ISSN:0069-3030    

DOI:10.1039/OC97067FX001

出版商:RSC    

年代:1970

数据来源: RSC

ISSN:0069-3030    

DOI:10.1039/OC97067BX003

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

2 Physical Methods Part (i) Mass Spectroscopy By R. T. APLlN The Dyson Perrins 1aboratory Oxford University DURING 1970 the number of papers on this topic has further increased," notably in areas of applied mass spectrometry particularly in the natural product and biochemical fields. There has also been an increase in the number of papers concerned with detailed studies of the kinetics and mechanisms of fragmentation processes. Two new techniques ion cyclotron resonance' (ICR) and ion kinetic energy spectroscopy' (IKES) have been employed in the interpretation of various fragmentation processes. This Report will attempt to cover the more generally interesting aspects of both the detailed and applied papers. General Methods of Interpretation.-The quasi-equilibrium theory (QET) whose validity for small molecules is well established has been shown to give rate constants which agree well with those observed from a study of substituent effects on normal and metastable ion abundances as well as ionisation and appearance potentials of 1,2-diphenylethane~.~ A probability distribution of internal energies has been derived4 for those aromatic molecular ions which undergo decomposi- tion to afford a single product whose relative abundance and appearance potential are each functions of Hammett sigma constants.This approach provides a rationalisation for the unexpected relationship between sigma constants and the loss of substituents from biphenyl molecular ions.5 Both +I and -Z substituents are capable of increasing the migratory aptitude of aryl groups in the spectra of diary1 sulphones.This rearrangement also affords a Hammett correlation with total ion abundances at 20 eV.6 Zon Energies and Structure. The production and subsequent decomposition of benzoyl ions (m/e 105) derived from N-(substituted pheny1)benzamide (1) are related to the energy distribution in the molecular ion.' The substituent effects ' G. C. Goode R. M. O'Malley A. J. Ferrer-Correia and K. Jennings Chem.in Britain 1971 7 12. ' J. H. Beynon R. M. Caprioli W. E. Baitinger and J. W. Amy Internut. J. Muss Spectrometry Ion Phys. 1969 3 313. F. W. McLafferty T. Wachs C. Lifshitz G. Innorta and P. Irving J. Amer. Chem. SOC.,1970 92 6867. ' R. P. Buck and M. M. Bursey Org. Mass Spectrometry 1970 3 387.M. M. Bursey and P. T. Kissinger Org. Mass Spectrometry 1970 3 395. T. Nagai T. Maeno. and N. Tokura Bull. Chem. SOC. Japan 1970,43,462. ' R. H. Shapiro J. Turk and J. W. Serum. Org. Muss Spectrometry 1970 3 171. * Many of the papers are mentioned in the first volume of 'Mass Spectroscopy' ed. D. H. Williams (Specialist Periodical Report) The Chemical Society London 197 1. R. T. Aplin NH' co+ ~NH!~'" -+ + \ -+ C,H,+ 6 Y Y (1) mle 105 observed in the spectra of NN'-diarylethylenediamines (2) are best interpreted as affording the fragments (a)and (b)with open-chain rather than the closed structures + Y0 (2) a b shown.* Electron-withdrawing substituents increase the abundance of the mol- ecular ion in the spectra of substituted styrene ozonides; the intensities of the fragments XC6H4CHO+'follow a Hammett relationship.' Ground-state bond- orders in molecular ions derived from MO analysis can be used as a reliable guide to the low-energy (ground-state) fragmentation of heterocycles.The subsequent decomposition of the M -42 ions derived from methoxy- and dimethoxy-phenyl acetates' ' suggests that these ions have the structure of the corresponding phenols. '3CLabelling has established that the [C6H60]+' ion in the spectrum of C,H,OC,H has the same structure as the phenol molecular ion.'2 Steric effects suggest that the [YC,H,N] +.ions from phenyl-substituted acetanilides have the structure of the corresponding aniline. A study of appear-ance potentials and metastable ion abundances has shown that the m/e 165 ions 0 C6H 5 C6HS c6H5vc6H5 0 0 (5) (6) * H.Giezendanner M. Hesse and H. Schmid Org. Mass Spectrometry 1970 4 405. J. Carles Y. Rousseau and S. Fliszar Canad. J. Chem. 1970 48 2345. lo R. C. Dougherty R. L. Foltz and L. B. Kier Tetrahedron 1970 26 1989. l1 C. B. Thomas J. Chem. SOC.(B) 1970 430. P. D. Woodgate and C. Djerassi Org. Mass. Spectrometry 1970 3 1093. l3 A. A. Gamble J. R. Gilbert and J. G. Tillett Org. Mass Spectrometry 1970 3 1223. Physical Methods-Part (i)Mass Spectroscopy (C,,H,+) from fluorene and phenalene do not have the same structure^;'^ similarly the ions C ,H and C 2H,N+ from 1-(benzy1ideneamino)benzo-+ triazole do not have the fluorenyl or carbazole structures.’ p-Fluoro-labelling has established that the (C,Ar,)+’ ions derived from tetracyclone (3) and tetra- phenylquinone (4)are produced after complete scrambling in the molecular ion that partial scrambling occurs in pentaphenylcyclopentadienol(5) and that there is virtually no scrambling in tetraphenylthiophen SS-dioxide (6).l6 A detailed study of the fragmentation of tetralin and related heterocycles [(7) and (8)] has shown that only isothiochroman (7 ;X = S) gives a true retro-Diels- Alder (RDA) fragmentation.In the series (7; X = 0 NH and S) the ion of (7; X = CH, 0,NH S) (8; X = CH, 0,NH S) m/e 104 is produced almost exclusively by process (i). However for tetralin only 45‘xis produced by this route the remainder by (ii).In the series of compounds mx’+’ -+ a’+’ + CH =X (1) + CH = X (ii) (8) the RDA fragmentation is not important.” The spectra of the related systems (9) and (10)are dominated by processes equivalent to (i).18 The full details of the ICR study of the double McLafferty rearrangement reported last year” have appeared.20 The subsequent decomposition of the enol J. H. Bowie and T. K. Bradshaw Austral. J. Chem. 1970 23 1431. U. Rapp H. A. Staals and C. Wunsche Org. Mass Spectrometry 1970 3 45. l6 M. K. Hoffman T. A. Elwood P. F. Rogerson J. M. Tesaret M. M. Bursay and D. Rosenthal Org. Mass Spectrometry 1970 3 891. A. G. Loudon A. Maccoll and S. K. Wong J. Chem. SOC.(B) 1970 1727. A. G. Harrison M. T. Thomas and I. W. J. Still Org. Mass. Spectrometry 1970 3 899.l9 G. Eaden J. Dickmann and C. Djerassi J. Amer. Chem. SOC.,1969 91 3986. G. Eaden J. Dickmann and C. Djerassi J. Amer. Chem. SOC.,1970 92 6205. R. T. Aplin ions (ll) (12) and (13) produced in the McLafferty rearrangement of simple ketones is via initial ketonisation.21 (1 1) (12) (13) The technique of ion kinetic energy spectroscopy (IKES) has been applied to study the processes involved and the energetics of the spectra of a series of aromatic hydrocarbons,22 and also used to study the triply charged molecular ion of biphenyl.23 The release of 4.5 eV in its decomposition C12H1O3++ CI1H7'++ CH3+ suggests the charge-separated structure (14) for this ion. Conventional spectra have also been used to study similar processes in other condensed aromatic corn pound^.^^ Fragmentation and Rearrangement Processes.-The studies of carbon and hydrogen randomisation reported last year2 have been continued this year by the use of deuterium and '3C-labelled systems.The spectrum of the 13C- labelled benzene (15) shows complete carbon scrambling in the molecular ion prior to the loss of C2H2.26 The spectrum of the doubly labelled benzene (16) D (15) * = I3C (16) (17) showed that ca. 30% of the ions C3H3+and C4H4+arise by paths in which the carbon atoms are scrambled without breaking C-H bonds. In the remaining 70 % the hydrogens are scrambled over and beyond whatever carbon scrambling ' D. J. McAdoo F. W. McLafferty and J. S. Smith J. Amer. Chem. Soc. 1970,92,6343.22 J. H. Beynon R. M. Caprioli W. E. Baitinger and J. W. Amy Org. Mass Spectrometry 1970 3 455. '' J. H. Beynon R. M. Caprioli W. E. Baitinger and J. W. Amy Org. Mass Spectrometry 1970 3 661. 24 P. Nounou Internat. J. Mass Spectrometry Ion Phys. 1970 4 219. 25 R. T. Aplin Ann. Reports (B) 1969 66 5. 26 I. Hormon A. N. Yeo and D. H. Williams J. Amer. Chem. Soc. 1970 92 2131. Physical Methods-Part (i) Muss Spectroscopy 11 occurs.27 The loss of methyl radicals from m/e 168(M") and m/e 167(M" -H') in the spectra of diphenylmethanes is preceded by a complete hydrogen and carbon scrambling.28 Complete loss of positional identity of both a- and ring- hydrogen atoms has also been established for the simple molecular ion fragmenta- tions (M -H' M -H, M -CH,' and M -CH,) of triptycene and tri- ~henylmethane.~~ The spectrum of the benzo[b]thiophen (17) showed that car- bon scrambling also occurs before or during the formation of many of the fragments.,' Randomisation of all nine hydrogens uia ring expansion occurs in methylquinolines prior to fragmentati~n.~' In the dimethylquinolines ring expansion precedes loss of H' and CH,'.Expansion in the benzenoid ring is favoured over the pyridine ring.32 The molecular ions of fluoro- and chloro- toluenes like those of substituted chlor~benzenes,~ undergo ring-expansion rearrangement prior to fragmentation ;in contrast the bromo- and iodo-toluenes do not rearrange prior to fragmentati~n.~~ The loss of HCN and C2H2 from the phenylnitrenium ion generated from [2,4,6-'H3]phenyl azide is preceded by H-D rand~misation.~~ Hydrogen scrambling in the molecular ion is also observed between the two phenyl rings in halogenated diphenyla~etylenes.~' In contrast evidence of hydrogen randomisation has been found to be absent from the spectra of hydr~cinnamaldehyde,~ the triphenyl/tetraphenyl derivatives of the Group IV and V elements,,' and 1,2,2a,3-tetrahydrocyclobuta[b]quin-oxaline (18).39 Similarly p-fluoro-labelled penta-arylpyridine and related CH,(CH,),OCH = CH H (19) (18) compounds show little or no randomisation prior to fragmentation of their molecular ions.40 In the 70 eV spectra of normal4' and bran~hed-chain~~ ali-phatic ketones hydrogen randomisation has been shown to occur prior to a-cleavage.Extensive carbon rearrangement precedes the loss of CH,' and C,H,' '' W. 0.Perry J. H. Beynon W. E. Baitinger J. W. Amy R. M. Caprioli R. N. Renaud L. C. Leitch and S. Meyerson J. Amer. Chem. Soc. 1970 92 7236. " T. K. Bradshaw J. H. Bowie and P. Y. White Chem. Comm. 1970 537. 29 S. Meyerson Org. Mass. Spectrometry 1970 3 119. 3n R. G. Cooks and S. L. Bernasek J. Amer. Chem. SOC. 1970 92 2129. " P. M. Draper and D. B. Maclean Canud. J. Chem. 1970 48,747. 32 P. M. Draper and D. B. Maclean Canud. J. Chem. 1970 48 738. 33 P. Brown Org. Muss. Spectrometry 1970 3 639. 34 A. N. H. Yeo and D. H. Williams Chem. Comm. 1970 886. 35 D. G. I. Kingston and J. D. Henion Org. Muss. Spectrometry 1970 3 413. 36 S. Safe Org. Mass Spectrometry 1970 3 239.37 A. Venema N. M. M. Nibbering and Th. J. de Boer Org. Muss Spectrometry 1970 3 583. 38 J. H. Bowie and B. Nussey Org. Muss Spectrometry 1970 3 933. 39 C. W. Koch and J. H. Markgraf J. Heterocyclic Chem. 1970 7 235. 40 M. M. Bursey and T. A. Elwood J. Org. Chem. 1970 35 793. 41 A. N. H. Yeo Chem. Comm. 1970 987. 42 G. Eadon and C. Djerassi J. Amer. Chem. SOC.,1970,92 3084. R. T.Aplin from various isomeric hexane~.~~ A further example of the rare triple hydrogen transfer observed in the higher esters of trimellitic anhydride,25 is present in the spectra of alkyl vinyl ethers (19; n >4);deuteriation has established the sequence shown in Scheme 1 for the loss of C2H60.44Skeletal rearrangements have been Scheme1 observed in the following systems acetylenic sulphoxides and s~lphones,~’ acetylenic ethers of cyclic p0lyols,4’-~~ thiobenzoates and thio- acetates,’ thionyl[1-’3C]aniline,52 nitrophenyl hydrazones of aldehydes and tetrasila-adamantane~,~~ ketones,53 chroman~,~~ 3-phenylnitropropane and 3-phenylpropyl nitrite,56 2-methyl-2-hydroxy(or 2-amino)-propane~,~’ phenyl-ox as tannin^,^ and diaryl thiosulphinates and diaryl thio~ulphonates.~~ In spite of further evidence for the migration of trimethylsilyl groups in the spectra of TMS ethers of aldonic and deoxyaldonic acids,60 these derivatives have proved invaluable in the study of ketoses and aldoses,61 sugar phosphates,62 and inositols 43 C.Corolleur S. Corolleur and F. G. Gault Bull. SOC. chim. France 1970 158.44 M. Katoh and C. Djerassi J. Amer. Chem. SOC.,1970 92 731. 45 T. H. Kinstle W. R. Oliver and L. A. Ochtymowycz Org. Muss Spectrometry 1970 3 241. 46 R. T. Aplin and R. Mestres Org. Mass Spectrometry 1970 3 1067. 47 R. T. Gray J. Diekman G. L. Larson W. K. Musker and C. Djerassi Org. Mass Spectrometry 1970 3 973. 48 J. Winkler and H.-Fr. Griitzmacher Org. Mass. Spectrometry 1970 3 11 17. 49 A. Casper G. Teller and R. E. Wolff Org. Mass spectrometry 1970 3 1351. 50 P. D. Woodgate R. T. Gray and C. Djerassi Org. Mass Spectrometry 1970 4 257. 5‘ A. Ohno T. Koizumi Y.Ohnishi and G. Tsuchihashi Org. Mass Spectrometry 1970 3 261. 52 A. S. Siegel Org. Mass Spectrometry 1970 3 875. s3 J. Seibl Org. Mass Spectrometry 1970 3 417. 54 J. R.Trudell S. D. Sample Woodgate and C. Djerassi Org. Muss Spectrometry 1970, 3 753. 55 R. S. Gohlke and R. J. Robinson Org. Mass Spectrometry 1970 3 967. 56 N. M. M. Nibbering and Th. J. de Boer Org. Mass Spectrometry 1970 3 487. 57 A. S. Siegel Org. Mass Spectrometry 1970 3 1417. 58 I. Lengyel and M. J. Aaronson Chem. Comm. 1970 129. 59 S. Kozuka H. Takahashi and S. Oae Bull. Chem. SOC.Japan 1970 43 129. ‘O G. Peterson Tetrahedron 1970 26 3413. 61 S. Karady and S. H. Pines Tetrahedron 1970 26 4527. 62 M. Zinbo and W. R. Sherman J. Amer. Chem. SOC.,1970,92 2105. Physical Methods-Part (i) Mass Spectroscopy by the combined g.c.-m.s. te~hnique,~~ and show promise for the sequencing of nucleoside~.~~ Although the spectra of the bicyclic alcohols (20) (21) and (22) (20) (21) (22) are complex involving extensive rearrangements a characteristic ion m/e 57 (X = H) m/e 58 (X = D) is produced without rearrangement; the ion can be used to analyse the amount of migration occurring during the solvolysis of various deuteriated derivatives of these alcohols.65 The predicted potentialb6 of mass spectrometry for stereochemical studies has been realised in two papers.The endo esters (23) eliminate methanol through a seven-membered transition state ;the stereoisomeric exo diesters (24) do not appreciably eliminate methanol but eliminate MeO' instead. The trans diesters (25) eliminate methanol via a five-membered transition state.b7 Deuteriation has shown that the loss of water ,C02Me (23) (24) (25) (n = 14) from the cis-and trans-4-isopropylcyclohexanol proceeds as shown in Scheme 2.68 Similar differences are apparent in the spectra of the isomeric 3,4-diethyl- muconic acid dimethyl esters.69 trans cis Scheme 2 '' W.R. Sherman N. C. Eilers and S. L. Goodwin Org. Muss Spectrometry 1970 3 829. 64 J. J. Dolhun and J. L. Wiebers Org. Muss Spectrometry 1970 3 669. 65 H. Kwart and T. A. Blazer J. Org. Chem. 1970,35 2726. " E. L. Eliel H. L. Allinger S. J. Angyal and G. A. Morrison 'Conformational Analysis' Interscience New York 1965 p. 1878. " J. Deutsch and A. Mandelbaum J. Amer. Chem. SOC.,1970 92 4288. " M. M. Green and R. B. Ray J. Amer. Chem. SOC.,1970 92 6368. 69 E. Gil-Av J. H. Leftin A. Mandelbaum and S.Weinstein Org. Mass Spectrometry 1970 4 475. 14 R. T Aplin Application of Various Techniques.-Field ion spectroscopy has been employed to examine substituent effects in aryl-O-gluco~ides~~ and to determine the sequence of small peptides. Chemical ionisation (CI) spectroscopy as antici-~ated,~’ is proving a valuable structural tool and has been used to examine amino-acid~,~~ alcohols,73 alkaloids,74 and sensitive photodimer~.~’A very promising application is in combined g.c.-m.s. analysis where the carrier gas is the ionising gas eliminating the need for a separator between the gas chromato-graph and the mass spe~trometer.~~ The CI spectra of a series of substituted benzophenones have been investigated with several reactant gases methane ethane propane and butane.77 Amino-acid derivative^^^.^^ and peptides have been further examined by mass spectrometry and spectacular success has been achieved in determining the structure of the antibiotic cycloheptamycin via sequencing of the permethylated derivative (26).80 The insecticidal cyclodepsi-peptides Destruxin A and B have also been successfully sequenced.8 Mass sequence ions M.W.1092 142 271 462 547 674 817 1061 H C-MeVal; MeThr MeTyr I MeAIa MeaIlel /3-hydroxyMeNva I.5-methoxyMeTrp IOMe 0 I I I I Me Me Me Me spectrometry has also established that synthetic L-pyroglutamyl-L-histidyl-L-prolinamide is identical to the natural thyrotropin-releasing hormone (TRH).~ Structural elucidation of antibiotics including two new heptaene macrolides from StreptomycesB3and the macrolide primycin whose polyether (27) afforded a molecular ion,84has been greatly facilitated by analysis of the mass spectra of degradation products.Mass spectrometry was also successful in the elucidation ’O G. 0. Phillips W. G. Filby and W. L. Mead Chem. Comm. 1970 1269. 71 P. Brown and G. R. Pettit Org. Muss Spectrometry 1970 3 67. 72 G. W. A Milne T. Axenrod and H. M. Fales J. Amer. Chem. SOC.,1970 92 5170. i3 F. H. Field J. Amer. Chem. SOC.,1970 92 2672. ” H. M. Fales H. A. Lloyd and G. W. A. Milne J. Amer. Chem. SOC.,1970,92 1590. ” H. Ziffer H. M. Fales G. W. A. Milne and F. H. Field J. Amer. Chem. SOC.,1970 92 1597. 76 G. P. Arsenault J. J. Dolhun and K. Biemann Chem. Comm.1970 1542. ” J. Michnowicz and B. Munson Org. Mass Spectrometry 1970 4 481. 78 M. S. Manhas R. S. Hsiech and A. K. Bose J. Chem. Sac. (C) 1970 116. ’’ I. Lengyel R. A. Salomone and K. Biemann Org. Mass Spectrometry 1970 3 789. 8o W. 0.Godtfredson S. Vangedal and D. W. Thomas Tetrahedron 1970 26 4931. A. Suzuki N. Takahashi and S. Tamura Org. Mass Spectrometry 1970 4 175. 82 D. Gillessen A. M. Felix W. Lergier and R. 0.Studer Helv. Chim. Acta 1970,53,63. x3 F. Bohlmann E. V. Dehmlow H.-J. Neuhahn R. Brandt and H. Bethke Tetrahedron 1970 26 2199. 84 J. Aberhart T. Fehr R. C. Jain P. de Mayo 0.Motl L. Baczynskyg D. E. F. Gracey D. B. Maclean and I. Szitagyi J. Amer. Chem. SOC.,1970 92 5816. Physical Methods-Part (i) Mass Spectroscopy of the structures of other complex antibiotics including Roridin H8' and E,86 Phomine,87 Aranciamycin,88 and the Mitomycin~,~~~~~ Bun OR' H OR' R4 (27; R' = RZ = R3= Me R4 = COMe) M.W.1319 The A"6'-aromatic Erythrina alkaloids [(e.g.(28)] undergo the characteristic fragmentation shown," which has been applied to identify new members of this group." Mass spectrometry was largely responsible for determining the structures 1" -+ Me0 OH of the highly complex bis-indole alkaloids amataine goziline and ~werreine.'~ The characteristic cleavage of the side-chain of the unusual marine sterol gorgo- sterol (29)94 was used to determine the absence of the 23-methyl group in the related sterol (30).95 The characteristic fragmentation of the insect moulting hormones has been utilised in determining the structures of related '' P.Traxler and Ch. Tamm Helv. Chim. Acta 1970 53 1846. 86 P. Traxler W. Ziircher and Ch. Tamm Helv. Chim. Acta 1970 53 2071. " N. Rothweiler and Ch. Tamm Helv. Chim. Acta 1970 53 696. 88 W. Keller-Schierlein J. Sauerbier V. Vogler and H. Zahner Helv. Chim. Acra 1970 53 779. " G. E. Van Lear Tetrahedron 1970 26 2587. 90 G. 0. Monton G. E. Van Lear and W. Falmor Tetrahedron 1970 26 2588. 9' R. B. Boar and D. A. Widdowson J. Chem. SOC.(B) 1970 1591. 92 D. H. R. Barton P. N. Jenkins R. Letcher D. A. Widdowson E. Hough and D. Rogers Chem. Comm. 1970 391. 93 V. Agwada M. B. Patel M. Hesse and H. Schmid Helv. Chim. Acta 1970,53 1567. 94 R. L. Hale L. Leclerq B. Tursch C.Djerassi R. A. Gross jun. A. J. Weinheimer K. Gupta and P. L. Scheuer J. Amer. Chem. SOC.,1970,92 2179. 95 F. J. Schmitz and T. Pattabhiraman J. Amer. Chem. Soc. 1970 92 6074. R. T. Aplin (29; R = Me) (30; R = H) compounds.96-100 The potential of mass spectrometry in the sequencing of oligo-saccharides has been demonstrated by the use of 1-phenylflavazole peracetates to sequence di- to penta-saccharides. lo The spectra of peracetylated cardenolides similarly give information about both the aglycone and sugar moietie~.'~~*'~~ Methoxymercuration-demercuration followed by combined g.c.-m.s. analysis has been developed as a general method for the location of olefinic links in long- chain esters as shown in Scheme 3.'04 Further papers on the use of computers R'-CH=CH-R2 Me0 HgOAc 4 MeOH AcOHg OMe II I1 R'-CH-CH-R2 R'-CH-CH-R~ 1NaBH 1NaBH OMe I 1 1 + + + MeO+ OMe OMe OMe I1 II II II RICH + CHCH,R2 R'CH2CH + CH-R2 Scheme 3 96 H.Hikino. K. Nomoto and T. Takemoto Terralredron. 1970. 26 887. 97 A. Faux M. N. Galbraith D. H. S. Horn E. J. Middleton and J. A. Thomson Chem. Comm. 1970 243. 9a M. Koreeda and K. Nakanishi Chem. Comm. 1970 351. 99 S. Imai E. Murata S. Fujioka T. Matsuoka M. Koreeda and K. Nakanishi Chem. Comm. 1970 352. loo Y. K. Chong M. N. Galbraith and D. H. S. Horn Chem. Comm. 1970 1217. lo' G. S. Johnson W. S. Ruliffson and R. G. Cooks Chem. Comm. 1970 587. lo' B. Blessington and I. M. Morton Org. Mass Spectrometry 1970 3 95.B. Blessington Y. Nakagawa and D. Sotoh Org. Mass Spectrometry 1970 4 215. Io4 D. Abley F. J. McQuillin D. E. Minnikin K. Kusamran K. Maskens and N. Polgar Chem. Comm. 1970 348. Physical Methods-Part (i) Mass Spectroscopy for the interpretation of mass spectra have appeared from the Djerassi-Lederberg group; these are concerned with the spectra of saturated arnine~'~~~'~~ and iso- meric ketones of the composition C,H,00.'07 Two small on-line computer systems have also been described in detail.' 08*'O9 lo' A. Buchs A. B. Delfino A. M. Dufield C. Djerassi B. G. Buchanan E. A. Feigen-baum and J. Lederberg Helu. Chim. Acfa 1970 53 1395. A. Buchs A. M. Duffield G. Schroll C. Djerassi A. B. Delfino B. G. Buchanan G. L. Sutherland E. A. Feigenbaum and J.Lederberg J. Amer. Chem. Soc. 1970 92,6831. lo' V. M. Shiekh A. Buchs A. B. Delfino G. Schroll A. M. Duffield C. Djerassi B. G. Buchanan G. L. Sutherland E. A. Feigenbaum and J. Lederberg Org. Mass Spectro- metry 1970 4 493. Io8 R. J. Himowski R. Venkataraghaven F. W. McLafferty and F. B. Delany Org. Mass Spectrometry 1970 4 17. '09 H. S.Hertz D. A. Evans and K. Biemann Org. Mass Spectrometry 1970 4 453.

