4 Reaction Mechanisms Part (ii)Polar Reactions By H.R. HUDSON Department of Chemistry The Polytechnic of North London Holloway Road London N7 8DB 1 Introduction Nucleophilic substitution at saturated carbon particularly in solvolysis reactions continues to account for a substantial proportion of the research publications coming under this heading. The first section of this year’s Report deals with some recent studies on structural effects in this area whilst a critical account of medium effects on the rate and mechanism of solvolysis reactions is given elsewhere.’ Also included below are sections on nucleophilic substitution at unsaturated carbon in compounds containing carbon-carbon (vinylic) or carbon-nitrogen double bonds carbocations addition and elimination.Carbanions reactions of carbonyl compounds and other relevant topics are deferred to make way for a new section on ion-molecule reactions in the gas phase in so far as these throw light on the mechanisms of polar organic reactions. Full coverage of all aspects of organic reaction mechanisms is given in an annual review of this subject.* 2 Nucleophilic Substitution at Saturated Carbon The tool of increasing electron demand which was introduced to study partic- ipation and the non-classical carbonium-ion pr~blem,~ has become a powerful means for the investigation of solvolytic processes. The method involves the attachment of a series of substituted aryl groups to the potential carbocation centre and a determination of the p+ value of the system as a measure of its sensitivity to electronic influences.In the solvolysis of aryldialkylcarbinyl p-nitrobenzoates (1) in 80% aqueous a~etone,~ the similarity in p+ values for t-cumyl 3-methyl-2-buty1 and 3-pentyl derivatives indicates that the stabilizing effect of the alkyl groups (Me Et and Pi) must be nearly the same in each case. High negative values for the cyclopropyl and cyclobutyl members of the 1-aryl- 1-cycloalkyl p-nitrobenzoate series (2) have been attributed to the effect of I-strain which destabilizes the carbocation and results in T. W. Bentley and P.von R. Schleyer Ado. Phys. Org. Chem. 1977,14 1. ‘Organic Reaction Mechanisms 1977’ ed. A. R. Butler and M. J. Perkins Wiley London 1978. H. C. Brown ‘The Non-Classical Ion Problem’ Plenum New York 1977.H. C. Brown M. Ravindranathan E. N. Peters C. G. Rao and M. M. Rho J. Amer. Chem. Soc. 1977 99,5373. 71 H. R. Hudson R' I Ar-C-X (dH2)n-l C(Ar)X I R2 (1) X = p-N02C6H4C02-; Ar =p-XC6H4 (X = MeO Me H or CF3)or 3,5-(CF3)2C6H3 an increased electron demand on the aryl system. Cyclohexyl also gives rise to a relatively high negative p+ value which has been attributed to the resistance of this conformationally stable system to the introduction of an sp2 centre. Unambiguous evidence for participation of carbon has been obtained by the use of a similar procedure in the solvolysis of a series of 9-aryl-9-pentacyclo-[4,3,0,02*4 03,' O5.']nonyl p-nitrobenzoates (3).' The p+ value for this system (-2.05) is comparable to that observed in the solvolysis of 7-norbornenyl deriva- tives in which n-participation is significant.Comparison of solvolysis rates with those for the corresponding 7-norbornyl derivatives (4) shows also that with increasing electron demand at the cationic centre the rates of solvolysis of the pentacyclic derivatives increase markedly relative to those for the 7-norbornyl compounds. Solvolysis of the parent substrate (3; R =H) is 10'o-1012 times faster than for the related 7-norbornyl derivative. The results which are also supported by low 9-Me/9-H and 9-Ph/9-Me rate ratios in the pentacyclic series are inter- preted in terms of (To)-participation by the remote cyclopropane bond leading to the trishomocyclopropenyl cation (5). X =p-NO2C6H4CO2-;R =p-XC6H4(X = MeO H or CF3) or 3r5-(CF3)2C6H3 Absence of significant a-participation has been demonstrated in the solvolyses of tertiary 2-aryl-2-norbornyl (6) and 2-aryl-2-camphenilyl p-nitrobenzoates (7).6 In X =p-NO2C6H4Co2-;Ar =p-XC6H4 (X =MeO Me H or CF3)or 3,5-(CF3)&H3 these series the effect of deactivating the aromatic ring and thereby increasing electron demand at the cationic centre should be to increase the exolendo rate ratios if cr-participation is an important factor.Essentially constant exolendo rate H. C. Brown and M. Ravindranathan J. Amer. Chem. SOC. 1977 99 299. H. C. Brown K. Takeuchi and M. Ravindranathan J. Amer. Chem. SOC.,1977,99 2684. Reaction Mechanisms-Part (ii) Polar Reactions ratios are however obtained within each series.The results imply that the high exolendo rate ratios observed in the tertiary 2-norbornyl systems are due mainly to decreased rates of reaction in the sterically hindered endo direction of the norbor- nane structure; and by extrapolation a similar conclusion has been drawn for the corresponding secondary systems. A fundamental difference in the behaviour of tertiary and secondary systems has been reported in the solvolysis of 5-norbornen-exo -2-yl substrates.’ Whereas the secondary ester (8) undergoes assisted ionization during acetolysis to yield the symmetrical norbornenyl-nortricyclyl cation (9) and thence racemic products (10) and (11) (Scheme l) solvolysis of optically active 1,2-dimethyl-5-norbornen-exo -2-yl p -nitrobenzoate (12) in 90% aqueous acetone yields 2-methylene- l-methyl-5-norbornene (16) (with 62% retention of configuration) 1,2-dimethy1-5-norbornen-exo-2-o1 (15) (with 15% retention of configuration) and racemic 1,6-dimethyl-3-nortricyclanol(17)(Scheme 2).The results which are also similar for methanolysis are consistent with the initial formation of a sym-metrical tertiary cation (13). /(10) (93%) HOAc* &Gis (9) (11) (7%) Scheme 1 /1 1 (X= p-N02C6H4C02-) Scheme 2 ’H.L. Goering and C.