1)was also determined by a visual packing analysis coupled with the minimization of repulsive energies.l4 I. L. Karie J. Amer. Chem. Sac. 1975,97,4379. H. Hauptmann Acra Crysf.,1974 AM 822. H. Schenk Actu Cryst. 1974 AM,477. lo H. Hauptmann Acra Cryst. 1974 AM,472. G. T. De Titta J. W. Edmonds D. A. Langs and H. Hauptmann Acru Cryst. 1975 A31,472. l2 (a) P. S. White and M. M. WooIfson,Acta Crysf.,1975 A31,53;(b)J. f.Declerq G. Germain and M. M. Woolfson ibid. p. 367. l3 S. D. Stelfman,B. Hingerty,S. B. Broyde,E. Subramanian T. Sato and R. Langridge,Biopolymers 1973 12 2731. l4 B. S. Hass T. V. Willoughby C. N. Morimoto D. L. CuIlen and E. F. Meyer Acru Cryst. 1975 B31 1225. M.B.Hursthouse and S.Neidle In the structure determination of coumarin by potential energy calculations coupled with minimum residual analysis attempts were made to assess the relative importance of van der Waals and dipole-dipole interactions in deciding the actual packing minima.” The results suggest that in spite of the high (ca. 4.50 D) moment for the molecule dipole-dipole interactions do not seem to determine the packing. The success of the application of these studies to unknown structures depends on the availability of accurate energy parameters and of course these can be determined from known structures. Lifson et al. have outlined16” a procedure for determination of such parameters and have shown it to be applicable to other fields of conforma- tional analysis.The derivation of a consistent force field for amides by the fitting of parameters of various trial functions to such experimental data as heats of sublima- tion dipole moments and crystal-structure parameters has also been described.16’ A further ‘by-product’ of these studies has been the development of methods for representing molecular geometries and effecting changes in them. For example Mackay has described” how arbitrary combinations of bond lengths bond angles and torsion angles can be used as generalized co-ordinates for describing molecular models and how these and conventional Cartesian or fractional unit cell co-ordinates can be interconverted. In the ‘method of local change’ the computer manipulation of moleCular conformation is effected by movement of only one atom at a time giving considerable simplification of the programming required.l8 Also relevant to the study of molecular geometries and conformations derived from crystal structure analyses is the descriptionlg of a new computer program for the comparison of these features by a least-squares-fitting procedure for equivalent molecules or fragments found in different structural environments. Energy considerations are also involved in the study of strained molecules and a number of structure analyses have been reported in this area. The analysiszo of the two isomers of 2,3:6,7:2’,3’:6’7-tetrabenzoheptafulvalene(2)confirms an earlier assignment of the trans and syn isomers. Both are severely overcrowded and the strain is to some extent relieved by buckling of the non-alternant heptafulvalene ring as well as significant non-planarities of the phenylene rings.The overcrowded polycyclic aromatic hydrocarbon tetrabenzo[ a cd j lmlperylene (3)assumes a non- planar shape largely in order to relieve the overcrowding between C-2and C-30 and C-13 and C-19,which would otherwise be some 2.4 A apart instead of the 3 A separations observed.2’ In spite of the severe deformations the bond lengths still suggest a large measure of aromatic character for the molecule. *5 E. GavBzzo F. Mazza and E. Giglio Actu Cryst. 1974,B30,1351. l6 (a)A.T. Hagler and S. Lifson Acra Oysr. 1974 B30 1336; (b)A.T.Hagler E. Huler and S. Lifson J. Amer. Chem. Soc. 1974,% 5319. A.L.Mackay Actu Cryst.1974 A30,440. l8 J. Hermans jun. and J. E. McQueen jun. Actu Cryst. 1974 A30,730. l9 S.C.Nyburg Acra Cryst. 1974 B30,251. 2o K. S.Dichman S. C. Nyburg F. H. Pickard and J. A. Potworvorski Actu Cryst. 1974 B30,27. 21 Y.Kohno M. Konno Y. Saito and H. Inokuchi Acru Oyst. 1975 B31,2076. Part (iii)X-Ray Crystallography co The structure determination of l-methoxycarbonyl-5,7,12,14,16(4)-tetracyclo[9,2,2 14311,08*’6]hexadecapentaene (4) is of interest in that a simultaneous analysis of both quantitative strain-energy calculations and ‘Hand I3Cn.m.r. spectra was carried out.22 The molecule exhibits many of the characteristics of strained molecules such as long C-C single bonds. In a series of nine papers,23 Dunitz and Winkler have described studies on amide deformations in medium (7-12) ringlactams,and Iactam salts.The results compare quite well with those from force-field calculations on cyclo-olefins. An attempt was also made with some success to derive the form of the potential energy surface for amide-group out-of -plane deformations. Similar deformations but in carbonyl groups which arise out of short N * * C=O and 0 * * C=O contacts have also been and the correlation between the short contacts and the out-of-plane deviations is discussed in terms of incipient chemical reactions involving addition of a nucleophile to a carbonyl group and the reverse breakdown of the tetrahedral species produced. As in previous years many structural studies of biologically active molecules have been reported and of particular interest are studies from which details of the intermolecdar interactions provide some insight into the structure-activity relation- ships.Interactions between drugs possessing planar aromatic groupings and nucleic acid are of particular current interest. Two structures which model such systems have been reported with dinucleotide monophosphates mimicking the natural nucleic acids. In the complex between 9-aminoacridine and adenylyb3’,5‘-uridine the drug molecules stack between non-Watson-Crick base-pair~.~’ However in the ethidium-bromide-uridylyl-3‘,5’-adenosine the drug molecules interca- ~ompIex,*~ late between the Watson-Crick base-pairs of an unwound RNA double-helical fragment. Also in the biological field the first structure analysis of a phospholipid the synthetic compound 1,Z-dilauryl-D-p hosphatidylethanolamine (5) has been de~cribed.~’ The analysis has provided much detailed information relevant to the 22 E.Maverick S. Smith L. Kozerski F. A. L.Anet and K. N. Trueblood Acfa Cryst. 1975 B31,805. 23 J. D. Dunitz and F. K.Winkler Acta Crysf. 1975 B31,251 et seq. 24 H.B. Burgi J. D. Dunitz and E. Shefter Acra Cryst. 1974 BM,1517. 25 N. C. Seeman R.0.Day and A. Rich Nature 1975,253,324. z6 C. C. Tsai S. C. Jain and H.M. Sobell Roc. Nat. Acad. Sci. U.S.A. 1975,72,628. 2’ P.B.Hitchcock R. Mason K.M. Thomas and G. G. ShipIey,Roc. Nat. Sci. U.S.A.,1974,71,3036. M. B.Hursthouseand S. Neidle ' 0 II CH2 -O-C-(CH2) o-CH2 CH,-O-P-O-(CH2)2 -NH3+ I 0- (5) packing and conformation of lipids in both artificial and natural membranes; in particular the observed packing of phospholipid molecules is exactly that of the classic bilayer model.Finally mention is made of a group of three papersz8 describing a study of the reaction of solid crystalline aromatic carboxylic acids and related compounds with ammonia and amines. Generally the reaction proceeds anisotropically and the reactivities along the principal directions through crystals have been correlated with the crystal structures of the substrates in particular the arrangement of the reactive functions. 28 R.S. Miller D. Y.Curtin and I. C. Paul J. Amer. Chem. Soc. 1974,% 6329 6334,6340.

ISSN:0069-3030    

DOI:10.1039/OC9757200024

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

2 Physical Methods and Techniques Part (iv)Infrared and Raman Spectroscopy By G.A. NEWMAN Research Division Kodak Ltd. Harrow Middx. HA I 4 TY 1 htroduction It is surprising that this topic has never been reviewed in Anlsual Reports (B). This Report is concerned with highlights in infrared and Raman spectroscopy and their application to organic chemistry with the exclusion of metal-organic compounds over the years 1971-5. It is divided into separate sections on infrared spectroscopy and Ramar; spectroscopy the latter covering the Raman and resonance Raman effects only. It is not intended to be comprehensive. Where appropriate the relevant review papers are cited but workers should also consult the SpeciaIist Periodical Reports.' The references cited are where possible the most recent provided they contain therein key referencesto provide the readerwith retrospective coverage.2 Infrared Spectroscopy Remarkably infrared (i.r.) spectroscopy shows no sign of reaching a senescent phase. At a time when other spectroscopic techniquesare advancing,particularlyin areas of structural determination and analysis previously dominated by ir* the technique shows no sign of decline. The number of publications increased by nearly 20%in 1972-3. Excellent comprehensivereviewshave been published bi-annuaHy by McDonald;' the latest covering 1972-3 contained 856 references. Twogrowth areas are those applicationsmade possible when spectrometers are interfaced with computers and also the field ofenvironmental protection and control.To appreciate these recent developments advances in instrumentation are described. Instrumentation.-A clear indication of the state of health of i,r. spectroscopy is evident from the wide range of conventiona1 (dispersive) spectrophotometers available. These have been listed together with recent trends in de~ign.~ There is a tendency towards more automation and therefore simplicity of operation and the widespread provision of ordinate scale expansion(%T)of up to x 20 enables results to be obtained more easily in energy-limited situations such as microsampIing. 'MolecularSpectroscopy',ed. R. F.Barrow D. A. Long and D. J Millen (SpecialistPeriodical Reports), The ChemicaI Society London,1975 VoI. 3. R. S.McDonald Analyr. Chern. 1974,46,52lR.3 1. A. Degen and G. A. Newman Lab. *actice 1974,23,583,and 1976 in the press. 29 30 G.A.Newman In Fourier4 and Hadamard5,6 transform methods major advances have been made in instrumentation. In dispersive instruments a great loss in energy occurs when the sample and reference beams pass through entrance and exit slits. Both of the transform methods avoid or modify this approach. Furthermore since all wavelengths are detected simultaneously interferograms of the sample are collected rapidly. These two advantages are utilized in applications. A computer is essential to perform a Fourier transform (FT) on the interferogram; consequently many applications have appeared from users of FT instrument^.^ Griffiths has written a book on chemical i.r..FT spectroscopy.’ Although an interferometer is not essential many applications are difficult if not impossible without a computer.In micro~ampling~ the energy advantage is used together with the ability of the computer to store a spectrum and rapidly to multiscan the spectrum in the signal- averaging mode (CATting) so common in n.m.r. spectroscopy. It enables i.r. spectroscopy to break the 1pg barrier spectra having been obtained from samples as small as tens of nanograms! Work has also been reported on microsampling with dispersive Here the limit is about 10 pg and use is made of beam condensers and ordinate scale expansion. Methods of identification of microquan-tities have been reviewed,12 although the coverage of references is not as up-to-date as one would like.These advances find application in the identification of products of small-scale syntheses such as electrochemical or photochemical. Microsampling methods are applicable to environmental problems. The detection of small amounts of mineral oil in both sea-water and fresh water has been widely Even with the use of dispersive spectrometers the i.r. method is very good for this (sub-p.p.m.). Hydrocarbons in water are extracted with a halogenated solvent; a freon is preferred to. the more toxic carbon tetra~hloride.’~*~~ Long-path-length liquid cells are used in the determination. The results of g.c. and i.r. methods have been compared.16 Brown and co-workers” have used i.r. spectra as a fingerprint for the identification of the sources of oil slicks.Pierre” has pursued an on-site method for this. Atmospheric pollution has been studied with FT i.r. in~trument~’~~~~ or a fast-scanning dispersive instrument.21 Hanst Lefohn and Gay” detected 18 gases in the atmosphere at the one part per American billion level. They developed multiple-pass gas cells operated at typical path lengths of 200 4 P. R. Griffiths Analyt. Chem. l974,46,645A. 5 J. A. Decker jun. Analyt. Chem. 1972,44 127A. 6 A. G. Marshall and M. B. Comisarow Analyt. Chem. 1975,47 491A. J. L. Koenig Appl. Spectroscopy 1975,29,293. * P. R. Griffiths ‘Chemical Infrared Fourier Transform Spectroscopy’ Wiley-Interscience Chichester Sussex 1975. 9 P. R. Grif€iths and F. Block Appl. Spectroscopy 1973,27,431. 10 M. Yu. Nefedova Zhur.priklad. Spektroskopii 1974,20 664. 11 R. C. Blinn Adv. Chem.Ser. 1971 No. 104 p. 81. 12 G. M. Ayling ‘Spectroscopic Methods of Identification of Microquantities of Organic Materials’ in ‘Applied Spectroscopy Reviews’ ed. E. G. Brame jun. Dekker New York 1974,Vol. 8,Part A,p. 63. 13 D. R. Hughes R. S. Belcher and E. J. OBrien Bull. Environ. Contam. Toxicoi. 1973,10 170. l4 M. Gruenfeld Environ. Sci. Technof. 1973,7,636. H. B. Mark jun. T.-C. Yu,J. S. Mattson and R. L. Kolpack Environ. Sci. Technol. 1972,6 833. l6 R. Jeltes and W. A. M. Den Tonkelaar Water Res. 1972,6 271. P. F. Lynch S.-Y.Tang and C. W. Brown Analyt. Chem.,1975,47 1696. L. J. Pierre jun. Appl. Optics 1973,12,2035. l9 P. L. Hanst A. S. Lefohn and B.W. Gay jun. Appl. Specfroscopy 1973,27 188.2o S. H. Chan D. Nelson M. J. D. Low,and H. Mark J. Quant. Spectroscopy Radiative Transfer 1974,14 287. 2’ J. R. Combertiati Analyt. Chem. 1971,43 1497. Part (iv) Infrared and Raman Spectroscopy 31 and 700 m and used spectral subtraction of a reference air background. A portable single-beam i.r. gas analyser is used for field work this apparatus having proved useful in the determination of vinyl chloride at the p.p.m. There has been considerable activity in the use of combined techniques such as g.c.-i.r. An FT instrument is advantageou~~~ because the rapid rate of accumulation of data from a multiplex instrument enables the g.c.-separated components to be measured directly (known as ‘on-the-fly’!). A gas chromatograph has been linked to a fast-scanning dispersive spectrometer.Other workers favour trapping of the components in a vapour-phase i.r. cell.24 Ths use of i.r. spectroscopy in identifying fractions separated by means of t.l.~.~’ and h.p.l.c.26 has wide interest. Polymers.-The application of i.r. spectroscopy to polymer chemistry continues its popularity. Numerous papers are concerned with molecular orientation and confor- mation and in copolymers the stereoregularity of units and determination of composition. Two results are highly significant. Koenig and co-workers have used an FT instrument to compute the i.r. spectrum of 100°/~crystalline truns-1,4-poly~hloroprene.~~ Samples of 100%amorphous material exist in the molten state and a mixture of amorphous and crystalline material exists at room temperature and the spectrum was recorded in both states.By means of computer subtraction of one spectrum from the other the spectrum of 100%crystalline polychloroprene was simulated although a sample was not available. Koenig7 has written an excellent feature article on the applications of data-manipulated i.r. spectroscopy to chemical systems. Numerous interesting polymer applications were indicated and the differ- ence spectroscopy of plasticized PVCappears to be a method of direct determination of percentage plasticizer which has great application in industry. Miscellaneous Applications and Interpretation.-The use of a computer evables the i.r. spectra of aqueous solutions to be obtained much more rapidly. Even 1% transmission is sufficient to accumulate and replot the data full scale.This could cause a resurgence in the i.r. spectroscopy of biochemical systems on the scale which has occurred in Raman spectroscopy. Parker2* has reviewed the current status of biochemical applications of vibrational spectroscopy and Morton’s books2’ also contain references to this. Douse and Tooke3’ have characterized over 200 amines from the spectra of their hydrochlorides and Doss3lclaims that a band in the region of 1270-1291 cm-’is characteristic of sultam rings (1). 22 ‘The Determination of Vinyl Chloride a Plant Manual’ ed. W. Thain Chemical Industries Association 1974. 23 K. L. Kizer Amer. Lab. 1973,5 No.6 p. 40. 24 R. F. Brady jun. Analyr. Ckrn. 1975,47 1425. z5 R.Kellner Mikrochim. Acta 1975 253. 26 A. A. Juhasz J. 0.Doali and J. J. Rmhio Amer. Lab. 1974,6 No. 2,23. 27 M. M. Coleman P. C. Painter D. L. Tabb and J. L. Koenig J. PolymerSci. PartB PolymerLetters 1974 12 577. 28 F. S. Parker Appl. Spectroscopy 1975,29 129. 29 R. A. Morton ‘Biochemical Spectroscopy’ Vols. 1 and 2 Halstead Press Wiley New York 1975. 30 C. S. Douse and P.‘B. Tooke Canad. Spectroscopy 1973,18,101. 31 S. H. Doss Rev. Roumaine Chim. 1972,17 1611. G.A.Newman R’ (1) R’ R2,R3 R4 = alkyl The use of audiovisual aids for the interpretation of spectra is a useful advance there being several systems commercially available. As Bellamy has remarked there are no new interpretations to report; much of the information published is an extension or refinement of previously established work.Nevertheless it is pleasing to report that the third edition of his book to which so many of us are indebted has appeared.32 3 Raman Spectroscopy Raman spectroscopy is attempting to consolidate its position since the late 1960’s as an established structure-characterization technique. The literature is prolific and several reviews have a~peared.~~-~~ The bi-annual reports in Analytical Chemistry are the latest one covering 1972-3 (348 references). Sh~ader~~ has reviewed chemical applications (355 references) and numerous books are available.3740 Instrumentation and Sampling.-There have been no major changes in instrumentation. The triple monochromator is widely used to discriminate weak Raman scatter from stray light and coherent scattering effects.The rotating sample holder has been very This is used to study coloured solids and liquids. Such compounds tend to be destroyed by the laser beam but this is reduced by spinning the sample at about 2500r.p.m. Results have been obtained from azo- compounds coloured dyes and even black compounds. This sampling method enabled extensive studies to be made of the resonance Raman effect (RRE). The RRE has been described by Bern~tein.~~ It is obtained when a sample is exposed to laser radiation of energy almost coincidental with the energy spacing of an electronic absorption band. The corresponding spectrum may exhibit either intensity enhance- ment of some bands relative to others or overall intensity enhancement of all bands.This enables weak solutions to be studied such as those of biological importance. 32 L. J. Bellamy ‘Infrared Spectra of Complex Molecules’ Vol. 1 3rd Edn. Chapman and Hall London 1975. 33 W. L. Grossman Analyt. Chem. 1974,46,345R. 34 B. Schrader Ber. Bunsengesellschaft phys. Chem. 1974,75 1187. 35 M. Delhaye and J. C. Merlin Biochimie 1975 57 401. 36 B. Schrader Angew. Chem. Infernat. Edn. 1973,12 884. 37 ‘Advancesin Infrared and Raman Spectroscopy’ ed. R. J. H. Clark and R. E. Hester Heyden London 1975 Vol. 1. 3* R. A. Nyquist and R. 0.Kagel ‘Infrared and Raman Spectroscopy of Organic Materials’ in ‘Practical Spectroscopy’ Vol. 1,ed. E. G. Brarne and J. S. Grasselli Dekker New York 1975. 39 ‘The Raman Effect’ Vol.2 ‘Applications’ ed. A. Anderson Dekker New York 1973. 40 W. Kemp ‘Organic Spectroscopy’ Macmillan London 1975. 41 H. J. Sloane and R. B. Cook,Appl. Spectroscopy 1972,26 589. 42 H. J. Bernstein in ‘Advances in Raman Spectroscopy’ ed. J. P. Mathieu Heyden London 1973 Vol. 1 p. 305. Part (iv) Infrared and Raman Spectroscopy 33 The RR spectra of ferrocytochrome c and oxyhaemoglobin solutions have been at solute concentrations approximately three orders of magnitude lower than those required normally. Kiefer44 has reviewed the RRE results on small molecules. A great obstacle to widespread use of Raman spectroscopy is its inability to combat luminescence observed as a broad intense band which often obscures Raman shifts. Two new approaches to reduce or eliminate this effect have been reported.Shriver and co-w~rkers~~ use a mode-locked tuneable pulsed laser and a triggered gate mechanism to reject much of the luminescent emission. This depends on the difference in time-scale between the Raman scatter which is essentially instantaneous and the luminescence which requires a longer time to build up. The other method is coherent anti-Stokes Raman Spectroscopy (CARS).46 A pulsed laser is frequency-doubled in order to pump a dye laser. The sample is pumped to an excited state by the dye laser and irradiated by the pulsed laser as it might be in conventional Raman spectroscopy. By populating the higher-energy levels the anti-Stokes Raman spectrum i.e. bands at shorter wavelength than the exciting line may be recorded and luminescence is less troublesome.Applications.-Raman activity tends to be a function of the covalent character of bonds; the vibrations of non-polar groups and molecular skeletons (backbone structure). Totally symmetric vibrations are strong since they modulate strongly the polarizability of the molecule. Generally vibrations which are strongly i.r.-active are weakly Raman-active and vice versa Very small amounts of sample may be examined for example single beads of polystyrene 40pm in diameter47 and ‘nibs’ (microscopic defects) in plastic films. The identification of trapped g.c. fractions is a routine method. Since the intensities of the Raman shifts are proportional to concentration the technique is directly quantitative.The level of pollutants in water has been deter- mined from the intensity of the C-H stretching vibrations of the total organic content.48 Interpretation.-The appearance of two books which aid interpretation has been welcomed. Freeman’s book49 contains applications of Raman spectroscopy as well as group frequency assignments. The one by Dollish Fateley and Bentley” is already a standard text on characteristic frequencies of organic compounds. The number of methyl groups bound to ethylenic groups in di- and tri-substituted aliphatic and alicyclic molecules may be deterrnir~ed.~’ A characteristic band for the thiomethyl group5* has been found near 690 cm-’. A group-frequency correlation 43 G. J. Thomas jun. in ‘Vibrational Spectra and Structure A Series of Advances’ ed.J. R. Durig Vol. 3 Dekker New York,1975. 44 W. Kiefer Appl. Spectroscopy 1974,211 115. 45 R. P. Van Duyne D. L. Jeanmaire and D. F. Shriver Analyt. Chern. 1974,46,213. 46 R. F. Begley A. B. Harvey R. L. Beyer and B. S. Hudson Appl. Phys. Letters 1974,25 387. 47 G. J. Rosasco E. S. Etz and W. A. Cassatt Appl. Spectroscopy 1975,29 396. 48 G. Breunlich G. Games and M. S. Petty Water Res. 1973,7 1643. 49 S. K. Freeman ‘Applications of Laser Raman Spectroscopy’ Wiley-Interscience Chichester Sussex 1974. F. R. Dollish W. G. Fateley and F. F. Bentley ‘Characteristic Raman Frequencies of Organic Compounds,’ Wiley-Interscience Chichester Sussex 1974. 51 S. K. Freeman and D. W. Mayo Appl. Spectroscopy 1972,26 543.52 S. K. Freeman and D. W. Mayo Appl. Spectroscopy 1973,27 286. 34 G.A.Newman of pyra~ines~~ was established from a study of 32 compounds. Schrader and Meier54 have produced a scheme for characterizing some substituted benzenes that is more reliable than the corresponding i.r. method. Collections of spectra are always useful. A book of assignments for the vibrational spectra of 700 benzene derivatives has been published.ss A Sadtler collection totalling 2000 spectra has been produced together with the i.r. spectra in a continuing series.s6 An atlass7 is available of the Raman i.r. and far-i.r. spectra of 1000 compounds. The identification of unknown compounds may be achieved by means of a computer search pr~gram.’~ OrganicCompounds.-The coverage of aliphatic compounds has been fairly random except for n-alkanes which has been an active area.The interest here has been in the low-frequency vibrations of the solids particularly the determination of the lon- gitudinal acoustic (LA or accordion) modes9 of the carbon backbone (2) which enables each homologue to be identified. Similarly the chain length may be determined in some fatty acids.60 This has been used for the qualitative and quantitative analysis of mixtures of acids in the range C1z-Cz4. 2495*86 (2) LAmodeAv=-cm n n =number of carbon atoms Aromatic alicyclic and heterocyclic compounds have been extensively studied but there are no known systematic collations of such work. Polymers.-This has been an active area with the emphasis of study shifting from synthetic polymers to natural polymers particularly those of biological importance.Hendra has reviewed the field.61 Compared with other spectroscopic techniques the method of direct sampling is attractive. For certain functional groups the Raman effect is strong but it also has the ability to detect slight changes in the skeletal backbone of the polymer. These can be interpreted in terms of chain conformation. In polymers with unsaturation geometrical isomerization is of interest. Stereoregu- larity may be determined. This is important because of the greatly improved physical and chemical properties which are dependent on the regular geometrical arrange- ment of molecular structure. 53 R. P. Oertel and D. V. Myhre Analyt.Chem.,1972 44 1589. 54 B. Schrader and W. Meier 2.analyt. Chem. 1972,260,248. 55 G. Varsanyi ‘Assignments for Vibrational Spectra of Seven Hundred Benzene Derivatives’ Vols. 1 and 2 Akademiai Kiado Budapest and Adam Hilger London 1974. 56 Sadtler Standard Spectra-Raman Spectra Vols. 1-5,1974-5 Heyden London. 5’ B. Schrader and W. Meier ‘Raman/IR Atlas of Organic Compounds’ Verlag Chemie Weinheim West Germany 1974. 58 I. A. Degen L. Birmingham and G. A. Newman Analyst 1976,101,212. 59 H. Takeuchi T. Shimanouchi M. Tasumi G. Vergoten and G. Fleury Gem. Phys. Letters 1974,28 449. 60 C. H. Warren and D. L. Hooper Canad.J. Chem. 1973,51,3901. P. J. Hendra in ‘Polymer Spectroscopy’ ed. D. 0.Hummel Verlag Chemie Weinheim West Germany 1974. Part (iv)Infrared and Raman Spectroscopy 35 Pol ye thylene despite its structural simplicity has been subjectto much discussion of its vibrational assignments.These can be used to determine the state of crystallinity. The LA mode similar to that found in n-alkanes was first found in highly crystalline materials. More recently the variation in LA mode with bulk sample crystallinity and annealing has been st~died.~'.~~ The long polyethylene chain is directed roughly parallel to the lamellar surface and folds back and forth many times. The nature of the chain folds is of current intere~t.~~ Polypropylene is interesting because of its tacticity; it occurs in three isomeric forms of stereoregular-ity of which the isotactic and syndiotactic structures assume planar and helical conformations re~pectively.~~ The spectrum of the atactic form of disordered conformation remains to be unravelled.The vibrational spectrum of syndiotactic PVChasbeenreported.66 Biochemicals and Biopo1ymers.-This is probably the most rapidly growing and exciting area of application. Molecular structure may be studied in H20or D20and over a range of pH's or pD's. New information much ofit conformational has been obtained from amino-acids lipids carbohydrates,6* steroids and nudeic acids. Some extensive general reviews have appeared.43*69,70 Much interest in amino-acids is centred around the assignment of Raman-active vibrations to certain functional group motions particulary the amide groups. The various amino-acids are recognized by the vibrations of their side chains.This knowledge has been applied to the study of proteins and polypeptides. Their structures are built up from information concerning the peptide and amino-acid side-chain residues derived from the assignment of spectral bands their intensities and polarizabilities and comparison with model compounds such as poly-a -amino-acids. In gelatin amino-acids such as poly-L-proline and poly-L-hydroxyproline and their relative composi-tions have been identified.71 In the spectra of collagen and gelatin use was made of the amide I bands (1668 cm-') and amide 111bands (1271and 1248cm-') to deduce possible arrangements of the molecules. The amide I band is due predominantIy to C=O stretching and the amide III band to C-N stretching and NH in-plane bending in the polypeptide backbone.In particular the number and positions of the amide III bands may be interpreted in terms of conformational structure of proteins (Table).72 Much workhas been reported on the diflerences in spectra between native and denatured proteins such as insulin. 62 H. G. Olf A. PeterIin and W. L. Peticolas J. Polymer Sci. Part A-2 Polymer Phys. 1974,12 359. 63 J. L. Kuenig and D.L. Tabb J. Mucromol. Sci.,1974,9 141. 454 M.3. Folkes A. Keller,J. Stejny P.L. Goggin G. V. Fraser andP.J. Hendra Kulloid-2. Polymere 1975 253 354. 65 R.T. Bailey A. J. Hyde and J. J. Kim Spectrochim. Actq 1974,30A,91. 66 W. M. Moore and S. Krimm Makromol. Chern. 1975 Supp!. I 491. 67 J. L. Koenig and B. G. Frushour in 'Advances in Infrared and Raman Spectroscopy',ed.R. J. H. Clark and R. E. Hester Heyden London 1975 Vol. 1. 6% J. J. Caei K.H. Gardner J. L. Koenig and J. BIackwelI 1Chem. Phys. 1975,62,1145. 69 'Chemical and Biochemical Applications ofLasers' Vol. 1,ed. C. 3.Moore Academic Press New York 1974. 70 W. L. Peticolas Biochimie 1975,57,417. 71 0. G. Frushour and J. L. Koenig Biopolymers 1975,14,379. 72 M. C. Chen and R. C. Lord J.Arner. am.Soc. 1974,96,4750. G.A.Newman Table Vibration wavenumbers/cm-’ and conformations of sume proteins Conformation Amide I Amide III a-Helix 1660 1265-1300 Random coil (H-bonded)Antiparallel p -structure 1665 1672 1243-1253 1229-1235 Some significant advances have been made in the study of the very complex nucleic The primary structures of the constituents are elucidated by the identifica- tion of bases such as purine pyrimidine adenine uracil guanine and cytosine and their tautorneric equilibria.Base and sugar residues and ribose phosphate diester backbones have been identified in the spectra. The secondary structural investiga-tions involve weak hydrogen-bonding between the bases (70-1 25 cm-’) base-stacking interaction and backbone conformation. All of the prominent bands in the spectrum of aqueous yeast phenylalanyl transfer RNA (tRNg::sJ have been assigned. Comparison has been made with the spectrum of tRNA~,~oii in terms of similar conformation but with the absence of a pyrimidine base in tRNAz:dp74 The RRE has been utilized in coloured systems such as plant and respiratory pigments visual pigments enzymes vitamin derivatives metal porphyrins and haemoglobin~.’~ Outstanding examples are the This work has been re~iewed.’~ spectra obtained from live carrot root and live tomato fruit which are similar to the spectra obtained from canned carrot juice and bottled tomato sauce.In turn these spectra are similar to those of @-caroteneand lycopene respectively examined in n-he~ane.~~ 73 G.J. Thomas,jun.,Conferenceon ‘ImpactofLasers in Spectroscopy’ Prm.Soc.Pholo-opfkd1nstrurnen-tation Engineers 1974,49 127. 74 M.C. Chen and G. J. Thomas jun. Biopolymers 1974,13,615. 7s T. G. Spiro Accounts Chem. Res. 1974,7 339. 76 T. G.Spiroand T. M. Loehr ref. 37 chapter on ‘Resonance Raman Spectra of Heme Proteinsand other Biological Systems’. 77 L. Rimai D. Gill and J. L. Parsons J. Amer. Chem. Soc. 1971 93 1359.