ISSN:0069-3030    

DOI:10.1039/OC9706700007

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

2 Physical Methods Part (ii) Electron Spin Resonance Spectroscopy By B. C.GILBERT Department of Chemistry University of York Heslington York YO1 500 RELEVANTreviews which have appeared during 1970 include those by Luckhurst on the physical and theoretical aspects of e.s.r.' and on the detailed information afforded by the use of anisotropic solvents.2 Evidence concerning the structure of organic radicals has been reviewed by Norman3 and aspects of line-broadening phenomena discussed by Chang4 (electron-transfer reactions) and by Sullivan and Bolton' (the alternating line-width effect). Applications in organic electro- chemistry,6 the theory of isotropic hyperfine splittings,' and the usefulness of the rotating cryostat (which has now been employed to detect intramolecular and transannular reactions)8 have also been reviewed.As last year,' this report is concerned primarily with organic radicals in solu-tion and specifically excludes gases the experimental method double resonance spin-labelling liquid crystals inorganic systems. and triplets. Results for transi- tion metal ions" and for radicals in solids will only be mentioned where they are relevant to the main theme. For instance attention is drawn to the observation of isotropic spectra of radicals trapped in an adamantane matrix;8*11*12 in this way well-resolved spectra have been observed during the X-irradiation of amines [CH(NH2)CH,CH3from n-propylamine for example]' and during the photoly- sis of these initially-formed radicals.' 1 Hyperfine Splittings Structure,and Conformation Theory.-Ab initio UHF calculations on several small radicals,' including G.R. Luckhurst Ann. Reports (A) 1969 66 37. G. R. Luckhurst Roy. Inst. Chem. Rev. 1970 3 61. R. 0. C. Norman Chem. in Britain 1970 6 66. R. Chang J. Chem. Educ. 1970,47 563. P. D. Sullivan and J. R. Bolton Adv. Magn. Resonance 1970 4 39. ' B. Kastening Chem.-lng.-Tech.,1970,42 190. ' K. D. Sales Ado. Free Radical Chem. 1969,3 139. * J. E. Bennett B. Mile A. Thomas and B. Ward Adv. Phys. Org. Chem. 1970 8 1. C. Thomson Ann. Reports (B) 1969 66 15. lo 'Spectroscopic Properties of Inorganic and Organometallic Compounds' ed. N. N. Greenwood (Specialist Periodical Reports) The Chemical Society London 1970 Volume 3 p. 160. I ' D. E. Wood and R.V. Lloyd J. Chem. Phys. 1970,52 3840; ibid. 53 3932. I' D. E. Wood R. V. Lloyd and D. W. Pratt J. Amer. Chem. SOC.,1970 92 41 15. I3 T. A. Claxton D. McWilliams and N. A. Smith Chern. Phys. Letters 1970 4 505; T. A. Claxton and D. McWilliams Trans. Faraday SOC.,1970,645 513; T. A. Claxton and N. A. Smith ibid. p. 1825; T. A. Claxton Nature 1970 226 1242. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy 19 methyl,I4 have appeared. Semi-empirical calculations reported include an extended McLachlan method for a-radicals (e.g. vinyl iminoxyl radicals),' and methods for calculating isotropic h.f.s. for 'H 13C I7O,and I9F in a variety of n-radicals,I6 proton splittings in odd alternant hydrocarbon radical^,'^ and the angular dependence of methyl splittings ;l spin polarization in benzyl and related radicals has been studied using a perturbation-variation approach." Various INDO calculations will be discussed later together with the correspond- ing experimental results ;Thomson2' has reported estimated splittings for the calculated minimum energy configurations of HBO- HCO.and HCN-. A simple non-empirical model is proposed to reproduce both the a-and p-proton splittings in alkyl radicals;21 the p C-H bonds are assumed to contribute electrons to the n-system (hetero-atom model) and the a-protons appear to gain unpaired electron density partly via an inductive effect. Barfield22 employed a VB method to calculate long-range proton splittings in some n-radicals obtaining good agreement for the y-H splitting in n-propyl and for they- and 6-H splittings in cyclohexyl radicals.In another (MO)cal~ulation,~~ the minimum splitting at the y- but not at the &position is also correctly pre- dicted for the latter radical. Proton Sp1ittings.-The INDO method has been used to calculate with good agreement the h.f.s. for some new o-radicals. For example Krusic and Rettig24 detected the benzoyl radical (PhCO.) when a solution of benzaldehyde and di-t- butyl peroxide in cyclopropane was photolysed. The radical has g = 2.0014 a(I3C)= 128 G and aH(meta) = 1.16G the h.f.s. being consistent (INDO) with a a-radical having a low barrier to rotation of the phenyl group about a planar conformation. The 7-norbornenyl radical results from photolysis of t-butyl anti-peroxy-2-norbornene-7-carboxylate at about -100 0C,25 and comparison of the splittings with those for the 7-norbornyl radical indicates that 7-norborn- enyl is best regarded as a classical species with some bending at the radical centre.Alkylimino (a) radicals have been prepared from a-aminoalkyl radicals by photolysis,'* and by hydrogen atom addition to nitriles both in solids26 and in electron-irradiated aqueous s~lution.~' For CH3CH=N.,27 aN= 10.2 uH= 81.98 and uH(CH3) = 2-49G (g = 2,00283) in reasonable agreement with INDO calculations.' 2*26 (It is suggested27 that these radicals may also be responsible I4 S. Y. Chang E. R. Davidson and G. Vincow J. Chem. Phys. 1970. 52 1740. l5 T. Yonezawa T. Kawamura and H. Kato Bull. Chem.SOC.Japan 1970,43 74. l6 M. F. Chiu and B. T. Sutcliffe Theor. Chim. Acta 1970 16 331. " J. Nowakowski Theor. Chim. Acta 1970 18 133. H. Nakatsuji H. Kato and T. Yonezawa Bull. Chem. Soc.Japan 1970,43 698. l9 H. Lebrun and M. Suard Theor. Chim. Acta 1970 16 43. '' C. Thomson Theor. Chim. Acta 1970 17 320. '*R. Fantechi and G. A. Helcke J. Chem. SOC.(A) 1970 1294. 22 M. Barfield J. Phys. Chem. 1970 74 621. 23 I. A. Abronin G. M. Zhidimorov and A. L. Buchachenko; Zhur. strukt. Khim. 1970 11 229. " P. J. Krusic and T. A. Rettig J. Amer. Chem. SOC.,1970,92,722. 25 P. Bakuzis J. K. Kochi and P. J. Krusic J. Amer. Chem. SOC. 1970,92 1434. 26 P. Svejda and D. H. Volman J. Phys. Chem. 1970,74 1872. '' P. Neta and R. W. Fessenden J. Phys.Chem. 1970,74 3362. 20 B. C. Gilbert for the unusual signals observed28 from irradiated malonamide and cyanourea). It is clear that many substituted alkyl radicals are not strictly of n-type (ie. planar). For example a(13C) for .CH,OH is 47.0 G29 and a(a-l3C) for -C(CH3),0H (produced phot~lytically~~) is 65.05 G both of which indicate a slight degree of bending about the trigonal carbon. [By comparison for the planar radical CH,COO- the values of (+)32.0 and (-)1345G are in excellent agreement with Karplus-Fraenkel calculations for a(a-C) and a(P-C) respec- ti~ely.~']. Further oxygen substituents cause marked bending as evidenced by higher a(a-' 3C) and less negative or even positive a(a-H) values :H-atom abstrac- tion from trioxan gives a radical with a(13C) = 98.8 G and a(a-H) = 0.47 G.29 The factors causing non-planarity [which are not peculiar to the radicals since a(a-H) values are correlated with J(13CH) for the parent compounds] are appar- ently the inductive (-I) and mesomeric effects of the substituent ;the importance of electronegativity has been stressed ~eparately.~' Calculations support the suggestion that the temperature dependence of the splittings for CH3 arise from out-of-plane vibration^,^' and it is also perhaps relevant that non-planar CH (aH= 19 G) appears to be stabilised on porous glass.33 Hyperfine splittings for some oxygen- and sulphur-conjugated radicals (from .OBu' and ethers or thioethers) indicate that there is more delocalisation onto the hetero-atom in the latter cases but that the bending is greater for the former.34 There also exists evidence for non-planarity about the trigonal carbon in the radicals CH(NH,)R (INDO calculations have been performed for various geo- metries)' and also for C(NH,)(CH,)CO,- which results when glycine is oxidised with .OH at high pH and which has anomalous aNand a(a-H) values.35 The low g-values for these radicals are also As expected CFC1 is n~n-planar.,~ The effect of methyl substitution on the pyramidal silyl radicals (from .OBu' and silanes) is to decrease the deviation from planarity;37 u(,~S~) for .Si(CH,) is 183 G smaller than for 4iH3 (but see ref.37a). Difluoro-nitroxide F,NO- (formed by photolysis of trifluoramine oxide at -196°C) is also nonplanar as indicated by the large splittings aN= 94.3 and aF = 142.2 G,,* and INDO calculations for (CF,),NO.suggest that the variation in aNwith tempera- ture results from ready inversion of a pyramidal structure of minimum energy.39 28 P. W. Lau and W. C. Lin J. Chem. Phys. 1969,51 5139. 29 A. J. Dobbs B. C. Gilbert and R.0.C. Norman Chem. Comm. 1969 1353. 30 R.Livingston J. K. Dohrmann and H. Zeldes J. Chem. Phys. 1970,53,2448. 31 T. A. Claxton and N. A. Smith J. Chem. Phys. 1970,52,4317; A. Begum J. H. Sharp and M. C. R. Symons J. Chem. Phys. 1970,53,3756. 32 S. Y. Chang E. R. Davidson and G. Vincow J. Chem. Phys. 1970,52 5596. 33 N. Shimamoto Y. Fujita and T. Kwan Bull. Chem. SOC.Japan 1970,43 580; G. B. Garbutt and H. D. Gesser Canad. J. Chem. 1970,48,2685. 34 A.Hudson and K. D. J. Root J. Chem. SOC.(B),1970,656. 35 H. Paul and H. Fischer Ber. Bunsengesellschaft Phys. Chem. 1969 73 972. 36 A. J. Bowles A. Hudson and R. A. Jackson Chem. Phys. Letters 1970,5,552. 37 S. W. Bennett C. Eaborn A. Hudson R. A. Jackson and K. D. J. Root J. Chem. SOC. (A) 1970 348. 37aJ.H. Sharp and M. C. R. Symons J. Chem. SOC.(A),1970,3084. 38 W. B. Fox B. Sukornik J. S. Mackenzie R.L. Sturtevant A. F. Maxwell and J. R. Holmes J. Amer. Chem. SOC.,1970,92 5240. 39 G. R. Underwood and V. L. Vogel Mol. Phys. 1970,19,621. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy 21 N.m.r. has been employed in conjunction with electron resonance to determine the proton h.f.s. with signs for some hindered aryl nitroxide~.~' It was concluded both from the ratio of aHto a(CH,) and from the ordering of ring-proton splittings (ortho Y meta > para) that the orbital of the unpaired electron has some CT-character ;this refers to twisting of the plane of the aryl group rather than bending about the nitrogen.McLachlan and INDO calculations predict the observed trend in proton ~plittings.~' Molin4' has suggested that both (T-and n-effects should be allowed for in estimating spin density distributions for conjugated ligands in paramagnetic complexes and for radicals containing twisted phenyl groups. Analysis of the '3C and proton splittings for diphenylmethyl and some related radicals (produced by photolysis of the corresponding diazo-compounds in hydrogen-donor solvents)42 suggests that the trigonal carbon is sp2 hybridised ; in CHPh the rings are probably twisted (6 'v 50").Twisting and substituent effects for a variety of triarylmethyl radicals have also been discussed.43 Other radicals where steric hindrance causes aromatic rings to be forced out of coplanar- ity with the radical centre include phenylxanthyl( 1)44 and its sulphur and selenium homol~gues~~.~~ (0 = 60-70") and the cation and anion radicals of 9,10-di-(z- naphthy1)anthracene (6' Y 75")46 and of a series of nitrophenyl-substituted aro- matics [O = 90" for the anion radical of 9-(p-nitrophenyl)anthra~ene].~'An elegant investigation4* of anisotropic and isotropic splittings for radicals in liquid crystals has indicated that Ph,C. is probably constrained to become less twisted in this environment and that the temperature dependence of aNand aHfor both 4-amiilo-2,6-di-t-butylphenoxyl and Wurster's Blue probably originates from the vibrations of the amino-group ;the acquisition of more quantitative data is limited by the inaccuracies in the theoretical anisotropic hyperfine tensor.48 Several interesting conclusions have resulted from examination of P-proton splittings.For instance for a methylene group flanked by two positions with Q do. HH '0' (1) 'O A. Calder A. R. Forrester J. W. Emsley G. R. Luckhurst and R. A. Storey Mol. Phys. 1970 18,481 ;A. R. Forrester and R. Ramasseul Chem. Comm. 1970 394. " Yu. N. Molin Chem. Phys. Letters 1970 5 51 1. " D. R. Dalton and S. A. Liebman Tetrahedron 1970 26 3265.43 W. J. Van der Hart Mol. Phys. 1970 19 75. 44 K. Maruyarna. M. Yoshida and K. Murakami Bull. Chem. Soc. Japan 1970,43 152. 45 L. Lunazzi A. Mangini G. Placucci C. Vincenzi and 1. Degani Mof. Phys. 1970 19 543. See also I. Degani L. Lunazzi G. F. Pedulli C. Vincenzi and A. Mangini Mol. Phys. 1970 18 613. 4h L. S. Marcoux A. Lomax and A. J. Bard J. Amer. Chem. Sac. 1970,92,243. " G. R. Underwood D. Jurkowitz and S. C. Dickerman J. Phys. Chem. 1970,74 544. " H. R. Falle and G. R. Luckhurst J. Mugn. Resonance 1970 3 161. B. C.Gilbert appreciable spin density it has been confirmed that the h.f.s. is proportional to the square of the sum of the corresponding n-orbital coefficients; thus the indane- semidione (2)shows an anomalously small CH splitting (2.8 G) and MO calcula-tions predict opposite signs for the coefficients of the orbital of the unpaired electron at the adjacent carbon atoms.49 The low a(P-H) of 11.5 G for .CH,CH,Cl (from -OBu' Et,SiH and BrCH,CH,Cl) and the unusually large chlorine splitting (17.4 G) provide evidence that the preferred conformation has the chlorine eclipsing the orbital of the unpaired electron with possible deformation towards a bridged str~cture.,~ In the nitroxides RCH2NR10.where R is a chiral group (e.g. 2-tetrahydrofurfuryl) two different P-methylene proton splittings are observed since the two protons concerned are never magnetically equivalent restricted rotation need not be postulated to account for the difference. A conformational analysis for a variety of substituents (R R') has been presented." Halogen Splittings-The factors which relate a-and /I-halogen splittings to structure and spin density distribution still remain obscure.For instance values for the parameters QZF and QFc of -85 and 1043 G respectively lead to good agreement for meta-and para-F splittings in fluorinated triphenylmethyl radicals and benzophenone ketyls as long as the para-splitting is negative and the meta-splitting positive.'' But signs were not determined and to have aFand pc oppo-site in sign (e.g. for p-F) is contrary to most previous results and assumptions. Evidence was also presented for direct interaction between the o-F atoms and the radical centre. Consideration of some photolytically produced fluorinated benzyl radicals and benzaldehyde ketyls together with McLachlan an3 UHF calculations leads to the suggestion that QF is positive and probably dominant but the possibility of a positive Qg is also discus~ed.~~~~~ The solution to this problem lies in the experimental evaluation of pc pF,and the sign of the splitting.The angular dependence of B-F splittings and the mechanism of interaction (hyperconjugation and/or 1,3-p7c interaction) are similarly unclear. Results for the following anions s~ggest~~,~~ that the angular dependence of a(P-F) is similar to that for a(P-H) at least for 8 =25-45' (CF3),c-O- CF2FF2\(5-0 CF3-N-N-CF3 CF2-CF2 N=N1-1 \/ CF2 49 E. T. Strom E. G. Janzen and J. L. Gerlock Mol. Phys. 1970,19,577;G. A. Russell C.L. Meyers P. Bruni F. A. Neugebauer and R. Blankespoor J. Amer. Chem. SOC. 1970,92 2762. 50 P. Tordo M. P. Bertrand and J.-M.Surzur Tetrahedron Letters 1970 1799. S. V. Kulkarni and C. Trapp J. Amer. Chem. SOC.,1970,92,4801,4809. 52 A. Hudson and J. W. E. Lewis Ma/. Phys. 1970 19 241. 53 E. G. Janzen B. R. Knauer J. L. Gerlock and K. J. Klabunde J. Phys. Chem. 1970 74 2037. 54 J. L. Gerlock E. G. Janzen and J. K. Ruff J. Amer. Chem. SOC.,1970 92 2558. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy 23 For a series of fluoroalkyl nitroxides Bu'NRO- prepared by spin trapping," the results are qualitatively similar. When R = CF, aF = 12.27 G at W whereas for R = CF(CF,), a(P-F) = 2-30G becoming smaller as the tempera- ture is lowered (see also ref.56),as expected for a cos2 8relationship if the P-F in the fluoroisopropyl group approaches a preferred conformation in the nodal plane of the unpaired electron's orbital. In complete contrast a(P-F) for the radical anion of (CF,),CF-N=N-CF(CF,) is 62-45 G; in this case the narrow line-widths (second-order splittings were observed) indicate that fluorine atoms occupy highly equivalent environments probably with the P-F atoms again in the nodal (C-N=N-C) plane.54 This leads to the suggestions4 that the P-F h.f.s. may go through a minimum as 8 varies between 30" and 90" and it also appears that preferred conformations may well differ for alkyl and fluoroalkyl counter- parts. INDO calculations for (CF,),NO. predict a P-F splitting of zero for An 8 = 90" as expected for a hyperconjugative me~hanism.~~ interesting experimental result is that fluorine atoms in the nodal plane for semiquinones from triptycene derivatives do show appreciable coupling ;this has been inter- preted as evidence for pn interaction^^^' (see also ref.57b) although a (B + Bcos' 6) dependence for a(B-F),with B appreciable and possibly nega- tiveS6 would also offer an explanation. Nitro~ides~~ containing 8-Cl have also recently and alkoxy nitra~ides~~ been reported. From measurements of both uHand acI for a variety of radicals it is concluded that in the former case a B cos2 8 dependence for acIis followed,58 whereas in the latter case the behaviour is the reverse and a 1,3-pn interaction is favoured.59 As with fluorine it appears that the apparently discordant results will only be rationalised when spin densities and dihedral angles are both known ;60 perhaps spatial proximity and hybridisation of the central atom are both important.2 Relaxation Line-widths and Kinetics Of fundamental importance are the recent observations of emission and anoma- lous absorption spectra for short-lived radical^,^ 1-64 although the underlying theory has not yet been developed comprehensively. For example the radical CH(OH)CH(OH)(CO,H) is detected during the photolysis of acidified aqueous solutions of tartaric acid with all eight lines in emission.6' When the pH is 55 K. J. Klabunde J. Amer. Chem. SOC.,1970,92 2427. 56 G. R. Underwood V. L. Vogel and I. Krefting J.Amer. Chem. SOC., 1970,92 5019. 5' (a) D. Kosman and L. M. Stock J. Amer. Chem. SOC.,1970 92 409; (b) M. Iwasaki J. Amer. Chem. SOC.,1970,92 6348. 58 E. G. Janzen B. R. Knauer L. T. Williams and W. B. Harrison J.Phys. Chem. 1970 74 3025. 59 N. H. Anderson M. McMillan and R. 0.C. Norman J. Chem. Soc.(B) 1970 1075. 6o E. T. Strom and A. L. Bluhm J. Phys. Chem. 1970,74 2036. " R. Livingston and H. Zeldes J. Chem. Phys. 1970 53 1406. H. Paul and H. Fischer Z. Naturforsch. 1970 25a 443. 63 H. Fischer Chem. Phys. Letrers 1970,4,611. See also G. L. Closs and A. D. Trifunac J. Amer. Chem. SOC.,1970,92 2183 and succeeding papers. 64 P. W. Atkins I. C. Buchanan R. C. Gurd K. A. McLauchlan and A. F. Simpson Chem. Comm. 1970 513. 24 B.C. Gilbert increased the radical life-time is lengthened [it undergoes acid-catalysed re- arrangement to CH(CO,H)CHO] and the spectrum becomes progressively transformed into an absorption (high-field lines first). The initial radical appears then to be generated with a non-equilibrium population of its Zeeman levels. Emission (low-field lines) and enhanced absorption (high-field lines) have also been observed for e.g. CH(CH,)CO,-(produced with Ti1"-H,02 in a flow system) when excess of H,O shortens its life-time by chemical reaction.62 Fi~cher~~ has proposed a unified mechanism to account for this and related A/E 'multiplet' effects in n.m.r. (CIDNP) based on the adiabatic development of radical-pair spin-states during reaction. (The 'multiplet' effect in CIDNPdepends on the signs of the h.f.s.and on the g-values of the combining radicals,63 which should prove a useful method for determining e.s.r. parameters e.g. g for RO.). Signals from radicals generated by laser flash photolysis have been at a fixed magnetic field as a function of time (measurements at different fields yield the complete spectrum) ;for the anion of 2-chlorobenzaldehyde the spectrum is observed in emission (after 5ps) but this changes to absorption with a time constant of 14ps and then the radical decays (T+ = 2.4 ms). The mechanism64 of the emission phenomenon appears to differ from that responsible for the effects described ab~ve.~~.~ Spin-relaxation for radical anion (and cation) pairs65 and for nitroxide com- plexes with transition metal chelateP has been discussed and TI and T have been determined for radicals in solids and liquids by a pulse method.67 Spin- rotational relaxation has been discussed for C102 and SO2-as a function of the solvent6' and also for the cation radical of phenoselenazine and for the corres- ponding nitroxide ;69 the 77Se splittings (and 33Ssatellites for the phenothiazine cation) have been observed.Line-width measurements have been used to derive the rates of electron exchange between cyclo-octatetraene anion radical and its di-ani~n,~' and between the anions of benzene toluene and p-xylene and their parents.71 Heterogeneous and homogeneous exchange rates have also been compared.' The alternating line-width for potassium 9,lO-dihydroanthracenideat low temperatures in DME appears mainly in the ring h.f.s.from which it is concluded that K+ is exchanging between positions close to the aromatic rings (rather than close to the CH groups as in an alternative The modulation of ring- proton h.f.s. for the barium acenaphthene semiquinone in DME between -20 and + 100 "C apparently arises from motion of Ba2+ between equivalent sites 65 D. C. McCain J. Magn. Resonance 1970,3,281. 66 D. Wilbur and R. Kreilick J. Chem. Phys. 1970,52 1643. 67 R. Brandle G. J. Kriiger and W. Muller-Warmuth Z. Nufurforsch. 1970 25a. I. 68 L. C. Dickinson and M. C. R. Symons Trans. Faraday Soc. 1970,66 1334. 69 M. F. Chiu B. C. Gilbert and P. Hanson J. Chem. Soc.(B) 1970 1700. 'O F. J. Smentowski and G. R. Stevenson J.Amer. Chem. Soc. 1969 91 7401. '' G. L. Malinoski jun. W. H. Bruning and R. G. Griffin J. Amer. Chem. Soc. 1970 92 2665. l2 A. E. J. Forno M. E. Peover and R. Wilson Trans. Faraday SOC.,1970,66 1322. l3 M. Iwaizumi and J. R. Bolton J. Magn. Resonance 1970,2,278. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy unsymmetrically located with respect to two anions,74 and the broadening for the ion pair K+ -9,lO-anthrasemiquinone (A) in THF between -65 and 20 "C suggests that the cation undergoes intramolecular transfer between the oxygen atoms of the anion.75 A further kind of broadening is observed for the triple ion Na,A+ (and also Na,pyra~ine+);~~ incomplete averaging of the g and hyperfine tensor anisotropy generates asymmetric broadening of the alkali metal h.f.s.and a consistent model is proposed.75 Exchange between duroquinone (DQ) and the triple ion (Na,DQ)+ has also been studied and the observation of splittings from two equivalent sodium atoms in the fast exchange region indicates that both sodium ions are e~changed.~~ Evidence was also obtained for complexes involving the quinone. Analysis of line-width alternation also leads to activation parameters for various conformational changes including the inversion of some 4-alkylpiperi- dine nitr~xides,~~ the rotation of the OCH group in 2,6-dimethyl-4-methoxy- phen~xyl,~~ and the interconversion of possible conformations for some hindered anion radicals -CR(N0,)22-.79 Further unusual line-width effects have been observed for some sulphur-containing cation radicals produced with AIC1,-CH2C1 at room temperature (MeS),C=C(SMe) t shows twelve equivalent proton splittings (2.70 G) whereas at -90 "C there are two non- equivalent sets (0.93 and 4.22 G).Analysis of the broadening at intermediate temperatures gives k = 5.8 x lo7s-(at -10"C)and E = 8.6 kcal mole- for the interconversion of (3) and (4). For the ethyl derivative additional non- equivalence at -90 "C indicates there to be restricted rotation about the S-CH bonds. (3) (4) Restricted rotation in the cation radicals of some alkylaminoethylenes (gener- ated electrochemically or with Br,) is also revealed ;in Me2NCH=CHNMe t for instance the methyl splittings become inequivalent as the temperature is lowered.81 The rate of rotation about the N-CSpzbond is diminished appreciably (kD/kH < 0.1) when the methyl groups are completely deuteriated.For the anion radicals of some dinitro-benzene and -naphthalene derivatives line-width alterna- 74 E. Warhurst and A. M. Wilde Trans. Faraday SOC.,1970,66 2124. 75 T. E. Gough and P. R. Hindle Trans. Faraday SOC.,1970.66 2420; S. A. Al-Baldawi and T. E. Gough Canad. J. Chem. 1970 19,2798. 76 R. F. Adams T. L. Staples and M. Szwarc Chem. Phys. Letters 1970,5,474;see also A. W. Rutter and E. Warhurst Trans. Faraday Sac. 1970 66 1866. 77 R. E. Rolfe K. D. Sales and J. H. P. Utley Chem. Comm. 1970 540. 78 W. J. Van den Hoek W. G. B. Huysmans and M. J. C. Van Gemert J. Magn. Reson-ance 1970 3 137. 79 C.Lagercrantz S. Forshult T. Nilsson and K. Torssell Acta Chern. Scand. 1970 24 550. 80 D. H. Geske and M. V. Merritt J. Amer. Chem. SOC.,1969,91 6921. 81 B. C. Gilbert R. H. Schlossel and W. M. Gulick jun. J. Amer. Chem. SOC.,1970,92 2974. 26 B. C. Gilbert tion is induced by asymmetric solvation.82 A novel form of line-broadening observed for the cation of 2,5-dimethylhydroquinone depends on the sign of and on the relative signs of aCH3 OcH3 and a for particular lines; it is suggested that the OH groups are rotating in an instantaneously equivalent manner.83 Conventional applications of e.s.r. to reaction kinetics include the measure- ment of some bimolecular decay rates for photochemically prepared radicals using a rotating sector and a CAT.84,85 Two types of behaviour are distinguished for semidiones :84 radicals from cyclic cis-a-diketones react via disproportiona-tion (k = 1-4 x lo7l mol-l s-l) whereas flexible a-diketo-semidiones terminate by coupling (k = 2-4 x lo81 mol-' s-') as is also found for ketyls from some a-keto acids and esters.85 By similar methods the rate of dimerisation of tri- methylsilyl radicals (from -0Bu' and SiMe,H) has been determined as 2.2 x lo9 1 mol-' s-' at 25 "C." The rate of recombination of tri-t-butylcyclohepta- trienyl (prepared photochemically from the corresponding dimer) has been compared with that for the unsubstituted radical.87 There have been further detailed studies of the behaviour of peroxyl radicals R0,-generated by photolysis of Bu'O.OBu' in oxygen-saturated alkanes (RH).88 Below -115 "C there is reversible formation of tetroxide (RO,R) with ASo * -38 cal deg- mol-',AH" .v -8.9 kcal mol- ;between -60 and +20 "C there is irreversible decomposition and the activation energy is estimated as 8 kcal mol- for tertiary alkylperoxyl radicals and 2 kcal mol- ' for secondary alkylperoxyl radicals.The small value in the latter case supports a mechanism proposed for termination via a cyclic transition state involving the tetroxide. A formal similarity between the self-reactions of alkylperoxyl radicals and those of the isoelectronic nitroxides has also been pointed out :89 parameters have been measured both for the reversible equilibrium involving diethyl nitroxide and its dimer and for the decomposition of the latter to a nitrone and a hydroxylamine probably by way of a cyclic mechanism.A kinetic investigation also establishes the role of dibenzyl nitroxide in the autoxidation of NN-dibenzylhydroxylamine?' Finally the rate constant of the SH2reaction of t-butoxyl radicals with tri-n- butylborane has been determined as 7.3 x lo61 mol-s-' at 40 "C by a method involving a competitive abstraction reaction the rate of which is known;9' Bu'O.OBU' '' C. J. W. Gutch W. A. Waters and M. C. R.Symons J. Chem. SUC.(B) 1970 1261. " P. D. Sullivan and J. R.Bolton J. Phys. Chem. 1969 73 4387. S. A. Weiner E. J. Hamilton jun. and B. M. Monroe J. Amer. Chem. SOC.,1969,91 6350; E. J. Hamilton jun. D. E. Wood and G. S. Hammond Rev. Sci. Instr. 1970,41 452." T. Fujisawa B. M. Monroe and G. S. Hammond J. Amer. Chcrn. SOC.,1970.92 542. 86 P. T. Frangopol and K. U. Ingold J. Organometallic Chem. 1970 25 69. " M. L. Morrell and G. Vincow J. Amer. Chem. SOC.,1969,89,6389. " J. E. Bennett D. M. Brown and B. Mile Trans. Faraday SOC. 1970 66 386 397. 89 K. Adamic D. F. Bowman and K. U. Ingold J. Amer. Chem. SOC. 1970,92 1093. 90 D. J. Cowley and W. A. Waters J. Chem. SOC.(B) 1970 96. 91 A. G. Davies D. Griller B. P. Roberts and R. Tudor Chem. Comm. 1970 640. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy 27 3 Short-lived Radicals Photo1ysis.-A wealth of further detailed information has been derived from applications of the photolysis of peroxides in organic liquids.For example Adams has reacted SOBu' with sulphides and disulphides and observed H-atom abstraction to give sulphur-conjugated radicals,92 and the structure of the radicals obtained from acetylenes and allenes (e.g.C3H3)has been discussed.93 Methyl- substituted thiophens react uia abstraction and McLachlan calculations for these radicals and for some ketyls of thiophen derivatives suggest that a p-orbital model rather than d-orbital model is appropriate for S ;different rotamers were detected for the ketyl~.~~ The e.s.r. evidence for the rearrangement of the cyclopropylmethyl radical (5) to allylcarbinyl (6) has been discussed95 and since dimeric products derived from both radicals were isolated when (5) was generated from the corresponding diacyl peroxide it is concluded that cage recombination of (5) proceeds faster than rearrangement for which the rate constant has a lower limit of lo8s-'.CH FCH --+ (5) (6) However the ring-closing rearrangement of 5-hexenyl radicals to cyclopentyl- methyl radicals (also confirmed using e.s.r.) cannot compete with cage recombina- ti~n.~' The rate of the conversion of (5) into (6)has also been compared with that for the cage combination of alkoxyl and alkyl radicals generated from per ester^.^^ Spectra from the o-radicals CONR1R2and C02R have been obtained by photolysis of t-butyl perbenzoate in formamides and formates respectively and extended Huckel calculations have been perf~rmed.~' Azo-compounds can also successfully replace peroxides ; thus aliphatic nitrile radicals (CR'R2CN)98 and dialkylamino radicals (.NR2)99are obtained from the corresponding pre- cursors.For the dimethylamino radical (from tetramethyltetrazene in cyclo- propane at -90 "C),aN = 14-78 and a,. = 27.36 G. (The reportedlOO value for uN of 32 G for this radical trapped in solids may possibly represent the sum of anisotropic and isotropic splittings). Other workers' O1 did not directly observe the dialkylamino radical from this source but inferred its production and partici- pation in a homolytic substitution reaction since .Bunwas detected in the presence of BBu" and similar gallium and aluminium alkyls. " J. Q. Adams J. Amer. Chem. SOC. 1970 92 4535. 93 J. K. Kochi and P. J. Krusic J. Amer. Chem. Sac. 1970,92 41 10. 94 A.Hudson and J. W. E. Lewis Tetrahedron 1970,26,4413. 95 R. A. Sheldon and J. K. Kochi J. Amer. Chem. SOC.,1970,92,4395. 96 R. A. Sheldon and J. K. Kochi J. Amer. Chem. SOC. 1970,92 5175. " H. Hefter and H. Fischer Ber. Bunsengesellschaft Phys. Chem. 1970 74,493. " S. Brumby 2.Naturforsch 1970 2JA 12. y9 W. C. Danen and T. T. Kensler J.Amer. Chem. SOC. 1970,92 5235. loo S. G. Hadley and D. H. Volman J. Amer. Chem. SOC. 1967,89 1053. lo' A. G. Davies S. C. W. Hook and B. P. Roberts J. Organometallic Chem. 1970,22,C37. B. C. Gilbert Electron-transfer reactions investigated include the reduction of oxalic acid and its esters with donor radicals (produced photolytically) to semidiones and neutral radicals -C(OH)(CO,R)OR.' O2 The neutral cis-isomers exhibit fast intramolecular hydroxy-proton exchange whereas in the trans-isomers there is acid-catalysed tautomerism.Emission effects were also observed. 9-Hydroxy- fluorenyl radicals are produced by photolysis of fluorenone in tertiary amines probably via electron transfer from nitrogen to carbonyl group followed by proton abstraction by the ketyl from the amine cation radical;lo3 solvent effects on the spectra have been interpreted in terms of solvation by hydrogen bonding. Radiolytic reactions of amino-acids in aqueous solution have also been studied by e.s.r. ;lo4 for example glycine (NH3+CH,COO-) reacts with hydrated electrons readily at pH -6.5 to give CH2COO- by deamination. Flow Systems.-There has been further clarification of the origin of the singlets observed during the reaction of hydrogen peroxide with various metal ions.With Ti"' two sharp singlets due to co-ordination of .O,H to Ti1"-H2O2 com- plexes are detected in addition to the broad line from 'naked' perhydroxyl radicals; with CeIV both -02H and .O,H-Ce"' complexes result.'059106 Per- hydroxyl (from Fe" or CeIV and H202) also forms a complex with oxyvanadium(v) = ion VO,- with u(~~V)4.3 G;lo7 vanadyl sulphate decomposes hydrogen peroxide and depending on the time between mixing and observation both [V02+] and [.02H-VV] can be monitored.'08 In addition evidence exists for the co-ordination of perhydroxyl radicals to other metal ions including Zr02 + and V0,2+.109 The -0,H-Ti'" singlets [which also result from photolysis of H202 in the presence of titanium(rv)] are slightly sensitive to the presence of various ions and chelates.' lo The solid-state spectra for .O,H and these singlets are consistent with a perturbation of g and uHproduced by co-ordination.' lo It should perhaps be stressed that these complexed specks (relatively stable compared with .OH and .02H) are not thought to be responsible for reactions in the presence of added substrates.The reactions of .OH (from Fe'l-or Ti1*1-H202) investigated include the initiation of co-polymerisation of vinyl esters in aqueous solution (this work also involved reaction with .NH and a study of the scavenging effect of metal ions).'' ' Reaction of hydroxyl radicals with dimethyl sulphoxide leads to both CH,SO,-and CH3."2 Glycine reacts at pH 4 to give a spectrum assigned to IoZ H.Zeldes and R.Livingston J. Phys. Chem. 1970 74 3336. lo3 R. S. Davidson and R. Wilson J. Chem. SOC.(B) 1970 71. lo4 P. Neta and R. W. Fessenden J. Phys. Chem. 1970,74 2263. Io5 G.Czapski H. Levanon and A. Samuni Israel J. Chem. 1969,7 375. A. Samuni and G. Czapski Israel J. Chem. 1970,8 551. lo' M. S. Bains J. C. Arthur jun. and 0.Hinojosa J. Amer. Chem. SOC.1969 91 4673. M. Setaka Y.Kirino T. Ozawa and T. Kwan J. Catalysis 1969,15,209. Io9 M. S. Bains J. C. Arthur jun. and 0.Hinojosa Inorg. Chem. 1970,9 1570. Y.Shimizu T. Shiga and K. Kuwata J. Phys. Chem. 1970,74,2929. 'I1 K. Takakura and B. Ranby J. Polymer Sci. Part A-1 1970,8,77. ' W. Damerau G. Lassman and L. Karlheinz 2.Chem.1969,9 343. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy CH(NH,)CO,H (not the ~witterion),"~ and at pH 10 to give CH(NH2)C02-. Alanine gives CH2CH(NH3+)C02H [with a little .C(CH,)(NH,)(CO,H)] and C(NH2)(CH3)C02- respectively. Cysteine and cysteamine are oxidised to thiyl radicals (RCH,S. with g = 2-015and aH= 9 G);114*115 using a three-way flow it was shown114 that organic radicals of varied structure also react similarly with thiols this constituting a likely repair mechanism for biomolecules damaged by radiation R'. + RSH --* R'H + RS-Thiyl radicals also result from reaction of .OH with disulphides probably oia the short-lived cation RSSR t this providing evidence for an electron-transfer radio-protective action.' l4 Nucleosides add .OH and .NH to the pyrimidine base ;''' various pyrimidines' '' and acetylated amino-acids' have also been studied.The reduction of a-chloronitroalkanes with donor radicals produces a variety of signals dependent on the pH and the structure of the s~bstrate.'~ In addition to spectra from R1R2CC1N02 T signals are detected from R'R2CC1N02R3 (combination of the anion radical and a carbonium ion) from CR'R'NO (lossof el-) and by reduction of this to the aci-anion followed by radical trapping from NO,CR'R2-CR'R2NO2 T. Protonated nitroalkane radical anions were also detected a,(OH) 'v 3 G. Other radical trapping reactions of aci-nitroalkane anions and oximes with CO,H and .C02-have been rep~rted."~ The reaction of Ti"' and persulphate (S2Os2-)produces SO4' (cf.peroxide decomposition) which although not directly detectable via e.s.r. is characterised by its adducts with olefins.'20 Compared to .OH SO4-is more electrophilic12' so that whereas the former adds to R'R2C=N02- the latter causes oxidation to CR1R2N02 which is subsequently trapped by the aci-anion to give the meso-and (+)-forms of N02CR1R2-€R1R2N027. 4 Stable Radicals Cation Radicals.-yovel one-electron oxidation systems reported include Co"' in CF3CO2H (used to prepare the cations of some aromatic hydrocarbons including azulene in a flow system)'22 and BCl (or BF,) in SO2 (INDO and McLachlan calculations are reported for some polynuclear hydrocarbon cations 'I3 P. Smith W. M. Fox D. J. McGinty and R. D. Stevens Canad.J. Chem. 1970 48 480. IL4 C. Nicolau and H. Dertinger Radiation Res. 1970 42 62. 'I5 W. Wolf J. C. Kertesz and W. C. Landgraf J. Magn. Resonance 1969 I 618. H. Dertinger and C. Nicolau Biochim. Biophys. Acra 1970 199 316. H. Taniguchi J. Phys. Chem. 1970,74 3143. H. Taniguchi H. Hatano H. Hasegawa and T. Maruyama J. Phys. Chem. 1970 74 3063. l9 D. J. Edge and R. 0.C. Norman J. Chem. SOC. (B),1970 1083. '" R. 0.C. Norman P. M. Storey and P. R. West J. Chem. SOC.(B) 1970 1087. D. J. Edge R. 0.C. Norman and P. M. Storey J. Chem. SOC.(B) 1970 1096. R. M. Dessau S.Shih and E. I. Heiba,J. Amer. Chem. SOC., 1970,92,412;R. M. Dessau and S. Shih J. Chem. Phys. 1970 53 3169. B. C. Gilbert prepared in this way and appropriate Q values for cations and the corresponding anions are compared).123 Contrary to an earlier report there appears to be no e.s.r.signal from carefully purified ClF3-SbF or ClF5-SbF .'24 Cation radicals result from the reactions of several aromatics with XeF in CH,Cl in the presence of HF below 0 0C;125 both toluene and 4,4'-dimethylbiphenyl are oxidised to the cation radical of the latter and polyphenyl derivatives are obtained from benzene. The "0and I3C h.f.s. have been measured for the hydroquinone cation radical (from HQ in CH3N02-A1C13)'26 and used to derive the spin-density distribution. The results have been compared to those for PBSQ; in DMSO and in water and MO calculations were used to re-evaluate r-n parameters for C and 0 (for a theoretical estimate of these quantities see ref.127). The temperature dependence of a,(OCH3) for some dimethoxy-substituted cation radicals apparently origin- ates from torsional oscillations of the methoxy-groups about in-plane conforma- tions.l 28 E.s.r. and electrochemical evidence indicate that the cation radicals from dialkylamino-substituted alkenes react further e.g. by coupling ; (Me,N),C=CH ? reacts to form 1,1,4,4-tetrakis(dimethylarnino)butadiene.'29 Cation radicals of some cis-1,2-ethylenedithiolsare obtained in the oxidative solvolysis (H2S04-CH3N02) of some nickel bisdithienes ;I3' again further reaction is possible and cis-PhC(SH)=C(SH)Phf is a precursor of (7). The cation radicals of (8) and (9) have been produced from the parents by oxidation (7) (8) (9) electrochemically,131 and with C1 ,'32 respectively.The mechanism of trans- mission of spin density to 8-protons in these and related sulphur radicals is still unclear [see the discussion in refs. 80 and 131-the low temperature data in the former suggest that non-bonded interactions affect a,(SCH3) markedly]. Anion Radicals.-Signals produced when benzene is reduced with Na-K alloy in DME-THF and previously attributed to a non-degenerate state of C6H6 also result when phenyl-substituted phospholes are reduced with potassium in J. T. Cooper W. F. Forbes and J. C. Robinson Cunad. J. Chem. 1970,48 1942; see also J. T. Cooper Cunad. J. Chem. 1970,48 1996. lZ4 K. 0.Christe and J. S. Muirhead J. Amer. Chem. SOC.,1969,91 7777. 125 M. J. Shaw J. A. Weil H.H. Hyman and R. Filler J. Amer. Chem. SOC.,1970 92 5096. lz6 P. D. Sullivan J. R. Bolton and W. E. Geiger jun. J. Amer. Chem. Sac. 1970 92 4176. 12' R. Poupko B. L. Silver and M. Rubinstein J. Amer. Chem. SOC.,1970,92 4512. "* P. D. Sullivan J. Phys. Chem. 1970,24 2563. 129 J. M. Fritsch H. Weingarten and J. D. Wilson J. Amer. Chem. SOC.,1970 92 4038. 130 G.N. Schrauzer and H. N. Rabinowitz J. Amer. Chem. SOC.,1970,92 5769. 13' J. Q. Chambers N. D. Canfield D. R. Williams and D. L. Coffen Mof.Phys. 1970,19 581. 13' F. Wudl G. M. Smith and E. J. Hufnagel Chem. Comm. 1970 1453. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy 31 DME or THF ;they probably arise uia radical polymerisation involving in the latter case a cleaved phenyl fragment.133 The importance of LiAlH4 (used for purification of the solvent) has been reported for both reactions.'"*' 34 Reduc-tion of benzocyclobutene and 1,2-bismethylene-cyclobutenewith alkali metals at (10) (1 1) low temperatures does give (10) and (ll) respectively and not valence tauto- mers.13' The inequivalence of the methylene protons in (10) arises from the influence of the counter ion;136 at higher temperatures and in DME-HMP the protons become equivalent.An in~estigation'~~ of a variety of ion-pairs suggests that for Na'X' when X = naphthalene or biphenylene the metal ion oscillates between each six- membered ring whereas when X = anthracene the counter ion is positioned over the central ring; the effect of cation size is important.This is also indicated for a variety of ion pairs by the variations of g with temperature.13* For Naf naphthalene in THF the temperature dependence suggests an equilibration between two different types of ion-pair whereas for the caesium ion-pair in DME an alternative model of vibrational effects within a tight pair is fav0~red.I~~ Anion radicals obtained by reduction with solvated electrons in liquid ammonia include those of some styrenes vinylpyridines,' 39 and aromatic carboxylic acids (A~CO:;).'~' For a variety of radicals appropriate values of Q& and QN (pyridine) are found to be 50 and 28.5G respectively. Further reactions can also be monitored; thus phenylacetylene is reduced to PhC-CHy and PhCH=CH,T.' 39 The low g-value for Ph-CGC-PhT has been rati0na1ised.l~~ Other anion radicals reported include those of some substituted fl~orenes,'~~ di~lieadane,'~~ and a variety of nitrogen-containing 1,l'-and 2,2'-bia~ulenyl'~~ heterocycles;145 the reader is referred to these for details of Q-values spin (ArCOir).140 For a variety of radicals appropriate values of Q& and QN 133 C.Thomson and D. Kilcast Angew. Chem. Internat. Edn. 1970,9 310. 134 J. Kelm and K. Mobius Angew. Chem. Internat. Edn. 1970 9 73. 13' N. L. Bauld F. Farr and G. R. Stevenson Tetrahedron Letters 1970 625. 136 R. D. Rieke S. E. Bales P. M. Hudnall and C. F. Meares J. Amer. Chem. SOC.,1970 92 1418. 13' I. B. Goldberg and J. R. Bolton J. Phys. Chem. 1970,74 1965. 138 W. G. Williams R. J. Pritchett and G.K. Fraenkel J. Chem. Phys. 1970 52 5584. 39 A. R. Buick T. J. Kemp and T. J. Stone J. Phys. Chem. 1970,74,3439. I4O A. R. Buick T. J. Kemp G. T. Neal andT. J. Stone J. Chem. SOC.(A) 1970 2227. 14' I. B. Goldberg and A. J. Bard Chem. Phys. Letters 1970 7 139. 14' D. Casson and B. J. Tabner J. Chem. SOC. (B) 1970 1560 1565. 143 R. F. C. Claridge D. R. A. Leonard and B. M. Peake Mof.Phys. 1970,19,737. 144 Y. Ikegami and S. Seto Bull. Chem. Sac. Japan 1970.43 2409. 145 L. Lunazzi A. Mangini G. F. Pedulli and F. Taddei J. Chrm. Soc. (B) 1970 163; L. Lunazzi A. Mangini G. Placucci and F. Taddei J. Chem. SOC.(B) 1970,440; M. D. Sevilla J. Phys. Chem. 1970 74 865; H. Malkus M. A. Battiste and R. M. White Chem. Comm. 1970,479; M. K. V. Nair K. S. V. Santhanam and B.Venkataraman Mof. Phys. 1970 19 585; G. A. Russell and P. Bruni Tetrahedron 1970 26 3449; F. A. Neugebauer Tetrahedron 1970,26,4843,4853. 32 B. C. Gilbert distribution etc. Anion radicals of some 1,6-disubstituted-[lO]annulenes,(12; X = NH NMe 0,or CH2) have also been prepared.146 The h.f.s. for the ring protonsin(l2;X = NH)areintermediatebetweenthosefor(l2;X = 0)and(l2; X = CH,) and whereas when X = NMe the radical decays to azulene' in the other examples the product is naphthalene'. This radical also results together with the parent anion when tri-1-naphthylborane is reduced with Na-Hg.14' 0-0- (12) (13) (14) The proton splittings for anion radicals of some trimethylsilyl-substitutedole-fins aromatics and amines suggest that SiMe has an overall electron-with- drawing effect but that N(SiMe& is electron-d~nating.'~~ ,'Si splittings have been observed,' 49 and analysis in conjunction with HMO and McLachlan calculations (A = 0.4) suggests that QZsi = 20 G and QZ = 0; d-orbital participa- tion is invoked to explain this unusual finding.The dimethylphenylphosphine radical anion has now been ~btained'~' (a secondary radical was previously observed) and the ring-proton splittings indicate that PMe is electron attracting probably by a dn-interaction (cf. C-Si). Tris-( 1-naphthy1)phosphine is reduced by alkali metals under various conditions to naphthalenes 1,l'-binaphthyl; perylene5 and (Np),P-M 7;'51 the oxide sulphide and selenide have also been studied. Other Group VI-containing compounds reduced include some NN-dialkylthiobenzamides,' 52 methyl phenyl ~ulphone,"~ some sulphoxides,' 54 and 2,1,3-benzoselenadiazole.' E.s.r.spectra of semidiones and ketyls continue to provide information of structural and mechanistic interest. For example Russell has discussed the conformations of semidiones from cycloheptanes from bicyclo[3,2 lloctane from bicyclo[3,3,2]decane and from bicycl0[3,2,2]nonane~~~ and has also established the valence isomerisation of (13) and (14) the latter structure being favoured." 146 F. Gerson J. Heinzer and E. Vogel Helv. Chim. Acta 1970 53 95 103. 14' H. J. Shine L. D. Hughes and P. Gesting J. Organometallic Chem. 1970 24 53. F. Gerson U. Krynitz and H. Bock Angew. Chem. Internat. Edn.1969,8 767; Helu. Chim. Acta 1969 52 2512. 149 F. Gerson J. Heinzer and H. Bock Mol. Phys. 1970,18,461. '50 F. Gerson G. Plattner and H. Bock Helv. Chim. Acta 1970 53 1629. '' M. H. Hnoosh and R.A. Zingaro J. Amer. Chem. SOC.,1970,92,4388. J. Voss and W. Walter Annalen 1970 734 1. '53 Sr. E. Keller and R.G. Hayes J. Phys. Chem. 1969,73,3901. '54 A. Trifunac and E. T. Kaiser J. Phys. Chem. 1970,74,2236. 15' M. Kamiya and Y. Akahori Bull. Chem. SOC.,Japan 1970,43,268. G. A. Russell and R.G. Keske J. Amer. Chem. SOC.,1970,92,4458,4460. '" G. A. Russell T. Ku and J. Lokensgard J. Amer. Chem. SOC.,1970,92 3833. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy 33 The mechanisms of carbonyl insertion in two different reactions of ketones to form semidiones have now been examined.' 58 Electrolytic reduction of aceto- phenone in DMF leads probably via the addition of the ketone dianion to DMF followed by rearrangement (possibly carbenoid) to PhCOCOCH ; and whereas 2,2,4,4-tetramethylcyclobutanoneis reduced by potassium in THF at -90 "C to the ketyl at -50 "C 3,3,5,5-tetramethylcyclopentane-1,2-semidione is formed via CO insertion.For a series of p-substituted semidiones (ArCOCOCH y) the spectra indicate that SiMe and GeMe are moderately good electron-withdrawing groups (dn) and that there is evidence for d-orbital participation for the SPh and SePh groups but not for SMe and SeMe.15' Some aliphatic enone anion radicals have also been prepared polarographically ;160 for Bu'CH=CHCOBu'- it is estimated that approximately 40 % of the unpaired electron density resides on the 8-carbon.Other relevant investigations include the use of ENDOR and e.s.r. to obtain h.f.s. for the semiquinones of Vitamins E and K,16' the observation of radical anions from triquinocyclopropane' 62 and of some N-substituted-2-amino-l,4-naphthosemiquinones,' 63 and the recognition of solvent effects on the h.f.~.'~~ and g-value~'~' for some semiquinones; the spectra of PBSQS and related compounds have been studied as a function of solvent counter ion and tempera- ture.'66 Barriers to rotation for some anions (PhNO' and p-X-C6H4COCH3 :) have also been determined.167 Anion radicals of aromatic nitro-compounds arise during reduction with NaBH (probably via electron transfer)16' and also by radical-anion coupling reactions both between phenyl and NO2- and between p-nitrophenyl and CN-.I6' The interested reader is referred to investigations of the perturbing effects of solvent and counter ion (including Bu",Nf) on aN for some nitrobenzene anions,170 and also of ion-pairs of C6H5N02T in nitri1es.I7' Nitroxides.-Interest here has mainly centred around the applications of the 'spin trap' method normally involving Bu'NO (for which a straightforward G.A. Russell D. F. Lawson and L. A. Ochrymocycz Tetrahedron 1970,26,4697. ' 59 E. T. Strom and J. R. Norton J. Amer. Chem. SOC. 1970 82,2327. 16* K. W. Bowers R. W. Giese J. Grimshaw H. 0.House N. H. Kolodny K. Kronberger and D. K. Roe J. Amer. Chem. SOC. 1970,92,2783.M. R. Das H. D. Connor D. S. Leniart and J. H. Freed J. Amer. Chem. SOC.,1970,92 2258. R. West and D. C. Zecher J. Amer. Chem. SOC. 1970,92 161. 163 A. T. Bullock and C. B. Howard Trans. Furuduy SOC. 1970,66 1861. ' 64 D. Lunney J. Bailes and J. D. Memory J. Chem. Phys. 1970,53,3387;A. G.Evans J. C. Evans and E. H. Godden J. Chem. SOC.(B) 1970 149. 165 T. Yonezawa T. Kawamura M. Ushio and Y. Nakao Bull. Chem. SOC. Japan 1970 43 1022. 166 J. Oakes and M. C. R. Symons Trans. Furuduy SOC. 1970,66 10. W. Kaminski Z. Nuturforsch. 1970 25a 639; W. Kaminski and K. Mobius Z. Nuturforsch. 1970 25a 635. 16' M. G. Swanwick and W. A. Waters Chem. Comm. 1970,63. D. E. Bartak W. C. Danen and M. D. Hawley J. Org. Chem. 1970 35 1206. "O J.Oakes J. Slater and M. C. R. Symons Trans. Furuduy SOC.,1970,66 546. I" J. M. Gross and J. D. Barnes J. Phys. Chem. 1970,74,2936. 34 B. C. Gilbert synthesis has been rep~rted).'~ Quantitative aspects of its utility have been discussed on the basis of competitive abstraction reactions of ethylbenzene and toluene with .OBu' (from di-t-butyl peroxyoxalate)." Abstraction from various solvents is followed by addition of the resulting radical to the spin-trap to give nitroxides. With Pr'OH hydrogen atom transfer was detected ; further with dimethyl malonate as substrate it was demonstrated that .OBu' is more electro- philic than alkyl radicals. The advantages of Bu'NO over nitrones have been discussed by Klabunde,' 'who employed the nitroso-compound to trap fluoro- radicals formed by photolysis of some fluoroalkyl iodides.Spin-trapping evidence' 74 indicates that hydroxyl radicals (from the photolysis of H202) react with methyl ethyl ketone by hydrogen abstraction from all three positions ;with cyclohexanone it is a first-formed hydroperoxide that is decom- posed. Radicals have also been trapped from the homolytic fission of alkyl iodides from oxidative decarboxylation effected by Tl"',' 74 and in the photolysis of some aliphatic carboxylic acids in donor solvent^."^ Evidence has also been adduced' for the intramolecular addition of alkoxyl radicals (from an alkyl nitrite by photolysis) to a suitably-situated double bond. C6H,S02. (from benzene sulphonic a~id),"~ (from y-irradiated sodium ph~sphite)'~~ and CH2CH2CH2CH0 (formed by ring-opening of the radical from cyclo- propylcarbinol and SOBu')' 79 have all been successfully trapped with nitroso- compounds.Decomposition of N-nitrosoacetanilide (NNA) in ether leads to a nitroxide by addition of CH,CHOCH,CH to the nitroso-group in "A;'*' the ether radical is also apparently responsible for the one-electron reduction of phenyl- diazonium ions to phenyl radicals which are also trapped. Photolysis of chloro- nitrobenzenes in ethers yields phenyl alkoxy nitroxides ArN(0R)O. by addition of solvent-derived radicals ;18' in one case the nitroxide decomposes to ArNO and RO.,and thence via p-fission of the latter to an alkyl radical which is trapped. Attempts to trap succinimidyl radicals (S.) from t-butyl succinimideper- carboxylate with Bu'NO lead to the radical formed by addition of S.to the nitrone CH,=NBu'O; this is probably generated in situ by hydrogen-atom loss from Bu'(CH,)NO.obtained via p-fission of .OBu'.' 82 The nitrone is demonstrated to be an effective trap for Ph. and PhCO,. (from dibenzoyl peroxide) and suc- cinimidyl (from NBS or the tetrazene S-N=N-S). Use of the modified nitrone (15) as a trap enables 'oxygen' radicals (which react by abstraction to give a R. J. Holman and M. J. Perkins J. Chem. Soc. (0,1970 2195. M. J. Perkins P. Ward and A. Horsfield J. Chem. SOC. (B) 1970 395. 174 K. Torssell Tetrahedron 1970 26 2759. 175 I. H. Leaver and G. C. Ramsay Tetrahedron Letters 1970,2507. 176 P. Tordo M. P. Bertrand and J-M.Surzur,Tetrahedron Letters 1970 3399. I" Th. A. J. W. Wajer H. W. Geluk J. B. F. N. Engberts and Th. J. de Boer Rec. Trau. chim. 1970 89 696. G. Adevik and C. Lagercrantz Acta Chem. Scand. 1970,24 22.53. R. Stammer J. B. F. N. Engberts and Th. J. de Boer Rec. Trav. chim. 1970,88 169. I8O J. I. G. Cadogan R. M. Paton and C. Thomson Chem. Comm. 1970,229. D. J. Cowley and L. H. Sutcliffe J. Chem. SOC.(B) 1970,569. lX2 G. R. Chalfont M. J. Perkins and A. Horsfield J. Chem. SOC.(B) 1970,401. Physical Methods-Part (ii) Electron Spin Resonance Spectroscopy phenoxyl radical) and 'carbon' radicals (which add to give a nitroxide) to be distinguished;'83 evidence has been presented for the separate existence of the acetoxyl radical. Nitroxides have also been obtained from nitrones by photo- oxidation,' 84 and result from the reactions of NOz with dimethyl sulphoxide' 85 (15) and with olefins'86 (the spectra are not due to complexes of NO2).Nitroxides are also formed in the reaction between imines and nitr0~0benzene.l~~ No less than eight nitroxides can be obtained from caryophyllene nitrosite (photolysis or halogens)! The reduction of nitrobenzene with Na,Co(CN) produces a radical with splittings very similar to those of C6H5N02- but with extra interaction from 59C0(l= z),a 2 10G,'89*190 This may be due to a complex between C6H5NO2 and pentacyanocobaltate(~r),' but since the same signal also results from reaction of C6H,NO and CO(CN),~ -the aryl pentacyanocobalt nitroxide structure [(NC),CoN(Ar)0-l3- is favoured.'89 Long-range splittings in some iminoxyl radicals have been discu~sed.'~ ',l9* 5 MiscellaneousRadicals Among the interesting radicals also observed this year are some stable lead-con- taining radicals,'93 tris(pheny1thio)methyl' 94 and '70-labelled peroxyl radi- cal~,~ 95 the pentachlorocyclopentadienylradical,196 and some ally1 radicals complexed with Ag .' 97 + J.G. Pacifici and H. L. Browning jun. J. Amer. Chem. SOC. 1970,92 5231. A. L. Bluhm and J. Weinstein J. Amer. Chem. SOC.,1970 92 1444. '13' C. Lagercrantz Acta Chem. Scand. 1969,23,3259. L. Jonkman H. Muller C. Kiers and J. Kommandeur J. Phys. Chem. 1970,74 1650; M. C. R. Symons J. Phys. Chem. 1970,74 3834. R. W. Layer Tetrahedron Letters 1970,4413.A. A. McConnell S. Mitchell A. L. Porte J. S. Roberts and C. Thomson J. Chem. Sac. (B) 1970,833. M. G. Swanwick and W. A. Waters Chem. Comm. 1970,930. lYo J. Basters and P. J. J. M. Van der Put J. Magn. Resonance 1970 2 114. H. Caldtiraru N. Barbulescu L. Ivan and V. E. Sahini Tetrahedron Letters 1970 3039 and preceding paper. F. A. Neugebauer Tetrahedron Letters 1970,2345. 193 H. B. Stegmann K. Schemer and F. Stocker Angew. Chem. Internat. Edn. 1970,9,456. D. Seeback A. K. Beck and H. B. Stegmann Tetrahedron Letters 1970 1933. '95 K. Adamic K. U. Ingold and J. R. Morton J. Amer. Chem. SOC. 1970,92,922. 196 F. Graf and H. H. Gunthard Chem. Phys. Letters 1970,7,25. 19' D. R. Gee K. E. Russell and J. K. S. Wan Canad.J. Chem. 1970,48,2740.

ISSN:0069-3030    

DOI:10.1039/OC9706700018

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

2 Physical Methods-Part (iii) Optical Rotatory Dispersion and Circular Dichroism By P. M. SCOPES Westfield College Hampstead London N.W.3 OVERthe past ten years the chiroptical techniques optical rotatory dispersion (0.r.d.) and circular dichroism (c.d.) have increasingly become routine tools for the study of dissymmetric molecules. An important review of c.d. for 196@-70 has recently been published.' The first correlations between stereochemistry and the sign of Cotton effect were based entirely on empirical generalizations. Subsequently semi-empirical regional rules which relate the geometry of a molecule to the sign of its Cotton effect were developed for some chromophores and in only a few cases has it been possible to determine the absolute configura- tion of a molecule directly by calculation of the expected sign of the Cotton effect for a particular configuration.This select list has now been extended by two more examples. The (-)-tris-2,2'- biphenylylenephosphorus(v) ion has been shown2 to have the form of a left- handed screw when viewed along the three-fold rotation axis (1) [i.e. the (M)-configuration in the Cahn-Ingold-Prelog nomenclature3] by analysis of its c.d. and absorption spectra in terms of an exciton model. (+)-trans-Stilbene oxide in which the dichroism derives principally from coupling between the excitation moments of the two aryl chromophores has been shown4 to have the (R)-configuration at both asymmetric carbon atoms. This result agrees with that obtained by chemical degradation and acts as a check on the validity of non-empirical calculation of absolute configuration.' L. Velluz and M. Legrand Bull. SOC.chim. France 1970 1785. D. Hellwinkel and S. F. Mason J. Chem. SOC.(B) 1970,640. R. S. Cahn C. K. Ingold and V. Prelog Angew. Chem. 1966,78,413. G. Gottarelli S. F. Mason and G. Torre J. Chem. SOC.(B) 1970 1349. Part (iii) Optical Rotatory Dispersion and Circular Dichroism Eyring and his colleagues' have used bond-bond coupling theory to calculate rotational strengths for a number of nucleosides and the agreement with experimental observation suggests that coupled oscillator theory accounts for most of the observed optical activity in pyrimidine nucleosides. Another general approach by Hoffmand based on electric transition moments yields calculated rotatory strengths of the correct order of magnitude for a twisted diene but the results are not in quantitative agreement with experiment.Wagniere and Hug have suggested a very simple relationship between the chirality of molecules of C,-symmetry [e.g.helicenes dienes diones and -enone (pseudo C2)],the direction of polarisation of the transition with reference to the C2 axis and the sign of their long-wavelength Cotton effect7 For com- pounds of right-handed chirality transitions in which the electric and magnetic dipoles are parallel (or anti-parallel) to the two-fold axis give rise to negative Cotton effects ;transitions in which the dipoles are perpendicular to the two-fold axis give positive Cotton effects.If the direction of polarisation is known the sign of Cotton effect can be predicted for a given absolute configuration or conversely if the absolute configuration is known the polarisation of the transi- tions can be determined by studying experimentally the sign of the Cotton effect. 1 Regional Rules for Symmetrical Chromophores In its original form,8 the Octant Rule for saturated ketones established a relation- ship between the geometry of the molecule around the carbonyl group and the sign and magnitude of the contribution made to the Cotton effect by alkyl groups or carbon-carbon bonds. More recently the influence of other functional groups close to the chromophore has been investigated by two independent groups of workers who have established that a-hydroxy- and a-acetoxy-ketones in steroidsg and in camphor derivatives" show anti-octant behaviour (i.e.make a contribution opposite in sign to that shown by an alkyl group at the same position).Snatzke and Eckhardt" in a detailed study of 8-substituted adaman- tanones (2) have found that OAc ON02 and SCN groups in an equatorial (ax) (2) W. H. Inskeep D. W. Miles and H. Eyring J. Amer. Chem. SOC.,1970 92 3866; D. W. Miles W. H. Inskeep M. J. Robins M. W. Winkley R. K. Robins and H. Eyring J. Amer. Chem. SOC.,1970 92 3874. R. R. Gould and R. Hoffmann J. Amer. Chem. SOC.,1970,92 1813. ' G. Wagniere and W. Hug Tetrahedron Letters 1970 4765. * W. Moffitt R. B. Woodward A. Moscowitz W. Klyne and C. Djerassi J. Amer. Chem. SOC.,1961 83,4013.J. R.Bull and P. R. Enslin Tetrahedron 1970 26 1525. lo L. Bartlett D. N. Kirk W. Klyne S. R. Wallis H. Erdtman and S. Thoren J. Chem. SOC.(C) 1970,2678. " G. Snatzke and G. Eckhardt Tetrahedron 1970,26 1143. P.M. Scopes configuration obey the octant rule but are anti-octant in an axial configuration. The hydroxy-group is anomalous and obeys the Octant Rule in both the p-equatorial and axial configurations. Other authors have shown that a methyl group in the p-axial position is also anti-octant12 and they relate this to the prediction of Pao and Santry13 that the sign of rotation for a B-axial substituent should be opposite to that predicted by the Octant Rule. In a short but important general survey HudecI4 has suggested that there are two ways in which one of the lobes of the carbonyl 7c* orbital may interact through cbonds with a lone pair on a nitrogen atom.If the chain of G bonds is formed entirely of anti-peri-planar links (W arrangement) the nitrogen substituent has an octant effect (3); I '€4 H (3) if the chain includes one (or more) syn-clinal links the nitrogen has an anti-octant effect (4). Further details of this important work are still to be published. In related work with 3-aryl norbornan-2-ones Thomas and Mis10w'~ have shown that the 3-substituent makes an anti-octant contribution to the ketone Cotton effect attributed to transition moment coupling between the carbonyl and aryl chromophores. Full details have now been publishedI6 of the symmetry rule for chiral olefins which relates the absolute configuration to the sign of the n-n* Cotton effect near 200nm.The rule has been tested on about seventy olefins and appliedI7 in the assignment of absolute configuration to some derivatives of taxane. How- ever a report has also been publishedI8 of the c.d. of eighteen exocyclic methylene steroids which do not obey the Scott-Wrixon rule. The French authors and also Scott in another paperIg note that the situation is made complex by the l2 M. E. Herr R. A. Johnson W. C. Krueger H. C. Murray and L. M. Pschigoda J. Org. Chem. 1970,35 3607. l3 Y.H. Pao and D. P. Santry J. Amer. Chem. Soc. 1966,88,4157. l4 J. Hudec Chem. Comm. 1970,829. Is H. T. Thomas and K. Mislow J. Amer. Chem. Soc. 1970 92 6292. Ih A. I. Scott and A.D. Wrixon Tetrahedron 1970 26 3695. D. P. D. C. de Marcano T. G. Halsall A. I. Scott and A. D. Wrixon Chem. Comm. 1970 582. Is M. Fetizon and I. Hanna Chem. Comm. 1970,462. Iq A. I. Scott and A. D. Wrixon Chem. Comm. 1970,43. Part (iii) Optical Rotatory Dispersion and Circular Dichroism 39 presence of at least three transitions occurring near 200 nm which may overlap and may be of opposite sign. At present there is no explanation for this difference between cyclic and exocyclic double bonds. Snatzke and his colleagues have made detailed studies of two series of com- pounds containing aryl chromophores (2-aminotetralols and 2-aminoindanol~),~~ and the alkaloids of the tetrahydroberberine group.21 The authors suggest that if the second sphere (i.e.the non-aryl ring fused to the aryl chromophore) is chiral this determines the sign of the ‘L Cotton effect but that a sector rule with six regions above and below the aromatic plane determines the third or fourth sphere effects. An extension of this treatment to the ‘Laband is proposed and the absolute configurations of several alkaloids are allotted on this basis. In cases where regional rules cannot yet be formulated empirical correlations can often be made by comparison with 0.r.d. or c.d. data for closely analogous compounds. For example a detailed survey22 of flavanones and their glycosides has shown that flavanones having the (2s)-configuration and an equatorial 2-aryl substituent have a positive Cotton effect at -330 nm (n-+ .n* transition) and a negative Cotton effect at 280-290nm (n-+ TC*transition).Optically active [2,2]paracyclophane derivatives have also been surveyed.23 Among new chromophores the first resolution of a selenoxide has been achieved24 and the Se(R)-and Se(S)-phenylselenoxides of cholestane (from 5a-cholestane-6-selenols)have been shown to give positive and negative Cotton effects respectively. Aliphatic C-nitroso-compounds have also been investi- gated2’ but the c.d. curves although qualitatively reproducible could not be used for quantitative measurements. A correlation has also been achieved between the sign of Cotton effect and the absolute configuration of a series of (2R)-halogenoalkane~.~~ For iodo- bromo- and chloro-alkanes the c.d. maxi- mum occurs at -253 nm -204 nm and <200 nm respectively.Compounds containing the carboxyl chromophore are particularly significant because of their relationship to natural biopolymers including polyesters and proteins. Goodman and his colleagues27 have made a detailed study of three rigid compounds containing a -COO-chromophore (lactide diphenyl- glycolide and a-campholide) and have compared them with the acyclic analogues. It is significant that the relationship between the c.d. of acyclic methyl O-acetyl- @)-lactate and (S,S)-lactide is not the same as that between N-acetyl-(Qalanine amide and (S,S)-alanine diket~piperazine.~ The importance of using carefully ’O E. Dornhege and G. Snatzke Tetrahedron 1970 26 3059. ” G. Snatzke J. Hrbek L. Hruban A. Horeau and F.SantavJ; Tetrahedron 1970 26 5013. 22 W. Gaffield Tetrahedron 1970 26 4093. H. Falk P. Reich-Rohrwig and K. Schlogl Tetrahedron 1970 26 5 1 1. 24 D. N. Jones D. Mundy and R. D. Whitehouse Chem. Comm. 1970 86. 25 N. D. Vietmeyer and C. Djerassi J. Org. Chem. 1970,35 3591. 26 B. A. Chaudri D. G.Goodwin H. R. Hudson L. Bartlett and P. M. Scopes J. Chem. SOC.(C) 1970 1329. 27 C. Toniolo V. Perciaccante J. FaIcetta R. Rupp and M. Goodman J. Org. Chem. 1970 35 6. 40 P. M. Scopes chosen analogies is emphasised in other work on cc-campholide.28 Greenfield and Fasman2’ have studied the n -+ n* transition of the isolated amide bond in (R)-(+ )-3-methylpyrrolidin-2-one and Blaha and FriE3’ have surveyed the 0.r.d. of a large number of diketopiperazines as models for the peptide bond in macromolecules.Other work has been published on the 0.r.d. and c.d. of a-amino- and a-hydroxy-acids3 and on sesquiterpene lac tone^.^^ 2 Configurational Assignments Allotments of absolute configuration by 0.r.d. or c.d. may be made either by application of firmly based regional rules or by direct comparison of the un- known with a closely analogous compound of known stereochemistry. For example the absolute configuration of a rigid ketone related to perhydrotri- phenylene has been assigned33 by application of the Octant Rule. In contrast empirical correlations have been used to allot configurations to C-6 in l~tein~~ and to C-6 in semi-a-~arotenone.~~ The aromatic chirality rule36 has been applied to determine the absolute configuration of the antibiotic cervicarcin3 and by comparison of closely related series of compounds configurations have been allotted to alkaloids of the seredamine group (indole chrornoph~re)~ and the roemeramine-mecambrine group (tetrahydroisoquinoline nucleu~).~’ The structure and configuration of panepoxydone and related compounds have been established4’ by a combination of chemical transformations and physical measurements.A number of workers have noted the hazards of configurational assignments based on c.d. measurements. For example daphnetoxin (5) and phorbol (6) of known absolute configuration give c.d. curves of opposite sign4’ X-Ray measurements on derivatives of daphnetoxin and phorbol show that the a/3-unsaturated carbonyl chromophores have opposite chirality in the two molecules despite their configurational identity.In another ‘configuration’ us. ‘conforma-tion’ problem the absolute configuration of a flexible diene for which the skew sense is not known has been allotted by empirical comparison with a closely analogous compound (1,2-dihydroarene-l,2_diol~).~~ 28 A. F. Beecham and R. R. Sauers Tetrahedron Letters 1970 4763. 29 N. J. Greenfield and G. D. Fasman J. Amer. Chem. Soc. 1970,92 177. 30 K. Blaha and I. Frit Coll. Czech. Chem. Comm. 1970 35 619. 31 J. C. Craig and W. E. Pereira Tetrahedron Letters 1970 1563; Tetrahedron 1970 26 3457. 32 W. Stocklin T. G. Waddell and T. A. Geissman Tetrahedron 1970 26 2397. 33 M. Farina and G. Audisio Tetrahedron 1970 26 1839.34 D. Goodfellow G. P. Moss and B. C. L. Weedon Chem. Comm. 1970 1578. 35 R. Buchecker H. Yokoyama and C. H. Eugster Helu. Chim. Actu 1970,53 1210. 36 N. Harada H. Sato and K. Nakanishi Chem. Comm. 1970 1691. 37 S. Marumo N. Harada K. Nakanishi and T. Nishida Chem. Comm. 1970 1693. 38 M. Hanacka M. Hesse and H. Schmid Helu. Chim. Acta 1970,53 1723. 39 J. Slavik P. Sedmera and K. Blaha CON. Czech. Chem. Comm. 1970,35 1558. 40 Z. Kis A. Closse H. P. Sigg L. Hruban and G. Snatzke Helv. Chim. Acta 1970 53 1577. 41 G. H. Stout W. G. Balkenhol M. Poling and G. L. Hickernell J. Amer. Chem. SOC. 1970 92 1070. 42 D. M. Jerina H. Ziffer and J. W. Daly J. Amer. Chem. SOC. 1970,92,1056. Part (iii) Optical Rotatory Dispersion and Circular Dichroism 41 The relationship between the sign of Cotton effect and absolute configuration may be completely reversed if a new substituent is introduced.This has been HOCH~ emphasised by Fischer and Dreiding in a study of cyclodopa derivative^^^ and also in connection with phenyl-substituted tetrahydro-isoq~inolines.~~ The situation is particularly complex when a molecule contains two chromo- phores absorbing at (or near) the same wavelength ;e.g. the acid-lactone trans-n-camphanic acid (7).45 Me 0 3 Conformational Studies; Solvent and Temperature Dependence For compounds of known configuration the chiroptical techniques are a powerful tool for the study of conformation. This year c.d. has been used to study the conformation of the five-membered ring in hexahydroindanone~~~ and of the five- and seven-membered rings in some ~-nor-~-homo-steroids.~~ The conformation of the carboxy-group in acids and esters has been studied by three groups of ~orkers.~~-~~ have studied Djerassi and his co-worker~~~ the solvent and temperature dependence of the c.d.spectra of a series of a-43 N. Fischer and A. s.Dreiding Helv. Chim. Acta 1970,53 1937. O4 V. Toome J. F. Blount G. Grethe and M. UskokoviC Tetrahedron Letters 1970,49. O5 M. J. Brienne and J. Jacques Tetrahedron 1970 26 5087. O6 M. J. Brienne A. Heymes J. Jacques G. Sn'atzke W. Klyne and S. R. Wallis J. Chem. SOC.(0,1970,423. " M. Lj. Mihailovic Lj. Lorenc J. ForSek H. NeSovic G. Snatzke and P. TrSka Tetrahedron 1970 26 557.O8 G. Barth W. Voelter H. S. Mosher E. Bunnenberg and C. Djerassi J. Amer. Chem. SOC.,1970 92 875. O9 1. Listowsky G. Avigad and S.Englard J. Org. Chem. 1970 35 1080. 50 W. P. Mose and P. M. Scopes J. Chem. SOC.(0,1970,2417. 42 P. M. Scopes substituted phenylacetic acids which they have regarded as conformationally mobile homo-conjugated systems. Listowsky and his colleagues49 have com- pared the c.d. spectra of a-hydroxy- and a-alkyl-carboxylic acids. For the a-hydroxy-acids they suggest a conformation in which the hydroxy and carbonyl groups are eclipsed and for the a-alkyl-substituted acids coplanarity of car- boxy-group and the a-substituent. The influence of solvent on carbonyl Cotton effects has been studied for rigid steroid ketones5' and for the more flexible pulegone oxide.52 Solvent effects for the 0.r.d.x.d.of a-chlorosulphoxides have also been reported.53 The 0.r.d. curves of several a-silyl ketones (8) have been studied in a series of twenty sol- vent~~~ and a correlation has been drawn between the basicity of the solvent 0 Br (8) and the Cotton effect. The authors suggest that this is due to co-ordination of the solvent molecule with the available 3d orbitals of the silicon atom. 4 Miscellaneous Although the first extensive group of papers on magnetic 0.r.d. and c.d. were published three years ago the cost of the equipment is prohibitive and only a few papers have appeared this year e.g. an important paper55 which compares c.d. and m.c.d. for chlorophyll and related pigments.The proceedings of a major symposium on magneto-optical effects (held in December 1969) have now been p~blished.~~ The development of 0.r.d. and c.d. has been closely linked to the instrumenta- tion available and it is interesting to note that the c.d. of (+)-3-methylcyclo- pentanone has been measured'' down to 165 nm in the gas phase using a newly developed instrument. Electric-field-induced dichroism has been explored58 in a number of polyamino-acids. Finally the first resolution of a chiral borane has been reported.59 Iso-docosahydro-octadecaborane (B 8H22) has been resolved by the formation of diastereoisomeric compounds with (+)-camphidine hydrochloride and shows 0.r.d. curves with several Cotton effects between 500 and 200nm.51 D. N. Kirk W. Klyne and S. R. Wallis J. Chem. Sac. (C) 1970 350. 52 T. M. Feeley and M. K. Hargreaves J. Chem. SOC.(0,1970 1745. 53 M. Cinquini S. Colonna I. Moretti and G. Torre Tetrahedron Letters 1970 2773. 54 R. Corriu and J. Masse Tetrahedron 1970 26 5123. 55 C. Houssier and K. Sauer J. Amer. Chem. SOC.,1970 92 779. 56 Symposia of the Faraday Society 1969 No. 3. 57 0.Schnepp E. F. Pearson and E. Sharman Chem. Cornrn. 1970 545. *' E. Charney J. B. Milstien and K. Yamaoka J. Amer. Chem. SOC.,1970,92 2657. 59 S. Heimanek and J. PleSek CON. Czech. Chem. Comm. 1970 35 2488.

