3 (Part ii) REACTION MECHANISMS By N. S. Isaacs (Department of Chemistry The University Whiteknights Park Reading) Stable Carbonium Ions.-Rates of reaction of the tris-(p-methoxypheny1)- carbonium ion with water hydroxide ion and ammonia have been measured by a stopped-flow technique. The second-order rate constants are 0.28 4-6 x lo3 and 2.1 x lo3 1. mole-1 set.-' respectively and a negative salt effect was observed. The spectroscopic properties of a large number of sub-stituted and bridged trityl cations have been recorded2 and resolution of the first asymmetric carbonium ion (1)(by virtue of restricted rotation) has been achieved. The n.m.r. spectra of some diphenyl (2-and 3-pyridinium)methyl dications (2) have shown that the heterocyclic ring protons are more deshielded than the phenyl proton^.^ Among new aromatic cations are the ditropylium dication (3) which exhibits a singlet n.m.r.spectrum at z 0.05 (cf:the tropylium ion at z 1-31) and is assumed to be twisted about the central bond.5 The tri-t-butylcyclopropenium ion appears to be less stable (pKR+ = 6.1) than the tri-isopropyl analogue (pKR+= 7.0) as measured by titration against sodium hydroxide in 50% aqueous acetonitrile.6 How much this is due to steric crowding and how much to a reduction in electron release by the t-butyl group is difficult to assess but it may be relevant that the heptaphenyltropylium ion is less stable than ' E. A. Hill and W. J. Mueller Tetrahedron Letters 1968 2565. R Breslow S.Garratt L. Kaplan and D. La Follette J.Amer. Chem. Soc. 1968 90 4051 ; R. Breslow L. Kaplan and D. La Follette ibid. p. 4056. B. L. Murr and L. W. Feller J. Amer. Chem. SOC.,1968,90,2966. G. A. Olah and M. Calin J. Amer. Chem. SOC.,1968,90,943. I. S. Akhrem E. I. Fedin B. A Kvasov and M. E. Vol'pin Tetrahedron Letters 1967 5265. J. Ciabat'toni and E. C. Nathan J. Arner. Chem. SOC.,1968,90,4495. 104 N. S. Isaacs the corresponding hexaphenyl compound which is almost certainly due to crowding and lack of coplanarity of the rings.7 The n.m.r. spectra of the benzo-(4)* and dibenzo-homotropylium ions' have been recorded for sul- phuric acid solutions at room temperature. The em-and endu-methylene -73 HO.70 0.80 H .1.29 protons are quite distinct being shielded and deshieIded respectively by the aromatic ring current.At 0" slow deuterium exchange of the latter is observed in deuteriosulphuric acid but only at quite elevated temperatures does general deuterium exchange occur. The stable carboxonium ion (5) has been reported.'O The all-trans-retinene cation (A,,, 600 nm.) was observed to be stable for several minutes in aqueous acidic solution at 4" its low reactivity being at- tributable to the sharing of the charge by the 11 carbon atoms of the con- jugated chain. '' The i.r. spectra of the acetylium and trideuteroacetylium ions (as hexafluoroantimonates) show a carbonyl-stretching frequency in the vicinity of 2300 cm.- l2 indicating considerable triple-bond character (oxonium character) of this species; this was confirmed by X-ray diffraction measurements of the bond lengths.A number of 3-phenyl-3-benzocyclo-butenyl cations (6) have been observed by n.m.r. spectroscopy in sulphuric acid. From a consideration of the pK,+ values these ions appear to be more stable than the analogous benzhydryl cations possibly because one ring at least and perhaps both are coplanar with the positive centre.13 7.7 Me 1.5-2.0 Cl Me (6) ' M. A. Battiste and T. J. Barton Tetrahedron Letters 1968,2951. W. Merk and R. Pettit J. Amer. Chem. SOC. 1968,90 814. R. F. Childs and S. Winstein J. Amer. Chem. SOC.,1967,89 6348. lo K. Dimroth and W. Mach Angew. Chem. Internat. Edn 1968,7,461. l1 P. E. Blatz and D. L. Pippert,J. Amer. Chem. SOC. 1968,90 1296. l2 P. N. Gates and D. Steele J.Mol. Struct. 1968 1 349. l3 H. Hart and J. A. Hartlage,J. Amer. Chem. Soc. 1967,W. 6672. Reaction Mechanisms 105 Allylic cations are greatly stabilised by substituent chlorine. Pentachloroallyl tetrachl~roaluminate'~has been isolated as bronze crystals (hmax 435 nm.) and the n.m.r. spectrum of the 1,2,3-trichloroallyl cation has been observed in solution (7).15 The n.q.r. spectrum of the trichlorocyclopropenium ion has been studied'6 and has been interpreted as showing 16% n-character in each C-CI bond and from 50-75% of the excess positive charge carried on chlorine. Strong electrolyte character is exhibited by trityl hexachloroant- imonate in dichloromet hane solution as judged by conductance measure-ment~.~~ The i.r. spectrum of the benzoyl cation1* has been reported and crystalline acetyl- and thiobenzoyl-hexafluoroantimonatesl9 have been iso- lated and have been shown to be ionic.The latter compound is a highly reactive electrophile and with benzene gives thiobenzophenone in a rare example of a Friedel-Crafts thione synthesis (8). A significant volume of new work has PhC=S + -g+PhCSPh (8) appeared concerning the properties of highly acidic solvents such as antimony pentafluoride-fluorosulphonic acid ; the subject has been reviewed by Gilles- pie.20 Cyclopropane at -100" in this system shows an n.m.r. spectrum con- sisting of two closely spaced doublets (z 7.7 and 7.9) and a septuplet (T 3.6). These signals were tentatively assigned to a protonated cyclopropane.2 At higher temperatures decomposition to the 1-methylethyl cation and various C-4 and C-5 cations occurs.Cyclobutane under the same conditions undergoes a hydride loss to give a cyclobutyl (or cyclopropylmethyl) cation also unstable above -loo" while the same behaviour is shown by cyclopentane up to -10". The greater stability of this ion compared with cyclobutyl would be expected on grounds of ring strain. The cyclopropyl cation can be generated and shows only a singlet n.m.r. signal. This evidently indicates that rapid hydride migration around the ring is taking place. However above -lo",ring-opening and alkylation leads to the pentyl cation. The same stable cation is formed when either norbornane norborenene tricyclane or norbonyl halides are dissolved in SbF,-HF-FSO 3H.22 The structure suggested for this species is (9) on the grounds that the Raman spectrum shows similarities to that of tricyclane (lo) the n.m.r.spectrum being in agreement. Halogenocyclopro- panes are pr~tonated~~ at -78" but rearrange to halogenium ions (1l),species l4 K. Kirchhoff F. Boberg D. Friedemann and G. R. Schultze Tetrahedron Letters 1967 3861 P. T. Kwitowski Diss Abs. 1967,28B 583. K. Kirchhoff F. Boberg and D. Friedemann Tetrahedron Letters 1968,2935. l6 E. A. C. Lucken and C. Mazeline J. Chem. Soc. (A),1968 153. N. Kalfoglou and M. Szwarc J. Phys. Chem. 1968,72 2233. H. Perkampus and W. Weiss Angew. Chem. 1968,80,40. l9 (a)F. P. DeBoer J. Amer. Chem Soc. 1968,90,6706;(b)E. Linder and H. G. Karmann Angew. Chem. Internat.Edn. 1968 548. 2o R. J. Gillespie Accounts Chem. Res. 1968 1 202. 21 G. A. Olah and J. Lukas J. Amer. Chem. SOC.,1968,90,933,938. 22 G. A. Olah A. Commeyras and C. Y. Liu J. Amer. Chem. SOC.,1968,90,3882. 23 G. A. Olah and J. M. Bollinger,J. Amer. Chem. Soc. 1968,90,6082. 106 N. S. Isaacs Me Me H (9) 00) (11) observed previo~sly,'~ which in turn above -10" eliminate Hhal to give a species the spectrum of which is compatible with the 2,3-dimethylbut-3- enyl cation (12). This appears to have a localised structure which indicates that an allylic interaction provides less stabilisation than a tertiary position. The n.m.r. spectra of a number of ally1 cations have been studied over a range of temperatures and the energy and entropy barriers to rotation about the carbonxarbon bonds have been estimated to be in the range E = 4-6 kcal.mole- and ASs = ca -30 e.u. ;this is due apparently to the resonance energy of the allylic cation rather than to nonbonded interactions. Halo- genium ions (13;Z = C1 Br I) have been prepared by ionisation of the fluoro- compounds (14),in SbF,-HF the stereochemistry has been shown to be that Me Me SbF -Me CH derived from rearside displacement of fluoride only for the iodidesz5 Both threo-and erythro-(15; Z = C1 or Br) lead to the same mixtures of cis-and trans-halogenium ions.24 Evidently the cyclic ion is in equilibrium with an open carbonium form in which rotation can occur. The 1,l-dimethyl-2- chloroethyl cation is more stable than the corresponding chloronium ion form from which the n.m.r.spectrum readily distinguishes it. Five- and six- + threo or Erythro (15) cis + trans (16) membered halogenium compounds (16) have also been recognized and can be formed by dissolution of the 1,6-dihalogenohexane or 5-halogenohex-1 -ene in SbF5-HS03F at low temperatures.26 A variety of hydroxycarbonium ions have now been shown to be stable in these strong acid solutions. Carboxylic 24 G. A. Olah J. M. Bollinger and J. Brinich J. Amer. Chem. Soc. 1968,90,2587 25 G. A. Olah and J. M. Bollinger J. Amer. Chem. SOC.,1968,90,947. 26 G. A. Olah and P. E. Peterson,J. Amer. Chem. SOC..1968,90,4675. Reaction Mechanisms 107 acids,27 dialkyl carbonates and hydrogen carbonates2* protonate to give (17) and (18) respectively ; protonated carbonic acid (trihydroxycarbonium OR' 4,-R3-C:.+ \-OR' (17) R' = RZ = H (19) X = Y = Z = OH SH NHZ (18) R' = R3.R' = H X = Y = OH,Z = SH,NH' R' = RZ = R3 X = OH,Y = Z = SH,NH (20) X = OH;Y,Z =OH,OR ion) is stable to 0". The complete series of sulphur and nitrogen analogues have also been observed2' (19) (formed from thiocarbonic and carbamic acids urea and guanidine). Hydrogen cyanide and aliphatic nitriles protonate on nitrogen3' but carbamates protonate on oxygen (20). It is of great interest to observe such species many of which are implicated in acid-catalysed hydrolyses as transient intermediates. Dialkoxycarbonium ions (isolable as the tetrafluoroborates) behave as oxygen analogues of the ally1 cation and show a considerable rotation barrier about the C-0 bonds (21).31 At -30" R' I I I R' (21) RZ the alkyl groups R2 are distinguishable pointing to a preferred configuration but the separate signals collapse to a single one above 0" when rapid rotation brings both groups into a time-averaged identical environment.Protonation of methane to CHZ has been suggested to account for the isotopic exchange which takes place between CD and SbF,-HSO,F although an alternative route via the methyl cation might also be considered parallel to the behaviour of ethane. At higher temperatures (80-140") telomerisation of methane to t-butyl and di-isopropylmethyl cations occurs. 32 In superacid solutions diketones give rise to the bis-carboxonium ions3 (22) while at low temperatures diprotonated glycols can be observed and *' (a) G.A. Olah and A M. White J. Amer. Chem SOC.,1967,89 7072; (b)G. A. Olah and M. Calin J. Amer. Chem. SOC. 1968,90,405. 28 G. A. Olah and A. M. White J. Amer. Chem. SOC.,1968,90,1884. 29 G. A. Olah and A. M. White J. Amer. Chem SOC.,1968,90,6087. 30 (a) G. A. Olah and T. E. Kiovsky J. Amer. Chem. SOC. 1968 90 4666; G. A. Olah and M. Calin ibid. p. 4672; (b)G. A. Olah and M. Calin J. Amer. Chem. SOC.,1968,90,401. " R. F. Borch J. Amer. Chem. SOC.,1%8,90,5303. 32 G. A. Olah and R. Schlosberg,J. Amer. Chem. SOC.,1958,90,2726. 33 D. M. kouwer Rec. Trav. chim. 1968,87,225. 