-S. Chang I. Amer. Chem. Soc.,1977,99,1547. H.R. Hudson Evidence for C-C 0-delocalization in simple secondary carbocations has been obtained in the acetolysis of some N-alkyl-N-nitroso-acetamides which give small yields of primary acetates.' For example the cyclohexyl derivative gives cyclohexyl acetate and cyclopentylmethyl acetate in the ratio 99.05 :0.95.Rearrangement of 1-ethylpropyl to 2-methylbutyl (0.3%)and of s-butyl to isobutyl (0.2%) similarly occurs. It has been argued that the equilibrium coefficient between a secondary and a primary cation (70-80 kJ mol-' apart in energy) will be ca. 10l2 and would require a physically unrealistic difference of lo9or more in the reaction rates of two assumed classical intermediates to account for the product ratios observed. A non-classical ion or protonated cyclopropane (19) generated only when the R-C and C-A bonds of the substrate (18) are anti-parallel has been proposed to account for these strongly endothermal secondary to primary rearrangements (Scheme 3) and it has been suggested that C-C 0-delocalization in simple carbocations may be more widespread than has frequently been implied.RZ-CHz R,-CH R'-CH2 \ -* CH,,\C -\C-A ,,' \ I H 'Ri H (18) (19) Scheme 3 Evidence has been obtained for the involvement of protonated cyclopropane intermediates in the trifluoroacetolysis of n-[ 1-l4C]buty1 mercuric perchlorate at 50 or 72 0C.9 Under these conditions the 14C label appears at all positions of the major solvolysis product (2-butyl trifluoroacetate) at positions 1 and 2 of the n-butyl ester and is divided in a 50 50 ratio between C-1 and the rest of the molecule in the small amount of isobutyl ester (ca. 2%) which is formed. The results are consistent with 8-14% of the products being formed from a series of equilibrating CH y3 (743 I CH .c.H2 / +*.\ **:y ,' t I\ H,C-CH H,C--CH3 H3c'--m (20) (21) (22) m=14~ CH3 I C.M. Cooper P. J. Jenner N. Perry H. Storesund J. Russell-King and M. C. Whiting J.C.S. Chem. Comm. 1977,668. C. C. Lee and R. Reichle J. Org. Chem. 1977,42. 2058. Reaction Mechanisms-Part (ii) Polar Reactions 75 edge- or corner-protonated cyclopropanes [(20)-(291. At 35 OC only successive 1,2-hydride shifts appear to be involved (Scheme 4). CH3CH2CH214&H2 + CH3CH26H14CH3$ CH36HCH214CH3 Scheme 4 The description of secondary solvolysis in terms of competing neighbouring- group (ka)and nucleophilic solvent-assisted (k,)processes is now well established [equation (l)].'"In limiting or unassisted solvolyses the rate constant is represen-kl= k,+ k (1) ted by k, and there has been much debate on the possible importance of such a process in secondary systems.l1 Recent studies on the solvolysis of cyclo-octyl tosylate have now shown that the solvolysis of a secondary substrate by the k process may not be unusual even in a rather nucleophilic solvent and where there are no obvious barriers to back-side approach by the nucleophile provided that relief of ground-state strain is sufficient to provide a competitive pathway.12 The kinetic evidence is based on comparisons with adamantyl tosylate in aqueous ethanol or aqueous 2,2,2-trifluoroethanol and is supported by theoretical cal- culations on the ionization of methylcyclo-octane (Scheme 5) (the methyl group Scheme 5 being considered sterically similar to a leaving group such as chloride or p-nitrobenzoate).The calculations indicate a value of -3.06 kcal mol-' for the S-strain whereas other acyclic or monocyclic substrates show positive 6-strain values. In another context new light has been thrown on the importance of steric acceleration in solvolytic reactions by a determination of the X-ray crystal struc- ture of tris(t-buty1)methyl p-nitr~benzoate.'~ Both B-strain which results from crowding of the bulky t-butyl groups and F-strain which results from steric interference between the t-butyl groups and the p-nitrobenzoate moiety are clearly demonstrated by distortions of bond lengths and bond angles. The relief of both types of strain as the transition state is formed must therefore be assumed to have significant effects on reaction rate.3 Nucleophilic Substitution at sp2 Carbon Vinylic Substitution.-In spite of considerable work in recent years on vinyl cations as reaction intermediates l4 a number of fundamental questions related to the lo €3. Capon and S. P. McManus 'Neighbouring Group Participation' Vol. 1 Plenum New York 1976. J. R. Pritt and M. C. Whiting J.C.S. Perkin II. 1975 1458 and references cited therein. J. M. Harris D. L. Mount M. R. Smith and S. P. McManus J. Amer. Chem. SOC. 1977,99 1283. l3 P. T. Cheng S. C. Nyburg C. Thankachan and T. T. Tidwell Angew. Chem. Internat. Edn. 1977,16 654. I4 Z. Rappoport Accounts Chem. Res. 1976 9 265; M.Hanack ibid. p. 364; Ann. Reports (B),1975 72.71. H. R. Hudson extent of bond-breaking in the transition state and to substituent effects have remained unanswered. Recent studies on the solvolysis of ring-substituted -styryl trifluoromethanesulphonates (triflates) (26) and their dideuterio-analogues (27) HK=C(Ar)OS02CF3 D2C =C(Ar)OS02CF3 (26) (27) Ar = XC6H4 (X =H P-C~, m-Cl p-CF3 or P-NO~) have gone some way towards elucidating these factor~.