ISSN:0069-3030    

DOI:10.1039/OC9706700036

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

2 Physical Methods Part (iv) X-Ray Crystallography By A. F. CAMERON and N. J. HAIR Chemistry Department The University of Glasgow Glasgow W.2 Two reports of general interest to crystallographers and to those interested in crystallographic results have been published by the International Union of Crystallography Commission on Crystallographic Apparatus. The first' discusses a statistical evaluation of seventeen sets of data collected for D( +)-tartaric acid using a variety of diffractometers and diffractometer techniques. The results show that two scaled sets of experimental data will most probably differ by 6% by no less than 3% and by no more than 10%. It is concluded that there are unsuspected sources of error in data collection and that further experi- ments should be designed to examine such problems.The second report2 discusses the significance of calculated estimated standard deviations derived from least-squares refinement. For positional parameters calculated e.s.d.s. are not infrequently a factor of 2 too small and are on average 3 too small. For vibrational parameters the corresponding factors are 4 and 23. These results confirm that structures of possible high precision but real low accuracy are not uncommon. The number of reported structure analyses during 1970has increased as it has done in recent years and including inorganic structures the volume of crystallo- graphic work now occupies several thousand papers in any one year resulting in the exclusion of many interesting analyses from this report.We have classified the selected compounds very much as in previous reports but have made one important addition. As distinct from the structural studies of natural products the structure-activity relationship of biologically active molecules (including pharmacologically useful compounds) is now well established and we have included a section devoted to analyses undertaken specifically to investigate such problems. Multicyclic Small and Large Ring Compounds.-Analysis of the interesting tricyclic compound 3,4 :7,8-dibenzotricyclo[4,2,0,02*5]octa-3,7-diene (1),3reveals that the molecule is centrosymmetric and in the anti configuration with two planar benzocyclobutene systems on opposite sides of the planar central cyclo- butane ring. Conformational strain may affect rates of solvolysis and the S.C. Abrahams W. C. Hamilton and A. McL. Mathieson Acta Cryst. 1970 A26 1. W. C. Hamilton and S. C. Abrahams Acra Cryst. 1970 A26,18. B. L. Barnett and R. E. Davies Acra Cryst. 1970 B26,1026. A. F. Cameron and N. J. Hair structure of trans-bicyclo[4,2,0]octan-l-yl3,5-dinitrobenzoate (2)4 was studied to determine the effects of the ring strain in relation to solvolysis studies. In this case the cyclobutane ring is non-planar with a dihedral angle of 147" and the strain of the bicyclic system is accommodated by the cyclohexane ring which is in a slightly flattened chair conformation. Of the twenty-three non-hydrogen atoms seventeen are planar. The conformation of the bicyclo[3,2,2]non-6-ene system has been the subject of two analyses one of 5-norbornene-2,3-endo- dicarboxylic anhydride,' and the other of syn-3-exo-p-bromobenzo yloxybicyclo-[3,2,2]non-6-ene-8,9-endo-cis-dicarboxylic anhydride.6 In both molecules strain is relieved by slight flattening of the three-carbon bridge and there is no evidence of twisting of the bicyclic skeleton about the bridgehead axis.The existence of an almost flat cyclohexane ring has been confirmed by the investigation of trans-8,8-dibromo-1,4,4-trimethyltricyclo[5, 1,0,03.5 ]octane (3).' This compound Me Me (3) is unusual crystallographically in that it crystallises in the space group P1 with three molecules in the unit cell each molecule having a slightly different con- formation. Spectroscopic methods were unable to distinguish between the planar and rapidly-inverting boat conformations of 1,4-cyclohexadiene.However the analysis of 1,4-cyclohexadiene-1-glycine' shows that in this case the cyclo- hexadiene ring is planar. The cyclobutane ring of trans-1,2-cyclobutane dicar- boxylic acidg has been shown to be puckered with a dihedral angle of 150" and B. L. Barnett and R. E. Davies Acta Crysf.,1970 B26 326. R. Destro G. Filippini C. M. Gramaccioli and M. Simonetta Acta Cryst. 1969 B25,2465. A. F. Cameron and G. Ferguson J. Chem. SOC.(B) 1970,943. ' G. Reck Tetrahedron 1970,26 599. R. J. Jandacek and S. H. Simonsen J. Amer. Chem. SOC.,1969,91,6663. E. Benedetti P. Corradini and C. Pedone Acta Cryst. 1970 B26,493. Physical Methods-Part (iu) X-Ray Crystallography as a result the two carboxy-groups have a quasi-equatorial relationship.The analysis of perchloro[4]radialene (4)" is the first reported structural investigation of this system. The molecule is symmetrical and non-planar and although there is considerable theoretical and spectroscopic interest in the possibility of cross-conjugation between the exocyclic double bonds the normality of the bonded distances indicates that there is little conjugation. The related compound tri-isopropylidenecyclopropane(5)' has also been studied and although it is planar the cyclopropane bonds are only slightly shortened and the exocyclic double bonds are of normal length. The cis-azaridine substitution in cis-1 1 -(p-iodobenzenesulphony1)-1l-azabi-cyclo[8,1,0]undecane (6)'' results in a non-ideal conformation of the cyclodecane ring.On the other hand the cyclodecane rings in both 1-hydroxycyclodecyl dimethyl pho~phonate'~ each and trans-3,10-dibromocyclodecane-1,2-dione,14 possess the boat-chair-boat conformation. In the latter compound the bromine atoms occupy semi-axial positions and the orientations of the carbonyl groups are such that the number of short H-..H contacts is minimised. The centro- symmetric molecules of all-cis- 1,6-dichlorodeca- 1,3,6,8-tetraeneI5 are not (6) (7) unexpectedly found to be distorted from stable cyclodecane conformations. A sulphur analogue of cyclodecane perhydrodibenzo[ 1,2,3,6,7,8]hexathiecin (7),16 has the 8-synclinical and 2-antiperiplanar partial conformation and is directly comparable with cyclodecane.The molecules possess a (crystallographic) centre of inversion and deviations from the higher 2/m symmetry are not signi- ficant. The cyclododecane ring in 1-hydroxycyclododecyl dimethyl phosphonate' possesses 222 symmetry. Substituted Benzene and Other Aromatic Compounds.-Salts containing the anion radical 7,7,8,8-tetracyanoquinodimethanide(TCNQ) include some of the best electrically conductive organic compounds known. An analysis of one such salt triethylarnmonium-bis-(TCNQ),' reveals face-to-face stacking and the intermolecular distances are such that the activation energy required for an electron to move from (TCNQ)- to (TCNQ)' is 0.06eV. The dimensions of lo F. P. van Remoortere and F.P. Boer J. Amer. Chem. SOC. 1970,3355. I' V.H.Dietrich Acta Cryst. 1970 B26 44. H. Zacharis and L. M. Trefonas J. Heterocyclic Chem. 1970,7,755. l3 G. Samuel and R. Weiss Tetrahedron 1970,26,3005. l4 P.Groth Acta. Chem. Scand. 1970,24 1051. l5 0.Kennard D. G. Watson J. K. Fawcett and K. A. Kerr Tetrahedron 1970 26 607. l6 F. Lemmer F. Feher A. Gierin S. Hechtfischer and W. Hoppe Angew. Chem. 1970 82,319. G. Samuel and R. Weiss Tetrahedron 1970 26 3951. l8 H. Kobayashi Y. Ohashi F. Marumo and Y. Saito Acta. Crysr. 1970,B26,459. A. F.Cameron and N. J. Hair the aromatic ring in the p-sulphobenzene diazonium inner salt (8)’’ suggest that it is quinoid in character. The tilt of the carboxy-group in substituted benzoic (8) acids may be related to whether the substitution pattern is ortho diortho or para the last producing a very much smaller tilt.The gross effect of diortho substitution is shown by the tilt of 48.5” in 2,4,6-trimethylbenzoic acid,” whereas in 3,4,5- trimethylbenzoicacid” the tilt is only 5.1”. Other substituted benzenecompounds which have been studied include p-methylaminophenol sulphate (metol),” p-nitroperoxybenzoic acidYz3 and hexaiodoben~ene.~~ Considerable effort has been devoted to studies of multi-phenyl compounds. The angle between the aromatic rings in 4-a~ety1-3’-bromophenyl~~ is reported to be 386”,although this is probably influenced by crystal-packing forces. Similarly p-terphenyl (9)26is non-planar but in this case there is found to be significant shortening of those aromatic bonds which do not run in the direction of the molecule.The average value of the joining bonds is 1.496(6)A. 1,l‘-Binaphthyl is claimed to be the simplest example of an aromatic hydro- carbon with a formal double bond. The molecule possesses two-fold symmetry (9) and the configuration is cis with an angle of 68”between the two naphthalene planes. The linking bond length of 1.475(5)A is in good agreement with the theoretical value. Both hexa-m-phenylene (1 1) and penta-m-phenylene (12) are described in one paper.28 Relief from overcrowding in these molecules is achieved both by deformations of the benzene rings and by twists of ca. 18” about axes joining the mid-points of adjacent exocyclic bonds. In the molecule of 5,6,11,12,17,18-hexadehydrotribenzo[aei]cyclodecene (13),29 variations are l9 R.L. Sass and J. Lawson Acta Cryst. 1970 B26,1187. ” F.Florencio and P. Smith Acta Cryst. 1970 B26,659. ’ F. H. Cano S. Martinez-Carrera and S. Garcia-Blanca Acru Cryst. 1970 B26,972. 22 L. Cavalca G. F. Gasparri A. Mangia and G. Pelizzi Acru Cryst. 1970 B26,498. ” H.S. Kim S-C. Chu and G. A. Jeffrey Acra Cryst. 1970 B26,896. 24 R.J. Steer S. F. Watkins and P. Woodward J. Chem. SOC.(C) 1970 403. 25 H. H. Sutherland and T. G. Hoy Acta Crysf. 1969 B25,2385. 26 H.M. Rietveld E. N. Maslen and C. J. B. Clews Acta Cryst. 1970 B26,693. 27 K.A. Kerr and J. M. Robertson J. Chem SOC.(B) 1969 1 146. H. Irngartinger L. Leiserowitz and G. M. J. Schmidt Chem. Ber. 1970,103 1132.29 H. Irngartinger L. Leiserowitz and G. M. J. Schmidt Chem. Ber. 1970,103 1119. Physical Methods-Part (iv)X-Ray Crystallography N CJ C C (13) (14) observed in the aromatic C-C bond lengths as a result of differences in hybridisa- tion of the ring carbon atoms. The molecule possesses rn point-symmetry loss of am2 symmetry being ascribed to crystal-packing effects. The non-aromaticity of [16]annulene (14)30has been investigated by structure analysis. Although the molecule is almost planar and possesses non-crystallo- graphic S symmetry the bond distances show almost complete alternation with the average single bond (alternately trans and gauche) 1.454(12)A and the Br R Me (15) (16; R = N and 0) average double bond (alternately cis and trans) 1- 333(12) A.Other non-benzenoid aromatic compounds which have been studied include tr~polone,~ which forms hydrogen-bonded dimers and 5,7-dimethyl-Zphenylcyclopent[cd]azulene (15),32 which is almost planar with dimensions in good agreement with SCF calculations. 30 S. M. Johnson I. C. Paul and G. S. D. King J. Chem. SOC.(B) 1970,643. H. Shimanouchi and Y. Sasada Tetrahedron Letters 1970,2421. 32 H. J. Lindner J. Chem. SOC.(B) 1970,907. 48 A. F. Cameron and N. J. Hair Of relevance to studies of charge-transfer complexes are the analyses of the two fluorene derivatives 2-bromodiazofluorene (16; R = N2)33and 2-bromo- ketofluorene (16; R = O).34 Fluorene forms charge-transfer complexes with a wide variety of molecules and is often used when a substance is not suitably crystalline or when a heavy-atom derivative is required.An example of a structure determined using its fluorene complex derivative is provided by the analysis of the 1 :1 complex between hexahelicene (17)35 and 4-bromo-2,5,7- trinitrofluorenone. The analysis allowed examination of the helical conformation of the severely overcrowded hexahelicene molecule. An investigation of the 1 1 perylene-tetracyanoethylene complex36 reveals that the molecular planes are almost parallel. Tetracyanoethylene is also the basis of a novel anthracene add~ct.~’ The crystals of this adduct also contain methylene chloride complexed with the tetracyanoethylene and in one triclinic unit cell (space group PI)there are eight molecules of the anthracene-tetracyanoethylene adduct two molecules of methylene chloride and one molecule of tetracyanoethylene.In the molecular complex of quinone-resor~cinol,~~ the quinone and resorscinol molecules are alternately linked side by side to form infinite molecular chains. These chains are packed plane-to-plane by charge transfer the perpendicular distance between planes being 3.1 A. The complex of s-trinitrobenzene-s-triamin~benzene~’ has the component molecules stacked alternately in charge- transfer arrangements. This is the first analysis of a complex with s-triamino- benzene as donor molecule. 2-Methylthio-l-phenylvinyl-2,4,6-trinitrobenzene-sulphonate (lS)40 is an example of a self-complexing molecule and the crystal 0 H3CSC 0-SIt 9 H II NO* 33 A.Griffiths and R. Hine Acta Cryst. 1970 B26 34. 34 A. Griffiths and R. Hine Acta Cryst. 1970 B26 29. 35 I. R. Mackay J. M. Robertson and J. G. Sime Chem. Comm. 1969 1470. 36 I. Ikemoto K. Yakushi and H. Kuroda Acta Cryst. 1970 B26 800. 37 I. L. Karle and A. V. Fratini Acra Cryst. 1970 B26 596. 38 T.Ito M. Minobe and T. Sakurai Acta Cryst. 1970 B26 1145. 39 F.Iwasaki and Y. Saito Acta Cryst. 1970 B26 251. 40 M.Meyers and K. N. Trueblood Acta Cryst.. 1969 B25 2588. 49 Physical Methods-Part (iv)X-Ray Crystallography structure consists of molecular complexes formed between two molecules by use of the electron-accepting trinitrobenzene and electron-donating phenyl- t hiomethylethenyl moieties. Heterocyclic Molecules Containing Nitrogen Sulphur and Phosphorus.-Investigations of the stereoselectivity of N-quaternisation of heterocyclic compounds led to the analysis of l-ethyl- l-methyl-4-phenylpipridiniumper-~hlorate.~' The results show that the alkylating agent approaches from the axial position while the piperidinium ring is in a chair conformation.The nitroxide structure 2,2,6,6-tetramethyl-4-piperidinol-l-oxy14zis of interest because it is used as a 'spin-label' in structure-function studies of biological molecules. The analysis reveals that the nitroxide plane is twisted 21" from the plane of the ring. That substitution of methyl groups for the N-hydrogen atoms of diketopiperazine results in a significantly non-planar but flattened chair conformation is shown by an analysis of NN'-dimethyl-diket~piperazine.~~ A centrosymmetric chair conformation has also been found for 1,4-dimethyl- hexahydro-s-tetra~ine~~ in the solid state although there is the possibility of other conformations in solution.The analysis of N-phenyl-2,4,6-trimethylpyridiniumperchlorate (1 9)45 is the first examination of this type of compound and it is found that the planes of the two aromatic rings are inclined at 83.5",thus precluding the possibility ofextended conjugation. Two analyses of hydroxypyridine hydrochlorides are discussed in the same and again represent the first crystallographic examinations of this class of compound. The structures were studied because there is the possibility of tautomerism with the hydroxypyridinium cations being in equili-brium with the pyridone forms.However the dimensions of the two molecules 2-hydroxypyridinium chloride (20a) and 2,6-dihydroxypyridinium chloride (20b) show that in the solid state the pyridinium tautomeric form is preferred. (19) (201 The analysis of ( + )-1-m-bromobenzoyl-4-methylazetidin-2-one (21)47 deter- mines the absolute configuration of the n-iolecule the four-membered p-lactam ring of which is almost planar with the N-atom very slightly out of the plane of the other atoms. The imidazolidine ring of 1-thiocarbamoylimidazolidine-Zthione " W. Fedeli F. Mazza and A. Vaciago J. Chem. SOC.(B) 1970 1218. '' L. J. Berliner Acru Cryst. 1970 B26,1 198. 43 P. Groth Acra Chem. Scand. 1970,23 3155. 44 G. B. Ansell J.L. Erickson and D. W. Moore Chem. Comm. 1970,446. O5 A. H. Camerman L. H. Jensen and A. T. Balaban Acru Cryst. 1969 BE,2623. *' S. A. Mason J. C. B. White and A. Woodlock Terrahedron Letters 1969 5219. '' E. F. Paulus D. Kobelt and L. H. Jensen Angew. Chem. 1969,81 1048. A. F. Cameron and N. J.Hair has been shown to be planar with the thiocarbamoyl group tilted 2.8" from the plane of the ring.48 The structures of the addition products of thioureas and dimethyl acetylenedicarboxylate have been subject to much controversy but BrW an analysis of one product formed by the addition of N-thiocarbamoylpiperidine and dimethyl acetylenedicarboxylate has shown that in this case the product is 5-methoxycarbonylmethylene-2-piperidino-A2- 1,3-thiazol-4-one Analyses of 1,3-dimethyl-2(3H)-imidazolethione,50 1,l-dimethyl-3-phenylpy- razolium-5-0xide,~ 2-a~etyl-3-indazolinone,~ and 4-amino-3-hydrazino-5-mer-capto- 1,2,4-tria~ole,~~ were all undertaken to study the detailed geometries and dimensions of the five-membered heterocyclic rings in relation to the possibilities of electron delocalisation.In each case the molecule is or nearly is planar and while the results do not suggest the formation of aromatic structures they do suggest that extensive delocalisation takes place and that the allocation of formal single- or double-bond character may be misleading. Similar results are obtained for the tetrazole structures dehydrodithizone (23),54 anhydro-5-mer- capto-2,3-diphenyltetrazolium hydr~xide,'~and the 5-tetrazole ylide (24).56 Conformations of carbazole molecules have been studied by analyses of trans-6,8-dibromo-1,2,3,4a79a-hexahydro-4a,9-dimeth ylcarba~ole~ and 1,2,3,4,4a,9u-hexahydro-4~,9-propanocarbazolium hydro bromide.' Three studies of hexamethylenetetramine (HMT) derivatives have been reported.In the 1 :3 adduct of HMT and the phenol molecules are 48 G. Valle G. Cojazzi V. Busetti and M. Mammi Acta Crysf. 1970 B26,468. 49 A. F. Cameron N. J. Hair N. F. Elmore and P. J. Taylor Chem. Comm. 1970 890. 50 G. B. Ansell D. M. Forkey and D. W. Moore Chem. Comm. 1970,56. 51 W. H. de Camp and J. M. Stewart J. Heterocyclic Chem. 1970 7 895. 52 D. L. Smith and E. K. Barrett Acta Cryst. 1969 BE,2355. 53 N. W. Isaacs and C. H. L.Kennard Chem. Comm. 1970,631. 54 Y. Kushi and Q. Fernando Chem. Comm. 1969 1240. 5s Y. Kushi and Q. Fernando J. Amer. Chem. SOC.,1970,92 1965. s6 G. B. Ansell Chem. Comm. 1970,684. 57 A. Bloom and J. Clardy Chem. Comrn. 1970 531. 58 S. Gottlicher Chem. Ber. 1970 103 46. 59 T. H. JordanandT. C. W. Mak J. Chem. Phys. 1970 52 3790. Physical Methods-Part (iu)X-Ray Crystallography 51 linked to each HMT molecule by O-H..-N hydrogen bonds in the form of a three-leaved propeller. A notable feature of the structure is the existence of hollow channels through the crystal in which there is the possibility of inclusion of guest molecules. The 1 :1 adduct of HMT and tri-iodomethane6' is formed by C-He * -N hydrogen bonds and by intermolecular N.* .I charge-transfer bonds. A neutron and X-ray diffraction study of HMT itself6' resulted in the location of the lone-pair electrons on the nitrogen atoms. Amongst other nitrogen-heterocyclic compounds reported are the 28-membered ring dimeric model of Nylon 66 1,8,15,22-tetra-aza-2,7,16,21-tetraoxocyclo-octacosane (25),62 cyclotetrasarcosyl,63 and the perhydromethiodide of an unsymmetrical N-alkoxycarbonylazepine dimer (26).64 0 0 II I1 Me HN-C-(CH2),-C-NH I I H N -C-(CH 2)4 -C-NH II !I 0 0 Ph (27; R = 3-quinolyl) (28) Analyses65 of the thiathiophthenes (27) and (28) reveal that in (27) the S*..S and S.. .N distances are 2.364(7) 8 and 1.887(7) 8 respectively whilst in (28) the corresponding distances are 2.814(8) 8 and 1.717(7) 8,.These distances suggest that S-methylation weakens the S * -S interaction in (28) and allows formation of a formal S-N bond which probably does not exist in (27). This interpretation is supported by analyses of the isothiathiophthene (29)66 and the similar com- pound (30),67 in both of which the exocyclic S..-S distances are appreciably shorter than twice the van der Waals radius for sulphur and in which there is probably exocyclic S-S partial bond formation. The structure and conformation of cis-9-methy1thioxanthene-10-oxide6*is reported the phenyl rings being in- clined at 127" and the central ring about which the molecule is folded being quite rigid. 'O T. Dahl and 0.Hassel Acta Chem. Scand. 1970 24 377. '' J. A. Duckworth B. T. M. Willis and G.S. Pawley Acta Cryst. 1970 A26 263. 62 M. G. Northolt Acta Cryst. 1970 B26 240. 63 P. Groth Acta Chem. Scand. 1970 24 780. 64 S. M. Johnson and I. C. Paul J. Chem. SOC.(B) 1969 1244. 65 F. Leung and S. C. Nyburg Chem. Comm. 1970 707. 66 R. J. S. Beer D. Frew P. L. Johnson and I. C. Paul Chem. Comm. 1970 154. '' J. Slatten Acta Chem. Scand. 1970 24 1464. 68 J. Jackobs and M. Sundaralingam Acta Cryst. 1969 B25 2487. A. F. Cameron and N. J. Hair Two phosphorus analogues of pyridine 2,6-dimethyl-4-phenylphosphorin (3 1),69 and 1,1-dimethyl-2,4,6-triphenylphosphorin(32)” have been reported. In both cases the molecule possesses two-fold (or approximate two-fold) symmetry and the C-P distances of 1.743(5) 8 and 1.749(5) 8 respectively in each molecule suggest significant C-P 7t-bonding.The C-C distances have average values of 1-390(8).$ and in both cases the heterocyclic ring is planar. The ring of 1,1,4,4- 1,4-diphosphoniatetraethyl-2,5-dimethylcyclohexadiene- 1,4-dibromide7 is also planar although in this case it is suggested that the dimensions correspond to a diene rather than to a delocalised structure. Other six-membered phosphorus Me, MefJ PyJh / Me Me& Ph Ph R (31) (32) (33; R = Ph or CI) heterocyclic compounds studied include 1,2,3,4-tetrahydro-l,2,2,3,4,4-hexa-methylphosphinoline-l-oxide,722,4,6-tris-(2,2’-dioxybiphenyl)cyclotriphospha- propane- 1,3-diol cyclic ph~sphate,’~ ~ene,~~ and bis(cyclopentamethy1ene)-diphosphine di~ulphide.’~ There are also two reports of four-membered phos- phorus cyclic compounds 1-chloro-2,2,3,4,4-pentamethylphosphetan-l-oxide (33; R = Cl)76 and the corresponding phenyl derivative (33; R = Ph).77 The four-membered rings are puckered and the stereochemistry around the phos- phorus atom is considerably distorted from tetrahedral geometry.Hydrogen-bonding Studies and C1athrates.-Potassium hydrogen malonate has been investigated both by X-ray7* and by neutron diffra~tion’~ techniques. The hydrogen malonate residues which possess two-fold crystallographic symmetry are linked in infinite chains by very short hydrogen bonds [2-459(5) A] 69 J. C. J. Bart and J. J. Daly J. Chem. SOC.(A) 1970 563. 70 J. J. Daly J. Chem. SOC.(A),1970 1832. 71 R. L. R. Towns R.Majeste J. N. Brown and L. M. Trefonas J. Heterocyclic Chem. 1970 7 835. 72 Mazhar-U1-Haque J. Chem. SOC.(B) 1970 71 1. 73 H. R. Allcock M. T. Stein and J. A. Stanko Chem. Comm. 1970,944. 74 Mazhar-U1-Haque C. N. Caughlan. and W. L. Moats J. Org. Chern. 1970.35 1446. 75 J. D. Lee and G. W. Goodacre Acta Cryst. 1970 B26 507. 76 Mazhar-U1-Haque J. Chern. SOC.(B) 1970,934. 77 Mazhar-U1-Haque J. Chern. SOC.(B) 1970,938. 78 J. G. Sime J. C. Speakman and R. Parthasarathy J. Chem. SOC.(A) 1970 1919. 79 M. Currie and J. C. Speakman J. Chem. SOC.(A) 1970 1923. Physical Methods-Part (iu)X-Ray Crystallography which lie across centres of inversion. Both carboxy-groups are coplanar with the methylenic carbon atom. The neutron diffraction analysis allows precise location of the hydrogen atoms although the fact that the hydrogen bonds lie across crystallographic centres of inversion does not necessarily imply that the bonds themselves are symmetrical.Neutron and X-ray studies of a-oxalic acid dihydrate and its deuterium analogue have also been rep~rted.~*-~~ It is observed that the hydrogen bonds expand slightly on substitution of deuterium for hydrogen. These four analyses also show bonding and lone-pair electrons and the significance of these results is discussed along with the techniques necessary for their observation. The ethynyl H. -SOinteraction in crystals of methylprop-2-ynylammonium-p-brom~benzenesulphonate~~ has been investigated. The lowering of the C-H i.r. stretching frequency is in accord with the bonding of the acetylenic hydrogen atom to the sulphonate anion the C-H-* -0distance being 3.36 A.The crystal structure of acetic acid has been redetermined” at both +5 “C and -190 “C. The dimensions of the molecule do not vary significantly with the changes in temperature although there are minor changes in the packing of the hydrogen- bonded chains. The two C-O distances within the molecule are however significantly different C=O being 1-220(6)8 and C-O(H) 1.318(7) A. The previous determination indicated no significant difference between these bonds. Dianin’s compound (34;X = 0)86 and its sulphur analogue (34;X = S)87have both been investigated by X-ray techniques. Both compounds are versatile organic clathrates and form crystalline inclusion compounds with ethanol (34; X = 0 or S) chloroform and many other organic solvents.The structures are isomorphous six host-molecules of Dianin’s compound linking by hydrogen bonds to form a cavity which has an ‘hour-glass’ shape. The guest molecules tend to be disordered and varying cell dimensions with different guest molecules indicate that the cage can expand slightly to accommodate different sizes of guest molecules. 8o R. G. Delaplane and J. A. Ibers Acta Cryst. 1969 B25 2423. 81 T.M. Sabine G. W. Cox and B. M. Craven Acta Cryst.. 1969. B25.2437. 82 P. Coppens and T. M. Sabine Acta Cryst. 1969 B25 2442. P. Coppens T. M. Sabine R. G. Delaplane and J. A. Ibers Acta Cryst. 1969 B25 2451. 84 J. C. Calabrese A.T. McPhail and G. A. Sim J. Chem. SOC.(B) 1970 282. 85 I. Nahringbauer Acra Chem. Scand. 1970 24 453. 86 J. L. Flippen J. Karle and I. L. Karle J. Amer. Chem. Suc. 1970 92 3749. 87 D. D. Macnicol H. H. Mills and F. B. Wilson Chem. Cumm. 1969 1332. A. F. Cameron and N. J. Hair Natural Products.-Two analyses of the diterpenoid alkaloid denudatine (35) have been rep~rted.~~p*~ The alkaloid has an asitine-type skeleton and may therefore serve as an intermediate in the biogenetic transformation of asitine- type alkaloids to acanitum-type alkaloids. Denudatine is isolated from Delphinium denudatum from the seeds of which is isolated the other novel alkaloid delnudine (36).90 Two lunarine (37)derivatives have also been ~tudied,~',~~ both analyses correcting the structure and stereochemistry wrongly assigned on the basis of chemical and spectroscopic evidence.The cyclohexanone ring adopts a twist- boat conformation which is stabilised by cis fusion to the dihydrofuran ring. A rigid cage structure of a new type is found in stemofoline (38),93isolated from the stems and leaves of Stemona juponica. The molecule is closely related to (37) (38) protostemonine. Another alkaloid from the same source stemonine hydro- bromide hemih~drate,'~ has also been studied. The structure of yohimbane hydr~bromide,~~ the unsubstituted parent compound of yohimbine P-yohimbine and coryanthine has also been reported. Lappaconine (39),96 studied as the hydrobromide proves to have a ring system identical to that of lycotonine and contains an intramolecular hydrogen bond which is part of a heterologous bifurcated hydrogen-bond system.As part of a systematic study of the alkaloids F. Brisse Tetrahedron Letters 1969 4373. 89 L. H. Wright M. G.Newton S. W. Pelletier and N. Singh Chem. Comm. 1970 359. K. B. Birnbaum Tetrahedron Letters 1969 5245. 9L C. Tamura and G. A. Sim J. Chem. SOC.(B) 1970,991. 92 J. A. D. Jeffreys and G. Ferguson J. Chem. SOC.(B),1970 826. 93 H. Irie N. Masaki K. Ohno K. Osaki T. Taga and S. Uyeo Chem. Comm. 1970 1066. 94 H. Koyama and K. Oda J. Chem. SOC.(B) 1970 1330. 95 J. P. Fennessey and W. Nowacki Z. Krist. 1970 131 342. 96 G. I. Birnbaum Acta Cryst. 1970 B26 755. Physical Methods-Part (iv)X-Ray Crystallography of perennial rye-grass the crystal structure and base synthesis of perlolyrine have been described.Analysis of hunteracine (41),98 a quaternary alkaloid representative of a series of quaternary bases for which no structures had been OH (42) postulated verifies that although the molecule is quaternary there is no N-alkyl residue and the dihydroindole moiety has the -OH group at the P-position. Amongst other alkaloids whose structures and stereochemistries have been determined are hetidine,99 the solanum alkaloid solanocapsine,loo bromo- dihydroacronycine,' O' rhoeagenine,' O2 verticinone,'03 6-epimesembran01,'~~ narcissidine,' O5 dichotine,'06 and meloscine-N,-methobromide.'07 Solstitialin (42),'O8 isolated from yellow star thistle causes 'chewing disease' in horses.The X-ray analysis has determined the structure and absolute stereo- chemistry and has shown it to be the first guaianolide-type structure isolated from this source. Analysis of ( +)-dibromodehydrotetrahydrorugolosin,'09 a heavy-atom derivative of (+)-rugolosin (43) has also established the structures and stereochemistries of (-)-luteoskyrin and (-)-rubroskyrin. Recent studies have implicated amino-acids as biogenetic precursors of the cyanogenetic 97 J. A. D. Jeffreys J. Chem. SOC.(C),1970 1091. 98 R. H. Burnell A. Chapelle M. F. Khalil and P. H. Bird Chem. Comm. 1970 772. 99 S. W. Pelletier K. N. Iyer V. K. Bhalla M. G. Newton and R. Aneja Chem. Comm. 1970 393. 100 E. Hohne H. Ripperger and K. Schreiber Tetrahedron.1970. 26 3569. 101 J. Z. Gougoustas and B. A. Kaski Acta Cryst. 1970 B26 853. I02 C. S. Huber Acta Cryst. 1970 B26 373. 103 F. Brisse Acta Cryst. 1970 B26 171. 104 P. Coggon D. S. Farrier P. W. Jeffs and A. T. McPhail J. Chem. SOC.(B) 1970 1267. 105 J. C. Clardy W. C. Wildman and F. M. Houser J. Amer. Chem. SOC.,1970 92 1781. 106 N. C. Ling C. Djerassi and P. G. Simpson J. Amer. Chem. SOC.,1970,92 222. 107 W. E. Oberhansli Helu. Chim. Acta 1969 52 1905. 10s W. E. Thiessen and H. Hope Acta Cryst. 1970 B26 554. 109 N. Kobayashi Y. Iitaka and S. Shibata Acta Cryst. 1970 B26 188. A. F. Cameron and N. J. Hair (43) (44) glucosides. The investigation of the unusual structure of gyanocardin,' lo with its cyclopentenoid nucleus has shed light on the nature of a possible amino-acid precursor.The structure of the chromophore (44)'''from the fluorescent peptide produced by the iron-deficient Azobacter uinelandii has been determined and proves to be a zwitterion. The molecule is almost planar and forms a layer structure with each layer of organic molecules separated by a layer of water molecules. 5a-Acetoxy-6~-bromohexahydrophysalin A' ' has the biogenetically interesting and novel 13,14-seco-16,24-cyclo-C28-steroidal structure in which the spiro-ring system leads to very short non-bonded distances. Two analyses of pulchellin derivatives' '3*1l4 have proved the structure and stereochemistry of pulchellin which are both in agreement with the biogenetic pathway involving the guaiano- lide guaillardin.Crystallographic studies of terpenoids include an analysis of the ten-membered ring sesquiterpene pregeijerene (49,'' the trisubstituted double bonds of which have a trans configuration and analyses of shiromodiol acetate (46)Il5 and elephant01 p-bromobenzoate (47).'lS The @-orientations of the 14- and 15-methyl groups in shiromodiol are locked by the 4,Sepoxide; otherwise the epoxide would be inside the ring resulting in prohibitive transannular over-crowding. The structure of a triterpene dimethylester E -1actone from dammar resin is reported,'16 and indicates that the compound is probably formed by I LO H. S. Kim G. A. Jeffrey D. Panke R. C. Clapp R. A. Coburn and L. Long,jun. Chem. Comm. 1970,381. Ill J.L. Corbin I. L. Karle and J. Karle Chem. Comm. 1970 186. I12 M. Kawai T. Matsuura T. Taga and K. Osaki J. Chem. SOC.(B) 1970,812. I13 T. Sekita and S. Inayama Tetrahedron Letters 1970 135. I14 K. Aota C. N. Caughlan M. T. Emerson W. Herz S. Inayama and Mazhar-U1-Haque J. Org. Chem. 1970,35 1448. 115 R. J. McClure G. A. Sim P. Coggon and A. T. McPhail Chem. Comm. 1970 128. 116 S. Brewis T. G. Halsall H. R. Harrison and 0.J. R. Hodder Chem. Comm. 1970 891. 57 Physical Methods-Part (iv)X-Ray Crystallography oxidation of asiatic acid. The analysis of methyl-6a-bromo-12-methoxy-7-oxopodocarpate' ''resolves conflicting n.m.r. and spectroscopic configurational evidence for 6-bromo-7-0x0-diterpenoids. The origin and structure of a-caryo- phyllene alcohol' ' are discussed in a report which is one of a series describing sesq ui terpenoid investigations.A novel variant of squalene cyclisation is produced by the presence of a seven-membered ring in the bromoindole derivative of 3P-methoxy-21 -keto-A1 3-serratene.'lg The analysis of this compound has uniquely defined the absolute 0 stereochemistry of the serratene family. OctahydrodipyridoC1,2-a 1',2'-c] imidazol-10-ium bromide (48),' 2o which is isolated from orchids represents a type of compound not previously found in nature. Analyses of naturally-occurring sugars include the studies of coriose,'2 'raffinose pentahydrate,'22 and D-manno- 3-heptulose.' Biological Studies.-Reported crystallographic investigations of large biological molecules are becoming more numerous and have included two reports of observed diffraction from crystals of t-RNA'24,'25 which should make near- atomic resolution possible.Enzymes which have been studied include a-and y-chymotryp~in,'~~,'~~ carboxypeptidase A,128 human lysozyme,' 29 lactate dehydr~genase,'~' and ela~tase.'~' In some cases the structures of the enzymes are already known and the reported studies are of enzyme-substrate complexes which yield specific information about the enzyme-substrate binding and hence about the possible mode of action of the enzyme. l7 G. R. Clark and T. N. Waters J. Chem. SOC.(C) 1970 887. K. W. Gemmell W. Parker J. S. Roberts and J. M. Robertson J. Chem. SOC.(B) 1970,947. 'I9 F. H. Allen and J. Trotter J. Chem.SOC.(B),1970 721. lZo E. Soderberg and P. Kierkegaard Acta Chem. Scand. 1970 24 397. 12' T. Taga K. Osaki and T. Okuda Acta Cryst. 1970 B26 991. '22 H. M. Berman Acta Cryst. 1970 B26 290. lZ3 T.Taga and K. Osaki Tetrahedron Letters 1969 4433. H. H. Paradies and J. Sjoquist Nature 1970 226 159. 125 R.D. Blake J. R. Fresco and R. Longridge Nature 1970 225 32. '26 T. A. Steitz R. Henderson and D. M. Blow J. MoI. Biol. 1969,46 337. ''' G. H. Cohen B. W. Mathews and D. R. Davies Acta Crysf. 1970 B26 1062. lZ8 W. N. Lipscomb J. A. Hartsuck F. A. Quiocho and G. N. Reeke Proc. Nat. Acad. Sci. U.S.A. 1969 64 28. E. F. Osserman S. J. Cole I. D. A. Swan and C. C. F. Blake J. Mol. Biol. 1969,46 21 1. 130 D. J. Haas and M. G. Rossmann Acta Cryst. 1970 B26 998.13' H. C. Watson D. M. Shotton J. M. Cox and H. Muirhead Nature 1970 225 806. 58 A. F. Cameron and N. J. Hair Closely related to such studies are the more conventional X-ray examinations of the nucleotide and nucleoside constituents of proteins and other large biological molecules since the bases often have preferred conformations which persist in the biological environment and a knowledge of these conformations may be of assistance in the investigations of the larger molecules. There is also consider- able interest in the chemical and biological effects of U.V. irradiation of nucleic acids and the possible correlation between the stereochemistries of the photo- products and the biological consequences. As part of such studies the structures of the cis-antiphotodimer ofuracil,' 32 the cis-syn photodimer of 6-methyluracil,' 32 and of a photodimer of 1,3-dimethylthymine'33 have all been reported.The latter compound is of particular significance since the photodimerisation of thymine in DNA has been shown to be a major factor in the inactivation of micro- organisms by exposure to U.V. radiation. Closely related to this study of thymine is the analysis of dihydr~thymidine'~~ which is produced by catalytic reduction of thymidine resulting in only one diastereoisomer. The analysis of 4-thio~ridine'~~ has shown it to be the first pyrimidine nucleo- side proved to exist in the syn conformation. Investigations of S-bromoguano- sine136,137 and of 8-bromoadenosine show that these two purine nucleosides also exist in the unusual syn conformation and it is suggested that this rotational isomerism produced by the 8-substitution of bromides reflects the inability of Q replicase and E.coli transcriptase to use 8-substituted nucleoside triphosphates as substrates for RNA polymerisation. The 8-bromine also has a significant effect on the solid-state base packing. Guanosine itself has also been studied as guanosine-5'-phosphate trihydrateI3* and as guanosine dih~drate,'~~ and two analyses of the closelyrelated compound inosine' 39-141 are also reported. Sundaralingam and P~tkey'~~?'~~ have described DL-0-serine phosphate and L-0-serine phosphate. The molecule is a zwitterion and the studies were under- taken to investigate the hydrogen-bonding properties of biological phosphates in relation to biological phosphorylation and similar processes.The structure of a new natural amino-acid 2,3-cis-3,4-trans-3,4-dihydroxy-~-proline,'~~ isolated from the cell walls of Navicula pelliculosa has been reported as has the structure of m-proline hydrochloride. 145 132 J. Konnert J. W. Gibson I. L. Karle M. N. Khattak and S. Y. Wang Nature 1970 227 953. 133 N. Camerman and A. Camerman J. Amer. Chem. SOC. 1970,92,2523. '34 J. Konnert I. L. Karle and J. Karle Actu Cryst. 1970 B26 770. 13' W. Saenger and D. Suck Nature 1970,227 1046. 13' C. E. Bugg and U. Thewalt Biochem. Biophys. Res. Comm. 1969,37,623. 13' S. S. Tavale and H. M. Sobell J. Mol. Biol. 1970 48 109. '38 W. Murayama N. Nagashima and Y.Shimizu Acta Cryst. 1969 B25 2236. 139 U. Thewalt C. E. Bugg and R. E. Marsh Acta Cryst. 1970 B26 1089. I4O A. R. I. Munns and P. Tollin Actu Cryst. 1970 B26 1 101. 14' A. R. I. Munns P. Tollin H. R. Wilson and D. W. Young Actu Cryst. 1970 B26 1114. 142 E. Putkey and M. Sundaralingam Actu Cryst. 1970 B26 782. 143 M. Sundaralingam and E. Putkey Actu Cryst. 1970 B26 790. I. L. Karle Actu Cryst. 1970 B26 765. 145 Y. Mitsui M. Tsubodi and Y.Iitaka Actu Cryst. 1969 B25 2182. 59 Physical Methods-Part (iv) X-Ray Crystallography A study of the polynucleotide complex polyinosinic acid plus polydeoxycytidilic acid,'46 shows it to be a double-helical molecule similar in structure to RNA and the DNA-RNA hybrid of which it is an analogue.Other complexes reported'47 include the 1 :1 hydrogen-bonded complexes 1 -methyluracil-9-ethyl-8-bromo-2,6-diaminopurine and l-ethylthymine-9-ethyl-8-bromo-2,6-diaminopurine. These complexes exhibit different base-pairing configurations which suggest that the energy difference between them is small. The cyclic polypeptide composed of four glycine and two alanine units,148 and the cyclic dipeptides CYC~O-D-alanyl-~-alanyl'~~ have also been investigated. and cyclo-~-alanyl-~-alanyl~~~ The latter two compounds show conformational differences the DL-form being nearly planar while the LL-form is puckered. Other compounds studied include DL-N-chloroacetylalanine,' L-alanylglycine' ''and N-methyl-DL-leucylglycine hydrobromide.lS2 A feature of the preceding reports is the almost universal importance attached to the hydrogen bonding and packing of such molecules in the solid state since these factors may be extrapolated to the biological environments of the molecules.Flavin and flavanone derivatives have been the subjects of several analyses. Two charge-transfer complexes a flavin-naphthalenediol complex,' 53 and a riboflavin-hydroquinone complex' 54 have been studied the results suggesting that the flavin 'chelate site' may be significant in flavin-protein binding. Flavins are widely involved in biological energy-conserving redox processes and the analysis of the 'reduced' compound 5-acetyl-9-bromo- 1,3,7,8,10-pentamethyl- 1,5-dihydroisoalloxazine (49)' 55 shows that the molecule is folded about the N(5)-N(10) axis the dihedral angle being 35.5".In the oxidised state the molecule is planar as demonstrated by the analysis of the 'oxidised' neutral molecule 9-bromo-3,7,8,10-tetramethylisoalloxazine monohydrate (5O).ls6 On the other 146 E. J. O'Brien and A. W. MacEwan J. Mol. Biol. 1970,48 243. 14' G. Simundza T. D. Sakore and H. M. Sobell J. Mol. Biol. 1970,48,263. '" I. L. Karle J. W. Gibson and J. Karle J. Amer. Chem. SOC.,1970 92 3755. 14' E. Sletten J. Amer. Chem. Soc. 1970 92 172. 150 F. E. Cole Acta Cryst. 1970 B26 622. 151 M. H. J. Koch and G. Germain Acta Cryst. 1970 B26 410. R. Chandraseken and E. Subramanian Acta Cryst. 1969 B25 2599. 153 C. A. Langhoff and C. J. Fritchie jun. Chem. Comm. 1970,20. 154 C. A. Bear J. M. Waters and T.N. Waters Chem. Comm. 1970 702. P. E. Werner and 0.Ronnquist Acta Chem. Scand. 1970 24,997. 156 M. yon Glehn P. Kierkegaard and P. Norrestam Acta Chem. Scand. 1970 24 1490. 60 A. F. Cameron and N. J. Hair hand 10-methylisoalloxazinium bromide dihydrate,' 57 which is a model for protonated riboflavin shows only minor deviations from planarity. The structure of the flavanone obtusifolin (51),15' has been determined and an analysis of ribitol'59 shows that the conformation of the free molecule is identical to the of-$Me -HOW \ OH 0 (51) conformation of the ribitol residue in the isoalloxazine moiety of riboflavin. It is possible that this ribitol conformation may be a structural property of the ribitol molecule. The structures of many pharmacologically useful compounds have been studied in attempts to relate the detailed molecular geometries to the biological activities.Cholinergic molecules are amongst those which have been studied in this way. Acetylcholine itself has been studied as acetylcholine chloride160 which proves to possess a hitherto unsuspected conformation and as erythro( +-)-A,& dimethylacetylcholine iodide.'61 The structure and absolute stereochemistry of ( +)-trans-Zacetoxycyclopropyltrimethylarnmoniumiodide,I6* an analogue of acetylcholine have also been determined since the (+)-trans isomer is very much more active than the (-)-trans isomer. L-( +)-cis-2-(S)-Methyl-4-(R)-trimethyl-ammonium-methyl-1,3-dioxolan iodide (52)' 63 is a potent agonist of acetylcholine Me I-Me (52) (53) at the parasympathetic postganglionic (muscarinic) junction.Its conformation is very similar to that of other muscarinic agonists and the synclinal conforma-tion of the nitrogen relative to the ester or ether oxygen atom now seems well 15' R. B. Bates T. C. Sneath and D. N. Stephens J. Org. Chem. 1970 35 1625. Is8 P. Nurayanan K. Zechmeister M. Roehrl and W. Hoppe Tetrahedron Letters 1970 3643. s9 H. S. Kim G. A. Jeffrey and R. D. Rosenstein Acta Cryst. 1969 B25,2223. I6O J. K. Herdklotz and R. L. Sass Biochem. Biophys. Res. Comm. 1970 40 583. 16' T. F. Brennan F. K. Ross W. C. Hamilton and E. Shefter J. Pharm. Pharmacol. 1970 22 724. 162 C. Chothia and P. Pauling Nature 1970 226 541. 163 P. Pauling and T.J. Petcher Chem. Comm. 1969 1258. 61 Physical Methods-Part (iv)X-Ray Crystallography established in this class of compound. Analyses of the local anaesthetic procaine (53)'64 and of the 1 :1 procaine-bis-p-nitrophenylphosphate complex,'65 show that procaine has structural similarities to acetylcholine and other molecules active in the cholinergic system and suggest a common membrane receptor. A compound which is very similar to procaine 2-diethylamino-p-methoxybenzoate hydrochloride,'66 is also described as is the anti-cholinergic drug quinuclidinyl di-ma'-thienylglycollate.'67 The similarity of thalidomide N-(a-glutarimide)phthalimide,' 68 to both fiucleosides and barbiturates has prompted two X-ray determinations one of thalidomide itself,'68 and the other of 4-brom0thalidomide.~~~ It is thought that the biological significance of thalidomide may lie in the fact that it is an N-substituted phthalimide.Analyses of the barbiturate drug 5-ethyl-5-( 1-methylbuteny1)barbituric acid,17' and of chlorpromazine (Largactil) (54)' 71 are described the molecule of chlorpromazine being folded about the N-S axis with a dihedral angle of 139.4". Such folding is similar to that found in the flavins and is also a feature of the anti-depressive agent 5-(bromomethylene)-lO,l l-dihydro-5H-dibenzo[~cycloheptene,72 in which the seven-membered ring exists in a boat conformation and of thiethyl-perazine (55),173the two aromatic rings of which are inclined at 139". The analysis of isoproterenol sulphate dihydrate,' 74 a bronchodilatory agent shows that its conformation is identical to the conformations of ephedrine and noradrenalin which also display the same activity.Other drugs studied by X-ray analyses include the antimalarial and antileprotic agent 4,4'-di-aminodiphenyl sulphone cc-2-ethyl-5-methyl-3,3-diphenyltetrahydrof~ran,~ 76 R. Beall J. Herdklotz and R. L. Sass Biochem. Biophys. Res. Comm. 1970 39 329. 16' M. Sax J. Pletcher and B. Gustaffson Acta Cryst. 1970 B26,114. 166 R. Beall and R. L. Sass Biochem. Biophys. Res. Comm. 1970,40 833. 167 A. Meyerhoffer Acta Cryst. 1970 B26 341. F. H. Allen and J. Trotter Chem. Comm. 1970 778 C. S. Peterson Acta Chem. Scand. 1969 23 2389. I7O B. M. Craven and C. Cusatis Acta Cryst. 1969 B25 2291. 17' J.J. H. McDowell Acta Cryst. 1969 B25 2175. 172 J. J. H. McDowell Acta Cryst. 1970 B26 954. 173 K. Larsson Acta Chem. Scand. 1970,24 1503. M. Mathew and G. J. Palenik Biochem. Biophys. Res. Comm. 1970,39 123. C. Dickinson J. M. Stewart and H. L. Ammon Chem Comm. 1970 920. I" 76 P. Singh and F. R. Ahmed Acta Cryst. 1969 B25 2401. A. F. Cameron and N. J. Hair histamine diphosphate monohydrate,' 77 the sweetening agent saccharin,'78 silydianin,"' and sodium ascorbate .Iso Antibiotics studied include Gramicidin S"' and Monensin,'" isolated from Streptomyces cinnamonensis. Both molecules complex with metal ions and in the latter case it is suggested that it is the ability to complex with Na' and K+ ions and to make them soluble in lipid portions of cellular structures which may be responsible for the activity.The barium salt of antibiotic X-537A,183isolated from an unidentified Streptomyces and the structures of viocidic acid hydro- bromide' 84 and of 00'N-trimethylpyoluteorin's5 have all been described. There have been several analyses of steroids and of steroid-related structures including a conformational study of two 4,4-dimethyl-ster0ids,'~~and the structures of Sa-bromo-6/3 19-oxido-pregnan-3~-ol-20-one,'s 6/3,7/3-methylene-17/3-hydroxyandrost-4-en-3-one-17-acetate,1ss 8/3-methyltestosterone-l7/3-mono-bromoacetate,'89 and testosterone-17~-p-bromobenzoate.'89Testosterone has also been studied as the 1:1 testosterone-p-bromophenol complex.1g0 which reveals that it is the a-face of the steroid which is involved in the specific site binding of the steroid when it influences metabolic processes.The complex is significant because p-bromophenol resembles the portion of the tyrosine molecule available for complex formation in the protein backbone. Two synthetic com- pounds diethylstilbestr~l''~ and 1-p-(2-dimethylaminoethoxypheny1)-1,2-cis-diphenyl-b~t-l-ene,"~which display oestrogenic activity have both been studied. Diethylstilbestrol inhibits the binding of 17P-oestradiol to a stereospecific pro- teinaceous receptor in uterine cells and although the conformation of the mole- cule cannot resemble the conformation of the natural steroid rotation of the benzene rings results in the molecular dimensions being similar to the thickness of a steroidal oestrogen.17' M. V. Veidis G. J. Palenik R. Schaffrin and J. Trotter J. Chem. SOC.(A) 1969 2659. 17' Y. Okaya Acta Cryst. 1969 B25,2257. D. J. Abraham S. Takagi. R. D. Rosenstein R. Shiono H. Wagner L. Horhammer 0.Seligmann and N. R. Farnsworth Tetrahedron Letters 1970 2675. lSo J. Huoslef Acta Cryst. 1969 B25 2214. G. Camilletti P. de-Santis and R. Rizzo Chem. Comm. 1970 1073. M. Pinkerton and L. K. Steinrauf J. Mol. Biol. 1970,49 533. S. M. Johnson J. Herrin S. J. Lui and I. C. Paul Chem. Comm. 1970 72. P. Coggon,J. Chem. SOC.(B) 1970 838. Y. Utsumi A. Furusaki and Y. Tomiie Bull. Chem. SOC.Japan 1970,43 2640. G. Ferguson E. W. Macaulay J. M. Midgley J. M. Robertson and W. B. Whalley Chem. Comrn. 1970,954. E. M. Gopalakrishna.A. Cooper and D. A. Norton Acta Cryst. 1969 B25 2473. P. B. Braun J. Hornstra and J. I. Leenhouts Acta Cryst. 1970 B26 352. lE9 (B) 1970,443. H. Koyama M. Shiro T. Sato. and Y.Tsukuda J. Chem. SOC. 190 A. Cooper G. Kartha E. M. Gopalakrishna and D. A. Norton Acfa Cryst. 1969 B25 2409. C. M. Weeks A. Cooper and D. A. Norton Acra Cryst. 1970 B26,429. lg2 B. T. Kilbourn and P. G. Owston J. Chem. SOC.(B) 1970 I.