108 N. S. Isaacs undergo pinacolic rearrangements at higher temperatures.34 35 Brouwer has observed the n.m.r. spectra of some hydroxyallyl cations e.g. (24).36A temperature-dependent study of the n.m.r. spectrum of the t-pentyl cation37 has revealed the occurrence of Wagner-Meerwein rearrangements of methyl groups and hydride ions which retain their integrity throughout (25). Hexa-1,5-diene is converted to the methylcyclopentyl cation. 38 Further studies of benzenonium ions have included the crystal structure of heptamethylbenzenonium tetrachloroaluminate (26),39which shows bond lengths fairly close to those predicted from simple HMO theory (26 ;bracketed figures). Fluorot oluenes protonate in superacid media to give methylfluoro- Me \+ C-CH,-Me/Me Me\ ++ Me-C-CH-Me H / \/+ C-C-Me H’ \Me HMe + .+MeCH,-C Me + Me / \ (25) 1.536 1-497-,MeMe> 1.489 H H I7 (27) -Hf(40%) +0.092 +0.01 9 (281 benzenonium ions.“ Brouwer has observed and analysed the mixtures of isomeric benzenonium ions4’ produced by protonation at different sites in halogenotoluenes [e.g.(27)l. The same author has studied the kinetics of methyl migration among methylated benzenes in SbF,-HF by direct n.m.r. spectral observation^.^^ The 1,2-and 1,4-dimethylbenzenonium ions are transformed into the corresponding I,3-dimethyl ions at unimolecular rates of80 and 335 set.-at 25 ; 1.2.3,4-tetramethylbenzenoniumion gives 1.2.3.5- 34 G. A. Olah and J. Sommer J. Amer. Chem. Soc. 1968,90,927. ” G. A. Olah and J. Sommer J. Amer. Chem. Soc. 1968,90,4323. 36 D. M. Brouwer Tetrahedron Letters 1968,453.37 M. Saunders and E. L. Hagen J. Amer. Chem. SOC.,1968,90,2436. 38 D. M. Brouwer Rec. Trav. chim. 1968,87,702. 39 N. C. Baenziger and A. D. Nelson J. Amer. Chem. Soc. 1968,90,6602. 40 G. A. Olah and T. E. Kiovsky J. Amer. Chem. SOC.,1968,90,2583. 41 D. M. Brouwer Rec. Trav. chim. 1968,87,335. 42 D. M. Brouwer Rec. Trac. chim. 1968,87 611. Reaction Mechanisms 109 (155 sec ') and 1,2,3-trimethylbenzenoniumion is slowly converted to 1,2,4- trimethyl (8-9 sec ') and very slowly in turn into 1,3,5-trimethyl (lo-' sec '). Enthalpies and entropies of activation are in the range 19-23 kcal. mole-' and ca. -3 e.u. respectively. It will be of interest to compare these values with computed stabilities of the benzenonium ions. From l3C-n.m.r. data the charge- densities on each carbon of the 2,4,6-trimethylbenzenoniumand trityl cations have been measured and have been compared with theoretical values obtained by simple HMO and by SCF theories (28).43*44The superiority of the latter values are evident but still tend to exaggerate the values.CNDO (Complete Neglect of Differential Overlap) calculations on some simple carbonium ions have been reported and give a plausible account of the geometries and charge distributions although energies are not well reprod~ced.~' Reasonable agreement with experimental ionization potentials has been obtained by an SCF technique and calculated electronic structures of carbonium ions and protonated hydrocarbons have been reported.46 Calorimetric determination of the heats of formation of benzenonium ions has shown that their stabilities increase with increasing alkyl s~bstitution~~ as predicted.The pentamethylbenzenonium ion has been observed to be formed from the pentamethylcyclopentadienylmethylcation in FS03H (29a) rearranges to (29b) which undergoes a degenerate scrambling of the ring carbons.48 Transient Carbonium Ions.-Methods used for the generation of carbonium ions have included the oxidation of radicals by and the transfer of NO; from tetranitromethane to an olefin. The decomposition of N-nitroso- (or N-nitro-)-N-alkylamides and carbamates (30) gives rise to alkyl carbonium ions recognizable from the products5'* 52 of their subsequent reactions. The 43 G. J. Ray A. K. Colter D. G. Davies D. E.Wisnosky and R J. Kurland Chem Comm. 1968 815. 44 V. Koptyug A. Rezvukhin E. Lippmaa and T. Pehk Tetrahedron Letters 1968 4009. " K. Wiberg J. Amer. Chem. SOC.,1968,90,59. 46 T. Youezawa H. Nakatsuji and H. Kato J. Amer. Chem. SOC.,1968,90 1239. 47 E. M. Arnett and J. W. Larsen J. Amer. Chem. SOC.,1968,90 791 792. 48 R F. Childs M. Sakai and S. Winstein J. Amer. Chem SOC. 1968 90 7146; R F. Childs and S. Winstein J. Amer. Chem. SOC.,1968,90 7146. 49 (a) J. K. Kochi and A. Bemis .I.Amer. Chem. SOC. 1968,90 4038; (b) A. B. Evnin and A. Y. Lam Chem. Comm. 1968,1184. 50 S. Penczek J. Jagur-Grodzinski and M. Sczwarc J. Amer. Chem. SOC. 1968,90,2174. 51 E. H. White H. P. Tiwari and M. J. Todd J. Amer. Chem. SOC. 1968,90,4734. 52 E. R. Stedronsky J. Gal.R. A. M. O'Ferrall and S. I. Miller J. Amer. Chern. SOC.,1968.90.993. 110 N. S. Isaacs N2NHAr / Ar C=C -H+ Ar,C=&Ar ‘Ar + N2+ ArNH2 (31) (32) anodic oxidation of radicals (the ‘abnormal’ Kolbe reaction from carboxylate ions) has been used to generate the pinacolyl cation53 and the neopentyl cation.54 In both cases a mixture of rearranged and unrearranged products was obtained. Triaryltriazenes (3 1) undergo acid-catalysed cleavage to vinyl cations (32).55 A primary vinyl cation is also formed by addition of the ada- mantyl cation to a~etylene.’~ It rearranges to the (presumably) more stable secondary vinyl cation by a hydride shift the products on hydrolysis being acetyladamantane and adamantylacetaldehyde. A good correlation was observed between solvolytic rates of formation of benzylic cations in the polynuclear hydrocarbon series and changes in the Huckel x-energies from which may be deduced a resemblance between the transition state for the reaction and the carbonium ion.57 Arylsilylcarbonium ions have been generated e.g. (33); silicon appears to be less ready totransfer aphenyl group thandoescar- bon but the reaction can be achieved.58* ’’It is possible that greater stabilisation f Ar,Si-CHAr R$iH + Ri6 + R$i+ + RiCH (33) (34) of the positive charge occurs when adjacent to the silicon atom thus permitting back-donation through d-orbital participation. This however cannot mean that carbonium ions are more stable than their silicon analogues since trityl cations are readily reduced by triarylsilanes and silyl cations are formed (34).6o The solvolysis of ferrocenylethyl acetates bearing substituents in the second cyclopentadienide ring (35) shows a general correlation of rates with q,,or 0,values (rather a better one with the combination (om+ op/3))and a 103-fold difference in rates between (35; R = Me) and (35; R = CN).6’ It is clear that substituent effects are transmitted interannularly in the ferrocenyl Fe 53 P.S. Skell and P. H. Reichenbacher J. Amer. Chem. SOC.,1968,90,3436. 54 P. S.Skell and P. H. Reichenbacher J. Amer. Chem. SOC.,1968,90,2309. 55 F.W. Miller Diss. Abs. 1967 BB 1857. 56 T. Sasaki S. Eguchi and T. Toru Chem. Comm. 1968 780. 57 G.J. Gleicher J. Amer. Chem. SOC.,1968,90 3397.58 K.H.Pannell Diss.Abs. 1968,BB 4505. 59 A. G.Brook K. H. Pannell and D. G. Anderson J. Amer. Chem. SOC.,1968,90,4374. 6o F.A.Carey and H. S. Tremper J. Amer. Chem. SOC.,1968,90,2578. 61 D.W.Hall E. A. Hill and J. H. Richards J. Amer. Chem. SOC.,1968,90,4972. Reaction Mechanisms 111 system but the mechanism by which this occurs is not certain. The acid-catalysed hydrolysis of vinyl ethers,62 which occurs much more readily than with the saturated analogues proceeds via the oxocarbonium ions (36); the stability of these ions and hence rate of formation falls in the order R' R2 = H > R' = H R2 = Me > R1,R2= Me. The ease of formation of highly branched tertiary carbonium ions increases very rapidly as the relief of steric strain becomes increasingly important (37a-e).6 Rearranged products were not +PNB $\PNI3 krcl 1 13,000 19,000 68,000 560 PNB = -0.C O O NOz obtained and alkyl participation seems to be unimportant. However a high degree of configurational retention was observed in the deamination of [l *HI neopentylamine to account for which methyl participation has been The formation of the alkyl-migration product (in ca. 3% yield) during the deamination of (38) is claimed65 to be due to the rather unfavourable 0 geometry for the preferred phenyl migration which indeed occurs to give the large majority of products; the plane of the ring is inclined however at ca. + 60"to the C(a)-CH bond instead of the 90"usually assumed most favourable. The result is suggestive but needs more definitive evidence to support this interpretation.Ion-pair return in the acetolysis of arylsulphonates has been 62 T. Okuyama T. Fueno T. Nakatsuji and J. Furukawa J. Amer. Chem. SOC.,1967,89,5826. 63 P. D. Bartlett and T. T. Tidwell J. Amer. Chem. SOC., 1968,90,4421. 64 R. D. Guthrie,J. Amer. Chem. SOC. 1967,89,6718. 65 W. E. Parkham and L. J. Czuba J. Amer. Chem. SOC.,1968.90.4030. 112 N. S. Isaacs studied using '*O-labelled substrates.66 The label originally placed specific- ally accumulates in the singly bound oxygen due to return from the symmetrical sulphonate ion (39) at a rate amounting to 5-100/ of the acetolysis rate. 18 0 +1 R 1 .,\ -':S-ORz ,;/ co+ 6o (39) (40) (4 1) Bridgehead acyl cations such as (40) are more stable towards decarbonylation than those which may give rise to a planar carbonium In such cases acylated products may be obtained.The carbonium ions produced from cis-and trans-9-chlorodecalins and from 4-cyclohex-1 -enylbutyl toluene-p- sulphonate are apparently different as judged from the different proportions of produ~ts-A'(~)- and A'-octalins and cis-and trans-decal-9-01s-which are cbtained on hydrolysis under otherwise identical conditions.68 The results suggest that the presumed common intermediate the 9-decalyl cation (41) or an ion-pair exists as different conformers or in different solvation states although alternative explanations could include the incursion of different amounts of bimolecular substitution and elimination reactions and in the latter case 71-assistance.The cyclohexyl cation generated by the reaction between the acetyl cation and cyclohexane rearranges to the more stable methylcyclopentyl cation from which the majority of the products are derived.69 The solvolyses of 4,4'-disubstituted benzhydryl halides were observed to show (42) 66 A. F. Diaz I. Lazdins and S. Winstein J. Amer. Chem. SOC.,1968,90 1904. 67 D. G. Pratt and E. Rothstein J. Chem. SOC.(C),1968 2548. A. F. Boschung M. Giesel and C. A. Grob Tetrahedron Letters 1968 5169. 6q 1. Tabushi. K. Fujita and R. Oda Tetrahedron Letters. 