~’ For both series excellent Hammett plots were obtained with p = -4.1 which is indicative of considerable charge development in the transition state even with the strongly deactivating p-nitro-substituent present. A P-deuterium isotope effect of kH/kD = 1.45 for the parent compounds agrees well with earlier results.Taken with other literature data a full range of kH/kD values from 1.21 for p-methoxy to 1.71 for p-nitro is obtained and shows a linear correlation with substituent u+values. The results indicate that rotation of the aryl group to deconjugate with the C=C double bond and to conjugate with the nascent empty p-orbital occurs early and must be complete or nearly so at the transition state leading to the vinyl cation. Novel rearrangements of the vinyl cation have been reported in the solvolyses of the spiro-triflate (28) and the primary vinyl triflate (30).16 At 130°C in aqueous ethanol or aqueous trifluoroethanol buffered with pyridine the spiro substrate gives a yield of 90-98% of diene (29). It has been concluded that migration of the adjacent cyclohexyl bond to the vinyl cation centre occurs probably in a concerted fashion with anchimeric assistance (Scheme 6).Cycloheptanone is the principal product obtained under similar conditions from the primary vinyl substrate and it has been suggested that in this case concerted ionization and bond migration acruss the vinyl group occurs to give the cyclic vinyl cation (31) as the first intermediate (Scheme 7). The rearrangement suggests that a ‘bent’ secondary vinyl cation of this type is more stable than the corresponding linear primary vinyl cation. (30) (31) Scheme 7 *’P. J. Strang R. J. Hargrove and T. E. Dueber J.C.S. Perkin IZ 1977 1486. l6 P. J. Strang and T. E. Dueber Tetrahedron Letters 1977 563. Reaction Mechanisms-Part (ii) Polar Reactions 77 acetolysis of triaryl[2- ‘3C]vinyl bromides (Scheme 8) in the presence of silver shown that the relative extents of isotopic scrambling which occur during the acetolysis of triaryl[2-13C]vinyl bromides (Scheme 8) in the presence of silver Ar213C=C(Ar)Br HoAc+ Ar213C=C(Ar)OAc+A~O’~c(Ar)=cArz Scheme 8 acetate are in the approximate ratio 1 :2 :3 for the phenyl p-tolyl and p-anisyl derivatives respectively.l7 The differences are much smaller than would be expec- ted if migratory aptitude was the predominant factor in determining the extent of rearrangement and it has been suggested that the stability of the initial cation and the effect of the particular aryl group on the electrophilic character of the migration terminus are also important.Higher percentages of rearrangement occur in trifluoroacetic acid. Kinetic solvent isotope effect studies show that an addition- elimination sequence can occur although it becomes less significant if a salt such as silver or sodium acetate is added. The acid-catalysed hydrolysis of vinyl sulphides has been shown to proceed by a mechanism analogous to that of vinyl ethers.l* Slow proton transfer to the C=C double bond gives a sulphur-stabilized carbenium ion which reacts rapidly with water to form products (Scheme 9). Scheme 9 An interesting controversy has arisen over the stereochemistry of nucleophilic substitution of (E)-and (Z)-3-chloro-2-phenylpropenonitriles[(32)and (33);X= Cl].” Whilst retention of configuration is confirmed in reactions of these isomers Ph X Ph H \/ \c=c / NC/c=c\H /\ NC x (€)-isomer (2)-isomer (32) (331 with weak bases such as morpholine piperidine and phenol-triethylamine it is claimed that 1:1 mixtures of the corresponding (E)-and (2)-vinyl ethers are obtained in reactions with strong bases such as sodium ethoxide in ethanol or sodium phenoxide in THF.20 Such a result is explicable by initial retention followed by a number of ‘racemization’ mechanisms,’l and could possibly be due to the use of higher concentrations of reactants in the later work.Of more fundamen- tal importance is the view2’ that the previous configurational assignments for (E)-and (Z)-3-ethoxy-2-phenylpropenonitriles[(32) and (33); X=OEt]” should be C. C. Lee A. J.Paine and E. C. F. KO Canad.J. Chem. 1977,55 2310. R. A. McClelland Canad.J. Chem. 1977 55 548. 19 2. Rappoport and A. Topol J.C.S. Perkin IZ 1975 982. 2o G. Le Guillanton and M. Cariou J.C.S. Perkin 11 1977 997. 2’ Z.Rappoport J.C.S. Perkin IZ,1977 1000. H. R. Hudson reversed. This would imply that an unprecedented inversion of configuration had occurred in the substitution reaction with ethoxide and the result should be viewed with caution at this stage. Nucleophilic Attack on C=N Double Bonds.-Nucleophilic substitutionsof diaryl-imidoyl chlorides (34;X = C1) by secondary amines in benzene or acetonitrile show complex mechanistic behaviour. In benzene both first- and second-order terms in [amine] are observed and the Hammett plots show minima which are indicative of two competitive processes having opposite electronic demands.22 The results have been ascribed to a combination of an SN2(ion-pair) process for electron-donating substituents (Scheme 10) and a nucleophilic addition-elimination process (AdN-E) for electron-attracting substituents (Scheme 11).Superimposed on these schemes are less important third-order amine-catalysed routes in which the amine may serve as a base electrophile or bifunctional catalyst. In acetonitrile the amine-catalysed route disappears and it has been suggested that the AdN-E process occurs together with reaction either ria ion-pairs or free nitrilium ions. X IAr-C=N-Ar’ NR2I I (34) R2NH Scheme 11 The less reactive imidoyl cyanides (34;X =CN) undergo nucleophilic substitu- tion by amines in acetonitrile or by alkoxides in alcohols only by an addition- elimination sequence.23 It has been suggested that a common initial step involves nucleophilic attack on the imidoyl cyanide by the amine alkoxide ion or alcohol and that the subsequent expulsion of the leaving group may be uncatalysed or amine-catalysed in acetonitrile or solvent-assisted in the alcohol.4 Carbocations Preparation and Rearrangements in Super-acid Media.