ISSN:0069-3030    

DOI:10.1039/OC9757200029

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

3 Theoretical Chemistry By G.KLOPMAN Chemistry Department Case Western Reserve University, Cleveland Ohio44106 1 New Methods and Modern Trends The scope and applications of theoretical chemistry continue to expand as the quantum mechanical methods become better and more efficient. Thanks to improv-ing computational techniques the a6 initio procedures can now deal with fairly large molecules. The use of the STO/nG formalism has become common practice even for relatively complex systems and the generalized valence bond method is progres-sively applied to larger systems. A new entry the PNO (pair natural orbital)’ with configuration interaction CI or coupled electron pair approximation CEPA is claimed to reaver ca. 80% of the correlation energy. The method has already been used to calculate the properties of a fairly large number of small molecules with consis tent success.2 The literature was particularly rich last year in new formalisms designed to improve the scope and reduce the computational time of ab initio techniques.Thus several authors suggested procedures for the calculation of valence-shell molecular orbitals in a pseudopotential formed by the nucleus and care Others proposed to simplify the ab initio formalism by approximatingsome of the integrals in a minimal STO basis The SAM0 (simulated ab initio MO)’ method makes use of the transferability of Fock matrix elements between closely related groups in different molecules. The procedure was applied to the calculation of the conformation of cyclohexane with moderate success.An interesting and rare attempt was also made to develop a non-empirical MO theory of the electronic structure of molecular crystals.’ The semi-empirical field has been equally active with the development of several new formalisms. Animproved IOC (inclusionof overlap charges) omega techniqueg provided better agreement for some properties of aromatic derivatives. lo The R.Alrichs H. Lischka V. Staemmler and W. KutzeInigg J. Chem. Phys. 1975,62,1225. 2 R.Alrichs F. Driessler,H.Lischka V.Staemmler,and W.Kutzelnigg J. &m. Phys. 1975,62,1235. J. N.Murrell and I. G. Vincent J.J.C.S.Furaday II 1975,71,890. P.Coffey,C. S. Ewig and J. R.Van Wazer J. Amer. Chem. SOC.,1975,97 1656. M. J. Zerner J. am. Fhys. 1975,62,27SS. P.Volkmer H.J.Kohler D. Mopper and F. Birnstock Chern. Phys. ,!hers 1975,31,566. ’J. E. Eilers B. O’Leary B.J. Duke A. Liberies and D. R.Whitman J. Amer. Chem. Soc. 1975 97 1319. S. F. O’Shea and D. P.Santry new. aim. Acra 1975,37 1. S. C. Sharma A. K. Srivastava and B. Krishna J.C.S. Faraday 11 1975,71,168. lo S. C. Sharma A. K. Srivastava,and B. Krishna J.C.S. Faruday 11 1975,71,172. 37 38 G. Klopman extended Huckel method was improved by Anderson“ and now provides better bond distances and force constants in diatomic molecules. The CND0/2 method was ‘simplified’ by Gayoso12 (CND0/2-S) who claims that in spite of his simplifica- tions the new formalism gives equivalent or better results than the original method. The one-centre integrals of the INDO formalism were reparametrized from atomic promotional energies by Figeys et all3 The resulting method yielded improved heats of formation for various molecules formed of second-row atoms.An interesting parametrization of the CNDO formalism for Pt was suggested by Sakaki et all4 Both the electronic spectra of PtC1:- and the electronic structure of PtR molecules where R is ethylene or acetylene were calculated with credible success. This may open the door to possible future usage of CNDO-type techniques in the study of inorganic complexes. The new semi-empirical method whose development last year had the strongest impact was undoubtedly MIND0/3. The new MINDO method” differs from its predecessor by the fact that new orbital exponents are used for the calculation of the overlap integrals used in the determination of the resonance integral.The method has immediately been applied to the calculation of the properties of a wide range of molecules including atoms of the second and third row.16 The numerous applications of the successive MINDO methods were also reviewed by Dewar.” The claims of MIND0/3 to be an inexpensive and reliable theoretical technique for investigating energetic and structural features of molecules were challenged by Pople” on the basis of energetic considerations and by Hehre” on the basis of structural data. These criticisms were answered by Dewar,” who pointed out that the reported deficiencies of MIND0/3 were all implied in the unusually large error obtained for the heats of formation of only three compounds C& C(CH3)4 and CH,C=CCH,.Actually such criticisms should really not be restricted to one particular semi- empirical method. It should be well understood that limitations are implied in every method including the ab initio ones and it is only if we understand the limitations of our theoretical tools that we can use them properly. In this respect cross- comparison of various methods is often beneficial and this has been done in a few instances. For example Combs and Holloman2’ compared the ability of various semi-empirical methods to predict internal barriers of rotation in small organic molecules but they found no trends. The predicted barrier can be too small or too large but among the tested methods (CND0/2 INDO and MINDO/2’) INDO was found the most reliable.The failure of the CND0/2 method to predict the conformation of systems where the twisted bond is delocalized was confirmed by Sieiro et ~1.~~ The method was also 11 A. B. Anderson J. Chem. Phys. 1975,62 1187. l2 J. Gayoso Compt. rend. 1975,280 C,105. 13 H. P. Figeys P. Geerlings and C. Van Alsenoy Bull. Soc.chim. beiges 1975,84 145. l4 S. Sakaki H. Kato andT. Kawamura Bull. Chem. Soc. Japan 1975,48 195. Is R. C. Bingham M. J. S. Dewar and D. H. Lo,J. Amer. Chem. Soc. 1975,97,1285. l6 R. C. Bingham M. J. S. Dewar and D. H. Lo,J. Amer. Chem. SOC., 1975,97,1294. 1’ M. J. S. Dewar Gem. In Britain 1975 11 97. J. A. Pople J. Amer. Chem. Soc. 1975 97 5306. l9 W. J. Hehre J. Amer. Chem. SOC.,1975,97 5308.2O M. J. S. Dewar J. Amer. Chem. SOC. 1975,97 6591. 21 L. L. Combs and M. Holloman J. Phys. Chem. 1975,79 512. 22 C. Sieiro P. Gonzalez-Dim and Y. G. Smeyers J. Mol. Structure 1975 24 345. Theoretical Chemistry 39 found to fail in the case of some localizedbonds particularly when the two atoms that constitute the bond possess lone pairs.23 Both CNDO/2 and INDO predicted the correct conformation of the central CO bond in dirneth~xymethane,~~ but EHT and MIND0/2 produced the wrong confor-mation. Heats of Formation.-Only a few of the semi-empirical methods (e-g. MIND0/3) are capable of providing heats of formation that are directly comparable with experimental values. Yet several empirical procedures exist or have been proposed recently for achieving such a purpose.Benson and Luria assigned a partial positive charge to each hydrogen of a molecule and a neutralizing charge to the corresponding carbon atoms. The resulting electrostatic energy provided a good estimate (better than 0.5 kcal) of the heat of formation of alkanes,25 dkenes,26 and free radicals.27 Bond energies of saturated molecules were also found satisfactory in Sanderson's empirical proce- dure which is based on electronegativities and atomic radii.28 The calculationof strain energies was realized by MaksiE et from a considera- tion of the angular strain due to the bending of local hybrid orbitals. Resonance energies of benzenoid hydrocarbons equivalent to the best obtainable by SCF procedures were obtained simply by counting resonance An interesting paper by Kruszewski and Krygowski3' proposes an extension of the Huckel 4n +2 rule to non-alternant hydrocarbons.The proposed rule apparently permits predictions as to substituent effects on the stability of the hydrocarbons. 2 Electronic Structures of Organic Molecules Ab initio methods are making increasing inroads into organic chemistry. After the successful demonstration of the usefulness of the ST0/3G programs in organic problems the Generalized Valence Bond programs are beginning to be used. Goddard and his collaborators have used their GVB program to study the ground and low-lying states of dia~omethane,~' and f~rrnarnide.~~ f~rmaldehyde,~~ The calculations proved valuable; the excitation energies and dipole moments are in excellent agreement with experiment.The allyl radical was also studied by the GVB35method and a resonance energy of 11.4 kcaI was found in good agreement with the thermochemical estimate of 11.6kcal. The allyl radical the pentadienyl radical and several ions were studied by Hinchcliff e using a high-quality Gaussian program. 36 23 A. Veillard Chem. Phys. Letlers 1975,33,15. 24 C.Ivaroska and T. Bleha J. Mol Saucture 1975,24,249. 25 S. W.Benson and M. Luria J. Amr. Chem. Soc. 1975,97,704. 26 S.W.Benson and M. Luria J. Amer. am.SOC.,1975,97,3337. 27 S.W.Benson and M. Luria 3. Amer. Chem. Sm.,1975,97,3342. R.T.Sanderson,J. Amer. Chem. Soc. 1975,97,1367. 29 Z. B. MaksiC K. KovakviE and M. Eckert-Maksie TetrahedronLetters 1975 101.3o R.Swinborne-Sheldrake,W. C. Herndon and I. Gutman Tetrahedron Letters 1975,755. 31 J. Kruszewski and T. M. Krygowski Canad. J. Chem. 1975,53,945. 32 S.P.Walch and W. A. Goddard J Amer. Chem. Soc. 1975,97,5319. 33 L. B.Harding and W. A. Goddard J. Amer. Chem. Soc.,1975,97,6293. 34 L. B.Harding and W. A. Goddard J. Amer. Chem. Soc. 1975,97,6300. 35 G. Levin and W. A. Goddard J. Amer. am. Sac. 1975,97 1649. 36 A.Hinchdiffe J. Mol. Strucmre 1975,27,329. 40 G.Klopman It was found3’ that the mean C-C bond length at 0 K is longer in GH6 than in C2D6by 0.0015 A. The C,& molecule as well as the C2H4 and C2H2 systems were also studied by the CEPA-PNO method by Alrichs et aZ.38 A very extensive CI calc~lation~~ of the ground and excited states of trans-butadiene produced values of 7.05 and 8.06 eV for the llBu and 2’B states respectively compared with the observed values of 5.9 and 7.1eV.The use of simulated ab initio molecular orbital (SAMO)was suggested as a valid alternative to full ab initio calculation for large organic molecules. In this method some of the Fock matrix elements are transferred from pattern molecules. The method was found successful in calculations for aromatic hydrocarbon^^^ but required modifications when applied to ionic RX species.41 Ab initio calculations on large molecules could also benefit from the inclusion of ‘molecular fragments’. This is the approach chosen by Spangler et al. to investigate the electronic structure of ethyl chlorophyllide as well as the free and Mg-bound porphin and ~hlorin.~~ An extensive study of 0,S N and P heterocycles was undertaken by Palmer Findlay and their co-w~rkers.~~ Their LCGO calculations provided interesting results concerning the aromaticity and electronic structure of these heterocycles.Excellent agreement has been between the calculated and the experi- mental relative energies of the C4H4 and C4H,systems. The ST0/3G method was also used to calculate the electronic structure of several carbonylnitrenes XC(0)N45 and ethylenedione O=C=C=0.46 Both classes of compounds are believed to be ground-state triplets. However in contrast to previous studies the ethylenedione is now found to be unstable with respect to ‘bent’ dissociation into two COs. 3 Molecular Conformational Analysis Although attempts are being made to isolate the essential features that determine whether one or another conformation is the more most current contribu- tions in this area simply perform a geometry search for the most stable conformation.An increasingly popular method is to use a relatively simple procedure such as CNDO or STO/3G to obtain a rough description of the molecule and follow up by a more complete procedure such as STOInG where n >3. 37 L. S. Bartell S. Fitzwater and W. J. Hehre J. Chem. Phys. 1975,63 3042. R. Alrichs H. Lischka B. Zurawski and W. Kutzelnigg,J. Chem. Phys. 1975,63,4685. 39 R. P. Hosteny T. H. Dunning jun. R. R. Gilman A. Pipano and I. Shavitt J. Chem. Phys. 1975,62 4764. 40 J. E. Eilers B. O’Leary A.Liberles and D. R. Whitman J. Amer. Chem. SOC.,1975,97,5979. 41 B. J. Duke M. Pickering,B. O’Leary and J. E. Eilers J.C.S. Faraday 11 1975,71. 1401. 42 D. Spangler R. McKinney R. E. Christoffersen G. M. Maggiora and L. L. Shipman Chem. Phys. Letters 1975,36 427. 43 M. H. Palmer R. H. Findlay W. Moyes and A. J. Gaskell J.C.S. Perkin 11,1975,841;M. H. Palmer and R. H. Findlay ibid.,pp. 974 1223. 44 J. S. Binkley J. A. Pople and W. J. Hehre Chem. Phys. Letters 1975 36 1. 45 J. F. Harrison and G. Shalhoub J. Amer. Chem. SOC.,1975,97 4172. 46 R. C. Haddon D. Poppinger and L. Radom J. Amer. Chem. SOC.,1975,97 1645. 47 J. E. Eilers and A. Liberles J. Amer. Chem. SOC.,1975,97 4183. 48 G.M. Gimarc Accounts Chem. Res. 1974,7 384. Theoretical Chemistry 41 Among the systems recently studied by CND0/2 are some phosphorus deriva- tives such as the phosphoranyl radicals,49 found to have a trigonal-bipyramidal ge~metry,~' some di-t-butylph~sphines,~' and the strongly pyramidal aminophos- phine.52 Other systems include some hindered a-diazo-ketones XCH2COCHN2,53 di- nitrogen heterocycle^,^^ halogenocyclohexanes,55 and the cyclopropylmethyl ati ion,'^ where it was found that the rotation of the methylene group around the three-membered ring requires an activation energy of 31kcal mol-'.A somewhat modified CNDO procedure was also used to calculate the geometry and electronic structure of a series of highly fluorinated alkanes ketones and aldehyde^.'^ The INDO method was used to optimize the geometry in the special cases of poly(viny1 borane~)~~ systems.An interesting comparison6' was and s~ccinimidyl~~ made between the optimal geometries of several bridged aromatic compounds (ArXAr) calculated by EHT CND0/2 MIND0/2 and PCILO. The results are substantially different depending on which method was chosen. EHT and CND0/2 judged on the basis of experimental values give the most satisfactory results. The geometry of a number of molecules was investigated with the ST0/3G method. It was found that peroxyacetic acid6' exists in a planar cis-configuration. Similarly hexachlorobenzene to no one's surprise was also found planar as shown by the 84-orbital basis set calculation of Pedersen and Carlson.62 In contrast the hydroxymethyl radical was to be non-planar.The out-of-plane angle of the CH2 group was calculated to be 25" but with a barrier of only 0.4 kcal mol-'. The unexpected observation that cyclohexa-l,4-diene may exist in a planar rather than a boat conformation received support from an ab initio cal~ulation~~ showing the planar conformation to be ca. 7 kcal mol-' more stable than the bent one. Other ST0/3G calculations include65 a systematic study of the influence of substituents on the electronic structure and geometry of a series of carbonyl derivatives. ST0/3G as well as semi-empirical methods was used to calculate the conformation of phenethylamine66 and of p -propi~lactone~~ in an effort to under- stand their biological activity. Radom and Stiles6* reported the intriguing observation that the rotational barrier in ethane increases when one of the hydrogen atoms is replaced by a fluorine atom 4y Y.I. Gorlov and V. V. Penkovsky Chem. Phys. Letters 1975,3525. J. M. F. van Dijk J. F. M. Penning and H. M. Buck J. Amer. Chem. SOC. 1975,97,4836. 51 M. Corosine and F. Crasnier J. Mol. Strucfure 1975,27 105. 52 M. Barthelat R. Mathis J.-F. Labarre and F. Mathis Compt. rend. 1975,280 C 645. 53 S. Sorriso F. Stefani A. Flamini and E. Semprini J.C.S. Furuduy ZI 1975,71,682. 54 Z. Latajka H. Ratajczak W. J. Orville-Thomas and E. Ratajnak J. Mul. Strucfure 1975 28 323. 55 V. M. Grimmer D. Heidrich H.-J. Kohler and M. Scholz,2.phys. Chem. (Leipzig) 1975,255,1084. 56 E. Yurtsever and J. Moreshead Chem. Phys. Letters 1975,36 365. ST V. P.Zhukov and V. A. Gubanov J. Mol. Structure 1975,28,247. 58 N. L. Allinger and J. H. Siefert J. Amer. Chem. SOC.,1975,97 752. 5y T. Koenig and K. A. Wielesek Tetrahedron Letters 1975,2007. 6o V. A. Zubkov T. M. Birshtein and I. S. Milevskaya J. Mol. Structure 1975,27 139. L. M. Hjelmeland and G. H. hew Chem. Phys. Letters 1975,32 309. 62 L. G. Pedersen and G. L. Carlson J. Chem. Phys. 1975,62,2009. 63 Tae-Kyj Ha Chem. Phys. Letters 1975 30 379. 64 G. Ahligren B. Akermark and J.-E. Backvall Tetrahedron Letrers 1975 3501. 65 J. E. Del Bene G. T. Worth F. T. Marchese and M. E. Conred Theor. Chim. Acfu 1975,36 95. 66 M. Martin R. Carbo C. Petronogolo and J. Tomasi J. Amer. Chem. Soc. 1975,97 1338. 67 L. M. Boggiz 0.M. Sorarrain J. A. Frones and M.C. Villani,Zphys.Chern.(Leipzig),1975,255,44. 68 L. Radom and P. J. Stiles Tetrahedron Letters 1975 789. 42 G.Klopman but decreases with additional geminal fluorine substitutions. Jordan6' came to the no less intriguing conclusion that the geometry of pyridinium chloride is such that the N,H and C1 atoms are callinear. The structure where the N-H and H-Cl bonds are each 1.4 A is 17 kcal mol-' more stable than the separated pyridine and Ha and 148 kcal mol-' more stable than the infinitely separated pyridinium cation and chloride anion. The question of whether the elusive cyclobutadiene would exist as a square or a rectangular ground state has been discussed. Borden7' suggested that cyclo- butadiene could indeed be a square singlet but Dewar and Kollmar71 found it to be 13.1 kcal mol-' less stable than square triplet.Haddon and Williarn~,'~ on the other hand favoured a ground-state rectangular singlet. The latter authors pointed out that the observed single band ascribed to a low-temperature matrix isolated form of cyclobutadiene could be assigned to a transition from the rectangular 'A form rather than as has been suggested from a square form (see also Chapter 10 p. 240). 4 Bonded Pairs of Molecules Hydrogen Bonding.-In an attempt to analyse the mechanism of hydrogen bonding Morokuma and collaborators devised an energy decomposition which coupled with an ab initio technique was applied to the study of the water dimer as well as to the formaldehyde-water cyclopropanone-water,74 and a~rolein-water~~ pairs.Hydrogen-bonded carbonyl-water pairs were also investigated by Paoloni et uZ.,~~who showed that correlations exist between the stretching frequency of the carbonyl group the shift of the OH absorption band the amount of charge transfer and the dipole-moment increment. An extensive of the various possible hydrogen-bonded formamide-water complexes showed that the formation of a hydrogen bond leads to increased conjugation of the NCO fragment. The formamide-water system was also studied by Del Bene,7'a along with a series of other and di-substit~ted~' carbonyl compounds. In this thorough investigation equilibrium geometries and energies as well as singlet n-m* ionization energies were determined by a minimal ST0/3G procedure." It was found that the dimers usually assume open-chain trans struc-tures (1) and that n +?r* excitation is probably accompanied by rupture of the hydrogen bond.The stereochemistry of intramolecular hydrogen-bonding presents a special chal- lenge because of the delicate balance that exists between the tautomeric forms. This 69 F. Jordan J. Amer. Chem. Soc.,1975,97 3330. 70 W.T.Borden J. Amer. Chem. SOC.,1975,97,5968. 71 M. J. S. Dewar and H. W. Kollmar J. Amer. Chem. SOC.,1975,97,2933. 72 R.C.Haddon and G. R. J. Williams J. Amer. Chem.Soc. 1975,97,6582. 73 H. Umeyama K. Kitaura and K. Morokuma Chem. Phys. Lefters 1975,36 11. 74 S.Yamabe and K. Morokuma J. Amer. Chem. Soc. 1975,97,4458. 75 S.Iwata and K. Morokuma J. Amer. Chem. SOC.,1975,97 966. 76 L.Paoloni A.Patti and F. Mangano J. Mol. Structure 1975,27 123. 77 T.Ottersen and H. H. Jensen J. Mol. Structure 1975,26 355,375; T.Ottersen ibid. p. 365. 78 (a)J. E. Del Bene J. Chem. Phys. 1975,62,1961; (b)J. E.Del Bene ibid. p. 1314. 79 J. E.Del Bene J. Chem. Phys. 1975,63,4666. J. E. Del Bene J. Chem. Phys. 1975,62,666. Theoretical Chemistry is illustrated by the case of malonaldehyde,s'~s2 where repeated calculations failed to resolve the question of whether the C (2) or the C2"(3)configuration is preferred. The case of salicylic acid is somewhat easier to deal with because of the inequality of the two oxygens that share the proton. Here CND0/2 predictss3 the correct position of the proton in both the ground and the excited state of the molecule.Ion Pairsand Charge-transfer Complexes.-Both the Li' and Na' formaldehyde ion pairs have been in~estigated~~ by ab initif techniques. metal-oxygen distances were found to be very short (LiO = 1.46 A NaO = 1.9 A) and curiously enough the oxygen bond with Na was found to be strongly polar whereas that with Li was mostly covalent. The sodium complex and one of the two stable Li' complexes with formaldehyde were found to be such that the metal lies above the oxygen atoms. In contrast the Li' was found to be collinear with the C=O bond in the Li'-formic acid complex.s5 Indeed both this and the pyrazine-lithium complexes were found to be planar. Although semi-empirical methods do not always reproduce the ab initio they can often be used advantageously in problems of ionic association.86 For example extended HMO was shown to provide satisfactory association con-stants for equilibria between nitrobenzene radical anion" and allene8' with various univalent cations.CND0/2 calculations have been used by Fukui and his collaboratorssg to investigate ion-molecule complexes such as N&+CH4 and H30+CH4.They found that the systems are stabilized by some unusual type of hydrogen- bonding. In the unusual system consisting of a fluoride ion and an allyl fation the ion pair was foundg0 to be unsymmetrical ,with the fluoride ion lying 1.8 A above the central carbon of the allyl plane. Other molecular orbital studies of donor-acceptor complexes include the benzoquinone-benzene,91 benzene-carbonyl cyanide," and tetracyanoethylene- waterg3 complexes.G. Karlstrom H. Wennerstrom B. Jonsson S. Forstn J. Almlof and B. ROOS J. Amer. Chem. SOC. 1975,97,4188. 82 A. D. Isaacson and K. Morokuma J. Amer. aem. Soc. 1975,97,4453. 83 J. Catalan and J. 1. Fernandez-AIonso,J. Mol. Structure 1975,27,59. 84 F. Bernardi and G.F. Pedulli J.C.S.Perkin 11,1975,194; F. Bernardi G.F. Pedulli M. Suerra and H. B. Schlegel Gazzetta 1975,105,711. 85 B. M. Rode B. Breuss and P. Schuster Chem. Phys. Letters 1975,32,34. 86 S.Miertus and 0.Kysel Chem. Phys. Letters 1975,35 531. 87 T. M. Krygowski M. Lipsztajn and P. Radzilkowski J. Mol. Structure 1975,28 163. 88 E. V.Borisvo,V. L. Lebediv A. A. Bagatur'yants T. V. Fokina A. M. Taber and I. V. Kalechits Russ. J. Phys. Chem. 1975,48 1374.89 K. Tanaka T. Yamabe H. Kata and K. Fukui Bull. Chem. Soc. Japan 1975,48 1740. * F. Bernardi N. D. Epiotis and R. L. Yates J. Amer. Chem. Soc.,1975,97 1334. 91 0.Mo M. Yanez and J. I. Fernandez-Alonso,J. Phys. Chem. 1975,79,137. 92 W. A. Lathan G. R. Pack and K. Morokuma J. Amer. Gem. Soc. 1975,97,6624. 93 W. A. Lathan and K. Morokuma J. Amer. Chem. Soc. 1975,97,3615. 44 G.Klopman Dimem.-Ethylene dimers were investigated by unrestricted MO LCAOg4 and ~alence-bond~’ methods. The neutral dimer is unstable but the positively charged one was found to be stable by 0.6-0.7 eV with respeCt to dissociation. Two acetonitrile dimers were found to be more stable than the isolated m01ecules.~~ Of the two the skewed Tconfiguration (4) was favoured over the antiparallel one (5).The relative stability of the latter species is worth noting in view of the fact that its formation would occur along a symmetry ‘forbidden’ path. H3C-C-N NEC-CH < 0 N H3C-CSN Ill C I CH3 (4) Catalysis.-Catalytic activity and the role of the catalyst have been discussed in terms of frontier orbital~,~’ and a formalism was proposed to estimate the effect of a catalyst on the frontier The theory was tested on Lewis-acid-catalysed Diels-Alder and Meerwein-Ponndorf reactions. 5 Chemical Dynamics Reaction Intermediates.-Carbocations. The geometry of protonated alkanes has been re-examined by the MINDO/3 method.99 As in other recent calculations a C’ geometry was found for the pentaco-ordinated carbon atom.This was also true in an ‘a6 initio’ study’00of the protonation of cyclobutane where both edge and corner protonations were found to be equally favourable. In this latter study it was found that the protonation energy of cyclobutane is significantly lower than that of cyclopropane. This result supports the fact that cyclopropyl carbonium ions are often postulated as reaction intermediates whereas cyclobutyl carbonium ions are rarely encountered. Other interesting contributions in this area include the study of the protonation of cresols,’o’ of azulene,’** and an attempt to correlate the 13C chemical shifts of phenyl-substituted onium ions’03 with CNDO calculated charge densities. The controversy between the supporters of edge and corner protonation con- tinues and is reaching other cationic species.It has been found’04 that the bridged form (6)of the chlorovinyl cation is 11kcal mol-’ less stable than a slightly bent open form (7). An EHT calculation of the site of protonation of methylcyclopropane 94 J. Almlof A. Lund and K. Thuomas Chem. Phys. Letters 1975,32 190. 95 P. E. S. Wormer and A. Van der Avoid J. Chem. Phys. 1975,62 3326. 96 L. Paoloni and S. Hauser Bull. SOC.chim. belges 1975,84 219. K. Fukui and S. Inagaki J. Amer. Chem. SOC. 1975,97,4445. 