ISSN:0069-3030    

DOI:10.1039/OC9706700043

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

3 Reaction Mechanisms Part (i) By J. G. TILLETT Chemistry Department University of Essex Colchester NEWbooks published this year include the second editions of two classic works in organic chemistry Hammett’s ‘Physical Organic Chemistry” and Ingold’s ‘Structure and Mechanism in Organic Chemistry’.2 1 Acidity Functions and Molecular Basicity New acidity-function data reported this year include values of Ho for aqueous H2S04 over the temperature range 15-55 OC3 and Do for D2S0,4 (values of pK,,+ for a set of Hammett bases are also recorded). A further study of the effect of added micelles and electrolytes on the Ho” and H,”‘ acidity functions5 and a different approach to the study of electrolyte effects on the activity coefficients of aromatic amines6 have also been reported.Values of H-have been obtained for 40-95 mol ”/ dimethyl sulphoxide in water containing tetramethylammonium hydroxide using a set of substituted fluorenes as indicators.’ Arnett and his co-workers have discussed some of the problems associated with the determination of the pK values of weak organic acids by acidity function methods and in an attempt to avoid some of the difficulties have suggested that heats of ionization be used as an alternative criterion of base strength.’ A good linear correlation was found between the enthalpies of protonation of some 35 aromatic and aliphatic amines and the pK values of the corresponding conjugate acids in water. A wide range of other compounds were found to fit the AH-pK correlation and the pK,’s of alcohols ethers and water could be esti- mated.A study of the temperature variation of the thermodynamic acidity constants of some substituted aminesg and phenols” has been carried out to determine the standard enthalpies and entropies of protonation. Substituent L. P. Hammett ‘Physical Organic Chemistry’ 2nd edn. McGraw Hill Book Co. New York 1970. C. K. Ingold ‘Structure and Mechanism in Organic Chemistry’ 2nd edn. Cornell Univ. Press Ithaca New York 1969. P. Tickle A. G. Biggs and J. M. Wilson J. Chem. SOC.(B) 1970 65. J. Sierra M. Ojeda and P.A. H. Wyatt J. Chem. SOC.(B) 1970 1570. C. A. Bunton and L. Robinson J. Phys. Chem. 1970,74 1062. M. Lucas and J. Steigman J. Phys. Chem. 1970 74 2699. ’ K. Bowden and A. F. Cockerill J.Chem. SOC.(B) 1970 173. E. M. Arnett R. P. Quirk and J. J. Burke J. Amer. Chem. SOC.,1970,92 1260. P. D. Bolton and F. M. Hall J. Chem. SOC.(B) 1970 1247. ’* P. D. Bolton J. Ellis and F. M. Hall J. Chem. SOC.(B) 1970 1252. J. G. Tillett effects on both these properties were found to be strictly additive. A similar linear free-energy-enthalpy correlation was observed for both weakly basic and strongly basic members of the series thus providing further confirmation that the extension of proton ionization studies to weak bases by the indicator overlap method does give meaningful pK data.' The acidity of carbonyl compounds continues to attract interest. An n.m.r. chemical shift method has been used to determine the pK,'s of some very weak ketone bases in superacid media.I2 The use of a series of ketones to determine acidity over a wide range (Ho = 0 to -17.5)in both superacid and conventional acid systems is described.The same method has been used to determine the pK values for 3-pentanone 2-butanone and 3-methyl-2-b~tanone.'~ Arnett and his co-workers have devised a basicity scale for carbonyl compounds based on the relative heats of protonation in fluorosulphuric acidI4 for those compounds which protonate cleanly in this solvent. The data for aromatic ketones correlate well with those for aromatic amines determined by this method (loc. it).^ The protonation of ap-unsaturated ketosteroids was found to correlate with HA and the effect of substituents on pK,,+ to be similar to those previously found for simple ap-unsaturated ket~nes.'~ Both the rate of protonation of dimethylacetamide and dimethylbenzamide,16 and the protonation of several ring-subs titu ted N-(2,2,2- trifluoroe th yl)benzamides' follow the HA acidity function the latter observation suggesting that no separate acidity function based on secondary amides seems to be needed.The effect of substituents on the pK values of 4-substituted 4'-aminobenzanilides and 4'-hydroxybenzanilides shows that there is no conjugative transmission between the phenyl groups of (1) (1) + (Y= NH, OH ;X = MeO Me H C1 NO,) through the amide group.' The effect of substituents on the protonation of azo- compounds' and on the dissociation constants of 4-(substituted styry1)tropo- lones2' have also been investigated.The correlation of acidities of weak carbon acids in the fluorene series with molecular orbital and linear free-energy relation- '' P. D. Bolton C. D. Johnson A. R. Katritzky and s.A. Shapiro J. Amer. Chem. SOC. 1970,92 1567. G. C. Levy J. D. Cargiol and W. Raccla J. Amer. Chem. Soc. 1970 92 6238; G. C. Levy and D. Campioli Tetrahedron Letters 1970 919. I3 D. G. Lee Canad. J. Chem. 1970,48 1919. l4 E. M. Arnett R. P. Quirk and J. W. Larsen J. Amer. Chem. SOC.,1970,92 3978. R. I. Zalewski and G. E. Dunn Canad. J. Chem. 1970,48,2540. l6 B. G. Cox J. Chem. SOC.(B),1970 1780. '' D. W. Farlow and R. B. Moodie J. Chem. SOC.(B) 1970 334. l8 J. A. Donohue R. M. Scott and F. M. Menger J. Org. Chem. 1970,352035. l9 G.A. Eian and C.A. Kingsbury Bull. Chem. SOC.Japan 1970,43 739. *O K. Imafuku. S. Nakama and H. Matsumura Tetrahedron 1970 26 1821. Reaction Mechanisms-Part (i) ships,21 and of trisubstituted methanes22 with oR-have been reported. An extended Hiickel M.O. treatment has been used to correlate the protonation behaviour of meta-and para-substituted aryl~arbinols.~~ Apparent dissociation constants have been measured for meta- and para-substituted benzoic acids with substituents of the -M and +I -M type in either aqueous dioxan ethanol or methyl cello~olve,~~*~~ and a number of new values of Hammett constants 6 and cg,calculated. A linear correlation has been observed between the rate constant for neutralisa- tion by hydroxide ion (log k2) of substituted 1-phenyl-1-nitroethane and the ionisation constants (pK,) with a Brsnsted coefficient p of 1-17-1-20.26 The Brsnsted coefficient of greater than unity is considered to arise from differential substituent effects ; as the electron-withdrawing effect of the substituent is increased the rate constants for neutralisation are affected to a greater extent than the ionisation constants.A similar explanation of the anomalous Brsnsted coefficients obtained in substituted nitroalkanes has also been given by Kre~ge.~’ Using an n.m.r. method Delpuech et al. have studied the rates of deprotonation of mono- di- and tri-methylammonium ions.28 They suggested that the relative (2) + + + order of reactivity MeNH >> Me2NH2 > Me,NH for a reaction with a rate i expression of the form :rate = k,[MeNH,] [HC02 -1 results from a symmetrical transition state (2) which could arise from attack by a HC02H molecule of an internally hydrogen-bonded ion pair in a push-pull mechanism.On the basis of an extensive n.m.r. study of methyl-substituted alcohols and ketones Jackman and Kelly have proposed that the methyl group should be regarded as an electron-attracting group rather than its normally accepted r61e observed in e.g. strengths of acids and bases.29 Such a suggestion has been rejected by Robinson and Lewis who have drawn attention to some of the problems associated with the interpretation of n.m.r. data in terms of the electronic proper- ties of groups.30 Indeed Robinson has suggested that the symbol C +Me should ” K.Bowden A. F. Cockerill and J. R. Gilbert J. Chem. SOC. (B) 1970 179. 22 L. A. Kaplan N. E. Burlinson W. M. Moniz and C. F. Poranski Chem. Comm. 1970 440. 23 A. C. Hopkinson I(.Yates and I. G. Csizmadia Tetrahedron 1970 26 1845. ’* K. Kalfus M. Vecera and 0.Exner Coll. Czech. Chem. Comm. 1970 35 1195. 2s 0. Exner and J. Latomy Coll. Czech. Chem. Comm. 1970,35 1371. ” M. Fukuyama P. W. K. Flanagan F. T. Williams L. Franier S. A. Miller and H. Shechter J. Amer. Chem. SOC. 1970 92 4689. 27 A. J. Kresge J. Amer. Chem. Soc. 1970 92 3210. 28 J. J. Delpuech J. Ducois and V. Michon Chem. Comm. 1970 1187. ’’ L. M. Jackman and D. P. Kelly J. Chem. SOC.(B) 1970 102. .’’ P. M. E. Lewis and R. Robinson Tetrahedron Letters 1970 2783. 66 J.G.Tillett 6-b+ b+ b-not be interpreted as a dipole C-Me implying a reversal of the dipole C-H if H 6+ 6-is replaced by Me but rather as a reduction of the C-H charge ~eparation.~’ Similarly the fact that simple MO theory predicts that a methyl group is electron- attracting (relative to hydrogen) in amines alcohols and ethers suggests that energies of proton transfer reactions do not necessarily correlate with charge densities on the atom to which the proton is atta~hed.~’ Olah and his co-workers have given a comprehensive review of the evidence for the site of protonation of a large number of organic conjugate acids.33 Much of the evidence stems from their own n.m.r. studies in superacid solutions. A recent study in their laboratory has been of the protonation of the meso-ionic 3-phenylsydnone (3).This has now been shown to protonate on the exocyclic oxygen atom rather than on the nitrogen-2 atom as previously supposed.34 Ph-N-C-H P 4\ NkC 2\ 0/5** 1 (3) 2 Acid-Base Catalysis Carboxylic Esters Ethers Acetals and Related Compounds.-The dienone-phenol rearrangement is an example of an A1 reaction. The acid-catalysed iso- merisation of 4,4-dimethylcyclohexadienoneto 3,4-dimethylphenol is a three- step process35 (Scheme 1). Use of kinetic isotope effects shows that the rate- determining step (k’)is the isomerisation of (4)to (5). The dependence on acidity 0 OH Me Me Me. Me (4) lk’ ?H ?H Me Me Scheme 1 (5) 31 R. Robinson Tetrahedron 1970 26 2067. 32 W. J.Hehre and J. A. Pople Tetrahedron Letters 1970 2559. J3 G. A. Olah A. M. White and D. H. O’Brian Chem. Reo. 1970,70 561. 34 G. A. Olah D. P. Kelly and N. Sucin J. Amer. Chem. Soc. 1970,92,3133. 35 V. P. Vitullo and N. Grossman Tetrahedron Letters 1970 1559. Reaction Mechanisms-Part (i) 67 of the activity coefficient ratio fsH+/f+ for this step suggests that the transition state is less solvated than the ground state by one water 2,6-Di-t-butyl-4-methyl-4-(1-phenylethy1)cyclohexadien-1-one does not undergo a typical dienonephenol rearrangement in acid solution but hydrolyses by a unimolecular solvol ysis to form 2,6-di-t-bu tyl-4-methylphenol. The hydrolysis of vinyl acetate can proceed either by attack of water on the protonated carbonyl carbon atom as for saturated esters or by an A-S,2 mechan-ism involving protonation of the double bond (Scheme 2).In 6% H2S04 the 0 0 II + It CH,=CH.OC.Me + H+'2CH,CH.O-C.Me 0 0 + II II CH,-CH.OC.Me+ H,O -* CH,$H.O.C.Me 1 +OH* + I1 CH,.CHO + CH3-C02H+ H+ +-CH,CH.O-C.Me II OH H Scheme 2 A-S,2 mechanism accounts for less than 0.5% of the rate for vinyl acetate and about 20% of the rate for isopropenyl acetate.38 At higher acidities however this mechanism becomes increasingly more important. The studies of substituent effects on the hydrolysis of ring-substituted a-acetoxystyrenes reported earlier39 have been extended to an investigation of steric effects in the hydrolysis df both cis-and trans-acet~xystilbene.~' Studies of the acid-catalysed hydrolysis of cyclic vinyl esters"' and the alcoholysis of isobutylene oxide4' have also been reported.The rate-determining step in the decarboxylation of 2,4-dihydroxybenzoic acid changes with increase in acidity over the range 0.1-8 N aqueous HCl from a slow proton transfer to a rate-limiting cleavage of the carbonxarbon bond.43 The kinetics of the decarboxylation in dioxan-water of some substituted benzoyl- acetic acids have also been in~estigated.~~ A study of the decarboxylation of the 2-cyano-2-phenylacetate ion in water aqueous ethanol and aqueous dioxan has been made so as to elucidate the mode of action of cycloamyloses as model cata- lyst systems in decarb~xylation.~~ The results suggest that the rate acceleration observed is due solely to a change in polarity of the local environment when the substrate complexes with the amylose and that catalysis is not due to interaction 36 V.P. Vitullo Chem. Comm. 1970 688. 37 K. Okarnoto I. Nitta and H. Shinga Bull. Chem. SOC.Japan 1970,43 1768. " D. S. Noyce and R. M. Pollack J. Amer. Chem. SOC.,1969 91 7158. '' D. S. Noyce and R. M. Pollack J. Amer. Chem. SOC.,1969,91 119. D. S. Noyce and A. M. Myers J. Org. Chem. 1970,35,2460. " L. H. Branningen and D. S. Tarbell J. Org. Chern. 1970,35 639. S. Sekiguchi K. Matsui and Y. Yasuraoka Bull. Chem. SOC.Japan 1970,43,2523. " A. V. Willi M. H. Cho and C. M. Won Helv. Chim. Arta 1970 53 663. '* R. W. Hay and K. R. Tate Ausrral. J. Chem. 1970 23 140. 45 A. Thomson J. Chem. SOC.(B) 1970 1198.J. G. Tillett with the hydroxy-groups on the outside of the cycloamylose. The spontaneous decarboxylation of the benzisoxazole-3-carboxylateion (Scheme 3) increases markedly as the solvent is changed from water to less polar and especially aprotic solvents because of the different solvation requirements for the initial state (6) with its localised charge and the transition state (7) with its more delocalised Scheme 3 charge.46 The effect of cetyltrimethylammonium bromide micelles on this reac- tion is consistent with the concept that micelles catalyse reactions by changing the microscopic en~ironment.~’ A comprehensive review of micellar catalysis in organic reactions has recently been published.48 A careful study of carbon and oxygen isotope effects on the decarbonylation of benzoylformic acid combined with a detailed kinetic analysis of the steps involved shows that the rate-limiting step in >99 % H,S04 is carbon4xygen bond fission49 and confirms the mechan- ism originally proposed by Hammett.” The rates of the acid-catalysed hydrolysis of a series of benzylidene diacetates were found to correlate with Ho,and to give Bunnett w values consistent with an A1 mechani~m.’~ Furthermore the correlation of rate with c’ and the low 0 II ,o.Co.Me -Hi /o-c.Me APCH -ArCH \ \ OCO.Me 0-C-Me II ‘OH I OH Y J \ArCHO + 2MeC0,H Scheme 4 46 D.S. Kemp and K. Paul J. Amer. Chem. SOC.,1970,92,2553. 47 C. A. Bunton and M. J. Muich. Tetrahedron Letters 1970.3881. *‘ E. J. Fendler and J. H. Fendler Ado. Phys. Org. Chem. ed. Gold 1970 8 271. 49 Z. Margoliu and D. Samuel Chem. Comm. 1970 802. 50 L. P. Hammett ‘Physical Organic Chemistry’ McGraw Hill New York 1940 283. M. J. Gregory J. Chem. Soc. (B) 1970 1201. React ion M echanisms-Part (i) 69 values of AS‘ obtained led to the formulation of this reaction in terms of a cyclic AA,t mechanism (Scheme 4). N.m.r. data for the acid-catalysed [2H,]ethanolysis of alkyl orthoacetates is consistent with the formation of a keten dialkylacetal from the intermediate carboxonium ion by elimination of a proton.52 Lahti and KanKaanpera have reported further studies of the hydrolysis of ethyl orthoformate in aqueous dioxan which confirm their earlier assignment of an A1 mechanism to this rea~tion.’~ The Finnish workers have also discussed the use of solvent effects to distinguish between the A-S,2 and A2 mechanisms of orthoester hydrolysi~.’~ Concurrent but not concerted catalysis by acidic and basic buffers has been found for the lactonisation of a series of /?/?-dimethyl(2-hydroxy-5-substituted)-hydrocinnamic acids.” Although the kinetic effects isotope effects and ASf values do not distinguish between rate-determining formation or breakdown of the tetrahedral intermediate the p values are considered to support the later mechanism which can be catalysed by general acid and water (8) or general base and water (9).The lactonisation of some substituted o-hydroxymethylbenzoic (3 P H-A H rH-OH -& 1 H-X X (8) (9) acids and 8-hydroxymethyl-1-naphthoic and electrostatic participation by carboxylate groups in the formation of lactone?’ have also been investigated.Topping and Burrows have now published a full account of their investigation of base-catalysed intramolecular nucleophilic catalysis by a keto-group in 2-acetylphenyl mesitoate.’8 The Sussex workers have also been reported on neighbouring carboxy-group catalysis in 2-carboxyphenyl me~itoate.’~ The results obtained illustrate the importance of steric effects in determining which of the kinetically indistinguishable mechanisms -general-base catalysis or nucleo- philic catalysis -actually occurs. The products resulting from treatment of the ester with tris(hydroxymethy1)aminomethane in anhydrous methanol were mesitoic acid and methyl salicylate in quantitative yield.These must arise from 52 L. R. Schroeder J. Chem. SOC.(B). 1970 1789. 53 M. Lahti and A. KanKaanpera Acta Chem. Scand. 1970,24 706. 54 M. Lahti and A. KanKaanpera Acta Chem. Scand. 1970 24 360. 55 S. Milstein and L. A. Cohen J. Amer. Chem. SOC.,1970 92 4377. 56 D. P. Weeks and X. Creary J. Amer. Chem. SOC.,1970 92 3418. 5’ F. G. Bordwell and A. C. Knipe J. Org. Chem. 1970 35 2956 2959. H. D. Burrows and R. M. Topping J. Chem. Sac. (B) 1970 1323. ’’ H. D. Burrows and R. M. Topping Chem. Comm. 1970 1389. J. G.Tillett intramolecular nucleophilic attack of the carboxylate anion to form an anhydride intermediate (Scheme 5). Methyl mesitoate and salicylic acid which could arise -0 (Mes = 2,4,6-trirnethylphenyl) Scheme 5 only from the carboxy-group acting as either an intramolecular general-base or acid (Scheme 6),or from intermolecular attack of alkoxide ion on the ester could not be detected Thus the general-base mechanism which is now considered to /p H L-0-c \0-c $0 NO 1 J Q0I-I + MesC0,R C0,- Scheme 6 occur exclusively in the solvolysis of aspirin is entirely suppressed when the carboxy-group is sterically hindered and it is replaced by a nucleophilic catalysis mechanism.The hydrolysis of para-substituted phenyl hydrogen succinates in the pH range below 2 proceeds by an A,,2 me~hanism.~'The constant value of the rate of hydrolysis over the range pH 5.8-7 is attributed to nucleophilic attack by the carboxy-group leading to succinic anhydride formation.In an 6o F. G. Baddow S. A. Wahhab B. M. Awad N. M. Guindy M. Wahba and B. A. Malek J. Chem. SOC.(B) 1970 739. Reaction Mechanisms-Part (i) 71 attempt to investigate further the importance of proximity effects in enzymic catalysis Bruice and Turner have studied the rates of bimolecular attack of acetate ion on substituted phenyl acetates and of intramolecular attack by carboxyl anion on some phenyl succinates phthalates and 3,6-endoxo-A4-tetrahydrophth-alate.6 It was concluded that carboxy-group solvation cannot contribute significantly to the large values of kintra/kinter often obtained when covalently rigid intramolecular models are considered. Another illustration of the influence of steric effects on neighbouring-group participation is shown in the alkaline Intramolecular hydrolysis of methyl 8-acyl- and 8-ar0yl-l-naphthoates.~~ catalysis by the neighbouring carbonyl group occurs for the 8-formyl and 8-(3’-and 4’-substituted benzoyl) esters (Scheme 7) whereas the 8-acetyl 8-propionyl OH I R-C-0-C02Me + OH-1 fast + MeOH t + MeO-(R = H or XC,H,.) Scheme 7 and 8-isobutyryl esters undergo catalysis by the strongly nucleophilic carbon acid anion (Scheme 8).Aniline trapping experiments have confirmed the forma- tion of N-acetylimidazole in the imidazole-catalysed hydrolysis of aryl acetates with both good and poor leaving groups.63 Kinetic studies of naphthylimidazole- catalysed hydrolysis of phenyl esters have also been Menger has reported detailed studies of the imidazole-catalysed hydrolysis of p-nitrophenyl laurate at a heptane-water boundary.65 A determination of the Arrhenius parameters for the alkaline hydrolysis of some aromatic cyclic and open-chain carbonates shows that the kinetic accelera- tion observed is due to a combination of both enthalpy strain and entropy b’ T.C. Bruice and A. Turner J. Amer. Chem. SOC.,1970,92 3422. 62 K. Bowden and A. M. Last Chem. Comm. 1970 1315. 63 D. G. Oakenfull J. Chem. SOC.(B) 1970 197. 64 T. Kunitake S. Shinkai and C. Aso Bull. Chem. SOC.Japan 1970,43 1109; T. Kuni-take and S. Shinkai ibid. p. 2581. b5 F. M. Menger J. Amer. Chem. SOC.,1970,92 5965. J. G.Tillett H I R1-C-CO C02Me Rl-E-CO COzMe I + OH-* + H2O '2w 1 R2 /R' /c\ o=c c=o 1 H I R'-C-CO CO2-I R2M + MeOH +H20 + MeOH strain.66 The imidazole-catalysed hydrolysis of bis(4-nitrophenyl) carbonate proceeds by a nucleophilic catalysis mechanism whilst the corresponding hydroly- sis of 0-(4-nitrophenylene) carbonate is general-base-catalysed ( Studies of (10) the alkaline hydrolysis of dihydrouracils,68 some xanthine complexes of acetoxy-cinnamic acids6' and of polynuclear methyl /3-arylacrylate~,'~ and of the mer- cury(I1)-catalysed hydrolysis of isopropenyl acetate7 and some thiol esters and related compounds72 have been reported. " J. G. Tillett and D. E. Wiggins J. Chem. SOC.(B) 1970 1359. 67 T. H.Fife and D. M. McMahon J. Org. Chem. 1970,35 3699. 68 I. Blagoeva B. J. Kurtev and I. G. Pojarlieff J. Chem. SOC.(B) 1970 232. 69 H. Stelmach and K. A. Connors J. Amer. Chem. SOC.,1970,92,863. '' M. K. Hoffman and E. Berliner J. Org. Chem. 1970 35 745. '' J. E. Byrd and J. Halpern Chem. Comm. 1970 1332. D. P. N. Satchel1 and I. I. Secemski J. Chenz. SOC.(B) 1970 1306. Reaction Mechanisms-Part (i) 73 The effects of substituents on the reaction of ortho-substituted phenylacetic acids with diazodiphenylmethane in various alcohols have been correlated in terms of polar and steric effects.73 Substituent effects on the alkaline hydrolysis of substituted benzoylcholine esters74 and of substituted pyridine carboxy- lates75-77 and the solvolysis of 1-arylethyl acetates78 have been analysed by the use of linear free-energy relationships.Shorter has given a concise review of the use of such relationships in the separation of polar steric and resonance effects in organic reaction^.^' General-acid catalysis of the hydrolysis of tropone diethyl ketal has been observed and a mechanism involving partial rate-determining protonation has been suggested (11).80 Thus if the intermediate carbonium ion is of sufficient A6-H (11) stability general-acid catalysis can be observed even with ketals of aliphatic alcohols where the leaving group is poor. The pH-independent mechanism of hydrolysis of 2-(pnitrophenoxy)tetrahydropyran is strongly accelerated by increase in solvent polarity has a deuterium kinetic solvent isotope effect of about unity and AS' is +2.2 e.u.and is therefore considered to involve uni- molecular decomposition to p-nitrophenoxide ion and the resonance stabilised carbonium ion (12).81 Solvent effect studies on the A1 hydrolyses of 2,2-dimethyl- and 2-isopropyl-2-methyl- 1,3-dioxolones and 2,2-dimethyl-4-hydroxymethyl-l,3-dioxolone have shown that activation parameters are affected by solvation of 7J N. B. Chapman J. R. Lee and J. Shorter J. Chem. SOC. (B) 1970,755. 74 J. J. Zimmerman and J. E. Goyan J. Medicin. Chem. 1970 13 492. 75 A. D. Campbell S. Y. Chooi L. W. Deady and R. A. Shanks J. Chem. SOC.(B),1970 1063. 76 A. D. Campbell E. Chan S. Y. Chooi L. W. Deady and R. A. Shanks J. Chem. SOC. (B),1970 1065. 77 A. D.Campbell E Chan S. Y.Chooi L. W. Deady and R. A. Shanks J. Chem. SOC. (B),1970 1068. '' E. A. Hill M. L. Gross M. Stasiewicz and M. Manion J. Amer. Chem.SOC.,1969,91 738 1. 79 J. Shorter Quart. Rev. 1970 24 433. E. Anderson and T. H. Fife J. Amer. Chem. SOC.,1969,91 7163. T. H. Fife and L. H. Brod J. Amer. Chem. Soc. 1970,92 1681. 74 J. G. Tillett both ground state and transition state.” Neighbouring carboxy-group catalysis has been observed in the general-acid-catalysed hydrolysis of methyl phenyl acetals of f~rmaldehyde.~~.~~ An electrostatically assisted mechanism is pre- ferred over the mechanistically indistinguishable general acid catalysis involv- ing essentially complete proton transfer in the transition state. The additional rate enhancement caused by a second ortho-carboxy-group has been investigated and the implications of the results on the mode of action of lysozyme are discussed.Bruice and his group have also shown by studies of the hydrolysis 1 HO OMe (13) of methyl-2,6-anhydro-a-~-altropyranoside (13) and related pyranosides that fixing the ground state of the C-2 C-1 0 C-5 region of the glycoside in a planar configuration does not change the mechanism from A1 to an A-S,2 pro~ess.~’ The hydrolyses of the isomeric 2,3-0O-benzylidene-norbornane-exo-2 exo-3-diols are thought to proceed through bimolecular attack of water on the conjugate acid of the cyclic acetal.86 The hydrolysis of 8-hydroxy- quinoline-/l-D-glucoside by Cu” ions has also been studied.” Secondary deuterium isotope effects show that whereas the transition states for the hydroly- sis of orthoesters resemble the substrate those for acetal hydrolysis resemble more the carbonium ion intermediate.88 It is of interest to note that the extent of proton transfer to the substrate in the transition state for orthoester hydrolysis as indicated by the Bronsted or-value does not parallel the extent of C-0 bond cleavage as indicated by the deuterium isotope effects.The acid-catalysed hydrolysis of a series of benzaldehyde methyl S-(substituted phenyl) thioacetals proceeds via the normal A1 mechanism of acetal hydr~lysis.~~ No general-acid catalysis could be detected. Further details of studies on the formation and breakdown of hemithioacetals for which a diffusion-controlled step becomes rate-determining have been described.” The products of the reaction of a series of para-substituted methyl orthobenzo- ates with substituted amines arise from partitioning of the carbonium ion derived from the orthoester between the amine and water.” (Scheme 9).The aminolysis 82 L. L. Schaleger and C. N.Richards J. Amer. Chem. SOC.,1970,92 5565. ’’ B. M. Dunn and T. C. Bruice J. Amer. Chem. SOC.,1970,92,2410. M4 B. M. Dunn and T. C. Bruice J. Amer. Chem. SOC.,1970,92,6589. 85 T. A. Gindici and T. C. Bruice Chem. Comm. 1970 690. 86 B. Capon and M. I. Page Chem. Comm. 1970 1443. ’’ C. R. Clark and R. W. Hay Chem. Comm. 1970,794. 88 H. Bull T. C. Pletcher and E. H. Cordes Chem. Comm. 1970 527. T. H. Fife and E.Anderson J. Amer. Chem. SOC.,1970 92 5464. 90 R. E. Barnett and W. P. Jencks J. Amer. Chem. SOC.,1969,91 6758. ” K. Koehler and E. H. Cordes J. Amer. Chem. SOC.,1970,92 1576. Reaction Mechanisms-Part (i) Adduct acid Scheme 9 of acetylimidazole by ethylenediamine shows a rate enhancement of more than lo3relative to glycine which is attributed to intramolecular general-base catalysis by the second amino-gr~up~~ (Scheme 10). There appears to be no significant rate enhancement however in the reaction of ethylenediamine with the acetylimida- zolium ion which has a better leaving group. Further studies of the base-catalysed Scheme 10 hydrolysis and aminolysis of some substituted phenyl acetates and propionates have been rep~rted.’~ The self-catalysed reaction of decylamine with p-nitro- phenyl acetate provides an example of an amine-catalysed aminolysis of an ester with an excellent leaving The nature of the transition state for aminolysis in aprotic solvents has also been disc~ssed.~~*~~ Jencks and his co-workers have examined the site at which proton transfer occurs in the general-acid-catalysed aminolyses of acetylimidazole by replacing the proton of the acetylimidazolium ion (AcImH) by a methyl group.97 No methylimidazole catalysis of the aminolysis of l-acetyl-3-methylimidazolium chloride (AcIm+Me) or of its aminolysis by ethylamine could be detected.This is consistent with a mechanism involving proton donation to the leaving group (Scheme 11)rather than proton removal from the attacking amine by general-base R’NHAc + ImH + Hh Scheme 11 ” W.P. Jencks and K. Salvesen Chem. Comm. 1970 548. y3 T. C. Bruice A. F. Hegarty S. M. Felton A. Donzel and N. G. Kundu J. Amer. Chem. SOC.,1970 92 1370. “ D. G. Oakenfull Chem. Comm. 1970 1655. ” F. M. Menger and J. H. Smith Tetrahedron Letters 1970 4163. 96 D. P. N. Satchel1 and I. I. Secemski J. Chem. SOC.(B) 1970 1013. ’’ W. P. Jencks D. G. Oakenfull and K. Salvesen J. Amer. Chem. SOC.,1970 92 3201. J. G. Tillett catalysis (Scheme 12). When the attacking amine is a weaker base than the leaving group however e.g. as in the imidazole-catalysed aminolysis of AcIm'Me by trifluoroethylamine proton transfer occurs at the other end of the system and the + B + R'NH,! + AcImR2 + BH' + R'NHAc + ImR2 Scheme 12 mechanism shown in Scheme 12operates.In such reactions therefore the proton transfer involves the less basic of the attacking or leaving groups. The general- acid- and -base-catalysed methoxylaminolysis of methyl thioformate proceeds via four different transition states one of which involves a diffusion-controlled proton tran~fer.'~ Robinson has published full details of his observation of a tetrahedral inter- mediate in amidine hydrolysisg9 and Jencks and Fersht on the formation and 0 0 II NH-C NH*C \ NHR CNHR 0 0 0 I H NR 0 0 H Scheme 13 (14) y8 G. M. Blackburn Chem. Comm. 1970,249. y9 D. R. Robinson J. Amer. Chem. Sor. 1970,92 3138. Reuction Mechanisms-Part (i) hydrolysis of the acetylpyridinium ion intermediate in the pyridine-catalysed hydrolysis of acetic anhydride.'" Structure-reactivity correlations have also been investigated for the reactions of a series of nucleophiles with substituted N- acetylpyridinium ions.As a model system for biotin action Hegarty and Bruice have studied the hydrolysis and aminolysis of 2-amino-4,5-dibenzo-6-oxo-l,3-oxazine." '*lO2 The mechanism of intramolecular nucleophilic attack by the ureido-group at the carbonyl carbon of esters and amides of o-ureidobenzoic acids have been investigated. O3 For o-(H,NCONH)C,H,COX three different reaction pathways could be delineated (Scheme 13); when X-is a strong base (0-,NH, NMe, OMe and OCH,CF,) reaction occurs through the ureido nitrogen anion to give the quinazoline (14),path (c); as the basicity decreases (e.g.with SMe,) reaction occurs increasingly through the oxygen anion to give the benzoxazine (15) path (b);for good leaving groups participation by the oxygen of the undissociated ureido-group again gives the benzoxazine (15) path (a). An oxygen- 18 tracer study of the hydrolysis of N-phenylmaleisoimide has confirmed that hydrolysis in acid solution involves attack at imino-nitrogen whereas in basic solution attack occurs at the carbonyl group'04 (Scheme 14). coo" 0 y C'*ONHPh CO + Hz"O N.Ph Scheme 14 The effects of substituents on the alcoholyses of some N-aroyl-N'-phenyldi- imides and N-benz~yl-N'-aryldi-imides'~~ and on the hydrolyses of substituted salicylideneanilines'06 have been examined.The rate of hydrolysis of N-iso- butylidenemethylamine varies in a complex manner with pH."' The rate constant increases at pH -= 0 where decomposition of the zwitterion Pr'-CH(0-)NH,Me is rate-controlling up to cu. pH 4.5,where it begins to level off as the attack of water on the iminium ion becomes rate-controlling. The rate then falls to a constant value about pH 8 where hydroxide ion attack predominates. The mechanism of formation of N-isobutylidenemethylamine from isobutyralde- hyde and methylamine was also studied."* looA. R. Fersht and W. P. Jencks J. Amer. Chem. SOC. 1970,92 5432 5442. lo' A. F. Hegarty and T. C. Bruice J. Amer. Chem. SOC.,1970 92 6568. lo* A. F. Hegarty and T. C. Bruice J. Amrr.Chrm. Soc. 1970 92 6561. lo' A. F. Hegarty and T. C. Bruice J. Amer. Chem. SOC.,1970,92 6575 lo4 C. K. Sauers Tetrahedron Letters 1970 1149. lo' T. Carty and J. M. Nicolson Tetrahedron Letters 1970 4158. Io6 J. Hoffmann J. Klienar V. Sterba and M. Vecera Coll. Czech. Chem. Comm. 1970 35 1387. J. Hine J. C. Craig J. G. Underwood and F. I. Via J. Amer. Chem. Soc. 1970,92 5194. 'On J. Hine F. A. Via J. K. Gotkis and J. C. Craig J. Amer. Chem. SOC. 1970 92 5186. J.G. Tillett The rate-determining step for the hydrolysis of acetophenone oxime in acidic solution is thought to be the general-base-catalysed loss of hydroxylamine from a tetrahedral intermediate"' (Scheme 15). A study of the rearrangement of ortho-substituted acetophenone oximes has established that an N-arylnitrilium ion (17) is an intermediate in the Beckman rearrangement in sulphuric acid' ( =-90 %) (Scheme 16).For those oximes which will rearrange in <70% H2SO4 or in Me -C -NHGy Me-C=NaY OH 'OH2 II I Scheme 16 HC104 the reactive species will be the 0-protonated oxime (16) and not the oxime-0-sulphonic acid. Enhanced reactivity of nucleophiles with lone pairs of electrons adjacent to the nucleophilic centre (the so-called 'a-effect') has been attributed to either (a) electron repulsion due to p,-p interaction or to (b)intramolecular catalysis.' For the reactions of p-nitrophenyl acetate with oximate anions in which a lone pair on oxygen is conjugated the former effect is ruled out and the observed rate enhancement must be due to intramolecular catalysis.The rate enhancements observed for the acylation of hydroxamic acids are also attributable to such 'OD B. J. Gregory and R. B. Moodie J. Chem. SOC.(B) 1970 862. 'lo B. J. Gregory R.B. Moodie and K. Schofield J. Chem. SOC.(B) 1970,338. '" J. D. Aubort and R. F. Hudson Chem. Comm. 1970 937. Reaction Mechanisms-Part (i) catalysis (Scheme 17).' The rate enhancement however for N-substituted hydroxamic acids which cannot tautomerise in this way can arise either from 0-I 0 R' H Scheme 17 intramolecular catalysis or from steric hindrance which removes the nitrogen from conjugation with the carbonyl group. An alternative explanation of the a-effect in terms of the theory of charge and frontier controlled reactions has been suggested.lI3 Studies of the acid-catalysed hydrolysis of acetamide l4 the Cu"-catalysed hydrolysis (and methanolysis) of NN-di-(2-pyridylmethyl)amides,' and the Co"'-catalysed hydrolysis of chelated glycine amides and esters' l6 have been reported.The 2-imino-A3- 1,3,4-oxadiazolines ( 18) hydrolyse readily in dilute acid to form azocarboxylic acid lactones (19) (Scheme 18).' '' The ring-opening (18) (19) (R' = R2 = Me; R' = Me R2= Et) Scheme 18 reactions of some model thiazolium ions have also been described."* The acid- catalysed ring-opening of 3-phenylsydnone and 3-m-nitrophenylsydnone are thought to proceed via a rapid protonation followed by nucleophilic attack by the anions of the acids involved.' l9 The acid-catalysed Wallach rearrangement of azoxybenzene (20) in sulphuric acid is considered to involve a rate-determining proton transfer concurrent with N-0 bond-fission (Scheme 19) rather than the formation of a dication."' Leverson and Thomas have shown that the entropies of activation for the acid-catalysed hydrolysis of o-diazoacetophenones in aqueous dioxan vary considerably with solvent composition and provide a 'I2 J.D. Aubort and R. F. Hudson Chem. Comm. 1970,938. I' G. Klopman K. Tsuda J. B. Louis and R. E. Davis Tetrahedron 1970 26 4549. M. M. Mhala and M. H. Jagdale Indian J. Chem. 1970 8 147. 'I5 R. P. Houghton and R. R. Puttner Chem. Comm. 1970 1270. 'I6 D. A. Buckingham C. E. Davis D. M. Foster and A. M. Sargeson J. Amer. Chem. SOC.,1970,92 5571.'I7 S. L. Lee G. B. Gubelt A. M. Cameron and J. Warkentin Chem. Comm. 1970 1074. P. Haake and J. M. Duebo Tetrahedron Letters 1970 461. 'I9 S.Aziz and J. G. Tillett J. Chem. Soc. (B) 1970 416. IZo E. Buncel and W. M. J. Strachan Canad. J. Chem. 1970,48 378. J. G. Tillett doubtful criterion of mechanism in this case.'" N.m.r. studies on primary diazoketones in superacid solutions show that 0-protonation occurs,122 rather 0-+ OH I +H,O I + Ph-N=N-Ph Ph-N=N-Ph -+ Ph-N-N-Ph + + I; OH.-H--A (20) 1 ++ products +-Ph-NrN-Ph Scheme 19 than as previously assumed at the a-carbon atom. The mechanism of the acid- catalysed rearrangement of N-chl~roacetanilide'~~ and of the nitramine re-arrangement'24 have been further investigated.Esters of Inorganic Oxy-Acids.-The mechanisms of hydrolysis of orthophos-phate esters have been reviewed by B~nt0n.l~~ The rates of the acid-catalysed hydrolysis of N-(p-nitropheny1)diphenylphosphinamide(21) correlate with H but with a low slope ( -O-5-0.6).'26 The correlation of log k for (21)with the pK,'s of anilinium ions and the observed deuterium solvent isotope effect suggests pro- tonation on nitrogen and an A1 mechanism (Scheme 20). That protonation occurs predominantly on nitrogen has been established for some phosphinamides by n.m.r. studies.'27 The hydrolysis of (21) has also drawn attention to a possible 0 0 II II + Ph-P-NHAr + H,O+ Ph-P-NH,Ar I Ph (21) -0 II 6+ 6+ products + Ph-P--NH,Ar I -Ph Scheme 20 anomaly in the use of the entropy of activation as a criterion of mechanism when protonation occurs on nitrogen.The observed value of AS' is -22 e.u. At first sight this is hardly consistent with an A1 mechanism. The observed entropy of activation is the sum of both the entropy change for the protonation step and of 12' C. W. Thomas and L. L. Leverson J. Chem. SOC.(B) 1970 1061. lz2 C. Wentrup and H. Dahn Helv. Chim. Acta 1970 53 1637. lZ3 A. H. El Nadi W. J. Hickinbottom and S. Wasif J. Chem. SOC.(B) 1970 I131 lz4 W. N. White C. Hathaway and D. Huston J. Org. Chem. 1970,35,737. lZ5 C. A. Bunton Accounts Chem. Res. 1970 3 257. lz6 P. Haake and D. A. Tyssee Tetrahedron Letters 1970 3513. P. Haake and T. Koizumi Tetrahedron Letters 1970 4849.Reaction M echanisms-Part (i) 81 the rate-determining step. Whereas the first term is likely to be small for oxygen bases which have only one acidic hydrogen to be solvated in the conjugate acid a value of -22e.u. was estimated for formation of (22) which has two acidic protons. Taking this into account the entropy change is now consistent with that expected for a unimolecular mechanism. The reactivity towards hydrolysis of the normally unreactive phosphate diester anion depends critically on the basicity of the leaving group and is much more sensitive to this than are the reactions of the corresponding monoanions of phosphate monoesters.'28 Thus the differences in reactivity between the two series of esters should disappear with a good leaving group having pK -2.The solvent isotope effect and entropy of activation are consistent with a simple bimolecular mechanism (Scheme 2 1) involving a pentaoxyphosphorane inter- mediate (cf:also ref. 129) although a concerted S,2(P) reaction is not ruled out. ArO 0 OAr +I HlO + \ P/*#< -H,O-P-OAr / \'.0 / \o-ArO -0 11 ArO 0 OAr \ /; 1 P;'-HO-P-OAr / \;.. + ArO-HO 0 HO/ '0-Scheme 21 The effect of varying both the nucleophile and leaving group on the reactivity of a series of aryl methyl phosphates in SN2(P)reactions has been compared with displacement of the same anion from a triester and from the dianion of a mono-ester.'30 The rate retardation observed (ca. 100 times) for the attack of anionic nucleophiles on phosphate diester monoanions is attributed to electrostatic repulsion between the anion and nucleophile.The attack of neutral nucleophiles is slower than the corresponding reactions of either of the other phosphate esters. This is considered to arise from the S,l(P)-like or borderline character of the transition state for displacements at the phosphorus centre of phosphate dianions XP0,2-with good leaving groups (e.g. X = p-NO,.C,H,.). The transition states are dominated by the bond-breaking process with only a small amount of bond-formation. Evidence for an S,l(P) mechanism has also been found in the formation of six-membered cyclic phosphonates.' Neighbouring carboxy-group catalysis has been observed in the hydrolysis of the 2-carboxyphenyl anion (23).'32 The rate enhancement of 107-108 is 12' A.J. Kirbyand M. Yournas J. Chem. SOC.(B) 1970 510. 129 C. A Bunton and S. J. Farber J. Org. Chem. 1970 34 769. 130 A. J. Kirby and M. Yournas J. Chem. SOC.(B) 1970 1165. j3' W. Wadsworth and H. Horton J. Amer. Chem. SOC.,1970,92 3785. 132 S. A. Khan A. J. Kirby M. Wakselsman D. P. Homing and J. M. Lawlor J. Chem. SOC.(B),1970 1182. J. G. Tillett attributed to intramolecular nucleophilic catalysis (Scheme 22) in which both the appearance and disappearance of the salicyclic acid cyclic phosphate intermediate (24) have been observed spectroscopically. The specific displacement of phen- oxide ion at the expense of salicylate ion despite their similar leaving-group qp 0 0,II r0At 0,II 0-0opo:-0 qi’+ I co-0-\ \ \ co2-0 0 (23) (24) Scheme 22 properties is explained in terms of the pseudorotation of quinquevalent phos- phorus intermediates.Thus. the intermediate involved (25) will have the two negatively charged oxygen atoms equatorial and the phenoxy-group apical correctly aligned as a leaving group. Pseudorotation of (25)to allow the salicylate OPh 0 (25) anion to leave from an apical position would also bring a negatively charged oxygen into an apical position giving an energetically unfavourable intermediate and only phenoxide ion is displaced. Phenyl cis-4-hydroxytetrahydrofuran 3-phosphate (26) has been studied as a model system for ribonuclease action.133 In morpholine or acetate buffers it reacts initially to give only the cyclic phosphate (27) and phenol.In the amine buffer specific-base catalysis amounts for 60 of the observed rate and general acid-base catalysis the remainder. Further confirmation has been obtained + PhO-0 00 00 OH 1; \/ -0’ \ RP\ OPh 0 0-(26) (27) Scheme 23 ”’ D. A. Usher D. I. Richardson and D. G. Oakenfull J. Amer. Chem. SOC.,1970 92 4699. Reaction Mechanisms-Part (i) that hydroxide ion catalysis involves a pre-equilibrium followed by an in-line' S,2(P) displacement of phenoxide ion by the neighbouring alkoxide group (Scheme 23). Neighbouring hydroxy-group catalysis in the hydrolysis of 3-hydroxy-2-pyridylmethyl phosphate has also been observed.' 34 The reactivi- ties of a wide range of nucleophiles towards phosphorus in a series of dialkyl substituted-phenyl phosphite esters have been examined.' 35 General-base catalysis of hydrolysis is the narmal mechanism for catalysis when the catalysing 0 .-H,O H-0 I-OAr I /\ H RO.'OR (28) base is much less basic than the leaving group (28). With strongly basic nucleo- philes however the mechanism changes to nucleophilic catalysis (Scheme 24). RO 0-\p//o -I Y-+ -YIP-OAr '\ RO' 'OAr RON OR * (RO),P(O)Y + ArO-Scheme 24 Structure-activity correlations for the cholinesterase inhibition of diethyl substituted-phenyl phosphates' 36 and studies of the hydrolysis of trimethyl phosphate in DMSO-H,O and ethylene glycol-H,O mixtures'37 have been reported. The hydrolysis of ethyl P-hydroxy-trans-cinnamic acid cyclic phosphate (29) is catalysed by hydroxide ion hydrogen ions and by general bases.'38 The most likely mechanism for the latter mechanism involves the formation of a tetrahedral intermediate (30) (Scheme 25).It is interesting to note that nucleo- philic attack does not occur at the phosphorus atom of (301 in contrast to the reported reactions of the corresponding five-membered cyclic ester. Further studies of the effects of micellar catalysis on the hydrolysis of phosphate esters by Bunton and his and a detailed re-investigation of the hydrolysis of acetyl phosphate catalysed by various uni-and bi-valent have also been reported. The reactions of phenyl methylphosphonic acid and p-nitrophenyl methylphosphonic acid and their anions with nucleophiles have been '34 Y.Murakami J. Sunamoto and H. Ishiza Chem. Comm. 1970 1665. S. A. Khan and A. J. Kirby J. Chern. SOC.(B) 1970 1172. S. Hausch J. Org. Chem. 1970 35 620. 13' P. T. McTigue and P. V. Renowden Austral. J. Chem. 1970 23 297. 13' J. F. Merecek and D. L. Griffith J. Amer. Chem. Sac. 1970,92,917. 139 G. J. Buist C. A. Bunton L. Robinson L. Sepuiveda and M. Stam J. Amer. Chem. Sac. 1970 92 4072. I4O C. A. Bunton L. Robinson and L. Sepulveda J. Org. Chem. 1970,35 1081. I" P. J. Briggs D. P. N. Satchell and G. F. White J. Chem. SOC.(B) 1970 1008. J. G. Tillett H H (30) Ph-C+ C-COZH I Scheme 25 H ~tudied.'~~,'~~ Peroxide and hydroxamate ions show a large a-effect for this reaction with p-nitrophenyl methylphosphonate anion.'43 The reaction of this anion with most amines proceeds via an SN2(P)mechanism with attack at phos- phor~~.~~~ With piperidine however approximately 35 "/ of the total reaction 0 A 0 0-= occurs at aromatic carbon (Scheme 26) with the formation of 1-(p-nitropheny1)-piperidine.Neighbouring oxime group participation facilitates the acid-catalysed hydrolysis of alkyl a-hydroxyimino-p-nitrobenzylalkylpho~phonates'~~ (Scheme 27). R' I 0% /0!- 0 P --H R( I 1-\\/OH + R'.OH O\ /Od-R2' 'O-C=NOH C=N I I Ar Ar (Ar = p-N02C,H,. R' = Bu'CHMe R2 = Me) Scheme 27 '42 E. J. Behoman M.J. Biallis H. J. Brass J. 0.Edwards and M. Isaks J. Org. Chem. 1970 35 3063. 14' E. J. Behoman M. J. Biallis H. J. Brass J.0.Edwards and M. Isaks J. Org. Chem. 1970,35 3069. 144 H. J. Brass J. 0. Edwards and M. J. Biallis J. Org. Chem. 1970,35 4675. 14' J. I. G. Cadogan and D. T. Eastlick Chem. Comm. 1970 1546. Reaction Mechanisms-Part (i) 85 Mislow has given a general review of the r61e of pseudorotation in the stereo- chemistry of nucleophilic displacement rea~ti0ns.I~~ Haake and his group have recently shown that both the chloride (31 ;X = C1) and the amide (3 1 ;X = NMe,) are hydrolysed much more slowly than the corresponding acyclic compounds (32 ; X = C1 NMe,) whereas for the corresponding esters (31 32; X = OEt) the reverse is the case.I4' It was suggested that this rate inhibition could be used as a Me H Me Me Me*Me Me4 )-Me Me p Me P \ \ X X mechanistic probe to determine the mechanism of reaction at phosphorus.Thus the more rapid hydrolysis of the phosphetan ester was ascribed to relief of ring strain on forming an intermediate in which the four-membered ring spans an apical-equatorial position. On the other hand the slower rate of reaction of the four-membered ring indicates increased strain in the transition state which requires entering and leaving groups co-linear with phosphorus and suggests an SN2(P)mechanism. Trippett and his co-workers however have criticised this criterion and have proposed that all displacements at phosphorus in a four- membered ring proceed via a trigonal-bipyramidal intermediate in which the ring spans apical-equatorial positions and that the rate of reaction depends critically on the electroneghivity of the leaving Substitution at the phosphetanium ring is accelerated by relief of strain in (33) but is retarded because only one electro-negative group occupies an apical position compared with two groups occupying such a position in the corresponding intermediate for an acyclic compound.The more electronegative groups are usually better leaving 14' 'JI Scheme 28 K. Mislow Accounts. Chem. Res. 1970 3 321. 14' P. Haake R. D. Cook T. Koizumi P. S. Ossip W. Schwarz and D. A. Tyssee J. Amer. Chem. SOC.,1970,92 3828. '" J. R. Corfield N. J. De'ath. and S. Trippett Chem. Comm. 1970 1502. J. G.Tillett groups and the greater will be this retardation for X = C1 or &Me,. Such a theory also explains the observed stereochemical changes.When X is highly electronegative the preferred pseudorotation will be (33) *(34) resulting in retention of configuration whilst if X and R have comparable electronegativities (33) -P (35) is energetically favourable and inversion of configuration occurs (Scheme 28). Retention of configuration at a phosphoryl centre in the reaction of methoxide ion with the trans-cyclic phosphinate ester (36) is attributed to attack of MeO- along an apical co-ordinate to give the intermediate (37) which pseudorotates about 0-as a pivot group to give (38).14’ Displacement of CD,O-from an apical position in (38) which is required by the principle of microscopic reversibility leads to the trans product (Scheme 29). The alkaline (37) Scheme 29 hydrolysis of cis-and trans-1,4-dibenzyl- 1,4-diphenyl- 1,4-diphosphoniacyclo- hexane dibromide,’ of some tris-(2-thienyl)phosphonium salts,’’’ and of cis-and trans- l-benzyl-4-methyl- l-phenylphosphorinanium bromide’ 52 have been studied.The nucleophilic ring-opening of cyclic OS-ethylene phosphorothioate derivatives (39) proceeds with P-0 bond-fission* 53 whereas the reactions of the corresponding acyclic 0sesters and of OS-ethylene O-methyl phosphorothioate (39) (40) (40)involve P-S bond-fission.154 Initial attack is considered to involve the for- mation of (41 ;R = OMe) where the more electronegative oxygen atom occupies 149 S. E. Cremer and B. C. Trivedi J. Amer. Chem. SOC.,1969 91 7200. G. E. Driver and M. J. Gallagher Chem.Comm. 1970 150. 15’ D. W. Allen J. Chem. SOC.(B) 1970 1490. ls2 K. L. Marsi and R. T. Clark J. Amer. Chem. SOC.,1970,92 3791. 153 D. C. Gay and N. K. Hamer J. Chem. SOC.(E) 1970 1123. Is4 D. C. Gay and N. K. Hamer J. Chenr. SOC.(B) 1970 1564. Reaction Mechanisms-Part (i) 87 an apical position even though the thiolate is a better leaving group (Scheme 30). The pseudorotation (41)-+(42) is more favourable for R = OMe than for 0-and leads to P-S bond-fission. Kinetic solvent isotope effects in the alkaline hydrolysis of phosphonium salts suggest that in the transition state very little P-C bond-breaking has occurred and only a small degree of proton transfer to the incipient carbanion. The considerable energy barrier to pseudorotation if 0-is not the pivot atom is used to explain that the lack of oxyen-18 exchange in the hydrolysis of phosphine oxides with a benzyl leaving group does not neces- sarily exclude the formation of a quinquecovalent intermediate.' 56 Reviews have been published of the acid-base-catalysed hydrolysis of organic sulphites'" and of the enzymatic and non-enzymatic reactions of cyclic sulphate and sulphonate esters.' 58 Neighbouring imidazoyl group catalysis in the hydroly- sis of 2-[4(5)-imidazoyllphenyl sulphate (43) is considered to involve mainly intramolecular general-acid catalysis (Scheme 31).' 59 Micellar effects on the " " I H I H IH (43) Scheme 31 hydrolysis of 2,4-dinitrophenyl sulphate have also been reported.160 The entropy of activation and kinetic solvent isotope effect for the hydrolysis of the phenyl phosphosulphate monoanion are consistent with an A 1 mechanism involving uni- molecular elimination of sulphur trioxide.' The reaction of p-nitrophenyl sulphate with thiophenol in aqueous DMF is also considered to follow a similar mechanism (Scheme 32).16' 0-Sulphobenzoic anhydride hydrolyses more rapidly (X = H Br Me or MeO) Scheme 32 155 J.R. Corfield and S. Trippett Chetm Comm. 1970 1267. 56 P. Haake and G. W. Allen Tetrahedron Letters 1970 31 13. 15' J. G. Tillett Mech. React. Sulfur Compounds 1969 4 129. IS' E. T. Kaiser Accounts Chem. Res. 1968 3 145. '59 S. J. Benkovic and L. K. Dunikoski Biochemistry 1970,9 1390. 16* E. J. Fendler R. R. Liechte and J. H. Fendler J.Org. Chem. 1970 35 1658. "' S. J. Benkovic and R. C. Hevey J. Amer. Chem. Soc. 1970 92,4971. 16' T. Kuroso W. Tagaki and S. Oae Bull. Chem. SOC.Japan 1970,43 1553. 88 J. G. Tillett under neutral conditions than either the corresponding carboxylic anhydrides or sulphonyl halides.' Unlike the hydrolysis of carboxylic anhydrides no evidence of acid catalysis could be found. Further details of the reactions of anhydrosul-phites (mixed carboxylic-sulphurous anhydrides) have been published by Tighe and his group. 16&' 66 Sulphonyl fluorides are usually unreactive towards hydrolysis under acidic or neutral conditions. The relatively rapid hydrolysis of o-acetamidobenzenesulphonyl fluoride suggests neighbouring-group catalysis by the acetamido-group (Scheme 33).16' The reactions of benzenesulphonyl chloride Me Me I I Scheme 33 with aniline azide imidazole and fluoride lead to stable product^.'^^^^^^ The hydrolysis reaction is catalysed by other nucleophiles such as pyridine and acetate and is considered to proceed via a similar nucleophilic catalysis mechanism although no evidence of intermediates was obtained.A comparison of Brransted slopes for nucleophilic attack by amines at saturated carbon sulphonyl sulphur and carbonyl carbon indicates that sulphonyl sulphur is midway in hardness (in the sense of hard and soft acids and bases) between the other two centres. The hydrolysis of aryl or-disulphones in aqueous dioxan is catalysed by added nucleophiles such as F-or AcO- via a nucleophilic catalysis mechanism (Scheme HzoP' ArS0,H + H++ Nu-Scheme 34 16' R.M. Laird and M. J. Spence J. Chem. SOC.(B) 1970 388. 164 M. D. Thomas and B. J. Tighe J. Chem. SOC.(B) 1970 1039. 165 D. J. Fenn M. D. Thomas and B. J. Tighe J. Chem. SOC.(B) 1970 1044. 166 B. W. Evans D. J. Fenn and B. J. Tighe J. Chem. SOC.(B) 1970 1049. 167 M. E. Aberlin and C. A. Bunton J. Org. Chem. 1970 35 1825. 168 0.Rogne J. Chem. SOC.(B) 1970 727. 169 0. Rogne J. Chem. SOC.(B) 1970 1056. Reaction Mechanisms-Part (i) 89 34). 70 With primary and secondary amines the intermediate (44)formed does not react further and can be isolated. Kice and Kasperek have now shown that the major effect of added tertiary amines on the hydrolysis of disulphones arises from general-base catalysis (Scheme 35) -nucleophilic catalysis being reduced to a minimum because of steric hindran~e.'~' The effect of the basicity of entering 00 0 I1 II Et3N + H-0 + Ar-S-S-ArII -+Et3NH+ + Ar.S-OH + ArS02-II II II HI 00 0 Scheme 35 and leaving groups on nucleophilic substitution at bivalent sulphur in p-substi- tuted phenyl sulphenate esters favours a loose S,2 transition state in which bond- breaking is far more advanced than bond-formation.' 72 The base-catalysed hydrolysis of some 2-nitrobenzenesulphenate esters has also been studied.'73 + Ph-S-S-Ph + H+ Ph-S-S-Ph II I l80 180H + k* 18 NU-+ Ph-S-S-Ph GPh.S*Nu+ Ph.S.OH 1 k-2 "OH Ph?3.1sOH + H+ + Nu-kSPhSNu + H2180 Ph.S.Nu + Ph-SOH kif Nu-+ Ph-S-6-Ph I 11 OH NU-+ Ph-S-S-Ph + H+ II 0 (NU= Bu",S) Scheme 36 The mechanisms of oxygen exchange reactions of sulphoxides have been reviewed.'74 The acid- and nucleophile-catalysed oxygen-exchange of phenyl benzenethiolsulphinate proceeds in a multi-stage process (Scheme 36).The fact that benzenesulphenic acid is more than lo5times more reactive as a nucleo- + phile towards Ph-S-S-Bun than is water (i.e. k-,/k- > 10') provides an explanation of why thiolsulphinates are usually the first isolable products of the hydrolysis of reactive sulphenyl derivatives in water."' As soon as any benzene- 170 J. L. Kice G. J. Kasparet and D. Patterson J. Amer. Chem. SOC.,1969,91 5516. 17' J. L. Kice and G. J. Kasparet J. Amer. Chem. SOC.,1970 92 3393.L. Senatore E. Ciuffarin and A. Fava J. Amer. Chem. SOC.,1970,92 3035. D. R. Hogg and P. W. Vipond J. Chem. SOC.(B) 1970 1242. 174 S. Oae Quart. Reports Sulfur Chem. 1970,5 53. J. L. Kice and J. P. Cleveland J. Amer. Chem. SOC.,1970 92 4757. 90 J. G.Tillett sulphenic acid is formed by hydrolysis of PhSNu it reacts with some of the remaining PhSNu faster than the latter hydrolyses. The nucleophile-catalysed racemisation of 2-methylsulphinyl benzoic acid has also been examined.' 76 The hydrolysis reactions of nitrate esters have also been covered in a recent review.'77 3 Electrophilic Aromatic Substitution Several MO studies of substitution effects on aromatic substitution have been reported.' 78-1 81 Reviews of the r81e of n-complexes as reaction intermediatesand of the effect of substituents on n-electron systems have been published by Ban- thorpe' 82 and by Katritzky and Topsom,' 83 respectively.Whereas the nitrations of many aromatic compounds by anhydrous nitric acid in carbon tetrachloride are zeroth-order in aromatic substrate the nitration reactions of mesitylene and p-xylene are sixth-order in nitric acid and the reaction rate has a negative temperature ~0efficient.l~~ The high order in nitric acid is attributed to the r81e of nitric acid as a solvating agent in non-polar media. The rates of nitration in sulphuric acid and perchloric acid of polyhalogenobenzenes deviate considerably from the additivity principle and have been discussed in terms of MO theory and a simple electrostatic t~eatment.'~' The distribution of products in the nitration of substituted benzo[b]thiophen derivatives has been st~died.'~~,'~' The high percentage of dinitrobibenzyl found in the nitronium tetrafluoroborate nitration of bibenzyl in sulpholan has been shown to arise from reaction occurring during the mixing procedure.'88 Ridd and his group have also shown that one of the consequences of such behaviour is that competi- tive nitration of similar aromatic substrates under these conditions should give apparent relative reactivities near unity and does not therefore provide a proper measure of the selectivity of the nitronium ion towards different substrates.3-Hydroxy- and 3-methoxy-pyridine undergo nitration through their conjugate acids at the 2-position whereas nitration of reactive pyridones proceeds through the free base form.'89 Furthermore the latter substrates react at or near the encounter rate under the conditions used.S. Allenmark and C. E. Hagberg Acra Chrm. Scund. 1970 24 2225. N. W. Connon Eastman Org. Chem. Bull. (Eastman Kodak Co.) 1970,42 No. 2. A. Streitwieser P. C. Mowery R. G. Jesaitis and A. Lewis J. Amer. Chem. SOC., 1970 92 6529. 179 G. R.Howe Chem. Comm. 1970 868. 0. Chalvet R. Daudel and T. F. McKelIop Tetrahedron 1970 26 349. W. T. Dixon J. Chem. SOC.(B) 1970 612. IR2D.V. Banthorpe Chem. Rev. 1970 70 295. A. R. Katritzky and R. D. Topsom Angew. Chem. Internrij. Edn. 1970. 9 87. IB4 T. G. Bonner R. A. Jancock F. R. Rolle and G. Yousif J.Chem. SOC.(B) 1970,314. lE5R. G. Coombes D. H. G. Grant J. G. Hoggett R. B. Moodie and K. Schofield J. Chem. SOC.(B) 1970 347. J. Cooper D. F. Ewing R. M. Scrowston and R. Westwood J. Chem. SOC.(0,1970 1949. 187 G. C. Brophy S. Sternhall N. M. Brown I. Brown K. I. Armstrong. and M. Marten- Smith J. Chem. SOC.(C),1970,933. P. F. Christy J. H. Ridd and N. D. Stears J. Chem. SOC.(B) 1970 797. A. R. Katritzky H. 0.Tarhan and S. Tarhan J. Chem. SOC.(B) 1970 114. Reaction Mechanisms-Part (i) Primary deuterium isotope effects for the nitrosation of a number of aromatic and hetero-aromatic compounds confirm that the rate-determining step involves decomposition of the Wheland intermediate (45) (Scheme 37).I9O N-Nitrosation H A NO NO Scheme 37 is known to be the rate-determining step at low acidities in the diazotisation of aromatic amines (Scheme 38).Further studies of the chloride-ion-catalysed ArNH -+Ar.NH.NO -+ ArN=N.OH 1 Ar'N Scheme 38 diazotisation of toluidines suggest that the initial step approaches closely to a diffusion-controlled proce~s.'~' The kinetics of the diazo-coupling reactions of substituted benzenediazonium chlorides with a~etoacetanilide'~~ and of p- methoxyphenol with sulphanilic acid and p-nitroaniline' 93 have also been investigated. The rates of formation and decomposition of the a-complex intermediate in the diazo-coupling reactions of sulphanilic acid with some 8- substituted-2-naphthols have been determined.Ig4 The Hammett correlation between log k and a,fet,suggests that 8-substituents influence the rate offormation N.Ar N =N-Ar Scheme 39 I9O B.C. Challis R. J. Higgins and A. J. Lawson Chem. Comm. 1970 1223. 19' A. Aboul-Seoud and M. Ahmad Bull. SOC. chim. belges. 1970 79 53. 19* V. Machacek J. Panchartek V. Sterba and M. Vecera Coll. Czech. Chem. Comm. 1970 35 844. lg3 I. Dobis J. Panchartek V. Sterba and M. Vecera Coll. Czech. Chem. Comm. 1970,35 1288. F. Snyckers and H. Zollinger Helv. Chim. Acta 1970 53 1294. J. G. Tillett of the intermediate only by their electronic properties and not by their size and it also excludes steric destabilisation of the intermediate (i.e. k- insensitive to steric bulk) (Scheme 39). The steric effect operates mainly on k and the depend- ence of kJk on a newly defined steric parameter suggests an asymmetrically shaped intermediate (47) with the sp3-hydrogen in a pseudo-equatorial position and the electrophile pseudo-axial.In this position steric interactions between the electrophile and the peri-substituent would be minimised. The diazo-coupling of 8-(2’-pyridyl)-2-naphthol provides an interesting example in which intermolec- ular base catalysis is excluded on steric grounds whilst the bulky group itself has a basic nitrogen site conveniently situated for intramolecular base catalysis [see (48)].1g5 It was also concluded that attack of the basic site on the leaving proton (47) (48) occurs before the electrophile swings into the plane of the naphthalene nucleus and that a linear a-complex-hydrogen-base transition state is not a necessary requirement for base catalysis.The additivity principle has been tested for the rates of bromination of mono-and di-methyl naphthalene^."^ The observed partial rate factors correlated better with approximate molecular orbital parameters derived from a transition- state model than from an isolated-molecule approach. The additivity principle has also been used to obtain indirect estimates of the partial rate factor meta to chlorine (fk’)for molecular chlorination in acetic acid by comparison of rates of chlorination of 2-chloroacetanilide with that of acetanilide. 97 Me 1 CH,Br Scheme 40 (49) ly5 F. Snyckers and H. Zollinger Tetrahedron Letters 1970 2759. L96 J. B. Kim C. Chen J.K. Krieger K. R. Judd C. C. Simpson and E. Berliner J. Amer. Chem. SOC.,I970,92,910. 19’ 0.M. H. el Dusouqui M. Hassan and 9. Ibrahim J. Chem. SOC.(B) 1970 2926. Reaction Mechanisms-Park (i) 93 The formation of 9-bromomethyl-2-methylanthracene (49) by bromination of 2,9-dimethylanthracene with bromine in carbon tetrachloride is considered to proceed uia a free-radical mechanism (Scheme 40)."* With rigorous exclusion of both light and oxygen however normal electrophilic substitution occurs and l0-bromo-2,9-dimethylanthracene (50) was formed exclusively (Scheme 41). mMe @Me H Br 1 Me Scheme 41 Bromodeacylation accompanying substitution previously only clearly established in the naphthalene series has now been observed in benzene derivative^.'^^ In the bromination of some 2,6-dialkylphenyl acetates in nitromethane a number of products are obtained (Scheme 42).The chlorination of adamantane by ferric 02CR2 02CR2 OH Br, ~10~1~ 1 0 + ~~11 0 ~ 1 MeNO \ \ \ 0,CR2 OH (R' = Me,Pr'; R2 = Me) Scheme 42 chloride and antimony pentachloride is thought to proceed uia a radical path- way.2oo Earlier reports that electrophilic substitution of 4-hydroxy-3,5,2',6'-tetramethyldiphenyl ether (51) occurs mainly in the 4'-position have been shown to be in Detailed spectroscopic identification of the product shows 19' J. Flood A. D. Mosnaim and D. C. Nonhebel Chem. Comm. 1970 761. 199 P. B. D. de la Mare and B. N. B. Harman Chem. Comm. 1970 156. P. Kovacic and J. H. Chen Chang Chem.Comm. 1970 1460. S. B. Hamilton and H. S. Blanchard J. Org. Chem. 1970,35 3341. 202 S. B. Hamilton and H. S. Blanchard J. Org. Chem. 1970,35 3348. J. G. Tillett it to be (52) (Scheme 43). The absence of the 4-product is attributed to the steric effect of the two methyl groups ortho to the aryl-ether linkage which push the MegMe MeQMe OH OH Br MeoMe I Br2 I 0 + 0 MeOMe ..bMe ring almost perpendicular to the non-bonding orbitals of oxygen and so prevent any conjugative activation of the 4'-position. The reversible bromination of p-bromophenols has also been in~estigated."~Another example of steric hindrance of conjugation of an aromatic ring with oxygen is found in the sulphuryl chloride chlorination of 2,6-disubstituted phenols for which the additivity principle breaks down.204 A study of the bromination and Friedel-Crafts acetylation of thioanisole has also been reported.205 A study of salt effects activation para-meters and isotope effects on electrophilic attack on the thiophen ring confirms that this follows the usual two-stage substitution mechanism.'06 The application of linear free-energy treatments to electrophilic substitution on the thiophen ring207*20' have been reported.and to the bromination of 2-aminopyridine~~~~ The iodination of acenaphthene and fluorene with iodine-paracetic acid gives 5-iodoacenaphthene and 2-iodofluorene. respectively.' lo Although the 2,7-di-iodofluorene could be obtained with excess of the reagents attempts to di-iodinate acenaphthene were unsuccessful.A solution of iodine in 20% oleum can be conveniently used to iodinate aromatic nitro-compounds although it will not replace a hydrogen atom ortho to a nitro-group.'ll The protonation of 9-ethyl-10-methylanthracene (53) in HF or CF3C02H-H,0-BF3 gives a mixture of the ions (54) and (55).212 The small difference in energy between these ions (0.9-1.0kcal mol-') suggests that contrary to conclusions based on calorimetric data there is no large Baker-Nathan effect in alkylarenium-ion formation. The rates of protodetritiation of a large number of polycyclic aromatic hydrocarbons in '03 E. J. O'Bara R. B. Balsley and I. Starer J. Org. Chem. 1970 35 16. '04 R. Bottom J. Chem. SOC.(B) 1970 1770. '"'S. Clementi and P. Linda Tetrahedron 1970 26 2869.206 A. R. Butler and J. B. Hendry J. Chem. SOC.(B) 1970 170. '07 A. R. Butler and J. B. Hendry J. Chem. SOC.(B) 1970 848. '08 S. Clementi P. Linda and G. Marino J. Chem. SOC.(B) 1970 1153. 'OY P. J. Brignell P. E. Jones and A. R. Katritzky J. Chem. SOC.(B) 1970 117. ''" Y.Ogata and I. Uraseki J. Chem. SOC.(C) 1970 1689. '" J. Arotsky R. Butler and A. C. Darby,J. Chem. Sac. (0,1970 1480. '" D. M. Brouwer and J. A. Van Doorn Rec. Trau. chim.,1970 89 88. Reaction Mechanisms-Part (i) CF,CO,H-HCIO and in CF,CO,H-CCl have been determined. ’ The rela- tive order of reactivity towards detritiation of the five non-equivalent positions in fluoranthene has been determined (3 > 8 > 1 > 7 > 2) and the results have been correlated with various theoretical reactivity parameter^.^'^ The acid- catalysed hydrogen exchange of phenalone is initiated by nucleophilic attack on its conjugate acid by a water molecule (Scheme 44).’15 A re-investigation of the D Scheme 44 acid-catalysed detritiation of 1,3,5-trirnethoxyben~ene[2-~H] confirms the earlier value of a(0-56 & 0.03).,’‘ Correlations based on subsets of data however give rise to values ranging from 0-56-0.71 and suggest that the extent of proton trans- fer in the transition state may be a function of the type of catalyst (see also refer- ence 27).Protodetritiation studies of 2-and 3-tritiothiophen confirm that the mechanism of hydrogen-exchange in thiophen is similar to that in benzene com- pounds.” ’ Substituent effects on the para-substituted benzoylation of benzene in non- polar solvents such as ethylene chloride or tetrachloroethane correlate with the ’I3 A.Streitwieser,A. Lewis I. Schwager R. W. Fish and S. Labonn J. Amer. Chem. SOC. 1970,92,6525. ’I4 K. C. C. Bancroft and G. R. Howe J. Chem. SUC.(B),1970 1541. 2L5 A. A. El-Anani C. C. Greig and C. D. Johnson Chem. Cornm. 1970 1024. A. J. Kresge S. Slae and D. W. Taylor J. Amer. Chem. SOC.,1970,92,6309. *I7 A. R. Butler and J. B. Hendry J. Chem. SOC.(B) 1970 852. 96 J. G. Tillett Hammett equation whereas in nitrobenzene the correlation breaks down prob- ably as a result of complex formation between aluminium chloride and nitro- benzene.218 The relative reactivities of a variety of acylating agents towards benzene and mesitylene2 l9 and the reaction of acetic anhydride with 2-benzyl- pyridine and 2- and 4-picoline N-oxides have been studied.22o The Kostanecki- Robinson acylation reaction involves the formation of trans-enol esters as inter- mediates which subsequently cyclise to 4-~yrones.~~'-~~~ Olah and his co- workers have published a preliminary report of their studies on the titanium tetrachloride-catalysed benzylation of benzene and toluene with substituted benzyl chlorides which provides evidence that the position of the transition state in electrophilic substitution can be changed from a late one resembling the Wheland intermediate to an early one resembling the reactants by changing the electrophilicity of the reagent (by change of substituent in the reagent A photochemical counterpart of the Friedel-Crafts reaction has also been reported.22 The toluene-p-sulphonylationof halogenobenzenes occurs ex-clusively at para-positions but with toluene 13 % ortho- and 86.6 % para-isomers were obtained.226 The data so far obtained for arylsulphonoxylation of aromatic compounds are consistent with an ionic electrophilic substitution mechan- ism.227,228 This reagent provides an alternative to the Friedel-Crafts route for the synthesis of phenols.Further studies of the oxidation of dimethoxybenzenes with lead tetra-acetate show that whereas plumbylation is a typical electrophilic substitution acetoxylation is abnormal.229 4 Substituent Effects and Linear Free-energy Relationships This year many reports of correlations of substituent effects with linear free-energy relationships are included in other sections and are not repeated here.Substituent constants have been reported for a number of groups including the pentafluoro- ~henyl,~~' b~ta-l,3-diynyl,~~~ 3,5-dichlor0-4-cyanophenyl,~~ difluoroamino-alkyl and gern-bis(difluoroamino)alky1,233and 2-and 3-thien~l~~~ groups. Substituent effects in the trifluoroacetylation of substituted thiophens furans and 218 I. Hashimoto T. Nojiri and Y. Ogata Tetrahedron 1970 26 4603. P. H. Gore J. A. Hoskins and S. Thorburn J. Chem. SOC.(B) 1970 1343. 220 S. Oae S. Tamagaki T. Negoro and S. Kozuka Tetrahedron 1970 26 4051. 221 T. Szell L. Dozsai M. S. Zarandy and K. Mengharth Tetrahedron 1969 25 715.222 T. Szell K. Kalman M. S. Zarandy and A. Erdohelyi Helv. Chim. Acta 1969 52 2636. 223 T. Szell Gy. Schobel and L. Balaspiri Tetrahedron 1969 25 707. 224 G. A. Olah M. Tashiro and S. Kobayashi J. Amer. Chem. SOC.,1970,92 6369. 225 D. Bryce-Smith R. Deshpande A. Gilbert and J. Grzonka Chem. Comm. 1970 561. 12' M. Kobayashi H. Minato and Y. Kohara Buff. Chem. SOC. Japan 1970,43 234. 22' R. L. Dannley and G. E. Corbett J. Org. Chem. 1970,35 153. 228 R. L. Dannley J. E. Gagen and 0.J. Stewart J. Org. Chem. 1970 35 3076. 2zy R. 0.C. Norman and C. B. Thomas J. Chem. SOC.(B) 1970,421. 230 W. A. Sheppard J. Amer. Chem. SOC.,1970,92 5419. 23' P. G. Gassman and A. F. Fentiman Tetrahedron Letters 1970 1021. 232 C. Eaborn A. R. Thompson and D.R. M. Walton J. Chem. SOC.(B) 1970,357. 233 K. Baum J. Org. Chem. 1970 35 1203. 234 F. Fringuelli G. Marino and A. Taticchi J. Chem. SOC.(B) 1970 1595. Reaction Mechanisms-Part (i) 97 pyr~les~~~ and the temperature dependence of the Hammett reaction constant p for the hydrogen-exchange reactions of various substituted NN-dimethylani- lines2 have also been investigated. Linear free-energy relationships have also been used to correlate the bromination of ~tilbenes,~~' the half-wave potentials of substituted N-aroyl-N'-phenyl di-imides and N-benzoyl-N'-aryl di-imide~,~~~ and the ethanolysis of l,l'-thio~arbonyl-bis-pyrazoles.~~~ Bowden and his co-workers have reported further studies on 8-substituted 1-naphthoic acids and cis-and trans-ortho-substituted cinnamic acids which con- firm earlier observation of reversed dipolar substituent effects in these systems.240 A mathematical model for the direct field electrostatic effect has also been re- ported.241 Good linear free-energy correlations observed in the cleavage of X.C,H,.(C-C),GeRt compounds by aqueous mathanolic perchloric acid between the effects of substituents X in these reactions and those involving the compounds with n = 1 and 0 suggest that the balance between inductive and resonance effects of the systems remain constant despite the varying distance between the substituent and the reaction 5 Nucleophilic Aromatic Substitution The nature of intermediates in nucleophilic aromatic substitution reactions continues to attract interest.Strauss has given a comprehensive and up-to-date account of this rapidly moving The reaction of 1,3,5-trinitrobenzene with ethylamine and the corresponding ketone leads to the formation of (56).244 + Et,N + NBS -? ozNoNoz + (n = 3 Of 4) NH + Et,NH.Br-Scheme45 0 +c in the presence of N-bromosuccinimide (NBS) (56) is converted to (57) (Scheme 45)in high yield.245 The 'H n.m.r. spectra observed in solutions containing equal 235 S. Clementi and G. Marino Chem. Comm. 1970 1642. 236 T. E. Biherwolf R. E. Linder and A. C. Ling J. Chem. SOC.(B) 1970 1673. " M. F. Rusasse and J. E. Dubois Tetrahedron Letters 1970 1163. 238 J. T. Larkins H. Evans and J. M. Nicholson Tetrahedron Letters 1970,4159. 239 L. 0. Carlsson and J. Sandstrom Acta Chem.Scand. 1970,24,299. 240 K. Bowden M. J. Price and G. R. Taylor J. Chem. Soc. (B) 1970 1022. 241 K. C. C. Bancroft and G. R. Howe Tetrahedron Letters 1970 2035. 242 C. Eaborn R. Eastmond and D. R. M. Walton J. Chem. SOC.(B) 1970 752. 243 M. J. Strauss Chem. Rev. 1970 70 667. 244 M. I. Foreman R. Foster and M. J. Strauss J. Chem. SOC.(B) 1970 147. 245 A. Regnick and M. J. Strauss Tetrahedron Letters 1970 4439. J. G. Tillett concentrations of 1,2,3,5-tetranitrobenzeneand either sodium ethoxide or sodium hydroxide correspond to structure (58).246 There was no evidence of complex NO2 NO NO (58; R = H or Et) (59) formation between 1,2,4,5-tetranitrobenzeneand hydroxide ion but with ethano- lic ethoxide or dilute aqueous sodium sulphite blue colours probably attributable to (59; Nu = OEt or SO,-) were observed.Substituted picramides (60) on treatment with methanolic potassium methoxide give the complex (61) which on treatment with an equivalent amount of hydrochloric acid forms (62)247(Scheme 46). This provides a further example of a neutral Meisenheimer complex. The (R = CHMeCO.NHMe) (62) Scheme 46 contrasting behaviour of 2-and 4-methoxy-3,5-dinitropyridinein a-complex formation with methoxide ion in DMSO is attributed to differential steric and solvation effects.248 Meisenheimer complexes with alkyl groups co-ordinated to the ring (63)and (64),have now been isolated.249 Other Meisenheimer complexes H Me H Bu a -,. As+Ph . r NMe No NO (63) (64) 246 M.R. Crampton and M. El Ghariani J. Chem. SOC.(B) 1970 391. 247 E. Bergmann N. R. McFarlane and J. J. K. Boulton Chem. Comm. 1970,511. 248 M. E. C. Biffin J. Miller A. G. Moritz and D. P. Paul Austral. J. Chem. 1970,23,957. 249 R. P. Taylor J. Org. Chem. 1970 35 3578. Reaction Mechanisms-Part (i) reported formed from heteroaromatic substrates include the 4-aza-1,l-dimeth- 0xy-2,6-~~’ and 2-aza-l,3-dimethoxy-4,6-dinitrocyclohexadienate2s ’ ions (65) and (66) respectively. Rate and equilibrium constants for the formation and Me0 OMe .I N Me0 N (65) (66) decomposition of 1,l-dimethoxy o-complexes of 2,6-dicyano-4-nitroanisole and 2,4-dicyan0-6-nitroanisole,~and 2,4,5-trinitr~naphthalene~have been re-ported. The formation of the intermediate in the reaction of 2,4-dinitro-l-naph- thy1 ethyl ether with primary aliphatic amines is not base-catalysed but its de- composition involves general-acid catalysis254 (Scheme 47).Three distinct NR-NHR Scheme 47 relaxation times were observed in a temperature-jump study of the reaction of 1,3,5-trinitrobenzene with aliphatic amines in aqueous dio~an.~~ The first of these arises from formation of the conventional Meisenheimer complex ; the second from an oxyhydroxylamine and the third from formation of a Meisen- heimer complex between the substrate and hydroxide ion. The rate-coefficients for complex formation between 1,3,5-trinitrobenzene and hydroxide methoxide and ethoxide ions are in the ratio 1 188 :918.256 As with 2,4,6-trinitroanisole 250 P.Bemporad G. Illurninatti and F. Stegel J. Amer. Chem. SOC.,1969 91 6742. 25’ C. Abbolito C. Iowarone G. Illurninatti. F. Stegel and A. Vazzoler J. Amer. Chem. SOC.,1969 91 6746. 252 E. J. Fendler J. H. Fendler C. E. Griffin and J. W. Larsen J. Org. Chem. 1970 35 3378. 253 E. J. Fendler and J. H. Fendler J. Org. Chem. 1970,35 3378. 254 J. A. Orvik and J. F. Bunnett J. Amer. Chem. SOC.,1970 92 2417. 255 C. F. Bernasconi J. Amer. Chem. SOC.,1970 92 129. 256 C. F. Bernasconi J. Amer. Chem. SOC.,1970,92 4682. 100 J. G.Tillett 1,3-complexesof 1,3,5-trinitrobenzene are formed more rapidly than 1,l-complexes but are thermodynamically less stable. The reaction of anions with 3,5-dinitro- pyridine2” and base catalysis in the reactions of primary and secondary amines with methyl 4-nitrophenyl phosphate,258 and of piperidine with 2,4-dinitrophenyl aryl ethers259 and 4-chloro-3-nitrobenzotrifluoride260 have also been studied.Micellar and electrolyte effects on the reaction of 2,4-dinitrofluorobenzene with amines261.26 2 and on the decomposition of the l,l-dimethoxy-2,4,6-trinitro-cyclohexadienylide and studies of kinetic isotope effect^^^^.'^^ and of primary steric effects266 in nucleophilic aromatic substitution have been re-ported. The reaction of o-and p-fluoronitrobenzenes with sulphite ions involves Ph \CH-CN + oN02 NaNH, -Ph-C 0NO, / R CN Scheme 48 a transition state which closely resembles the reactant^.'^' The direct nucleo- philic replacement of a hydrogen atom in nitrobenzene has also been reportedz68 (Scheme 48).The photoreactions of some methoxynitro- dimethoxynitro- and dinitronaphthalenes in alkaline solution269 and the reaction of o-dinitrobenzene with triethyl phosphite and diethyl methylpho~phonite~’~ have been described. 257 R. Schaal F. Terrier J. C. Halle and A. P. Chatrousse Tetrahedron Letters 1970 1393. 258 A. J. Kirby and M. Yournas J. Chem. SOC. (B) 1970 1187. 259 J. F. Bunnett and C. F. Bernasconi J. Org. Chem. 1970 35 70. 260 F. Pietra and F. D. Cima Tetrahedron Letters 1970 1041. 261 C. A. Bunton and L. Robinson J. Org. Chem. 1970,35,733. 262 C. A. Bunton and L. Robinson J. Amer. Chem. SOC. 1970 92 356. 26’ E. J. Fendler and J. H. Fendler Chem. Comm. 1970 816. 264 P. Beltrame M.G. Cattania G. Massolo and M. Sumonetto J. Chem. SOC.(B) 1970 453. 265 G. Ayrey and W. A. Wylie J. Chem. SOC. (B) 1970 738. 266 F. Pietra D. Vitali F. Del Cima and G. Cardinali J. Chem. SOC. (B),1970 1659. 267 C. W. L. Bevan A. J. Foley J. Hirst and W. 0.Vivamu J. Chem. SOC.(B) 1970 794. 268 M. Makosza and M. Jawdosiuk Chem. Cornm. 1970 648. 269 G. M. Van Henegoniven and E. Havinga Rec. Trau. chim. 1970,89 907. 270 J. I. G. Cadogan and D. T. Eastlick J. Chem. SOC.(B) 1970 1314.