1968.4247. Reaction Mechanisms rather poor obedience to the additivity rule of substituent effects.70 A thorough survey of the products of solvolysis of some classical secondary carbon- ium ions (4-octyl 4-t-butylcyclohexyl and 2-decalyl) has been published.' Products derived by an initial hydride shift are shown to be significant and provide a clearer insight into the fate of these ions i~ a variety of solvent. The ease of ionisation of bridgehead halogen substituents in bicyclic systems appears to be governed by the amount of steric strain which the carbonium ion can accommodate. A good linear plot was obtained relating calculated strain differences between halide and cation with log k for the systems (42a- f).72-74Relief of ring-strain is apparently responsible for the great enhance- ment of solvolytic rates of bicyclo[2,2,0]hexylmethyl p-nitrobenzoate (43) (to form bicyclo[2,2,l]heptyl derivative^)^^ compared with the neopentyl (44):X =-OCO.C,H,.CH compound.A factor of 7 x lo6 was recorded. A good correlation between rates of solvolysis and strain-energy release was found for six l-bicycloalkyl- methyl compounds (43,Ua-e). Changes in strain energy in forming a trigonal carbon may be implicated in the ob~ervation~~ that (45) solvolyses some 6.5 times more rapidly than (46) but the fact that the isomer (47) reacts some ten times more readily than (45) suggests that perhaps the relief of 1,3-diaxial 'O E. Berliner and M. Q. Malter J. Org. Chem. 1968,33,2595. N. C. G. Campbell D. M. Muir R R Hill J. H. Parish R M. Southam and M. C. Whiting J. Chem. SOC.(B),1968 355. 72 P. v. R. Schleyer P. R. Isele and R. C. Bingham J. Org. Chem. 1968,33 1239.73 W. G. Dauben and C. D. Poulter J. Org. Chem. 1968,33 1237. 74 W. G. Dauben J. L. Chitwood and K. V. Sherer J. Amer. Chem. SOC.,1968,90 1014. 75 C. W. Jefford D. T. Hill and J. Gunsher J. Amer. Chem. SOC. 1967,89,6881. 114 N. S. Isaacs interactions may be more important. Curiously the ratio of exo-to endo-reactivities is the reverse of that found in the 2-norbornyl system. (45) X = OTOS,Y= H (47) X = H Y = OTOS In the present case observed rates were not too dissimilar from values calculated by the Halford-Foote-Schleyer relations hi^^^ but as in all such studies more certain energetic relationships would be obtained by comparison of free energies of activation rather than relative rates. A combination of strain release and enhanced conjugation is probably responsible for the isomerisation of protonated he~amethyldewarbenzene~~ (48) to the hexa- methylbenzenonium ion in very strong acid medium.Two indirect pathways are postulated. A 1,3-hydrogen shift in (49) competes almost equally with 1,Zcarbon migration the products being (50)and (51)respectively.78 However at -78" in SbF,-HSO,F both hexamethyl Dewar benzene and hexamethyl- prismane protonate to a species with four distinct methyl groups in their n.m.r. spectrum which was identified as (51a).79 &-ax H / 76 C. S. Foote J. Amer. Chem. Soc. 1964,86 1853; P. von R. Schleyer ibid. pp. 1854 1856. 77 H. Hogeveen and H. C. Volger Rec. Trau. chim. 1968,87,385. 7B R. A. Appletoq J. C. Fairlie R. McCrindle and W.Parker J. Chem. SOC. (C) 1968 1716. 79 L. A. Paquette G. R Krow J. M. Bollinger and G. A. Olah J. Amer. Chem Soc. 1968 90 7 147. Reaction Mechanisms "on-Classical' Carbonium Ions and IT-Assisted Ionization.-Two contro-versial systems continue to stimulate a considerable volume of work namely derivatives of bicyclo[2,2 llheptane (norbornane) and cyclopropylmethyl cations. It has been long established that the cyclopropyl group together with other similarities to the ethylenic double bond acts as a carbonium ion stabilising group and carbon scrambling occurs between the ring- and exocyclic atoms. Extended Hiickel calculations" suggest that the classical cyclopropylmethyl structure (52) is more stable than the symmetrical nonclassical representation (53),but should readily undergo a degenerate rearrangement by a suprafacial methide migration via the bent cyclobutonium species (54)" The same authors support this hypothesis by studies on a rigid cyclopropylmethyl cation that is formed by solvolysis of 9,lO-dehydroadamantyl toluene-p- sulphonate (55).82 The reaction occurs faster than that of adamantyl toluene-p- sulphonate by a factor of 5 x 10' and deuterium initially in position 2 is distributed equally in positions 2 9 and 10 in the products.The scheme (55) -+(56) is consistent with the facts. Wiberg and S~iemies*~ have attempted to distinguish between mechanisms for the cyclopropylmethyl rearrangement by a stereochemical argument. Rearrangement of an unsymmetrically sub- stituted ion such as (57) could occur by overlap of the vacant p-orbital with either the interior or exterior lobes of the opposite o-bond with different stereochemical consequences [(58) and (59)].The product (59) also be formed by transformation through a bent cyclobutonium ion but a mixture of (58) and (59) would result from a planar cyclobutonium ion.The hypothesis was examined by analysis of the products of acetolysis of bicyclobutane in acetic 8o L. C. Allen and J. D. Russell J. Chem. Phys. 1967,46 1029 (ref. 81 J. E. Baldwin and W. D. Fogelsong J. Amer. Chem. SOC.,1968,90,4311. '* J. E. Baldwin and W. D. Fogelsong J. Amer. Chem. SOC.,1968,90,4303. 83 K.B. Wiberg and G. Szeimies J. Amer. Chem. SOC.,1968,90,4195. 116 N. S.Isaacs 1+3% (60) [2H]acid when the product cyclopropylmethyl acetate had the isotopic composition denoted in (60).Almost all the deuterium is found in the carbinyl and trans-2-positions which indicates that the cyclopropylmethyl-cyclo-propylmethyl rearrangement is occurring and the specificity of this labelling must result from the regeneration of the same labelling pattern at each re- arrangement either by process (59b) or via the nonplanar cyclobutonium ion.The solvolytic fate of the cation (61) has been interpreted as follows.84 It was found that the product (62) contained no deuterium in the vinylic positions from which the initial shift was deduced to lead to a cyclopropylethyl-type (63) of ion which then rearranges to the presumably more stable cyclopropyl- methyl type (64).It seems curious that this is not produced initially although possibly the answer lies in the relative bond strengths of the C(lkC(7) and C(4)-C(7) bonds. Some sort of interaction between a cyclopropane ring and a + & (6 1) OAc (62) OBs Kos' -+ bAC AcOH (65) (653) (66) (67) 84 J. M. Berson G. M. Clarke. D. Wege. and R.G. Bergrnan. J Amer. Chem. SOC.. 1968.90 3238. Reaction Mechanisms P-carbonium ion centre may be inferred from the enhanced reactivity of (65a) compared to (65).85 A factor of only ten is involved but racemisation of (65a) is four times faster than solvolysis which leads to rearranged products (66) and (67). The cyclopropane ring in 2-bicyclo[ 3,1,0] hexyl chloride (68) brings a rate enhancement by a factor of lo4compared to cyclopentyl chloride which seems too large to ascribe to steric factors.86 It would be interesting to examine possible scrambling of the carbons in the five-membered ring during this reaction.Triarylbicyclo[3,1,0] hexan-3-01s ionise in concentrated sulphuric acid or in the presence of Lewis acids to give coloured species8' (hmax -500nm.) clearly not due to simple benzyl cations but possibly trishomocyclopropenyl cations (69).Further information on these interesting species would be welcome for instance from the n.m.r. equivalence or nonequivalence of the methylene protons and by observation of migration of the hydroxyl-group after hydrolysis. However only very slight rate enhancement was noted for the hydrolysis of 2-cyclopropylethyl p-bromobenzenesulphonate compared with the ring- opened analogue whereas in the 7-norbornyl series a 103-fold rate increase is brought about by the endo,anti-cyclopropano-group.88* 89 There are many observations which are still poorly understood concerning these systems.A method for obtaining estimates of relative lifetimes of carbonium ions employs their generation from the diazotate (70) in *O-enriched water. Short-lived ions tend to capture the diazotate oxygen (l60)by internal return. while longer-lived species are assumed to react more with water to give a labelled alcohol (71). From such studies the cyclopropylcarbonium ion appears to have a longer lifetime than the 2-octyl cation." Two neighbouring spiro- cyclopropane rings are highly effective in promoting ionization although not 'CH \ (7 O) OTos n = 2,3,4 (72) 85 J.A. Berson D. Wege G. M. Clarke and R G. Bergman J. Amer. Chem. SOC. 1968,90,3240. 86 P. R. Brook R. M. Ellam and A. S. Bloss Chem. Comm. 1968,425. 87 W. Broser and D. Rahn Chem. Ber. 1967,100,3472. 88 M.J. S. Dewar and J. M. Harris J. Amer. Chem. SOC.,1968,90,4468. 89 Y. E. Rhodes and T. Takino J. Amer. Chem. SOC.,1968,90,4469. 90 R. A. Moss F. C. Shulman. and E. Emery J. Amer. Chem. SOC..1968,90,2731. 118 N. S. Isaacs as effective as when the cyclopropane rings are fused and occupy a more coplanar situation relative to the vacant p-orbital of the carbonium ion.g' Related studies show that a major factor which governs solvoly$ic rates in the spiran series (72) is the ring strain imposed in generating the carbonium 93 The series of exo-bicyclo[n,l,O]alkylmethyl toluene-p-sulphonates (n = 1-7) has been prepared and their solvolytic reactivities have been mea~ured.~~,~~* 96 A sharp maximum in rate appears for the n = 4 compound and the authors interpret the reactions as going initially through a cyclo-propylmethyl cation after which numerous rearrangements occur.No assist- ance to ionisation was evident in the compound (73) which could be ascribed to the three-membered ring." The compound (74) was designed as an example in which reversible heterolysis to (75) might occur in a polar solvent. It was (CH ) OTos Me ?;?r"02ph MASO,Ph= Me COzMe Me CO Me observed that the rate of racemization exceeded the rate of solvolysis in metha- mol at 150" by a factor of 9 which was interpreted as evidence for the dipolar intermediate (75).98 It was noticed that," of the four stereoisomeric bicyclo- [4,2,0]octyl toluene-p-sulphonates two the cis,exo-(76) and the trans,exo- (77)give single product types on acetolysis.It was postulated that the rearrange- ments of cyclobutyl cations are subject to orbital symmetry control and in these cases are further limited by steric factors. The trans-cyclo-octenol produced from (77) was trapped as its adduct with phenyl azide. 91 P. Krapcho R. C. H. Peters and J-M.Conia Tetrahedron Letters 1968 4827. 92 D. Applequist and W. A. Bernett Tetrahedron Letters 1968 3005. 93 K. W. Wiberg and J.E. Hiatt Tetrahedron Letters 1968 3009. 94 A. J. Ashe Diss.Abs. 1967,27B 4298. 95 K. B. Wiberg and A. J. Ashe J. Amer. Chem. SOC.,1968,90,63. 96 P. v. Schleyer and G. W. Van Dine J. Amer. Chem. SOC.,1966,88,2321. 97 G. D. Sargent R. L. Taylor and W. H. Demisch Tetrahedron Letters 1968,2275. 98 D. J. Cram and A. Ratajczak J. Amer. Chem. SOC.,1968,90,2198. 99 K. B. Wiberg and J. G. Pfeiffer J. ,4mer. Chem. Soc.. 1968,90,5324. Reaction Mechanisms x Y X X ce Gpi I J. The norbornane system is still providing great scope for experimental work. It has been long known that startlingly large rate enhancements are observed in the 7-norbornyl series when double-bonds are placed in the 2,3- (anti) and 5,6-positions (78a-d). loo Explanations which have been put forward include x-participation either by way of a homoallylic (78e) or symmetrical non- classical ions (780 and steric considerations in particular the widening of the C(l)-C(7)-C(4) angle whose constraint in (78a) is primarily responsible for its greatly depressed solvolytic activity.Since major structural changes bring about alterations in both steric and electronic factors recent work has con- centrated on systems in which independent control of the variables could be realised. A search for 'bridge-flipping' (79) in the norbornadienyl cation has revealed by the n.m.r. spectrum of this stable cation that such a rearrangement does not occur rapidly at -78" in fluorosulphonic acid."' Two separate kinds of vinyl protons are observed a 'bound' pair resonating at z 2.54 considered due to a bishomocyclopropenium system and a 'free' pair at z 3.90 more nearly R R (7 9) (801 normal.The 7-hydrogen resonates at T 6.77 from which it appears that a great deal of positive charges has been removed from the 7-carbon atom (compare the %hydrogen in the 2-propyl cation at T -3-5).At higher tempera- loo H. Tanida Accoultts Chem. Res. 1968,1,239. lo' R. K. Lustgarten M. Brookhart and S. Winstein J. Amer. Chem. Soc. 1967,89 6350. 