98 A. Imamura and T. Hirano J. Amer. Chem. SOC.,1975,97,4192. 99 P. K. Bischof and M. J. S. Dewar J. Amer. Chem. SOC.,1975,97,2278. loo T. Pakkanen and J. L. Whitten J. Amer. Chem. Soc. 1975,97,6337. Io1 M. M. Bursey R.S. Greenberg and L. G. Pedersen Chem. Phys. Letters 1975 36,470. lo2 E. Stilla J. Bertran and J. I. Fernindez-Alonso J.C.S. Perkin 11 1975 366. Io3 G. A. Olah P. W. Westerman and D. A. Forsith J. Amer. Chem. Soc. 1975,97,.3419. lo4 V. Lucchini G. Modean and I. G. Csizmadia Gazzetta 1975 105 675. Theoretical Chemistry 45 revealed that two reaction pathways are equally favourable lo5 formation of a corner-protonated methylcyclopropane and hydride abstraction from the methyl group giving H2 and the cyclopropyl carbinyl cation (8). Pl ,c1 (6) (7) (8) The study of trico-ordinated carbenium ions has mostly centred around the determination of the stabilizing effect of adjacent substituents. Thus the influence of cy cloprop yl,'06 phenyl,'06,' O7 and aminophenylloS groups was investigated by ST0/3G methods.The influence of heteroatoms was also investigated and it was found that the stabilizing effect of an NH group on an adjacent C' is practically nil1'* compared with that of a BH2 for example. A comparison was also made between cH2SHand 6H,0H.Io9 It was found here that the effect of the sulphur was very different from that of the oxygen. Thus whereas SH releases electrons to the carbenium centre both from its CT-and 7r-orbitals OH behaves as a 7r-donor but a cT-acceptor. Furthermore geometrical isomerization of CH2+SH proceeds by rptation about the C-S bond with a barrier of ca. 36 kcal mol-' whereas that of CHzOHproceeds by linear inversion at oxygen. Curbunions. Very little new information has been gathered on the electronic structure of carbanions.The problem is difficult because of the importance of correlation energy in these electron-rich states. Furthermore the orbital exponents used for the neutral molecules are unsatisfactory to describe the expanded atomic orbitals of negatively charged species. In spite of these difficulties the geometry and electronic structure of the methyl ethyl vinyl and ethynyl anions have been satisfactorily calculated.110 Sulphur d -Orbitals. Evidence continues to accumulate against a strong participation of the sulphur d-orbitals in 7r-bonding. Thus it was found that the sulphur atom strongly stabilizes the adjacent carbanion centre in -CH,SH even though its d-orbitals were not included in the basis set."' Including the d-orbitals lowers both the energy of -CH,SH and that of CH,SH thus showing no effect on the proton affinity of the carbanion.A similar conclusion was reached from a comparative study112 of -CH,SH and -CH20H. Ab initio113 and CND0114studies show a modest d-orbital contribution to the bonding in the episulphones (9). *05 A. H. Andrist J.C.S. Chem. Comm. 1975,446. IM J. F. Wolf P. G. March R. W. Taft and W. J. Hehre J. Amer. Chem. SOC.,1975,97,2902. lo7 J. D. Dill P. von R. Schleyer and J. A. Pople Tetrahedron Letters 1975 2857. Io8 P. Kollman J. McKelvey and P. Gund J. Amer. Chem. SOC., 1975,97 1633. lo9 F. Bernardi I. G. Csizmadia H. B. Schlegel and S. Wolfe Canad.J. Chem. 1975,53 1144. 110J. E. Williams jun. and A. Streitwieser jun.J. Amer. Chem. SOC.,1975,97 2639. A. Streitwieser jun. and J. E. Williams jun. J. Amer. Chem. Soc. 1975,97 191. 11* F. Bernardi I. G. Csizmadia A. Mangini H. B. Schlegel M. H. Whangbo and S. Wolfe J. Amer. Chem. SOC.,1975,97,2209. 113 M. M. Rohmer and B. Roos J. Amer. Chem. SOC.,1975,97,2025. 114 C. Muller A. Schweig and H. Vermeer J. Amer. Chern.SOC.,1975,97 982. G.Klopman O\ S/O /\ H,C-CH2 (9) Oxidation Reactions. The reaction of singlet molecular oxygen with olefins was investigated by Dewar Thiel and their collaborators using MINDO/3 potential energy surfaces. They found the most favourable path to be that yielding the corresponding peroxirans (lo) with an activation energy of ca. 11.4 kcal m~l-'."~ The rearrangement of the peroxirans into 1,2-dioxetans (1l),which are the normal products of such reactions is postulated on the fact that 1,2-dioxetan is ? 0-0I I 0-0 02('AR)+ H,C=CH2 -+ ;'% --* ,$)< -* /?T"+ I1 ., H2C'-CH2 H2C-CH H2C-CH2 H2C-CH2 (10) (1 1) 49.4 kcal mol-' more stable than the corresponding peroxiran.However the activa- tion energy required to achieve this process was given as 34.1 kcalmol-' which seems relatively high. Indeed the peroxiran could have also reacted either with another singlet molecular oxygen to give an oxiran and ozone (exothermicity 36.2 kcal mol-' activation energy 29.2 kcal mol-') or even better with another alkene to give two oxiran molecules (exothermicity 98.1 kcal mol-' activation energy 8.6 kcal mo1-')."6 Although oxirans have been suggested as the products of such reactions it is not clear from these results why it is the 1,2-dioxetans that are the usually observed product.The structure of the zwikerion H2C=O+-O- postulated as an intermediate in the ozonolysis of alkenes was studied by Wadt and G~ddard."~ The results indicate that the molecule would rather exist as a biradical(l2) and would rearrange into the singlet biradical(l4) by way of the cyclic dioxiran (13) found to be more stable than (14) by 23 kcal mol-'. An ST0/3G study''8 of the electrolytic oxidation of formic acid showed the cyclic structure (15) to be preferred to the open-chain structure. (15) However it is now widely recognized that Gaussian methods tend to overestimate the stabilityof small rings and caution should thus be exercised when considering the above results.M. J. S. Dewar and W. Thiel J. Amer. Chem. SOC.,1975,97,3978. 116 M. J. S. Dewar A. C. Griffin W. Thiel and I. J. Turchi J. Amer. Chem. SOC.,1975,97 4439. 11' W. R. Wadt and W. A. Goddard J. Amer. Chem. SOC.,1975,97 3004. 118 W. F. Maier and M. T. Reetz J. Amer. Chem. Soc. 1975,97,3687. Theoretical Chemistry Potential Energy Surfaces.-Inversion Barriers. The inversion barriers about the nitrogen of a set of mines amides and heterocycles were calculated by the CNDO meth~d."~It was estimated that the contribution of correlation energy to such inversion barriers is very small; in ammonia it was found to be less than 10%of the total.12o The influence of the electronegativity of the atom X about which inversion occurs in XH has been examined by Levin.'" It was found that the barrier increases drastically as the electronegativity of X decreases.This was related to the decrease in the splitting between the highest occupied and lowest unoccupied orbitals in the C3h transition state. Internal Rotation Barriers. Internal rotational barriers were examined for several compounds. In ethane the barrier was assigned to the required orthogonality of the CH bonds on opposite ends of the The barrier to internal rotation in thioacetaldehyde was also in~estigated'~~ and a comparison was made between the results obtained from PCILO and CND0/2. The PCILO calculations yielded a satisfactory value (1.06 kcal mol-') but the CND0/2 calculations resulted in the wrong conformation.Valence Tautomers. The tautomerism of pyridinealdoximes and acetamidopyridines was investigated using the CND0/2 method. It was found that the lactim forms are generally more stable than the lactam forms and that the tautomers are more stable when their substituents appear in a ~yn-configuration.~~~ The potential surface for the valence tautomerism of 4-thioformyl1,2-dithiole-3-thione (16) and other thiocarbonyl derivatives was examined by the Huckel method. (16) Isomerization. The rules of conservation of symmetry proposed by Woodward and Hoffman continue to stimulate the interest of theoreticians eager to find the most favourable rearrangement reaction paths. Although most of the work in this area is done by quantum mechanical methods some inroads are also made by empirical force-field procedures such as that recently proposed for the study of the stereoisomerization pathway of several trimesityl derivatives.126 119 B.E. Ley A. E. Foti and S. M. Rithstein J. Amer. Chem. SOC.,1975,W 2030. N. C. Dutta and M. Karplus Chem. Phys. Letters 1975,31,455. 121 C. C. Levin J. Amer. Chem. Soc.,1975,W,5649. 122 P. A.Christiansen and W. E. Palke Chem. Phys. Letters 1975,31,462. 123 T.Weller D. Klopper and H.-J. Kohler Chem. Phys. Letters 1975,36,475. lZ4 J. S.Kwiatkowski W. Herzog (Boniewicz) and B. Czaodrowska J. Mol. Structure 1975,26,333. n5 G. Calzaferri and R. Gleiter J.C.S. Perkin ZZ,1975 559. lZ6 M. R. Kates J. D. Androse P. Finocchiam-D. Gust and K.Mislow J. Amer. Chem. Soc.,1975,97 1772. 48 G.Klopman Among the recently published quantum mechanical calculations of potential- energy surfaces for isomerization reactions we noted the ab initio (SCF-CI) calcula-tion of fhe cyanide-isocyanide rearrangement. 127 The activation barrier was found to be between 35 and 40 kcal mo1-' while the HNC isomer is calculated to be less stable than HCN by 9-15 kcal mol-'. The rearrangement of methylcarbene to ethylene was examined by an a6 initio procedure using a double-zeta basis. The reaction was found to proceed smoothly along an 'allowed' pathway.'** The thermal rearrangement of cyclic organic molecules was investigated by Dewar and Kirschner using MIND0/3. They found that the forbidden thermal rearrange- ment of Dewar benzene to benzene'29 requires an activation energy of 114 kcal mol-' and that of bicyclo[2,1 ,O]pent-2-ene to cy~lopentadiene'~~ 111.7 kcal mol-l.These results thus generally agree with the predictions of the conservation of symmetry rules in that they find high activation energies for forbidden processes. The situation is not as clear in the rearrangement of bicyclobutane to b~tadiene.'~' In this case it was found that the activation energy for the path proceeding to an unsymmetrical biradicaloid transition state is only 2.7 kcal mol-' above that of the 'allowed' reaction intermediate. The rearrangement of benzvalene to benzene132 is even more interesting because the activation energy needed to reach the biradicaloid transition state was found to be only 21.5 kcal mol-' making it a very favourable pathway.The 'allowedness' of the reaction was further emphasized by the fact that no HOMO-LUMO crossing exists when going from reactants to products. The thermal 173-sigmatropic rearrangements of bicyclo[3,2,0]heptanes to norbor- nenes were investigated by Gavezzotti and Simonetta in an attempt to define the relative ease of various reaction paths.133 Bimoleculur Reactions. The concerted elimination of HCI from ethyl chloride was investigated by Hibert~'~~ with a singledeterminant ab initio MO. His conclusions are that the reaction proceeds as is usually believed uia a planar four-membered transition state. However he found that cis-elimination is more favourable than trans-elimination.This was rationalized on the basis that one of the chlorine's lone pairs takes a prominent part in the proton-abstraction process. The halide exchange reaction Br- +RBr where R is an alkyl group was investi- gated by Abraham et ~1.'~'with a force-field method. Three transition-state models were investigated a stiff model a flexible model with one bondbending mode and a plastic model with several degrees of freedom. Both the flexible and plastic model reproduced experimental data satisfactorily. On the basis of their results the authors postulated that steric effects alone are responsible for the observed differ- ences in reactivity. 1z7 P. K. Pearson H. F. Schaefer and U. Wahlgren J. Chem. Phys. 1975,62 350. lZ8 J. A. Altmann I.G. Csizmadia and K. Yates J. Amer. Chem. Suc. 1975,97 5217. 129 M. J. S.Dewar and S. Kirschner J.C.S. Chem. Comm. 1975,463. l3O M. J. S.Dewar and S. Kirschner J.C.S. Chem. Comm. 1975,461. 131 M. J. S. Dewar and S. Kirschner J. Amer. Chem. Soc. 1975 97 2931. I32 M. J. S. Dewar and S. Kirschner J. Amer. Chem. SOC.,1975,97 2932. 133 A. Gavezzotti and M. Simonetta Tetrahedron 1975,31 1611. 134 P. C. Hiberty J. Amer. Chem. SOC.,1975,97 5975. 135 M. H. Abraham P. L. Grellier and M. J. Hogarth J.C.S. Perkin ZI,1975 1365. Theoretical Chemistry 49 Reactivity Control.-Reactiility Indices. The once popular 'static' reactivity indices e.g. free valence index localization energy etc. are seldom used nowadays in view of the success of the 'dynamic' reactivity indices such as HOMO and LUMO energies and orbital coefficients.The advantage of the latter indices over the former ones is that they provide a much better picture of the reaction paths by taking both reagents into consideration. The failure of a single or 'universal' index to account for the reactivity of a set of molecules or the various positions of a molecule has thus been recognized. This was lately re-emphasized for heterocyclic where it was shown that no single index could account for the observed electrophilic substitutions. One of the recent developments in this field consists of the determination of the electrostatic potentials that exist around a molecule. This allows one to visualize the possible path to be followed by an approaching reagent usually a proton.Such calculations have recently been made for the dimethylphosphate anion,'37 where it was found that the anionic oxygens are surrounded by circular zones of nearly constant negative potentials while smaller potential wells occur around the ester oxygens. The diprotonation of adenine and some of its derivatives was also studied by such a te~hnique.'~' It was found that the N-1 and N-7 are the most favourable sites for double protonation of adenine itself while the N-7 methyl derivative was preferentially diprotonated at N-3 and N-9. Gas-phase acidities and basicities have also been calculated by more conventional methods i.e. differences in stability. These include a CNDO/2 calculation of the basicityof a series of ph~sphines'~~ and an ab initio study of the basicity and acidity of a series of alcohols alkyl amines and alkyne~.'~' In the latter cases it was found that the bulkier alkyl groups increase both acidities and basicities and that these groups can function on demand as electron donors and acceptors.ControE of Reaction Path. The search for new and better descriptions of the orbital control of reaction paths continues to stir the interest of theoreticians. Several new concepts have emerged lately. For example Desl~ngchamps'~~ presented a new stereoelectronic theory for the study of the most favourable cleavage path of the tetrahedral intermediate of carboxylic derivatives and Liotta14' proposed to study nucleophilic and electrophilic reactions by an orbital-distribution technique.Salem and his co-workers introduced a new classification of photochemical reactions based on the consideration of avoided surface crossing^.'^^ These can be found by drawing state-correlation diagrams between the reactants low-lying excited states and the primary product. The application of the theory to new systems has also been fruitful by helping to uncover new physical and chemical propertie~.'~~ Epiotis Yates and Bernardi discovered that subjacent orbital control can be 136 S. Clementi A. R. Katritzky and H. 0.Tarhan Tetrahedron Lerrers 1975 1395. 137 H. Berthod and A. Pullman Chem. Phys. Letters 1975,32,233. 138 R. J. Bartlett and H. Weinstein Chem. Phys. Letters 1975,30,441. 139 M. Graffeuil J.-F. Labarre M. F. Lappert C. Leibovici and 0.Stelzer J.Chim. phys. 1975,72,799. 140 L. Radom Austral. J. Chem. 1975,28 1. 141 P. Deslongchamps Tetrahedron,1975,31 2463. 142 C. L. Liotta Tetrahedron Letters 1975 519 523. 143 L. Salem C. Leforestier G. Segal and R. Wetmore J. Amer. Chem. SOC. 1975,97,479. 144 W. G. Dauben L. Salem and N. J. Turro Accounts Chem. Res. 1975,8,41. G.Klopman important in sigmatropic reaction^.'^'" The same authors also called attention to the importance of non-bonded attractions in the determination of the conformation of rn01ecules~~~~ and the stereochemistry of displacement reactions.’45o Jorgensen and Borden presented extended Huckel calculations explaining Hoge-veen’s observation of the drastic difference of Diels-Alder reactivity between (17) and (18).They found that the low reactivity of (17) is due to the unfavourable interaction between the orbitals of the bridge and the newly formed double bond compared with what it was before reaction.’46 The Walsh orbitals of the cyclopropyl groups in dispiro[2,2,2,2]deca-4,9-diene (19) were similarly shown to interact through conjugation with neighbouring double bonds.’47 This was found to be the case irrespective of whether the vinylcyclopropanes are in a syn or anti periplanar conformation. The analysis of the correspondence between the Woodward and Hoffman rules for pericyclic reactions and the Hiickel-Mobius rules of aromaticity was discussed by Day.148 Other discussions of orbital correlation diagrams were presented by ma ha^^,'^^ for X+R reactions and in terms of valence bonds by Silver and Karpl~s.’~~ Considerable interest has been shown lately in attempts to express the laws of conservation of symmetry by means of mathematical and graphical methods.In the former category Stanton and McIver’” and Hale~i’~~ described new ways by which group theory can be used in the study of the distortion of molecular orbitals produced by their reaction. In the latter group Ras~af”~ has attempted to describe the Woodward-Hoffman rules in terms of parity rules and Cvetkovic Gutman and Trinaj~tic”~ presented a graphical method for correlating the non-bonding molecu- lar orbitals of reactants and products. In st related vein Sinanoglu’” presented a geometric description of reaction mechanisms along with a set of rules for possible use in computer-assisted design of organic syntheses.Computer-assisted graph analysis was also used by Gund ef ~1.’’~to analyse the mechanism of diamantene formation from various pentacyclotetradecanes. In this work however the search (a) N.D. Epiotis R. L. Yates and F. Bernardi J. Amer. Chm Soc. 1975,97,4198; (b)R. L. Yates N. D. Epiotis andF. Bernardi ibid.,p. 6615;(c)N.D. Epiotis,R. L.Yates andF. Bernardi,ibid.,p. 5961. 146 W. L.Jorgensen and W.T.Bordem Tetrahedron Lerrers 1975,223. 14’ P. Asmus M.Klessinger L. U. Meyer and A. de Meijere TetrahedronLetters 1975,381. 148 A. C. Day J. Amer. Chem. Soc. 1975,97,2431. 14q B. €3. Mahan Accounts Chem. Res. 1975,8,55. lSo D. M.Silver and M.Karplus J. Amer.Chem. Soc. 1975,97,2645. l5I R. E. Stanton and J. W. McIver J. Amer. Chem. Soc. 1975,97,3632. 152 E. A. Halevi Helv. aim. Acru 1975,58 2136. 153 A. Rassat Tetrahedron Letters 1975,4081. 154 D. Cvetkovic,I. Gutman and N. Trinajstic 1.Mol. Smture 1975,uI 289. 0.Sinanoglu,3. Amer. Chem. Soc. 1975 37 2309. lSc T. M.Gund P. von R. SchIeyer,P. H.Gund and W.T.Wipke J. Amer. Chm. Soc. 1975,97,743. Theoretical Chemistry 51 was not guided by quantum mechanical considerations but rather by an empirical formfield program. 6 Calculation of Physical Properties of Large Organic Molecules Ionization Potentiah-The determination of new experimental ionization poten- tials by photoelectron spectroscopy and ESCA techniques continues to stimulate the interest of theoreticians.In most recently treated cases however the molecules were rather large and could be treated only by semi-empirical methods. Thus Bieri and Heilbr~nner'~~ attempted to resolve the order of orbitals in Dewar-benzene in an effort to determine the relative importance of through-bond and through-space interaction between the two double bonds. They found CND0/2 inadequate to explain the experimental order of orbital energy but both ST0/3G and SPINDO gave adequate results. On these bases they concluded that the b state lies below the a1state and that the through-bond and through-space effects acciden- tally cancel in this molecule. In a similar study on a different system it was found that ab initio and INDO methods as well as CND0/2 provide a reasonable picture of the photoelectronic spectra of 1,6-methano[ 1OIann~lene.'~~ On the basis of these calculations it was concluded that the system possesses only weak aromaticity.Other interesting CNDO/2 calculations of photoelectronic spectra include those of a series of substituted benzothiazole~'~~ and of a group of nucleic acid bases,'60 where the results are also correlated with the ability of the bases to associate with riboflavine. Electronic Spectra.-Electronic spectra calculations were amongst the first to be satisfactorily performed for organic molecules yet no method seems to have achieved a scope wide enough to establish predominance. Indeed new parametriza- tions of the basic molecular orbital framework are being proposed in the literature at a greater rate than in any other area of theoretical chemistry.For example Hayashi and Nakajima16' parametrized the local core matrix elements of a CND0/2 framework to calculate the spectra of a few unsaturated hydrocarbons. The most consistent parametrization of the CNDO formalism for the evaluation of U.V. transitions was suggested a couple of years ago by Jaffe and collaborators as the CNDO/S and has now been modified by its authors16* in such a way as to allow the direct calculation of triplet states. The resulting procedure was used to calculate spectroscopic data of various substituted and heterocyclic aromatic derivatives. Two new parametrizations CNDO/S2 and CNDO/S3 involving a change in the orbital exponent of the conjugated carbon atoms have been used to calculate the excited states of alkyl-substituted aromatics and polycyclic aromatic derivative^.'^^ lS7 G.Bieri and E. Heilbronner Tetrahedron Letters 1975 581. lS8 G.L. Grunewald,I. M. Uwaydah R. E. Christofferson and D. Spangler,TetruhedronLetters,1975,933. Is9 G. Salmona R. Faure and E.-J. Vincent Compt. rend. 1975,280 C 605. 160 N. S. Hush and A. S. Cheung Chem. Phys. Letters 1975,34 11. T. Hayashi and T. Nakajima Bull. Chem. Soc.Japan 1975,48,980. 16* H. M. Chang H. H. Jaffe and C. A. Masmanides J. Phys. Chem. 1975,79,1109 1118. 163 N. 0.Lipari and C. B. Duke J. Chem. Phys. 1975,63,1748; C. B. Duke N. 0.Lipari W. R. Salaneck and L. B. Schein ibid. p. 1758; N. 0.Lipari and C. B. Duke ibid. p. 1768. 52 G.Klopman Electronic spectra have also been calculated for fluorophenols and anilines (CNDO/S),lWnaphthalene (CNDO/S CI),16' stilbene (IND0),'66and a series of di-and tri-atomic linear radicals with degenerate ground states (IND0/CI).l6' Limited configuration interaction Pariser-Parr calculations (SCF-MO CI) have also been used to calculate the spectra of benzoquinolines168 and a large series of nitrogen heterocyclic aromatic molecules.169 Application to biochemical problems is illus- trated by the calculation,of the excitation energy of various isomers of refinall7' in an attempt to understand the process of vision. An interesting attempt to correlate luminescence and SCF-CI calculations was presented by Fratev and Tadjer.171 A rare attempt to calculate the U.V.spectra of a fairly large organic molecule tetracyanoquinoline by an ab initio technique (4 12 primitive Gaussians) was presented by J0han~en.l'~ The ability of various semi-empirical (CNDO type) methods to predict the dipole moments of molecules containing second-row atoms was tested by Gordon Richards and K0~th.I~~ They found that none of the methods was capable of reproducing magnitudes or even qualitative trends. Vibrational Spectra.-The calculation of the force constants necessary to evalu- ate i.r. frequencies can be done with any quantum mechanical method provid- ing that the geometry predicted by this method is sufficiently realistic. Both the CNDO and MIND0 formalisms fulfil this criterion and have been successfully used to calculate the harmonic force constants of GH, G&,and CJ&,174 and HCN.17' A study of the effect of deuterium substitution on the i.r.spectrum of silaethylene H,Si=CH, has been re~0rted.l~~ N.M.R. Specga.-Olah and his co-workers have related the I3Cchemical shifts of phenyl-substituted onium ions to the CND0/2 calculated total \ charge of the electron-deficient atoms. lo3 On the basis of a comparison between the experimental and MIND0/2 calculated 13 C chemical shielding anisotropy of acetic acid it was postulated that the molecule exists as a dime^.^^^ Coupling constants have also been calculated usually by the finite perturbation method in INDO wavefunctions. Thus l3C-I3Ccoupling constants were calculated for various conformations of a series of aliphatic and bicyclic and compared with the corresponding experimentally determined values.1e4 J. S. Yadav P. C. Mishra and D. K. Rai Chem. Phys. Letters 1975,31 129. H. Meyer K. W. Shulte and A. Schweig Chem. Phys. Letters 1975,31 187. 166 D. A. Luippold Chem. Phys. Letters 1975 35 131. 167 P. Carsky J. Kuhn and R. Zahradnik,J. Mol. Spectroscopy 1975,55 120. H. Yamaguchi T. Ikeda and H. Mametsuka Bull. Chem. Soc. Japan 1975,48,1118. 169 R. W. Wagner P. Hochmann and M. A. El-Bayoumi J. Mol. Spectroscopy 1975,54,167 170 B. Honig A. Warshel and M. Karplus Accounts Chem. Res. 1975,8 92. 171 F. Fratev and A. Tadjer J. Mol. Structure 1975 27 185. 172 H. Johansen International J. Quantum Chem. 1975,9,459. 173 M. S. Gordon B. Richards and M.Korth J. Mol. Structure 1975,28,255. 174 K. Kozmuza and P. Pulay Theor. Chim. Acta 1975,37,67. 17s T. Miyazaki M. Ikeda and M. Shibata Bull. Gem. SOC. Japan 1975,48 1138. 176 H. B. Schlegel and S. Wolfe J.C.S. Chem. Comm. 1975 246. I. Ando and A. Nishioka Bull. Chem. Soc. Japan 1975,48,841. l78 M. Barfield I. Burfit and D. Doddrell J. Amer. Chem. SOC.,1975,97,2631.