ISSN:0069-3030    

DOI:10.1039/OC9706700063

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

3 Reaction Mechanisms Part ( ii) By N. S. ISAACS Chemistry Department The University Reading Carbonium Ions and Solvolytic Reactions.-New aromatic carbonium ions reported include the cyclopropenium ion (1 a) stabilised by alkyl substitution (Me > Pr" > Pr' > Bu').' The trimethylcyclopropenium ion (lb) is one of the most stable hydrocarbon cations known.2 The tetraphenylcyclobutadiene dication (21 stable in highly acidic media has substantial charge delocalisation as shown from I3C n.m.r. measurements which also confirm its ~ymrnetry.~ .928 0.928 RAR (1) (a) R = H (b) R = Me Two bridged bishomotropylium ions (3) and (4) have been reported the presence of a diamagnetic ring-current being evident from the 'H n.m.r. A bridged [lllannulene cation (5) a 10n aromatic system has also been pre- pared.7 The perchlorotrityl cation is extremely stable,* as also are the corre- sponding radical and anion ;chirality in a number of difluoromethyl-substituted ' R.Breslow and J. T. Groves J. Amer. Chem. SOC.,1970,92 984 988. ' J. Ciabattoni and E. C. Nathan Tetrahedron Letters 1969,4997. G. A. Olah and G. D. Mateescu J. Amer. Chem. SOC.,1970,92 1430. ' G. Schroder U. Prange N. S. Bowman and J. F. M. Oth Tetrahedron Letters 1970 3251. M. Roberts H. Hamberger and S. Winstein J. Amer. Chem. Soc. 1970,92 6347. P. Ahlberg D. L. Harris and S. Winstein J. Amer. Chem. SOC.,1970,92 2146. ' E. Vogel R. Feldmann and H. Duwel Tetrahedron Letters 1970 1941. M. Ballester J. Rieva-Figueros and A.Rodriguez-Siurana Tetrahedron Letters 1970 3615. 102 N. S. Isaacs trityl cations has been demonstrated by the temperature-dependence of the 19F n.m.r. ~pectra.~ The doublet spectrum of (6)at room temperature becomes an octet at -71 "Cas rotation is quenched AFS = 48.5 kJmol-' for racemiza- tion. Heats of protonation of 1,l-diarylethylenes show a dependence on CT' (p = 4.59) as do those of benzophenones (p = 6-75) both indicating the import- ance of conjugation in the stabilisation of the cations (7)." The benzenonium ion (8) which at -80 "Cis characterised by a single n.m.r. line at t 1.91 undergoes a degenerate rearrangement which is arrested below -110"C where a more complex spectrum appears.' Protonation of the aceheptylene system (9) occurs under kinetic control at -15 "C at position 2 but at positions 4 and 6 at room temperature under thermodynamic control.l2 The results require a crossing of the two potential-energy pathways predicted as allowed for non- alternant (but not for alternant) hydrocarbons.' The protonation of 9-ethyl- 10-methylanthracene forms almost equal proportions of 9-H and 1 O-H isomers indicating the lack of importance of the Baker-Nathan effect in stabilising the ions.14 A considerable Baker-Nathan effect is reported to be operating in the protonation of P-diketones (lo).' The isomeric 1- and 4-phenylbenzenonium ions are in equilibrium (20:80 % respectively at 0 "C)in superacid solution. l6 J. W. Rakshys S. V. McKenly and H. H. Freedman J. Amer.Chem. Soc. 1970 92 3518. lo E. M. Arnett J. V. Carter and P. P. Quirk J. Amer. Chem. Soc. 1970 92 1771. 'I G. A. Olah R. H. Schlosberg D. P. Kelly and G. D. Mateescu J. Amer. Chem. Soc. 1970,92 2546. lZ E. Hasselbach Tetrahedron Letters 1970 1543. l3 R. D. Brown Quart. Rev. 1952 6 63. l4 D. M. Brouwer and J. A. Van Doorn Rec. Trav. chim. 1970 89 88. J. W. Larsen J. Amer. Chem. Soc. 1970 92 5136. l6 V. A. Koptyug and L. Mozulenko Zhur. obshchei. Khim. 1970,40 102. Reaction Mechanisms-Part (ii) Complex rearrangements of the bicyclo-[2,2,2]- and -[3,2,1]-octyl cations in SbF,-HS0,F lead ultimately to the bicyclo[3,3,0]oct-l-yl cation (1 l) the most stable isomer." The isomeric pentamethylcyclopentenyl cations (12) and (13) OH OH R vR ?-+R R H+ Me Me +-+ -H Me H Me H MeH (12) (13) have been separately observed and their degenerate rearrangements studied by n.m.r.spectroscopy.' Activation parameters for rotation about the partial double bonds in ally1 cations have been measured (Scheme 1) and shown not to be due to prototropy :19 the substituted cyclopropylmethyl cation (14) has the E 73 100 kJ mol-' 65.8 logA 11.8 14.0 Scheme 1 conformation with two non-equivalent methyl groups. The rates of reaction of a series of carbonium ions with carbon monoxide (R+ + CO+ RCO') have been proposed as measures of carbonium ion stability ;while measurements have been carried out at various temperatures the rates span a range of 108 so should be highly sensitive to the stability of the ion R+.20 Cyclic halonium ions are well-established species which can exist as stable entities in superacid media ; the methylene derivatives (1 5) have recently been characterised,2' and a series of dimethylhalonium hexafluoroantimonates (1 6) have been isolated G.A. Olah S. M. Bollinger and D. P. Kelly J. Amer. Chem. Suc. 1970 92 1432. D. M. Brouwer and J. A. Van Doorn Rec. Trav. chim. 1970,89 333. l9 N. C. Deno R. C. Haddon and E. N. Nowak J. Amer. Chem. SOC. 1970,92,6691. 'O H. Hogeveen and C. J. Gaasbeek Rec. Trav. chim. 1970,89 395. J. M. Bollinger J. M. Brinich and G. A. Olah J. Amer. Chem. Suc. 1970,92 4025. 104 N. S. Isaacs as crystalline compounds stable at room temperat~re.~~?~~ 3C n.m.r. indicates increasing positive charge on carbon for the series (16 ha1 = C1 > Br > I); even such weak nucleophiles as ethers displace halide from these compounds.+ Me,O Hb &Me Cf\CH2 Me-hal-Me -+ Me,O+ + Mehal Me H (16) X = C1 Br I (141 (15) Evidence for protonated cyclopropane intermediates has come from several studies ; the rearrangements of many butyl pentyl and hexyl cations in tritiated superacid demonstrate the exchange of a single proton with solvent (Scheme 2).24 Complete carbon scrambling occurs in the rearrangement of the Scheme2 1-propyl cation via (17) in the presence of AlC1 and ZnClz.25-27 Several new degenerate rearrangements of cations have received intensive study. The bicyclo- nonatrienyl cation (18) does not behave as if especially destabilised’* (although classed as anti-bicycloaromatic by Goldstein”) but can pass by a facile route to the 9-barbaralyl cation (19).This species which has been observed directly exhibits a single n.m.r. resonance even at -125 “C due to its rapid degenerate 22 G. A. Olah and J. R. DeMember J. Amer. Chem. SOC.,1970,92,2562. 23 G. A. Olah and J. R. DeMember J. Amer. Chem. SOC.,1970,92,718. 24 G. M. Kramer J. Amer. Chem. SOC.,1970,92,4344. 25 C. C. Lee and D. J. Woodcock J. Amer. Chem. Soc. 1970,92 5991. 26 G. J. Karabatsos C. Ziondron and S. Meyerson J. Amer. Chem. SOC. 1970 92 5996. 21 G. J. Karabatsos C. E. Orzech J. L. Fry and S. Meyerson J.Amer. Chem. SOC.,1970 92 606 614 621. 28 J. B. Grutzner and S. Winstein J. Amer.Chem. SOC.,1970 92 3186. 29 M. J. Goldstein J. Amer. Chem. SOC.,1967 89 6357. Reaction Mechanisms-Part (ii) I05 rearrangement through a series of Wagner-Meerwein shifts and Cope rearrange-ment~.~*-~~ The analogous rearrangements in the 9-methylbarbaralyl cation are somewhat slower although they have an activation energy of only 46kJ mol- 1.34 The dissolution of bicyclo[2,2,l]heptane in HF-SbF initially / H H H results in the formation of the methylcyclohexyl cation (20),which in turn forms the 1,2- and 1,3-dimethylcyclopentyl cations each of which undergoes degenerate rearrangements oia 1,2 hydride and methide migrations to form (21).35 Phenyl cations are believed to result from the decomposition of phenyldiazonium ions in dipolar aprotic solvents ; in the presence of aromatic substrates arylation occurs typical of an electrophilic reaction and no deuterium isotope effect is sho~n.~~-~~ 3.8 30 J.C. Barbarak J. Daub D. M. Follweiler and P. von R. Schleyer J. Amer. Chem. SOC. 1969,91 7760. ” J. C. Barbarak and P. von R. Schleyer J. Amer. Chem. SOC.,1970,92 3184. 32 J. B. Grutzner and S. Winstein J. Amer. Chem. SOC.,1970 92 3186. ” P. Ahlberg D. L. Harris and S. Winstein J. Amer. Chem. Soc. 1970,92,4454. 34 P. Ahlberg J. B. Grutzner D. L. Harris and S. Winstein J. Amer. Chem. SOC.,1970 92 3478. ’’ H. Hogeveen and C. J. Gaasbeek Rec. Trau. chim. 1969,88 1305. 36 M. Kabayashi M. Minato E. Yamada and N. Kabori Bull. Chem. SOC.Japan 1970 43 215 219. ” K. Ishida N. Kabori M.Kabayashi and H. Minato Bull. Chem. SOC.Japan 1970 43 285. ” N. Kabori M. Kabayashi and M. Minato Bull. Chem. SOC.Japan 1970,43 223. Recent molecular orbital calculations by the method of Pople indicate that alkyl cations prefer the staggered conformation (22a) to the eclipsed (22b);39 however the opposite is predicted by Clark and Lilley4* for 1-and 2-fluoroethyl cations the more stable conformer in either case being that with hydrogen eclipsed to fluorine (23). Solvolytic Reactions.-The rate-enhancing effect of an a-methyl group has been proposed as a diagnostic test for the limiting behaviour of a substrate in sol- v01ysis.~~The value of the solvolytic rate constant for a secondary substrate is typically times that of the corresponding a-methyl (tertiary) compound.This is not a maximum value but is reduced by rearside solvent interactions. The maximum effect (k,,condary/ktertiary ca. lo-*) is realised in the 2-adamantyl = system (24) in which no rearside approach by solvent is possible.42 The depar- ture from this value can be taken as a measure of the solvation of the transition state. 2-Adamantyl bromide solvolysis has been used as a means of assessing the extent of solvent participation in the ionisation process to produce a solva- tion parameter analogous to Y. The new values correlate well with Y substan-tiating the essentially limiting behaviour of t-butyl chloride on whose solvolyses the Y scale is based. Solvolytic rates of a series of substituted polycyclic aryl- methyl compounds have been measured.43 Plots of relative rates (variation of substituent) versus (a)relative rates in different solvents of benzyl chloride and (b) relative rates with different leaving-groups show slopes which vary more widely in the latter case.It is concluded that the leaving-group has a greater effect upon rate than does the solvent. The rate of solvolysis of trityl chloride (ca. lo31 mol-s-' in aqueous acetonitrile) is subject to special salt effects by 39 L. Radom J. Pople V. Buss and P. von R. Schleyer J. Amer. Chem. SOC.,1970 92 6380. 40 D. T. Clark and D. M. J. Lilley Chem. Comm. 1970,603. 41 J. L. Fry J. M. Harris R. C. Bingham and P. von R. Schleyer J. Amer. Chem. SOC. 1970,92 2540. 42 D. J. Raber R. C. Bingham J. M. Harris J.L. Fry and P. von R. Schleyer J. Amer. Chem. SOC.,1970,92,5977. 43 M. D. Bentley and M. J. S. Dewar J. Amer. Chem. SOC.,1970,92 3991. Reaction Mechanisms-Part (ii) 107 perchlorate due to ion-pair exchange.44 In aqueous ether the rate of hydrolysis is accelerated 7 x 109-fold by added lithium per~hlorate.~' Charge-transfer excitation energies for a series of substituted benzenes with tetracyanoethylene are used as models to describe the stabilisation of the corresponding benzylic cations by substituent groups (with whose solvolytic rates they ~orrelate).~~ Pressure effects on solvolytic rates of t-butyl chloride have been further in- vestigated :47 the activation volume -2 cm3 mol- * in water at 0 "C becomes progressively more negative as the proportion of ethanol in the solvent is in-creased due to increasingly great nucleophilic interactions between solvent and transition state.This behaviour contrasts with that of a number of unimolecular decompositions to neutral products for which AVt = +9-16 cm3 mol- '. tt-Participation.-2-(Cycloheptatrienyl)ethyl esters (25)solvolyse some 16 times more rapidly than cyclopentylethyl analogues (26) regarded as suitable model compounds incapable of n-participation k25/k26 = 16. Some remote parti- cipation is inferred but less than in the case of 3-~yclopentenylethy1(27) for which kunsaturated/ksaturaled = 95. The products (28) however are those from rearranged TosO OTos CH,CH ,OTo s (26) +OH carbonium ions.t8 Little if any participation by phenyl occurs in the rate- determining ionisation of (29) as its rate is slightly less than the syn isomer (30).However phenyl migration occurs presumably subsequent to i~nisation.~~ Some (Ar-5)-participation is claimed to occur in the solvolysis of (31) since abnormally high rates were obtained for X = Me or OMe.50 Cyclopropane migration occurs in solvolysis of (32) probably assisting the ionisation which occurs at a rapid rate for a primary compound;" the participation of the cyclo- propane ring is stereospecifi~'~ in the ring-expansion reactions (33) -+ (34) and 44 K. T. Leffek Canad. J. Chem. 1970,48 1. 45 Y. Pocker and R. F. Buchholz J. Amer. Chem. SOC.,1970,92 2075. 46 W. Hanstein H. J. Berwin and T. G. Traylor J. Amer.Chem. Sac. 1970 92 829. 47 B. T. Baliga and E. Whalley Canad. J. Chern. 1970 48 528. 48 G. D. Sargent and T. E. McLoughlin Tetrahedron Letters 1970 4359. 49 J. W. Wilt and T. P. Malley J. Amer. Chem. Sac. 1970 92 4747. 5" R. J. Ouellette R. Papa M. Attea and C. Levin J. Amer. Chem. Sac. 1970 92 4893. 51 Y. E. Rhodes and T. Takino J. Amer. Chem. Sac. 1970,92 5270. 52 C. D. Poulter and S. Winstein J. Amer. Chem. SOC.,1970,92 4282. 108 N. S. Isaacs TosO (30) (35) -+(36) (the major product in either case being ~nrearranged).~~ Calcula-tions show that the substituted cyclopropylmethyl cation prefers the conforma- tion (37)rather than (38) and this has been confirmed by n.m.r. studies ;rotation Hg+ AcOH (p -CoAc X X (31) (32) 35% 40% 21 % about the central bond has a surprisingly high activation barrier E = 57.6 kJ mol-This explains the lack of cyclopropyl participation in the rigid bB (33) H (34) OH OPNB 53 C.D. Poulter E. C. Friedrich and S. Winstein J. Amer. Chem. SOC.,1970,92 4274. D. S. Kabakoff and E. Namanworth J. Amer. Chem. SOC., 1970,92 3234. Reaction Mechanisms-Part (ii) system (39),’ whereas in the open 2-cyclopropylethyl esters (40) participation by the three-membered ring is indicated by the large contribution to the rate due 4” H C+-Me / Me4 Me Me (37) (38) to methyl substitution which should make the ring more nucleophilic but could have no purely inductive effect.’ Very marked cyclopropyl acceleration is found in the norbornadiene analogue (41) 1010-10’2 times more reactive than norbornyl p-nitrobenzoate and which leads to a degenerate ion (42) ;57 likewise in ,OPNB OPNB -P (43).’ High-pressure kinetic studies have shown that activation volumes for soholytic reactions of -15 to -20 cm3 mol- ’ are typical for limiting solvolyses probably associated with solvent electrostriction.Much less negative values typify reactions which involve neighbouring groups ;” solvolysisof 2-b-hydroxy-pheny1)ethyl chloride has V = -1 cm3 mol- ’ which may prove a useful diagnostic test. CI-and fi-secondary deuterium isotope effects in solvolysis of 3-phenylbut-2-yl tosylate (44) are not quite equal (1.104 1.097) from which it ’’ B. R. Ree and J. C. Martin J. Amer. Chem.Soc. 1970,92 1660. 56 M. J. S. Dewar and J. M. Harris J. Amer. Chem. SOC.,1970 92 6557. 57 ’’ R. M. Coates and J. L. Kirkpatrick J. Amer. Chem. SOC.,1970 92,4883. M. A.Battiste J. Haywood-Farmer H. Malkins P. Seidl and S. Winstein J. Amer. Chem. Soc. 1970,92,2145. 59 W. J. LeNoble and B. Gabrielson Tetrahedron Letters 1970 45. 110 N. S. Isaacs appears that the transition state for solvolysis is slightly unsymmetrical (though a symmetrical phenonium ion may later form).6o Two mechanistic pathways are inferred in the acetolysis of this compound which could also explain the inequality of the isotope effects. The total rate has been partitioned into assisted (Fk,) and solvent-displacement (&,) components the former giving only reten- tion of configuration.61 The component k is independent of substituents in the aromatic ring while Fk increases with the conjugative ability of the ring.62,63 Ph k 1 YCSH CH,-CH-CH-CH, I OTos (44) Co-ordination of a metal to a n-system can reduce its ability to participate in a solvolytic reaction e.g.compare (45) p = -0.78 and the non-metallated Cr(W3 (45) analogue p = -2.35.64 Iron co-ordination confers retention of configuration on the solvolysis of (46).65 Alicyclic Systems.-Solvolyses of 2-adamantyl compounds (24a) promise to be useful as a mechanistic probe. Rates are moderately fast but the rigid skeleton excludes nucleophilic attack and solvation from the rear side of the reaction centre. The 2-adamantyl system has been proposed as a model having limiting behaviour since it reacts by an unassisted pathway (&,).66 Since this pathway should be independent of solvent the ratio k, [where x refers to a second (ester) substrate] is a measure of the difference in unassisted solvolysis rates 6U S.L. Loukas M. R. Velkon and G. A. Gregoriou Chem. Comm. 1970,251. 61 S. L. Loukas M. R. Velkon and G. A. Gregoriou Chem. Comm. 1969 1199. 62 H. C. Brown C. J. Kim C. J. Lancelot and P. von R. Schleyer J. Amer. Chem. SOC. 1970,92 5244. 63 M. D. Bentley and M. J. S. Dewar J. Amer. Chem. SOC.,1970,92 3996. 64 R. S. Bly R. C. Strickland R. T. Swindell and R. L. Veazey J. Amer. Chem. SOC. 1970 92 3722. 65 N. A. Clinton and C. P. Lillya J. Amer. Chem. SOC.,1970 92 3065.66 P. von R. Schleyer J. L. Fry L. K. M. Lam and C. J. Lancelot J. Amer. Chem. SOC. 1970,92 2542. Reaction Mechanisms-Part (ii) 111 between the second substrate and the 2-adamantyl ester. Thus the value of the rate ratio k (2-propy1):k (2-adamantyl) increases from 10-2'25 in trifluoroacetic acid to lO+ 3'0 in ethanol as nucleophilic participation becomes increasingly important for the 2-propyl substrate. The former value is taken as a provisional limit to the ratio and therefore the (minimum) amount of solvent assistance to the reaction is the difference between 10-2.2sand the appropriate rate ratio. This therefore amounts to 105'5 for ethanolysis of isopropyl tosylate. This approach is substantiated by an examination of the effects of added azide ion on the reaction :67 several related studies in this series have been rep~rted.~*-~' Limiting conditions apparently prevail in the solvolysis of cyclopentyl bromide by aqueous ethanol to judge from the typical isotope effects observed; kH:kDtcis-z,= 1.1533 kH:kDct,ans-2) = 1.1803 kH:kD,, = ~1869.~'Even larger values of isotope effects are found in the solvolysis of 2,4-dimethyl-3-pentyl brosylate (47) suggesting that some H-participation is This would OBros (47) accord with the products even the 3-pentyl (48) system yields a small amount of 2-pentyl products on ~olvolysis.~~ Extensive hydride shifts in the bicyclo- H + -+MeCHCH,CH,Me Me AH/CH2\ dr Me (1 %) (48) '' J.M. Harris D. J. Raber R. E. Hall and P. von R.Schleyer J. Amer. Chem. Soc. 1970 92 5729. 68 J. L. Fry C. J. Lancelot L. K. M. Lam J. M. Harris R. C. Bingham D. J. Raber R. E. Hail and P. von R. Schleyer J. Amer. Chem. SOC.,1970,92,2538. '' J. A. Bone and M. C. Whiting Chem. Comm. 1970 115. 'O L. Baiocchi M. Gianangeli and G.Palazzo Tetrahedron Letters 1970,5025. 71 J. 0. Stoffer and J. C. Christen J. Amer. Chem. SOC.,1970 92 3190. '' V. J. Shiner and J. 0.Stoffer J. Amer. Chem. SOC.,1970,92 3191. 73 H. R. Hudson and D. Ragoonanan J. Chem. SOC.(B),1970 1755. 112 N. S. Isaacs [3,3,2]decyl cation (49) originate from a remote carbon atom.74 A remote double bond in the cyclo-octane series (50) causes a rate retardation in solvolysis com- pared to the saturated analogue (51).75 Presumably n-participation is absent or OoBrOs OOBros OOBros OOBros OBros OBros (51)kre 1700 (50)39 (53)cis 1 cis (52)0.058 trans 4.1 trans 0.65 if it occurs is less effective than transannular hydrogen participation.The effect is somewhat smaller in the diesters (52)and (53). Isomeric cations from the solvo-lysis of cis-and trans-9-decalyl chlorides are known and differ in energy by 6 kJ mol-' similarly isomeric hydrindyl cations (54) have been identified &-+ + o._l"' H H (54) though differing in energy by only 17 kJ mol-1.76 A case of alkyl participation in the steroid series has been investigated i.e.(55)-(56).77Remote n-participa- XCH OH XCHz (55) (56) tion in bicyclic compounds is a potentially useful method for the synthesis of complex ring structures e.g.(57)+(58).78 74 M. P. Doyle and W. Parker Chem. Comm. 1970 755. 7s W. D. Closson J. L. Jernow and D. Grey Tetrahedron Letters 1970 1141. 76 K. Becker A. F. Boschung and C. A. Grob Tetrahedron Letters 1970 3831. l7 J. G. L. Jones and B. A. Marples Chem. Comm. 1970 126. D. J. Raber G.J. Kane and P. von R. Schleyer Tetrahedron Letters 1970 41 17. Reaction Mechanisms-Part (ii) Aliphatic Systems-Secondary deuterium isotope effects have been measured for solvolyses of the allylic systems (59) and The y-methyl effect is normal indicating that positive charge is accumulating at the y-carbon. The (60) 1.132 inverse effect for P-methyl substitution indicates that this is not the case at the P-carbon. This is therefore taken to indicate the absence of 1,3-interaction in the ally1 cation which would require a contribution from the structure (61).The preferential migration of CH rather than CD in the pinacolic rearrangement of (62) (k,:k = 1.15-1.20) is indicative of positive charge accumulating at the ,CH3 Ph,C-C-CD I OH AH (62) methyl group in the transition state and therefore of methyl migration occurring in the rate-controlling step." Rates and isotope effects on the solvolyses of ethyl (63) and n-propyl trifluoromethanesulphonates (triflates) have been measured in trifluoroethanol and trifluoroacetic acid conditions favouring the SN1 process as far as possible." Both a-and P-isotope effects [la06 and 1.05 Rates in trifluoroacetic CH3CH20Tf 1.37 x lOP5s-' acid at 50 "c CD3CH20Tf 1.19 x 10-5s-1 (63) per deuterium respectively for (63)] are less than a third the full values expected for a limiting solvolysis and indicate that even under these conditions primary substrates react by a largely bimolecular route (ksj.Solvolyses of a-arylethyl acetates in 30% ethanol evidently occur by an S,1 process since the relative log rates correlate with Q+ (p = -5.7).*' A mechanistic change is inferred for solvolyses of some benzylic sulphonate~.~~ The charge on the benzyl carbon in the appropriate 79 R. H. Griffin and J. G. Jewett J. Amer. Chem. SOC.,1970,92 1104. W. M. Schubert and P. H. LeFevre J. Amer. Chem. SOC., 1970,92,7746. G. A. Dafforn and A. Streitweiser Tetrahedron Letters 1970 3159." E. A. Hill M. L. Gross M. Staseiwicz and M. Manion J. Amer. Chem. SOC.,1969 91 7381. 83 A. Streitweiser H. A. Hammond R. H. Jagow R. M. Williams R. G. Jesaitis J. Chong and R. Wolf J. Amer. Chem. SOC.,1970 92 5141. 6' from the break (or curve) in the Hammett plot against 114 N. S. Isaacs cation calculated by the CNDO method is found to correlate with the observed rates. The rate of solvolysis of di-t-butylcarbinyl chloride (64) would be predicted on steric grounds to be some lo4 times greater than that for isopropyl chloride (65). In fact it is somewhat less reactive although the factors responsible for this discrepancy have not been identified with certainty.84 Intermolecular hydride (65) 94-5 kJ mol-' transfer has been shown to occur between a transient secondary cation and a tertiary hydrogen (Scheme 3).85 The rearrangement of the 2-adamantyl cation Scheme 3 (24a) to the 3-adamantyl(66) is presumed to occur by an intermolecular hydride transfer since the rate is reduced by dilution.86 The generation of carbonium H ions in the absence of nucleophilic species can be achieved by the action of nitrosonium tetrafluoroborate on an alkyl azide (67) :87 Ph2CHN3 + NO+BF,-+Ph,CH+BF,-+N2 +NzO (67) Nucleophilic displacements of p-nitrocumyl and a,p-dinitrocumyl chlorides occur by a radical chain process which is more favourable than the carbonium ion mechanism for these deactivated systems.88 A consequence of this radical- initiated reaction is that the addition of a weak nucleophile may be achieved 84 S.H. Liggero J. J. Harper P. von R. Schleyer A. P. Krapcho and D. E. Horn J. Amer. Chem. SOC.,1970.92 3791. 85 D. N. Kirsonov V. N. Setkina V. A. Kurichev R. V. Kudryavtsev and Yu. Lyakhavek- skii Izvest. Akud. Nuuk. S.S.S.R. Ser. khim 1969 2344. 86 P. von R. Schleyer L. K. M. Lam D. J. Raber J. L. Fry M. A. McKervey J. R. Alford B. D. Cuddy V. G. Keizer H. W. Geluk and J. L. M. A. Schlatmann J. Amer. Chem. SOC.,1970 92 5247. M. P. Doyle and W. Weirenga J. Amer. Chem. SOC.,1970 92 4999. ** N. Kornblum R. T. Swiger G. W. Earl H. W. Pinnick and F. W. Stuckal J. Amer. Chem. SOC.,1970,92 5513. Reaction Mechanisms-Part (ii) in the presence of a catalytic amount of a strong initiating nucleophile. Thus azide ion does not react with the dinitrocumyl chloride alone but in the presence of a trace of the 2-nitroisopropyl anion 97 % of the cumyl azide (68) is formed.Me CH,NO Me CH,NO NO Hydrolysis of the diazoketone (69) is general-acid-catalysed and proceeds via a carbonium iong9 H H I I CH3COC-R 5CH3-CO-C-R -+ CH,CO$-R II I N2 N2 + I products (69) Norbornyl Systems.-The ‘H n.m.r. spectrum of the 2-methyl-7-norbornenyl cation (70) has been cited as evidence of the non-classical formulation of this Me Me 7.58 (70) and by analogy the parent carbonium ion (71).” The 3-H resonance is identified at 7 3.53 which is close to that found in the stable norbornenyl cation (71) (72-93). It is argued that the alternating classical formulation (72 r+ 73) would (72) (73) (74) be expected to exist preponderantly in the tertiary cation form (73) and therefore the resonance of 3-H would be much nearer to the appropriate proton (H,) N9 H.Dahn and M. Ballenegger Helv. Chim.Acta 1969 52 2417. ’O R. K. Lustgarten P. G. Gassmann D. S. Patton M. Brookhart S. Winstein H. G. Richey and J. D. Nichols Tetrahedron Letters 1970 1699. 116 N. S. Isaacs in the substituted cyclopropylmethyl cation (74) (5 7-8). The 7-p-anisylnorborn- enyl cation (75) appears to exist in the classical structure as judged by the con- siderable downfield shift of the aromatic protons and lack of such in the olefinic protons.' The chlorine nuclear quadrupole resonances of the 7-norbornenyl (75) (76) chlorides differ by 860 kHz between the syn- and anti-isomers indicating greater s-character of the C-Cl bond in the former possibly on account of Cl-z orbital repulsion as shown in (76).92 The 2-norbornyl cation has been observed in superacid solution at -154 "C; H 3C n.m.r.and Raman spectra have been interpreted in terms of the corner- protonated nortricyclene structure (77).93 All protons are rapidly interchanging Y H -1,2,6 r 5.00 H-3,5,7 8.14 H -4 7-18 above ca. -50 "C by two processes a 3 +2 hydride shift (EA= 45 kJ mol-') and the 6 +1+2 proton migration which is not slowed sufficiently until -154"C (EA= 5.9 kJ mol-I). By contrast 2-halogenonorbornyl cations have the localised structure (78).94 Carbon scrambling in the 2-norbornenyl cation &) 3.38 3.68 4.5 1.76 F (78) (79) has been re-examined and discrepancies in the results of earlier workers have been largely resolved :95 it appears that the skeletal rearrangements are quite slow and for example in acetic acid-potassium acetate at 45 "C for 1h 33 % of 2,3 +1,4,7 rearrangement takes place in accordance with Roberts et al.91 H. G. Richey J. D. Nichols P. G. Gassmann A. F. Fentiman S. Winstein M. Brook-hart and R. Lustgarten J. Amer. Chem. SOC., 1970,92,3783. 92 H.Chihora. N. Nakamura and T. Irie Bull. Chem. SOC.Japan 1969,42 3034. 93 G.A. Olah A. M. White J. R. DeMember A. Commeyras and C. Y. Liu J. Amer. Chem. SOC.,1970,92,4627. 94 G. A. Olah P. R. Clifford and C. L. Jenell J. Amer. Chem. SOC.,1970,92,5531.95 C. C. Lee and B.-S.Halen J. Amer. Chem. SOC.,1970,92,2583. Reaction Mechanisms-Part (ii) while 11 h at 24 “C yields 48 % rearrangement (as found by Cristol and co-workers). By the addition of acetic and trifluoroacetic acids to norbornene the (79) labelled esters with a greater proportion of D at the 3-exo position (80) than at 7-syn are formed.96 This may indicate either an asymmetry in the carbonium ion formed (due possibly to the presence of the anion) or a secondary isotope effect which possibility is supported by the observed lack of temperature depen- dence of the product ratio.” The generation of the norbornyl cation by the thermolysis of exo-2-norbornyl thiocyanate (81) leads to C-14-2 scrambling by a Wagner-Meerwein shift but not of C-6 with C-1 or C-2 suggesting that these hy- dride shifts are slower.’* An inverse /I-deuterium isotope effect (kH:k = 0,958 at 150“C)seems to indicate that C-2 is not bearing positive charge in the transition state.The 1,2-dimethoxynorbornyl cation is stable in fluorosulphonic acid solution and undergoes a rapid degenerate rearrangement to (82) which is sufficiently slow below 0°C for the individual species to be observed (AGS = 55 kJ mol-I).’’ Rearrangements of several (x)-hydroxy-(x)-phenyl-2-norbornyl cations have been Products from the 3-substituted cation (83) 96 H. C. Brown J. H. Kawakami and K-T. Liu J. Amer. Chem. SOC.,1970,92 5536. ” J. L. Holmes D. McGillivray and N. S. Isaacs unpublished data. ’’ L. A. Spurlock and J. E. Parks J. Amer.Chem. SOC.,1970,92 1279. 99 A. Nickon and Y. Lin J. Amer. Chem. SOC.,1969,91 6861. loo C. J. Collins V. F. Raaen and M. D. Sckert J. Amer. Chem. SOC.,1970 92 1787. lo’ C. J. Collins and B. M. Benjamin J. Amer. Chem. SOC.,Q70 92 3182. lo’ B. M. Benjamin and C. J. Collins J. Amer. Chem. SOC.,1970 92 3183. 118 N. S. Isaacs MeO+ OMe (82) depend upon the geometry of the leaving group and indicate the short lifetime of the cation. a-and P-secondary deuterium isotope effects on norbornyl solvolyses have been measured for (84)-(87). The p-effects are quite small especially for the exo-isomer; the a-effect upon the exo-ester is considered too large to support HONO &OH -ocoph'x NH2 18.5 % 22-1 9.7 HONO 0.4 29.2 37.2 (83) a classical formulation of the cati~n.'~~~'~~ The attachment of a methoxy-group to part of a system which is acting as a nuclophile in a solvolytic reaction x = oso,QBr normally enhances the rate to a considerable extent e.g.(88) (89). The methoxyl probe has been systematically applied to the 1 4,5 6 and 7-positions in both exo- and endo-norbornyl tosylates. Their solvolytic rates are not however enhanced (with the possible exception of 4-OMe which is five times faster than '03 B. L. Murr and J. A. Conkling J. Amer. Chem. SOC.,1970,92 3464. Io4 B. L. Murr and J. A. Conkling J. Amer. Chem. SOC.,1970 92 3462. Reaction Mechanisms-Part (ii) OTos RA CH2-0DNB Ril (88) (89) 1 R=H krel = 1 Me 22 11 OMe 2400 791 4-H) and are otherwise retarded due to the inductive effect of the oxygen.This study therefore gives no support to the delocalisation of charge at C-5,6,7.'05 Solvolysis of 7-norbornyl compounds appears to show the greatest electronic demand of many cyclic analogues to judge from Hammett p-values for the series (90a-f).'06 This demand may be satisfied both by a 7-p-anisyl group or (a) (b) (4 (4 (el (f) -4.48 -4.1 -4.65 -5.64 -4.83 -4.54 (90) a cyclopropane ring (91a-~).'~' A four-membered ring is also capable of stabilising the 7-norbornyl cation (92a-f).'08,'09 A sharp mechanistic change krel 1 1014 3 10'7 (91) occurs on solvolysis of the series (93) at the point at which double-bond participa- tion yields to aryl participation. The break in the Hammett plot comes at X = OMe.For substituents with a smaller value of cr' p = -2.30 and for those with larger p = -5.1 which is identical with the solvolytic behaviour of the corresponding saturated compounds (94).' An unusual rearrangement of a '05 P. von R. Schleyer P. J. Stang and D. J. Raber J. Amer. Chem. Sac. 1970,92,4725. lob H. Tanida and T. Tsushima J. Amer. Chem. SOC.,1970 92 3397. lo' P. G. Gassmann and A. F. Fentiman J. Amer. Chem. SOC.,1970,92 2551. log M. Sakai A. Diaz and S. Winstein J. Amer. Chem. SOC.,1970 92 4452. '09 M. A. Battiste and J. W. Nebzydoski J. Amer. Chem. SOC.,1970 92 4450. P. G. Gassmann and A. F. Fentiman,'J.Amer. Chem. SOC., 1970,92 2549. 120 N. S. Isaacs H OTos e!. 608 000 k,, 1 1-2 20 800 8 (e) X = OTos Y = H; 1.1 (f) X = H Y = OTOS 72 700 (92) five-membered to a four-membered ring occurs in part in the solvolysis of 1-methoxynorbornyl brosylate (95)." Some variants on the norbornyl system (93) (94) have been studied; skeletal rearrangement of (96) is deduced to precede sol-volysis."* Solvolyses of both exo-and endo-(97) appear to be abnormally fast 0 (95) (by factors of 250 and 800 respectively) according to predictions based on the Halford-Schleyer-Foote rule,' l3 though the exo:endo rate ratio is less than (96) 'I1 Y.Lin and A.Nickon J. Amer. Chem. SOC.,1970,92 3496. IL2 R. R. Sauers and B. R. Sickler Tetrahedron Letters 1970 1067. J. 0. Halford J. Chem. Phys. 1956 24 830; C. S. Foote J. Amer. Chem. Soc.1964 86 1853; P.von R. Schleyer ibid. p. 1854 1856. Reaction Mechanisms-Part (ii) one.' l4 Solvolysis of 4-tricyclyl triflate (98) proceeds very slowly (estimated as 2.8 x lo4 times less fast than 2-norbornyl triflate at 295 "C); there is no Tf = -OSOZCF, Gb (97) (98) evidence therefore for participation from the face of the three-membered ring.' I Deltacyclyl esters (99)both exo and endo,solvolyse to produce the exo-deltacyclyl products ;a degenerate rearrangement of the cation may be detected by deuterium -RD-& &oBros = +& D D D (99) 1 scrambling e.g. (99)-(100)."7.'18 An am-analogue of the norbomenyl system (101) solvolyses with loss of nitrogen and an exo:endo ratio of 117."' Small Rings.-Very large end0:exo reactivity ratios have been found in the solvolyses of bicyclo[2,1,0]pentyl (102) and bicyclo[2,1,1 Jhexyl (103) tosylates.The reactions are clearly highly assisted compared with cyclobutyl esters and 114 I. Rothberg J. C. King S. Kirsch and H. Skidanow J. Amer. Chem. SOC.,1970 92 2570. 115 S. A. Sherrod R. G. Bergman G. I. Gleicher and D. G. Morris J. Amer. Chem. SOC. 1970,92 3469. 116 R. C. Bingham W. F. Sliwinski and P. von R. Schleyer J. Amer. Chem. SOC.,1970 92 3471. 117 P. K. Freeman and J. N. Blazevich. Chem. Comm. 1969 1357. 118 P. K. Freeman D. M. Balls and J. N. Blazevich J. Amer. Chem. SOC.,1970,92 2051. 119 E. L. Allred and C. R. Flynn J. Amer. Chem. SOC.,1970 1064. 122 N. S. Isaacs participation by the electrons of the four-membered ring is postulated.' 2o Large rate differences have also been recorded between cis-and trans-isomers of (103) exo 1 endo 10' bicyclo[4,2,0]oct-l-yl (104) and bicyclo[3,2,O]hept-l-y1 (105) dinitrobenzoate solvolyses.'2 These effects probably reside in angle strain differences in the derived cations.Deamination of the deuterium-labelled spiropentylamine (106) leads to isomeric methylenecyclobutanols (107) and (108) in which the labelling dCH2- D NH D (107) labelled 100 % 3,4-D,; (108) labelled 75 % 2,2-D, 25 % a,a-D (107) pattern accords best although not precisely with the scheme shown.'*' Exten-sive participation is also proposed for the very facile solvolysis of the bicyclo- [l,l,l]pentyl system (109) which despite the a-phenyl group is more reactive than the cyclobutyl analogue (110a).'23 A 3-ethoxy-group either cis-or trans- retards solvolysis of cyclobutyl esters (1 IOU).The effect cannot be steric as it would then be limited to the trans-isomer the reaction being disrotatory as shown in (1 11).'24 The products of hydrolysis of 3-ethoxybutyl esters are mainly K. B. Wiberg J. E. Hiatt and K. Hseih J. Amer. Chem. SOC.,1970,92 544 553. Iz1 K. B. Wiberg R. A. Fenoglio V. Z. Williams and R. W. Ubersax J. Amer. Chem. SOC. 1970 92 564 568. l2 D. E. Applequist M. R. Johnson and F. Fisher J. Amer. Chem. SOC.,1970 92 4614. '23 A. Padwa and E. Alexander J. Amer. Chem. SOC..1970,92 1796. See 125 refs. 1-5. Reaction Mechanisms-Part (ii) 123 -. the corresponding (but inverted) 3-ols and it seems therefore that the ethoxy- group suppresses cyclobutane ring participation by its -I Differences doTos doTos EtO$x (11oc) (110b) JfOTos EtO” (1lOd) 0-0035 0.0013 in product ratios during solvolysis of cis-and trans-(112) are interpreted in terms of partial specific internal return with differential leakage to a classical cyclopropyl cation.126 Spiro[2,3]hexyl tosylate (I 13) is hydrolysed in part to a @MeCH,OBros ’ CH,OBros de cis-(112) trans-(112) 1 product (114) derived by homoallylic rearrangement.127 Reactions of this type have been examined in fluorosulphonic acid in which the ion (115)is stable lZs I.Lillien and L. Handloser Tetrahedron Letters 1970 1213. ‘*’ J. J. Gajewski R.L. Lyle and R. P. Gajewski Tetrahedron Letters 1970 1189. R. Maurin and M. Bertrand Tetrahedron Letters 1970 5065. 124 N. S. Isuucs though degenerate and exchanges methyl groups by two rearrangements k being rapid and k2 much slower.'28 N-Chloroaziridines (116) ionise by a dis- rotatory process analogous to cyclopropyl cations to form the aza-ally1 cation (117) at a rate which is greatly enhanced by terminal methyl substitution.'29 Participation by the cyclopropane ring and by the double bond are competitive ar"' c1-N in the solvolysis of (118) each process leading to distinct products. The latter is more effective by a factor of 4.l3O The stable degenerate carbonium ion resulting from the dissociation in superacid medium of either cyclobutanol or cyclopropylmethanol shows an n.m.r.spectrum (r 3.5 double quartet; z 5.3 doublet ; r 5.8 doublet) consistent either with the rapidly equilibrating non- classical cyclobutonium ion (119) or a bisected cyclopropylcarbinyl cation (12O).' 31 The methylcyclobutyl cation (121) also undergoes rapid degenerate 12* T. S. Sorensen and K. Ranganayarkava Tetrahedron Letters 1970 659. lz9 P. G. Gassmann D. K. Dygos and J. E. Trent J. Amer. Chem. Sac. 1970,92 2084. J. B. Lambert J. W. Hamersman A. P. Jovanovich F. R. Koeng S. A. Sweet and P. J. Kucinski J. Amer. Chem. SOC.,1970 92 6372. 13' G. A. Olah D. P. Kelly C. L. Jewell and R. D. Porter J. Amer. Chem. SOC.,1970 92 2544. Reaction Mechanisms-Part (ii) do" rearrangement in this medium.'32 Solvolyses of allylic esters are retarded by bond-angle strain at the a-carbon such as produced by a small ring e.g.(122b (125).'337134 However acceleration by electrons from neighbouring highly- strained bonds fits the solvolytic data for a series of such systems as (126H128) 6- CH2--X &FCH2, @cH2x -+ (126) (127) (1 28) (129) which are believed to assist ionisation by conjugation e.g.(129).'35 Vinyl Cations.-Vinyl cations are now well-established intermediates in the solvolysis of particularly a-arylvinyl halides (130) and related compounds. Such solvolyses have been found to proceed more or less readily in highly ionis- ing solvents although at rates quite low compared to the saturated analogues the products being vinyl esters from carboxylic acid solvents and ketones from IJ2 M.Saunders and J. Rosenfeld J. Amer. Chem. SOC.,1970 92 2548. lJJ G. D. Sargent and M. J. Harrison Tetrahedron Letters 1970 3699. IJ4 H. G. Richey R. Fletcher and R. G. Overmayer Tetrahedron Letters 1970 3703. IJ5 N. A. Clinton R.S. Brown and T. G. Traylor J. Amer. Chem. SOC.,1970,92 5228. 126 N. S. Isaacs aqueous solvents. Recent work has been concerned with the verification of the S,1 mechanism (A) and the elimination of other possible contenders (e.g.R-F).'36 A sNI Ph Ph OAc AcOH )=+-Ph --+ R R Ph B S,2 Ph OAc C addition -H Ph Br Ph R Ph H-R Ph (130) AcOH ph E elimination PhCrCPh addition H Ph Ph F aryl participation -I,+'\ AcOH Ph OAc 'A --)M R Ph R Ph Route E can be eliminated since in many cases studied there is no /3-hydrogen.The rates of vinyl solvolyses are greatly accelerated by an aryl group and are sensi- tive to its substituents (p = -3.6);there is a moderate sensitivity to solvents (Grun- wald-Winstein m = 0.3-0-5),137 but first-order kinetics are usually observed and no acceleration by added lyate ion which thereby excludes the direct displace- ment route B. When such solvolyses are carried out in deuteriated solvent there is typically neither a solvent isotope effect of any significance (k,:k = 1.04 in AcOD and 1.3-143 in EtOD) nor is deuterium incorporated in the The latter observation excludes the elimination-addition route An An m 136 Z. Rappoport T. Bassler and M.Hanack J. Amer. Chem. SOC., 1970,92,4985. '" Z. Rappoport and Y. Apeloig Tetrahedron Letters 1970 1817 1845. 13' M. A. Imhoff R. H. Summerville P. von R. Schleyer A. G. Martinez M. Hanack T. G. Dueber. and P. G. Stang J. Amer. Chem. SOC.,1970 92 3802. 139 P. Beltrame M. G. Cattania G. Massolo and M. Simonetta J. Chem. SOC.(B) 1970 453. Reaction Mechanisms-Part (ii) 127 E and the former excludes routes C and D since a rate-determining proton- addition should be accompanied by a large (ca. 7) solvent isotope effect. Rates OTf (1 32) (133) show a dependence on leaving-group similar to that of typical S,1 reactions e.g. in (131) X = Me > H > N02.14' Wagner-Meerwein rearrangements can Me Me Me \ Ht Me + II Me'] .C-C-CH Me*j>>-C=CH2 -+ +C-C=CH2 I Me Me Me k-,"a (134) Me Me \/ ,C-C --Me c1-'/ j Me apparently occur in the 1-adamantylvinyl cation (132) +(133),'38 and in the cation produced by protonation of t-butylacetylene (134).14' P-Aryl groups facilitate reaction ; for instance (135) solvolyses 100 times faster than (136).142 Ph OS02F H OSO2F Ph>=( H>=( Ph Ph (135) (136) The same authors confirmed the lack of solvent isotope effect in these solvolyses (AcOD) the lack of effect of added acetate ion and the rate ratio in solvents of equal ionising power k(AcOH):k(90% aq. EtOH) = 1.6 a value expected to be near unity for route A but only by extreme coincidence to be so for reaction by route D. The P-deuterium isotope effect was found to be 1.45 in [2H]-(136) similar to typical values in known S,1 reactions.The stereochemistry of vinyl solvolyses frequently leads to mixtures of cis-and trans-isomers in the products or to isomerisation of the starting material prior to reaction by ion-pair to a linear cation. Acetolysis of 1 -anisylvinyl bromide is accompanied by no return but extensive bromide ion return occurs in tri- anisylvinyl bromide. '43 cis-and trans-l,2-Dianisylvinyl bromides react in acetic acid at quite similar rates the cis being somewhat faster (which argues I4O 2.Rappoport and J. Karpi J. Amer. Chem. SOC.,1970,92 3220. 