4 Reaction Mechanisms Part (ii) Polar Reactions By D. L. H. WILLIAMS Department of Chemistry University of Durham Durham DHl 3LE 1 Introduction After 10 years of deliberation the IUPAC Commission on Physical Organic Chemistry has produced its recommendations regarding the system for the rep- resentation of reaction mechanisms.' Rather than modify the widely used system based on the Ingold notation the working party has decided to recommend a totally new system. Basically the system lists the bonds made and broken (as association A or dissociation D) with subscripts to indicate the apportionment of electrons. This has the advantage of being a more precise method and removes some of the ambiguities inherent in the presently used system. However since it represents such a major change it is bound to stimulate much discussion and argument.Time will tell whether physical organic chemists will take kindly to the recommendations. The feeling of this reviewer is that chemists who have been unwilling to abandon the kcal in favour of kJ are unlikely to make the change and that SN2etc. will be with us for some time to come. A summary of the new method is given along with a number of specific examples by Guthrie and Jencks.* The 1989 volume of Advances in Physical Organic Chemistry includes an article on the mechanisms and catalysis of nucleophilic substitution in phosphate ester^.^ The authors discuss dissociative and addition-elimination mechanisms together with the biological chemistry of phosphate esters The same volume includes a contribu- tion on perchloro-organic chemistry," which deals with aspects of the structure spectroscopy and reaction pathways of polychlorinated organic systems.Jorgensen' claims a breakthrough in the modelling of organic reactions in solution. He uses molecular dynamics and statistical mechanics simulations as a basis for free energy calculations from which solvent effects can be studied theoretically more quantitatively than previously. Abraham and co-worker8 have also produced a review of their ideas and treatment of solvent effects in organic chemistry (in a 1988 article which arrived too late for inclusion in last year's Report). Their treatment in terms of multiple linear regression analysis has been applied to a wide range of ' IUPAC Commission on Physical Organic Chemistry Pure Appl.Chem. 1989 61 23 57. R. D. Guthrie and W. P. Jencks Acc. Chem. Rex 1989 22 343. G. R. J. Thatcher and R. Kluger Adu. Phys. Org. Chem. 1989 25 99. M. Ballester Adv. Phys. Org. Chem. 1989 25 267. W. J. Jorgensen Acc. Chem. Res. 1989 22 184. M. H. Abraham P. L. Grellier J.-L. M. Abboud R. M. Doherty and R. W. Taft Can. J. Chem. 1988 66 2673. 57 D. L. H.Williams processes including solubility of gases as well as both equilibrium and rate constants of chemical reactions. The equations derived by Koppel and Palm and by Abraham Kamlet and Taft cope satisfactorily. Steric effects on amine basicity have been reviewed by Alder.' The result of angle strain and steric inhibition of solvation is base weakening for monoamines whilst for a number of diamine systems base strengthening can occur due to the formation of an intramolecular hydrogen bond in the monoprotonated cation.The need for more quantitative work in this area is stressed. 2 Solvolysis and Carbocations All the kinetic evidence (including the common-ion effect) and the results of azide trapping experiments are consistent with an ionization mechanism giving a carboca- tion intermediate in the solvolysis (equation 1) of 2-chloromethyl- 1-methyl- imidazole.* It is suggested that the carbocation (and so the transition state leading HNyNMe ZNyNMe -NyNMe F I7 m CH2Cl CHiCl CH2OH to its formation) is stabilized by the 2-imidazoyl ring by way of extensive delocaliz- ation of the positive charge.Further work' in the area of solvolysis of benzoyl halides has revealed that the fluorides undergo a dissociative mechanism (&I) only when there are powerful electron-releasing groups present (e.g. 4-dimethylamino) otherwise an associative addition-elimination mechanism prevails. Conversely ben- zoyl chlorides generally react via the dissociative route but a change to the associa- tive mechanism can be brought about with strongly electron-attracting substituents (e.g. 4-nitro). These differences are readily recognized experimentally by the sign of p (or p+) the dependence on the leaving group the solvent isotope effect and the common-ion effect. Bentley and Roberts" have extended the study of solvent effects on SN1reactivity to include two new leaving groups trifluoroacetate and heptafluorobutyrate.The relatively low reactivity witnessed in fluorinated solvents is explained in terms of nucleophilic solvent assistance for reactions in the more nucleophilic solvents. A good correlation is reported for the solvolyses of substituted benzyl p-toluenesul- phonates in eleven solvents using the extended Grunwald- Winstein equation." The results including the magnitude of the I and rn values suggest an sN2 mechanism with a variable transition state structure for all except one of the esters. Large anchimeric effects by y-aryl groups are reportedI2 for the solvolysis of organosilicon iodides which are not found in the corresponding carbocation reac- tions. The difference is explained in terms of severe steric hindrance to solvation of cationic centres in the transition state of the organosilicon iodide reactions.R. W. Alder Chem. Rev. 1989 89 1215. J. L. Bolton and R. A. McClelland Can. J. Chem. 1989 67 1139. 'B. D. Song and W. P. Jencks J. Am. Chem. SOC.,1989 111 8470. lo T. W. Bentley and K. Roberts J. Chem. SOC.,Perkin Trans. 2 1989 1055. " D. N. Kevill and H. Ren J. Org. Chem. 1989 54 5654. '*C. Eaborn K. L. Jones and P. D. Lickiss J. Chem. SOC.,Chem. Commun. 1989 595. Reaction Mechanisms -Part (ii) Polar Reactions By varying substituents X and Y in both rings in substituted benzene azoxyarenesulphonates it has been shown that solvolysis occurs (equation 2) by synchronous concerted bond heter~lysis.'~ x I X A full account has been p~blished'~ describing intramolecular proton transfer catalysis of nucleophilic catalysis in acetal hydrolysis using 8-dimethylamino-l- methoxymethoxynaphthalene ( 1).The principal feature of intramolecular catalysis is the formation of an intramolecular hydrogen bond with the leaving group oxygen atom which is absent in the reactant but strong in the transition state (and the product). The same effect is believed to be involved in the hydrolysis of 8-hydroxy-l- methoxymethoxynaphthalene (2).15 The solvolysis of acetals of propionaldehyde derivatives proceeds via very short-lived oxocarbenium ions as outlined in equation 3. The lifetimes of these intermediates have been determined from kinetic measure- ments with added azide ion and are found to be too short to allow for diffusion to nucleophilic reagents so that substitution reactions with nucleophiles (other than the solvent) must occur by a concerted bimolecular pathway.16 The selectivity Br-/C1- as measured by the ArBr/ArCl product ratios in the capture of aryl cations produced by the dediazoniation of three arenediazonium l3 I.M. Gordon and H. Maskill J. Chem. SOC.,Chem. Commun. 1989 1358. 14 A. J. Kirby and J. M. Percy J. Chem. SOC.,Perkin Trans. 2 1989 907. F. Hibbert and K. J. Spiers J. Chem. SOC.,Perkin Trans. 2 1989 377. 16 T. L. Amyes and W. P. Jencks J. Am. Chem. SOC.,1989 111 7888 7900. D. L. H. Williams ions is independent of the viscosity of the solvent;” this suggests that the aryl cation reactions with halide ions are diffusion controlled.Experimental evidence has been presented18 that hyperconjugation with strained bonds [in the cyclopropyl phenyl cation (3)] produces a very large stabilization effect in this case by at least 27.6 kcal relative to the phenyl cation. The prop-2-yl cation (4) is believed to be chiral. The prediction is made by ab initio calculations and supported by the correspondence of the experimental and calculated I3C NMR chemical shifts for that conformation (a twisted structure with C symmetry).’’ R McClelland and co-workers have generated the xanthylium cations (5) by flash photolysis of the corresponding 9-xanthenols and have measured the rate constants for reaction with a number of nucleophiles.20 Some show a correlation with the Ritchie N equation but the reactions of the more reactive cations may be diffusion controlled or desolvation controlled.Further results reported by the same group2’ have been obtained on the reaction of 18 triarylmethyl and 10 diarylmethyl cations (generated in the same way) with water. There is a better correlation of the rate constants with ac+ (obtained from analysis of NMR spectra of carbocation sol- utions) than with a+. 