ISSN:0069-3030    

DOI:10.1039/OC9757200037

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

53 D. W. Jones stereoselectivity (e.g. exo-endo in the Diels-Alder reaction). It has however been pointed out that in certain cases interaction involving the superjacent orbital of one partner may be imp~rtant.~" In the cyclopentadiene-fulvene addition the addition mode predicted by considering both HOMO-LUMO interactions is that shown in (1)' but the observed mode (2) is correctly predicted if interaction between the cyclopentadiene HOMO and the next-LUMO of fulvene is also considered. The FMO method has been extended to include a rationale for the possible role of catalysts in pericyclic processes as well as insertion reactions and olefin metathe~is.~~ It will be of interest to see if the FMO method can be applied in a quantitative way to reactivity problems in pericyclic reactions involvirg a-bonds.Considerable attention has been devoted to so-called forbidden processes. For the thermal racemization and cis-truns-isomerization of cyclopropanes earlier studies with substituted cyclopropanes cast doubt on Hoffmann's suggestion 4a of a 0,O-trimethylene biradical intermediate (3). Support for (3) is now provided4b by a study using optically active trans-[ 1,2-2H2Jcyclopropane (4)(a365+0.168"!). This = undergoes trans-cis-isomerization 1.07 times faster than racemization in accord with a process involving double methylene rotation e.g. rotation at both C-1and C-2 converts (4) into its enantiomer (3,and it is consistent with the intermediacy of (3). H DD Since an alternative explanation of the results requires a blend of a random biradical intermediate and/or a single methylene rotation process with a large fraction of a triple methylene rotation process the authors4" believe that the double methylene rotation operates exclusively.The same conclusion has been drawn from a study using 1-phenyl[2-2H]cyclopropane.4" The continuous-biradical hypothesis4d is the functional equivalent of a single methylene rotation mechanism and so is inconsis- tent with the present results. As a consequence of through-bond coupling involving the C-1 and C-2 orbitals of (3) and the C-3 methylene orbitals the HOMO of the 0,O-biradical should have the symmetry shown. It should therefore undergo conrotatory rather than disrotatory closure. However no information on this point is currently available.In the related opening of methylenecyclopropanes e.g (6) an intermediate trimethylenemethane could be an orthogonal methylene-ally1 biradical (a)R. Hoffmann J. Amer. Chem. Soc. 1968,90,1475;(6)J. A. Berson and L. D. Pederson ibid. 1975 97,238; (c)J. A. Berson L. D. Pederson and B. K. Carpenter ibid.,p. 240; (d)W. von E. Doering and K. Sachdev ibid. 1974,% 1168. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions (7) or a planar conjugated species (8). Since (6) is thermally converted into its diastereoisomer (9) with partial retention of optical a~tivity,~" the symmetrical (4) (7) (8) (9) orthogonal trimethylenemethane (7) cannot be the only intermediate. The unsym- metrical planar trimethylenemethane (8) must also be involved but to a smaller extent.The energy difference between (7) and (8) thus appears to be smaller than suggested by the calculations of Dewar and Salem5* and more in line with the results of others." Although the stereochemistry of the opening of bicyclobutanes to butadienes e.g. (10)-+ (1l) is nicely rationalized6" in terms of a concerted u2s+ u2a process H-H Me (10) (1 1) biradical intermediates have been suggested. Thus (12)rearranges 2700 times faster than the compound in which the double bond is saturated,6b in accord with allylic stabilization of one radical site in the postulated intermediate (13) (Scheme 1). Scheme 1 MIND0/3 calculations locate an intermediate biradical (14) in the opening of bicyclobutane to butadiene.6c The radical lobes in (14)are coupled by through-space overlap so that (14) is more stable than the classical non-interacting biradical.This serves to explain the stereoselectivity of the ring-opening since an interesting biradical retains a memory of the stereoisomer from which it is formed. Presumably the conversion of benzvalene into benzene cannot be a u2s+ a2aprocess leading to trans-benzene. It is surprising therefore that in contrast to the simple bicyclo- butane to butadiene conversion the opening of benzvalene is predicted6d to be concerted proceeding via a very unsymmetrical TS in which one bicyclobutane bond (a) W. R. Roth and G. Wegener Angew. Chem. Intentat. Edn. 1975,14,758;(b)M. J. S. Dewar and J. W. Walton J. Amer. Chem.Soc. 1971,93,3081; W. J. Hehre L. Salem and M. R. Willcott ibid. 1974 96,4328;(c)D. R. Yarkonyand H. F. Schaefer tert. ibid. p. 3754; W. T. Borden ibid. 1975,97,2906. (a) R. B. Woodward and R. Hoffmann 'The Conservation of Orbital Symmetry' Academic Press 1970 p. 77; (b)M. Christl U. Heinmann and W. Kristof J. Amer. Chem. SOC.,1975,97 2299; (c) M. J. S. Dewar and S. Kirschner ibid. p. 2931; (d)ibid. p. 2931. D. W.Jones [‘a’ in (15)] is greatly weakened whilst the other [‘b’ in (15)J is almost intact. Participation of the double-bond and greater stretching of bond ‘a’ than bond ‘b’ may 6 secure a prevailing aromaticity for the TS.6d The forbidden disrotatory opening of bicyclo[2,1 ’OIpent-2-ene to cyclopentadiene is predicted7“ to proceed via a sym- metrical TS as a result of geometrical constraints.The 2-methyl derivative (16) rearranges to a mixture of (17) and (18). This could be due to a secondary (16) (17) (18) rearrangement of (18) to (17) possibly by a ‘hot-molecule’ process since conversion of (16) into (18) is strongly ex other mi^.^' An alternative pathway7d involving cr2s+u2a addition of either the C-1-C-2 and C-4-C-5 or the C-1-C-5 and C- 3-C-4 bonds of (16) is predicted7” to have an activation energy >>250kJ mol-’ and is therefore much less likely. A similar calculation of the TS for the opening of Dewarbenzenes to benzenes7’ allows the suggestion that the TS veers towards the zwitterion (19); this accounts for the more rapid ring opening of (20) compared to Dewarbenzene itself.(19) (20) MIND0/3 Calculations suggest that the reaction of singlet oxygen with olefins is non-concerted proceeding via peroxirans (21) in the case of simple olefins and zwitterions (22) for electron-rich olefins (X = OR or NR2).8a Whilst the peroxirans can rearrange to ene products easily conversion into dioxetans is more difficult. On the other hand zwitterions can readily close to either dioxetans or peroxirans. Thus the best target for detection or trapping would be a peroxiran that is incapable of forming an ene product. Further calculations8’ give support to a proposed mechan- ism for oxiran formation in the reaction of hindered olefins with singlet oxygen (a)M. J. S. Dewar and S. Kirschner,J.C.S. Chem. Comrn. 1975,461; (b) ibid.p. 463; (c)M. C. Flowers and H. M.Frey J. Amer. Chem.Soc. 1972,94,8636;J. I. Brauman W. E. Farneth and M. B. D’Amore ibid. 1973,95 5043; (d)J. E. Baldwin and G. D. Andrews ibid. 1972,94 1775. ((I) M. J. S. Dewar and W. Thiel J. Amer. Chem. Soc. 1975,97,3978; (6)M. J. S. Dewar A. C. Griffin W. Thiel and I. J. Turchi ibid. p. 4439. Part (i) Orbital Symmetry Correlations and Peric yclic Reactions involving ‘reduction’ of a peroxiran intermediate (21) with singlet oxygeq to give ozone and the oxiran. Alternative formulations of the Woodward-Hoff mann rules continue to appear.’ In a very clear exposition Day provides’“ formal proof of the equivalence of the aromaticity and generalized Woodward-Hoffmann rules as well as compact new rules equivalent to the Dewar-Evans-Zimmerman rules.These are particularly easy to apply e.g. analysis of the Diels-Alder addition (23) simply involves choosing an (23) arbitrary connectivity cycle (--). The reaction is thermally allowed because the connectivity cycle crosses no atomic orbital modes (N= 0) and three electron pairs are involved (M= 3) so that M +N = 3 (odd number thermally allowed). Whilst this analysis is equivalent to Zimmerman’s reactivity index,96 it may have pedagogi- cal advantage. It has been notedgd that multicentre reactions e.g. the opening of prismane to benzene which cannot be directly analysed by the generalized Woodward-Hoff mann rules can be so analysed if they are first (artificially) divided into steps e.g. the prismane into benzene conversion is analysed as proceeding via Dewarbenzene and shown to be forbidden.The thermal cyclization of unsaturated carbonyl compounds has been reviewed.26 It involves enolization and intramolecule ene-reaction (Scheme 2). For reactions Scheme 2 leading to five-membered rings the syn-TS (24) giving a cis-relationship between the carbonyl group and the newly formed methyl group is preferred. A neat synthesis of chiral acetic acid” from the ether (25) involves an intramolecular ene-reaction (25; 9 (a)A. C. Day J. Amer. Chem. Suc. 1975,97,2431;(b)H. E. Zimmerman and H. Iwamura ibid. 1970 92,2015; (c) A. Rassat TetrahedronLetters 1975,4081;(d)P. Wieland Tetrahedron,1975,31,1641. lo C. A. Townsend T. Scholl and D. Arigoni J.C.S.am. Comm.1975,921. D. W. Jones arrows) to give (26) which undergoes allylic ether pyrolysis (retro-ene reaction) to (27); Kuhn-Roth oxidation then gives CHDTC02H,of (R)-configuration. 2 Cycloaddition and Cheletropic Reactions In the addition of difluorocarbene to norbornadiene (28; R =H) the normal non- linear cheletropic 1,2-addition to one double bond competes with apparent non- linear addition to the homoconjugated diene system giving (29; X = F; R =H). Steric inhibition of exo-attack on (28; R =Me) leads to predominant 1,4-addition of RR (29) difluorocarbene as well as the hitherto unobserved 1,4-addition of dichlorocar-bene giving (29; X =C1; R =Me).'' Photochemical opening of the azirine (30)gives Me n /Na + PhCEN-C -/ ?Me < ..\ Me Me (30) (31) (32) (33) the 1,3-dipole (31) which can rehybridize to the carbene (32); this then undergoes an unprecedented unturu-addition to the double bond giving (33).12 Loss of sulphur dioxide from (34) and its trans-isomer give respectively truns,trans-hexa-2,4-diene MeeMe (34) and the cis,trans-isomer with >99.9% stereoselectivity. Extrusion of sulphur dioxide from (35) and its trans-isomer is also highly stereoselective but here the polyene formed indicates unturu-elimination of SO2 e.g. (35)gives cis,cis,truns- H Me 02 0 (35) (36) C. W.Jefford W. D. Graham and U. Burger TetrahedronLetters 1975,4717; q.R.A. Moss and C. B. Malion J. Amer. Chem. Soc. 1975,97 344. l2 A. Padwa and P. H. J. Carlsen J. Amer. Chem.Soc. 1975,97,3862. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions octa-2,4,6-triene with ca. 98% stereoselectivity despite the congested environment of one methyl group the antaru-TS arrangement (36).13 ~ In the photochemical (2+2)~ addition of singlet excited trans-stilbene to cis- piperylene there is preference for addition to the more substituted double bond of the diene in accord with FMO consideration~.'~ In an interesting application of 'photochemistry without light' thermolysis of dioxetan (37) gave a mixture of (38) (37) (38) (39) and its known photo-product (39) in accord with cleavage of (37)to triplet excited (38) which then rearranges in part to (39).15The w2s+ T2aaddition of ketens to olefins continues to attract attention.The addition of diphenylketen to cis-ethyl propenyl ether is ca. lo2 times faster than addition to the trans-isomer. This is consistent with less steric hindrance in orientation complex (40) than in (41). In 0 =$ :H -1-'&;/ OEt Ph Ph 0 EtO\ -+. 11 /Me c= =$ H/ \H .a'\-Ph Ph (40) (41) contrast the cis- and truns-ethers react at about the same rate with tetra- cyanoethylene via dipolar intermediates. The TS's for the keten additions are thought to resemble the orientation complexes of the reactants closely with little bond formation. The large negative entropy of activation of the ethyl cis-propenyl ether addition (AS' = -45 e.u.) constitutes 67% of the activation energy (AH' = 7.0 kcal mo1-').16a Some of the adducts produced in this study lose alcohol if they are left to stand over alumina to give cyclobutenones e.g.(42),'6b which undergoes electrocyclic ring-opening (42; arrows) on heating or irradiation. 16' Whilst acyclic (partially) optically active 1,3-dialkylallenes add ketens to give mainly 2-2-alkylidenecyclobutanones(43) having little or no optical activity the l3 W.L. Mock J. Amer. Chem. Soc.,1975,97,3666 3673. l4 F. D. Lewis C. E. Hoyle and D. E. Johnson J. Amer. Chem. Soc. 1975,97,3267. H. E. Zimmerman and G. E. Keck J. Arner. Chem. Soc. 1975,97,3527. (a)R. Huisgen and H. Mayr TetrahedronLetters 1975,2965,2969;(b) H. Mayrand R. Huisgen Angew. Gem. Internat. Edn. 1975,14499;(c) H. Mayr ibid.,p. 500. D. W.Jones (43) (44) (45) addition of optically active 1,3-diphenylallene to t-butylcyanoketen is now shown17a to give the E-isomers (44)and (49,both of which are optically active and therefore formed to some extent via chiral TS’s.The difference between diaryl- and dialkyl- allenes may be rationalized using the usual orientation complex for w2s+ w2a addition. Thus (46; R = Ph) leads to (44)’whilst the more hindered complex with But and CN groups interposed leads to the minor adduct (45). When R = Ph positive charge accumulating at C-1 is stabilized by the phenyl group so that rotation ‘A’ leading to allylic stabilization of this charge can be delayed until far along the reaction path. When R = Alk rotation ‘A’ may run ahead of rotation ‘B’ so that zwitterionic intermediate (47),leading to 2-adducts is formed.Related dipolar 0 (46) (47) intermediates have been invoked to explain the products obtained from cyclo- propenes and ketens. Whilst the concerted ene-reaction of bis-trifluoromethylketen with 1-methylcyclopropene is favoured in the gas phase a dipolar addition becomes competitive in sufficiently polar solvents (Scheme 3).17’ The synthetic potential of 0 -44e &;;3 -(cF4y -::F)-0 CF3 Reagents i (CF,),CCO Scheme 3 additions involving ketens and allenes is indicated by the addition of dimethylketen to the cyclic allene (48) giving (49) which is strongly reminiscent of caryophyl-Iene.17‘ (48) 17 (a) H. A. Bampfield P. R. Brook and W. S. McDonald J.C.S.Gem. Comm. 1975; 132; (b)Dt H. Aue D.F. Shellhamer and G. S. Helwig ibid. pp. 603,604; (c) M. Bertrand R. Maurin J.-L. Gras and G. Gil Terruhedron 1975,31 849; H. Bertrand J.-L.Gras and J. Gore ibid.,p. 857. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions Two fine studies of Diels-Alder diene dimerization differ in their conclusions. Deuterium-labelled piperylene (50) affords a mixture of the endo-(51) and exo-adduct (52) indicating suprafacial addition to both the diene and olefin systems.'8" Me Me [Me Me /Me On the contrary the analogous dimerization of cis,cis- 1,4-dideuteriobutadiene apparently involves ca. 90% supra and 10% antara-addition to the double bond. Whilst the mode of addition to the diene is not established it is suggested that the 10% antarafacial addition may represent a concerted forbidden 7r4s +7r2uprocess the major process being the more familiar 7r4s3-r2s addition."* The intramolecular Diels-Alder reaction has been reviewed and numerous further examples have been provided.196-d The amide (53) undergoes preferred intramolecular addition uia the endo-arrangement shown which best preserves conjugation between the amide group and the diene system. On the other hand amide (54) in which the whole of the amide system is within the connecting bridge (53) (54) prefers the exo-arrangement shown which in this case best maintains analogous ~verlap.''~A cautionary note is sounded by the observation that (55) failed to give the expected product but instead isomerized to (56) which then gave (57).19' Ncm H,CH ,H Me Hcy2CH2 C0,Me CH2I* C0,Me .I Hr=iH (55) (56) (57) (a)J. A. Berson and R. Malherbe J. Amer. Chem. SOC.,1975,97 5910; (6)L. M. Stephenson R. V. Gernrner and S. Current ibid. p. 5909. ly (a)R. G. Carlson Ann. Reports Medicin. Chem. 1974,9 270; (b)W. Oppolzer W. Frostl and H. P. Weber Helv. Chim. Acta 1975,58,590,593;(c)R. F. Borch A. J. Evans and J. J. Wade J. Amer. Chern. Soc. 1975,97,6282;(d)P. G. Sarnrnes and R. A. Watt J.C.S. Chem. Comm. 1975,502;M. T. Cox ibid. p. 903; E. J. Corey and M. Petrzilka Tetrahedron Letters 1975 2537; J. J. S. Bajorek and J. K. Sutherland J.C.S. Perkin I 1975 1559; P. Yates and D. J. Bichan Canad. J. Chem. 1975 53 2045 2054; J. Auerbach and S. M. Weinreb J. Org. Chem. 1975,22,3311;R. H. Martin J. Jespers and N.De Fay Helv. Chirn. Acra 1975,58,776;Y. Nakamura W. E. Oberhansli R. Hollenstein J. Zsindely and H. Schrnid ibid.. p. 1949. D. W. Jones The great reactivity of both cyclobutadiene and cyclopentadienone towards dimerization follows from the small HOMO-LUMO energy gap predicted for these molecules. Frontier MO interactions will be particularly strong in the Diels-Alder dimerization of these species. A related effect is noted2' for the pyridinium betaines (58) which undergo (4+ 2)~dimerization to (59) more \rapidly as the electron- withdrawing effect of the group R increases. The HOMO coefficient at the nitrogen 0-6 no-\+ N R (58) (59) atom of such betaines is small whilst the corresponding LUMO coefficient is large.3u Electron withdrawal by R consequently reduces the HOMO-LUMO separation and promotes dimerization.The cycloaddition of electron-poor olefins to C-2 and C-6 of (58)is mainly determined by the betaine HOMO-dipolarophile LUMO interaction. Replacement of C-2 by a nitrogen atom lowers the HOMO energy and the resulting 3-oxidopyridazinium betaine shows reduced reactivity. The betaines add as 47r-components to fulvenes (60; arrows). Approach of the reactants as in (61) is LUMO 0-% *o 2%oMo lo HOMO R N R (60) (61) (62) favoured over the alternative (62) by the secondary interactions that are indicated between the betaine HOMO and fulvene LUM0.20 The triazine (63) adds dimethyl acetylenedicarboxylate at the indicated posi- tions,21 and so behaves as a 1,ll- rather than a 1,3-dipole.This accords with control +& -0.41t f0.41 by the dipole HOMO which has the Huckel coefficients indicated on (63) at the competing sites.3a 2o N. Dennis B. Ibrahim and A. R. Katritzky J.C.S. Chem. Cornm. 1975,425; see also N. Dennis A. R. Katritzky and M. Ramaiah J.C.S. Perkin I 1975 1506. 2' S. F. Gait M. J. Rance C. W. Rees R. W. Stephenson and R. C. Storr J.C.S. Perkin I 1975 556. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions Secondary orbital interactions can influence the regioselectivity as well as the exo- endo -selectivity of Diels-Alder reactions.22a A pretty example2" is provided by the addition of (64) to (65) which would yield regio-isomer (66) under the control of the coefficients at the termini of the diene system but regioisomer (67)if secondary MeoPh MeON02Ph Ph NO2 (64) (65) (66) (67) interaction between the nitro-group and C-2 or C-3 of the diene is dominant.The uncatalysed reaction gives the exo- and endo-forms of (66) because the secondary interactions are weak. In the catalysed reaction the secondary interactions are expected to be stronger,22C and the product is exclusively the endo-form of regio- isomer (67). The activation volume for the (6 +4)m-addition of tropone to cyclopentadiene is only -7S* 1cm3mol-' compared to values of cu. -35 cm3 mol-' for typical Diels-Alder reactions.23 The small partial molar volume of tropone associated with its dipolar character and consequent electrostriction accounts for this result in terms of a concerted reaction.As for Diels-Alder additions in which secondary interac- tions are possible the TS for this (6 +4)~-addition is smaller than the final state. It is pointed out that a secondary interaction is possible in the exo-TS (68). The 10&kMO secondary interaction shown in (69) has been proposed to explain the syn-selectivity observed for low-temperature addition of amino-nitrenes to diene~.~~ 3 Sigmatropic Reactions In the Stevens rearrangement of optically active (70)to (71)and (72) the degree of retention of configuration in the migrating a-phenylethyl group depends markedly Ph H Ph H Ph Me Me )-Me 'rH Me2yCH2COPh Me,NCHCOPh Me,NCHCOPh (70) (71) (72) (a) P. V. Alston R. M. Ottenbrite and D.D. Shillady J.Org. Chern.,1973,38,4075;(b)P.V.Alston and R. M. Ottenbrite ibid. 1975,40,1111;(c) K.N.Houk and R. W. Strozier J. Amer. Chern. Soc. 1973,95 22 4094. 23 W. J. le Noble and B. A. Ojosipe J. Amer. Chem. Soc. 1975,97,5939. 24 R.S.Atkinson and J. R. Malpass J.C.S. Chem. Comrn. 1975,555;see too R.S. Atkinson and R. Martin ibid. 1974 386. D. W.Jones on reaction conditions.2s" With sodium hydroxide-water at 0 "Cthere is 99f1Oh net retention of configuration but with sodium methoxide-methanol at 55 "C this figure drops to 56*2% and CIDNP and products of crossed radical coupling are observed. The stereoselectivity and intramolecularity of the reaction both decrease as the viscosity of the solvent decreases in agreement with a caged radical-pair intermediate (73) in which the rate of radical coupling is very fast k ca.lo1' s-'). [ Ph-?Ce] Me,NCHCOPh (73) Some contribution from a concerted process is not excluded by these results or those of a quantitative CIDNP study where the observed enhancement factors were 25% or less. than expected for a reaction proceeding. only by a free-radical path.'" However rapid recombination of the radicals may preclude evolution of the spin wavefunction; it is difficult to distinguish between a concerted pathway and the interaction of radical pairs which do not separate or even The photochemical ring expansion of bicyclo[2,2,l]heptan-2-ones to carbenes e.g. (74) to (75) has been reviewed and structural factors favouring the process have (74) (75) (76) been delineated.26" Unlike the corresponding ring-expansion of cyclobutanones,26b these reactions are believed to involve biradical intermediates e.g.(76) from (74). Thermal 1,3-sigmatropic shifts have been the subject of theoretical ~al~ulation,~~~-~ Epi~tis~~" pointing out that sub-jacent orbital control is important for non-polar but not polar 1,3-shifts and DewarZ7' predicting a biradicaloid forbidden pathway for the vinylcyclopropane to cyclopentene rearrangement. The photochemical 1,3-shift of the optically inactive diastereoisomer (77) affords a mixture of (78) and H H OMe (77) (78) (79) 2s (a)W. D. Ollis M. Rey I. 0.Sutherland and G. L. Closs J.C.S. Chem. Comm. 1975 543; (6) U. H. Dolling G. L. Closs A.H. Cohen and W. D. Ollis ibid.,p. 545. 26 (a)P. Yates and J. C. L. Tam J.C.S. Chem. Comm. 1975,737,739; (b)W.-D. Stohrer P. Jacobs K. H. Kaiser G. Wiech and G. Quinkert Forrschr. Chem. Forsch 1974,46 181. 27 (a)N. D. Epiotis R. L. Yates and F. Bernardi,J. Amer. Chem.Soc. 1975,97,4198;(b)W. W. Schoeller ibid. p. 1978; Chem.Ber. 1975 108 1285; A. Gavezzotti and H. Simonetta Tetrahedron 1975 31 1611; (c) M. J. S. Dewar G.J. Fonken S. Kirschner and D. E. Minter J. Amer. Chem. Sm. 1975,97 6750; (d)J. Gloor and K. Schaffner ibid. p. 4776; (e)G. R. Krow and J. Reilly ibid.,p. 3837; (f) J. J. Eisch and J. E. Galle ibid. p. 4436. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions (79) and is thought to proceed via a geminate radical pair.27d Thermal rearrange- ment of (80; R =H) to (81;R =H) is shown by deuterium labelling to involve retention of configuration at the migrating methylene group.Corresponding rear- rangement of (80; R =CH,Ph) is slow. It is believed that steric effects associated with the group R destabilize those conformations e.g. (82) in which the nitrogen (82) lone-pair can best overlap with the migrating ~r-bond.~~~ The borepin (85),isoelec-tronic with the tropylium cation is formed by heating (83); this could involve a PBPh mph6 /I D Phr P'h Ph Ph6 Ph (83) (84) (85) 1,3-boron shift to (84)followed by electrocyclic ring-~pening.~'~ Thermolysis of (86) gives the exo-isomer (86; Ac and C-5-Me interposed) and the cyclopentene (87). The two products are not formed from a common intermediate and only endo- isomer (86) gives (87).The large negative entropy of activation for the process giving (87) suggests a concerted rearrangement of novel type.28 (84) Functionalization a to a sulphur atom (88)-+(89) required in a biologically patterned synthesis of penicillins was achieved using benzoyl peroxide and may involve a 2,3-sigmatropic shift in the intermediate (90).29a A scheme involving repeated 2,3-sigmatropic shifts has been proposed for the 'growing' of macrocyclic rings.29b x OCOPh I S-CH S-CH "'00 b-r S-CH /\ // /+ \ (88) (89) (90) 28 J. P. Grosclaude H. U. Gonzenbach J. C. Perlberger and K. Schaffner J. Amer. Chem. Soc. 1975,97 4147. 29 (a)J. E. Baldwin,A. Au M. Christie,S.B. Haber and D. Hesson J. Amer. Chem.Soc. 1975,97,5957; (b)E. Vedejs and J. P. Hagen ibid. p. 6878. 66 D. W. Jones Cross-over experiments confirm that the low-temperature Cope rearrangement (<240 "C) of simple hexa-1,5-dienes is concerted. The rearrangement at higher temperatures (259-295 "C) is also concerted but at higher temperatures still (360-390 "C) rearrangement is by a dissociation-recombination mechanism.3oo The syn-anti-isomerization of bicyclononatrienes e.g (91)*(92) is believed to involve Cope rearrangement to intermediate cyclobutenes (93) and (94) which open to the Z,E,Z,Z-nonatetraenes (95) (Scheme 4).30bSince in (95) reverse cyclization to (93) is just as likely as forward-going electrocyclization to (94) the rate of conversion of (91) into (92) should be half the limiting rate at which (95) is trapped by tetra~yanoethylene.~"Thisrate relationship has now been established and provides strong evidence for this mechanism (Scheme 4),30bas opposed to an alternative It Reagents i (NC)&=C(CN) Scheme 4 recently Cope rearrangement of the type (96) -+(97) is accelerated by a factor of 1010-10'7 in the related potassium alkoxides and a further acceleration is observed in the presence of 18-cro~n-6.~~~ Whilst Claisen rearrangement of the geometrical isomers of propenylbutenyl ether (98) proceeds mainly via chair-like 30 (a) D.C. Wigfield and K. Taymaz Tetrahedron Letters 1975,3121;(b)C. P. Lewis and M. Brookhart J. Amer. Chern. Soc. 1975,97,651;(c) G. Boche H. Weber and J.Benz Angew. Chem. Internat. Edn. 1974,13,207;(d)J. M. Brown and M. M. Ogilvy,J. Arner. Chem. Soc. 1974,96,292;(e)D.A. Evans and A. M. Golob ibid. 1975,97,4765. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions TS'S,~'~ * the related rearrangement (99; arrows) adopts a boat-like TS.31 Although cation (100) undergoes the indicated 3,4-sigmatropy the corresponding rearrange- ment in cyclohexadienyl cations is much less imp~rtant.~'" MeCH=CHOCH,CH=CHMe BzO (98) Ph D 0-J (99) (100) There is growing appreciation of the structural factors influencing migratory aptitude in the 1,5-sigmatropic shift.32 Two pathways operate in the thermal conversion of cyclohexadienes (101) into meta -substituted toluenes (102) (Scheme 5).32a As judged by the incorporation of 13Clabel (*C) from the methyl group of 40' H PH2 -Me Scheme 5 (101) into the aromatic ring of the product path (a)is the major one for R =CHO COMe and CO,Me whilst path (6)is followed for R = Ph.This is taken to indicate that the migratory aptitude of the phenyl group is very much less than that of the methoxycarbonyl group. Very rapid 1,Sformy1 migration is observed for the 1-formylindene (103;Y = H) which racemizes at 50 "C by rearrangement to the isoindene (104; Y =H). Since racemization of (105) is twice as fast as its conversion into (103; Y =CDO) each act of racemization involves formation of (104; Y = CDO) in which there is a 50% chance of CHO-CDO exchange.326 Migration of a 31 (a)P. Vittorelli H.-J.Hansen and H. Schmid Heiv. Chim Acta 1975,58 1293; (b)B. Lythgoe and D. A. Metcalfe Tetrahedronhtters 1975,2447;(c)P. Vittorelli J. P. Katalinic G. Mukherjee-Muller H.-J. Hansen and H. Schmid Helv. Chim. Actu. 1975 58 1379. 32 (a)P.Schiess and R. Dinkel TetrahedronLetters 1975,2303;(b)D.J. Field D. W. Jones and G. Kneen J.C.S. Chem. Comm. 1975,754;(c)L.A. Paquette and M. J. Carmody J. Amer. Chem. Soc. 1975,97 5841;(d)J. Backes R. W. Hoffmann and F. W. Steuber Angew. Chem. Znfenurt. Edn. 1975,14,553;(e) A. P.ter Borg H. Kloosterziel and Y. L. Westphal Rec. Trav.chim. 1963,82,717;(e)J. J. McCullough and A. J. Yarwood J.C.S. Chem. Comm. 1975,485;(f)M. R.Willcott and I. M. Rathburn J. Amer. Chem. Soc. 1974,96,938;(g) W.R. Dolbier L. Mdullagh D. Rolison and K.E. Anapolle ibid.,1975 97,934;(h)J. S.Swenton K. A. Burdett D. M. Madigan and P. D. Rosso J. Org. Chem.,1975,40,1280; (i)U.Widmer H. Heimgartner and H. Schmid Heiv. Chim.Actu 1975,58,2210;(j)J. H. M. Hill T. R. Fogg and H. Guttmann J. Org. Chem. 1975,40,2562. D. W.Jones Me /CHO Me Me ,CDC A (103) (104) (105) butadienyl unit also occurs under mild The rate of the ester shift converting (106) into (107) is strongly dependent on the group R at the migration origin; (106; R = NMe,) rearranges 260 times faster than (106; R= Me).32d Similar E&' E E& E E EE (106) E = CO,Me (107) E = C0,Me (108) E = COzMe effects were observed earlier for 1,Shydrogen shifts in cy~loheptatrienes.~~" In the present correlation of rearrangement rate with the HOMO energy of the radical (108) is observed.For the transient isoindenes (109) observed by flash photolysis the indicated 1,5-H shift is faster for (109;Ar=Ph) than for (109) (110) (109; Ar =p-CNC6HJ.32e Alkyl migration in the related isoindene (1lo) is in contrast to that in simple cy~lopentadienes,~'~ a concerted process; ethyl migration is preferred to methyl migration by a factor of 7.32g Most of the data on migratory aptitude agree with accumulation of positive charge at the migration origin and negative charge on the migrating group at the rearrangement TS. Similar charge separation has been for a photochemical 1,7-hydrogen shift. The accelerating effect of phenyl substitution on thermal 1,7-hydrogen shifts has also been and a kinetic study of 1,5-shifts investigates the effect of incorporating the migrating group into rings of varying size.32i 4 Electrocyclic Reactions An ab initio SCF confirms and refines conclusions of an earlier336 VB study of the photochemical disrotatory closure of butadiene to cyclobutene.The generalized electrocyclic reaction (1 11) is predicted to proceed thermally in a 33 (a) D. Grimbert G. Segal and A. Devaquet J. Amer. Chem.SOC.,1975,97,6629; (6) W. Th.A. M. van der Lugt and L. J. Oosterhoff ibid. 1969,91 6042. Part (i) Orbital Symmetry Correlations and Pericyclic Reactions 69 conrotatory way and photochemically in a disrotatory way when Y =2=CH2and X =CH or NH. More surprisingly if X =2=NH and Y =CH2,all variations of the ring-closure are allowed whilst if X =CH and Y =2=NH the reactions are ther- mally forbidden and photochemically allowed for both modes of ring-~pening.~~" These predictions may be relevant to the that the symmetrical anion (112; X=N) closes stereospecifically to (113) but the unsymmetrical species (112; X =CH) undergoes non-stereospecific closure.Evidence favouring disrotatory opening of cyclopropyl radicals has appeared,35n and the opening of related Ph I A?. N-N H Ph Ph aziridinyl radicals The radical-anion (1 14) with cis-phenyl groups is stable to 0°C but if the phenyl groups are trans electrocyclic ring-opening (114; arrows) occurs at low temperature; the preference for conrotatory ring-opening indicated is in agreement with predictions made on the basis of a correlation diagram or INDO calculations and contrary to FMO prediction^.^^ A mechanism for thermal conversion of 5-into 3-substituted pyrones (Scheme 6) is supported by Scheme 6 18 0-labelling experiments the blocking of the reaction by a 6-methyl group and the more ready rearrangement of corresponding ~yran-2-thiones.~~ The anion (1 15) 34 (a)B.Schilling and J. P. Snyder,J. Amer. Chem. Soc. 1975,97,4422;(6)D.H.Hunter and R. P. Steiner Canad. J. Chem. 1975,53,355 35 (a)S. Sustmann and C. Ruchardt Chem.Ber. 1975,108,3043; (6)S.Sustmann R. Sustmann and C. Ruchardt ibid. p. 1527. 36 N. L. Bauld and J. Cessac J. Amer. Chem. SOC.,1975,97 2284. W. H. Pirkle and W. V. Turner J. Org. Chem. 1975,40 1617. 3' D.W.Jones undergoes rapid ring closure to (117) at -4 1 "C,possibly uiu the mono-trans-isomer (116).38 H H 38 S.W.Staley and A. S. Heyn J. Amer. Chern. Soc. 1975,97 3852.