-The first direct obser- vation of a long-lived cyclopropyl cation has been made by dissolving the highly strained 11-methyl-1 l-bromotricyclo[4,4,1,01~6]undecane(35) in S02CIF at -60°C and adding the solution slowly to SbF5 in SO2C1F at -120°C (Scheme 12).24 The ‘H n.m.r. spectrum at -90 “C reveals substantial deshielding of the 22 R.Ta-Shma and Z. Rappoport J. Amer. Chem. SOC.,1977,99,1845. 23 R. Ta-Shma and Z. Rappoport J.C.S.Perkin ZZ 1977,659. 24 G.A. Olah G. Laing D. B. Ledlie and M. G.Costopoulos J. Amer. Chem. SOC.,1977,99 4196. Reaction Mechanisms-Part (ii) Polar Reactions Scheme 12 methyl and methylene protons which is indicative of a discrete carbocation struc- ture. The I3C n.m.r. spectrum shows that the ion is unsymmetrical and is best described as a ‘bent’ cyclopropane cation (36). Deshielding at C-1 C-6 and C-11 suggests that the positive charge is delocalized by interaction of the C-1-C-6 u-bond with the p-orbital at C-1I. Some new examples of substituted pyramidal dications have been prepared by dissolution of the precursors (37) and (38) in HFS03-SbF5 (1 :1) in S02ClF at -60°C.25 Those containing two ethyl or two isopropyl groups are found to have these substituents in the basal positions and their formation is rationalized as shown (Scheme 13).HS03F-SbF5 in HO R R=Et or Pr’ (37) Scheme 13 25 C. Giordano R. F. Heldeweg and H. Hogeveen J. Amer. Chem. SOC.,1977,99,5181. H. R. Hudson Ring closure of ally1 to cyclopropylcarbinyl has been systematically studied by treatment of 4-methylpent-1-en-3-01 (39; R' = Me R2 = H) 2,4-dimethylpent-1-en-3-01 (39; R'= R2= Me) and pent-1-en-3-01 (39; R' = R2= H) with FS03H- SbFs in S02C1F at -78 or -1200C.26 The corresponding cyclopropylcarbinyl cations (41) which are thought to be formed via the homoallylic ions (40) rear- range further at higher temperatures to the more highly substituted allylic s ructures (42) (Scheme 14).The general order of thermodynamic stability ffr ions in which R' = R2= H is (RCH=CH-CH2)+ < cyclo-C3H5C+R2< (RCH-CH-CHR)' and the stabilizing effect of a cyclopropyl group on a carbenium centre has been estimated as 11-17 kcal mol-' larger than that of a vinyl group. R2 I R' H R2 R' C R' R2 Ill I A\ I I H3C-C-C-C=CH2 + H3C-C-C CH2 + H3C-?-CH2-C=CH2 It II H OH HH (39) Scheme 14 A study of rearrangements and equilibria in the ions formed under stable ion conditions from P-arylethyl chlorides and their side-chain-substituted derivatives shows that u-bridged ethylenearenium (phenonium) ions are formed only from 2-chloroethylbenzene and its ring-substituted derivative^.^' The ethylene-benzenium ion (43) is formed quantitatively in HF-SbF5 at -60°C and subsequently rearranges at higher temperatures via the highly unstable 2-phenyl- ethyl cation (44) to give the benzylic ion (45) (Scheme 15).Substitution of methyl Scheme 15 groups at C or CBleads upon ionization to rearranged benzylic and/or equili- brating /3 -phenylethyl cations but the experimental determination of the energy difference between these two types is possible only in the case of the ions derived 26 H. Mayr and G. A. Olah J. Amer. Chern. SOC.,1977,99 510. 2' G. A. Olah R.J. Spear and D. A. Forsyth J. Amer. Chem. SOC.,1977,99 2615. Reaction Mechanisms-Part (ii) Polar Reactions from l-(p-methoxyphenyl)-2-chloropropane(Scheme 16).The relatively small energy difference (8-10 kcal mol-') has been interpreted in terms of stabilization of the @-phenylethyl cation by wbridging (46),although the concentration of this species at equilibrium is thought to be exceedingly low. CH2CHCICH CH -CIi -CH CH2-,CH-CH3 CH 2-,CH -CH I I .' Q' OCH OCH OCH (46) Scheme 16 The proton-decoupled and proton-coupled 13Cn.m.r. spectra of all C3to Cs alkyl cations show the methyl substituent effects to be constant and additive.28 They can therefore be used to estimate 13Cchemical shifts of static alkyl cations as well as of symmetrical or unsymmetrical equilibrating carbocations. There is little or no contribution from hydrogen-or methyl-bridged structures in equilibrating t-cations and the experimental data allow calculations to be made of AG AH and AS for the differences between them.Application of the additive substituent effect method to equilibrating secondary carbocations e.g. s-butyl shows significant deviations of the estimated from the experimental values and indicates that there is a contribution from partial hydrogen-bridging. Other Aspects.-A critical examination of the use of 13C chemical shifts for establishing electron densities in carbocations has been made on the basis of solvolysis rate studies for the p-nitrobenzoates shown [(47)-(49)J.29 The large (X =P-NO~C~H~CO~-) Relative kf 1.O 103 lo2.' 