120 N. S. Isaacs tures the two types of vinyl proton do not merge but a degenerate rearrangement sets in as shown by deuterium-labelling experiments. Scrambling of deuterium from the unbound vinyl position to all carbons except the bound vinyl is observed at -47" (80).It is possible that bridge flipping occurs at higher temperatures but a lower limit of 19.5 kcal. mole-' is estimated for the activa- tion energy. 7-Methylnorbornadienyl however,lo2 exhibits two types of vinyl signal at low temperatures which coalesce above -14" while the methyl signal remains sharp. This is interpreted as due to the equilibrium (79; R = Me) (AF* = 12-4 kcal. mole-') while 7-phenylnorbornadienyl (79; R = Ph) is rapidly interchanging even at -70" '03 giving an upper limit of AF* for the equilibrium of 7.6 kcal. mole- '. It is much less easy to obtain definite evidence for the existence of o-participation in the solvolysis of 7-norbornyl deriva- tives. Miles'04 has shown that predominant retention of configuration in the solvolysis of the isotopically labelled compound (8 1) occurs.The configura- tion-holding effect could conceivably arise from o-participation or from a front-side solvent interaction such as (81b). These results have been confirmed by other workers'05 who have also isolated a small (ca.3 %) amount of bicyclo- [3,2,0]heptyl acetate which was shown to consist of the isomers (82) and (83) in the ratio of 20 :1. The former can arise from a rearside 1,Zshift on the intimate ion-pair (81b) but the latter requiring a frontside 1,Zshift is unlikely to be derived immediately from (81 b) for steric reasons. Considering the small amount of (83) formed however it seems unnecessary to abandon the ion-pair intermediate entirely but for the formation of the major product some special configuration-retaining situation occurs.The energetics of the epimerisation of the bicyclo[2,2,l]heptan-2-ols (84) have been studied both from the view- point of racemisation and isomerisation rates. '07 The difference in activa- tion enthalpy for formation of the intermediate ion from either epimer (AH2-AHl) amounts to 4.3 kcal. mole-' for R = H but 7.8 kcal. mole-' for R = Me. The authors interpret this greater reactivity of (84) R = H as due to a contribu- tion from o-participation whereas the methyl analogue (84); R = Me) is supposed to ionise to an essentially classical tertiary carbonium ion. An '02 M. Brookhart R. K. Lustgarten and S. Winstein J. Amer. Chem. SOC. 1967,89,6352. M. Brookhart R. K. Lustgarten and S. Winstein J.Amer. Chem. SOC.,1967,89,6354. lo4 F. B. Miles J. Amer. Chem. SOC.,1968,90 1265. lo5 P. G. Gassman J. M. Hornback and J. L. Marshall J. Amer. Chem. SOC.,1968,90,6238. lo6 H. Goering and K. Humski J. Amer. Chem. SOC.,1968,90,6213 lo' H. L. Goering C. Brown and C. B. Schwene J. Amer. Chem. SOC.,1968,90,6214. Reaction Mechanisms alternative interpretation of this work views solvolyses of the exo-compounds as being normal whilst the endo-isomers as retarded by a steric factor,Io8 a further example of the dichotomy of viewpoint regarding nonclassical car- R (84) a; K = H OPNB b R =Me (85) (86) bonium ions. Steric hindrance to ionisation as an explanation of these rate differences has also been stressedlog on the grounds that high exo :endo rate ratios are also observed in the compounds (85) and (86) where similar steric environments of each isomer are found to the corresponding ones in the nor- bornyl series but a suitable situation for o-participation is absent.Interesting studies were reported concerning substituent effects in benzonorbornenes. The solvolyses of 6(7)-substituted benzonorbornene-anti-9-brosylatesshow great dependence on the electronic nature of the substituent.”’ A Hammett plot is linear with p = -4-8 [based on substituent effects assessed as gop+ op’)] or -5.1 [based on ~op’+ a,‘)],an extremely large dependence on electron availability. This may be emphasised by comparison of the rates for extreme cases (Z = OMe and Z = NOz) for the benzonorbornyl system (87) and the 3,4-benzocyclopentane system (88).In the former case koMe/kN02= 368,000 and in the latter 8. Less clear is the mechanism of participation of the aromatic ring in the reactions of 5-substituted benzo-2-norbornenes (89). Here the exo:endo rate ratio is lo4 and the introduction of methoxy-groups has very little effect from any position with the exception of the 6 (‘homo-para’) where a rather large enhancement is observed for the exo-isomer. The nonclassical view of this effect would regard the cation formed (90), as being ‘homobenzilic’. Y + lo’ H. C. Brown and M. Rei J. Amer. Chem. SOC. 1968,90,6216. lo9 H. C. Brown. I. Rothberg and D. L. Van der Jagt J. Amer. Chem. Soc. 1967,89.6380 122 N. S. Isaacs These results have been confirmed qualitatively but with somewhat different values for the relative rates.110-113 .As anticipated the 6-nitro-derivative is deactivating the em :endo rate ratio dropping to 10'. These effects have been treated theoretically by the method of bond superdelocalisabilities and general agreement with experimental values has been reported. 'I4 Even when the reaction centre is removed by a further two carbons (91) similar though attenuated effects are observed.'15 The syn:anti rate ratio drops to 20 and kMeO/kNO2= 150 for syn-compounds but zero for the anti-isomers. Such effects could result from conformations such as (91) and the interaction be- tween aromatic ring and positive centre amount to a charge-transfer interac- tion. Dewar has reported the existence of such charge-transfer com-plexes from spectroscopic evidence.A p-methoxyphenyl group on the same carbon atom as the leaving group. (92). satisfies the electronic demands of the ionisation such that a-participation (in the norbornyl system) and even x-participation (in exo-norbornenyl) is redundant .' 16* 'I7 The I OMe (93) (92) decarbonylation of (93) (forming tropilidine) is greatly facilitated by an endo- cyclopropane ring compared to the em while the benzo-analogue is very resistant to decarbonylation on account of the loss of aromaticity which this entails.'18 The system (94) exhibits what is probably the largest driving force H. Tanida T. Tsugi and S. Terataki J. Org. Chem. 1967,32,4121. '" D. V. Braddon G. A. Wiley J. Dirlam and S.Winstein J. Amer. Chem. SOC.,1968,90 1901. H. Tanida H. Ishitobi and T. Irie J. Amer. Chem. SOC.,1968,90,2688. H. C. Brown and G. L. Tritle,J. Amer. Chem. SOC.,1968,90,2689. 'l4 H. Tanida and T. Tsushima J. Chem. SOC.(Japan),1968,89,14. R. Muneyaki and H. Tanida J. Amer. Chem. SOC. 1968,90,656. '" H. C. Brown and K. Takeuchi,J. Amer. Chem. SOC. 1968,90,2691. 'I' P. G. Gassman J. Zeller and J. T. Lumb. Chem. Comm.. 1968. 69. Reaction Mechanisms to ionisation yet discovered."* The effect may be described in terms of a nonclassical ion (93 and perhaps as a n-butressing effect. The compound (96) is also extraordinarily reactive. A related subject of great interest at present is the identification of homoallylic and more distant n-participation.Homoallenyl systems seem to be considerably more reactive than homoallylic which in turn are more reactive than the saturated analogues (97a-c).' 19,I2O However the optically active allenic compound (98) in a polar medium undergoes racemization and also ring closure to the cyclopropane (99). It seems likely that the former originates by dissociation of (98) to a classical car- bonium ion followed by return of the anion while the latter involves rearside attack on the asymmetric carbon atom by the n-electrons thus retaining optical activity. An impressive demonstration of the involvement of at least three carbons of a homoallylic system is provided by the nucleophilic sub- stitutions with homoallylic rearrangement of (100) and its enantiomer which Ac Me 118 (a)B.Halton M. A. Battiste R Rehberg C. L. Deyrup and M. E. Brennan J. Amer. Chem. SOC. 1967,89 5964; (b)E. L. Allred and J. C. Hinshaw Tetrahedron Letters 1968 1293. T. L. Jacobs and R Macomber Tetrahedron Letters 1967,4877. '*' R. T. Swindell Diss Abs. 1967,28B 120. 124 N. S. Isaacs proceed in a completely stereospecific manner12 (ie. C~S-CCH, cyclopropyl-H -+ cis-olefins and also the reverse reaction. The reaction has potential pre- parative value. Stereospecific double homoallylic ring-expansions were also reported,'22 e.g. (101). OTos 101 The formation of 2-cyclopropyltetrahydrofuran (102) by the action of silver on 7-iodohept-4-en01 is suggested as having occurred by the internal trapping of a homoallylic cation (103)'24 and a similar interpretation may be put on the reaction (104) which proceeds with retention of optical activity,'25 although an alternative interpretation with good precedent involves rearside attack on the episulphonium ion (105).f-7 f +ArScl D-0 >-\7c + SAr (102) SAr Further information on the nature of the phenethyl cation of phenonium ion formed in the solvolysis of P-arylethyl toluene-p-sulphonates has been sought by Bentley and Dewar.'26 They argue that the rate of formation of the n-complex representation (106) should correlate with the n-energy dif- ference between ArH and (106) which is isoconjugate with ArCH; ;the rate of formation of the phenonium ion representation (107) however should correlate with the n-energy difference between ArH and the benzenonium ion (pentadienyl cation).A moderate correlation between log k for solvolysis and the nonbonding orbital coefficient for the benzyl cation is held to support 12' M. Bertrand and M. Santelli Chem Comm. 1968 718. 122 M. Gasic D. Whalen B. Johnson and S. Winstein J. Amer. Chem. SOC.,1967,89,6382. 123 D. Whalen M. Gasic B. Johnson H. Jones and S. Winstein J. Amer. Chem. SOC.,1967 89 6384. 124 L. A. Paquette and R. W. Begland J. Amer. Chem. SOC.,1968,90,5159. 125 T. L. Jacobs R. Macomber and D. Zunker J. Amer. Chem. SOC.,1967,89,7001. M. D. Bentley and M. J. S. Dewar J. Amer. Chem. SOC..1968,90. 1075. 