ISSN:0069-3030    

DOI:10.1039/OC9757200053

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (ii) Polar Reactions ~~~~~~ By T. W. BENTLEY Department of Chemistry University College of Swansea Swansea SAZ 8PP 1Introduction This report consists of a selection of topics. Some important items are omitted for this year; in particular nucleophilic substitution at a saturated carbon atom the mainstay of this chapter for many years and which was covered in detail last year [Ann. Reports (B) 1974,71,112] this year makes way for its offspring nucleophilic vinylic substitution. Also the many extensive and continuing studies of carbocations and of neighbouring group participation are not discussed here but comprehensive coverage of the literature on organic reaction mechanisms is presented elsewhere.' 2 Nudeophdic Vinylic Substitution Although simple vinyl halides are unreactive towards nucleophilic substitution the field of nucleophilic vinylic substitution of simple vinylic substrates has developed rapidly since more reactive leaving groups were examined; e.g.one of the most suitable leaving groups is trifluoromethanesulphonate (triflate TfO CF3SO20-) which is displaced over lo4times more rapidly than toluene-p-sulphonate. It is now well established that many nucleophilic vinylic substitution processes proceed under solvolysis conditions by an SN1mechanism (Scheme l) and it has been possible to R' R3 R' R3 \ /R2 slow \ / c=c R2' -R' /c=c+ \x R2 X-rearranged products R1(') -CrC-R3 Scheme 1 'Organic Reaction Mechanisms' 1975 ed. A. R. Butler and M. J. Perkins Wiley London 1976.71 T. W.Bentley exclude plausible alternative mechanisms such as nucleophilic addition followed by elimination.2 The co-occurrence of products derived by rearrangement or elimina- tion in the vinyl cation (or ion pair) intermediate (1)also supports the proposed mechanism (Scheme l) and similar intermediates may be formed by addition to alkynes [see Section 3 below and Ann. Reports (B) 1974,71 1261. 1,2-Hydride shifts a characteristic process in trisubstituted carbocations have now been shown to occur in the disubstituted systems. Amongst the various solvolysis products of the triflate (2) was the ketone (3),which was probably formed by a 1,2-hydride shift across the double bond as shown in Scheme 2.3 Following 4 /Me /Me substitution H/c=c\ A 4/c=c+ + + elimination OTf H OTf 11.2-hydride shift Reagent i CF,CH,OH-H,O 80°C Scheme 2 previous work on 1,2-alkyl shifts towards the positively charged carbon atom in a vinyl cation [Ann.Reports (B) 1970 67 1271 it has now been shown that the corresponding 1,2-hydride shift also occurs (Scheme 3).4 In Schemes 1-3 the Me Me I substitution H-C-C=CH -& H-&-C=CH -+ + I1 I+ elimination Me OTf Me -0Tf 1,2-hydride shift Me Me I \+ I C-CH=CH -+ CF,CH,O-C-CH=CH, / I Me -0Tf Me Reagent i CF,CH,OH-H,O SO°Cb Scheme 3 counter-ion has been added to the authors’ original mechanistic interpretations so that the results are consistent with earlier stereochemical investigations showing preferential inversion of configuration during substitution [Ann.Reports (B) 1972 69 172 3831. These stereochemical investigations were extended to include cyclization processes for which it was suggested that inversion is again preferred 2 L. R. Subramanian and M. Hanack J. Chem. Educ. 1975 52 80. 3 K,-P. Jackel and M. Hanack Annulen 1975 2305; see also C. C. Lee and E. C. F. ICo,J. Org. Chem. 1975,40,2132. K.-P. Jackel and M. Hanack Tetrahedron Letters 1975,4295. Part (ii) Polar Reactions 73 because the (E)-hexadienyl derivative (4) yields more cyclized products [(7) (9) (lo) and (1l)]than the corresponding (Z)-isomer.' In the ion pair derived from the latter the leaving group and the participating double bond would be on the same side of the positively charged carbon atom and so cyclization would have to occur in the linear cation rather than in the ion pair.However both the ion pair derived from (4) and the linear cation are capable of cyclizing. The same four cyclized products [(7) (9) (lo),and (ll)]were also formed in the trifluoroethanolysis of the cyclohexen-4- yl tosylate (8); these results implicate the homoallylic cation (5) as a possible intermediate which may yield the allylic cation (6)by hydride shift.' elimination + substitution HH HH (4) H+ (7) (9) (10) Reagent :i CF,CH,OH 60 "C Scheme 4 When the vinyl group is substituted with appropriately placed aryl groups there is more direct spectroscopic evidence for vinyl cation intermediates. The 'H and 13C n.m.r.spectra of a solution of 1-fluoro-l-(p-methoxyphenyl)-2-methylprop-1-ene and SbFS in S0,ClF at -70 "C provides strong evidence for production of the vinyl cation (12) [Ann. Reports (B) 1974 71 2481 and a similar cation (13) has been generated from the corresponding chloride in a 1 :5 mixture of SbF and SO2C1F at -130°C.6 For both cations [(12),(13)]the n.m.r. spectra show that the methyl (12) (13) groups are equivalent (C2vsymmetry). From the 13C and 'H chemical shifts it was proposed that the favoured conformation of (13) was the bisected one in which the T. C. Clarke and R. G. Bergman J. Amer. Chern. Soc.,1974,96 7934; see also M.J. Chandy and M. Hanack Tetrahedron Letters 1975,4515. 6 S. Masamune M. Sakai and K. Morio Canad. J. Chem. 1975,53,784. T.W.Bentley ring conjugates with the empty p-orbital of the vinyl cation rather than with the double bond; apparently very little charge resides at the @-carbon of the cation. Generation of both cations was also substantiated by quenching experiments the more convincing one being the quenching of (13)in methanolic sodium methoxide at -80 "Cto give the appropriate methoxystyrene in over 50% yield.6 As might be expected evidence for the formation of even more highly stabilized cations can be obtained from the classical kinetic technique common-ion rate depression. During acetolysis of the bromide (14) there is a strong common-ion rate depression within the run or by added bromide ion and it was estimated that >93% of the acetate product arose from the dissociated cation (15).' An An \ /An \+ C=C C=C-An + Br-An = p-methoxyphenyl / Ph ' 'Br Ph (14) (15) Thus the behaviour of vinyl substrates in SN1reactions appears to be very similar to that of other substrates and perhaps the most surprising feature is the thirty year delay before vinyl substrates began to be studied extensively.In contrast to the S,l reactivity discussed above vinyl substrates appear to be much less susceptible to bimolecular nucleophilic substitution than other substrates. 3 Addition There has also been considerable interest in the production of vinyl cations by electrophilic addition to alkynes. In an extension of work on the formation of cyclopent-2-enones by acylation of alkynes[Ann.Reports (B) 1974,71,254] it has been shown that the corresponding reaction (Scheme 5) of the cycloacyl system (16) (19) Reagent i AgBF, CH2CI,-C2H,CI, -60°C Scheme5 2.Rappoport and Y.Apeloig J. Amer. Chem SOC.,1975,97,821 836. Part (ii) Polar Reactions leads to the fluoride (20) rather than to the cyclopentenone (19). These results suggest that the vinyl cation (17) undergoes a novel 1,5-hydride shift to give the secondary cation (18).8 Further work is needed to establish the mechanism of the cyclization to give cyclopentenones which occurs when the developing cation [marked * in (17)] would be primary and part of an acyclic system. Despite their frequent appearance in the more speculative literature there is no satisfactory evidence that primary aliphatic carbocations are formed as reactive intermediates and as they appear to be so unstable it seems likely that this is the source of the divergence of mechanisms.One of the ‘development areas’ of physical organic chemistry is the effect of increased pressure on organic reactions. Recent work on the gas-phase addition of hydrogen chloride to propene at pressures of up to 30 atm suggests that the reaction is first order in propene and at least third order in hydrogen chloride. The results were explained by rate-determining attack of a dimer of HCl on an HC1-propene complex [equations (1)-(3)] HCI +CH3CH=CH2 K2ecomplex (2) (HCI):!+complex A 2-chloropropane+2HC1 (3) The overall rate is then given by equation (4) d[RCl]/d t = k3K1K2[HC1l3[CH3CH=CH2] (4) and the overall rate constant (kobs)by equation (5) kobs = k K K -AI~(AS,+AS~)/R~-(AH,+AH~+E:)/RT3 1 2- (5) where subscripts 1 and 2 refer to equations (1) and (2) respectively and EL is the activation energy for reaction (3).The rate of reaction decreases with increased temperature and this can be accounted for if EL< IAHl +AH2( and evidence that AHl and AH2 were both -2.5 kcal mol-’ was presented. Thus in terms of the simplest form of the Arrhenius equation (kobs=Ae-Ee/RT) the sum of the energy terms in equation (5) corresponds to a negative activation energy. The reaction was envisaged to occur when the alkene complexed on one side by one molecule of hydrogen chloride is attacked on the opposite side by the dimer of hydrogen chloride.’ A six-centre transition state [e.g.possibly (21)]was proposed by analogy with earlier work.” H Me \ HCI / H/,c=c*\H H’ Cl ‘Cl__ -H’ (21) * A.A. Schegolev W. A. Smit V. F. Kucherov and R. Caple J. Amer. Chem. SOC.,1975,97,6604. M. J. Haugh and D. R. Dalton J. Amer. Chem.SOC.,1975,97,5674; see also Ann. Reports (B),1974,71 126. 10 D. L. King D. A. Dixon and D. R. Herschbach J. Amer. Chem. Soc. 1974,% 3328. 76 T.W.Eentley 4 Elimination Many aspects of p-elimination continue to be actively investigated. It is now widely recognized that there is a whole spectrum of mechanisms from the carbanionic ElcB to the E2C which involves some interaction between the base and the a-carbon attached to the leaving group.Movement within the spectrum of mechanisms depends on reactants and reaction conditions (Scheme 6) and thus the various y 6-c-c (22) (23) (24) Electron withdrawal at C -B Electron donation at C 6 Changing to poorer leaving group + Changing to more electronegative leaving group -P Changing C from primary to secondary or tertiary + Increase in base strength + Scheme 6 mechanistic classifications can be merged. However neither the detailed mechan- isms of each classification (ElcB E2H E2C) nor the detailed mechanism of merging seems to be generally agreed. For the E2C reaction the following new hypothesis for the nature of the bonding between the attacking base and the substrate has been put forward." In the transition state (22) the good leaving group X has departed from C but the weak base B-has not 'gained control' of the p -proton to any great extent.Therefore the partial .n-bond was visualized to have a bond order of less than 0.5 and the electron deficiency at C was assumed to be substantial Then assuming that the B....H...-Csystem is non-linear there could be an electrostatic interaction between the base B-(hardly neutralized by bonding to the H) and the electron-deficient C,. This proposal adopts some of the features of Bunnett's E2H spectrum and some of the Winstein-Parker E2C-E2H spectrum. The vital difference between the new proposal and the Winstein-Parker E2C mechanism is the nature of the interaction between B-and C, and among the evidence claimed to favour the electrostatic interaction was a correlation of the rates of elimination and the rates of substitution for a wide range of nucleophiles.Weak polarizable neutral bases (e. g. thiourea) gave more substitution than predicted by the correlation possibly because the electrostatic stabilization shown in (22) was very small.'* However it should be emphasized that the structures (22)-(24) represent transition states and the possibility that the five-co-ordinate structure (25) could be 11 D. J. McLennan Tetrahedron,1975,31,2999. 12 J. R. Pritt and M. C. Whiting J.C.S. Perkin 11 1975 1458. Part (ii) Polar Reactions an intermediate [see Ann. Reports (B) 1974,71 1231 may have been dismissed too readily -the evidence cited against this proposal appears to be only capable of ruling out a common symmetrical intermediate for E2C and SN2processes.Also from studies of secondary solvolyses it appears that there may be an unusually long-range nucleophilic interaction between solvent molecule(s) and the electron-deficient carbon and that although this interaction is moderate in size it is less susceptible to extinction by steric hindrance.'* Thus it is not certain how an E2C would be affected by steric hindrance and earlier criticisms [see Ann.Reports (B) 1973 70 1441 assuming that steric effects in E2C reactions would be of comparable magnitude to those in S,2 reactions may have been premature. At the other end of the spectrum of bimolecular eliminations are the reactions involving the formation of carbanion intermediates the conjugate bases (cB) of the starting materials (Scheme 7).If the expulsion of the leaving group (X) from the BH+ carbanion (27) is rate determining i.e. k-,[BH+] >> k2 the carbanion is formed reversibly and the mechanism is designated (EIcB),. Experimental evidence characteristic of this mechanism is obtained by deuterium exchange with the reaction medium and/or from the absence of a primary kinetic isotope effect for removal of the p -proton. For the (ElcB)R mechanism the observed rate constant kobs is given by kob= kl[B]k2/k-l[BH+]. Assuming that the equilibrium constant (kI/kl) for carbanion formation is independent of the leaving group (X) then observed rate constants for a series of substrates (26) with the same activating group (PhS02) should be propor- tional to k2 which should reflect the leaving group abilities of various X substituents in 1,2-eliminations.Results for an unusually wide range of leaving groups (e.g. CMe2NO2 CN N(Me)Ac OMe S02Ph and 'SMePh) varying in relative rates by at least 10l6show a remarkable lack of correlation with the pK of X-H or the C-X bond strength or the nucleophility of X. Since the sceptics might state that there are now enough empirical scales to enable us to correlate anything it should be emphasized that the results appeared in preliminary form!13 Experimental evidence for 'irreversible' E1cB reactions (for which k2>> k-,[BH'] -Scheme 7) is necessarily less direct as it is difficult to distinguish 13 D. R. Marshall P.J. Thomas and C.J. M.Stirling J.C.S. Chem Comm. 1975 940. 78 T. W.Bentley Ar'CH,SO,ArZ + Et,N & Ar'CHS0,Ar' k-i + Et&H (6) Ar'CHS03ArZ 5Ar'CH=SO + OAr2 H,O + Et,N + Ar'CH=SO Ar'CH,SO; + Et,&H (assuming a steady-state k 1kz[Et3Nl carbanion concentration) kobs = + k-I[Et,NH) + kz Scheme 8 from the classical E2 mechanism. Recent interest in this mechanism can be illustrated by the formation of sulphenes from aryl arylmethanesulphonates (Scheme 8). It was established that the (ElcB) mechanism occurred when Ar2=p-nitrophenyl that the observed reaction rates for a range of electron-withdrawing substituents in Ar' gave a Hammett p-value of 0.54 and that the reaction showed specific base promotion. In contrast when Ar2=2,4-dinitrophenyl p-was 2.7 the reaction showed only general base promotion and deuterium exchange did not occur.For the substrates already established to be reacting by an (ElcB) mechan- ism another Hammett correlation of values of k was obtained from the rates of deuterium exchange. Extrapolation of the correlation line gave predicted values of k which were in good agreement with the observed rate constants for the substrates which did not undergo deuterium exchange. Thiz is in agreement with the 'irrever- sible' ElcB mechanism because when k-,[Et,NH] <k, equation (9) reduces to kohs = k,[Et,N]. Furthermore the effect of added Et,NH was as predicted by equation (9),also consistent with an irreversible ElcB mechanism rather than with a classical E2 mechanism.14 As the departing ability of (OAr2)- increases k increases until it reaches 1013s-' when the 'lifetime' of the carbanion would be less than the vibration time of the S-OAr bond.Then the carbanion would not exist as an identifiable species and the irreversible ElcB mechanism would have merged into a concerted E2 mechanism with carbanion-like character. l5 An extreme case of an ElcB reaction occurs with the cyanide (29) which reacts with trimethylamine to form such a stable carbanion that elimination does not occur. Using pyridine or collidine as bases elimination of CF3CH20-from the carbanion (30) to give the alkene (31)is first order in carbanion and first order in protonated base (BH'). The role of the BH' may be to assist electrophilically in the removal of the leaving group and this new mechanism was designated E2cB.16 14 J.F. King and R. P. Beatson Tetrahedron Letters 1975 973. 15 K. T. Douglas A. Steltner and A. Williams J.C.S. Chem. Comm. 1975 353; see also R. A. More O'Ferrall and P. J. Warren J.C.S. Chem. Comm. 1975,483. 16 M. Albeck S. Hoz,and Z. Rappoport J.C.S.Perkin II 1975 628. 79 Part (ii)Polar Reactions 5 CarbonAadity The acidities of weak carbon acids are relevant to wide areas of organic dhemistry from synthesis to electronic theory. Interpretation of substituent effects in the gas phase is important in evaluating electronic theories of organic chemistry and comparisons between gas phase and solution give information about solvent effects. There has been considerable activity recently in studies of gas-phase effects and dimethyl sulphoxide (DMSO)has been found to be a very useful solvent for studies in solution.One of the advantages of DMSO is its ability to increase the basicity of an aqueous hydroxide so1ution.” Also the pure solvent has a high dielectric constant is strongly dissociating and can be used to determine equilibrium acidities without complications from the effects of ion association.’8 In a short cautionary note Bordwell et al.19 have warned that the determination of acidities from kinetic l2 t. 10 14 18 22 26 30 34 38 42 46 50 Equilibrium Acidities in DMSO (kcal /mole) Figure Equilibrium acidities of carbon acids in DMSO solution plotted against intrinsic gas- phase acidities (Reproduced by permission from J.Amer. Chem. SOC.,1975,97,3226) 1’ W. S. Matthews J. E. Bares J. E. Bartmess F. G. Bordwell F. J. Cornforth,G. E. Brucker,2. Margolin, R. J. McCallum G. J. McCollum and N. R. Vanier J. Amer. Chem SOC.,1975,97,7006. 18 D. W. Earls J. R. Jones T. G Rumney and A. F. Cockerill J.C.S.Perkin ZI 1975 54. l9 F. G. Bordwell W. S. Matthews and N. R. Vanier J. Amer Chem. SOC.,1975,97,442. T. W.Bentley measurements (e.g. deuterium exchange) is particularly susceptible to complications from the effects of ion association and internal return -apparent carbanion stabilities based on kinetic acidities may change by several orders of magnitude depending on the nature of the cation anion and solvent. Consequently discussions of carbanion stabilities should relate to equilibrium acidities although in organic synthesis advantage can be taken of different kinetic acidities [e.g.Ann.Reports (B),1974,71 4451. As expected the degree of dissociation of an acid in solution is much greater than in the gas phase -e.g. the Hammett p value for dissociation of rnetu-and pura-substituted benzoic acids is 1.0in water (by definition) 2.5 in DMSO and 10.0in the gas phase.*' Thus it is surprising (at least to some chemists' expectations) that the gas-phase acidities of a series of nitriles and ketones closely parallel the equilibrium acidities in DMSO (Figure). However with the benefit of hindsight it may be argued that the failure of substituent effects to be attenuated appreciably is probably because the charge is delocalized in each case over the entire anion whereas for carboxylic acids the negative charge is largely localized on the carboxylate anion.21 Related studies of enthalpies of solvation of alkoxide anions in DMSO suggest that steric hindrance to ion solvation becomes increasingly important as the size of the alkyl group increases.22 Comparisons between DMSO and water can also be made -water is a strong hydrogen bond donor and also a strong hydrogen bond acceptor whereas DMSO acts as a strong hydrogen bond acceptor but is only a very weak donor.Consequently oxygen acids (e.g. phenols carboxylic acids) as well as carbon acids where the negative charge resides mainly on oxygen (e.g. nitroalkanes) are more acidic in water than in DMSO because the anions are solvated by strong hydrogen bonding.