13Cshift/p.p.m (from TMS) 329.2 254.4 280.6 (*80% aqueous acetone 25 "C) rate enhancements observed with phenyl or cyclopropyl substituents on the a-carbon atom appear to result from major electron supply from the ring system rather than from the relief of B-strain.Nevertheless the relative rates show no correlation with the 13Cchemical shifts for the corresponding carbocations and it has been questioned whether such shifts can be used in their present state of understanding to prove unequivocally the structures of ions such as 2-norbornyl or 2-bicyclo[ 2,1,1] hexyl. A 'bona fide free methyl cation' has been generated in the liquid phase by allowing tritiated methane to undergo @-decayin solution in benzene and toluene *' G. A. Olah and D. J. Donovan J. Amer. Chem. SOC.,1977,99,5026. z9 H.C. Brown and E. N.Peters J. Amer. Chem. Soc. 1977,99,1712. H. R. Hudson [equation (2)].30 Alkylation of the aromatic ring ensues. This novel approach appears to provide a means for observing the intrinsic reactivity in solution or even CT P-decay) CT;+ 3He+P-(2) in the solid state of a simple carbocation completely unperturbed by the effects of solvent or counterion etc. 5 @-Elimination The range of mechanisms available for /3 -elimination has been discussed previously [cf.Ann. Reports (B),1976 73 61; 1975 72 761. Substrates with good leaving groups attached to a s-or t-carbon atom and having no activation of the proton on CB react with weak bases which are also strong nucleophiles by a mechanism designated E2C. The precise nature of the ‘loose’ transition state involved is still a topic for active discussion which centres on whether there is a covalent ‘SN2-like,’ component to the interaction of the base with C,[(50) or (51)] or whether such interaction is electrostatic in nature (52).What is said to be compelling evidence ._ (50) (5 1) (52) against the extensive development of positive charge on C has been obtained by comparison of the secondary deuterium isotope effects associated with the P’C-H and rC-H bonds of cyclohexyl tosylate in its elimination reaction with tetra- butylammonium hydroxide in acetone.31 The similarity in magnitude of these effects (kSe-d/k,,-d= 0.98) is taken to indicate a substantial degree of formation of a double bond in the transition state. It has however been pointed that 1,3-diaxial interactions between the y-hydrogens and the leaving group will be relieved as the transition state is formed whatever the mechanism and that the changes in associated vibrational frequencies will induce an isotope effect at C of the type observed.An examination of the elimination (E2) and substitution (SN2) reactions of cyclohexyl tosylate with triphenylphosphine shows that this neutral weak base which is also a good carbon nucleophile is a poor reagent for elimina- tion compared to anionic weak bases which promote the E2C process (PhS- OAc- C1- PhO- Br- etc) or compared to strong neutral bases such as tri- ethylamine or 1,5-diazabicyclo[4,3,O]non-5-ene(DBN) whose reactions are more E2H-like in character.32 The results suggest that whilst interaction between an anionic base and C is important in the E2C transition state this interaction is primarily electrostatic.The methoxide-induced eliminations of l,l-diaryl-2,2-dichloroethanes[(p-XC6H4)2CHCHC12] and their 0-deuteriated analogues provide what is claimed to 30 F. Cacace and P. Giacomello J. Amer. Chem. SOC.,1977,99 5477. 31 D. Cook J. Org. Chem. 1976,41 2173. 32 D. J. McLennan J.C.S. Perkin IZ 1977 293. Reaction Mechanisms-Part (ii)Polar Reactions be the first example of mechanistic changeover from R (for X = H or C1) to ElcB (for X=NOz) as a result of changing the substituent in the @-bound aromatic ring.33 Similar conclusions have been reached as a result of studying chlorine isotope effects in the same system (X = MeO C1 H or NO,) and it has been shown that the C-Cl bond must be very nearly intact in the E2 transition [cf.Ann.Reports(B) 1976 73 63 for a preliminary communication]. The influence of changes in substituents on C on the mechanism followed is exemplified in the reactions of methanolic methoxide with 2,2-di-(p-nitrophenyl)-l 1,l-trifluoro-ethane 2,2-di-(p-nitrophenyl)-l-fluoroethane and their P-deuteriated ana-logue~.~~ The presence of three fluorine atoms on C leads to a clear example of reversible formation of the carbanion intermediate i.e. the (ElcB)R mechanism is in operation. In contrast the analogous trichloro-substrate has been shown to undergo elimination via the irreversible carbanion mechanism designated (E~cB)~.~~ With only one fluorine (i.e.the leaving group) on C, the reaction follows the E2 mechanism with a carbanion-like transition state.An interesting example of alkene formation with hydride ion as the leaving group is provided by the elimination reactions of organolithium and organomagnesium compounds in the presence of hydride acceptors e.g. tetraphenylcarbonium tetrafluoroborate tricyclohexylborane or tri-s-butylborane [equation (3)].37 M = Li or Mg;A = Ph4C+BF, (c~CIO-C~H~~)~B, or (s-C~H~)~B Preferential formation of the Hofmann product has been attributed to steric influences. 6 Electrophilic Addition Two possible mechanisms have generally been considered to be available for the acid-catalysed hydration of olefins. One involves the rate-determining protonation of carbon (the AsE2mechanism) (Scheme 17) whilst the alternative route which fast + H30+ slow )+--tH(+H20)) H O ~ + HH+ Scheme 17 reflects the dependence of reaction rate on acidity function rather than pH involves the initial formation of a .n-complex which subsequently undergoes rate-deter- mining conversion into the solvated carbocation (Scheme 18).A review of the literature data on olefin hydration together with numerous new experimental results now provides evidence that all olefin hydrations proceed by the AsE2 33 D. J. McLennan J.C.S. Perkin 11 1977 1753. 34 A. Grout D. J. McLennan and I. H. Spackman J.C.S. Perkin 11 1977 1758. 35 J. Kurzawa and K. T. Leffek Cunud. J. Chem. 1977,5S 1696. 36 D.J. McLennan and R. J. Wong J.C.S.Perkin 11 1974 1373. 