125 Reaction Mechanisms (10 8) the former postulate a positive slope confirming the assistance towards ionization of the aryl group.On this latter point an observation by Cram and Thomson is re1e~ent.l~’ The solvolysis products of both erythro-and threo-(108; Z = H) have a largely retained configuration but inversion occurs for (108; Z = NO2).It is suggested that phenyl-assisted ionisation (accompanied by retention) can no longer be supported by the p-nitrophenyl group. It has been shown that the intermediate carbonium ion if indeed the reaction pro- ceeds via a carbonium ion produced from the tricyclyl toluene-p-sulphonate (109) is unsymmetrical and leads to products of retained configuration.128 Intermediates such as (1 10)are therefore ruled out and a plausible mechanism seems to be a nucleophilic attack at C-3 more or less concerted with ring- enlargement the driving force for this reaction over a straightforward attack at the primary carbon being the release of steric strain.However in a somewhat similar situation the intermediate cation or transition state appears to be symmetrical as judged by the loss of optical activity on solvolysis of (111). A possible structure is suggested as being (ll2).I2’ A new type of fluxional system (1 13) has been observed.130 0 II 0 / NHC Mes It o=c PhC[CH,],-Cl. 6”- (113 (1 14) (115) (1 16) 12’ D. J. Cram and J. A. Thompson J. Amer. Chem. SOC. 1967,89,6766. 12’ J. A. Berson R G. Bergman G. M. Clarke and D. Wege J. Amer. Chem. SOC. 1968,90 3236. lZ9 H. J. Goering and G. N. Fickes J. Amer. Chem. SOC. 1968,90,2848,2856,2862. M. J. Goldstein and B.G. Odell J. Amer. Chem. SOC.,89 1967,6356. 126 N. S. Isaacs Participation by Unshared Pairs.-Considerable interest in neighbouring- group participation by the carbonyl group has been shown. Thus the displace- ment of halide from the compounds (114;n = 1-5) shows a sharp rate maximum at n = 4 (a 700-fold enhancement over the phenacyl compound) due to (C=O; 5) participation the product in this case being a tetrahydrofuran.13' In the hydrolysis of aspirin esters general intramolecular acid catalysis by the ortho-carboxylic acid group and general intramolecular base catalysis by the carboxylate ion have been identified. '32-' 36 The acetamide group participates in the hydrolysis of the ester group in (115) as shown by the isolation of the intermediate imide (116) which hydrolyses to mesitoamide;' 37 similar effects are reported to occur' 38 in the hydrolysis of 2-acetamidoglycosides.N.m.r. line broadening has been used to detect amide participation in glycoside hydrolysis catalysed by lysozyme ;140 the following scheme was proposed (117). Ester participation in the hydrolysis of the 1 -phenethyl bromide derivatives (118) was inferred from the considerable ortho-effect kortho/kpora = 7.7. 14' enzyme Me H QC02Me X Y Z krd c1 c1 1 b; H CO2Ek CO2Et 2 c; c1 C1 H 1 d; CO2Et CO2Et H 120 Me z I 13' H. R. Ward and P. D. Sherman J. Amer. Chem. SOC.,1968,90,3812. lJZ A. R. Fersht and A. J. Kirby J. her. Chem. SOC.,1968,90 5818. '33 A. R. Fersht and A. J. Kirby J.Amer.Chem. SOC.,1968,90,5826. 134 A. R. Fersht and A. J. Kirby J. Amer. Chem. SOC.,1968,90,5833. lJ5 T. St. Pierre and W. P. Jencks J. Amer. Chem. SOC.,1968,90,3817. 136 A. R. Fersht and A. J. Kirby J. Amer. Chem. SOC.,1967,89,5960 5961. 13' R. M. Topping and D. E. Tutt J. Chem. SOC.(B) 1967,1346. 13* D. Piszkiewicz and T. C. Bruice J. Amer. Chem. SOC.,1968,90,5844. lJ9 D. Piszkiewicz and T. C. Bruice J. Amer. Chem. SOC. 1967,89,6237. G. Lowe and G. Sheppard Chem. Comm. 1968 529. 14' M. J. Straws L. J. Andrews R M. Keefer and I. Horman J. Org. Chem. 1968,33,2194. Reaction Mechanisms This factor however is quite moderate compared to many participation effects and since strain release probably accounts for at least a part of it the mechanism is not unambiguous.In a similar fashion the acceleration of the hydrolysis of the benzyl bromides (119) by two neighbouring carbonyl groups is suggestive of nucleophilic assistance; it is however difficult to assess contri- butions from steric and electronic factors. 142 The racemization of the sulphoxide (120) appears to be assisted by a carboxyl f~ncti0n.l~~ With a variety of substituent groups at the bridgehead position em-2-bromo-norbornanes solvolyse with a wide range of rates; 1-methoxycarbonyl and acetyl groups are retarding while the amino-group and to a lesser extent the carboxylate anion are accelerating. 144 Competition between inductive retardation and anchi- BrI 0 II Fe ‘0 (122) D I H (125) (1 26) 14’ M. J. Strauss L.J. Andrews and R M. Keefer J. Amer. Chem. SOC. 1968,90 3473. 143 S. Allenmark and C-E. Hagberg Acta Chem. Scand. 1968,22 1461 1694. 128 N. S. Isaacs meric assistance is evident the latter being deduced as operating on the amino- substituted compound by the loss of ammonia (121). Thus an ethyleniminium ion (121a) is not involved. Other interesting examples of neighbouring group effects include the transfer of oxygen from nitrogen to carbon during the hydro- lysis of o-nitrobenzhydryl bromide (122) with an ortho:para rate ratio of 83 ;145 and the nucleophilic displacement of cyanide by neighbouring hydroxy- group in the ferrocenyl series (123). 14' The 2-paracyclophanyl group is apparently an efficient configuration-retaining group since the toluene-p- sulphonate (124) solvolyses with complete retention of configuration.147 A rearside interaction between the aromatic system and the vacant p-orbital of the cation may be responsible or the bulk of the substituent may both prevent rearside attack by a nucleophile and hinder rotation of the carbon-carbon bond. Neighbouring oxime groups are effective in the catalysis of phosphate ester hydrolysis. 14' Six-centre transition states in the elimination of hydrogen halide from but-2-enyl halides have been suggested (124a).14' No participation of methoxyl in the solvolysis of (125) was observed. 150One would suppose that for reasons of geometry the interaction of the syn-7-methoxyl-group would only be effective in the endo-series. Sulphamate esters hydrolyse with internal return of the 0-alkyl group to give the zwitterion (126).Alkyl exchange also occurs giving crossed products from mixed esters.15' Substitution at Saturated Carbon.-In a re-examination of the Hughes- Ingold' 52 relationship concerning steric and polar factors in the S,2 reaction it has been concluded153 that observed and calculated values of rates and acti- vation energies and entropies agree well for the exchange reaction between alkyl halides and tetraethylammonium bromide in dimethylformamide. The reagent is known to be a moderately strong electrolyte and counters criticism1 54 Me (4 (b) (4 (4 (127) 144 J. W. Wilt and W. J. Wagner J. Amer. Chem. SOC.,1968,90,6135. 145 A. D. Mease M.J. Strauss I. Horman L. .f. Andrews and R M.Keefer J. Amer. Chem SOC. 1968,90,1797. J. H. Peet and B. W. Rockett Chem. Comm. 1968 120. 14' F. L. Harris Diss.Abs. 1967,27B 4306. 14* C. N. Lieske J. W. Havanec G. M. Steinberg and P. Blumberg Chem. Comm. 1968 13. 149 C. J. Harding A. G. Loudon A. Maccoll P. G. Rodgers R A. Ross S. K. Won& J. Shapiro E. S. Swinbourne,V. R Stimson and P. J. Thomas Chem. Comm. 1967 1187. 150 P. G. Gassman and J. L. Marshall Tetrahedron Letters 1968 2433. 15' P. F. Ziegler and M. Orchin J. Org. Chem. 1968,33 443. P. B. D. De LaMare E. S. Hughes C. K. Ingold L. Fowden and J. D. H. Mackie J. Chem Soc. 1955,3200. lS3 D. Cook and A. J. Parker J. Chem. SOC.(B),1968 142. 154 S. Winstein S. G. Smith and D. Darwish Tetrahedron Letters 1959 24; S. Winstein L.G. Savedoff S. G. Smith I. D. R. Stevens and J. S. Gall ibid.. 1960 24. Reaction Mechanisms that previous tests of the theory were invalidated by the weak electrolyte nature of the reagent (lithium halide in acetone for example). A careful study of the hydrolysis of the allylic chlorides (127a-d) has yielded evidence from the detailed kinetic expressions and from the variation with temperature of AFf for a gradation of mechanisms ranging from SN1-like for the secondary chloride (127a) through mixed SN1-sN2 for (127b) and (127c) and to purely sN2 for compound (127d). 155 If carbonium-ion stabilities are responsible for this behaviour then second-order effects must be considered in (127b4). Competitive studies on the relative reactivities of hydroxide methoxide ethoxide and allyloxide ions towards displacement of halogen from n-butyl benzyl and trityl bromides have shown that hydroxide ion is a comparatively weak nucleophile.'s6 This is most pronounced with the primary halide and presumably sN2 reaction (relative rates for OH- OMe- OEt- OC3HF were 1 10,37,42) and least for trityl (1 1,2,7,2 respectively).However concentrations of the nucleophiles present were estimated from acidities of the solvent com- ponents (aqueous alcohol mixtures) and are doubtless approximate. Nucleo- philicities of some stabilised nitrogen anions have shown that sulphonamide ions are somewhat less reactive than methoxide and succinimide and phthal- imide ions more reactive in the reactions with methyl iodide.'56 The hydrolysis of t-butyl chloride in aqueous alcohol in the presence of added salts (LiBr and NaBr) up to 2~ in concentration shows complex effects not alone attributable to changes in the activity coefficients of the salts as measured independently.A non-uniformly increasing rate is characteristic of increasing lithium bromide concentration while sodium bromide causes an initial increase (up to IM) beyond which the rate is depressed.'57 Such studies high-light our lack of knowledge of reagent interaction with the medium and indicate the need for further research. The nitro-group of a-nitrobenzhydryl chloride unlike that in 1-methyl-2-nitroethyl chloride is not sufficiently electron-withdrawing to suppress ionisation in a polar solvent so the hydrolysis proceeds by an S,1 mechanism.The hydrolysis of chloromethyl methyl ether has been shown to be a unimolecular reaction by its kinetics and by a substantial secondary isotope effect (kH/kD= 1-24) for MeOCD,Cl characteristic of hydrogen attached to carbon whch is undergoing a change in hybridisation in the rate-determining step.159A remarkable study of the rates of reaction of methyl iodide with several series of amines has pointed to a balance between inductive effects and steric requirements in determining rates. Many of these reactions however are reported to be slower in methanol than in benzene even quaternizations such as between methyl iodide and triethylamine or tri-n-butylamine. This is attributed to a higher solvation energy of the amine than of the (polar) transition state but is clearly at variance with the results of for instance 15' L.J. Brubacher L. Treindl and R.E. Robertson,J. Amer. Chem. SOC.,1968,90,4611. lS6 W. Reeve and P. F. Aluotto Tetrahedron Letters 1968,2557. 15' J-Y. Conan and A. Nattaghe Bull. SOC.chim. France 1968 1177. D. G. Norten and C. D. Slater Tetrahedron Letters 1968 3699. lS9 T. C. Jones Diss. Abs. 1967,28B 106. 160 K. Okamoto S. Fukui I. Nitta and H. Shingu Bull. Chem. SOC.Japan 1967,40 2350 2354. 130 N. S. Isaacs Muchin et ~2.'~'Very low activation entropies (down to -47 e.u.) and low Arrhenius activation energies (e.g. 7.3 kcal.mole-') were quoted. When heated in dichloromethane allylbenzylmethylphenylammonium iodide displacement undergoes at the benzylic carbon-mild conditions for such a reaction,162 the basic hydrolysis of tetranitromethane evidently occurs by displacement of the trinitromethyl anion from nitrogen by OH-and also by NO,.'63 The + N-Me /u Me decomposition of NN-dimethylpiperidinium ions of fixed conformation (e.g.tropine camphidine derivatives) by thiophenoxide involves preferred attack at the axial methyl group [see (128)l. 164 The bridgehead halogen in 1-adamantyl bromide is by no means inert towards hydrolysis in aqueous dimethyl sul- phoxide (k = 1.25 x 10-' 1.nole-'set.