*' 6 Enolition of Ketones One of the first organic reactions to be investigated mechanistically the halogenation of acetone occurs by rate-determining enolization (except at very low halogen concentrations) and the rate law in acetate-buffered solution is well established [equation (lo)].The term kA[HA]is kinetically equivalent to kL[H,O'][A-] and is thought to represent a mechanism in which protonation of the ketone is followed by removal of a proton by acetate (Scheme 9).23 It was argued that the kB term represented general base catalysis of proton removal to give an enolate anion stabilized by hydrogen bonding to water because there would be no thermodynamic 20 R.Yamdagni T. B. McMahon and P.Kebarle J. Amer. Chem. Soc. 1974 % 4035. *J F. G. Bordwell J. E. Bartmess G. E. Drucker 2. Margolin and W. S. Matthews J. Amer. Chem. Soc. 1975,97,3226. 22 E. M. Amett D. E. Johnston and L. E. Small J. Amer. Chem. SOC.,1975,97,5598. 23 G. E. Lienhard and T. C. Wang J. Amer. Chem. Soc. 1969,91 1146; J. Toullec and J. E. Dubois J. Amer. Chem. SOC.,1974,96 3524. Part (ii) Polar Reactions kdA-1I + IH-C-C I / \ = 7 IH-C I -C /OH \ Scheme 9 advantage in transferring a proton from water to the enolate anion (pK =11)24325-note however that k,[B] is kinetically equivalent to kb[BH'][oH]. Recent studies have confirmed that the third-order term (k,) is not an artifact from a solvent or specific salt effect and a mechanism was proposed (similar to that for kB) in which the base-catalysed removal of the proton and the enolate anion was stabilized by hydrogen bonding to the This explanation implies that the Bronsted 0 values should be similar for kBand kAB,and from the known value of 0.88 for k a value of 0.68 was predicted for the p value for kAB.However the observed value of p for kAB was 0.15 which suggests that an increase in the effectiveness of the catalysing base is largely cancelled by a decreasing effectiveness of the catalysing acid.Consequently the dependence of k on the strength of the catalysing acid must be large and a Bronsted a! value of 0.5 was estimated. These and other results suggest that the third-order term represents true bifunctional catalysis with partial proton abstrac- tion by acetate ion and a significant movement of the proton of acetic acid towards the carbonyl oxygen atom in the transition Some authors have dismissed the possibility of termolecular processes but it may be that the involvement ofprotons as the third component of a termolecular reaction (as suggested for k,)* is not an unlikely process because an appropriate hydrogen may be in the solvent shell in close proximity to the reaction site (see also later discussion of ref.26). If the proton to be transferred is already hydrogen bonded to the appropriate atom (e.g. to the carbonyl oxygen for k,) it could be argued that this constitutes pre-equilibrium formation of a 'complex' and that the reaction is really bimolecular -e.g. for k the bimolecular reaction would be between acetate ion and the 'complex' of the ketone and acetic acid.However extension of this argument involves the reasonable though unusual proposition that a beaker full of water contains one 'complex' molecule made up of hydrogen-bonded H,O units. A much clearer case of electrophilic catalysis by complex formation of the general base-catalysed enolization of ketones has been observed in the iodination of acetylpyridines. Metal ions catalysed the reaction of 2-acetylpyridine (33) but not that of 4-acetylpyridine (32). It was calculated that the Zn2' complex reacted over * In contrast however the other terms (kAand kB) appear to represent stepwise processes (Scheme 9). E. S. Hand and W. P. Jencks J. Amer. Chem. SOC., 24 1975,97,6221.25 A. F. Hegarty and W. P. Jencks J. Amer. Chem. SOC.,1975 97 7188; see also R. Breslow 'Organic Reaction Mechanisms' Benjamin New York 2nd. Edn. 1969 pp. 52-56. 26 s. Rosenberg S. M. Silver J. M. Sayer and W. P. Jencks J. Amer. Chem. SOC.,1974,96,7986. T. W.Bentley Q lo3times faster and the Cu2+ complex over lo5times faster than the uncomplexed substrate presumably via a transition state like (34) whereas 4-acetylpyridine (32) could not form a similar complex.27 7 Tetrahedral Intermediates Carbinolrrmines.-The formation of imines hydrazones and related derivatives from carbonyl compounds is often drawn as a two-step process [equation (1l)] \ I / RNH,+ CEO * RNH-C-OH -* RN=C +H2O (11) / I \ As the dehydration step is acid catalysed at pH values below neutrality most reactions of this type undergo a change in rate-determining step from dehydration to formation of the carbinolamine.For the addition of methoxylamine (NH,OMe) to p-substituted benzaldehydes this change in rate-limiting step occurs at pH “4 inferred from the ‘break’ in the pH-rate profile (i.e.graph of kobsus. pH). At pH = 1 these reactions also show a second break in the pH-rate profile,26 whereas reactions between methoxylamine and acetone and between the aromatic aldehydes and semicarbazide do not.28 The mechanism shown in Scheme 10is consistent with this and other experimental evidence.26 + A-+I HA 2 RNH,-C-OH / RN-\CG k-1 I T+ qk- IRNH-C-OHI /% RN=C \ g To RN>\C& 5 R&H2-C-O-I Note Values for the 11 rate / k-2 I constants are given in ref.27 T* Scheme 10 27 B.G. Cox J. Amer. Chem. Soc. 1974,%,6823;see also P.Woolley J.C.S. Chem. Comm 1975,579. 28 J. M.Sayer B. Pinsky A. Schonbrunn and W. Washtien J. Amer Chem. SOC.,1974,96,7998;see also G. P. Tuszynskiand R. G. Kallen J. Amer. Chem Soc. 1975,97,2860. Part (ii) Polar Reactions According to this mechanism the reaction occurs as follows. Below pH =1 the dominant mechanism is the acid-catalysed addition of the amine to the aldehyde (k,) to give T'. Concurrent with this process around pH 1 and dominant towards pH 4 is the hydronium-ion catalysed 'trapping' (k3) of the highly unstable zwitterionic intermediate T. However this process has two possible rate-determining steps -in the lower pH region the uncatalysed addition step (k2)appears to be rate-limiting whereas towards pH 4 the concentration of the hydronium ion catalyst decreases and the amount of unprotonated methoxyamine available to react via k2 increases so that diff usion-controlled process (k3) becomes rate-determining.* Around pH 4 acid-catalysed trapping of T(k3)becomes so slow that it ceases to be a significant process and reaction occurs by rate-determining trapping of Tby proton transfer through the surrounding solvent (k,=lo6-lo7 s-') [see also Ann.Reports (B) 1974 71 1311. At higher pH the dehydration step (k5)is rate-determining. Consequently the second break in the pH-rate profile occurs when the acid- catalysed direct route to T' (k,)takes over from the uncatalysed route via T.For the reaction represented by k the following argument (as well as others) suggests that the hydronium ion acts as a general acid and that protonation is 'concerted' with nucleophilic attack by amine (see also discussion of reference 25).26 The rate constant k',for nucleophilic attack on the protonated aldehyde is given by k;=k,K (at pH 0). Assuming that pK for protonated p-nitrobenzaldehyde was -8.1 and knowing kl,this gives avalue of 2.4 x lo-" mol-' 1 s-' for k',,which would rule out this stepwise mechanism because k' is about lo2greater than the expected upper limit for diffusion-controlled processes. The authors26 note that the hydro- nium-ion catalysed reaction is the first example of a reaction involving rapid proton transfer to or from an electronegative atom that has been observed to proceed by concurrent kinetically distinct 'concerted' (k,)and stepwise (k2,k3) pathways for proton transfer with a single catalyst.Thus concerted catalysis may occur even when the intermediate (T) in the stepwise pathway is stable enough to have a finite lifetime (cf.reference 29). Studies of other amines supported the prediction that the concerted pathway would be favoured as the basicity of the amine decreased.28 From Esters.-An unusually large negative activation energy (ca.-10 kcal mol-') has been determined for the third-order reaction between n-butylamine and p-nitrophenyl trifluoroacetate in either chlorobenzene or 1,2-dichloroethane -also AS+is -70 cal K-' mol-'! When the reaction is catalysed by general bases it is first order in ester amine and catalyst but the rate constants do not follow the Bronsted catalysis law.The role of the catalysing base (or the second molecule of butylamine) appears to be to assist in the removal of a proton from the amine (Scheme 1l).30 The first reaction [equation (12)] is thought to be rapid and it may proceed by two sequential bimolecular processes or by one termolecular step. Unimolecular col- lapse of the intermediate [equation (13)] was thought to involve essentially simul- taneous breaking of the N-H and C-0 bonds so that formation of completely free ions was avoided. As equation (13) represents conversion of a zwitterion (35)into * Note that k refers to rate constant whereas reaction rate devends on k x appropriate concentrations.z9 W. P. Jencks Chem. Rev. 1972,72,705. 30 T. D.Sin@ and R. W. Taft J. Amer. Chem. SOC.,1975,97,3867; see also C.-W. Su and J. W. Watson J. Amer. Chem. SOC.,1974,96,' 1854. T. W.Bentley 0- CF,C//O + RNH + B CF,(!-OAr I \ OAr R-N+-H....B I H (35) Scheme 11 an ion pair (36)and a good leaving group is departing from an electron-rich centre the activation energy may be small but positive -the negative activation energy arises because reaction (12)is strongly exothermic [see also equation (5)J. However if the 1,2-dichloroethane solvent contains 0.487 mol I-’ methanol AH* for aminolysis is close to zero (a sharp increase from -10kcal mol-’!) whereas in the same solvent AH*for methanolysis is +4.4 kcal mol-’.Methanol may hydrogen- bond to the zwitterion intermediate (35) and it was suggesed that the marked change in activation parameters between ‘hydrophobic’ and ‘hydrophilic’ environments may provide a model for temperature regulatory action in certain enzymatic processes.3o 8 Micellar Catalysis Micelles are the high molecular weight aggregates of surface-active agents (e.g. detergents) containing a long hydrocarbon chain (hydrophobic) and a polar or ionic group (hydrophilic). Specific interactions between a substrate and either the hyd- rophobic or the hydrophilic part of the micelle in dilute solution can give rise to large rate effects either enhancement or inhibition and there is considerable interest in the kinetics and mechanism of these processes as catalysts and models for various biochemical processes.Consequently there have been many investigations of the reactions of carboxylic esters,31 but the following discussion will summarize some other recently published studies. The acid-catalysed rearrangement of hydrazobenzene (37)to benzidine (38) is accelerated by a factor of 1.5X lo3 by anionic micelles of sodium lauryl (37) (38) + o,p-isomer (39) sulphate larger than expected by analogy with rate accelerations observed in other specific hydrogen-ion catalysed reactions. The rearrangement is slightly inhibited by neutral micelles (possibly a solvent effect) whereas the reaction is sharply inhibited by the cationic micelles of cetyltrimethylammonium bromide presumably because 31 J.H. Fendler and E. J. Fendler ‘Catalysis in Mioellar and Macromolecular Systems’ Academic Press New York,1975; E. J. Fendler and J. H. Fendler Adu. Phys. Org. Chem 1970,8,271; see also Ann. Reports (A) 1973,70 167. Part (ii) Polar Reactions the hydrazobenzene is taken into the micellar phase from which hydrogen ions are excluded. The rate laws for both the normal and anionic micelle-catalysed reaction appear to be the same (first order in hydrazobenzene and second order in H+) although there is inevitably some uncertainty in the distribution of hydrogen ions between the micelles and the bulk solvent. Also addition of more of the detergent than is necessary to take up all of the hydrazobenzene into the micelles decreases the rate constant because it reduces the possibility of havingsubstrate plus two hydrogen ions in the same micelle.The anionic micelles did not change the product composition [80% of (38) 20% of (39)] and it was suggested that the micelles catalysed the reaction by bringing the three particles together in the micellar phase prior to formation of the transition state. Thus the effective concentrations of reactants increase and the unfavourable loss of entropy in forming the transition state is reduced. This argument suggests that such effects should be more important for third-order processes than for processes of lower order and is supported by the observation that the second-order rearrange- ment of 1,2-di-o-tolylhydrazine is only accelerated sixty-fold (cf.1500above) at the optimum micelle concentration.Also from more detailed studies of rearrangement of (37)at various acidities it was suggested that the second protonation step (either on carbon or nitrogen) may be rate-determining whereas previously it has been generally assumed that both proton transfers are pre-eq~ilibria.~~ Formation of micelles may also influence stereochemistry -e.g. hydrolysis of 2-octyl trifluoromethanesulphonate by alkyl-oxygen fission proceeds with predo- minant retention of configuration and is retarded about 300-fold by both cetyl- trimethylammonium bromide and sodium lauryl sulphate whereas predominant inversion occurs during normal hydroly~is.~~ As the stereochemistry of secondary solvolyses is known to be influenced by double inversion processes [e.g.Ann. Reports 1965,62 2391 it may be fruitful to check whether 2-octyl bromide or the corresponding sulphate are reaction intermediates. Deamination of amines (40) in aqueous perchloric acid has been shown to depend on micelle formation by the amines themselves. For (40a) the critical micelle concentration (the concentration at which the micelles first become detectable) is NH OH aq. HCIO Me pH 3.5 Me (40) (41) (42) (a) R = Et (b) R = CH2CH,CHMe2 0.35 moll-' whereas it is 0.1 mol I-' for (40b) which has a larger alkyl group. At the critical micelle concentrations direct substitution [(40a) to (41a)l occurs with excess inversion of stereochemistry whereas the 1,2-hydride shift [(40a) to (42a) and of (40b) to (42b)l occurs with excess retention of configuration.However at high micelle concentrations the opposite results are obtained -substitution occurs with excess retention of stereochemistry whereas the 1,2-hydride shifts occur with excess 32 C. A. Bunton and R. J. Rubin TetrahedronLetters 1975 55 59. 33 K. Okamoto T. Kinoshita and H. Yoneda J.C.S. Chem. Comm. 1975,922; see also C. N. Sukenik B.-A. Weissmann and R. G. Bergman J. Amer. Chem. Soc. 1975,M 445. 86 T. W. Bentley inversion. This correlation between direct substitution and hydride shift may be due to asymmetric ~olvation.~~ 9 Phase-transfer Catalysis Tetra-alkylammonium and tetra-alkylphosphonium salts catalyse reactions which are inhibited because of the inability of the reagents physically to come together -e.g.reaction between aqueous sodium cyanide and alkyl chlorides (Scheme 12). The RCI + QCN + RCN + QCl (organic phase) t 1 NaCl + QCN $ NaCN + QCl (aqueous phase) Scheme 12 quaternary salt (QX) brings the cyanide into the organic phase (e.g.benzene) as the soluble ion pair QCN and returns the displaced chloride ion to the aqueous phase where QCN can be regenerated. It appears that the rate-determining step takes place in ihe organic phase rather than in the aqueous phase at the interface or in micelles. Also the anions are less strongly solvated in the organic phase (e.g. no hydrogen bonding) and so displacement reactions occur more readily. This techni- que ‘phase-transfer is useful for many other types of reaction including generation of carbenes [Ann.Reports (B) 1974 71,1631 but only displacement reactions are reported here. The second-order reaction between thiophenoxide ion (PhS-) and 1-bromo- octane was independent of stirring speeds (200-2200 r.p.m.) and the rate of reaction was linearly dependent on catalyst concentration in contrast to micellar catalysis (Section 8). At fixed catalyst concentration the reaction rate was found to increase with the polarity of the solvent forming the organic phase (0-dichlorobenzene >benzene >heptane) and with the size of the alkyl groups in the catalyst. A correlation between rate constants and partition coefficients was noted which suggests that the major function of the catalyst is simply the solubilization of the nucleophile in the organic phase.This interpretation is supported by the increase in reaction rate with increasing ionic strength of the aqueous phase because the large organic ions are ‘salted out’ to the organic phase.36 Also from studies of Williamson ether syntheses requiring phase transfer of alkoxide anions (‘hard’) the use of bisulphates as the catalyst’s counter-ion was recommended because under the reaction conditions the unextractable ion SO:-was produced. In contrast if halide anions (‘soft’) are present either from the original catalyst (QX) or from the leaving group they are selectively transported and the reaction rates are reduced.37 Clear evidence that the phase-transfer reaction occurs in the organic phase has been obtained for displacement of n-octyl methanesulphonate with halide ions (X= C1 Br I) in water-chlorobenzene catalysed by C,H,,P’Bu,X- [equation (14)].It was shown that the activation parameters and the relative rates of the phase- n-C8H170S02CH3+KX -* n-CsH17X +CH,SO,K (14) 34 W. Kirmse G. Rauleder and H.-J. Ratajczak J. Amer. Chem. SOC.,1975 97,4141. 35 C. M. Starks and R. M. Owens J. Amer. Chem. SOC.,1973,95 3613. 36 A. W. Herriott and D. Picker J. Amer. Chem. SOC.,1975,97,2345. 37 H. H. Freedman and R. A. Dubois Tetrahedron Letters 1975 3251. Part (ii) Polar Reactions transfer reactions could be simulated under homogeneous conditions provided that small predetermined amounts of water were added to the chlorobenzene-it is known that the catalyst also transfers water to the organic phase and it was shown that this depended on the halide ion; in addition 0.15 mole of water per mole of substrate was calculated to be present in the organic phase.38 Quaternary ammonium groups anchored to a polystyrene resin have also been shown to catalyse displacement reactions and this technique may be convenient in syntheses because the catalyst can be removed by filtrati~n.~’ Insoluble polymers have also been used in a ‘three-phase test’ for reactive intermediates which involves the generation of a reaction intermediate from an insoluble polymeric precursor and its detection by trapping on a second solid phase suspended in the same solvent.Since only a fraction of the active sites of the polymer are at the surface it is assumed that any observed reaction between the two solid phases requires the existence of free intermediates.This ‘non-classical’ method has been applied to the detection of acylmidazoles from the imidazole-catalysed hydrolysis of o-nitrophenyl esters4’ and to the detection of free cy~lobutadiene.~~ 38 D. Landini A. M. Maia F. Montanari and F. M. Pirisi J.C.S.Chem. Comm 1975,950. 39 S.L. Regen J. Amer. Chem Soc. 1975,97 5956. 40 J. Rebek D. Brown and S. Zimmerman J.’Amer.Chern. SOC.,1975,97,454. 41 J. Rebek and F. Gavina J. Amer. Chem. SOC.,1975,W. 3453.