37 M. T.Reetz and W. Stephan Angew. Chem. Internat. Edn. 1977,16,44. H. R. Hudson Scheme 18 process.38 This conclusion is based on the extremely good correlation [equation (4)] which is obtained by plotting the second-order constants for olefin hydration in aqueous acid at 25 "Cagainst the sum of the relevant up' parameters for the alkyl substituents attached to the carbocation centre of the intermediate R'R2R3C+. For a range of ninety-six olefins including 1,l-and 1,2-disubstituted alkenes 2-substituted buta- 1,3-dienes substituted styrenes vinyl esters N-vinylacetamide and 2-bromopropene a correlation coefficient of 0.938 is obtained with p = -10.5 and C = -8.92. A comparison of ethylene with p-nitrostyrene at Ho-7.37 shows that ethylene is the less reactive as predicted by equation (4) and indicates that ethylene itself protonates through an AsE2 transition state to give the open ethyl cation.This quite remarkable conclusion is at variance with many currently held views on the role of carbocation intermediates in nucleophilic solvents. Indeed it has so far proved impossible to detect a free ethyl cation in super-acid media let alone in water and it seems likely that the interpretation of this result will come under careful scrutiny. Two sets of workers have now concluded that contrary to previous reports solvent effects do not cause significant changes in the relative rates of bromination of alkenes and alkynes although the absolute rates may change con~iderably.~~~~~ Structural effects are however significant in determining the rate-constant ratio kC=C/kCrC,which is ca.lo3 for styrene and phenylacetylene but ca. 1.0 for cinnamic acid (or its 4-nitro-derivative) and the corresponding acetylene in a range of hydroxylic solvents.39 The role of structural effects is greatly enhanced in chlorinated hydrocarbon solvents in which the reaction is also seen to be second- order in bromine.41 The importance of electrophilic solvent assistance to the leaving group (Br-) is clear but there is a difference of opinion as to whether the cationic intermediate is subject to specific nucleophilic ~olvation,~' or simply to a medium It has been proposed that the accepted mechanism of olefin bromination (Scheme 19) is also valid for acetylene^.^' Scheme 19 7 Ion-Molecule Reactions in the Gaseous Phase Increasing attention has been paid in recent years to the 'intrinsic' (ie.solvent-free) properties of basic processes such as proton transfer nucleophilic substitution V.J. Nowlan and T. T. Tidwell Accounts Chem. Rex 1977,10 252 and references cited therein. 39 G. H. Schrnid A. Modro and K. Yates J. Org. Chem. 1977,42 2021. M. F. Ruasse and J.-E. Dubois J. Org. Chem. 1977,42 2689. " A. Modro G. H. Schrnid and K. Yates J. Org. Chem. 1977.42 3673. Reaction Mechanisms-Part (ii) Polar Reactions 85 carbocation formation etc. as revealed by studies of ion-molecule reactions in the gaseous phase. Investigations have been made mainly with techniques such as pulsed ion cyclotron resonance (ICR) mass ~pectrometry,~~ pulsed electron beam high-pressure mass ~pectrometry,~~ or that photoionization mass spe~trometry,~~ involving the use of flowing afterglow apparatus.45 Apart from the inherent inter- est of gas-phase reactions the results can throw considerable light on the nature of solvation processes and can enable a clearer insight to be obtained into many aspects of solution chemistry.Proton Transfer.-Earlier work has shown that the presence of alkyl substituents in a molecule can increase both acidity and basicity in the gaseous phase an effect said to be due primarily to polarization of the alkyl group by the nearby ionic Distant alkyl groups however appear to destabilize a negative charge so that gas-phase acidities tend to be decreased by their influence in phenols carboxylic acids and acetylene^.^^ Gas-phase Acidities.The order of acidities for a series of alkanethiols has now been like that for to be exactly the reverse in the gaseous phase to that in aqueous solution i.e. for the gas-phase reaction shown [equation (5) (X = 0 RX-+ BU'XH -+ BU'X-+ RXH (5 1 (X = 0 or S) or S)]AG* increases for various R groups in the order Me<Et<Pr" (given for X=S only) <Pr'<Bu'. Whereas the reversal of acidity order for alcohols in dimethyl sulphoxide has been shown to result primarily from the effect of the size of the alkyl substituent on the heat of solution of the alkoxide anion,49 a similar analysis for alcohols in water cannot be made as only the free energies of ionization are available.A consideration of the effect of alkyl groups on the relative values of enthalpy and entropy of ionization for alkanethiols in water shows however that the main factor causing the inversion of order in this case is the entropy of ionizati~n.~~ It has further been concluded that the main factor controlling the relative gas-phase acidities of alkanethiols hydrogen sulphide and the alcohols is the electron affinity of the corresponding RS' or RO' radicals bond energies being nearly constant in each series. Water is anomalous The intrinsic acidities of some fifty substituted phenols and benzoic acids have been determined from equilibrium constants and AGO values for their gas-phase proton-transfer reactions with a range of standard aliphatic acids of known acidities [equation (6)]." The results show that phenol and acetic acid have similar acid 42 J.L. Beauchamp Ann. Rev. Phys. Chem. 1971,22,527. O3 A. J. Cunningham J. D. Payzant and P. Kebarle J. Amer. Chem. SOC.,1972 94 7627. 