141 K. Griesbaum and Z. Rehman J. Amer. Chem. SOC.,1970,92 1417. 142 W. M. Jones and D. D. Moness J. Amer. Chem. Soc. 1970,92 5457. 143 Z. Rappoport and M.Atidia Tetrahedron Letters 1970 4085. 128 N. S.Isaacs against j?-aryl participation) but the ratio of reactivities is quite affected by added base probably due to a component of reaction leading to elimination. Similarly the solvolytic rates of (137) and (138) are very similar and rearside An An An An X >=(Ph X c! )=+-An Ph x- 1_ )--(Ph An (137) (139) (138) -1ACOH An An Ph OAc>=( participation of the anisyl group in (137) cannot therefore be important. The rates of cis-trans isomerisation and of solvolysis are very similar arguing that both processes occur by way of the ion (1 39). 144 Chlorine exchange in (140) occurs with retention of configuration possibly by direct substitution.145 A cyclopropyl group can stabilise vinyl cations ; (141) reacts with acetic acid in the presence of silver ion at room ternperat~re.'~~ The conclusions to be drawn from intensive studies over the year are that vinyl cations are not especially intrinsically unstable [Rappoport compares the stability of (142)with p-methoxybenzyl The relatively low solvolytic rates appear therefore to be due to dficulties in the ionisation process and sound a warning against attempts to compare carbonium ion stabilities of widely different types by rate measurements in solvolysis reactions.The origin of vinyl halide inertness may lie in the conjugation of the C-ha1 bond with the 7c-system or in high s-character of the C-ha1 bond or in steric hindrance to rearside solvation due to the a-aryl group or a combination of these factors.The subject has been reviewed by Hanack,I4' who with Rappoport and Bassler has discussed and summarised 20 criteria for judging the solvolytic mechanisms of 12 vinylic 144 Z. Rappoport and Y. Apeloig Tetrahedron Letters 1970 1845. 145 P. Beltrame P. L. Beltrame G. Carboni and M. L. Ceveda J. Chem. SOC.(B) 1970 730. 146 D. R. Kelsey and R. G. Bergman J. Amer. Chem. SOC. 1970,92 228. 14' Z. Rappoport and A. Gol Tetrahedron Letters 1970 3233. 148 M. Hanak Accounts Chem. Res. 1970,3 209 149 Z. Rappoport T. Bassler and M. Hanack J. Amer. Chem. SOC. 1970,92,4985. Reaction Mechanisms-Part (ii) Bimolecular Displacements.-Several theoretical papers have appeared descri b- ing the calculation by sophisticated MO methods of the energies of model transition states for S,2 processes.Potential surface calculations of the system (143) suggest that the D, geometry is preferred and energy minimised at bond H (143) lengths a = 201 b = 330 pm the electron density on carbon being significantly lower than in methane.' 50 The corresponding positive ion a model transition state for the SE2reaction still apparently prefers D, geometry over C (143b) (which is usually assumed to account for retention of configuration in these reactions) although by a smaller margin than in the case of the negative ion.' ' An attempt to rationalise substituent effects upon S,2 reactions has been made by summing estimated changes in bending and stretching modes between ground and transition states.' s2 This field is notoriously ambiguous since the electronic perturbation due to a substituent at the central carbon will affect bond-making and bond-breaking processes to opposite but not necessarily equal or constant extents.It is predicted that for the transition state (144)an electron-withdrawing Y I /X-"-C-b-X Ix-f-c-6-z X = 2nd row element J ."\b H' H A Z = 1st row element (1 44) (145) group Y will increase the order of bond b (relative to Y = H) and decrease that of a.153If the two nucleophilic groups are in different rows of the Periodic Table as in (145) the changes in bond-order are predicted to be in the same sense. This seems to imply that for the displacement of a less electronegative atom by a more an electron-withdrawing substituent will shift the transition state to a less 'product-like' appearance.' 53 it seems that secondary a-deuterium isotope effects in the SN2reaction are very small or even inverse while the value of k,:k for the ionisation reaction is about 1.23.Measured values intermediate between these extremes for solvolyses of p-substituted benzyl brosylates have been taken to indicate a mixed mechan- ism. The magnitudes of these isotope effects (in CF,CH,OH-H,O and C,H,OH-H,O) increased with solvent polarity and with electron-donating 15" C. D. Richie and G. A. Chappell J. Amer. Chem. SOC.,1970,92 1819. l5 * N. L. Allinger J. C. Tan and F. T. Win J. Amer. Chem. SOC., 1970 92 579. M. Pahari and R. Baru J. Indian Chem. SOC.,1970,47 364. J. C.Harris and J. L. Kurz J. Amer. Chem. SOC.,1970 92 349. 130 N. S. Isaacs ability of para-substituents as the reaction became progressively more limiting.ls4 Primary chlorine (k,5:k 7) isotope effects have been reported for displacements of chloride from benzyl chlorides by PhO- and PhS- to lie in the range 1-0092-1~0098.'55 The hypothesis that nucleophilic displacements by free and by cation-paired nucleophilic anions can be treated independently -attributed to Acree (1912)ls6-has been examined in the case of iodine-exchange by the alkali-metal iodides on methyl iodide in methan01.l~' The results were analysed taking into account salt effects and the contribution to attack by free ions was separated out. This as required proved to be independent of the nature of the cation.New powerful nucleophilic systems have been examined. In dimethyl sulphoxide aryloxide may be displaced by thiolate ion :Is8 DMSO EtS-+ CH,OAr -EtSCH + OAr-and in molten KSCN benzoate ion may be similarly displaced:'59 ArCO-OCH + KSCN -+ ArCOO-Kf + CH,SCN. Low valence states of cobalt and iron e.g.(146)and (147),provide new and power- ful nucleophiles of potential importance.'60 The apparent displacement of OH-by aniline in the ferrocene derivatives (148)and (149)is remarkable if indeed the mechanism is of the SN2 type.16 Internal displacements (SNi),proceeding 0 154 V. J. Shiner M. W. Rapp and H. R. Pinnick J. Amer. Chem. SOC.,1970 92 232. 155 E. P. Grimsrud and J. W. Taylor J. Amer. Chem. SOC.,1970,92 739. lS6 S.F. Acree J. Amer. Chem. SOC.,1912,48 353. I 57 P. Beronius and L. Pataki J. Amer. Chem. Sac. 1970,92 4518. 15' G. I. Fentrill and R. N. Mirrington Tetrahedron Letters 1970 1327. 159 E. M. Wadsworth and T. I. Crowell Tetrahedron Letters 1970 1085 160 M. D. Johnson unpublished results. Ibl G. Marr B. W. Rockett and A. Rushworth Tetrahedron Letters 1970 1317. Reaction Mechanisms-Part (ii) through intimate ion-pairs have been proposed for the thermolysis of alkyl thiocarbonates (150).'62Partial racemization and '*O scrambling occurs at a rate in the unreacted material greater than the decomposition there being an estimated 80 % ion-pair return.'63 RS Ar \ I SR Ar c=o *-' c +I \/ coo-HT-O H Ph Ph Ph (150) Displacements at Nuclei other than Carbon.-The powerful nucleophile diphenyl- phosphide appears to prefer to attack bromine rather than carbon in propargylic bromides (151).'64 The displacement at sulphur of the aryloxy-group from a sul- -Ph2P-Br-CHR-C-CH -+ Ph2PBr + CHR-C=CH (151) phenic ester (152)has been interpreted as a synchronous process,165 since the rate Ph,C-ScO-PNB -+ Ph,C-S-OAr + OPNB-t ArO-(152) correlation with the basicity of the attacking nucleophile (Brmsted p = 0.25) and of the leaving group (y = -0.97) is satisfactory.However the displacement of chloride from benzenesulphenyl chloride (153) by aniline seems to involve the formation of a moderately long-lived intermediate since the apparent bi- molecular rate-constant increases to a constant value with increasing aniline concentration.' 66 Displacement of chlorine at phosphorus in the conformation- Ph-S-Cl + PhNH2 + [complex] + PhSNHPh + HCl (153) ally stable compound (154) probably occurs by a combination of SN2(P)and S,1(P) processes as judged from the products; that resulting from the bi- molecular process is suppressed by silver ion catalysis which promotes the conformationally mobile cation (155).'67 lb2 J.L. Kice R. L. Scriver E. Koubek and M. Barnes J. Amer. Chem. SOC.,1970 92 5608. 163 J. L. Kice and G. C. Hanson Tetrahedron Letters 1970 2927. 164 W. Hewertson and I. C. Taylor Chem. Comm. 1970 119. 165 L. Senatore E. Guffarin and A. Fava J. Amer. Chem. SOC.,1970 92 3035. lb6 E. Ciuffarin and F. Griselli J. Amer. Chem. SOC.,1970 92 6015."' W. Wadsworth and H. Horton J. Amer. Chem. SOC.,1970 92 3785. 132 N. S.Isaacs MeOH Neighbouring-group Participation.-Competitive participation by oxygen (R20-3) and the homoallylic double bond of (156)is revealed to favour the latter 1 by the relative amounts of the products of acetolysis. (C1-5)-Participation OBros OAc OAc 0 Q-oQ 9+ ao*c + 0 4% cis 69 % trans 22 % in (157) is substantiated by the formation of the halonium ion (158) stable in SbF solution from which the solvolysis products are obtained on addition of water alcohols et~.'~~ The urethane group acts as an ambident neighbouring (157) (158) group. At low pH the carbonyl oxygen is the reactive nucleophile but at high pH the nitrogen participates in the form of the anion (159).'70,17' The hydrolysis of salicylacetals (1 60) occurs by participation of the neighbouring carboxy-group as a specific Brsnsted a~id.'~~,'~~ The rate is independent of pH throughout a considerable range of the acidic region.A type of participation is postulated lb8 L. A. Paquette R. W. Begland and P. C. Storm J. Amer. Chem. Soc. 1970,92 1971. Ib4 P. E. Peterson P. R. Clifford and F. J. Slama J. Amer. Chem. Soc. 1970 92 2840. F. L. Scott and D. F. Fenton Tetrahedron Letters 1970 681 685. F. L. Scott and C. V. Murphy Tetrahedron Letters 1970 1731. B. M. Dunn and T. C. Bruice J. Amer. Chem. SOC.,1970,92 2410. B. M. Dunn and T. C. Bruice J. Amer. Chem. SOC.,1970,92 6589. Reaction Mechanisms-Part (ii) Ph EtO- I (159) to reinforce the nucleophilicity of ethylenediamine (161) which is considerably higher than expected for a simple primary amine.'74 The oxygen bridge of (162) (161) can participate to stabilise the carbonium ion leading to enhanced rates of solvoiysis and rearrangement.I7' Carbanions and Enolisation.-Conrotatory ring-opening of the anion of bicyclo-[6,1,0]nonatriene (1 63) leads to cis,cis,cis,trans-cyclononatetraenyl anion (164) an aromatic species by the n.m.r.criterion; the external protons are strongly '14 W. P. Jencks and K. Solveson Chem. Comm. 1970 548. L. A. Paquette and P. C. Storm J. Amer. Chem. SOC.,1970,92,4295. 134 N S. Isaacs deshielded and the internal one shielded confirming the presence of a dia- magnetic ring-c~rrent."~ Another new aromatic anion is the tridehydro- H 2 H-1 t 13.52 H-2,9 t2.73 (doublet) H-3-8 T 3-3.6 7 8 (163) (164) [17]annulene anion (165) an 187t species.'77 A number of conjugated carbanions have been studied in liquid ammonia solution.The cyclic dienyl anions (166)- OMe (168) show strongly alternating charges as is predicted by simple HMO theory. The coupling constants for adjacent protons are proportional to the calculated bond orders between the carbons which bear them but no evidence was found for a ring-current as in (169). The allylic systems (170) and (171) are in equilibrium.'78 N.m.r. studies also reveal that the pentadienyl anion (172) and analogues such as (1 73) preferentially adopt the 'W' conformation.Intramolecular 1,6-sigma- H Me +Me NH,-.- Me PhCHJyM" h. v Me gPh-C/ NH-3 p H O.*Me.-(172) (mj G. Boche D. Martens and W. Danzer Angew. Chem. 1970,81 1003. '" J. Griffiths and F. Sondheimer J. Amer. Chem. SOC.,1969,91 7518. H. Klooster and J. A. Van Drune Rec. Trav. chim. 1970 89 368; H. Klooster and G. J. Heiszwol ibid. p. 413. Reaction Mechanisms-Part (ii) tropic shifts can occur in pentadienyl anions (174) and as predicted are antara- facial on thermolysis and suprafacial when ph~to-induced.'~~ The perchlorotrityl H 48% (174) 520; anion is particularly stable; the tetramethylammonium salt (175) has been isolated.' 8o (C,Cl &C- &Me (175) Ionisation constants for a large number of aryldinitromethanes have been measured ;values of pK in general correlate with oo,presumably indicating that resonance contributions from the aryl moiety are unimportant.'81 Substituted fluorenes have been used as indicators to set up an acidity scale appropriate to the highly basic system 4+90 % dimethyl sulphoxide-Me,N+ OH-.These indicators were found to have dissociation constants which were rationally related to a-values of substituent groups and to molecular orbital parameters. /&Substituted vinyldinitromethanes (176) have been shown to possess thermodynamic acidities correlated by the two-term equation :l 84 log k/kO = zO,PI + ORPR showing that both inductive and resonance terms are important. Rates of base-catalysed isomerisation of a-cyano-cis-stilbenes (177) (in dimethyl sulphoxide- X = C02Me pK = 3.14 (O,N)ZCH.CH=CHX SO,Me 1.65 CN 1.93 (176) NO2 0-07 ethanol) correlate with the acidity function H-,appropriate to the medium and with a-values of substit~ents.'~~ A measure of the ability of the methylene H CN He RO CN Ph CN \/ ...I -/ \/ /c=c\ +OR-PC\* /c=c\ Ph Ar Ph Ar H Ar (177) G. J. Heiszwol and J. A. Van Drunen Rec. Trav. chim. 1969 88 1377; R. B. Bates S. Brenner W. H. Deines D. A. McCombs and D. E. Patter J. Amer. Chem. SOC. 1970,92,6345. lM0M. Ballester and G. de la Fuente Tetrahedron Letters 1970,4509. lM1G. I. Kolesetskaya I. V. Tselinskii and L. I. Bagal Reakts. spos. org. Soedinenti 1969 6 387. IMZ "' K. Bowden and A. F. Cockerill J. Chem. SOC.(B) 1970 173.K. Bowden A. F. Cockerill and J. R. Gilbert J. Chem. SOC.(B) 1970 179. L. A. Kaplan N. E. Burlinson W. B. Moniz and C. F. Poronski Chem. Cornrn. 1970 140. D. J. Kroeger and R. Stewart J. Chem. SOC.(B) 1970,217. 136 N. S. Isaacs group to transmit charge comes from a comparison of substituent effects upon the acidity of (178) and (179). Hammett p values for the former are 1.07 and for p-XC H CHNO p-X.C,H,.CH2CHN02 X = C0,Me I Me Me S0,Me CN (178) (179) NO2 the latter 0.4 but correlations of both were made with c rather than 0- giving a linear log-log plot.'86 On the other hand acidities of (180) correlate best with c-,implying a more important contribution from conjugative inter- actions between a carbanionic centre and the substituent group.187 Exchange reactions of vinylic'88 and of aromatic protons [e.g. as in (181)]189 occur when (180) (181) these are suitably activated. Second (and higher)-row elements stabilise adjacent carbanionic centres; sulphur for example is well known to do so. For the halogens the order is I Br > Cl in the acidities of (182).l9O a-Fluorine evidently CH,X I NO2 (182) destabilises dinitromethide anions (183) relative to the corresponding alkyl or chloro-compounds as seen in their relative nucleophilicities towards methyl acrylate."l*' 92 Br onsted plots of kinetic against thermodynamic acidity for a homologous series of carbon acids have been recorded which have slopes greater than unity,193 indicating that as electron-withdrawing capacity increases the X rate (lo4I mol-s-l) -Me 67-1 Et 70.7 c1 98.5 (183) F 164 000 IN* F.G. Bordwell W. S. Boyle and K. C. Yee J. Amer. Chem. SOC.,1970 92 5926. Is' L. A. Kaplan N. E. Burlinson and W. B. Moniz Chem. Comm. 1970 140. D. Daloze H. G. Viehe and G. Chiurdoglu Tetrahedron Letters 1969 3925. R. D. Guthrie and D. P. Wesley J. Amer. Chem. Soc. 1970 92,4057. 190 A. A. Abdullah Y. Iskander and Y. Riad J. Chem. SOC.(B) 1969 1178. 19' S. Wolfe A. Rauk L. M. Tel and I. G. Csizrnadia Chem. Comm. 1970 96. 19' L. A. Kaplan and H. B. Pickard Chem. Comm. 1969 1500. 193 M. Fukuyama P. W. K. Flanagan F. T. Williams L. Frainier S. A. Miller and H. Shechter J. Amer. Chem. SOC.,1970 92 4689. Reaction Mechanisms-Part (ii) 137 effect on the exchange rate is relatively much greater than on the dissociation constant.This has been interpreted by Kre~ge,'~~ using the ionisation of nitro- alkanes by hydroxide ion as a model as typical of a situation in which in the transition state (184) the substituent interacts more strongly with ionic base than with the activating group (NO,). A relatively high barrier to inversion may be inferred from the observation that deuterium exchange in (185) and (186) occurs with retention of configuration to a considerable e~tent.'~~*'~~ H CONH sh P 'Ph '* Ph Similar properties are ascribed to the sulphonyl carbanion which also exchanges hydrogen for deuterium with stereochemical retention. Base-catalysed addition of ethanol to fluorinated olefins probably proceeds via a carbanion e.g.(187) although stereochemical consequences cannot be judged from this experiment.I9' / F r + Ph PkoEt + xF FF F OEt 13 % 31 % Fluoride ion will add to fluorinated olefins such as (188) with the formation of a carbanion which can be captured by mercury(11). 198 Primary isotope effects for proton transfer are at a maximum when the proton is equally co-ordinated ly4 A. J. Kresge J. Amer. Chem. SOC.,1970,92 3210. 195 J. M. Motes and H. M. Walborsky J. Amer. Chem. SOC.,1970 92 3697. 196 H. M. Walborsky and J. M. Motes J. Amer. Chem. SOC.,1970,92 2445. 19' H. F. Koch and A. J. Kielbonia J. Amer. Chem. SOC.,1970 92 729. 19' B. L. Dyatkin S. R. Sterlin B. 1. Martynov and I. L.Knunyants Tetrahedron Letters 1970 1387. 138 N. S. Isaacs CF3 CF,\ HgX, \ F-C=CF2 -+ C-CF Hg(CR q2 / / R R to each base in the transition state when the base-strengths in the solvent used are comparable. This point has been nicely demonstrated by Dixon and Bruice who found k,:k = 10 in the ionisation of nitroethane by ammonia in water while smaller values of the isotope effect were noted for both stronger and weaker bases.'99 Similarly a maximum in the deuterium-exchange rate of menthone (k,:k = 6-5) occurs in aqueous dimethyl sulphoxide at a concentration of 30-40 % dimethyl sulphoxide.200 Camphenilone (189) is known to exchange protons (albeit with drfficulty) the carbanion being supposed to be stabilised by homoconjugation.No such process appears to operate with adamantanone (190),in which no exchange was detected under similar conditions.201 The non- classical carbanion (191) is protonated by methanol on the endo side and by (191) ..M~OD dimethyl sulphoxide on the presumably less-hindered exo side.202 The 7-nor- bornenyl anion shows little destabilisation compared to the saturated analogue (193) undergoes proton exchange at a rate comparable with that of (192). Anti- homoaromatic character is evidently not called into play in this instance.203 rel. kexch 1.0 1.4 lYy J. E. Dixon and T. C. Bruice J. Amer. Chem. SOC.,1970 92 905. *O0 R. P. Bell and B. G. Cox J. Chem. SOC.(B) 1970 194. 20' J. E. Nordlander S. P. Jintal and D. J. Kilko Chem. Comm. 1969 1136. 202 J.M. Brown and E. N. Cain J. Amer. Chem. SOC., 1970 92 3821. 203 R. Breslow R. Pagni and W. N. Washburn Tetrahedron Letters 1970 547. Reaction Mechanisms-Part (ii) On the other hand the system (194a) has its acidity reduced by more than 10” compared to cyclopentadiene since the anion (194b) has cyclobutadienoid character.’04 The substituted cyclopropane (195) undergoes racemisation in polar solvents. The mechanism suggested is by spontaneous heterolysi~.”~ The * ph*N e‘ Ph 3CN Ph+CO2Me ~ Ph C02Me Ph COzMe Ph CN (195) base-catalysed prototropic shift in tropyl compounds presumably occurs via a tropyl anion (196) an 8n (antiaromatic) system though possibly not planar.’06 _7 1_ Q Q r); (196) A transition state resembling a cyclopropenyl anion (197) makes 1,2 anionic shifts relatively unusual; a small amount of rearrangement occurs during the ArCMe2-CH2CI ArCMe2CH,Li + LiCMe,CH,Ph >it (198) p2 p2 (197) Ar.CMe,CH,CO,H PhCH2CMe2C0,H action of lithium on (198).207 1,2-Shifts ofallyl groups however are 6.n-rearrange-ments and are thermally allowed e.g.(199).208,209New polar’ ’* and oxidative” ‘ (199) coupling reactions of carbanions have been reported PhCHCN PhCH,CN Ns Ph-CH-CN [CHzCHzl~PhCHCN -PhCHCN I I I PhCHCN TI:”(SO5)z R’R2CHN02 + R1R2C2NO2 -R1R2C-CR1R2 II NO2 NO2 ’04 R.Breslow and W. N. Washburn J. Amer. Chem. SOC.,1970 92 427. ’OS E. W. Yankee and D. J. Cram J. Amer. Chem. SOC.,1970 92 6328,6329 6331. lob K. Takahashi H.Yamamoto and T. Nozoe Bull. Chem. SOC.Japan 1970,43 200. 207 E. Grovenstein and Y-M. Cheng Chem. Comm. 1970 101. 208 J. E. Baldwin J. de Bernardis and J. E. Patrick Tetrahedron Letters 1970 353. ’09 J. E. Baldwin and F. J. Urban Chem. Comm. 1970 165. lo ’ W. G. Kofron and C. R. Hauser J. Org. Chem. 1970,35,2085. D. J. Edge R. 0.C. Norman and P. M. Storey J. Chem. SOC.(B) 1970 1096. 140 N. S. Isaacs and an intramolecular aromatic cyclisation realised.2 Further evidence for the cyclopropenone intermediate in the Favorskii reaction comes from the I C02Et observation that the same products (200) and (201) result from the base-catalysed fission of the actual proposed intermediate (202) or its acetal as from the Favorskii reaction with the halogenoketones (203) or (204).2 Alkoxyketones which (73 PhCHCICOCH2CH3 PhCHCHCO2H 70% /r b 0 t-. (203) II (200) /“\ OMe-PhCH2COCHC1CH -+ PhCH-CHCH J (204) (202) PhCH2C-CHClCH3 + PhCH2COCHCH3 II I 0 (201) OMe 30 % may accompany the main products are derived from the intermediate chloro- enol by the route (205)+(206).2’4 Methyl substitution can dramatically change the course of a Favorskii reaction; a comparison of the rates of (207 R = H) and (207 R = Me) shows a 200-fold acceleration for the latter and a change in Hammett p value for the reaction from -5.0 to + 1.4 with in addition a considerable increase in the amount of alkoxyketone by-product and deuterium exchange prior to rea~tion.~” Despite this loss of C1 is rate-determining for ’’ R.Filler and A. Fiebig Chem. Comm. 1970 546. C. Rappe L. Knutsson N. J. Turro and R. B. Gascosian J. Amer. Chem. SOC.,1970 92 2032. ’I4 F. G. Bordwell and M. W. Carson J. Amer. Chem. SOC., 1970,92 3377. 215 F. G. Bordwell and M. W. Carson J. Amer. Chem. SOC.,1970,92 3374. 141 Reaction Mechanisms-Part (ii) (207 R = Me) and suggests a high degree of carbonium ion character on the halogen-bearing carbon possibly in a dipolar transition state (208). Elimination Reactions.-Studies on the halide- and thiophenoxide-ion-induced elimination reactions of 2-p-anisylbutyl menthyl and neomenthyl systems have been made.216 These reactions initiated by strong carbon bases on compounds with weakly acidic 8-protons and good leaving groups are believed to fall into the E2C mechanistic category involving the rather loose transition state (209).B B B (209) (210) (211) (212) A strong preference towards anti-elimination and the formation of the most stable olefin (Saytzev product) is shown by all systems. The similarity between the E2 (210) and Elcb (211) transition states might lead one to suppose that a gradation of mechanism could extend between these extremes i.e. (212). Elimination from 9-hydroxymethylfluorene (21 3) indicates that the Elcb process occurs (a-exchange more rapid than elimination k,:k = 7-2 solvent deuterium isotope effect k, k = 042) but detailed examination has suggested interpreta- tion in terms of a competing E2 process in addition to the Elcb mechanism.It is argued that in this case the borderline region between these two mechanisms is met. If a mechanistic continuum exists the intermediate carbanion should be of comparable energy to the E2 transition state and should be destroyed in a diffusion-controlled process. It is observed that the lifetime of the carbanion is ca. 10 times greater than this and hence it is inferred that the two mechanisms occur as independent pathways of the rea~tion.~”*~~* The Elcb mechanism typically occurs in systems with a rather acidic 8-hydrogen and a poor leaving group. Crosby and Stirling have examined Elcb reactions of a series of com- pounds XCH,CH,OPh where X is an electron-withdrawing gr~up.~’~,~~’ The + 4-most effective group (NO,) is closely followed by -PPh and -SMe, but -&Me is less effective by a factor of lo5,which points to the great effectiveness ’I6 G.Biale A. J. Parker S. G.Smith I. D. R. Stevens and S. Winstein J. Amer. Chem. Suc. 1970 92 115. ’” R. A. More O’Ferrall and S. Slae J. Chem. Sac. (B) 1970 260 268. ’” R. A. More O’Ferrall J. Chem. Sac. (B) 1970 274. ’I9 J. Crosby and C. J. M. Stirling J. Chem. Sac. (B) 1970 671. *’O J. Crosby and C. J. M. Stirling J. Chem. Sac. (B),679. 142 N. S. Isaacs of second-row elements in stabilising an adjacent carbanion. The a-deuterium secondary isotope effect k,:k = 0.67 is more typical for a reaction involving a relatively long-lived carbanion formed in a rapid pre-equilibrium. Elimination of methanol from (214) also shows Elcb characteristics,221 and a similar mechan- ism has been proposed for the hydroxide-catalysed elimination of benzoic OH (213) acid from (215) to give butenone.222 Electronic effects upon the SN2 E2C and S,l-El reactions of the series of compounds (216) have been compared.223 0II (a) Y = NO CH3 C-CH -CH 2 Ye yHCH2CH (b) H I (4 Me H Br (d) OMe (215) (2 16) The conditions were Bu4NfC1- in dimethylformamide (S,2) Bu4N+C1- in acetondutidine (E2C) and acetone-water (SN1-El).Hammett plots indicate that the E2C process is far less sensitive to conjugating substituents in the aryl group than the El [102.'-fold rate difference from (a)to (d) for the former 107'4- fold for the latter]. Rates of elimination of HCl from (217) by triethylamine and the ethanolamines are in the order of Brcansted base strength; values of the Hammett p decrease with decreasing basicity of the reagent which may be due (217) to a decrease in carbanionic character with base strength.224 Bordwell et.al. have classified Elcb reactions according to whether or not the fast prior ionisa- tion is reversible and if it is rate-determining. Attempts have been made to characterise examples according to this clas~ification.~~~ Hofmann eliminations of P-phenethylammonium salts (218) occur by a concerted (E2) process as judged by the lack of hydrogen-exchange with solvent and the strictly trans stereochemistry.226 The primary nitrogen isotope effect kI4:kl5 may be more 221 F. G. Bordwell K. C. Yee and A. C. Knipe J. Amer. Chem. SOC.,1970,92 5945.222 R. C. Cevestri and L. R. Fedor J. Amer. Chem. SOC.,1970,92,4610. 223 D. J. Lloyd and A. J. Parker Tetrahedron Letters 1970 5029. 224 Y. Yano and S. Oae Tetrahedron 1970,26 27. 225 F. G. Bordwell M. M. Vestling and K. C. Yee J. Amer. Chem. SOC.,1970,92 5950. 226 A. N. Bourns and A. 1. Frosst Canad. J. Chem. 1970,48 131. Reaction Mechanisms-Part (ii) or less than unity depending upon the substituent in the /3-aryl group and pre- sumably depends upon the degree of bond-breaking in the transition state.227 X (a) R = H QD (b) R = Me /+ CH -CH -NR D yMe3 / D (218) (219) Significant proportions of syn-elimination are reported from (219) induced by OH-[(a) 1-4 %; (b) 4h-50 %] and t-butoxide [(a) 46-50 % ;(b) ca.70 syn and anti-Eliminations appear to have quite different transition states charac- terised by primary isotope effects of 2 and 4.75 respectively.229 However the formation of both cis-and trans-2-butenes by HBr elimination from threo-2- brom0[3-~H]butane occurs by anti-elimination mechanisms. Eliminations from ex0-2-[3-~H]norbornyI tosylate (220a) and its 7,7-dimethyl derivative (220b) occur by an almost exclusively syn process presumably on account of steric hindrance towards the bulky base (2-cyclohexylcyclohexanolate) attacking the endo side.230 The transmission of electronic effects through sulphur is greater than through oxygen as evidenced by rates of elimination of (221) (a) and (b) with a variety of substituents Y for which values of pz=s = 0-37 and pz=o = ca.0 were found. It is suggested that sulphur participation is stabilising the transition state in the former case as shown in (222).231 E2 Mechanisms are proposed for YY V (a) Y = H (a) 2 = S (b) Y = Me (b) Z = 0 the formation of thiones from (223)232 and (224).233 Primary isotope effects of 3.0 and 6.1 respectively and the absence of hydrogen exchange with the solvent before reaction are further cited as evidence for the proposed mechanism. 227 P. J. Smith and A. N. Bourns Canad. J. Chem. 1970,48 125. 228 K. C. Brown and W. H. Saunders J. Amer. Chem. SOC.,1970,92,4292. 229 R. A. Bartsch Tetrahedron Letters 1970 297. 230 H. C. Brown and K. T. Liu J. Amer. Chem. SOC., 1970,92 200. 231 Y. Yano and S. Oae Tetrahedron 1970 26 67.232 A. Ceccon U. Miotti U. Tonellato and M. Padovan J. Chem. SOC.(B) 1969 1084. 233 U. Miotti U. Tonellato and A. Ceccon J. Chem. SOC.(B) 1970 325. 144 N. S. Isaacs Ph Ph \ % \ C=S + ROH + CN-/Y-s-cN Ar / Ar H (223) p = +3-5 Steric factors associated with the 6-substituent are probably responsible for the relative ease of elimination of the P-D-lyxofuranoside (225) ;no corresponding reaction occurs under the same conditions with the riboside (226),in which both Na. benzoate DMF 120"C possible ,&hydrogens (2 and 3) are shielded by the 6-tosyloxy-gro~p.~~~ A new pyrolytic cis-elimination [of tosyl carbamates (227)]occurs at lo@-150 "Cfrom secondary and at room temperature from tertiary substrates. As the carbamates are readily prepared from tosyl isocyanate this should prove a useful synthetic route to the ~lefin.~~~ A pyrolytic trans-elimination (228) -+ (229) is claimed and rationalised by invoking neighbouring-group participation by the methyl ester It was not established whether epimerisation at the P-proton was taking place (which should be fairly facile at the high temperature and especially in the presence of a trace of base) which could lead to a concerted cis-elimination.This elimination would be expected to take place more readily than usual since the neighbouring ester group labilises the P-proton. In fact an Elcb elimination is not ruled out. Eliminations from 2,3-diphenyl-2-propanol 234 J. Hildesche A. Gandemer and S. D. Gero Chem. and Ind.1970 94. 2JJ L. C. Roach and W. H. Daly Chem. Comm. 1970 606. 23h E. E. Suissman J. P. Li and M. W. Creese J. Org. Chem. 1970 35 1352. 145 Reaction Mechanisms-Part (ii) CH3 I C ?OdCH3 0’ +o I 350 “C + CH3C02H and its derivatives lead to some 40-55% of a-benzylstyrene (230) as the kinetically-controlled product a surprising result for a reaction which would be expected to obey the Saytzev rule. The thermodynamically formed product is a-me t hyls til bene (23 1).’ ’ Me Me tH2 I I Ph-C-CH,Ph -+ Ph-C-CH2Ph Ph-C=CHPh I X (230) (231) (a) X = OH ; TosOH benzene (b) X = OMe; TosOH MeCN (c) x = C1; pyridine (d) X = NH,; NH,- Additions to Unsaturated Systems.-The cornplex nature of additions of HCI to olefins in acetic acid is illustrated by a study of the kinetics and products from [1,3,3-2H3]cyclohexene leading to anti-addition of HC1 (third-order kinetics) syn-addition of HCI (second-order kinetics) and anti-addition of acetic acid (third-order kinetics) in three competing proces~es.~~~,’~~ The chloride :acetate ratio depends upon free chloride ion concentration showing that the reaction does not occur exclusively by way of the carbonium ion but probably by at least two distinct carbonium ion pairs.The addition of acetic acid to cyclohexene is general-acid-catalysed obeys the Brsnsted Law well and has a solvent isotope effect (k,:k = 1.42) interpreted as showing a slow protonation step analogous to that found in hydrati~n.’~’ Brown and co-workers have postulated that processes involving single-step addition to the double bond of norbornene are strongly retarded by 7,7-dimethyl substitution whereas those occurring by a two-step mechanism via a trivalent carbon intermediate are not generally re- tarded and yield endo-substituted products.On this basis catalytic hydrogena- tion hydroboration epoxidation and silver ion co-ordination come into the first category while oxymercuration HC1 addition and free-radical thiophenol 23’ I. Ho and J. G. Smith Tetrahedron 1970 26 4277. 238 R. C. Fahey M. W. Monahan and C. A. McPherson J. Amer. Chem. SOC.,1970,92 2810. 239 R. C. Fahey and M. W. Monahan J. Amer. Chem. SOC.,1970,92 2816. 240 R. Corrin and J. Guenzet Tetrahedron 1970 26 671.146 N. S. Isaacs addition come into the second ;for example (232).241 However [c~rboxy-~H]- acetic acid and trifluoro[~arboxy-~H]acetic acid add exclusively em e.g. (233). Me Me Me Me \ H C1 (232) The mechanism is shown to involve exo-protonation followed after hydride and Wagner-Meerwein shifts by exo-addition of trifluoroacetate or acetate V \/ ions.242 syn-7-Bromobenzonorbornadiene (234) suffers exclusive endo-attack by diborane and exo-attack by acetic acid again presumably for steric reasons.243 YB‘ 05vCOCH3 Additions to acetylenes have been reviewed.244 The additions of halogen hydracid to propiolic acid follow the rate law rate = k,[CH-CHCO,H] [hal-] and lead to predominantly trans-addition.It is proposed that the slow step 241 H. C. Brown and J. H. Kawakami f. Amer. Chem. SOC.,1970,92 201; H. C. Brown and K-T. Liu f.Amer. Chem. SOC.,1970,92 3502. 242 H. C. Brown J. H. Kawakami and K-T. Liu f. Amer. Chem. SOC.,1970 92 3816. 243 R. Caple and C. S. Ilenda J. Amer. Chem. SOC.,1970 92 3817. 244 E. Winterfeldt Chem. Acetylenes 1969 267. Reaction Mechanisms-Part (ii) in this reaction is the nucleophilic attack of halide ion (I-> Br-> Cl-) on the 0-protonated substrate to yield a carbanion (235) which rapidly shifts a proton.245 The addition of acyl chloride-aluminium chloride complex to (235) acetylenes leads to mixtures of p-chloro-ap-unsaturated ketones.246 The cis:trans ratio from benzoyl chloride and 3-hexyne is 6.6 decreasing in polar solvents;those for propionyl chloride and acetyl chloride with the same alkyne are 2.5 and 0.33.Transition states (236) and (237) are proposed for the cis-and pans-addition processes respectively ;the latter resembles an internally-stabilised d+ - - -AlCI R-c.. I* i *Cl 8 I, vinyl cation hence it might be surmised that more trans product would result if R = Ar. The rates of HC1 addition to phenylallene (238a) 1-methyl-3-phenyl- allene (238b) and 1-methyl-1-phenylallene (238c) are in the ratio 1 :200 :4000 (a) R' = RZ= H; (b) R' = Me R2 = H; (c) R' = H RZ= Me from which it is inferred that the transition state resembles the localised ally1 cation (239) although no p value was Vinyl cations are inferred as intermediates in the addition of DCl to allene from the structures of the products (total 0-83 %) (240) (241) and the cyclobutane (242) formed by cyclo- addition of the vinyl cation to alle~~e.~~' The bromination of 4-substituted 245 K.Bowden and M. J. Price J. Chern. SOC.(B) 1970 1466 1472. 246 H. Martens and G. Hoornaert Tetrahedron Letters 1970 1821. 24' T. Okuyama K. Izawa and T. Fueno Tetrahedron Letters 1970 3295. 248 B. S. Charleston C. K. Dalton S. S. Washburne D. R. Dalton and S. R. Schroeder Tetrahedron Letters 1969 5 147. I48 N. S. Isaacs stilbenes gives a curved Hammett plot showing that there is no sharp mechan- istic change but that the reagent attacks both vinylic carbons competitively throughout a wide range of sub~tituents.~~’ No rate enhancement at n = 3 was observed250 in the bromination and iodination of a series of olefins (243,n = 1-4) which might have been expected in the case of bromine stabilisation of the (243) (244) carbonium ion for n = 3 (244).Of course in this system bromine is not a par- ticularly efficient neighbouring group and (Br-3) stabilisation may indeed be more effective than (Br-5). None the less there seems every reason for seeking examples of anchimeric assistance during addition reactions. An example probably occurs in the addition of trifluoroacetic acid to the acetylene (245) which yields a rearranged bromotrifluoroacetate (246).” Michael addition of CG CF,CO,H H*ococF3 ,c/-71 cQ-+ R’ Br H’h B,’ R Br (245) (246) alkoxide to activated olefins is enhanced by polar aprotic solvents and retarded by hydrogen-bonding species.252 For alkoxide addition the rate law k[olefin] [OR-] rate = [ROHY is observed.The rate is clearly related to the effective nucleophilicity of the 249 M.-F. Ruasse and J.-E. Dubois Tetrahedron Letters 1970 1163. 2so E. Bienvenue-Goetz J.-E. Dubois D. W. Pearson and D. H. L. Williams J. Chem. SOC.(B) 1970 1275. 251 P. E. Peterson R. J. Bopp and M. M. Ajo J. Amer. Chem. SOC.,1970,92 2834. 252 B. A. Feit and Z. Bigon J. Org. Chem. 1969 34 3942. Reaction Mechanisms-Part (ii) 149 alkoxide ion. The parameters obtained from observations of the pressure depen- dence of the rate of acid-catalysed hydration of acrylic acid have been interpreted as ruling out a slow attack by water on a protonated substrate (247).The choice left is between a simultaneous process or a rate-determining protonation involv- ing a tautomeric change.253 The order of reactivity towards Michael addition OH HO CH,=CHCO,H H’ CH2=CH-Cf+ -&+CHz-CHZC02H \-I OH OH (247) of morpholine and pyrrolidine to CH,=CHX is shown to be X = PhCO > PhS02 > CHO > MeCO > C02Ph > CN > CONH2,254but is not identical to the order of carbanion stabilisation found for instance in Elcb elimination (ref. 211). Isotope effects (a,P-cis,and p-trans) for the addition of styrene to tetracyano- ethylene oxide (248) are identical indicating a process in which the two new bonds are equally developed in the transition state.,’ Homolytic processes are presumed to occur in the alkyl hypobromite addition to olefins (249) because the orientation of addition is affected by oxygen.256 Additions to olefins PhCH=CH p? PhCH-CH2 NC,HF-~H;CN NC /CN -3 NC\; j/CN --* c-c c--c c\ ,c NC’ 0 ‘CN NC’ &’ \CN NC’ ‘CN (248) of iodine azide and iodine nitrate INO, occur by stereospecific routes to the trans adducts no doubt by way of cyclic iodonium ions but bromine azide adds non-stereo~pecifically.~ Chlorine acetate is less stereospecific than 732 chlorine in its additions to 01efins.~~’ Whether a halonium ion is able to form or whether a cis molecular addition occurs may well depend on the ease of leaving of the nucleophile.The bromonium ion which is produced by the action of N-bromosuccinimide on stilbene (250) in dimethylformamide reacts with the latter to give a bromo-formate (251).260 New addition processes which have ”’ S.K. Bhattacharya and C. K. Das J. Amer. Chem. SOC.,1969,91 6715. 254 H. Shenhav 2.Rappoport and S. Patai J. Chem. SOC.(B) 1970,469. ’ W. F. Bayne and E. Snyder Tetrahedron Letters 1970 2263. 25b V. L. Heasley C. L. Frye G. E. Heasley K. A. Martin D. A. Redfield and P. S. Wilday Tetrahedron Letters 1970 1573. 257 A. Hassner F. P. Boerwinkel and A. B. Levy f. Amer. Chem. SOC.,1970,92 4879. U. E. Diner and J. W. Lourn Chem. Comm. 1970 333. 259 P. B. D. de la Mare C. J. O’Connor M. J. Rosser and M. A. Wilson Chem. Comm. 1970 731. 260 D. R. Dalton R. C. Smith and D. G. Jones Terrahedron 1970 26 575.150 N. S. Isaacs Bu LMeOBr_ By-/+ Bu)7 (249) Me0 Br Br OMe absence of O2 29 71 % presence of O2 71 29 % + OCH=NMe, /Ph / /o-cH CH=CH + CHBr-CH / NBS / + /CHBr-CH Ph Ph \Ph Ph \Ph (250) (251) been reported include those of mercury trifluoroacetate (252):261 K = 826 BuCH=CH + Hg(OCOCF,) ,a BuCHCH,HgOCOCF (?) I OCOCF, (252) chromyl chloride for which the intermediate is (253):262 R R,C-CH R2C-CH2 I/ 0 0 II Or O\CCo'I+ RCH2C-R I R H Cr OCl CI/\c1 (253) and N-chlorocarbamates in the presence of chromous the product being (254) 0 4 CrCl + RO-C-NHCI (254) cis:trans = 2-6.7 Carbonyl Reactions.-Evidence has been presented that many B-keto-esters undergo hydrolysis by the Elcb mechanism.264 Loss of the a-proton is followed by p-elimination of carboxylate ion to give an intermediate keten (255) which rapidly hydrolyses.The existence of secondary deuterium isotope effects on acetal and orthoformate (256) hydrolysis is typical of carbon undergoing a hybridisation change in the transition state.265 The hydrolysis of orthoacetates 26' H. C. Brown and M. H. Rei Chem. Comm. 1969 1296. 262 F. Freeman P. D. McCart and N. J. Yamachica J. Amer. Chem. SOC.,1970,92,4621. 263 U. Lessard and J. M. Paton Tetrahedron Letters 1970 4883. 264 R. F. Pratt and T. C. Bruice J. Amer. Chem. SOC.,1970,92 5956. z65 H. Bull T. C. Pletcher and E. H. Cordes Chem. Comm. 1970 527. Reaction Mechunisms-Part (ii) 151 0 0II IIR-C-CH2C-OAr 0 -0 I '--II5 R-C-CH-LC-Ar 0 I1 + R-C-CH=C=O + OAr- (255) R-CCH2C02H (257) is preceded by a rapid alkoxy-group exchange,266 and a slow deuterium (D)H ,OEt kH:k = 1.15 s'.\ NO2 (256) uptake from the solvent in the alkyl moiety. Acid-catalysed cleavage of ortho- esters yields oxocarbonium ions (258) whose reactivity towards amines (com- CH,-C-OR \ \ OR \OR 0R' (257) etc. R' = R or C2D petitively with water) depends upon their base strength.267 The pH-rate profile for the ammonolysis of some or-substituted phenyl acetates has been interpreted MeO + ,OMe C Ph C0,Me Ht Ph CONHR (258)MeOH as indicating the occurrence of a carbanion intermediate at moderate to high pH (259).268Tetrahedral intermediates are inferred in the aminolysis of phenyl (259) L.R. Schroeder J. Chem. SOC.(B) 1970 1789. z6' K. Koeler and E. H. Cordes J. Amer. Chem. SOC.,1970,92 1576. "' T. C. Bruice A. F. Hegarty S. M. Felton A. Danzel and N. G. Kundu J. Amer. Chem. SOC.,1970,92 1370. /OR C,D,OD +-' /OC2D /OR' CH3C-OR CHZDC-OR' 152 N. S. Isaacs acetates from rate data269 and directly observed by spectrophotometry in hydrolysis of the amidine (260).270The hydrolysis of (261) occurs with no loss n OH-A A Ph-N+N-Ph PhN NPh * NPh PhlN\H A, 255 nm c=o HkbH / (260) H of and rates of vinyl ether hydrolysis correlate with a*.272Hydrolyses of the cyclic sultones (262) show a moderate dependence on electronic influences (p = 1-23).273 (261) (262) The hydrolyses of some thiochloroformates exhibit activation parameters characteristic of an SN1reaction; for example the change in heat capacity AC; = -360 J mol-’ deg-1.274 26’ F.M. Menger and J. H. Smith Tetrahedron Letters 1970 4163. 270 D. R. Robinson J. Amer. Chem. SOC.,1970,92 3138. ’” L. H. Brannigan and D. S. Tarbell J. Org. Chern. 1970 35 693. 272 B. A. Trofinov I. S. Emel’yanov A. S. Atavin B. V. Prokop’ev and A. V. Gusarov Reakts. spos. org. Soedinenii 1969 334 351. 273 0. R. Zabarski and E. T. Kaiser J. Amer. Chem. SOC.,1970,92 860. 274 A. Queen T. A. Naur M. N. Paddon-Row and K. Preston Canad. J. Chem. 1970 48 522.