ISSN:0069-3030    

DOI:10.1039/OC9757200071

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

4 Reaction Mechanisms Part (iii) Electron Spin Resonance Spectroscopy and Free-radical Reactions By A. T. BULLOCK Department of Chemistry University of Aberdeen Old Aberdeen Scotland A69 2UE This year three specific areas have been selected for review. These are kinetic studies chemically induced electron polarization and equilibria involving free radicals and radical ions. 1 Kinetics and Mechanism In their continued studies of kinetic applications of e.s.r. Ingold and his co-workers have introduced the useful term 'persistent' to distinguish radicals which whilst not being stable in the thermodynamic sense are usually for steric reasons long-lived in solution. For example each radical in the formation of the alkyl radical Me,Si(Me,C)CCH(SiMe,) (1) has been observed2 (Scheme 1).At Me,Si. + Me,CC-CH + Me,CC=CHSiMe li Me,Si( Me C)CHCHSi Me +-Me,CCH=CHSiMe + Me,Si-4-H. Me,Si(Me,C)C=CHSiMe % Me,Si(Me,C)CCH(SiMe,) (1) Reagents i Me,SiH ;ii Me,Si. radical. Scheme 1 50 "C ti the half-life of (1)at an initial concentration of 3 X moll-' was 23 h. Further cases of radicals which are 'destabilized' yet persistent are certain vinyl and ally1 radicak2 One example must suffice. Radical (2) has been produced by the D. Griller and K. U. Ingold J. Amer. Chem. SOC.,1975,97,1813. * D. Griller J.'W. Cooper and K. U. Ingold J. Amer. Chem. SOC.,1975,97,4269. D. Griller K. Dimroth T. M. Fyles and K. U. Ingold J. Amer. Chem. Soc. 1975,97,5526. D. Griller L. R. C. Barclay and K. U. Ingold J.Amer. Chem. Suc. 1975,97,6151. 5 R. A. Kaba L. Lunazzi D. Lindsay and K. U. Ingold J. Amer. Chem. Soc.,1975,97,6762. 88 Part (iii) Electron Spin Resonance Spectroscopy and Free -radical Reactions addition of the trimethylsilyl radical to the appropriate di-t-butylvinylidenecyclopropaneaccording to Scheme 2. a(l3C,)=4.28 mT," which implies that the spin density on C is close to unity and that therefore the symmetry axis of the 2pz orbital on C has been twisted ca. 90" out of conjugation with the double bond. Clearly this represents maximum destabilization of (2) and yet the radical is very persistent. A comparative study4 has been made of the kinetic behaviour of the structurally related 2,4,6-tri-t-butyl-benzyl,-aniline -phenoxy and -phenylthiyl radicals (3a-d).Radical (3a) was readily prepared by photolysis of ArCH in di-t-butyl Bu' But (3) a X = -CH2; b X = -NH; c x = -0; d:X= -S peroxide. Cutting off the light resulted in a second-order decay with a rate coefficient of (5 f2) x 10' 1mol-' s-' at room temperature. Product analyses indicated the formation of the head-to-head dimer thus kl 2ArCH2 + ArCH2CH2Ar (1) (34 In contrast the anilino radical ArNH (3b) was found to be rather stable. Indeed the concentration of (3b) increased and decreased reversibly on raising and lowering the temperature ArNHNHAr 2ArNH k-z In the temperature range -40 to -65 "C AH = -54.8 f2.1 kJ mol-' and AS = -113f8 J moF1 K-'. Temperature-jump measurements enabled a determination of k-2 to be made and hence from the equilibrium constant K( = k2/L2),k was found.Expressed in Arrhenius form log(k-2/lmol-' ~-~)=6.3(=kl.0)-10.5(f3.3)/i9 (34 and log (k,/s-') = 12.2-65.3/e (3b) where 8 =2.303RT kJ mol-l. At room temperature k- =3 X lo41mol-' s-' which is some four orders of magnitude slower than the dimerization rate of the benzyl radical (3a). The arylthiyl radical (3d) showed complex kinetic behaviour but equilibrium constants for the dissociation of the dimer were 1.7x lo-'* moll-' and 1.3 X mol 1-1 at 18"C and 28 "C respectively (AH= -97.5 *8.4 kJ mol-'). In * All hyperfine coupling constants (hfcc's) are given in mT (1 mT= 10G) A. T.Bullock contrast the phenoxy radicals showed no tendency to dimerize or decay between room temperature and -100"C.There have been other reports of kinetic studies using similar techniques to those above namely monitoring the decay rate of photolytically generated radicals after the light was cut As an example we take the virtually thermoneutral hydrogen-atom transfer6 shown in Scheme 3. Under steady-state conditions a broad OOH k ROO* + d 3,ROOH + \ (4) a R = But \ b R = C2H4C(CH,)2 (5) (4) Scheme 3 singlet was observed with g = 2.015 (ie. ROO-). The concentration of this species was found to be proportional to the intensity of the light and hence to the rate of radical production but inversely proportional to [(5)]. This indicated that the alkylperoxy radical detected was (4a b) and that (6) did not contribute.The following rate law was found by following the rate of decay of the signal after shuttering the light -d[Bu'OO.]/dt = 2k3[ButO0.][~-CloH1 100HJ (4) (4b) Also followed equation (4) with values of k identical to those found for (4a). The results fitted the equation log (k3/l rno1-l s-l) = (6.0*0.5)-(18.8*2.0)/e (5) where again 8=2.303RTkJmol-'. A very large isotope effect was noted with a-C,,H,,OOD; at 21 "C k3H/k,D = 9. Further studies using 9,10-dihydro-9- hydroperoxyanthracene s-butyl hydroperoxide and triphenylmethyl hydroperox- ide showed identical kinetic behaviour. Furthermore from the absolute values of k it seems that the nature of the alkyl moiety associated with the hydroperoxide has little influence on the rate of the transfer reaction.An example of a rapid reaction which required the use of rotating-sector and signal-averaging techniques is the second-order decay of SF generated photolytic- ally by Scheme 4(a) and (b).' A plot of l/[SF,] versus time was linear; hence the rate equation is -d[SFS]/dt = 2k6[SFJ2 (6) (4 SFSCl SF + C1. (b) SF,OOSF % 2SF,O. SFSO-+ PF --* [SF,OPF,] -+ SF + OPF Scheme 4 J. H. B. Chenier and J. A. Howard Canad. J. Chem. 1975,53,623. ' J. C. Tait and J. A. Howard Chad. J. Gem. 1975,53,2361. Part (iii) Electron Spin Resonance Spectroscopy and Free-radical Reactions 91 In cyclopropane and CF2C12 values of k were identical and fitted the equation log (2k6/l mol-' s-')= (10.3*0.6)-(7.1 f2.1)/8 (7) with 8 defined as before. This is close to the diffusion-controlled limit.It would have been interesting if the authors had quoted values of the activation energy for viscous flow of the solvents. In the same study the adduct But2CCH2SF5 (7) was observed when SF5C1 was photolysed in the presence of 1,l-di-t-butylethylene [a(2H) = 0.975 a(4F) = 1.412 a(,,S) =9.171. The steady-state concentration of (7) had a light-intensity exponent of unity and decayed with first-order kinetics -4(7)i/dt = k8[(7)1 (8) with log (k*/~-')=(13k0.4)-(41.8*0.8/8) (9) This is strong evidence that the decay occurs by the unimolecular p-scission process (Scheme 5a) rather than the disproportionation shown in Scheme 5b. The authors BuiC=CH + SF Bu\CHCH2SF + Bu\C=CHSF Scheme 5 point out that the value of the pre-exponential term is consistent with a unimolecular scission process and that the low value of the activation energy is typical of the reversible addition of sulphur-centred radicals to olefins.There have been other examples of e.s.r. studies of p-scission in simple radicals. A series of ten a-alkoxyalkyl radicals have been produced by hydrogen-atom abstrac- tion from the ether precursors using Bu'O. radical.8 The p-scission process may be represented as R10CR2R3 2 R1 + 0=CR2R3 Certain trends were noted. In the series Bu'OCH, Bu'OCHCH, and Bu'OC(CH,), the first did not fragment at 0 or 30"C the second did not fragment at 0°C but &scission occurred at 30°C and a mixture of Bu'OCHCH and (CHJ3C was observed. Finally the radical Bu'0C(CH3) was found at neither 0 nor 30 "C the sole observable species being the scission fragment (CH3),C.Cumyl and benzyl ethers were also studied. 8-Scission has also been found in the fragmentation of several cyclic and acyclic dialkoxyalkyl radicals.' Measurements of the steady-state concentrations of the dialkoxyalkyl radicals [(R'O),CR2k showed a square-root dependence on the light intensity (I)at low temperatures (-60 to -136 "C) indicating that de!ay occurs by a second-order process. At higher temperatures however [(R'O),CR2] aI showing the dominance of the first-order p -scission process in removing the dialkoxyalkyl radicals. Simultaneous measurements of S. Steenken H.-P. Schuchrnann and C. von Sonntag J. Phys. Chem. 1975,79,763. M. J. Perkins and B.P. Roberts J.C.S. Perkin 11 1975 77. A. T.Bullock [(R'O),CR*] and [R']= lead to a value for 2kll/k10 where k, is the rate coefficient for the recombination process kll R' +R' +non-radical products (1 1) Estimates of .kll were available and hence klo the rate coefficients for the p-scission were obtained. An important finding was the large difference in rates for B-scission for the di-t-butoxymethyl radical and its cyclic analogue the 4,435 t e t rame t h yldioxolan y1radical (Scheme 6). rkH-1 klO(72"C)= 5.8 x 103s-' + O=CH-OCMe,CMe, 0-(CMe,),-0 Scheme 6 An extensive kinetic study has been carried out on a long series of aminophos- phoranyl radicals in solution." Both a-and p-scissions were found to occur. Kinetics of scission were measured using rotating-sector techniques combined with signal averaging.Before leaving the topic of @-scission and its kinetics an experiment designed to test for the presence or absence of a 'memory' in the @-scission of the tetra-t- butoxyphosphoranyl radical should be mentioned.' The problem may be briefly stated. Alkoxy radicals oxidize trialkyl phosphites (8) to trialkyl phosphates (10) according to Scheme 7. The tetra-alkoxyphosphoranylradical (9) is known to be the 4R. + OP(OR*)(OR) (9) (b) (10) Scheme 7 intermediate in this reaction. If the attacking alkoxy radical R*O. is identical to the alkoxy-groups RO of the phosphite then the question arises as to whether the &scission process has any 'memory' with respect to the attacking radical.In other words are either of routes (a)or (b) favoured in Scheme 7? The question has been resolved by the in situ photolysis of (i) (CD3),C02C(CD3) with [(CH,),CO],P and (ii)(CH,),CO,C(CH,) with [(CD,),CO],P in the cavity of the e.s.r. spectrometer. If the reaction has no memory then the ratio [(CH3),C*J/3[(CD,),C*] in experiment (i) should equal 3[(CH,),C]/[(CH,),C] in experiment (ii) (there is an obvious statisti- cal reason for the factors of 3). This was found to be the case over the temperature range -70 to +10"C although the individual ratios were all substantially greater than unity indicating a secondary isotope effect. That phosphoranyl radicals have a trigonal-bipyramidal structure with two apical and two equatorial ligands has been lo R.W. Dennis and B. P.Roberts J.C.S. Perkin ZZ 1975 140. Part (iii) Electron Spin Resonance Spectroscopy and Free-radical Reactions well established both experimentally'' and theoretically. l2 This leads to three possible interpretations of the absence of memory in the &scission process the most probable of which seems to be ligand exchange by for example pseudorotation (Scheme 8). For this interpretation to be correct kexch>> k, where k is the rate OR* OR I ,,OR* OR & .p' ,I' .P I'OR 1.0, OR OR Scheme 8 coefficient for the scission process. At -60°C k for P(OBu') lies in the range 1-3 x lo2s-*,depending on ~olvent.'~ Whilst there are no measurements of kexchfor this radical there have been some measurements of temperature-dependent linewidth effects in a series of alkoxyfluorophosphoranyl radicals; such effects clearly indicate rapid exchange of apical and equatorial fluorine ligand~.'~ Analysis using modified Bloch equations gave kexch(-70 "C)= 5 X lo6s-' for Bu'OPF,.This is 4-5 orders of magnitude faster than k for P(OBu'), and it seems improbable that the ligand-exchange frequency for this latter species will be significantly less than in the fluorophosphoranyl case. The pseudorotation model thus seems to be the correct interpretation of the 'memory loss'. The spin-trapping technique has been used to determine the rate of addition of phenyl radicals to benzene15 and the rate coefficients for hydrogen abstraction by the phenyl radical from methanol ethanol and propan-2-01.'~ In the first of these the kinetic Scheme 9 was found to hold.Analysis yields an expression for the initial rate PhN=NCPh 2 Ph. + N + Ph,C. (12) (not PAT trapped) Ph-+ PhCH=N(O)CMe Ph,CHN(O-)CMe PBN Ph-SA Ph-+ PhH k (not trapped) Scheme 9 l1 A.J. Gdussi J. R. Morton and K. F. Preston J. Phys. Chem. 1975,79,651. l2 J. M. F.van Dijk J. F. M. Penning and H.M. Buck J. Amer. Chem.Soc.,1975,97,4836. l3 G. B. Watts D. Griller and K. U. Ingold J. Amer. Chem.Soc. 1972,94,8784. l4 I. H.Elson M. J. Parrott and B. P. Roberts,J.C.S. Chem.Comm. 1975,586. l5 E.G. Janzen and C. A. Evans J. Amer. Chem.Soc. 1975,97,205. l6 E.G. Janzen D. E. Nutter jun. and C. A. Evans J. Phys. Chem. 1975,79,1983. A. T. Bullock of formation of phenyl adduct (Ph-SA) as a function of the nitrone concentration [PBN] uiz.It was found from the intercept that k12 (30 "C)is (1.5f0.2)x 10-5s-' in good accord with an earlier report on the kinetics of thermolysis of PAT (k12= 1 x 10" s-').I7 Further klJk13 = 0.0065. From an independent determination of k13(1.8f0.1 X lo71rno1-l s-')* the rate coefficient (30 "C)for the phenylation of benzene k14 was found to be 1.2 x lo51 mol-' s-'. Similar techniques were used to estimate the rate coefficients for hydrogen-atom abstraction by the phenyl radical from methanol ethanol and propan-2-ol16 accord- ing to the general reaction Ph. + R1R2CHOH 2R'R'COH + PhH (16) For methanol ethanol and propan-2-01 kI6was found to have the values 1.4X lo5 (2.3*0.1) X lo5 and (4.1kO.1) X lo51mol-' s-' respectively.The relative reac- tivities per a-hydrogen atom are thus in the ratio 1.0 2.4 8.8. These are perhaps fortuitously very close to the ratios of reactivities shown by these alcohols to the methyl radical in the gas phase namely 1.0 2.6 9.2 per a-hydrogen atom.17 There has been a long-felt need for the application of e.s.r. to the study of the kinetics of free-radical polymerizations. Apart from early flow-system work using redox initiators," it is only in the past three year^'^*^* that systems have been described which more closely resemble those used in conventional kinetic studies. The most recent study was of the photoinitiated radical polymerization of meth-acrylonitrile in toluene (Scheme Several assumptions of varying plausibility (CH,),C(CN)N=NC(CN)(CH,) !% 2(CH3),CCN + N (R-1 R.+ CH2=C(CN)CH3 RCH,-C(CN)CH (M) (P.1 P. + CH,=C(CN)CH PCH,-C(CN)CH (P.) 2P. 5 non-radical polymer Scheme 10 S. W. Benson 'The Foundations of Chemical Kinetics' McGraw-Hill New York,1960 p. 297. 18 H. Fischer and G. Giacometti J. Polymer Sci.,Part C,Polymer Symposia 1967,16 2763. l9 P. Smith and R.D. Stevens J. Phys. Chem. 1972,76,3141. 2o P. Smith L. B. Gilman and R. A. DeLorenzo J. Magn. Resonance 1973,10 179. *l P. Smith R. D. Stevens and L. B. Gilman J. Phys. Chem. 1975,79,2688. * This is a revised value from ref. 15. Part (iii) Electron Spin Resonance Spectroscopy and Free -radical Reactions 95 were made in the kinetic analysis.The first two are that ki= k and that k is independent of the chain length. Less reliable is the assumption that all radical recombinations (i.e. R-+P. R.+R.,and P. +Pa) have the same rate coefficient k,. A stationary-state treatment of the kinetics leads to ([P.I/rR*l)(rP.l+ [R.I)/[Ml= k,/2k (17) Measurements of [P-J and [ReJ for a range of values of monomer concentration [MI yielded a value of ca. 1x for the ratio k,/2 k,. The agreement with the literature value of 1.2 x is not impressive. The probable reason for the discrepancy is that k will almost certainly be strongly dependent on chain length for short chains. Unfortunately to detect the propagating radicals by e.s.r. it is necessary to have a rapid rate of initiation. Since this inevitably leads to short chains there is serious doubt whether such studies can appreciably contribute to our knowledge of the kinetics of free-radical polymerizations which lead to high polymers.An interesting difference between the mechanisms of the photochemical reactions of organoboranes with ketones and imines respectively has been found.22 It seems well established that the ketone reacts in its triplet state (Scheme 1la). Since imines (a) [R:CO13 + R3B --* RiCOBRi + R? c -10°C (b) Bu:C=NH + Et,B n-pentaner BuiCNHBEt + Et. Scheme 11 and ketones are isoelectronic it was supposed and found that photolysis of 2,2,4,4-tetramethylpentan-3-imine(11) with triethylborane (12) should give rise to the substituted alkyl radical (13) and the ethyl radical (Scheme llb).The hfcc's of (13) were a(14N)=0.281 a("B) = +1.022 and aEH= 3.345 mT. If the imine reacted via its triplet state (excitation energy 314-356 kJ mol-') then the reaction should be quenched by the addition of a conjugated diene. However the addition of butadiene or trans-penta-l,3-diene caused a considerable enhancement of the signal from (13). The authors" ruled out the possibility of triplet sensitization by the dienes since their triplet states are lower than those of the imines. However "B n.m.r. spectroscopy showed the formation of a strong 1 1complex of the imine with the triethylborane. It was suggested that the sensitizing effect of the dienes was attributable to their ability to transfer singlet energy to the imine-borane complex. The decay of (13) followed second-order kinetics with a rate coefficient (-80 "C)of 3 X lo31mol-' s-'.This is much more rapid than most other 1,l-di-t-butylalkyl radicals.23 Attention should be drawn to the first of the oxaziridinyl radicals (14a b) the preparation of which is summarized in Scheme 12 (14b) showed no significant decay at room temperature over a period of 24 h whereas (14a) decayed over a 22 J. C. Scaiano and K. U. Ingold J.C.S. Chem. Comm. 1975,878. 23 G. D. Mendenhall,D. Griller,D. Lindsay T. T. Tidwell and K. U. Ingold J. Amer. Chem. Soc. 1974,% 244 1. 24 R. F. Hudson A. J. Lawson and K. A. F. Record J.C.S. Chem. Comm. 1975,322. A.T.Bullock (14) a R = Ph; b R = Bu' Reagent i PbO, CCI Scheme 12 period of 1h at 50°C to give a strong e.s.r.signal of the corresponding oximino radical. The results of the investigation of the mechanism of this rearrangement are awaited with interest. Work has continued on alkylhydrazyls with a report on the kinetics mechanism and products of decay of some mono- 1,2-di- and tri-alkylhydrazyls.' The principal results were (i) that l-alkylhydrazyls undergo rapid diff usion-controlled second- order decays (ii) 1,2-di-isopropylhydrazylalso undergoes a rapid second-order decay which however is via a P-disproportionation and (iii) that trialkylhydrazyls decay by one of two routes according to structure. These are a fast second-order P-disproportionation when there is a small alkyl group bonded to the bivalent nitrogen and a slow p-scission for more hindered cases.These points are sum-marized by the examples in Scheme 13. 2CH3NNH * products k(25"C)= (1.0 & 0.5) x lO9Imol-'s-' 2Pr'NHNPr' -+ Pr'NHNHPr' + Pr'N=NPr' k(20"C)= (9.8 f 1.3) x lo7 Imol-'s-' k = (1.2 & 0.2) x lo71 mol-s-(E < 8 kJ mol-') log(k/s-') = (6.7 _+ 1.2) -(38 & 7)/d Scheme 13 There are well-established intramolecular 1,5-hydrogen shifts from carbon atoms to oxygen radical centres2' A reinvestigation of the hydrogen abstraction by Bu'O. 25 J. W. Wilt in 'Free Radicals' ed. J. K. Kochi Vol. I Wiley New York,1973 p. 17. Part (iii) Electron Spin Resonance Spectroscopy and Free -radical Reactions from substituted 1-cyclopropylcarbinols has revealed the occurrence mechanism and kinetics of a 1,5-hydrogen shift in the reverse direction i.e.from oxygen to a carbon radical centre.26 The mechanism of the rearrangement and subsequent hydrogen-atom shift is summarized in Scheme 14. For R=Me a steady-state trans-(16) (R = H Me 4,or Ph) Scheme 14 analysis of the relative concentrations of cis-(16) and (17) leads to an activation energy for the rearrangement of (20*4) kJ mol-' and a frequency factor of lo8s-l. The conclusion that trans-(l6)does not rearrange to (17) was reached by analysing the temperature dependence of the concentrations of cis-(16) trans-( 16) and (17; R =H). The authors26 account for the occurrence of this unusual shift in terms of the facile formation of a six-membered-ring transition state together with resonance stabilization.The only case where (15) could be observed was for R =Ph. There have been several e.s.r. studies of atom-molecule reactions in the gas phase using the fast-flow-microwave discharge method. The reactions of oxygen atoms ('P) with CH,Br and CH3ClZ7 over the temperature range 500-1000 K have the same rate coefficients (*lo%) given by k(O+CH,X) =3.5 x lo1 exp(-4560/T) cm3mo1-l s-l. Perhaps surprisingly the halogen has little if any effect on the rate of the primary reaction O('P) +CH,X -+ CH2X+ OH. This is further emphasized by the fact that k(O+CH,X) is very similar (especially in activation energy) to k(O +CH,) =2.1 x 1013 exp(-4550/ T)cm3 mol-' s-l. Other gas-phase kinetic studies include the systems O(3P)+CS -P CS+SO; O(,P)+ OCS -+ CO +SO (both ref.28); 0+SO +M -+SO +M" (M usually He);29 and H +ClF -B HF+ClF,.,' Finally it has been shown that two consecutive addition 26 H. Itzel and H. Fischer Tetrahedron Letters 1975,563. 27 A. A. Westenberg and N. deHaas J. Chem. Phys. 1975,62,4477. 28 C.-N. Wei and R. B. Timmons J. Chem. Phys. 1975,62 3240. 29 A. A. Westenberg and N. deHaas J. Chem. Phys. 1975,63,5411. 30 S. J. Pak R. H. Krech D. L. McFadden and D. 1. MacLean J. Chem. Phys. 1975,62,3419. 98 A. T.Bullock steps occur in the reaction of atomic fluorine with phosphorus trifl~oride;~' F. +PF3 + PF4-k(300 K) =(8.6* 0.6)X 10" cm3mol-' s-' F.+PF,. * PF5 k(300K)=(1.2*00.2)x10'3~3mol-'s-1 2 Chemically Induced Dynamic Electron Polarization Both time-resolved and steady-state measurements of chemically induced dynamic electron polarization (CIDEP) have been reported using pulsed laser^,^'-^^ pulsed radioly~is,~~ and conventional U.V.source^^^,^^ as means of generating radicals. The reader is referred to a recent review for details of the various theories proposed to account for the polarization phenomenon38 but the two principal mechanisms may be briefly described as follows. In a homolytic scission a level-crossing process is envisaged during the relative diffusion of the two radicals and gives rise to spin polarization. This is the radical-pair mechanism (RPM). The other mechanism is the triplet mechanism (TM),in which an intersystem-crossing step gives rise to polariza- tion provided that radical formation takes place in a time comparable to or less than the triplet spin-lattice relaxation time.Photolysis of solutions of pi~alophenone~~ in solvents of differing viscosities using 20 ns pulses from a nitrogen laser (A =337 nm) generates the benzoyl and t-butyl radicals both showing spin polarization. The evolutions of the polarizations with time were generally complex. Naphthalene quenching studies showed that the photolysis occurs through a triplet state which could be responsible for the weak emission in the spectrum of benzoyl. However the polarization of t-butyl showed a marked hyperfine dependence indicative of the RPM. Briefly the results were qualitatively interpreted in terms of a process involving two rates of separation of the initial radical pair. The first of these rates is separation from a triplet pair and the second is the slower departure from a singlet pair which arises from the initial triplet pair by the perturbations from the large t-butyl hyperfine interactions.It was pointed out that this interpretation was in accord with the theoretical model devised by Pedersen and Freed3' in which the rates of separation of the radicals are dependent on the exchange interaction. It is expected that the singlet pair separation would be retarded by this interaction. Polarized transient radicals from aqueous methanol and aqueous acetate solutions have been produced by pulse radiolysis (100ns electron pulses) and observed in the submicrosecond domain typically 300 ns after the The CH,CO radical has been studied in some detail.When produced by the reaction of -OH with CH3C0; the low-field emission high-field-enhanced absorption spectrum charac- teristic of the radical-pair model was observed. However the polarizations though 31 I. B. Goldberg H. R. Crowe and D. Pilipovich Chem.Phys. Letters 1975 33 347. 32 P. W. Atkins A. J. Dobbs and K. A. McLauchlan J.C.S. Faraday II 1975,71 1269. 33 B. B. Adeleke K. Y. Choo and J. K. S. Wan J. Chem. Phys. 1975,62,3822. 34 A. J. Dobbs and K. A. McLauchlan Chem. Phys. Letters 1975,30,257. 35 A. D. Trifunac K. W. Johnson B. E. Clifft and R. H. Lowers Chem.Phys. Letters 1975,35,566. 36 P. B. Ayscough T. H. English G. Lambert and A. J. Elliott Chem. Phys. Letters 1975,34,557. 37 J. B. Pedersen C. E. M. Hansen,H. Parbo and L. T. MUUS J. Chem.Phys. 1975,63,2398. 38 J. K. S. Wan S. Wong and D. A. Hutchinson Accounts Chem.Res. 1974,7 58. 39 J. B. Pedersen and J. H. Freed J. Chem. Phys. 1973 59 2869. Part (iii) Electron Spin Resonance Spectroscopy and Free -radical Reactions opposite were not equal (as predicted by RPM). It was suggested that since the spin-relaxation time TI, of .OH is expected to be very short then it would react with CH,CO with its spin states in equilibrium. Some transfer of this equilibrium population to *CH,CO would result in the observed decreased emission of the low-field line and enhanced absorption of the high-field line. This interpretation was supported by the nearly equal intensities of the polarized low- and high-field lines in the same radical produced by the reaction of the hydrated electron (e;J with CH,ICO; and CH,ClCO,.T, for e& is of the order of microseconds and thus cannot relax before the production of -CH,CO; radical. In discussing e.s.r. spectra showing CIDEP it is useful to define an enhancement factor Vqsuch that Vq=[S(4)-S,(q)]/S,(q) where 4 is an index of the nuclear spin state associated with the line under consideration S(4) is the amplitude of the enhanced signal and &(q) is the amplitude of the signal when there is no enhancement. An investigation of the dependence of Vq'son radical concentration and radical structure has been made.36 The radicals were generated under steady- state concentration conditions by 1ms pulses from a mercury lamp according to Scheme 15. Radicals (18) (19) and (21) all showed a linear dependence of Vqon n n hv Bu:02 -hv CH3CHO -CH3CHOH hv H2°2 -H°CH2CHoH (21) Scheme 15 the radical concentration as predicted by the theory due to Fe~senden.~' Thistheory predicts that the enhancement factor Vq,for a given pair of lines (high- and low-field lines with the same 9) is proportional to TT,k,n where T is the temperature TIthe spin-lattice relaxation time and k the radical-encounter rate constant.Values of VJn for (20) (19) and (18)were found to be 0.68,2.2,and 7.2 1mol-' respectively. It was concluded that these differences could not be explained in terms of the values of T,k for the three systems and that Vqmust depend markedly on radical structure. In particular the authors pointed out that the largest emission- absorption polarizations are found in cyclic radicals.It is possible that an anisotropic exchange interaction its dependence on radical structure and its effect on the separation rate of the radical pair need to be considered in the theory of Pedersen and Freed39 before the effects of radical structure on CIDEP can be explained. R.W.Fessenden J. Chem. Phys. 1973,58,2489. 100 A. T.Bullock Time-resolved techniques have been used to study the polarization mechanisms in the neutral p-benzoquinone radical (PBQH.) produced by photolysis of p-benzoquinone in solution by the steps indicated in Scheme ,16.37 The curves of the PBQ+hv + 'PBQ 'PBQ -+ 'PBQ 'PBQ + RH + PBQH. + R-solvent (PBQH. PBQ; + H') Scheme 16 time evolution of the intensity were fitted to theoretical curves.41 Two contributions to the polarization were observed when ethylene glycol was the solvent.These were (a)an initial hyperfine-independent polarization due to a triplet mechanism and (b) a hyperfine-dependent polarization caused by the RPM due to the radical-termination reaction. Observed values of the TM polarization indicated a triplet lifetime in the range 0.1-1011s and a zero-field parameter IDI>70mT. The magnitude and hyperfine dependence of the RPM polarization was in accord with the theory for an exponentially decaying exchange interaction J(r) with a maximum value Jo > lo9rad s-'. The photoexcited TM has received support from two groups who used plane- polarized Both studies have as their origin the calculations of Adrian:' who showed that if the TM is operative then the spin polarization of the radicals will depend on the orientation of the electric vector E of the polarized light with respect to B the external magnetic field.We conclude this section by reporting on the more extensive of the two experimen-tal The T-T* singlet-singlet transition in 1,4-benzoquinone is known to be polarized along the 0-0axis. Adrian's calculations predict that for a CIDEP process involving this species the TM using polarized light would result in a ~W/O increase in polarization going from EllB to E IB. In complete agreement with this both the benzoquinone and the 2,6-di-t-butylphenoxy radicals showed this polariza- tion when a solution of benzoquinone and 2,6-di-t-butylphenol (DTBP) was photo- lysed with plane-polarized light from a pulsed 20 kW nitrogen laser.In contrast to benzoquinone the T-T* singlet-singlet transition in 2-methylanthraquinone is perpendicular to the 0-0 axis. For a solution of this quinone with DTBP it was found that the emission magnitude of the phenoxy radical decreased by ca. 20%in going from EllB to ElB (the signal from the quinone radical was too weak to be useful for quantitative measurements). Again this result is substantially in agree- ment with Adrian's calculations although the predicted decrease is 10%. 41 J. B. Pedersen J. Chem. Phys. 1973,59,2656. 42 F.J. Adrian J. Chem.Phys. 1974,61,4875. Part (iii) Electron Spin Resonance Spectroscopy and Free -radical Reactions 101 3 Equilibria The use of precise measurements of g for the determination of equilibrium constants in a rapid dynamic equilibrium situation has been described43 for the ion-pair equilibrium between 2,6-di-t-butyl- 1,4-benzosemiquinone and IS+in hexamethyl- phosphoramide (HMPA).The relevant equation is l/AE =K,,/Ag'[K+]+ l/Ag' CW where Ag =gokneci-gfree ion Ag' = gfre ion -gion pair and Keg =[Ryl[K+I/CRT K+l i.e. the ion-pair dissociation constant. At 28 "C Keg=0.076 f0.009 which agrees well with the value of 0.091 f0.01 obtained by measuring time-averaged hfcc'~.~~ In this latter work ion-$air dissociation constants were measured over a range of temperatures for K' with the radical anions of 2,6-di-t-butyl- 1,4- benzosemiquinone p-dinitrobenzene p-nitrobenzaldehyde and p-nitrobenzophenone.All the relevant thermodynamic parameters were obtained for these systems. The equation is precisely analogous to (18) namely 1/(A -A")=Keq/[K+](A'-A")+ l/(A' -A") (19) where A is the observed hfcc for a particular magnetic nucleus A" is for the free ion and A' for the ion pair. Equations (18) and (19) are only valid when the frequencies of the forward and backward reactions are large compared to the relevant changes in the measured spectral parameters expressed in frequency units i.e. Ag'PB,/h [equation (l8)J and (A'-A") [equation (19)J. When this situation does not pertain two superimposed spectra are obtained and Keqis found by straightforward con- centration measurements on the two components.For ion-pair equilibria of K+with the radical ions of 2,6-di-t-butyl-l,4-benzoquinone, 9,10-anthraquinone and 1,4- naphthoquinone single spectra and the various thermodynamic parameters (K,AW AS") were obtained using g measurements. However for the unsubstituted benzosemiquinone slow exchange was observed and it was suggested on the basis of INDO calculations that fast exchange occurs if the sum of the electron densities on the oxygens <6.46; otherwise the exchange is slow. Another example of a fast exchange equilibrium studied using equation (19) includes the hydrogen-bond exchange reaction shown in Scheme 17.46 The results showed a linear correlation between the Taft parameter for the para-substituent u+and In Kes. XGN02 + HMPA--HOMe NO --HOMe+ HMPA .I .-I (X = H Bu' CN NO, CO,Me Cl or COMe) Scheme 17 Slow and fast exchange has been found in certain acid-base equilibria.The P-H hfcc's of seven P-hydroxyalkyl radicals have been found to be dependent upon 43 G. R. Stevenson and A. E. Alegria J. Phys. Chem. 1975,79 1042. 44 A. E. Alep'a R. Concepci6n and G. R. Stevenson J. Phys. Chem. 1975,79 361. 4s G. R. Stevenson A. E. Alegria and A. McB. Block J. Amer. Chem. Soc. 1975,91,4859. 46 G. R. Stevenson L. Echegoyen and H. Hidalgo J. Phys. Chem. 1975,79 152. 102 A. T.Bullock PH.~’The equilibrium is >H20H +OH->H20-+H20 A B and it may be shown that PKa =pH +loglo [(a-a’)/( uA-U)J (21) where u is the observed P-H hfcc and aB,(I~ are those for pure B and pure A respectively.Where comparisons are available pKa (radical)=pKa (alcahol)-(1.3*0.2). A similar result was found for radicals of the type HSCH2CXY,where again the radical pKa’s were lower than for the parent thiols (ca. 1.5-2 In the sulphur radicals however exchange was slow and the Ka’s were determined by relative concentration measurements of the ionized and unionized radicals as a function of pH. Acid dissociation constants have also been reported in an extensive study of the eiq adduct to fumaric acid.49 These may be represented thus pK,=8.1 pKa=10.8+0.l monoanion (two forms) dianion (one form) . trianion Resuits on three disproportionation equilibria have been reported in which radical monoanions are in equilibrium with their diamagnetic dianions and hydrocarbon precursors.The equilibria may be expressed as .rr2-+ n S 2nT. The enthalpy changes involved in this type of equilibrium for bemcyclo-octatetraene and naphthocyclo-octatetraene when compared with the parent cyclo-octatetraene did not reflect the expected strong decrease in electron-electron repulsions for the dianions.” The thermodynamic parameters controlling the disproportionation of the [16]annulene anion radical depended on the counterion (Li+ Na+ K+).51 The variations were ascribed to metal association with the dianion the monoanion existing essentially as a free ion in the solvent used (HMPA). The morphamquat radical cation (22) exists in equilibrium with its diamagnetic dimer in methanol (22) ~~lution.~~ For this system AH” = -45.05 *0.3 kJ mol-’ AGO298 = -10.6 kJ mol-’ and = -115.6J mol-’ K-’.Finally we conclude with two cautionary notes. The first concerns the use of crown ethers to complex with alkali-metal counterions and hence obtain spectra of 47 Y. Kirino J. Phys. Chem. 1975,79 1296. 48 Y. Kirino and R. W. Fessenden J. Phys. Chem.,1975,79 834. 49 0.P. Chawla and R. W. Fessenden J. Phys. Chem.,1975,79 76. 50 G. R. Stevenson M. Colbn I. Ocasio J. G.Concepcih and A. McB. Block J. Phys. Chem.,1975,79 1685. 5l J. G. Concepci6n and G. Vincow J. Phys. Chem. 1975,79,2037. 52 A. G. Evans J. C. Evans and M. W. Baker J.C.S. Perkin ZZ 1975 1310. Part (iii) Electron Spin Resonance Spectroscopy and Free -radical Reactions 103 'free' radical anions.The first report of the anion of mesitylene has appeared,53 prepared by the reaction of a solution of 18-crown-6 in mesitylene with a potassium mirror. In addition to the couplings to protons in the radical ion (a,", =0.491 mT a&=0.257mT) a further coupling to six equivalent protons was found (0.018mT). The authors suggest a model in which there is an ion pair between [mesitylene]' and [K -* -crown]+ ions. This was confirmed using the anion of toluene when two sets of hfcc's to the crown occur 0.012 mT (4H) and 0.018 mT (ZH).Secondly in a study of the association of di-t-butyl nitroxide with the Schardinger dextrin cyclohepta-amylose it was found that the concentration quotient for a simple association equilibrium was not constant.54 However a simple linear relationship between In yR (where yR is the activity coefficient of the radical) and d the total dextrin concentration adequately dealt with deviations from ideality.53 G. V. Nelson and A. von Zelewsky J. Amer. Gem. Soc.,197597,4279. 54 N.M.Atherton and S. J. Strach J.C.S. Faraday I 1975,71,357.