-' at 50" AH' = 20.4 k~al.mole-').'~~ A 2-phenyl group activates cyclopropyl chloride towards acetolysis by a factor of 104,166and vinylic halides containing a P-aryl substituent have also been shown to undergo substitution by strong nucleophiles such as thiophenoxide and methoxide.Such displacements on PP-diary1 halides show a Hammett p value of 5.1 indicating a high degree of carbanion character in the reaction. 16' The strong carbon-nucleophile thiophenoxide forms substitution products with both cis-and trans-p-nitro-P-bromostyrenes (possibly by addition-elimination) whereas the strong base methoxide brings about a considerable proportion of elimination to the acetylene.168* 169 R Et,Sn + Hg1,-EtHgI + Et,SnI R ' (129) .'Hi1 % HgI 16' G. Muchin R. Ginsberg and S. Moissieva Ukrain Chem. J. 1926 2 136; Chem. Zentr. 1926 2376. 16' K. T. Leffek and F. H. C. Tsao Canad. J. Chem. 1968,46 1215. 163 D. J. Glover J. Phys. Chem. 1968,72 1402.164 B. G. Hutley J. McKenna and J. M. Stuart J. Chem. SOC.(B),1967 1199. 16' J. Delhoste G. Gomez and G. Lamaty Compt. rend. 1968,266 C 1468. 166 J. W. Hausser and N. J. Penkowski J. Amer. Chem. SOC.,1967,89,6981. P. Beltrame D. Pitea and M. Simonetta J. Chem. SOC.(B),1967 1108. G. Marchese F. Naso and G. Modena J. Chem. SOC.(B) 1968,958. 169 G. Marchese G. Modena and F. Naso Tetrahedron 1968,24,663. Reaction Mechanisms 131 Several new electrophilic substitution reactions have been studied ;l70-’ 72 the activation parameters of the metal-exchange reaction (129) (AS* = -30e.u. AH* = 11.7 kcal.mole-’) indicate a tightly bound transition state such as (130) but the presence of a large positive kinetic salt effect suggests that (130b) is a better representation.1737 174 Possibly rigidity could be conferred on the latter by virtue of its crowded nature and the Coulombic forces present. Electro- philic displacements on allenyltin compounds have been shown to lead to allenic and acetylenic products by SE2 and SETmechanisms respectively,’ 75 the rates being somewhat greater than those of allylic analogues. Orbital overlap considerations have been suggested as responsible for the stereo- chemistry of bimolecular displacement reactions. Salem 176 has suggested that overlap of the lone-pair orbital in the nucleophile with the rearside lobe of the C-X antibondingo* orbital (being energetically and sterically most accessible) accounts for inversion while an attacking electrophile will need to approach the filled C-X a-orbital from the front leading to the often-observed retention of configuration.An attempt has been made to account for the stereochemistry of S,’ and S,’ reactions in molecular orbital terms. For nucleophilic displace- A ments new orbitals are constructed by mixing of the lowest vacant orbital of the allyl cation (the nonbonding orbital $J with 2s atomic orbitals on each carbon leading to the situation (131). Maximum overlap in the SN2 reaction required to be bonding to both N and X is achieved by an anti- geometry while for the SN1’transition state requiring bonding overlap to N :and antibonding overlap to X:the syn-geometry is most favourable. Similar arguments apply to SE reactions with the allyl anion now as basis.177 Such predictions should be amenable to experimental test.Carbaniom.-Hydrocarbon acidity has been reviewed.’ 78 The kinetic and thermodynamic acidities of some di- and tri-arylmethanes have been compared and shown to correlate in a nonlinear rnanner.l7’ In particular it appears that D. J. Cram and W. D. Kollmeyer J. Amer. Chem. SOC.,1968,90,1779 1784 1791 171 D. J. Cram W. T. Ford and L. Gosser J. Amer. Chem. SOC.,1968,90,2598. ’’’ W. T. Ford and D. J. Cram J. Amer. Chem. SOC., 1968,90,2606,2612. M. H. Abraham and T. R. Spalding J. Chem. SOC.(A),1968,2530. M. H. Abraham and T. R. Spalding Chem. Comm. 1968,46. 175 H. G. Kuivila and J. C. Cochrane J. Amer. Chem. SOC. 1967,89,7152. L. Salem J. Amer. Chem. SOC. 1968,90 543 553. 177 N. T. Anh Chem. Comm.1968 1089. H. Fischer and D.Rewicki Prog. Org. Chem. 1968,7,116. 179 D. J. Cram and W. D. Kollmeyer J. Amer. Chem. SOC. 1968,90,1784. 132 N. S. Isaacs isotopic exchange for the weaker carbon acids goes on at a higher rate than would be expected from their dissociation equilibria. The stereochemistry of carb- anions depends upon substituent groups. Highly conjugating substituents (and perhaps also crystal lattice requirements) can induce planar geometry as in the dinitrobutenamide ion (132) the crystal structure of which has been 0 0 H' reported. 8o The observation that deuterium exchange occurs at the carbon a to the carboxy-group rather than that a to the sulphonyl group in (133) (although the latter should be more acidic) has been explained by supposing that the latter carbanion if formed would be pyramidal and unable to invert on account of the methylene bridge hence bringing no relief of steric interac- tions between the two endo-groups.The carboxyl carbanion which forms in the basic medium is planar and hence can relieve steric strain.181 Also Streitweiser and Mares have shown that whereas two a-fluorine atoms greatly enhance the kinetic acidity of toluene (by a factor of lo4) a 9-fluorine atom diminishes the acidity of fluorene. This has been explained in terms of the conjugative destabilisation of the planar 9-fluorenyl anion in contrast to the inductive stabilisation of the pyramidal benzylic anion. 182 The allylic anion (134) shows restricted rotation about the C(lFC(2) bond as manifest by the collapse at go" of the multiplet absorption due to H2 coupled to H and H,.The enthalpy of activation is 19.8 kcal.mole-'. Rotation about.the C(3)-phenyl bond is also observable since at low temperatures the two phenyl Ar 'H H (134) (135) ortho-protons become distinct AH* for this process is 13-9 kcal.mole-1.'83 Vinyl carbanions are stabilised by adjacent sulphur. The compound (135) J. R. Holden and C. Dickinson J. Amer. Chem. SOC.,1968,90 1975. '13' G. Maccagnani F. Montanori and F. Taddei J. Chem. SOC.(B),1968,453. A. Streitwieser and F. Mares J. Amer. Chem. SOC.,1968,90 2444. V. R. Sandel S. V. McKinley and H. H. Freedman J. Amer. Chem. SOC.,1968,90,495. Reaction Mechanisms exchanges the 2-vinyl proton in NaOD-D,O without cis-trans isomerization and the sulphoxide and sulphone (136; X = SO SO,) also give carbanions of high conformational stability.'84 The emphasis upon C-H ionisation as a rate-determining step in the Favorskii rearrangement shifts towards greater carbanion character in the transition state as the leaving group varies from C1-to Br- to I- as judged by the increasingly large primary isotope effects (4-0,4-2 and 5.1 respectively)' 85 while 4,4-diaryl-2-chlorocyclohexanones react in the Favorskii rearrangement much more slowly than 2-chlorocyclo- hexanone but show a greater propensity towards "-deuterium exchange. Apparently reversible formation of a more stabilised carbanion occurs in the former case.'86 On the other hand 1 -bromobicyclo[3,3,1]nonan-9-one 0 0 c1 C02H >"=H +b-undergoes rearrangement with no deuterium exchange with solvent while 1-bromobicyclo[5,3,1]undecan-l1 -one incorporates one atom of deuterium per molecule during rearrangement.It is suggested that the former reacts by a semi-pinacolic mechanism rather than via the more usual cyclopropanone '" even though it possesses an a-hydrogen atom. If so the reason is presumably steric such as the strain imposed in forming a tricycl0[3,3,1,0~*~]nonane system. This observation can also be taken as evidence in favour of the normal cyclo- propane intermediate (137) rather than a dipolar ion (138) which would pre- sumably have less steric requirements than are shown. '88 The base-catalysed 1,3-proton-migration in 1,3-dimethylindene is stereospecific and leads to racemization with deuterium exchange.Amines however lead to exchange rates considerably in excess of racemization rates,' 89 suggesting a component of either rear-face attack of D+ at C-3 or front-face attack at C-1 (139). A number of new studies have been made of carbanion formation by base- catalysed proton exchange. Exchange and other accompanying reactions in olefins has been reviewed.lgO Strongly (-I +M) groups such as OMe de- activate a-hydrogens towards ionisation and exchange. Whereas a-hydrogen G. Maccagnani and F. Taddei Boll. sci. Fac. Chim. ind. Bologna 1968,26 71 83. la' H. R. Nace and B. A. Olsen J. Org. Chem. 1967,32,3438. la6 F. G. Bordwell R R Frame R G. Scamehorn J. G.Strong and S. Meyerson J. Amer. Chem. SOC.,1967,89,6704. la7 E. W. Warnhoff C. M. Wong and W. T. Tai J. Amer. Chem. SOC.,1968,90,514. la' G. Bergson and A. Weidler Acta Chem. Scand. 1963,17 1798. la9 J. Almy R. T. Uyeda and D. J. Cram J. Arner. Chem. SOC.,1967,89,6768. 190 C. D. Broaddus Accounts Chem. Res. 1968 1,231. 134 N. S. Isaacs exchange rates in compounds XYCH*CO,Rfor a wide variety of substituent groups X Y correlate quite well by the Taft (o*, p*) equation with a p*-value of 1.78,the compounds with an a-methoxy or fluorine substituent (X Y = MeO H ; F,H ; Me0,MeO ; F,F)are less active than predicted by the linear free-energy relationship by factors 104.7,lo7,and lo1 respe~tively.'~' These large disagreements must indicate that the factors measured by the Taft equation are not the most important in these cases.Possibly repulsive interactions between adjacent unshared pairs of electrons on carbon and on oxygen or fluorine account for these discrepancies. The effect is evidently a short-range one since fluorine in an aromatic ring labilises the benzilic hydrogen. 192* Exchange studies on sulphones have shown that the acidity of the a-hydrogen is diminished by an a-alkyl or alkenyl group and this to a greater degree than in ketones and nitro-alkanes. Ally1 sulphones exchange hydrogen only at the a-position (CH,). The acidity of the proton in a series of alkyldinitromethanes varies over two pK units according to the nature of the alkyl group. It appears that the bulk of the group is the factor most influencing acidity perhaps by affecting the planarity of theC(NO,) group by which the carbanion achieves stability.Hydrogen exchange in (140)occurs more rapidly by a factor of lo4 than in the cyclopropenyl analogue (141).'96Presumably the anion derived from the latter Ph Ph Ph Ph compound is destabilised by the antiaromatic 4n system. It has been pointed out that H-scales have a considerable dependence on the nature of the metal- ion associated with the base used on account of ion-pair association and that therefore correlations of rates with these acidity scales should be made and 19' J. Hine L. G. Mahone and C. L. Liotta .I. Amer. Chem. SOC.,1967,89 5911 19' R. Filler and C. S. Wang Chem. Comm. 1968 287. 193 A. Streitwieser and F.Mares J. Amer. Chem. SOC. 1968,90 644,648. lg4 C. D. Broaddus J. Arner. Chem. SOC. 1968,90,5504. lg5 M. E. Sitzmann H. G. Adolph and M. J. Kamiet J. Amer. Chem. SOC.,1968,90 2815. 