ISSN:0069-3030    

DOI:10.1039/OC9706700101

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

3 Reaction Mechanisms Part (iii) By 6. G. ODELL University Chemical Laboratory Lensfield Road Cambridge. CB2 1EW SOPHISTICATED stereochemical and kinetic arguments continue to be used to show whether reactions are concerted or not and hence whether the principles of orbital symmetry conservation’ are applicable. Orbital Symmetry Correlations.-The tendency to maintain bonding governs the complex motions of molecules in the course of reactions.2 This will direct the nuclear motions which may or may not be the least-motion ones. The non- least-motion paths will often however be discriminated against by ‘extrasym- metric factor^',^ and thus will often have higher activation energies than non- concerted processes but not always. Concerted processes have been studied theoretically by mapping analysis4 and by permutation symmetry.’ Dewar’s book on molecular orbital theory6 contains a good analysis of pericyclic processes.A method for obtaining approxi- mate activation energies for four-centre thermally forbidden reactions based upon estimation of the energy of the avoided crossing point in the state correla- tion diagram has been de~cribed.~ Cycloaddition Reactions.4rbital symmetry theory in cycloaddition reactions has been reviewed8 and the criteria for deciding whether polar cycloadditions are one- or two-step processes discussed.’ Dilling has reviewed the photochemical cycloadditions of conjugated polyenes. The mechanisms of many [2 + 21 cycloadditions continue to arouse interest. MIND0/2 calculations on the dimerisation of ethylene lead to a pref- erence for a biradical process but leave open the possibility of a [,2 + .2,] ’ R.B. Woodward and R. Hoffmann ‘The Conservation of Orbital Symmetry’ Verlag Chemie Gmbh Weinheim-Bergstr. 1970. ’ R. Hoffmann and R. B. Woodward Science 1970 167 825. ’ J. A. Berson and S. S. Oh J. Amer. Chem. SOC.,1970 92 1086. ‘C. Trindle J. Amer. Chem. SOC.,1970 92 3251 3255. J. J. C. Mulder and L. J. Oosterhof Chem. Comm. 1970 305 307. ’ M. J. S. Dewar ‘Molecular Orbital Theory of Organic Chemistry’ McGraw-Hill New York 1969. ’ R. A. Jackson J. Chem. SOC.(B) 1970. 58. J. J. Vollmer and K. L. Servis J. Chem. Educ. 1970,47 491. ’ R. Gommper Angew. Chem. Internat. Edn. 1969,8 312. W. L. Dilling Chem. Rev. 1969 69 845.154 B. G.Ode11 symmetry-allowed process." The thermal dimerisation of cis,trans-cyclo-octa-1,3-diene gives (1)as the major product suggesting that a predominant portion of the reaction occurs by the symmetry-allowed process.I2 Pyrolysis of bicyclo[2,2,0]-hexanedicarboxylicesters(2)also gives products compatible with orbital symmetry theory but a biradical process is preferred since both the cis,endo-and cis'exo-isomers give the same product ration and the concerted transition state would be extreinely congested in the former case. Pyrolytic decomposition of bicyclo- [4,2,0]octane may be in part ~0ncerted.I~ Thermolysis of 1,1,2,2-tetramethyl- cyclobutane yields isobutylene ;the recovered deuteriated molecule (3)was not **= -,.or +,-(5) epimerised or racemised." These results were discussed in terms of rotations in 1,4-butanediyl intermediates.Bartlett's Centenary Lecture16" on the mechanisms of cycloadditions presents much recent work. If a diradical or dipolar intermediate in a two-step [2 +21 cycloaddition is formed in an extended conformation (4)it is likely to have a sufficient lifetime for rotation about the terminal C-C bonds with resulting configurational loss to occur before closure to a four-membered ring. The addition of cis-anethole (5) to tetracyanoethylene (TCNE) proceeds with greater loss of configuration in acetonitrile which favours formation of an extended dipole than in benzene.16" The diradical intermediate formed in the addition of a diene to an olefin can close to a cyclobutane or a cyclohexene.It has been found however that [2 +21 addition of difluorodichloroethylenes to cyclo- pentadiene is a two-step process while the competing [4+21 reaction is M. J. S. Dewar and E. Haselbach J. Amer. Chem. SOC.,1970 92 590. C. L. Osborn D. J. Trecker A. Padwa W. Koehn and J. Masaracchia Tetrahedron Letters 1970 4653. I3 L. A. Paquette and J. A. Schwartz J. Amer. Chem. SOC.,1970 92 3215. l4 J. E. Baldwin and P. W. Ford J. Amer. Chem. SOC., 1969 91 7192. J. A. Berson D. C. Tompkins and G. Jones jun. J. Amer. Chem. SOC..1970,92 5799. l6 (a) P. D. Bartlett Quart. Rev. 1970 24 473; (6) R. Wheland and P. D. Bartlett J. Amer. Chem. SOC.,1970,92. 3822. Reaction Mechanisms-Part (iii) 155 ~0ncerted.l~~ Interesting thermal [TC + 01 processes such as those of (6),are probably examples of trapping of biradical intermediates by double bonds.' Photolysis of methoxycyclobutanones [e,g. (711 in methanol is a stereo-specific reaction yielding olefins cyclopropanes and cyclic acetals. A diradical intermediate formed by or-cleavage can give rise to all these products.18" Such a diradical(8) has been trapped by butadiene to form 3-vinylcyclohexanone.'8b 1)40-3+ -p + VoMe Me0 Me0 Me0 Me0 (7) 0 The mechanisms of the formation of cyclobutanes in the sensitized photolysis of isomeric diethyl deca-2,8-diene-l ,lO-oates,' the photochemical reaction of styrene with tetramethylethylene,20 and the butadiene to bicyclobutane phote isomerisation2' have also been studied.Reaction between singlet oxygen and olefins can lead to 1,2-dioxetans. With l,Zdiethoxyethylenes cis stereospecificity is maintained ; the adduct with tetramethoxyethylene is remarkably stable (tt = 102 min at 56 oC).22The thermolysis of 1,Zdioxetans leads to ketonic species in an excited state. It is not yet clear whether formation22 and fragrnentati~n~~ of dioxetans are concerted or stepwise processes. Photo-oxygenation of olefins to allylic hydroperoxides is not a concerted ene-reaction; perepoxides [e.g. (9) from indene] are probable intermediate^.^^ OOH OOH \ L. A. Paquette and L. M. Leichter J. Amer. Chem. SOC.,1970,92,1765; D. T. Longone and D. M. Stehouwer Tetrahedron Letters 1970 1017. (a) N. J. Turro and D. M. McDaniel J.Amer. Chem. SOC.,1970,92,5727;(b)P. Dowd A. Gold and P. Sachdev ibid. 1970 92 5724. l9 J. R. SchefTerand B. A. Boire Tetrahedron Letters 1970 4741. 'O 0.L. Chapman and R. D. Lura J. Amer. Chem. SOC.,1970,92,6352. 21 W. G. Dauben and J. S. Ritscher J. Amer. Chem. SOC.,1970 92 2925. 22 P. D. Bartlett and A. P. Schaap J. Amer. Chem. SOC.,1970 92 3223; S. Mazur and C. S. Foote ibid. p. 3225. 23 H. E. O'Neal and W. H. Richardson J. Amer. Chem. $oc. 1970 92 6553. 24 W. Fenical D. R. Kearns and P. Radlick J. Amer. Chem. SOC.,1969,91. 7771. 156 B. G. Odell Olefins react with azodicarbonyl compounds to give diazetidines in two steps and dihydro-oxadiazines in a concerted Diels-Alder process.25 Here high polarity or polarisability of the olefin favours the [2 + 21 process; ethyl vinyl ether yields four-membered rings while 1,2-dimethoxyethylene gives 1,4 add~cts.~~ 0 (10) In contrast the reaction of dibenzoyl-diimide with diphenylketen gives an azomethine imine (lo) a 1,3-adduct which reacts further with dipolarophiles.26 Cycloaddition reactions of allenes have been reviewed in a timely Codimerisation of allene and tetradeuterioallene shows an intermolecular deuterium isotope effect (kJkD)of 1.013.Therefore there is little disturbance at the labelled site in the rate-determining step. However the intramolecular iso- tope effect in the dimerisation of 1,l-dideuterioallene is 1-14. It follows that there is more than one energy barrier in the dimerisation of a11ene.28 This is consistent with the formation of a 2,2'-biallyl diradical which closes to 1,2- dimethylenecyclobutane.This diradical has been observed by e.~.r.~~ and has been the subject of semi-empirical molecular orbital calculation^.^^ The highly strained allene cyclohexa-1,2-diene which is generated from the dibromo- carbene adduct of cyclopentene oiu an untrappable carbenoid yields tetramers at low temperatures but the cis-and trans-dimers (11) in refluxing ether.31 The change in product distribution with temperature is also interpreted as evidence for an intermediate 2,2'-biallyl diradical. Cyclohexa- 1,2-diene can also be trapped in a [2 + 21 reaction with styrene.31 The reaction of benzyne with allenes has also been studied.32 Tetramethoxyallene reacts with TCNE in a two-step process involving the reversible closure of the dipolar intermediate (12).33 (1 1) (12) 25 E.Koerner von Gustorf D. V. White B. Kim D. Hess and J. Leitch J. Org. Chem. 1970 35 1155; cf. ref. 9. 26 J. Markert and E. Fahr Tetrahedron Letters 1970 769. " T. F. Rutledge 'Acetylenes and Allenes; Additions Cyclisation and Polymerisation Reactions' Reinhold New York 1969. 28 W. R. Dolbier jun. and S. H. Dai J. Amer. Chem. SOC., '' P. Dowd J. Amer. Chem. SOC.,1970,92 1066. 1970,92 1774. 30 B. G. Odell R. Hoffmann and A. Imamura J. Chem. SOC.(B) 1970 1675. 3' W. R. Moore and W. R. Moser J. Amer. Chem. SOC.,1970 92 5469; W. R. Moore and W. R. Moser J. Org. Chem. 1970,35 908. 32 H. H. Wasserman and L. S. Keller Chem. Comm. 1970 1483.33 R. W. Hoffmann and W. Schafer Angew. Chem. Internat. Edn. 1970,9 733. Reaction Mechanisms-Part (iii) I57 Gommper has suggested that the addition of ketens to olefins may proceed by way of the dipolar intermediate (13) which he shows can account for the experi- mental facts.34 This is an alternative to the allowed concerted [,2 + .2,] process with the olefin as suprafacial component and the keten as antarafacial.' Addition of ketens to cyclic olefins shows a large selectivity for production of bicyclic systems in which the larger (L) of the keten substituents is enda3' These reactions are interpreted in terms of a concerted process as depicted in Scheme 1 Scheme 1 for the case of addition to cyclopentadiene The smaller substituent (S)preferenti-ally takes up the less hindered orientation.That the addition of cis-mono-olefins to ketens is faster than that of the trans-isomers is further evidence for a crossed [,2 + ,2,) process.36 The mechanisms of addition of ketens to imine~,~" azodicarbonyl and carbodiimides have also been studied. The reaction with carbodiirnide~~~~ proceeds in a two-step manner the intermediate being trapped by water or sulphur dioxide. Pyrolysis of p-lactams is stereospecific and is probably a reverse [,2 + ,2,] process where HNCO is the antarafacial component.38 Reactions between chlorosulphonyl isocyanate and double bonds could also be concerted but interpretation of results in this field is often complicated by rearrangements of the primary ad duct^.^^ Cyclodimerisations of acetylenes and allenes which proceed via vinyl cations (also potentially concerted') have been re~iewed.~' Molecular orbital symmetry conservation in transition-metal catalysis has been re~iewed.~' Van der L~gt~~ has shown theoretically that both ds and d" transition metals can interact with excited electronic configurations in the transi- tion states of [2 + 21 cycloadditions in such a way as to lower the activation energy for the process.The metals however do not change a forbidden process 34 H. U. Wagner and R. Gommper Tetrahedron Letters 1970 2819. 35 See W. T. Brady and R. Roe jun. J. Amer. Chem. SOC.,1970,92,4618 for many further references. 36 N. S. Isaacs and P. F. Stanbury Chem. Comm. 1970 1061; H. M. Frey and N.S. Isaacs J. Chem. SOC.(B),1970 830; T. DoMinh and 0.Strausz J. Amer. Chem. Soc. 1970 92 1766. 37 (a) W. T. Brady and L. Smith Tetrahedron Letrers 1970 2963; (b) J. Decazes J. L. Luche and H. B. Kagan ibid. p. 3665; (c) R. C. Kerber and T. J. Ryan ibid. p. 703; (4W. T. Brady and E. D. Dorsey J. Org. Chem. 1970,35,2732. 38 L. A. Paquette M. J. Wyvratt and G. R. Allen jun. J. Amer. Chem. Soc. 1970 92 1763. 39 See T. J. Barton R. Rogido and J. C. Clandy Tetrahedron Letters 1970 2081; E. J. Moriconi J. G. White R. W. Franck J. Jansing J. F. Kelly R. A. Salamone and Y.Shimakawa ibid. p. 27. 40 K. Griesbaum Angew. Chem. Internat. Edn. 1969 8 933. 41 F. D. Mango Adu. Catalysis 1969 20 291. 42 W. T. A. M. van der Lugt Tetrahedron Letters 1970 2281.158 B. G. Ode11 into an allowed one. Cubane (14)is isomerised by Rh' catalysts to syn-tricyclu- octadiene (15) while interaction with Ag' leads to cuneane (16),a wedge-shaped (16) (14) (15) molecule. Cuneane itself rearranges in the presence of Rh' to semibullvalene. 43 The above type of [,2 + ,2,] isomerisations of compounds with strained o-bonds is general for homo- and bishomo-cubane derivative^.^^ Some further evidence for metal-containing intermediates in rhodium-catalysed processes has been presen ted.43*44 The role of secondary orbital interactions' in stabilising the endo-transition states of [4 + 21 cycloadditions in the absence of great steric demands has received much support. Cyclopentadiene gives more than 97 o/ em-adduct (17) with 2,5-dimethyl-3,4-diphenylcyclopentadienone while cyclopentene which has similar steric demands but lacks the second double bond gives approximately equal amounts of em- and endo-adduct~.~~ It is argued that dominant orbital interactions and not steric effects or angular dependence of overlap account for the stereochemical course of this process.The adduct (17) was found to equili- brate with (18) in a Woodward-Katz rearrangement. The volume of activation for the Diels-Alder reaction of maleic anhydride with dienes has been studied. It was concluded that the transition state probably has a smaller volume than the adduct produced a surprising result also indicating stabilisation of the endo-transition state by secondary orbital interaction^.^^ The stereoselectivities of the reactions of cyclic dienes with cyclopropenes~7" cycl0butenes,4~~ and alkylated dien~philes~~' have also been studied.Dienes capable of assuming a cisoid conformation react faster with hexachlorocyclopentadiene than those 43 L. Cassar P. E. Eaton and J. Halpern J. Amer. Chem. SOC.,1970 92 3515 6366; L. Cassar and J. Halpern Chem. Comm. 1970 1082. 44 W. G. Dauben M. G. Buzzolini C. H. Schallhorn D. L. Whalen and K. J. Palmer Tetrahedron Letters 1970 787; see L. A. Paquette G. R. Allen jun. and R. P. Henzel J. Amer. Chem. Soc. 1970.92 7002 for further references. 45 K. N. Houk Tetrahedron Letters 1970 2621. 46 R. A. Grieger and C. A. Eckert J. Amer. Chem. SOC.,1970,92 2918. " (a) M. A. Battiste and C.T. Sprouse jun. Tetrahedron Letters 1970 4661 ;(b) C. M. Anderson I. W. McCay and R. N. Warrener ibid. p. 2735; (c) Y.Kobuke T. Fueno and J. Furukawa J. Amer. Chem. Soc. 1970,92 6548. Reaction Mechanisms-Part (iii) which may assume non-cisoid conformations. A stabilising 2-4‘ endo interaction in the transition state (19) probably in addition to 3-3’ is suggested.48 The mechanism of the Lewis-acid-catalysed [4 + 21 cycloaddition has been clarified. 2-Phenylcyclohex-2-enonereacts with butadiene in a manner that is a variant of Friedel-Crafts alkylation ; the intermediate (20) closes to both (21) and (Z).“’ The rearrangement of basketene (23) to Nenizescu’s hydrocarbon (24)has been shown to proceed by a retro-Diels-Alder reaction followed by a Cope rearrange- ment.” The [2 + 2 + 21 cycloaddition of TCNE to (23) reported last year’’ (23) (25) (24) must therefore be reinterpreted as a trapping of the intermediate diene (25).Deuterium-labelling evidence has been given for the intermediate formation of (26) in the rearrangement of bicyclo[4,2,0]decatetraene to cis-9,lO-dihydro- na~hthalene.’~ Schmidt has presented further evidence for the synchronous nature of the polar [4+ 21 Gycloaddition of amidomethylium cations (27) to 01efins.’~ The ratio of diastereomeric oxazines such as (28) formed in the regio- and stereo- specific cis-addition is not consistent with initial electrophilic attack of the cation on the ~lefin.’~ An interesting competition between 1,4-and 1,5-dipolar cyclo- addition has also been ~bserved.’~ Oxazoles react with diphenylcyclopropenone to produce y-pyrones ; the intermediates (29) extrude nitriles in a retrohomo-Diels-Alder proces~.~ Further (26) (27) (28) 48 C.G. Cardenas Chem. Comm. 1970 134. 49 H. W. Thompson and D. G. Melillo J. Amer. Chem. SOC.,1970,92 3218. 50 H. H. Westberg E. N. Cain and S. Masamune J. Amer. Chem. SOC.,1969,91 7512. 51 B. G. Odell Ann. Reports (B) 1969 66 143. 52 R. T. Seidner N. Nakatsuka and S. Masamune Canad. J. Chem. 1970,48 187. 53 R. R. Schmidt and R. Machat Angew. Chem. Internat. Edn. 1970,9 31 1. 54 S. Farid Chem. Comm. 1970 303. 55 R. Grigg and J. L. Jackson J. Chem. SOC.(0,1970 552. 160 B. G. Ode11 examples of the [2 + 2 + 21 cycloaddition have been observed in the addition of TCNE to barbaralane and dihydrobullvalene to give (30).56 A related nitrogen extrusion process has also been reported.' (29) (30) Fire~tone~~ has continued to provoke discussion of the mechanism of 1,3- dipolar cycloadditions.When diradical intermediates in these reactions are written with paired electrons in Lewis structures it is found that the calculated losses in bond energies are greater than experimental activation energies." Firestone has shown that the use of Linnett structures (without close electron pairing) leads to bond energy losses that are in better agreement with experiment. He points out however that good Linnett structures can also be written for the transition states of concerted processes. The fact that acetylenic dipolarophiles exhibit about the same reactivity as their olefinic counterparts even when an aromatic system is being formed and when a concerted transition state would be expected to possess some of the stabilisation of the product is quoted as evidence for the diradical nature of the pro~ess.'~ However the concensus of opinion favours a concerted [,4 + ,2,] process in 1,3-dipolar cycloadditions.Kinetic secondary deuterium isotope effects in the reaction of allene6OU and styrene60b with the carbonyl ylide derived from tetracyanoethylene oxide have been studied. 1,l-Dideuterioallene gives an inverse intramolecular isotope effect kdkD = 0.97 per deuterium; inverse isotope effects are also observed for a-and P-deuteriostyrenes. Dolbier argues that both these results point to a concerted cycloaddition6'" while it has been suggested that the styrene results do not rule out a two-step process where destruction of the intermediate is rate-limiting.60b Huisgen has presented full reports of the dipolar cycloaddition reactions of azlactones and related mesoionic 1,3-dip0les.~' Azlactone (3 1) reacts as its tautomer (32) a view supported by the fact that (33) is stable to dipolarophiles.Examples of cycloadditions of allylic anions which are isoelectronic with many 1,3-dipoles have been described for the addition of indenyl and 54 H. P. Loffler T. Martini H. Musso and G. Schroder Chem. Ber. 1970 103 2109. 57 L. A. Paquette J. Amer. Chem. SOC.,1970 92 576.5; R. Askani Tetrahedron Letters 1970,3349.58 R. A. Firestone J. Chem. SOC.(A) 1970 1570. 59 R. Huisgen J. Org. Chem. 1968 33 2291. 6o (a)W. R. Dolbierjun. and S. H. Dai Tetrahedron Letters 1970,4645; (6)W. F. Bayne and E. I. Snyder ibid. p. 2263. 61 See R. Knorr R. Huisgen and G. K. Staudinger Chem. Ber. 1970 103 2639; H. Gotthardt R. Huisgen and H. 0. Bayer J. Amer. Chem. Soc. 1970 92 4340. Reaction Mechanisms-Part (iii) 161 cyclopentadienyl anions to benzene.62 The related addition of (34)to stilbene to yield (35)has also been observed.63 11 0 (341 (35) (36) 2,2-Dimethylcyclopent-4-ene-1,3-dione (36)is a poor dienophile but a normally active dipolarophile. It has been argued therefore that secondary orbital inter- actions which are important in Diels-Alder reactions are not important in 1,3-dipolar cycloadditions.They are probably governed by steric control of reactant ~rientation.~~ Azomethine carbonyl and thiocarbonyl ylides all of which are 1,3-dipoles have been studied. The disrotatory photochemical opening of epoxides at low temperature yields carbonyl ylides. cus-and trans-Stilbene epoxides give isomeric red ylides for which fragmentation to benzaldehyde and phenylcarbene is preferred to thermal reclosure which would lead to epoxide is~merization.~~ The bicyclic oxiran (37) on photolysis or thermolysis gives ylide (38) which is I Ph Ph (37) (38) (39) fairly stable towards reclosure (a forbidden process; t+ = 8 min at 22 "C). It reacts with dipolarophiles with cis-stereo~pecificity.~~ Thiocarbonyl ylides (39)are formed with retention of stereochemistry in the retro-[4 + 2,] decompo-sition of 1,3,4-thiadiazolines.They undergo allowed conrotatory thermal '' W. T. Ford R. Radue and J. A. Walker Chem. Comm. 1970,966. '' T. Kauffmann H. Berg and E. Kopelmann Angew. Chem. Internat. Edn. 1970,9,380. 64 W. C. Agosta and A. B. Smith tert. J. Org. Chem. 1970,35 3856. 65 T. Do-Minh A. M. Trozzolo and G. W. Griffin J. Amer. Chem. SOC.,1970,92 1402. 162 B. G. Ode11 closure to episulphides and retain their stereochemistry in cycloadditions with dipolarophiles.66 The two-fold extrusion principle which has been applied to the synthesis of hindered olefid7 is obviously related to these reactions. While aziridines often react in cycloadditions via C-C bond cleavage to give azomethine ylides aziridinium salts undergo C-N rupture.68 TCNE adds to bicyclo[6,1,0]nonatriene to give (40) which contains a nine- membered ring.The stereochemistry of the ring junction has not yet been deter- mined but it is suggested6’ that this product may be formed by way of cis,cis trans,cis-cyclononatetraene whose all-cis-isomer undergoes [4+ 21 addition to the potent dienophile N-phenylpyra~olinedione.~’ It has been claimed that this dienophile gives (41) with oxonin either by a [2 + 2 + 21 process or by [8 + 21 addition followed by electrocyclic ring-clo~ure.~’ The [6 + 41 cycloadduct of tropone and cyclopentadiene is converted thermally into four isomeric [4+ 21 adducts probably via dissociation-re~ombination.~Woodward and Houk have reported72 on the structure and interrelations of the cycloadducts formed from 2,5-dimethyl-3,4-diphenylcyclopentadienoneand both tropone and cyclohepta- triene.In both cases em-[6 + 41 adducts and endo-[4 + 21 products [(42)and Ph H Me Ph (43)respectively] are formed in agreement with the guiding influence of secondary orbital interactions. In the case of tropone an [8 + 21 adduct is also produ~ed.~’ 66 R. M. Kellogg and S. Wassenaar Tetrahedron Letters 1970 1987; R. M. Kellogg S. Wassenaar and J. Buter ibid. p. 4689. 67 D. H. R. Barton and B. J. Willis Chem. Comm. 1970 1225; D. H. R. Barton E. H. Smith and B. J. Willis Chem. Comm. 1970 1226. 68 D. R. Crist and N. J. Leonard Angew. Chem. Internat. Edn.1969 8 962. 69 W. H. Okamura and T. W. Osborn J. Amer. Chem. SOC.,1970,92 1061 ; C. S. Baxter and P. J. Garratt ibid. 1970 92 1062. 70 A. G. Anastassiou and R. P. Cellura Tetrahedron Letters 1970 91 1 ; Chem. Comm. 1970 484. 71 S. ItB K. Sakan and Y. Fujise Tetrahedron Letters 1970 2873. I?. K. N. Houk and R. B. Woodward J. Amer. Chem. Soc. 1970,92,4143,4145. Reaction Mechanisms-Part (iii) 163 1,6-Dimethylenecyclohepta-2,4-diene also gives [8+ 21 adducts with dieno- phile~.~~ The dimer of cycloheptatriene (44)is probably formed by successive [6 + 41 and [4 + 21 additions.74 Diphenylnitrilimine reacts as a 4n component in a novel but predictable [,6 + .4,] cycloaddition reaction with tropone to yield (45);the major product however arises from [,4 + ,2,] addition.75 Dimethylfulvene has been found to act as a 67c system in reactions with dia~omethane~~” and with tr~pone.~~’ In the latter case the initial adduct (46)undergoes rapid [1,5] hydrogen migration and can then participate in a further exo-[,6 + .4,] addition with tropone as (44) (47) (48) the 6n component.The term ‘perispecific’ has been suggested to describe a process which follows only one of the symmetry-allowed pathways available.76b Concerted [,6 + ,2,] processes are forbidden. Further examples of [6 + 21 cycloadditions continue to be reported. The reaction of alkoxycarbonyl-azepines with azodicarboxylate esters7 7c requires further study in order to check assignments and the interrelation of different modes of addition.Askani has discovered the stereospecific addition of homofulvenes to chlorosulphonyl is~cyanate,~~ which should proceed with inversion of configuration at C-6 if it is a [,2 + ,4s+ ,2,] process (47). The remarkable photochemical racemisation of the thermally stable molecule (48)is a [,2 + .2 + u2a + .2,] cy~loaddition.~~ Sigmatropic Reactions-MIND0/2 calculations correctly predict the chair-like transition state for the Cope rearrangement to be more stable than the boat by 6.6 kcal mol-’ as compared to the experimental value of 5-7. An equatorial ‘3 G. C. Farrant and R. Feldmann Tetrahedron Letters 1970 4979. 74 K. Takatsuki I. Murata and Y.Kitahara Bull. Chem. SOC.Japan 1970 43 966. 75 K. N. Houk and C. R. Watts Tetrahedron Letters 1970 4025.76 (a)K. N. Houk and L. J. Luskus Tetrahedron Letters 1970,4029; (b)K. N. Houk L. J. Luskus and N. S. Bhacca J. Amer. Chem. SOC.,1970,92 6392. 77 (a) E. J. Moriconi C. F. Hummel and J. F. Kelly Tetrahedron Letters 1969 5325; (b) A. S. Kende and J. Y.-C. Chu ibid. 1970 4837; (c) W. S. Murphy and J. P. McCarthy Chem. Comm. 1970 1129. ” R. Askani Angew. Chem. Internat. Edn. 1970 9 167. ‘9 D. G. Farnum and G. R. Carlson J. Amer. Chem. SOC.,1970,92 6700. 164 B. G. Ode11 methyl substituent on the chair is preferred by 1.5 kcal mol-’ to an axial; calculations predict a value of 2.0.s0 The rapid degenerate [3,3] rearrangements of homotropylidenes such as (49) have been studied by n.m.r. The more stable transoid conformation inverts to the cisoid which isomerises by way of a bis- homobenzene-type transition state (50).8’ Thermal rearrangements of (51) are initiated by a [3,3] sigmatropic shift to give (52)s2“and not by initial opening of the cyclobutene ring.82b (52) The sigmatropic shifts encountered in dienone-phenol rearrangements can be explained in terms of orbital symmetry theory by the rationalisation that n-protonation of the carbonyl group leads to little perturbation of the dienone ring and to normal [3,3] and [1,5] shifts while n-protonation results in shifts which are allowed for the hexadienyl Thermal rearrangements of allylic imino-esters of caprolactam (53) proceed with migration to C-3 (54) via the enamine ta~tomer.~~ A related thio-Claisen rearrangement has also been observeds5 and the synthetic scope and utility of the thio-Claisen rearrangement has been extended.s6 The degenerate rearrangement of (55) has been rationalised in terms of the intermediacy of cis,trans,cis-cyclo-octatrienerather than an antara,antara-Cope rearrangement.87 (2)-Q? (53) H (54) 8o A.Brown M. J. S. Dewar and W. Schoeller J. Amer. Chem. SOC.,1970,92 5516. L. Birladeanu D. L. Harris and S. Winstein J. Amer. Chem. Soc. 1970 92 6387. 82 (a) E. Vedejs Tetrahedron Letters 1970 4963; (b) L. A. Paquette and J. C. Stowell ibid. p. 2259. 83 B. Miller J. Amer. Chem. SOC.,1970 92,432 6246 6252. 84 D. St. C. Black and A. M. Wade Chem. Comm. 1970,871. *’ B. W. Bycroft and W. Landon Chem. Comm. 1970 168. E. J. Corey and J.I. Shulman J. Amer. Chem. SOC.,1970,92 5522. FJ’ J. E. Baldwin and M. S. Kaplan Chem. Comm. 1970 1560. Reaction Mechan isms-Par t (iii) 165 &JeDpeDmD D (55) [3,3] Sigmatropic rearrangement has been shown to be important in the oxygen scrambling process for diacetyl peroxide while [1,3] shifts are probable in the reactions of t-butyl peresters." It is to be expected that similar processes will be found for other acetoxyl migrations. The [1,3] sigmatropic rearrangement of (56; R' = Me R2 = H) proceeds with inversion of configuration at the migrating centre to yield (57;R' = Me R2= H) while the epimer (56; R' = H R2 = Me) gives the same product." In the latter case a biradical pathway is followed (56) (57) (58) since the interaction between the methyl group and the ring in the concerted transition state (58) would be too severe to allow bonding to be maintained.In the [1,3] allylic rearrangements of phenyl ally1 sulphides an intermolecular 'antipolar' process sometimes competes with a unimolecular noncatalysed one." The thermal [1,5] hydrogen shift of (S)-trans-3-methyl-7-deuterio-octa-4,6-diene (59) proceeds (as indicated in Scheme 2) by way of a suprafacial transition state which is at least 8 kcal mol-' lower in energy than the antarafacial one which would generate antipodal product^.^ ' [1,5] Carbon shifts in cyclopentadiene derivatives have been the subject of several ~tudies.'~ On heating (60)undergoes a suprafacial [1,5] carbon migration with retention of configuration followed by a [1,5] hydrogen shift.92 Silicon and germanium have been found to undergo [1,5] sigmatropic rearrangements more readily than hydrogen.l-trimethyl-silylindene rearranges to 2-trimethylsilylisoindene,which can be trapped with TCNE.'3 Other metallic elements may well be found to undergo similar M. J. Goldstein and H. A. Judson J. Amer. Chem. SOC.,1970,92,4119,4120. 89 J. A. Berson and G. L. Nelson J. Amer. Chem. SOC.,1970,92 1096. 90 H. Kwart and N. Johnson J. Amer. Chem. SOC.,1970,92,6064. ' W. R. Roth J. Konig and K. Stein Chem. Ber. 1970 103 426. 92 M. A. M. Boersma J. W. de Haan H. Kloosterziel and L. J. M. van de Ven Chem. Comm. 1970 1168 and references cited therein. 93 A. J. Ashe tert Tetrahedron Letters 1970 2105; R. B.Larrabee and B. F. Dowden ibid. p. 915; A. Davison and P. E. Rakita Inorg. Chem. 1970 9 289. 166 B. G. Ode11 rearrangements. Examples of stereospecific [1,5] hydrogen shifts in terpenes which proceed with induction of chirality at the migration terminus have been given.94 Me Me I I wMe 1 Me -+ Ph flgh-Ph Ph Ph Ph The photochemical rearrangements of homofulvenes to spiroheptadienes [of which (61)- (62) is an example] are stereochemically consistent with a first excited state [1,5] carbon shift with inversion followed by a thermal [1,5] shift with retention of configuration ;95u other interpretations have been suggested however.956 Equilibration of cis,cis-di-o-propenylbenzenewith its cis,trans-isomer has been shown96 to proceed by way of [1,7] sigmatropic hydrogen shifts (presumably v4 G.Ohloff Angew Chem. Internat. Edn. 1970 9 743. 95 (a)N. K. Hamer and M. Stubbs Chem. Comm. 1970 1013; (6) T. Tabata and H. Hart Tetrahedron Letters 1969 4929; H. E. Zimmerman D. F. Juers J. M. McCall and B. Schrbder J. Amer. Chem. Soc. 1970 92 3474. 96 H. J. Hansen and H. Schmid Chimia (Switz.) 1970 24 89; H. Heimgartner H. J. Hansen and H. Schmid Helv. Chim. Acta 1970 53 173. Reaction Mechanisms-Part (iii) antarafacial) as shown in Scheme 3. Similar rearrangements of hexatriene derivatives have also been studied. 97 The photochemical rearrangement of 2-vinylcyclopentadiene to 6-methylful~ene~~ is the first example of a [1,7] suprafacial shift other than those of cycloheptatrienes.The sigmatropic [5, 5,] rearrangement (63) +(64) has now been reported in detail. It is an analogue of R' OH the Claisen rearrangement and follows first-order kinetics ; a ten-membered cyclic transition state is pr~bable.~' Further [3,2] sigmatropic rearrangements have been studied for allylic ether anions,'"" phosphonium ylides,'OOb and the all-carbon system (65) [which produces some (66)].loot In most cases the radical dissociation-recombination mechanism competes with the concerted process ; this competition is more important at higher temperatures."' Transfer of chirality from N to C in the rearrangement of (67)to (68) points to a concerted rearrangement. Decomposi-tion of cinnamylbenzyldiazene does not however follow the [3,2] sigmatropic pathway but gives products of radical recombination.lo2 Schollkopf has reviewed the mechanism of [1,2] sigmatropic rearrangements in anionic ~ysterns.~'~" He notes that the anionic [1,4] shift"3b is a symmetry- allowed process.A systematic study of the thermal rearrangements of 2-alkoxy-pyridine N-oxides to N-alkoxypyridones (for which it had previously been shown 97 P. Courtot and R. Rumin Tetrahedron Letters 1970 1849. 98 L. J. M. van de Ven J. L. M. Keulemans-Lebbink J. W. de Haan and H. Kloosterziel Chem. Comm. 1970 1509. 99 G. Frater and H. Schmid Heiv. Chirn. Acta 1970 53 269. O0 (a)V. Rautenstrauch Chem. Comm. 1970,4;(b)J. E. Baldwin and M. C. H. Armstrong ibid. p. 631 ;(c) J. E. Baldwin and F. J. Urban ibid. p. 165. lo' M. Moriwaki S.Sawada and Y. Inouye Chem. Comm. 1970,419. Io2 W. D. Ollis I. 0.Sutherland and Y.Thebtaranonth Chem. Comm. 1970 1199. (a) U. Schollkopf Angew. Chem. Internat. Edn. 1970 9 763. (b) H. Felkin and A. Tambute Tetrahedron Letters 1969 821. 168 B. G. Odell that migrating ally1 groups were not invertedL0&) has given conclusive proof that it is a concerted [ls,4s] process (except for the case of benzhydryl migration where a radical pair process intervene^)."^^ (69) (70) [1,6] Hydrogen shifts have been observed in pentadienyl anions the rearrange- ment of (69) to (70) being typical. Cyclic anions in which antarafacial migrations would be sterically impossible are thermally stable but are isomerised photo- chemically by a [ls,6s] pro~ess."~ Electrocyclic Reactions.-Salem has pointed out that there is no preferred motion for reclosure of diradicals having degenerate molecular orbitals of opposite symrnetry.'O6 Silver-ion-assisted solvolysis of halogenocarbene adducts of cyclic olefins in hydroxylic solvents can lead to trans allylic ethers or alcohols.107 Compound (71) leads to the single diastereomer (72) by loss of the em-9-bromine with dis- rotatory opening of the three-membered ring to give a trans,trans-allylic cation which is captured by methanol on the same side as that from which the bromide left.' The observed stereochemistry is also that expected on electronic grounds if a free cation is not involved.It has been calculated that the cyclobutyl cation should open to a homoallyl cation in a disrotatory sense and this has received experimental confirmation.' O8 Photochemical cyclisation of azoxy-compounds to oxadia~irans'~~~ and the related 471 photochemical closure of enolate anions to epo~ides'~~' have been observed.The cyclopropyl anion (73) opens thermally in the allowed conrotatory sense to give the mono-trans-cyclononatetraenide anion.' lo Thermal isomerisation of bicyclopentenes to cyclopentadienes which had previously been accepted as a two-step process has been shown for the case of Io4 (a) J. E. Litster and H. Tieckelman J. Amer. Chem. SOC. 1968 90 4361; (b) U. Schollkopf and I. Hoppe. Tetrahedron Letters 1970 4527. '05 R. B. Bates S. Brenner W. H. Deines D. A. McCombs and D. E. Potter J. Amer. Chem.SOC.,1970,92,6345. lob L. Salem Chem. Comm. 1970 981; Bull. SOC. chim. France 1970 3161. lo7 (a) C. B. Reese and A. Shaw Chem. Comm. 1970 1365; (6) D. Duffin and J. K. Sutherland ibid. p. 626. Io8 K. B. Wiberg and G. Szeimies J. Amer. Chem. SOC.,1970 92 571; C. D. Poulter E. C. Friedrich and S. Winstein ibid. p. 4274. Io9 (a)F. D. Green and S. S. Hecht J. Org. Chem. 1970,35,2482;(b) E. E. van Tamelen J. Schwartz and J. I. Brauman J. Amer. Chem. SOC. 1970 92 5798. G. Boche D. Martens and W. Danzer Angew. Chem. Internat. Edn. 1969 8 984. Reaction Mechanisms-Part (iii) (74) (74) to be a thermally allowed [,2 + ,2,] cycloaddition."'" Previous studies had indicated that the 5-methylene group retains its integrity during such isomerisations.' '' This result will doubtless prompt more thorough considera- tion of non-least-motion processes before drawing the conclusion that reactions are not concerted The remote double bond in systems such as (75) has little electronic effect on the transition state for the thermally forbidden disrotatory cyclobutane opening relative to corresponding dihydro-compounds.' Direct kinetic evidence has been presented that cis-trans isomerisation of simple dienes involves the inter- mediate formation of cyclobutenes.' l3 The rates of electrocyclic closure of sterically hindered dienes have been correlated with their ground-state conforma- tions as determined by X-ray crystallography.' l4 The concept of 1,Sdipolar cyclisation (76)--* (77) has been presented as a rationale of many heterocycle-forming reactions.' ' Bicyclo[5,l,0]octadienyl anion (78)and cyclo-octatrienyl anion do not undergo thermal interconversion ;'l6 conrotation is forbidden for the 871 electron system.A review of cyclodecapentaene chemistry contains a feast of pericyclic pro- cesses.' ' Hoffmann has suggested that the major structural feature which stabilises norcaradienes with respect to their seven-membered valence-tautomers is the presence of a low-lying acceptor orbital in the group at the 7-position."* If it is in the correct orientation (79) it will interact with one of the filled Walsh 'I' (a) J. E. Baldwin and A. H. Andrist Chem. Comm. 1970 1561; (6) J. E. Baldwin R. K. Pinschmidt jun. and A. H. Andrist J. Amer. Chem. SOC.,1970 92 5249.H. M. Frey J. Metcalf and J. M. Brown J. Chem. SOC. (B) 1970 1586. 'I3 H. M. Frey A. M. Lamont and R. Walsh Chem. Comm. 1970 1583. G. A. Doorakian H. H. Freedman R. F. Bryan and H. P. Weber J. Amer. Chem. SOC.,1970 92 399. ' ' H. Reimlinger Chem. Ber. 1970 103 1900. ' l6 H. Kloosterziel and E. Zwanenburg Rec. Trav. chim. 1969,88 1373. " T. L. Burkoth and E. E. van Tamelen in 'Nonbenzenoid Aromatics' ed. J. P. Snyder, Academic Press 1969 p. 63. ' I' R. Hoffmann Tetrahedron Letters 1970 2907. 170 B. G. Ode11 cyclopropane orbitals of the bicyclic form so as to effect a net transfer of electrons from the ring to the acceptor orbital making the 1,6-bond stronger. Examples of this effect have been discussed in the cycloheptatriene oxepin and azepine series.' The first example of a monocyclic azepine reacting as its azanorcaradi- ene tautomer has been given.12' The valence tautomerism of bromocyclo- octatetraenes and their isomerisation to bromostyrenes have been studied in detail.' 21 The predicted' electrocyclisation of meso-cyclodecahexaene (80) to naphthalene has been observed.'22 Cheletropic and other Pericyclic Processes.-Decomposition of N-arylazoaziri-dines (81) to olefins and azides is a stereospecific process,122 as is the oxidative fragmentation of N-arylaziridines where the N-oxide may be an intermediate.'23 Deoxygenation of epoxides and oxetans by atomic carbon'24 and oxidative loss of nitrogen from 1 -aminoaziridines' 25 probably proceed by radical mechanisms.Pyrolytic elimination of dialkoxycarbenes from acetals of norbornadienone (82) which could be concerted in the linear sense appears to be a two-step process.126 Thermal loss of a carbene from tropone ethylene acetal probably takes the concerted non-linear pathway from the norcaradiene tautomer.'" This process competes with a [ 1,7] sigmatropic oxygen migration. Thermal stereospecific dimerisation of sulphur dioxide from 3-thiabicyclo- [3,l,O]hexane 3,3-dioxides and the related epoxysulpholanes e.g. (83)-+(84),is a fully concerted CU2 + u2 + 62] retrogression. As would therefore be expected 119 H. Gunther Tetrahedron Letters 1970 5 173. 120 H. Prinzbach D. Stusche and R. Kitzing Angew. Chem. Internat. Edn. 1970 9 377; see L. A. Paquette in ref. 11 7 p. 249 for a discussion of oxepin and azepine chemistry.121 R. Huisgen and W. E. Konz J. Amer. Chem. SOC.,1970,92,4102,and following papers. 122 M. H. Akhtar and A. C. Oehschlager Tetrahedron 1970 26,3245. 123 H. W. Heine J. D. Myers and E. T. Peltzer tert. Angew. Chem. Internat. Edn. 1970 9 374. 124 J. H. Plonka and P. S. Skell Chem. Comm. 1970 1108. 125 L. A. Carpino and R. K. Kirkley J. Amer. Chem. SOC.,1970 92 1784. 126 R. W. Hoffmann and R. Hirsch Tetrahedron Letters 1970 4819. 127 K. Fukunaga T. Mukai Y. Akasaki and R. Suzuki Tetrahedron Letters 1970 2975. Reaction Mechanisms-Part (iii) (85) is relatively stable; the conczrted pathway here would lead to the very strained tr~ns,tr~ns-cyclohepta-1,4-diene.'~~ Sulphur monoxide extruded from (86)by way of (87) has been trapped by reaction with dienes.'" Fragmentation of the isomeric sulphones (88) and (89) gives sulphur dioxide and cyclo-octa- 1,3,5-triene.Compound (88j which can fragment in a concerted linear manner decomposes at 100"C while (89) for which only the non-linear mode is available for concerted decomposition requires 250 "C. The latter may however follow a multistep pathway. The difference of activation energies between the linear and non-linear processes has been roughly estimated as 10kcal mol-'.'30 Cheletropic loss of triphenylphosphine from the pentacovalent phosphorane (90) can be photochemically or thermally initiated and produces syn-tricyclo- octadiene.I3' D Thermal fragmentation of (91j leads to ['H ,]benzene by symmetry-allowed loss of HD while (92) yields a mixture of deuteriobenzenes by a radical mech- anism.Attempts to observe allowed stereospecific hydrogen transfers from these molecules to various hydrogen acceptors were frustrated by the incursion of radical processes.' 32 W. L. Mock J. Amer. Chem. SOC.,1970,92,6918. Y. L. Chow J. N. S. Tam J. E. Blier and H. H. Szmant Chem. Comm. 1970 1604. I3O W. L. Mock J. Amer. Chem. SOC., 1970,92 3807. 13' T. J. Katz and E. W. Turnblom J. Amer. Chern. SOC.,1970 92 6701. 32 I. Fleming and E. Wildsmith Chem. Comm. 1970 223. 172 B. G. OdeN Carbenes-The structures of carbenes and the stereochemistry of their addition to 01efins'~~ have been reviewed. Further and the reactions of diazoalkane~'~~ theoretical evidence for the non-linearity of the triplet ground state of methylene has been pre~ented.'~' Calculations on the dimerisation of methylene~'~~ show that the non-least-motion approach where a a-lone-pair of one molecule impinges on an unoccupied n-orbital of the other is preferred.Reversibility of singlet-triplet interconversion of diphenylmethylene has been invoked to explain the dependence of product distribution on the concentration of added isopropanol in the decomposition of diphenyldiazomethane in aceto- nitrile.' 37 Diphenylmethylene is produced in the photolysis of tetraphenyl- methane.'38 The ratio of diastereomeric cyclopropanes formed in the reaction of phenyl- carbene with olefins has been found to depend upon the olefin concentration a result which has wide implications on mechanistic proposals based upon such ratios.'39 The reaction between carbon atoms (IDor IS)and many classes of carbonyl compounds at 77 K results in the production of free singlet carbenes and carbon m~noxide.'~' In most cases the carbenes could not be trapped but underwent intramolecular rearrangements to valence-satisfied products.However dichloro- carbene (from phosgene) and methoxycarbene (from methyl formate) were found to add in a tereospecific manner to olefins. Dimethylcarbene produced from acetone rearranges to propylene. Study of the intramolecular deuterium iso- tope effect for this process has lead to the prediction that kJkD values greater than 1.4 in related reactions are indicative of the presence of complexed carbenes.140 In contrast to the above results it was found that 3P carbon atoms insert into the C-H bonds of a~et0ne.I~' Evidence has been presented that quadricyclanyli- dene (93) decomposes with the chemical formation of carbon atoms.142 Insertion of dichlorocarbene into C-H bonds usually leads to complex product mixtures. A preparatively useful example has been found in the exclusive insertion at the bridgehead of adamantane.'43 Fluorochlorocarbene is produced by thermolysis of PhHgCC1,F. '44 Decomposition of trichloromethyl-lithium probably gives uncomplexed dichlorocarbene. '45 133 G. L. Closs Topics Stereochem. 1968 3 193. 134 G. W. Cowell and A. Ledwith Quart. Rev. 1970,24 119. lJ5 C. F.Bender and H. F. Schaefer tert. J. Amer. Chem. Soc. 1970,92,4984. 13' R. Hoffman R. Gleiter and F. B. Mallory J. Amer. Chem. SOC.,1970 92 1460; H. Kollmar Tetrahedron Letters 1970 3337. 13' D. Bethell G. Stevens and P. Tickle Chem. Comm. 1970 792. 13' T. D. Walsh and D. R. Powers Tetrahedron Letters 1970 3855. 139 M. Schlosser and G. Heinz Chem. Ber. 1970 103 3543. 140 P. S. Skell and J. H. Plonka J. Amer. Chem. Soc. 1970 92 836 2160; Tetrahedron Letters 1970 2603 4557. 14' P. S. Skell J. H. Plonka and L. S.Wood Chem. Comm. 1970 710. 142 P. B. Shelvin and A. P. Wolf Tetrahedron Letters 1970 3987. 143 I. Tabushi Z. Yoshida and N. Takahashi J. Amer. Chem. Soc. 1970,92,6670. 144 D. Seyferth and K. V. Darragh J. Org. Chem. 1970,35 1297. G. Kobrich H.Biittner and E. Wagner Angew. Chem. Internat. Edn. 1970,9 169. Reaction Mechanisms-Part (iii) The mechanism of the intramolecular rearrangement of vinylcarbenes to cyclopropenes has received further and the first example of the trapping CN dc" /Curan (93) yCN (94) of such a carbene by an olefinic double bond as exemplified by reaction of (94) with furan to give (95) has been observed. 147 Methylchlorocarbene in addition to rearranging to vinyl chloride has been shown to be moderately selective in its singlet reactions with olefins; the order of resonance stabilisation of singlet carbenes is suggested14* to be FCCl > CC1 > PhCCl > MeCC1. The mechanism of addition of halogenocarbenes to bicyclic olefins has been reviewed.14' Phenylcarbene produced by pyrolysis of benzyl fluoride undergoes ring contraction to fulveneallene (96) and expansion to cycloheptatrienylidene (97) as shown in Scheme 4.l5' The latter process is reversible and results in the Scheme4 interconversion of 0-,m-,and p-tolylcarbenes.In agreement with this hypothesis 1-methylcycloheptatrienylidenegives some styrene which is presumably formed through the intermediacy of phenylmethylcarbene. '51 The reversible rearrangement of acylcarbenes (98) to oxirens (99) accompanies the Wolff rearrangement of diazoketones.' 52 Peracid oxidation of acetylenes also leads to these interconverting species.' H. Diirr Chem. Ber. 1970 103 369. 14' M. Franck-Neumann and C. Buchecker Angew. Chem. Internat. Edn.1970 9 526. R. A. Moss and A. Mamantov J. Amer. Chem. SOC..1970,92,6951. C. W. Jefford Chimia (Switz.) 1970 24 357. I5O P. Schissel M. E. Kent D. J. McAdoo and E. Hedaya J. Amer. Chem. SOC.,1970 92 2147. W. J. Baron M. Jones jun. and P. P. Gaspar J. Amer. Chem. SOC.,1970 92 4739; J. A. Meyers R.C. Joines and W. M. Jones ibid. p. 4740. 15* D. E. Thornton R. K. Gosavi and 0. P. Strausz J. Amer. Chem. Soc. 1970 92 1768; G. Frater and 0.P. Strausz ibid. p. 6654. J. Ciabattoni R. A. Campbell C. A. Renner and P. W. Concannon J. Amer. Chem. SOC.,1970 92 3826. 174 B. G. Ode11 Ethoxycarbonyltrimethylsilylcarbeneinserts into C-H bonds and undergoes cis-addition to double bonds in contrast to the carbon analogue which stabilises itself almost entirely by intramolecular paths.' 54 Addition of dicyanocarbene to cyclo-octatetraene to give (loo) a rare example of 1,4 carbene addition to a diene system arises from the triplet which gives a stabilised diradical intermediate.' Bicyclo[3,3,l]non-2-en-9-ylidene (101) reacts intramolecularly in a way that suggests that there is an initial stabilising interaction between the electron-deficient centre and the double bond although addition to the double bond is sterically imp0ssib1e.l~~ The carbenoid formed in a Corey-Winter alkene synthesis was found to be trapped by intramolecular insertion into an 0-H bond.I5' Loss of bromide ion from 3-bromobicyclo- [3,2,l]octa-2,6-dienyl anion probably gives the homoconjugated carbene (102)' 58 Calculations' 59 and observations' 6o on the cyclopropylidene to allene isomer- isation have been reported.The carbene (free or complexed) probably opens in aconrotatory or monorotatory manner. Some tetrasubstitutedcyclopropylidenes where conrotatory opening is hindered undergo C-H insertion to give bicyclo- butanes.16' Nitrenes.-A review on nitrenes in organic synthesis has appeared.16' Phenylnitrene and not ring-expansion products is formed in the photolysis of 1-phenyliminopyridinium ylides. '62 Intermolecular electrophilic aromatic substitution by arylnitrenes is very rare. It has now been observed that activated benzene rings are attacked in the ortho-and para-positions by electrophilic phenylnitrenes which bear an electron-withdrawing substituent at the para-position (e.g.p-cyanophenylnitrene).' 63 Intramolecular attack of arylnitrenes on aromatic rings is in contrast commonly observed and it is interesting to note that o-biphenylnitrene can be diverted from carbazole formation by diethylamine.' 64 Nitrenes formed by the action of tervalent phosphorus compounds on aryl nitrophenyl sulphides undergo 54 U. Schollkopf D. Hoppe N. Rieber and V. Jacobi Annalen 1969 730 1. L55 A. G. Anastassiou R. P. Cellura and E. Ciganek Tetrahedron Letters 1970 5267. 56 M. H. Fisch and H. D. Pierce jun. Chem. Comm. 1970 503. 15' D. Horton and C. G. Tindall jun. J. Org. Chem. 1970,35 3558. 15' R. G. Bergmann and V. J. Rajadhyaksha J. Amer. Chem. SOC.,1970,92,2163. 159 M. J. S. Dewar. E. Haselbach and M. Shanshal J. Amer. Chem.SOC.,1970,92 3505. I6O W. R. Moore and J. B. Hill Tetrahedron Letters 1970 4343 4553 and refs. cited therein. R. K. Smalley and H. Suschitzky Chem. and Ind. 1970 1338. 162 V. Snieckus and G. Kan Chem. Comm. 1970 172. 16' R. A. Abramovitch and E. F. V. Scriven Chem. Comm. 1970 787. 164 R. J. Sundberg M. Brenner S. R. Suter and B. P. Das Tetrahedron Letters 1970 2715. Reaction Mechanisms-Part (iii) intramolecular insertion. Spiro-intermediates such as (103) have been invoked to explain the rearrangements observed.' 65 (103) 1 N-Azido-amines decompose by way of N-nitrenes. '66 The isoelectronic alkoxynitrenes RON are generated by oxidation of 0-alkylhydroxylamines ; they give N-alkoxyaziridines on reaction with olefins.'67 The adducts formed between singlet methanesulphonylnitrene and nucleo- philic aromatic compounds such as toluene and anisole ring-open to give sul- phonamides. When a deactivated aromatic ring is the substrate some or all of the nitrene becomes demoted to the triplet ground state which gives typical radical substitution products. Nitrobenzene which is too electron-deficient to give any singlet-derived products reacts only with the triplet. In this case the presence of molecular oxygen prevents any substitution by reacting rapidly with the triplet nitrene. ' * 165 J. I. G. Cadogan and S. Kulik Chem. Comm. 1970 233 792; J. I. G. Cadogan S. Kulik and C. Thomson ibid. p. 436. 166 G. Koga and J.-P. Anselme J. Org. Chem. 1970,35,960. 167 S. J.Brois J. Amer. Chem. SOC.,1970 92 1079. '60 R. A. Abramovitch G. N. Knaus and V. Uma J. Amer. Chem. SOC.,1969,91 7532.