ISSN:0069-3030    

DOI:10.1039/OC9757200088

出版商:RSC    

年代:1975

数据来源: RSC

摘要:

5 Arynes Carbenes Nitrenes and Related Species By R. C. STORR 0 Robert Robinson Laboratories University of Liverpool Liverpool L69 3BX 1 Arynes Non-ortho-dehydroarenes have provided the highlights of aryne chemistry in 1975. MIND0/3 calculations published last year indicated that the lowest-energy situation for rn -benzyne corresponds to a bicycle[3,1,O]hexatriene-like structure (1) (1) (2) (3) rather than a relatively unperturbed hexagon,' and a claim for the generation of this species starting from a C-1-C-5-bonded precursor has now appeared.* Formation of the fulvene (5) by treatment of the dibromide (4) with three equivalents of KOBu' at -78 "Cin the presence of HNMe was rationalized by nucleophilic attack of the amine on the electrophilic carbon of (1) (Scheme l).However an alternative explanation (Scheme 2) for the formation of the fulvene (9,avoiding a rn-benzyne has already been ad~anced.~ Br Br NMe2 @ -(1) i,(-j, shift ' OI/NMe2 1.5 --+ (4) (5) Reagent i HNMe Scheme 1 + a" Ql Br + (===J Br --* pN"" *.-. 1 Br (4) (5) Scheme 2 1 M. J. S. Dewar and W. K. Li J. Amer. Chem. Soc. 1974,96,5569; R.C. Storr Ann. Reports (B),1974 71 154. 2 N. N. Washburn J. Amer. Chem. SOC.,1975,97 1615. 3 A. H. Amaro and K. Grohmann J. Amer. Chem. Soc. 1975,97,5946. 105 106 R. C.Stow MIND0/3 calculations have also indicated that two 1,4-dehydrobenzene struc- tures (2) and (3)correspond to energy minima.' Bergman has recently described a p-benzyne which could be identified with (2).4 Now evidence for another p-benzyne corresponding to the butalene structure (3) is claimed.Again the approach involves dehydrohalogenation of a precursor (6) in which the dehydrocarbons are already a-bonded. Evidence for the intermediate formation of (3) is the predominant but not exclusive formation of p-deuteriated dimethylaniline in the presence of DNMe2and I Ph isolation of the diphenylisobenzofuran adduct (7) which appears to require initial reaction between the isofuran and butalene.' Further examples of the unusual 1,3-addition of 1,8-dehydronaphthalene to dienes have appeared.6 Both addition-elimination and elimination-addition mechanisms are involved in the reactions of halogenobenzocinnolines with KNH2.A small amount of 2-aminobenzocinnoline formed from the 4-chloro-compound raises the possibility of a 1,3-dehydro intermediate although an addition-rearrangement- elimination sequence via (8) and (9) seems more pr~bable.~ H2N H (8) (9i Arynes are not involved in dediazoniation of arenediazonium salts in water' or trifluor~ethanol,~ although they do appear to be so in some cases of telesubstitution in heterolytic dediazoniation by halide ions in pyridinium polyhydrogen fluoride 4 R.R. Jones and R. G. Bergman J. Amer. Chem. SOC.,1972,94,660. 5 R. Breslow J. Napierski and T. C. Clarke J. Amer. Chem. SOC.,1975,97 6275. 6 J. Meinwald L. V. Dunkerton and G. W. Gruber J. Amet. Chem.SOC.,1975,97,681; see also M.Kato S. Takaoka and T. Miwa Bull. Chem. SOC.Japan 1975,48,932.7 G. E. Lewis R. H. Prager and R. H. M. Moss Austral.J. Chem. 1975,28,2057; see also p. 2459. 8 C. G. Swain J. E. Sheats and K. G. Harbison J. Amer. Chem. Soc. 1975,97,783. 9 P. Burri G. H. Wahl and H. Zollinger Helu. Chim. Acru 1974 57,2099. Arynes Carbenes Nitrenes and Related Species solution." Matrix photolysis of the diazolactone (10) results in the formation of benzyne with sufficient efficiency for the CECstretch (2085 cm-')to be observed for the first time." Benzyne has been produced in low to moderate yield in the ther- mal decomposition of diphenyliodonium acetate nitrosation of N-phenylphosphylamidates deoxygenation of benzenediazotoluene-p-sulphonateN-oxide,12 and in the photolysis of o-nitrobenzaldehyde N-acetyl-N-alkylhydrazones.l3 This last reaction involves the intermediate brmation of o-(N-ace tyl-N-a1 kyltriazeno) benzoic acids.Use of the highly hindered base lithium tetramethylpiperidide allows Diels-Alder trapping of benzyne generated by dehydrohalogenation of chl~robenzene.'~The regioselectivity of addition of metal amide to 2,3-dehydrotoluene varies with the cation; the selectivity for NH attack ortho to the methyl group is greatest for the most covalent LiNH2. l5Benzyne gives products arising from 2 +2 and 2 +4 addition to benzylidineaniline. l6 Further applications of the additions of enolate anions to arynes have appeared."J' With polyhalogeno-compounds benzofurans can be produced by successive arynic substitution and cyclization. l8 The reaction of benzyne with (dimethylaminomethy1)phenylsilanesresults in the formation of a novel rearrangement product (1 1) in addition to the expected Stevens rearrangement product.l9 Me +,Me Me I CHSiPh3 +PhN-CHSiPh, I Me (1 1) lo G. A. Olah and J. Welch J. Amer. Chem. Soc.,1975,97,208. 0.L. Chapman C. C. Chang J. Kolc N. R. Rosenquist and H. Tomioka J. Amer. Chem.Soc.,1975,97 6586. l2 J. I. G. Cadogan A. G. Rowley J. T. Sharp B. Sledzinski and N. H. Wilson J.C.S. Perkin I 1975,1072. l3 Y. Maki T. Furuta M. Kuzuya and M. Suuki J.C.S. Chem. Comm. 1975,616. l4 K. L.Shepard Tetrahedron Letters 1975,3371. R. Levine and E. R. Biehl J. Org. Chem. 1975,40,1835. l6 J. Nakayama H. Midorikawa and M. Yoshida Bull. Chem. Soc. Japan 1975,48 1063.I. Fleming and T. Mah J.C.S. Perkin I 1975,964;P.G.Sammes and T. W. Wallace ibid. p. 1377. P.Caubere and L. Lalloz J. Org. Chem. 1975,40 2853 2859. I9 Y. Sato T. Toyo'oka T. Aoyama and H. Shirai J.C.S. Chem. Comm. 1975,640. 108 R. C.Storr 2 Nitrenes A griori theoretical studies of the electronic structures of carbonylnitrenes XCON (X =H F Me and OMe) indicate a triplet ground state in all cases with a closely spaced pair of singlet states at higher energy (singlet-triplet separation CQ. 35 kcal for X =H).20Calculations have also been performed for the polar nitrene LiN.21 A critical review concludes that the evidence for phosphindenes R-P as reaction intermediates is largely ambiguous.22 The initial step in the deoxygenation of nitro-arenes with tervalent phosphorous reagents appears to be nucleophilic attack by P on oxygen of the NO group.A survey of such deoxygenating agents indicates that EtOP(NEt,) is particularly reactive but for overall convenience P(OEt) is the best general reagent.23 Disilanes have been used to deoxygenate nitro-arenes at 240 0C.24 Likely examples of aryl- and sulphonyl-nitrene formation by a-dehydration of hydroxylamines have appeared.25 Photolysis of N-arylsulphonyl-S,S-dimethylsulphoximides gives aryl radicals but no sulphonylnitrenes.26 Phenylnitrene has been suggested as an intermediate in the formation of azobenzene in the gas-phase pyrolysis of benzenesulphonyl azide (360"C 0.1 T~rr).~' No Curtius rearrangement occurs in the decomposition of arylsulphinyl azides.Products arising from these very labile azides appear to involve the polar nitrene (12) which does not 0 0 It .-II Ar-S-N Ar-S=NH + ArSO,NH I 0 iyOH II II Ar-S-N + Ar-S=N +-Yo 0 II 0 Ar-S-N=SR, II II Ar-S-N 0 (12) insert but reacts with water as shown and which gives an unexpected adduct with sulphoxides.28 The formation of both aziridines and indoles from oximes (13) and Grignard reagents is consistent with a vinylnitrene intermediate. Only the E-oxime reacts suggesting that a cyclic transition state is involved in the dehydrati~n.~' In both the direct photolysis and thermal decomposition of a selection of steroidal azides the product distribution can be satisfactorily explained by migration of that 2O J.F. Harrison and G. Shalhoub J. Amer. Chem. Soc. 1975,97 4172. 2l C. E. Dykstra P. K. Pearson and H. E. Schaefer J. Amer. Chem. Soc. 1975,97,2321. 22 U. Schmidt Angew. Chem. Intemat. Edn. 1975,14523. 23 M. A Armour J. I. G. Cadogan and D. S. B. Grace J.C.S. Perkin 11 1975 1185. z4 F.-P. Tsui T. M. Vogel and G. Zon J. Org. Chem. 1975,40 761. 25 K. T. Potts A. A. Kutz,and F. C. Nachod Tetrahedron 1975,31,2163,2171. 26 R. A. Abramovitch and T. Takaya J.C.S. Perkin I 1975 1806. 27 W. B. Renfrow and M. Devadoss J. Org. Chem. 1975,40,1525. 28 T. J. Maricich and V. L. Hoffman J. Amer. Chem. SOC.,1974,96,7770. z9 R. Bartnik and A. Laurent Bull. Soc. aim. France 1975 173. Arynes Carbenes Nitrenes and Related Species 109 1 R' PhC R'MgBr phwR1 $Ph + R2 N Ph H a-bond which best overlaps the azide n-system in concert with loss of nitr~gen.~' New systematic kinetic studies of the decomposition of ortho and para-substituted aryl azides confirm that the very large rate enhancement by certain ortho-substituents (PhN=N NO2 or COR) is a genuine neighbouring-group effect.The mechanism of this participation is still a matter for debate. A coupled azide fragmentation-pericyclic reaction in which incipient aromatic character in the developing ring assists loss of nitrogen seems the best description at pre~ent.~' It is a sobering thought that our knowledge of even one of the best known and cleanest 'nitrene' reactions is far from complete. Photolysis of azidobiphenyls gives carbazoles in high yield but by at least two routes one of which involves an intermediate which can be diverted by secondary amines.Mechanistic schemes such as Scheme 3 and Scheme 4 are the simplest that will account for the available data although one involving two intermediates (Scheme 5) is also possible (there is as yet no evidence for A'). The nature of the intermediates A and B is not yet proved but A ArN !% A carbazole ArN !!h A carbazole lk/ RZNH B azepine B k b azepine where k,,k >> k, k where k z k > k-2 Scheme 3 Scheme 4 ArN A' \"; car bazole kz B ",:,, k3 * azepine where k; > k Scheme 5 30 A. Pancrazi and Q. Khuong-Huu Tetrahedron 1975,31,2041,2049. 31 L. K. Dyall Austral. J. Chem. 1975,28,2147. 110 R.C.Storr could reasonably be the singlet nitrene and B the azirine (14) or conceivably an isomer such as the azacycloheptatrienylidene. In the past triplet biphenylnitrene has been advanced as the precursor to carbazole following detection of a transient species with the expected spectrum which apparently was converted into carbazole. Flash-photolytic studies now reveal that the rate of decay of the transient and the appearance of carbazole are significantly different.32 A flash-photolytic study of the formation of 2-substituted-3H-azepinesfrom aryl azides in the presence of secondary amines is basically in line with the generally accepted picture. Two intermediates are detected the first which does not absorb above 300 nm and which has a lifetime of ca.5 ms is believed to be the azirine (15) which is formed rapidly from the singlet nitrene. This species reacts with the amine to give a lhl-azepine (16) which ultimately tautomerizes to the 3H-isomer (17). (16) (17) Kinetic studies reveal that 1W-azepine formation is somewhat more complicated than just attack by the amine on (15) and may involve an isomeric species which is in equilibrium with (15).33 Formation of 2-diethylamino-3H-azepines by deoxygena- tion of nitro-arenes can be interpreted in much the same way there being good evidence for a common intermediate in nitro-arene deoxygenation and azide photo1 ysis. 34 Ring expansion of bicyclic aromatic nitrenes is rare.35 In the case of 0-substituted azides the azirines appear to be formed but open with nucleophiles e.g.amines to give 1,2-diamine~.~~ A procedure has now been developed however for intercept- ing the intermediate azirine with methoxide ion to give aziridines e. g. (18) which are sufficiently stable towards N-C-2 bond cleavage under the basic conditions for thermal rearrangement to azepine (19) to be effected. Immediate neutralization of 32 R. J. Sundberg D. W. Gillespie and B. A. DeGraff J. Amer. Chem. SOC.,1975,97 6193. 33 B. A.DeGraff D. W. Gillespie and R. J. Sundberg J. Amer. Chem. Soc. 1974,96,7491. 3.) T. de Boer J. I. G. Cadogan H. M. McWilliam and A. G. Rowley J.C.S.Perkin 11 1975 554. 35 See for example B. Iddon M. W. Pickering H. Suschitzky? and D. S. Taylor J.C.S.Perkin I 1975,1686; R. N. Carde and G. Jones ibid. p. 519.36 S.E. Carroll B. Nay E. F. V. Scriven and H. Suschitzky Synthesis 1975,710. Arynes Carbenes Nitrenes and Related Species the aziridine solution gives the normal 1,2-disubstituted bicycle (20) and so the mode of reaction can be contr~lled.~' Oxidative ring contraction of 2-aminopyrazolidin-3-ones(21)to /3 -1actams has been achieved by a novel procedure involving addition of aminating agent to the pyrazolidinone anion in the presence of ~xidant.~' A low reaction temperature R c''0 0 !I H,NN9-R'c:fi 0 (21) reveals syn selectivity between heterocyclic ring and vinyl substituent in the addition of phthalimido and related nitrenes to diene~.~' The first 1,4-diazaspiro[2,2 Jpentane (22) has been obtained by double addition of phthalimidonitrene to an a11ene.40 \ (22)Phth Addition of aryl nitrenes to alkenes is very rare and has only been observed for highly electrophilic pentafluorophenyl and related nitrenes full details of which have now a~peared.~' Addition of a sym-triazinylnitrene to a nitrile to give a triazolotriazine has been claimed.42 Thermal decomposition of 3-azidopyridazine N-oxide leads to cleavage of the pyridazine ring.43 A 1,4 H-shift in a vinylnitrene appears to be 37 J.Rigaudy C. Igier and J. Barcelo Tetrahedron Letters 1975 3845. 38 P. Y. Johnson N. R. Schmuff and C. E. Hatch Tetrahedron Letters 1975,4089. 39 R. S. Atkinson and J. R. Malpass J.C.S. Chem. Comm.. 1975 555. 40 R. S. Atkinson and J. R. Malpass Tetrahedron Letters 1975,4305. 41 R. A.Abramovitch S. R. Challand and Y. Yamada J. Org. Chem 1975,40,1541. 42 H. Yamada H. Shizuka. and K. Matsui. J. Org. Chem 1975,40 1351. 43 R. A. Abramovitch and I. Shinkai J.C.S. Chem. Comm. 1975,703. 112 R. C.Storr involved in the pyrolysis of b~t-3-enyl-2H-azirines.~~ Matrix photolysis of 2,2-diazidobiphenyl gives benzocinnoline a product notably absent from solution photolysis at room temperatu~e.~~ 3 Carbenes Reviews of the gas-phase reactions of carbene~,~~ of the chemistry of phosphonylcar- bene~,~' and of the photochemical ring expansion of cycloalkanones to oxacar- bene~~~ have appeared. There is further kinetic evidence for a sizeable energy separation (ca. 38 kJ mol-') between triplet and singlet meth~lene.~~ Equation (1)provides a successful correlation between carbene selectivity for the addition of free CXY to simple alkenes (Mcxyis a measure of selectivity relative to CCI,) and substituent parame- ters for both X and Y and so paves the way for a discussion of structure-selectivity relationship^.^' Further use has been made of the addition of crown ether to give free carbenes in butoxide-induced a- elimination^.^' The use of this technique reveals that PhCX carbenoids are less selective than the free carbenes in alkene additions.The presence of K'Cl- in the transition state leads to greater charge dispersal hence less positive charge localization on the alkene and therefore damped discrimination. The greater the internal stabilization of the carbene the greater its tendency to be free in the presence of KOBu'." The catalysis by trial kylamines of the two-phase (CHC1,-aq.NaOH) generation of CCl is attributed to transport of CCl into the organic phase as an ammonium ylide (23).The carbene is regenerated from the ylide by reaction with chloroform. Such :cc12(as) phase . + + -R3N-CC12(org) GR3kHC12 CCI3 -+ R3kHC12 ci+ :cci2 R3N (0%) (23) tertiary amine catalysts are superior to the normal phase-transfer catalysts for the two-phase generation of CBr2.52 p-Hydroxyethyltrialkylammoniumsalts as phase- transfer catalysts lead to production of highly selective CC12 in contrast to the normal catalysts. They also allow a low degree of asymmetric induction to be obtained in the carbene additions.53 44 A. Padwa and N.Kamigata J.C.S. Chem. Comm. 1975,789. 45 A. Yabe and K. Honda Tetrahedron Letters 1975,1079. 46 M. Jones Accounts Chem. Res. 1974,7,415. 47 M. Regitz Angew. Chem. Internat. Edn. 1975 14 222. 48 P. Yaks and R. 0.Loutfy Accounts Chem Res. 1975,8,209;see also P. Yates and J. C. L. Tam J.C.S. Chem. Comm. 1975,737,739. 49 H. M. Frey and G. J. Kennedy J.C.S Chem. Comm. 1975,233. 513 R. A. Moss and C. B. Mallon J. Amer. Chem. SOC. 1975,97 344. 51 R. A. Moss M. A. Joyce and F. G. Pilkiewin Tetrahedron Letters 1975 2425; see also ref. 70. 52 M. Makosza A. Kacprowin and M. Fedorysnki Tetrahedron Letters. 1975 21 19. s3 T. Hiyama H. Sawada M. Tsukanaka and H. Nozaki Tetrahedron Letters 1975 3013. Arynes Carbenes Nitrenes and Related Species Some uncertainty surrounds the reactive species in a-elimination routes to carbenes and the term carbenoid is generally used for any species (usually ill- defined) on the continuum from free carbene to a-halogenomethylmetal.In this connection a carbenoid of specific structure most probably (24) has been detected V,C1 c1-M:c ()'a (24) together with CCI and CC13M in the reaction of alkali-metal atoms with CC1 in an argon Also chlorocyclopropanation with LiCHCl, via nucleophilic addi- tion and 1,3-elimination can be observed in the favoured case of the 5,6-double bond of fulvenes; significantly chlorocarbene produced from MeLi and CH,Cl gives diff erent products. 55 The effect of added scavenger on the stereochemistry of carbene addition has been used to determine the multiplicity of a carbene at its inception where singlet-triplet equilibration makes the usual trap-dilution technique ineffective.Application to the benzocycloheptatrienylidene-2-naphthylcarbenerearrangement indicates that the latter is formed as a singlet.56 It is now clear that carbene formation is a general process in the photolysis of a1 kenes (Scheme 6).57Pyrolysis of the readily available Meldrum's acid derivatives t Scheme 6 (25) has been widely exploited as a route to carbenes and keten~.~~ 3-Aryl-3H-diazirines have some advantages over diazo-compounds as arylcarbene precursors. 0 R' R' R2R1<Ix ___) \ C=C=OR2/ or \ / C R2 0 (25) They are more stable thermally and decompose to the carbene either directly or via prior isomerization to the diazo-cornpour~d.~~ There is some evidence for the 54 D.A. Hutzenbuhler L. Andrews and F. A. Carey J. Amer. Chem. SOC.,1975,97 187. 55 A. Amaro and K. Grohmann J. Amer. Chem. SOC.,1975,97,3830. 56 K. E. Krajca and W. M. Jones Tetrahedron Letters 1975 3807. 57 S. S. Hixson J. Amer. Chem. Soc. 1975 97 1981;S. S. Hixson J. C. Tausta and J. Borovsky ibid.,p. 3230; T. R. Fields and P. J. Kropp ibid. p. 7559; Y. Inoue S. Takamuku and H. Sakurai J.C.S.Chem. Comm. 1975,577. 5s G. J. Baxter R. F. C. Brown and G. L. McMullen Austral. J. Chem. 1974 27 2605 and references therein; G. J. BaxterandR. F. C. Brown ibid. 1975,28,1551;R. F. C. Brown,F. W. Eastwood andG. L. McMullen J.C.S. Chem. Comm. 1975 328; G.J. Baxter R. F. C. Brown F. W. Eastwood and K. J. Harrington Tetrahedron Letters 1975,4283. 59 R. A. G. Smith and J. R.Knowles J.C.S.Petkin 11 1975 686. 114 R. C.Storr formation of the aromatic nucleophilic carbene (27) in the photolysis of the azirine (26).60Photolysis of the azirine (28)gives the nitrile ylide (29),which in the absence of dipolarophiles behaves as a carbene to give the intramolecular [2 +13cycloadduct (30). Interestingly this process proceeds with inversion of alkene stereochemistry making it the first case of 02s +m2a carbene addition.61 The first clear example of carbene formation by loss of SO from a sulphene has been claimed,6z and the first arylsulphinylcarbene a highly stereoselective cyclo- propanating agent has been obtained from phenyldiazomethyl s~lphoxide.~~ The 0 carbene (3 1)has been generated by base-induced 1,5-elimination from the corre- sponding p-i~dophenol.~~ Copper salts are commonly used as catalysts in the carbenic decomposition of diazo-compounds a1 though the mechanism of their action is not yet clear.It has now been shown that tetraphenylethylene can catalyse these decompositions in much the same way even giving cyclopropanation to an equivalcnt extent. The reaction is obviously complex but a one-electron oxidation of the diazoalkane is probably a key The mode of decomposition of the tosylhydrazone salts (32) depends largely on steric factors associated with ring size. For n =2 pyrazole formation occurs; this is disfavoured for n = 1,and carbenic products result except where R' and RZare aryl in which case 3H-1,2-benzodiazepines are formed by 1,7-dipolar cyclization of the intermediate diazo-compound.66 60 A.Padwa and J. K. Rasmussen J. Amer. Chem. SOC. 1975 97,5912. 61 A. Padwa and P. H. J. Carlsen J. Amer. Chem. SOC.,1975,97,3862. 62 B. E. Sarver M. Jones and A. M. van Leusen J. Amer. Chem. SOC.,1975,97,4771. 63 C. G. Venier H. J. Barager and M. A. Ward J. Amer. Chem. SOC.,1975 97 3238. P. Bartholmei and P. Boldt Angew. Chem. Internat. Edn. 1975 14 64. 65 C. T. Ho R. T. Conlin and P. P. Gaspar J. Amer. Chern. Soc. 1974,96,8109. 66 J. T. Sharp R. H. Findlay and P. B. Thorogood J.C.S. Perkin I 1975 102. Arynes Carbenes Nitrenes and Related Species R' dR2 n=I ~ @R2 Interest continues in the ketocarbene eoxiren eq~ilibrium.~~ The isomeric carbena-oxiran system (34) has now been suggested as a possible intermediate in the formation of ketens from the norbornadiene derivatives (33).No evidence for its (33) equilibration with an oxiren was found.68 The photochemical and acid-catalysed decomposition of a-bisdiazo-ketones appears to involve initial formation of cyclo- propenones rather than Wolff rearrangements. This is certainly the case for 1,3- bisdiazo-1,3-diphenylpropan-2-one.Thermal decomposition of the latter is entirely different and leads to the novel 2,5-dipheny1-3,4-dia~apentadienone.~~ Isopropylidenecarbene generated from the vinyl triflate with KOBu' is a free ~inglet,~' and much less electrophilic than when generated by alternative route^.^' Such vinylidenecarbenes provide a route to methylenecyclopropenes by low- temperature addition to alkyla~etylenes,~~ and they are also involved in the forma- tion of acetylenes from KOBu' and vinyl triflates bearing a The resonance-stabilized vinylidenecarbenes (35) are generated from 1-bromoalk- 1-ynes with alkoxide This type of carbene shows a marked tendency to insert + RCH=C=C c-) RCH-C-C-(35) 67 K.-P.Zeller Chem. Ber. 1975,108,3566. 68 R. W. Hoffmann and R. Schuttler Chem. Ber. 1975,108,844. 6q B. M. Trost and P. J. Whitman J. Amer. Chem. SOC.,1974,96,7421. 70 P.J. Stang and M. G. Mangum J. Amer. Chem. SOC. 1975,97 1459,6478. 71 T.Bally and E. Haselbach Helv. Chim. Am 1975,58 321.72 P.J. Stang and M. G. Mangum J. Amer. Chem. SOC.,1975,97,3854. 73 P.J. Stang J. Davis and D. P. Fox J.C.S. Chem. Comm. 1975 17. 74 C.D.Beard J. C. Craig and M. D. Solomon,J. Amer. Chem. SOC.,1974,% 7944; C.D. Beard and J. C. Craig ibid. p. 7950. 116 R. C. Storr into C-H bonds a to oxygen. For primary alcohols this specificity can be attributed to a favourable orientation of the vacant carbene orbital brought about by H-bonding through the nucleophilic C-1(36);for alkoxides complexation via the electrophilic C-3(37)can be envisaged.74375 C,C 3 ,' 1 HR Rearrangements.-Further calculations suppert tIie non-least-motion pathway for rearrangement of methylcarbene to ethylene. The process starts with the C-H a-bond electron density flowing towards the vacant p-orbital but finishes with the H becoming bonded to the orthogonal lone-pair orbital (38).76 Support for the (38) generally assumed involvement of the singlet state in carbene 1,2-shifts comes from the singlet- and triplet-sensitized photolysis of diazophenylethane.In the presence of an alkene the former gives a high yield of styrene and there is stereospecific cyclopropanation whereas the latter gives only a trace of styrene and there is non-stereospecific cycl~propanation.~~ Interest in the isomerization processes of arylcarbenes continues. For the pyridyl- carbene system studies with the picolylcarbenes where the methyl group interrupts the isomerization process by the formation of cyclobuta-[b]-and -[c]-pyridines reveal that the 2-carbene proceeds mainly and effectively irreversibly to the tolylnitrene whereas for the 3-and 4-carbenes the carbene centre tends to oscillate over the 3- 4- and 5-positions with slow leakage to the 2-po~ition.~' A phenylcarbene-cycloheptatrienylidene rearrangement and not a silacyclopropane intermediate is involved in the pyrolysis of phenyl trime th ylsilyldiazome thane.79 Evidence for the rearrangement of silylcarbenes to silaethylenes has appeared.80 The 75 T. B. Patrick and D. L. Schutzenhofer Tetrahedron Letters 1975 3259. 76 J. A. Altmann I. G. Csizmadia and K. Yates J. Amer. Chem. Soc. 1975,97 5217. 77 S. Yamamoto S. I. Murahashi and 1. Moritani Tetrahedron 1975,31,2663. 78 W.D.Crow A. N. Khan and M. N. Padden-Row Austral.J. Cltem.,1975; 28,1741; W.D.Crow and M. N. Padden-Row ibid. p. 1755;W.D.Crow A. N. Khan M. N. Padden-Row and D. S. Sutherland ibid. p. 1763. 79 T.J. Barton J. A. Kilgour R. R. Gallucci A. J. Rothschild J. Slutsky A. D. Wolf and M. Jones J. Arner. Chern. SOC.,1975.97 657. 8" W. Ando A. Sekiguchi J. Ogiwara and T. Migita J.C.S.Chern. Cornrn.,1975 145; R. L.Kreeger and H. Shechter Tetrahedron Letters 1975 2061; see however W.Ando A. Sekiguchi T. Migita S. Kammula M. Green and M. Jones J. Amer. Gem. SOC.,1975,97,3818. Arynes Carbenes Nitrenes and Related Species carbene (39) undergoes the novel rearrangement shown." 2,3-Homocycloheptatrienylidene (40) undergoes electrocyclic ring expansion to the (40) (41) allene (41);82formation of the cyclic allene (43) from (42) however involves a cyclopropylcar bene fragmentation.83 Insertions.-Although the formation of abstraction-recom bination products in the photosensitized decomposition of diazo-compounds can be explained in terms of insertion by the triplet carbene an alternative chemical-sensitization mechanism in which the sensitizer abstracts H from the substrate and the resulting radicals induce decomposition of the diazo-compound has to be considered. Such a mechanism has been ruled out by CIDNP studies for the irradiation of methyl diazoacetate in the presence of benzaldehyde. In this case the triplet carbene is produced by energy transfer from benzaldehyde to the diazo-compound and it readily abstracts H from hydrocarbons and ben~aldehyde.~~ Triplet vinylmethylene produced by photosen- sitized decomposition of diazopropene undergoes intermolecular insertion reac- tions in contrast to the singlet which gives only intramolecular products.CIDNP studies indicate that the reactions proceed via radical abstraction-rec~mbination.'~ The CIDNP signals observed in the insertion of singlet methoxycarbonylcarbene (produced by thermal decomposition of methyl diazoacetate) into ether C-0 bonds are consistent with formation of an ylide followed by a Stevens rearrangement via homolysis and recombination.86 Phase-transfer catalysis has been used to effect dihalogenocarbene C-H inser-tions in hydrocarbons and Intramolecular C-Br insertion of a carbene has provided the first naphthalene with a single carbon peri bridge.88 81 M.Christ1 and M. Lechner Angew. Chem. Internat. Edn. 1975 14,765. 82 M. Oda Y. It6 and Y. Kitahara Tetrahedron Letters 1975 2587. 83 W. R. Dolbier 0.T. Garza and B. H. Al-Sader J. Amer. Chem. SOC.,1975,97 5038. H. D. Roth and M. L. Manion J. Amer. Chem. SOC.,1975,97 779. x5 M. L. Manion and H. D. Roth J. Amer. Chem. SOC.,1975,97,6919. Hh H. Iwamura and Y. Imahashi Tetrahedron Letters 1975 1401. 87 S. H. Goh K. C. Chan T. S. Kam and H. L. Chong Austral. J. Chem. 1975 28 381. 88 R. J. Bailey and H. Shecter J. Amer. Chem. Soc. 1974 96 8116. 118 R. C.Storr Additions.-Papers concerning carbene additions have ranged from the purely physical organic studies of the kinetics of the gas-phase reaction of singlet CH2 with methylenecycl~propane~~ to numerous routine synthesis of cyclopropanes.Points of interest not mentioned elsewhere include the first example of the addition of an a-oxocarbene to an aromatic system to give a stable norcaradiene,” the irradiation of FCHI in the presence of alkenes as a route to monofluorocyclopropanes,9’ satisfactory copper-catalysed vinylcyclopropanation with diaz~rnethane,~~ and the use of zinc catalysts in cyclopropanation with diaz~methane.~~ The carbenoid reagent prepared from diethylzinc and CHBr in the presence of O2is a good reagent for monobromocyclopropanation.94 89 H. M. Frey G. E. Jackson R. A. Smith and R. Walsh J.C.S. Faraday I 1975,71 1991. 90 C. G. F. Bannerman J. I. G. Cadogan I. Gosney and N. H. Wilson J.C.S.Chem. Comm. 1975,618. 91 J. L. Hahnfeld and D. J. Burton Tetrahedron Letters 1975 1819. 92 R. G. Salomon M. F. Salomon and T. R. Heyne J. Org. Chem. 1975,40,756. 93 D. S. Crumrine T. J. Haberkamp and D. J. Suther J. Org. Chem. 1975,40 2274. 94 S. Miyano Y. Matsumoto and H. Hdshimoto J.C.S. Chem. Comm. 1975 364.

ISSN:0069-3030    

DOI:10.1039/OC9757200105

出版商:RSC    

年代:1975

数据来源: RSC