196 R. Breslow and M. Douek J. Amer. Chem. SOC. 1968,90,2698. Reaction Mechanisms 135 interpreted with caution. lg7 The rate of proton exchange of acetophenone in the presence of OD-decreases with the cation present according to the order Mg2+ > Ca2+ > Ba2+ > Li' > Na' > K+,lg8 the order expected for decreasing coulombic association. Exchange in isopropyl methyl ketone occurs preferentially at the methyl hydrogen the methyl :methine rate ratio being 21 :1; in the structurally analogous methyl cyclopropyl ketone this rztio is 2225:l mainly due to diminished reactivity at the cyclopropane ring.lg9-'01 Diamines appear to enhance the reactivity of dimethylmagnesium towards the carbonyl group; a possible interpretation allows the amine to co-ordinate to the metal thus loosening the Mg4 bond (142).202 The enolate anion of benzocyclobutanone is very reactive towards C-C bond-cleavage and leads to dimeric pr~ducts.~"~ Ring-cleavage of the cyclo-octatetraenyl dianion is accomplished by acetyl chloride leading to the all-cis-dodecatetraene- 2,l l,-dione.'04 Nonclassical structures have been proposed for some carbanions. The monohomocyclo-octatetraene anion-radical has been prepared and its electron resonance spectrum has been recorded ;'05 the enhanced acidity (by a factor of lo4) of (143) compared to the mono-01efm,206 is considered due to n-participation in the 6n-structure [see (144)l.The n.m.r. spectrum of the 1,4-dianion of 1,1,4,4-tetraphenylbut~ne,~~~ shows the resonances of the three types of aromatic protons well separated on account of their differing inter- actions with the negative carbon atom (ortho z 2-9 meta 53 and para 4-3). The tetraphenylethylene anion-radical disproportionates reversibly to olefin and dicarbanion in ether although in hexamethylphosphoramide solution the equilibrium favours the anion-radical. '08 Coupling between radicals and carbanions has been demonstrated [e.g. (145)] a reaction which could prove useful ~ynthetically.~~~~ 'lo A base-catalysed rearrangement pathway from y2 Me / -Ph OzN-c-+ Q -e \ Me Me (146) 197 J.R. Jones Chem. Comm. 1968,513. 19' J. R. Jones Trans. Faraday SOC. 1968,64,440. 199 C. Rappe and W. H. Sachs Tetrahedron 1968,24,6287. 2oo C. Rappe and W. H. Sachs J. Org. Chem. 1967,32,4127. 201 J. Warkentin and C. Barnett J. Amer. Chem. SOC.,1968,90,4629. 202 H. 0.House and J. E. Oliver J. Org. Chem. 1968,33,929. 203 D. J. Bertelli and P. Crews J. Amer. Chem. SOC.,1968,90,3389. 204 T. S. Contrell and H. Shechter J. Amer. Chem. SOC.,1967,89 5868 5877. 205 F. J. Smentowski R. M. Owens and B. D. Faubian,J. Aver. Chem. SOC. 1968,90,1537. '06 J. M. Brown and L. V. Occolowitz J. Chem. SOC.(B),1968,411. 207 K. Takahashi and R. Asami Bull. Chem. SOC.Japan 1968,41,231. A. Cserhegyi J. Chandhuri E. Franta J. Jagur-Gradzinski and M.Szwarc J. Amer. Chem. SOC. 1967 89 7129. 209 G. A. Russell and W. C. Danen J. Amer. Chem. SOC.,1968,90,347. 'lo W. C. Danen Diss. Abs. 1968,28 B. 3639. 136 N. S. Isaacs epoxide to carbonyl compound (cfithe acid-catalysed reaction) has been shown to operate via the carbanion of (146).211 Reactions at the Carbonyl and Related Groups.-The complex interplay of steric and inductive effects among reagents and solvents continues to invite investigation. Esterification and ester hydrolysis are among the most common reactions studied for this purpose. The esterification by diphenyldiazomethane of meta-substituted benzoic acids in 14 mainly polar solvents has been studied and rate data have been recorded. Linear free-energy relationships were ob- served and the dependence of the rates on solvent followed moderately well a dielectric constant function.212 There is a problem in correlating rates with solvent properties however since proportions of monomeric and dimeric carboxylic acids change from solvent to solvent each form presumably having a different reactivity; more information would be welcome on the solvent de- pendence of these equilibria.A mechanism supported by kinetic evidence has been suggested for the esterification of benzoic acid by diphenyldiazomethane in toluene in which the reagents form an initial 1 :1 complex which is decom- posed by three routes uncatalysed and catalysed by monomeric and dimeric acid forms. The effects of trans-4-substituents on the esterification of cyclohexane- carboxylic acids shows a considerable increase in rate with increasing -I character of the substituent-a 10-fold rate increase from the 4-H to 4-OH compounds.l4 Steric factors are evidently of prime importance in the hydrolysis of trans-decalincarboxylic esters to judge from the greater reactivity of the 2-compared with the 1-esters and of equatorial over axial isomers.215 However it is unwise to make such generalizations since other factors may intervene. For instance the relative reactivities of cyclohexanecarboxylic esters and their 4-t-butyl analogues change with solvent the former being hydrolysed more readily in aqueous media and the latter in alcoholic. Although these effects may be explained in terms of changes in the axial :equatorial ratio especially of the unsubstituted esters their correct interpretation may be more subtle.From the acid-catalysed esterification of ortho-substituted benzoic acids two effects upon the variation of ASs with substituent have been suggested;216 an increase due to steric inhibition of solvation in the transition state is offset by a decrease due to the bulk of the substituent itself directed against the reac- tion site. All ortho-substituents depress AHS relative to hydrogen. Isotopic tracers have been used to show that the acid-catalysed ester exchange reaction,2 l7 involves alkyl-oxygen fission at the ester and the acetate-catalysed methanolysis of aryl acetates proceeds by a symmetrical intermediate presumably acetic an- "' G. R Treves H.Stanger and R. A. Olafson J. Amer. Chem. SOC., 1967,89,6257. '"A. Buckley N. B. Chapman M. R J. Dack J. Shorter and H. M. Wall J. Chem. SOC.(B),1968 631. 213 N. B. Chapman A. Ehsan J. Shorter and K. J. Toyne Tetrahedron Letters 1968 1049. '14 N. B. Chapman A. Ehsan J. Shorter and K. J. Toyne J. Chem SOC.(B),1968 931. '15 N. B. Chapman A. Ehsan J. Shorter and K. J. Toyne J. Chem. SOC.(B),1968 178. 2'6 N. B. Chapman M. G. Rodgers and J. Shorter J. Chem SOC.(B) 1968,157. 217 V. D. Parker and A. W. Baker. Chprn. Cornrn. 1968,691. Reaction Mechanisms hydride.2’8 This postulate was confirmed by Gold et al. by trapping this inter- mediate as acetanilide by addition of aniline to the reaction.219 The effects of different acids on several types of acid-catalysed ester hydrolysis have been studied by Bunton and his co-workers.220 For methyl 2,4,6-trimethylbenzoate (reacting by the AA,l mechanism) and t-butyl esters (AA1l) the catalytic order is HClO > H2S04 > HCl whereas in A,2 reactions the order is reversed.It was concluded that the anions play a part in the stabilisation of the transition state and that anions of a low charge-density stabilise best a transi-tion state with carbonium character while the opposite applies to transition states (such as the AA,2) in which there is considerable hydrogen-bonding to solvent. It was found that the salt effects upon the stability of the tri-p-methoxy- benzyl carbonium ion were in the order NaClO > LiClO > NaS0,Me > NaBr > NaCl > LiCl.The Reformatsky reaction between (+)-methyl-a- bromobutyrate and benzaldehyde has been reported to give optically active methyl a-ethyl-P-hydroxyhydrocinnamate.* Elimination.-An examination of the distribution of elimination products from the reaction of methoxide on 2-halogenohexanes (hex-1-ene cis and tram-hex-2-enes) has been made with a view to examining the validity of the theory222 that steric factors are primarily responsible for the direction of elimination. It was found that under E2 conditions the amount of hex-1-ene steadily decreased and the hex-2-enes increased as the leaving group was increased in size from fluoride to chloride bromide and iodide the reverse of what might be expected from a consideration of steric factors.223 Moreover the rates of formation of terminal olefin were accurately related to the rates of formation of cis-and tram-2-olefi11 separately suggesting that all three arise from the same transition state.These observations were interpreted by donsider- ation of a continuum of mechanistic types within the scope of the E2 mechanism varying from the ‘nearly El’ (147) through an intermediate type (148) to a ‘nearly carbanion’ type (149) with some degree of carbanion character on the P-carbon. The orientation of elimination is governed by the nature of the R. L. Schowen and C. G. Behn J. Amer. Chem. SOC.,1968,90,5839. V. Gold D. G. Oakenfull and T. Riley J. Chem. SOC.(B) 1968,515. 220 C. A. Bunton J. H. Crabtree. and L Robinson. J. Amer. Chem. SOC.,1968 m1258.221 J. Canceill. J. Gabard. and J. Jacsues. Bull. SOC.chim. France. 1968. 231. 222 H. C. Brown and I. Moritani J. Amer. Chem. SOC.,1956,78,2203. 223 R. A. Bartsch and J. H. Bunnett J. Amer. Chem. SOC. 1968,90,408. 138 N. S. Isaacs transition state ;thus since an a-alkyl group stabilises the intermediate and ‘nearly El’ transition states more than the ‘nearly carbanion’ one where the latter prevails Hoffman elimination will be preferred. The leaving group has an effect on the nature of the transition state which in the sequence from iodo to fluoro show a trend towards the ‘nearly carbanion’ as the electronegativity of the leaving group increases. The elimination of hydrogen halide from 3-halogenopropanes shows different values of the hydrogen isotope effect for the formation of cis-and tr~ns-pent-2-enes.’~~ However depending on the solvent used either may be the larger which suggests that this (rather small) isotope effect is bound up with solvation of the transition state rather than fundamental differences in mechanism for the two modes of elimination.Further evidence which envisages a continuum of mechanisms for elimination has been presented B6+ H I J__--It I * X6- 6‘B H’ I 7/.--‘v I I X6- I I H B;--1cI X6 - Y Ye Me-C -CH/\ CN Me E2H Intermediate E2C (150) (151) by Parker et ~1.~~~9 226 who suggest a shift in emphasis of attack by the base from the P-hydrogen (E,H-mechanism) through a transitional type to attack on the a-carbon (E,C) though the latter is distinct from an S,2 transition state (150).The evidence comes from correlations observed between elimination rates and either carbon nucleophilicities or bacicities (hydrogen nucleophilicities) of the base in a Brqhsted plot. Thus cyclohexyl toluene-p-sulphonate in aqueous medium correlates best with the carbon nucleophilicity and is deduced to follow an E2C path. It is concluded that the mechanism is affected by the nature of the leaving group ; weakly nucleophilic leaving groups prefer E,C mechanisms while stronger ones tend to react by E,H routes. Two eliminations with the characteristics of a prior reversible dissociation (E,cb mechanism) have been described first the trans-elimination of erythro-4,4’-dichlorochalconedi-chloride in ethanol is inhibited by acids2” while conditions suggested228 as being most likely to result in E,cb elimination-a strongly acidic P-hydrogen strong base and a poor leaving group-are met in compound (151) which shows the expected kinetic form in elimination of HCN.Carbanion mechanisms of elimination have been reviewed. 