ISSN:0069-3030    

DOI:10.1039/OC9706700153

出版商:RSC    

年代:1970

数据来源: RSC

摘要:

4 Free-radical Reactions’ By A. R. FORRESTER Department of Chemistry University of Aberdeen Aberdeen AB9 2UE ELECTRON spin resonance measurements2 have confirmed previous predictions that the benzoyl radical is a a-radical the unpaired electron occupying a hybrid orbital situated orthogonal to the n-system (cc the isoelectronic PhCN’ which is a n-radical3 and PhNO?). The observation that the major splitting in its spectrum (1.6G) is due to the meta-protons is complementary to the findings of an n.m.r. study4 of stable ‘twisted’ n-radicals. In view of the above result 00 Recent books and reviews dealing with aspects of free-radical chemistry include E. S. Huyser ‘Free Radical Chain Reactions’ Wiley New York 1970; E. G Rozant- sev ‘Free Nitroxyl Radicals’ Plenum New York 1970; ‘Methods in Free Radical Chemistry’ Vols.1 and 2 ed. E. S. Huyser M. Dekker New York 1969 these Vols. contain chapters on Free Radical Study by Electron Paramagnetic Resonance by L. Kevan Free-Radicals and Photochemical Reactions by D. C. Neckers Free Radical Chlorination of Organic Molecules by M. L. Poutsma Thiyl Radicals by R. M. Kellogg and Free Radical Brominations by W. A. Thaler; ‘Electrolytic Reduc- tive Coupling Synthetic and Mechanistic Aspects’ M. M. Baizer and J. P. Petrovich Prog. Phys. Org. Chem. 1970 7 189; The Application of Radiation Chemistry to Mechanistic Studies in Organic Chemistry E. J. Fendler and J. H. Fendler ibid. 1970 p. 229; The Study of Free Radicals and their Reactions at Low Temperature using a Rotating Cryostat J.E. Bennet B. Mile A. Thomas and B. Ward Ado. Phys. Org. Chem. 1970 8 1;Synthetic Uses of Free Radicals G. B. Gill in ‘Modern Reactions in Organic Synthesis’ ed. C. J. Timmons Van Nostrand London 1970; Stereoselectivity in Free Radicals of the Norbornyl Type P. D. Bartlett G. N. Fickes F. C. Haupt and R. Helgeson Accounts Chem. Res. 1970 3 177; Problems and Possibilities of the Free Radical Addition of Thiols to Unsaturated Compounds K. Griesbaum Angew. Chem. Internat. Edn. 1970,9,273; Interactions between Atoms and Radicals in the Liquid Phase E. T. Denisov Russ. Chem. Rev. 1970 39 31; Reactions of Epoxy Compounds by a Radical Mechanism A. P. Meleshevich ibid. 1970 39 213; The Present State of the Theory of the Oxidation of Cyclo-Olefins A.A. Syrov and U. K. Tsyskovskii ibid. 1970 39 373; Preparative Aspects of the Radiation Chemistry of Organic Compounds I. V. Vereshchinskii ibid. 1970 39 405. P. J. Krusic and T. A. Rettig J. Amer. Chem. Soc. 1970,92 722. ’ A. Carrington and P. F. Todd Moi. Phys. 1963 6 161. A. Calder A. R. Forrester J. W. Emsley G. R. Luckhurst and R. A. Storey Mol. Phys. 1970 18 481. A. R. Forrester the difference between structures such as (1) and (2) should be fully realised. These were formulated5 (wrongly as canonical forms) for the precursor of the cyclic disulphide (3) which arose during photolytic decomposition of 2-phenyl- 1,3-benzoxathian-4-one. In the absence of e.s.r. measurements it is of interest to speculate whether the analogous benzimidoyl radicals (4) formed by treatment of the corresponding benzaldimine with di-isopropylperoxydicarbonate are c-or .n-radicak6 These transitory intermediates fragmented spontaneously ArCH=N-R' + R0.j ArC=N-R' -P ArCN + R1 (4) to nitriles and alkyl radicals.Lack of a 'clean' source of aroyl radicals has greatly hampered examination of their chemistry most precursors of such radicals (PhCHO PhCON=NCOPh) reacting readily with the radicals they produce. In this respect thermolysis and photolysis of benzoylformyl chloride (the iodide was not examined) was disappointing in view of the encouraging results ob- tained using pyruvyl chloride as a source of acetyl radical^.^ Photolysis of phenyl benzoate in the presence of tributyltin hydride which is considered to produce benzoyl radicals by initial S,2 reaction of the tributyltin radical on the ester [equation (l)],also offers little advantage since other features complicate the reaction and a complex mixture of products results.8 Bu,Sn.+ PhOCOPh -+ Bu,SnOPh + PheO (1) + Evidence that acyl radicals are relatively nucleophilic species (RCO is more stable than RCO) has been obtained by acylating hetero-aromatic bases in acid solution with aldehydes in the presence of peroxide and ferrous ions;' acetyla- tion of quinoline in this way for example gave a mixture of 2-and 4-acetyl- quinolines. Formamido" (CONH,) and alkyl radicals similarly formed also exhibited nucleophilic behaviour on reaction with these bases in acid solution. Enhancement of the n.m.r.signal of the formyl proton of benzaldehyde during photolysis has been attributed12 to the generation of a radical pair (5) which may either disproportionate to benzaldehyde or couple to give benzoin. No such radical pairs are thought to participate in the photochemical isomerisation of o-phthalaldehyde to phthalide (8). Instead a chain process involving the isomeric propagating radicals (6) and (7) has been rn00ted.l~ The rate at which A. 0. Pedersen S.-0. Lawesson P. D. Klemmensen and J. Kolc Tetrahedron 1970 26 1157. H.Ohta and K. Tokumaru Chem. Comm. 1970 1601. ' D. D. Tanner and N. C. Das J. Org. Chem. 1970,35 3972. L. E. Khoo and H. H. Lee Tetrahedron 1970 26 4261. T. Carrona G. P. Gardini and F. Minisci Chem. Comm. 1969 201; G.P. Gardini and F. Minisci J. Chem. SOC. (C),1970 929. lo F. Minisci G. P. Gardini R. Galli and F. Bertini Tetrahedron Letters 1970 15. F. Minisci R. Galli V. Malatesta and T. Carrona Tetrahedron 1970 26,4083. l2 M. Cocivera and A. M. Trozzolo J. Amer. Chem. SOC.,1970,92 1774. l3 D. A. Harrison R. N. Schwartz and J. Kagan J. Amer. Chem. SOC.,1970 92 5793. Free-radical Reactions phenacetyl radicals decarbonylate (k = lo8s-') has been deduced by photo- lysing a benzyl ketone in the presence of a stable nitroxide and measuring the ratio of >N-0-alkyl to >N-0-acyl product f~rmed.'~ 0 0 0 II II 0 OH PhC- *CHPh II I ' CH Formation of products with polarised nuclear spins on thermolysis of t-amine N-oxides' (Meisenheimer rearrangement) and sulphonium ylidesI6 (Stevens rearrangement) has led to radical-pair mechanisms being advanced for these re- arrangement~.'.~ However in both cases diffusion of the radical pair must occur to some extent since 'scrambled products' were obtained on thermolysis of mixtures of structurally related N-oxides18 and ylides16 (see also ref.19). By comparison emission signals obtained from a mixture of picoline N-oxide and acetic anhydride at 90°C were shown2' not to arise from the principal product (10) and hence have no bearing on the mechanism of the rearrangement (9)--* (10). Also rearrangement of benzyl toluene-p-sulphenate to benzyl p-tolyl sulphoxide was considered not to proceed by way of radicals in spite of the initial emission signal obtained from the methylene protons of the sulphoxide.2 The theory22 developed last year to account for chemically induced dynamic nuclear polarisation (CIDNP) has been extended to systems containing several nuclear spins and it is now possible to predict the form of CIDNP spectra by considering transitions to and from those nuclear spin states of the product which are correctly polarised with respect to the electron spin of the radical l4 W.K. Robbins and R. H. Eastman J. Amer. Chem. SOC.,1970,92,6076,6077. G. Ostermann and U. Schollkopf Annalen 1970,737 170; A. R. Lepley P. M. Cook and G. F. Willard J. Amer. Chem. SOC.,1970 92 1101. J. E. Baldwin W. F. Erickson R. E. Hackler and R. M. Scott Chem. Comm. 1970 576 U. Schollkopf J. Schossig and G. Ostermann Annalen 1970 737 158.'-For a review see U. Schollkopf Angew. Chem. Internat. Edn. 1970 9 763. '' N. Castagnoli J. C. Craig A. P. Milikian and S. K. Roy Tetrahedron 1970,26 4319. G. F. Hennion and M. J. Shoemaker J. Amer. Chem. SOC.,1970,92 1769. 'O H. Iwamura M. Iwamura T. Nishida and I. Miura Tetrahedron Letters 1970 31 17. 21 J. Jacobus Chem. Comm. 1970 709. 22 G. L. Closs J. Amer. Chem. SOC.,1969 91 4552; G. L. Closs and A. D. Trifunac ibid. 1970 92 2186. A. R. Forrester precursor.23 Application of the theory to predict "F CIDNP spectra is awaited.24 The harmful effect which an excess of nitrite ions has on the stability of dia- zonium salts has been attributed2' to the formation of the adduct (11) which decomposes rapidly to phenyl radicals and nitrogen.Using dimethyl sulphoxide as solvent this reaction may be utilised for the preparation of unsymmetrical biaryls and indeed appears to have advantages over the Gomberg and Ullmann + Ph.+ Nz + PhN=N-O* PhSO,N=N-SMe, I 0- (12) reactions. The identity of the species which abstracts hydrogen from the inter- mediate cyclohexadienyl radical is uncertain NO2 [equation (2)] N203 or PhN=N -0-[equation (311 being likely candidates (cf. decomposition of N-nitrosoacetanilide26 and P-phenylazoxyto~ylate~~). Photolysis of aryl-lithium ditrifluoroacetates2' (recommended for synthetic work) and N-phenylsulphonyl- dimethyl sulph~xime~~ (12) are other new methods of generating phenyl radicals. In the latter case the phenyl radicals so-formed are apparently more electrophilic that those produced thermally from benzoyl peroxide values for FK of 1.95 and 1.35 respectively being obtained on competitive phenylation of mixtures of toluene and benzene by these methods.Although methylbenzenediazo sulphone on heating in non-polar solvents decomposed mainly by the expected homolytic route to phenyl radicals and sulphur dioxide3* (cJ ref. 31) the corres- ponding benzyl sulphone (13) did not.32 Instead it gave mainly benzaldehyde phenyl hydrazone almost certainly by a radical-chain process which is not yet fully understood and clearly requires further study. However the alternative 23 G. A. Ward and J. C. W. Chien Chem. Phys. Letters 1970 6 245. 24 J. W. Rakshys Chem. Comm. 1970 578. 25 M.Kobayashi H. Minato N. Kobori and E. Yamada Bull. Chem. SOC.Japan 1970 43 1131. 26 M. J. Perkins Ann. Reports (B),1969 66 169; ibid. 1968 65 181 ; C. Ruchardt and C. C. Tan Chem. Ber. 1970,103 1774. 27 L. A. Neiman V. S. Smolyakov Yu. S. Nekrasov and M. M. Shemyakin Tetrahedron 1970 26 4963. 28 E. C. Taylor F. Kienzle and A. McKillop J. Amer. Chem. SOC.,1970 92 6088. 2q R. A. Abramovitch and T. Takaya Chem. Comm.. 1969 1369. 30 J. L. Kice and R. S. Gabrielsen J. Org. Chem. 1970 35 1004. M. Kobayashi H. Minato and N. Kobori Bull. Chem. SOC.Japan 1970 43 219. 32 J. L. Kice and R. S. Gabrielsen J. Org. Chem. 1970 35 1010. Free-radical Reactions 181 schemes [equations (4) and (5)] postulated to account for the product are in- teresting conjectures.Kinetic measurements on a number of N-aroyl-N'-aryldi-imides has confirmed that production of aryl radicals by alcoholysis of PhCH,SO,NNPh + PhCH2-+ SO2 + PhCH,N=NPh PhCHy I lt CHzPh PhCH=NNHPh (4) PhCH,SO,N=NPh Tu3) PhCHSO,N=NPh + PhCHNNPh -+PhCHN=NPh (5) 'S6 this source is initially a heterolytic process yielding an aryl di-imide which after oxidation homolytically fragments to aryl radicals [equation (6)].33 ArN=NCOAr' + ROH + Ar'COOR + ArN=NH + Arm + N (6) Similarity in the rates of production of arene (via Ar.) and aromatic ether (via Ar') in the well-known but not well-understood reaction of diazonium salts with methanol has led to the proposal that a common intermediate participates in both routes (an ill-defined activated ArN species).34 Similar propagation + steps have been suggested35 for formation of arene both in the above reaction and in the thermal decomposition of N-nitrosoacetanilide in ether [MeCHOEt replaces CH,OH in (7)].In the latter case the participation of the propagating .CH20H + ArN2+ + Ar-+ N + +CH20H Ar.+ CH,OH -P ArH +.CH,OH (7) radical MecHOEt was confirmed indirectly by e.s.r. measurements. Reduction of diazonium salts to arenes may also be effected by stannyl or silyl hydride~.~~ The relatively low ratio of 2- to 3-phenylthiophen (72 :38) obtained on pheny- lating thiophen with phenylazotriphenylmethane compared with those (ca. 93 :7) obtained using other sources of phenyl radicals has been shown37 to be due to interception of the precursor (14; X = S) of 2-phenylthiophen by the triphenylmethyl radical thus producing a pair of stereoisomeric dihydrothio- phenes (15; X = S).The corresponding dihydrofurans (15; X = 0) were obtained from furan and phenylazotriphenylmethane. Furan which is homo- lytically arylated exclusively in the 2-position is 11.5 times more reactive than ph>o + ph,C. -jPhaPh HX HXH (14) (15) 33 T. Carty and J. M. Nicholson Tetrahedron Letters 1970 4155. 34 T. J. Broxton J. F. Bunnett and C. H. Paik Chem. Comm. 1970 1363. 35 J. I. G. Cadogan R. M. Paton and C. Thomson Chem. Comm. 1970 229; D. F. DeTar and T. Kosuge J. Amer. Chem. SOC.,1958 80 6072. '' J. Nakayama M. Yoshida and 0. Simamura Tetrahedron 1970 26 4609. 37 C. M. Camaggi R. Leardini M. Tiecco and A.Tundo J. Chem. SOC.(B) 1969 1251; ibid. 1970 1683. 182 A. R. Forrester benzene and 4.4 times more reactive than thiophen to phenyl radicals.38 By comparison the relative reactivities of benzene thiophen and pyridine to phenyl radicals generated from nitrobenzene at 600 "Care in the ratio 1:5 :2.3 respec- tively. Considerable differences in the behaviour of 2- 3- and 4-thiazolyl radicals towards mono-substituted benzenes have been noted. Surprisingly the 4thiazolyl radical seems to be more electrophilic than its 2-isomer which like the 2-thienyl radical is more electrophilic than ~henyl.~' Relative reactivities towards phenyl radicals of the ring positions of benzo-thia~oles,~' dimethylpyridines$2 na~hthalene,~~?~~ 2-rnethyl-na~hthalene:~ polyfluoroarene~,~~ have been evaluated.For the last-men- and a~obenzene~~ tioned the activating effect ofthe phenylazo-group is comparable with that of the nitro-group. Related studies of homolytic aroyloxylation of a number of mono-substituted benzenes have confirmed that para-substituents affect the polarity of aryloxyl radicals to a greater extent than they do aryl radicals.47 Benzoyloxy- lation of a series of mono-substituted arenes using benzoyl peroxide-iodine has been shown to be a free-radical process although isomer distributions do infer that the attacking species is larger than a simple benzoyloxyl radical.48 A considerable amount of information has accrued recently on polyfluoro- phenyl radical^.^^.^' These radicals are clearly more electrophilic than phenyl but like phenyl give good yields of biaryl when generated in benzene.However reaction of pentafluorophenyl with hexafluorobenzene is complex and is un- satisfactory for the preparation of decafluorobiphenyl. Doubt has now been cast on the claim that o-iodophenyl radicals yield benzyne by spontaneous elimination of atomic iodine by the discovery that thermal decomposition of p-iodophenylazotriphenylmethane gives products derived exclusively from triphenylmethyl and o-iodophenyl radicals. ' This result lends support to the argument that production of arynes by photolysis of o-di-iodoarenes entails concerted loss of two iodine atoms.50 38 L. Benati N. La Barba M. Tiecco and A. Tundo J. Chem. SOC. (B) 1969 1253; L. Benati M.Tiecco A. Tundo and F. Taddei ibid. 1970 1443. 39 E. K. Fields and S. Meyerson J. Org. Chem. 1970 35 62 67. 40 A. L. Lee D. Mackay and E. L. Manery Canad. J. Chem. 1970,48,3554; G. Vernin R. Jauffred H. J.-M. Dou and J. Metzger J. Chem. SOC. (B) 1970 1678. 41 G. Vernin H. J.-M. Dou G. Loridan and J. Metzger Bull. SOC. chim. France 1970 2705. 42 J. M. Bonnier J. Court and M. Gelus Bull. SOC. chim. France 1970. 139; J. M. Bonnier and J. Court ibid. 1970 142. 43 N. Kobori M. Kobayashi and H. Minato Bull. Chem. SOC.Japan 1970 43 223. 44 J. M. Bonnier and J. Rinaudo Bull. Sac. chim. France 1970 146. " P. H. Oldham G. H. Williams and B. A. Wilson J. Chem. SOC.(B) 1970 1346. 46 J. Miller D. B. Paul L. Y.Wong and A. G. Kelso J. Cherii. Soc. (B) 1970 62.47 M. Kurz and M. M. Pellegrini J. Org. Chem. 1970 35 990. 48 P. Kovacic C. G. Reid and M. J. Brittain J. Org. Chem.. 1970 35 2152. 49 P. H. Oldham and G. H. Williams J. Chem. SOC.(C) 1970 1260; J. Burdon J. G. Campbell and J. C. Tatlow ibid. 1969 822. so J. M. Birchall R. N. Haszeldine and J. G. Speight J. Chem. SOC.(C) 1970 2187; J. P. N. Brewer I. F. Eckhard H. Heaney M. G. Johnson B. A. Marples and T. J. Ward ibid. 1970 2569. " G. W. Clark and J. A. Kampmeier Chem. Comm. 1970 996. Free-radical React ions The c~nclusions~~ of a study of the products of thermal decomposition of a number of diacyl peroxides labelled with l80and/or optically active in the main endorsed earlier views that ester formation proceeded by both heterolytic (involving carboxy inversion) and homolytic (radical-pair coupling) paths simultaneously the extent to which each contributed depending inter alia on the structure of the peroxide.However some of the limits expressed in this and earlier work may have to be amended in the light of the assertion by Goldstein and Judson53 that [3,3]-and/or [1,3]-sigmatropic shifts (Scheme 1)play an important r61e in the oxygen scrambling of peroxidic substances and hence that such scrambling should not be taken as a measure of the extent of radical-pair re- combination. An explanation different from that expressed above for the mech- anism of decomposition of diacyl peroxides has been conceived by Walling and his co-~orkers.~~ They prefer a scheme in which all products arise via the same transition state which passes to a transient ‘intimate radical-ion pair’ (16); this in turn may yield either polar or radical products depending on such factors as the structures of the peroxide and solvent.Other phenomena such as anchimetrically-assisted and molecule-induced homolysis were explained R I o/CQ-o I o\c4* I R R I R I o/c,,-;-.0 I .\c,O I R Scheme 1 52 T. Kashiwaga S. Kozuka and S. Oae Tetrahedron 1970 26 3619. ” M. J. Goldstein and H. A. Judson J. Amer. Chem. Soc. 1970,92 41 19 4120. 54 C. Walling H. P. Waits J. Milovanovic and C. G. Pappiaonnou J. Amer. Chem. SOC.,1970 92 4927. A. R. Forrester using the same model. The general lack of agreement among workers in this area is further exemplified by Leffler and Zepp's'' rationalisation of the forma- tion of 4-naphthyloxy-l-naphthoicacid (18 ; Ar = l-naphthyl) on thermal decomposition of bis(1-naphthoy1)peroxide.To them this product is the result of cage recombination of a geminate radical pair with rotation of one of the partner radicals yielding (17 ; Ar = l-naphthyl) and hence the acid (18 ; Ar = l-naphthyl). Other routes to (18 ;Ar = l-naphthyl) which did not involve H ArCOO Arcoo (1 7) (18) caged radicals were considered to be no more likely than that given above. In contrast with the above discord there appears to be general agreement56*57 that the products obtained by photolysis of diacyl peroxides are mainly derived from radicals reacting inside or outside the solvent cage.Thus by assuming for the hexenyl radicals (19) produced by photolysis of the corresponding peroxide that the rates of coupling in and diffusion from a solvent cage of pentane were fast relative to that of intramolecular cyclisation to (20) (k = lo' s-l at 25 "C),an estimate (35 %) of the radicals which coupled within the solvent cage was made by measuring the relative yields of dimers with and without a pentane ring.57 Complementary e.s.r. studies revealed that at -90 "Conly the spectrum of the hexenyl radicals was observed and above -35 "C only that of the cyclo- pentylmethyl radicals. From these observations it was concluded that only those radicals which escaped from the solvent cage were observed by e.s.r.Alkyl radicals generated by photolysis of peresters in cyclo-propane at < -40 "C 55 J. E. Leffler and R. G. Zepp J. Amer. Chem. SOC., 1970 92 3713. 56 T. Kashiwaga K. Fujimori S. Kozuka and S. Oae Tetrahedron 1970 26 3639. ST R. A. Sheldon and J. K. Kochi J. Amer. Chem. SOC., 1970,92,4395. Free-radical Reactions 185 were also detectable but the geminate alkoxyl radicals whose ability to abstract hydrogen atoms makes their lifetime in bulk solution extremely short were not.58 By comparing the amounts of ether and alkene produced in these photolyses a measure of the ratio kdisproportionation for a caged pair of alkyl-alkoxyl :krearrangement radicals was obtained. These values were about twice as large as the correspond- ing ones for alkyl-alkyl radical pairs.Photolysis of t-butyl percyclopropylacetate was a particularly interesting case giving six times as much of the ether (21) as (22). Assuming that krearrangement was lo8s-' the rate of combination of the Wf-O-OBu' 0 + ">/\OBu+ OBu+ radical-pair (Bu'O. .-a)was estimated to be approximately lo9 s-' (this figure is in fact kcombinationx [Bu'O.]). Ring opening" of the analogous radicals (23) can occur either with C-0 fission to give alcohols or with C-C fission to give vinyl ethers via the radicals (24) and (25) respectively depending on the nature of the substituents R' and R2. A novel series of acyl carbamoyl peroxides which thermally decompose in three ways (Scheme 2) has been prepared; one of these provides a new route to aryl nitrenes.60 00 ArN + CO + PhC0,H II II ArNHCO-OCPh + ArNH.+ C02 + PhCOO. ArNH+ + CO + PhC02-Scheme 2 58 R. A. Sheldon and J. K. Kochi J. Amer. Chem. SOC.,1970,92 5175. 59 E. L. Stogryn and M.A. Gianni Tetrahedron Letters 1970 3025. 6o R. Okazaki and 0.Simamura Chem. Comm. 1969 1308. 186 A. R.Forrester Unlike di-t-butyl peroxide di-t-amyl peroxide when boiled in the absence of solvent gave very little of the expected oxiranes (26; R' = Et R2 = H and R' = R2 = Me). The principal product was acetone formed by fragmentation of the t-amyloxyl radical (note that elimination of ethyl is preferred to elimination of methyl).61 The obvious cyclic mechanism [equation (S)] to account for the considerable quantity of hydrogen together with products from sec-BuO- Me MeCH2C-0.+ Me,CO + Et-I :v:e I Me (26) on thermolysis of di-sec-butyl peroxide does not seem to explain fully all the available facts such as the failure of the peroxide to generate hydrogen on photolysis or on thermolysis in the gas phase.62 A large number of hydro-peroxides and amino-peroxides e.g. (27; R = H and But) and (28) have been prepared by treatment of mixtures of carbonyl compounds and hydrogen peroxide or t-butyl hydroperoxide with ammonia and their thermal and base catalysed decompositions have been extensively studied.63 Interestingly thermolysis of the peroxide (28) gave among other products caprolactam (29) L J possibly as indicated. An unusual product formed by heating or oxidising t- butyl hydroperoxide in the presence of tetracyclone has been ascribed64 the ring-expanded lactone structure (31).This Baeyer-Villiger type of oxidation 61 E. S. Huyser and K. J. Jankauskas J. Org. Chem. 1970,35 3196. 62 R. Hiatt and S. Szilagyl Canad. J. Chem. 1970 48 615. 63 E. G. E. Hawkins J. Chem. SOC.(C),1969 2663 2671 2678 2682 2686 2691. 64 N. L. Weinberg Canad. J. Chem. 1970 48 1533. Free-radical Reactions 187 product was considered to arise via the initial adduct (30) by the sequence of reactions shown. Bu'O 0 0 (30) Ph 1 c- 0 Bu' (31) The first in a series of three volumes which deals in depth with the chemistry of peroxidic substances is now available.6s Thermal decomposition of optically active azo-compounds has been further studied and results obtained last year66 which showed that randomisation of orientation of the radical pairs competed effectively with radical recombination within the cage have been c~nfirmed.~~ Size and shape of the participating radi- cals however would seem to be all important factors in such competing processes.68 The observation6' of a CIDNP emission signal during thermal decomposition of triarylpentazadienes (32) has been attributed to the inter- mediate production of an arylazo-triazenyl radical pair (33) which recombines before the arylazo-radical can lose nitrogen.This result has bearing on previous Ar N=N-N -N=NAr3 -Ar'N=N-NArZ ArZN=N-N-N=NAr3 I I Ar2 -Ar3N=N. Ar' 1 arguments7' in favour of cage recombination of arylazo-radicals formed by thermolysis of unsymmetrical azo-compounds which decompose with initial homolysis of only one bond e.g.p-nitrophenylazotriphenylmethane.The dependence of the rate constants for decomposition of free-radical initi- ators on the viscosity of the medium has been used as a criterion for classifying initiators into 'one bond' (those which decompose by initial cleavage of only one '' 'Organic Peroxides' Vol. 1 ed. D. Swern Wiley New York 1970. " e.g. K. R. Kopecky and T. Gillan Canad. J. Chem. 1969 47 2371. 67 F. D. Greene M. A. Berwick and J. C. Stowell J. Amer. Chem. SOC.,1970 92 867. '8 C. G.Overberger and D. A. Labianca J. Org. Chem. 1970 35 1762. 69 J. Hollaender and W. P. Neumann Angew. Chem. Internat.Edn. 1970,9 804. 70 W. A. Pryor and K. Smith J. Amer. Chem. SOC.,1967 89 1741. A. R. Forrester bond) and 'multi-bond' (e.g. symmetrical azo-compounds) ~ategories.~ For most initiators (but not for some peracetates) results obtained by this method agree with previously obtained data. The strong preference of cumyl radical pairs (and indeed for other aralkyl radicals in which there is substantial electron delocalisation) to couple rather than disproportionate apparently for no good reason has been uncovered again during an investigation of the decomposition of a-cumylazocyclohexane.72 Other work on azo-compounds has been con- cerned with their photosensitised decomposition7 and pressure dependence of the decomposition of di- t- bu t yl h yponi trite (But 0-N=N -0Bu').The ease of formation of the sulphate radical-ion by reduction of potassium persulphate with titanium(Ir1) in a flow system has allowed its reactions with a wide variety of organic substrates to be monitored by e.s.r. spectro~copy.~~ Using this technique it has been shown that SO,' will abstract hydrogen (from saturated compounds such as alcohols) or an electron [e.g. from acetate or nitr~alkane-anions~~ (cc ref. 77)] and will add to unsaturated (alkenes) and aromatic (arene di- and tri-carboxylic acids) compounds. In many respects the behaviour of this relatively electrophilic species is similar to that of the hydroxyl radical its rate of hydrolysis to which in aqueous solution increases with increasing pH. Determinati~n~~ of the products obtained on treatment of mainly phenyl- and phenoxy-acetic acids with the -OH and SO,' generating reagents [H202-Tirn and S2O8-Ti1I' respectively] supported the addition- fragmentation schemes [e.g.equation (911 formulated to account for the detection of benzyl and phenoxymethyl radicals in the parallel e.s.r.experiments. With the sulphate radical-anion however the formation of a o-bonded adduct such (34) as (34) is not mandatory electron transfer followed by fragmentation of the ensuing radical-cation being a feasible alternative. o-Phenylpheno~ymethy1~~ and o-phenylbenzamido8' radicals formed by thermolysis of persulphate in the presence of the corresponding acids and amides respectively cyclised efficiently onto the neighbouring ring to give benzopyrans and phenanthridones " W.A. Pryor and K. Smith J. Amer. Chem. SOC.,1970,92 5402. 72 R. C. Neuman and E. S. Alhadeff J. Org. Chem. 1970,92,3401. 73 P. S. Engel and P. D. Bartlett J. Amer. Chem. SOC.,1970 92 5883. " R. C. Neuman and R. J. Bussey J. Amer. Chem. SOC.,1970,92,2440. 75 R. 0.C. Norman P. M. Storey and P. R. West J. Chem. SOC.(B) 1970 1087. 76 D. J. Edge R.0. C. Norman and P. M. Storey J. Chem. SOC.(B) 1970 1096. '' A. H. Pagano and H. Shechter J. Org. Chem. 1970,35,295. 78 R. 0. C. Norman and P. M. Storey J. Chem. SOC.(B) 1970 1099. 79 P. S. Dewar A. R. Forrester and R. H. Thomson Chem. Comm. 1970 850. P. M. Brown P. S. Dewar A. R. Forrester A. S. Ingram and R. H. Thomson Chem. Comm. 1970 849. Free-radical Reactions 189 in good yield.Highly resolved e.s.r. spectra of phenoxyalkyl radicals have been observed" by irradiating anisoles dissolved in di-t-butyl peroxide at -35 "C in the cavity of the spectrometer. The hydrogens of the methoxyl group of anisole are in fact extremely reactive towards t-butoxyl radicals being only slightly less so than those of toluene.82 Isopropyl phenyl ether which would be expected to be even more reactive than anisole in such reactions gave mainly phenol and isomeric isopropylphenyl isopropyl ethers (37) but significantly no dimeric or trimeric products derived from phenoxyl radicals.83 This observa- tion led to the suggestion that phenol and not phenoxyl was eliminated from the adduct (39 the resulting cumyl radical (36) abstracting hydrogen to give the product.Full corroborative evidence for such a sequence of events has still to be presented. Me (35) (36) (37) The key step in the oxidative decarboxylation of aliphatic acids with persul- phate in the presence of silver@) ions is the initial oxidation by the persulphate of silver(1) to silver(Ir) the latter being the effective oxidant of the acids.84 The alk yl radicals formed on decarboxylation suffer further oxidation to carbonium Ag' + S2082-+ Ag" + SO,; + SO4'-SO,; + Ag' * Ag" + SO,2-Ag" + RCOzH -P R. + COz + H+ + Ag' ions by SO4- S,082- or silver(@ and products derived from both radicals and ions are obtained. The synergistic effect of copper(@ ions on this reaction has been ascribed to the facility with which they oxidise alkyl radicals to carbonium ions.Related studies of the oxidative decarboxylation of acids using mangan- ese(II1) gave broadly similar results.85 However because of the low oxidation potential of the Cu"-Cu' system the ability of Cu" to oxidise alkyl radicals by a simple electron transfer process has been questioned. Evidence has been adduced favouring simultaneous reaction of copper(1r) with the unpaired electron and the 8-hydrogen atom of alkyl radicals to form alkenes.86 In addition oxidation of the cyclohexenylbutyl radical (38) to alkene by copper(I1) in non- polar solvents is considered to proceed without participation of the corresponding " A. Hudson and K. D. J. Root J. Chem. SOC.(B) 1970,656. H. Sakurai A. Hosomi and M.Kumada J. Org. Chem. 1970,35,993. 83 A. Ohno and N. Kito Bull. Chem. SOC.Japan 1970 1272. 84 J. M. Anderson and J. K. Kochi J. Amer. Chem. SOC.,1970,92 1651 ;J. Org. Chem. 1970 35 986. " J. M. Anderson and J. K. Kochi J. Amer. Chem. Soc. 1970,92 2450. 86 K. Torssell Arkiu Kemi 1970 31 401. A. R. Forrester carbonium ion (which would rapidly cyclise to 1,9- and 9,10-octalins) but rather by way of an organo-copper intermediate (39) which undergoes concerted decomposition as shown.87 In view of the above results the conclusion that ,‘cu -0 -c’ A~O Me (39) 2-phenylcyclopropane carboxylic acids are oxidatively decarboxylated by lead tetra-acetate in the presence of copper(1r) to carbonium-ions (via the corres- ponding radicals) which ring open and are then acetoxylated in a non-stereo- specific manner requires further consideration.88 Photolysis of lead(1v) carboxylates in carbon tetrachloride solution has been recommended for the transformation of carboxylic acids into chlorides with one less carbon atom.89 Thermolysis of iodine triacylates (formed in situ by ozonisation of acid anhydrides in the presence of iodine) with mercuric oxide gave carbon dioxide and esters in good yield.” This conversion which is a close relation of the Simonini reaction has been assigned the radical-chain mechanism given here in abbreviated form.(RCO2)3I -+ Re + (RC02)zI + I. R. + (RC02)3I + RCOOR + (RCO2)2I --+ (RCOZ),I R.+ COZ + RCO,I + Re+ C02 + I. R-+ 1. RI The structural requirements for intramolecular hydrogen abstraction by alkoxyl radicals have been probed by oxidising the medium-sized ring alcohols cyclodecanolgl and 4-and 5-phenylcyclo-octanols92with lead tetra-acetate.D. L. Struble A. L. J. Beckwith and G. E. Gream Tetrahedron Letters 1970 4795. 88 T. Shono I. Nisuiguchi and R. Oda Tetrahedron Letters 1970 373. 89 V. Franzen and R. Edens Annalen 1970 735 47. 90 G. B. Bachman G. F. Kite S. Tuccarbasu and G. M. Tullman J. Org. Chem. 1970 35,3167. 91 M. L. J. Mihailovic V. Andrejevic M. Jakovljevic D. Jeremid A. Stojiljkovic and R. E. Partch Chem. Comm. 1970 854. 92 A. C. Cope M. A. McKervey N. M. Weinshenker and R. B. Kinnel J. Org. Chem. 1970 35 2918. Free-radical Reactions With cyclodecanol little of the expected 1,4-bridged ether was obtained the main etherial products being the trans-epoxycyclodecane (42) and diasterio- isomeric 7-oxabicyclononanes (44).Experiments with deuteriated cyclodecanols supported a scheme for formation of the former in which a second 1,5-hydrogen (or hydride) shift (40)+(41) precedes oxidation and ring closure. For the latter product p-scission followed by a 1,5-hydrogen shift and recombination seems a likely route to the precursor (43) of the bicyclononanes. The high yield of the ether (45) (72 %) formed from trans-5-phenylcyclo-octanolwith lead Ph B tetra-acetate is noteworthy since a seven-membered transition state is required in the hydrogen transfer step. Fisch et aLg3has a similar experience with the bicyclic alcohol (46) conversion into oxoadamantane (47) proceeding in -86 % yield.However neither of the adamantyloxyl radicals (48)and (49) (formed by thermolysis of their hypohalites) appears to possess the geometrical require- ments for intramolecular hydrogen transfer since both fragmented to give the halo-ketone as final product.94 Oxidation of alkylarenes and alkyl aryl ethers both electrochemically and with inorganic reagents continues to attract attention. With cobalt(111) acetate in acetic acid toluene gave principally benzyl acetate formation of which via the initially-formed radical-cation (SO) (detected by e.s.r.) is easily envisaged [equation In the presence of chloride ions which accelerate the overall rate of oxidation the course of reaction was partly diverted and nuclear halo- genated products were also formedg6 [equation (1 l)].By comparison man- 93 M. Fisch s. Smallcombe J. C. Gramain M. A. McKervey and J. E. Anderson J. Org. Chem. 1970 35 1886. 94 R. M. Black and G. B. Gill Chem. Comm. 1970 972. 95 P. J. Andrulis and M. J. S. Dewar J. Amer. Chem. SOC.,1966 88 5483. 96 E. I. Heiba K. M. Dessau and W. J. Koehl J. Amer. Chem. SOC.,1969 91 6830. A. R. Forrester ganese(m) acetate gave little side-chain acetoxylated product unless the toluene had an electron-donating para-substituent (MeO) to lower its ionisation poten- tia1.97 Although bromide ions accelerated the latter oxidations they did not X alter the course of the reaction. Formation of ring and side-chain acetoxylated and ring-chlorinated products on oxidation of dimethoxybenzenes with lead tetra-acetate in the presence of chloride ions can be explained in a similar way.98 In a study of the anodic oxidation of toluene an additional mechanistic possibility was proposed to account for the production of benzyl acetate." A radical generated by Kolbe electrolysis of the electrolyte may abstract a hydrogen from toluene yielding a benzyl radical which after anodic oxidation to a car- bonium ion is solvolysed.Attempted synthesis' O0 of o-tolualdehyde from o-xylene by oxidation with cerium(rv) in dilute nitric acid revealed the existence of two independent oxidation routes one of which gave the aldehyde via the alcohol and the other gave 2-methylbenzyl nitrate which resisted hydrolysis to the alcohol.Detailed mechanistic studies are required to resolve this apparent dichotomy. Close similarities in the modes by which chromate and permanganate oxidise 9CH to ?C-OH have been established by examining the kinetic and stereo- chemical aspects of the oxidation of optically active y-phenylvaleric acid to the lactone (50)with permanganate in alkaline solution. lo' The essential features 0 II Me ,0-C I P~I~~\CH,-CH2 97 J. R. Gilmore and J. M. Mellor Chem. Comm. 1970 507; E. I. Heiba K. M. Dessau and W. J. Koehl J. Amer. Chem. SOC.,1969 91 138. 98 R.0.C. Norman and C. B. Thomas J. Chem. SOC.(B) 1970,421. 99 S. D. Ross M. Finkelstein and R.C. Petersen J. Org. Chem. 1970 35 781. loo L. A. Dust and E. W.Gill J. Chem. SOC.(0,1970 1630. lo' J. I. Brauman and A. J. Pandell J. Amer. Chem. SOC.,1970,92 329. Free-radical Reactions of the mechanism are slow abstraction of the tertiary hydrogen by permanganate with formation of a caged radical pair which combines before the stereochemical integrity of the carbon radical is completely lost. Hydrolysis of the manganese(v) ester so-formed produces the hydroxy-acid and hence the lactone. 9C-H + Mn0,-+ [>C.MnO,H-] -+ SC-OMnO,H-1 >C-OH + MnV The efficiency with which alkyl halides are reduced to alkanes by a chromium(u)-ethylene diamine reagent in aqueous dimethylformamide has been attributed to the intermediate production of an alkyl chromium(1Ir)- ethylene diamine species [equations (12) and (1311 which rapidly undergoes acid-catalysed hydrolysis giving alkane.'02 Since reduction of a-bromoethyl benzene with chromous sulphate in aqueous dimethylformamide gave mainly RX + CrIlenz+ *R.+ CrIIIen,Xz+ (12) R.+ Cr"en,'+ -+ RCr"'en,'+ (13) equal quantities and meso-and dl-2,3-diphenylb~tane,'~~ and since the second step [equation (13)] is thought to be rapid when R = alkyl (estimated k = 4x lo71 mol-s-') it would seem that the complexing agent and/or the structure of the alkyl group are important factors in determining the course of the above reduction.In a selective review such as this it is inevitable although unfortunate that several areas of free radical chemistry in which there is current activity e.g. addition to alkenes and halogenation have been largely ignored.It is to be hoped that subsequent reports will strive to restore the balance. lo' J. K. Kochi and J. W. Powers J. Amer. Chem. SOC.,1970 92 137. '03 W. G. Brown and D. E. McClure J. Org. Chem. 1970,35 2036.

ISSN:0069-3030    

DOI:10.1039/OC9706700177

出版商:RSC    

年代:1970

数据来源: RSC