44 A. D. Williamson P. Le Breton and J. L. Beauchamp J. Amer. Chem. SOC.,1976,98 2705; P. R. Le Breton A. D. Williamson J. L. Beauchamp and W. T. Huntress J. Chem. Phys. 1975,62,1623; M. S. Foster A. D. Williamson and J. L. Beauchamp Znterngt. J. Muss Spectrometry Zon Phys. 1974,15,429. 45 D. K. Bohme R. S. Hemsworth J. W. Rundle and H. 1. Schiff J. Chem. Phys 1973,58,3504. 4d J. I. Brauman and L. K. Blair I. Amer. Chem. Soc. 1968 90,6561; 1970,92 5986. 47 (a)R. T. McIver jun. and J. S.Miller J. Amer. Chem. Sac. 1974,% 4323; (b)R. T. McIver jun. and J. H. Silvers ibid. 1973,95 8462; (c)K. Hfraoka R. Yamdagni and P. Kebarle ibid. 1973,95,6833. O8 J. E. Bartmess and R. T. McIver jun. J. Amer. Chem. Soc. 1977,99,4163. 49 E. M. Arnett L. E. Small R. T. McIver jun. and J. S. Miller J. Amer. Chem. Soc. 1974,96 5638. T. B. McMahon and P. Kebarle J. Amer. Chem. SOC. 1977,99,2222. H. R. Hudson A,H+A + Ar+A,H (6) strengths in the gaseous phase whereas benzoic acid is stronger by ca. 8.7 kcal mol-’. Solvation must account for the differences in water in which acetic and benzoic acids have similar strengths and are stronger than phenol by nearly 6pKa units. It can be visualized that the acetate anion with its relatively small methyl group and with its negative charge localized on the two oxygen atoms will be more strongly solvated than will the phenoxide anion which is larger and which has the charge delocalized over the aromatic ring.Ionization of acetic acid in water is therefore relatively more favourable. The relative acid strengths of benzoic acid in the gaseous phase and in aqueous solution have been interpreted in terms of contributions from charge-separated canonical forms for which solvation is more favourable than for the uncharged species and which are more important in the case of the acid than the anion. Substituent effects for meta -and para -substituted benzoic acids in the gaseous phase are revealed through linear plots of free-energy changes for the gas-phase reaction (7) against Taft’s go or Brown’s (+ values the former giving a slightly XCdH4C02-+PhC02H + XC6H4CO2H+PhCO2-(7) better correlation.o-and p-Hydroxybenzoic acids have anomalously high gas- phase acidities but it can be shown that in the gaseous phase the phenolic proton is in each case the more acidic and that the compounds are better regarded as substituted phenols in this context. Enhanced acidity of the phenolic proton can be attributed to the -M effect of the ortho- or para-carboxy-group. On the other hand the carboxy-group itself is made less acidic by the +M effect of a hydroxy- group in the ortho- or para-position. The strength of the ortho-hydroxy-acid is further increased by stabilization of the anion through internal hydrogen-bonding between 0-and the C02H group.A good linear correlation is obtained between the gas-phase and aqueous solu- tion acidities of meta- and para-substituted phenols as measured by AG* under these two conditions for the same proton-transfer reaction [equation (S)]. It is XC6H40-+ PhOH 4 XC6H4OH +PhO-(8) noteworthy that AGeis 6.8 times larger in the gas phase than in aqueous solution for phenols and 10.6 times larger for the acids. Although attenuations of substit-uent effects from gaseous phase to solution are not uncommon those for the phenols and benzoic acids in water are unusually large and are attributed to hydrogen-bonding in this solvent in which substituent effects are largely reflected in the entropy term. In keeping with a previous study of gas-phase acidities and solution acidities in dimethyl s~lphoxide,~~ the attenuation of substituent effects in phenols in this medium is small (factor of ca 2) and is contained in the enthalpy term.Gas-phase Basicities. It has been shown that the observed strengths of amines in the gaseous phase are consistent with a simple electrostatic An alternative ” F. G. Bordwell J. E. Bartmess G.E. Drucker Z. Margolis and W. G. Matthews J. Amer. Chem. Soc. 1975,97,3226. ’* D. H. Aue H. M. Webb and M. T. Bowers J. Amer. Chem. Soc. 1976,98 311,318. Reaction Mechanisms-Part (ii)Polar Reactions 87 approach53 shows that an excellent linear correlation is obtained by plotting AGe or AH0 values for the gas-phase proton-transfer reaction [equation (9)] against RCH2NH2+CH36H3 + RCH&H3 +CH3NH2 (9) new ‘intrinsic’ substituent constants uI,obtained from gas-phase ionization-potential data and polarizability rn~dels.’~ Two interpretations have been Either (a) the observed effects of alkyl substituents on gas-phase base strengths and the oxparameters are both determined by polarizability effects and involve no internal inductive effects or (b) the q parameters are a measure of internal inductive effects of alkyl groups but the observed effects of the alkyl substituents are a combination of polarizability and internal inductive effects both having very nearly the same structural dependencies on chain length and branch- ing.The second interpretation is probably correct in view of recent comparisons of the quantitative effects of alkyl groups on gas-phase acidities of alcohols with those of gas-phase basicities of amines.” Nucleophilic Substitution.-Studies of gas-phase SN2reactions [equation (lo)] have revealed a wide variety of reaction In certain cases intermediate X-+RY + Y-+RX (10) adducts between anions and alkyl halides have been obtained (e.g.C1CH3Br-) with stabilities ranging from 8.6 to 14.4kcal mol-’.’’ The possibility of detecting the neutral product RX has also been demonstrated and it has been shown that the interaction of chloride ion with either cis-or trans-4-bromocyclohexan-1-01pro-ceeds with preponderant inversion of configuration.’’ Reaction rates and efficien- cies (i.e.the fraction in each case of collisions resulting in reaction) for a wide range of systems (X=OH C1 Br F CN MeO MeS or Bu‘O; RY=MeCI MeBr CF3C02Me PhOMe MeOMe Me3CCH2Cl Me3CC02Et MeSH or MeC02H) lead to the conclusion that the reaction is best described in terms of a ‘double-well’ potential [curve (a) Figure 11 the energy barrier in many cases being lower than the energy of the reactants.59 The increase in the barrier in solution results solely from the differential solvation of the reactants and the transition state the more localized charge on the reactant anion making this species better solvated.In a polar aprotic solvent such as dimethyl sulphoxide the barrier is raised less than in a protic solvent which affords the possibility of specific hydrogen-bonding (Figure 1). The intrinsic nucleophilicities of anions in the gaseous phase follow the reverse order of the polarizabilities (e.g.MeO->MeS-and F->C1->Br-) a result which may be due to the stronger interaction which will occur between the more 53 R. W. Taft and L. S. Levitt J. Org. Chem. 1977 42 916. 54 L. S. Levitt and H. F. Wilding Progr. Phys. Org. Chem. 1976,12 119. 55 R. W. Taft in ‘Proton Transfer Reactions’ ed. E. F. Caldin and V. Gold Chapman and Hall London 1974 Ch. 2 p. 66. 56 J. 1. Brauman W. N. Olmstead and C. A. Lieder J.Amer. Chem. Soc. 1974,% 4030; K. Tanaka G. I. Mackay J. D. Payzant and D. K. Bohme Canad. J. Chem. 1976 54 1634 and references cited therein. 57 R. C. Dougherty J. Dalton and J. D. Roberts Org. Mass Spectrometry 1974 8,77; R. C. Dougherty and J. D. Roberts ibid.,p.81; R. C. Dougherty ibid. p. 85. 58 C. A. Lieder and J. I..Brauman J. Amer. Chem. SOC.,1974,96,4028; Internat. J. Mass Spectrometry Ion Phys. 1975 16 307. 59 W. N. Olmstead and J. I. Brauman J. Amer. Chem. SOC.,1977.99,4219. H. R. Hudson X-*RY X-R-Y -* RX + Y' REACTION COORDINATE Figure 1 Representative diagrams of the reaction co -ordinates for a nucleophilic displacement reaction (a) in the gaseous phase and (b) in dipolar aprotic and (c) in protic solvents (Reproduced by permission from J. Amer. Chem. SOC.,1977,99,4219) concentrated charge of the smaller anions and the carbon centre. The parallel between polarizability and nucleophilicity of anions in protic solvents is thus seen to be purely an artefact of solvation effects; indeed the order may be reversed in aprotic solvents.Carbocations.-Stabilities. Heterolytic bond-dissociation energies D(R'-Br-) have been determined for a range of alkyl carbenium ions acyl cations and cyclic halonium ions by examining the equilibria shown [equation (1l)].""A combina-Rf+R2X$[RIXR2+]*$R1X+R; (11) tion of the gas-phase data with heats of solution in HS03F-SbF5 gives via appro-priate chemical cycles the relative enthalpies of solvation which have been shown to be related to ion size the smaller ions being better solvated. Relative stabilities (measured as bromide affinities) for the cyclic bromonium ions are the same in the gaseous phase as in solution. In both cases stability increases with ring size and in the three-membered rings with methyl substitution.The range of stabilities is however attenuated in solution. The adamantyl cation is found to be more stable than t-butyl in the gaseous phase indicating that the strain energy due to non- planarity of the adamantyl system is smaller than the stabilization afforded by interaction of the charge with the hydrocarbon framework. Condensation Reactions. A number of gas-phase condensation reactions of carbenium ions of possible relevance to prebiotic synthesis have been shown to be 6o R. H. Staley R. D. Wieting and J. L. Beauchamp J. Amer. Chem. Soc. 1977,99 5964. Reaction Mechanisms-Part (ii) Polar Reactions analogous to the corresponding reactions in solution. With water the isopropyl and t-butyl cations yield protonated alcohols which can undergo further hydration (Scheme 20) or elimination to yield alkene.61 Other n-donors (MeOH NH3 + H20 C4H; -%[C4H9(OH2)]' %[C4H9(OH2h] __* [C4H9(OH2)3]' + etc.Scheme 20 MeNH2 etc.)probably condense in a similar fashion.61 The gas-phase equivalent of the Koch-Haaf synthesis has likewise been shown to occur with carbenium ions generated in methane containing small amounts of carbon monoxide and water (Scheme 21) the species produced being identified as the protonated acid.62 R+ CO-~R~O H20c RCOOH; Scheme 21 Formation of formic acid was also noticed but this underwent decarbonylatior, possibly as shown (Scheme 22). n Scheme 22 Ester Cleavage.-An interesting divergence between behaviour in the gaseous phase and in solution is seen in the mechanism of ester cleavage by alkoxide ion.Whereas the BAc2 mechanism is almost universal in base-catalysed hydrolyses in aqueous media the gas-phase reaction of deuteriomethoxide ion with methyl trifluoroacetate or methyl benzoate yields the carboxylate anion as the only detectable product [equation (12)].63 A possible mechanism involves attack on the CD30-+RC02CH3 + RC02-+CD30CH3 (12) ester alkyl group via an SN2transition state (54). In protic solvents on the other hand a tetrahedral intermediate (55) is more likely to be favoured by stabilization through hydrogen-bonding to the carbonyl oxygen atom. 0 0- It 8-R-C-0 8--CH3 --OCD3 R-C-OCH~ IOCD3 (54) (55) 61 K. Hiraoka and P. Kebarle J. Amer. Chem. SOC.,1977,99,360.62 K. Hiraoka and P. Kebarle J. Amer. Chem. SOC.,1977,99 366. M. Comisarow Canad. J. Chem. 1977 55 171.