229 El -Mechanisms for acid-catalysed 224 D. L. Grifith and B. Singerman Chem. Comm.,1968,438. 225 A. J. Parker M. Ruane G. Biale and S.Winstein Tetrahedron Letters 1968 2113. 226 D. J. Lloyd and A. J. Parker Tetrahedron Letters 1968,5183. 227 T.I. Crowell R. T. Kemp R. E. Lutz and A. A. Wall J. Amer. Chem. Soc. 90,4638. 228 Z. Rappoport Tetrahedron Letters 1968,3601. 229 D. J. McLennan Quart. Rev. 1967,21,490. Reaction Mechanisms I39 dehydrations of benzyl alcohols are indicated by two lines of research.A positive p-value of considerable magnitude is characteristic of dehydrations of 1-methyl-2-aryl-2-hydroxypropionicacids’ 30 while eliminations from 1,2-diphenylethanols substituted in both rings are best correlated by a com- pound Hammett expression involving a function of 0’ for the adjacent group showing conjugation and 0 for the nonadjacent group showing only an in- ductive interaction. 31 It has been pointed out that isomerization of terminal to nonterminal olefins may occur in the presence of strong bases,232 a process which is not always examined in studies of the orientation of base-catalysed elimination. Although E reactions have hitherto been assumed to proceed by an anti-geometry several authors have provided evidence that considerable proportions of syn-elimination can occur especially in medium-ring compounds.Sicher’s group in Prague have studied eliminations in medium- and large-ring cycloalkanes from which both cis- and trans-olefins are formed. They conclude that the cis-isomers arise from anti-elimination but the trans-olefins mainly by a syn-pro~ess.’~~ These conclusions rest on two lines of evidence firstly on the isotope effects and olefin isotope content of stereospecifically labelled p-deuterio-compounds and secondly on the more equivocal conclusions drawn from rate-profile measurements-the charactwistic and different dependence of cis-and trans-olefin formation rates as a function of ring size. These rates are equated with anti- and syn-elimination rates by the isotopic labelling technique in certain cases.The results show that the rate of trans-olefm formation from cycloalkylammonium hydroxides reaches a maximum at the Clo ring while cis-olefin formation maximises at C12.The effects of different leaving groups bases and solvents were studied. Very high stereospecificity was reported for elimination of ammonium ions (Hofmann elimination) under a wide variety of conditions and similarly for some toluene-p-sulphonate. The bromides elimi- nated in a stereospecific manner in t-butoxide-t-butyl alcohol but in more polar media (ethoxide-ethanol or t-butoxide-dimethylformamide) anti-elimination geometries were reported to give both cis-and trans- olefins. The evident nonequivalence of the P-protons may be rationalised in terms of the supposed preferred conformations of the macrocyclic rings although little unequivocal evidence on this is available.The deuterium-labelling technique was also used to demonstrate that cyclo-ostyltrimethylammonium bromide gives 35 % cis-cyclo-octene by a mixture of 85 % anti- and 15% syn-elimination routes while the 65 % trans-cyclo-octene formed originated by an entirely syn-mechanism. 34 Varying proportions of syn-elimination were reported 230 D. S. Noyce and S. K. Brauman J. Org. Chem. 1968,33,843. 231 D. S. Noyce D. R. Hartter and F. B. Miles J. Amer. Chem. SOC. 1968,90 3794. 232 B. Blouri C. Cerceay and P. Rumpf Ann. Chim. (France) 1968,3 127. 233 J. Sicher and J. Zavada Coll. Czech. Chem Comm.1967 32 2115 2122; J. Zavada and J. Sicher ibid. 3701; M. Pankova J. Zavada and J. Sicher Chem. Comm. 1968 1142; J. Zavada M. Pankova and J. Sicher ibid. 1145; J. Sicher J. Zaved and M. Pankova ibid. 1147 J. Sicher and J. Zavada Coll. Czech. Chem. Comm. 1968 33 1278; J. Zavada J. Krupicka and J. Sicher ibid. p. 1393. M. Svoboda J. Zavada and J. Sicher ibid. 1415; M. Havel J. KrupiEka M. Svoboda J. Zavada and J. Sicher ibid. p. 1429; J. Sicher M. Tichy J. Zaved and J. KrupiEka ibid. p. 1438. 234 J. L. Coke M. P. Cooke and M. C. Mourning Tetrahedron Letters 1968 2247. 140 N. S. Isaacs from cyclobutyl(90 %) cyclopentyl(46 %) cyclohexyl(4 %) cycloheptyl(35 %) 3,3-dimethylcyclopentyl (76 %) and norbornyl (100 %) trimethylammonium-hydroxides using specifically labelled compound^.^ 5-2 37 It seems likely that both processes require coplanar arrangements of the leaving group P-proton and two carbon atoms.The compounds which give the most syn- transition state but not a planar anti-transition state. Where both planar syn- and anti-conformations are equally possible the latter seems favoured as oox X = CS*SMe (1 52) (153) cis (154) trans shown in the elimination of the toluene-p-sulphonate (152) from which hardly any syn-product was discernable. '38 More information of the thermodynamics of these two processes would be welcome and also whether the results are affected by the incursion of an El component with subsequent hydride (deuteride) migration. The elimination of the xanthates (153) and (154) gives A'-and A'- olefins with k,/k = 1.5.A syn-mechanism (six-centre transition state) is indicated but the A'-olefin derived from the cis-xanthate still contains up to 44% of the deuterium.239 It would appear that when an anti-elimination is forced carbonium ion-pair mechanism is favoured. Rapid hydride (deuteride) shift then occurs giving a tertiary carbonium ion which then eliminates a proton or deuteron statistically. The methide shift which occurs during the elimination from ( +)-[2H)neopentyl toluene-p-sulphonate does so stereo-specifically the ['HI isopentene produced having retained c~nfiguration.~~' The elimination of halogen halide from cla-dimethylphenethyl halides which occurs by an E mechanism with considerable carbonium character (p = -1.5) gives quite large amounts (20%) of nonconjugated ~lefin.~~~ Di- and tri- chloroethanes have been found to eliminate hydrogen chloride at very high rates on molecular seive the products being mixtures of cis- and trans-1,Z and 1,l-dichloroethylenes from the latter.242 The very high primary isotope effects observed during the elimination by alkyl lithium of cis- and trans-1-chloro- [2H]~tyrene'~~ (kdkD = 8 and 15 respectively,) is explained by an E,cb 235 M. P. Cooke and J. L. Coke J. Amer. Chem. SOC. 1968,90,5556; J. L.Coke and M. C. Mourn- ing ibid. 5561. 236 J. L. Coke and M. P. Cooke Tetrahedron Letters 1968 2253. 237 J. L.Coke and M. P. Cooke J. Amer. Chem SOC. 1967,89,6701. 238 D. H.Froemsdorf W. Dowd W. A. Gifford and S.Meyerson Chem. Cornm. 1968,449. 239 W.S.Briggs and C. Djerassi J. Org. Chem. 1968,33 1625. 240 G. Sollaide M. Muskatirovic and H. S. Mosher Chem Comm. 1968 809. 241 L. F.Blackwell A. Fischer and J. Vaughan J. Chem. SOC.(B),1967 1084. 242 I. Mochida and Y. Youeda J. Org. Chem. 1968,33,2161. 243 M. Schlosser and V. Ladenberger,Chem. Ber. 1967,100,3877,3893,3901. Reaction Mechanisms 141 mechanism-the first instance of such a process (155). The Cope elimination of the asymmetric amine oxide (Ma) leads to optically active 4-methylcyclo- hexene. 44 Polar Additions.-The carbonium ion-like transition state for polar additions receives support from several lines of work. The hydroxymercuration of olefins shows a Taft p*-value of -3.3 from the linear correlation of log k with o*.~~’ The acid-catalysed hydration of phenylbenzoylacetylenes in strongly acid solution shows a dependence of log k on H with p = -4.2 and a correlation witho+.246 The hydrolysis of phenyl vinyl ethers has p = -2.21 but now log k correlates with o rather than 0’ since the substituent and positive centre are separated by oxygen.247 Stereochemical investigations include the report that bromine addition to 1 -phenylpropene and to trans-anethole occurs non-stereospecifically presumably by way of a carbonium rather than a bromonium ion.24 The substituted bicyclo[2,1,0]pentane (156) undergoes cis-catalytic hydrogenation mainly on the exo-side ;249 bicyclo[2,1,1] hex-2-ene adds mer- curic acetate DCI and deuterioacetic acid in cis-fashion but benzenesulphinyl chloride in a trans.250 @-Unsaturated acids have been shown to be less reactive towards bromide addition than their conjugate bases which presumably are able to stabilise positive charge on the a-carbon atom.251 By simple fickel MO theory it has been calculated (in agreement with experiment) that 1,2- hydrohalogenation of butadiene and isoprene is kinetically favoured as is 1,4:addition to chloroprene ; 1,4-addition is thermodynamically favoured by each diene.252 Fluorine diluted with fluorocarbon at -78”will add smoothly to acetylenes to yield 1,2,2,2,-tetrafluorohydrocarbons ;253 iodine nitrate generated from silver nitrate and iodine adds to cholestene with the formation of 2-ct-nitrato-3,P-iodocholestane.254 The metallation products of cyclic olefins depends on both ring size and base;255 either the vinyl or allylic metal derivative may be formed according to the conditions.A bromonium ion intermediate is implicated in the addition of bromine to unsaturated esters as judged by the trans-stereochemistry ;2 56 a charge-transfer complex inter- mediate has also been proposed for this rea~tion.~” An interesting observation of steric inhibition of resonance has come from bromination on studies on (157) and (1 58) for the former the rate of bromine addition is a function of the 244 F. L. Lam Diss.Abs. 1967,27B 4266. 245 J. Halpern and H. B. Tinker J. Amer. Chem. SOC.,1967,89,6427. 246 D.S.Noyce and K. E. deBruin J. Amer. Chem. SOC.,1968,90,372. 247 T.Fueno I.Matsumura T. Okuyama and J. Furukawa Bull. Chem SOC.Japan 1968,41,818. 248 R.C.Fahey and H-J. Schneider J. Amer. Chem. SOC.,1968,90,4429. 249 M.~J. Jorgenson Tetrahedron Letters 1968,4577. 250 F.T.Bond J. Amer. Chem. SOC.,1968,90,5326. 251 R.P.Bell and D. Dolman J. Chem. SOC.(B),1968,500. 252 M.D. Jordan and F. L. Pilar Theor. Chim. Acta 1968 10,325. 253 F.Merritt J. Org. Chem. 1967,32,4124. 254 J. E.Kropp A. Hassner and G. J. Kent Chem. Comm. 1968,906. 255 C. D.Broaddus and D. L. Muck J. Amer. Chem. SOC., 1967,89,6533. 256 G.Hueblin and R. Steudel Z. Chem. 1968,8 108. ’” F.Gamier and J-E. Dubois Bull. SOC.chim. France 1968,3797. 142 N. S. Isaacs Ph LI L H Ph- E- Li Ph Ph Me’ Ni‘CH,C(Me) 0- (156) x (158) Hammett constant 0,while for the latter of the polar constant o+.258 Thus considerable carbonium-character of the transition state must reside on the benzilic carbon which can only become co-planar with the phenyl group in (158).The chlorination of ap-unsaturated carbonyl compounds in acetic acid has been interpreted as partaking of a variety of mechanisms:chloronium-ion attack especially on rather electron-poor double-bonds ion-pair formation from molecular chlorine addition to more nucleophilic double-bonds and some cis-addition. 59 258 A. F. Hegarty and J-E. Dubois Tetrahedron Letters 1968,4839. 259 M. D. Johnson and E. N. Trachtenberg J. Chem. SOC.(B),1968. 1018; M. C. Cabaleiro M. D. Johnson B. E. Swedlund. and J. G. Williams. ihid.. 1022; M C.Cabaleiro. C. J. Cooksey M. D. Johnson B. E. Swedlund and J. G. Williams ibid.,p. 1026.