3 Other Nucleophilic Substitutions The question of SET involvement in nucleophilic substitution reactions continues to be addressed though apparently not with the same intensity as in recent years. Bordwell and Harrelson22 have used the Eberson approach of calculating kET using a Marcus-type equation and comparing it with the experimental second-order rate constant kobs.Application of this test to reactions of benzyl chloride with some carbanions substituted phenoxide ions and thiophenoxide ion gave very large values for the kobs/kET ratio and hence no evidence for an SET pathway. A test of the method gave ratios of -1 for the well-known SET acceptor 1,l-dinitrocylohexane. However with benzhydryl chloride and seven 9-(dialky1amino)fluorenideions there was close agreement between kobsand kET. These results together with unexpectedly low rate constant ratios for PhCH,Cl/ Ph2CHCI support the view that the reactions of Ph2CHCI with these fluorenide ions take place by SET mechanism^.^^ J. P. Lorand Tetrahedron Lett. 1989 52 7337. 18 E. Uggerud D.Arad Y.Apeloig and H. Schwartz J. Chem. SOC.,Chem. Commun. 1989 1015. 19 P.von R. Schleyer W. Kcch B. Liu and U. Fleischer J. Chem. SOC.,Chem. Commun. 1989 1098. 20 R. A. McClelland N. S. Banait and S. Steenken J. Am. Chem. SOC.,1989 111 2929. 21 R. A. McClelland V.M. Kanagasabapathy N. S. Banait and S. Steenken J. Am. Chem. SOC. 1989 111 3966. 22 F. G. Bordwell and J. A. Harrelson J. Org. Chem. 1989 54,4893. 23 F. G. Bordwell and J. A. Harrelson J. Am. Chem. SOC.,1989 111 1052. 24 E. S. Lewis J. Am. Chem. SOC.,1989 111 7576. Reaction Mechanisms -Part (ii) Polar Reactions stresses the distinction between the two mechanisms particularly with regard to methyl transfer reactions and concludes that they are rarely competitive SET occurring only with highly reducing nucleophiles.A three-variable system has been studied in the reaction of 2-substituted benzyl X-substituted benzenesulphonates (6) with Y-substituted N,N-dimethylanilines (7) in acetone for a Menschutkin-type SN2reaction.25 The three p values were measured and the interaction terms pxy,pyz and pzx obtained which are claimed to give the degree of bond making and breaking and hence are indicative of mechanistic changes from SN2 to sN1. In the continuing debate regarding changes in structure-reactivity parameters and transition state structure in bimolecular substitution reactions Dietze and Jencks26 have presented results of a study with 4-nitrobenzylsulphonates. They find a small increase in selectivity with decreasing reactivity but stress that a large range of reactivity may be required (in both the nucleophile and the leaving group) in order to detect the selectivity change.Analysis of the aminolysis reactions of benzoyl fluorides in water (equation 4) suggests that the reaction mechanism is one of concerted sub~titution,~~ although it is not possible to rule out completely the possibility of a stepwise reaction involving a tetrahedral intermediate. RNH,+ArCOF -+ RNHCOAr+H++F-(4) The secondary a-D kinetic isotope effect (KIE) and substituent effects in the reaction of substituted thiophenoxides with tetraalkylammonium ions (equation 5) X o S -+ PhCH2kMe,Ph -PhCHzS O X + MezNPh (5) are larger when the nucleophile is the free ion than when it is a solvent-separated ion pair complex (produced by addition of 1S-~rown-5-ether).~' The explanation is that one gets a tighter transition state (and hence smaller secondary KIE) for the solvent-separated ion pair resulting from a reduction of charge on the sulphur atom brought about by the sodium ion of the complex.The secondary-D KIE is unaffected by a change from protic to aprotic solvents (for the reaction of n-butyl chloride with PhS-).29 This confirms an earlier proposed 'solvation rule' for SN2reactions 25 S.-D. Yoh Y. Tsuno M. Fujio M. Sawada and Y. Yukawa J. Chem. SOC.,Perkin Trans. 2 1989 7. 26 P. Dietze and W. P. Jencks J. Am. Chem. SOC.,1989 111 5880. 21 B. D. Song and W. P. Jencks J. Am. Chem. SOC.,1989 111 8479. 28 Z.-G. Lai and K.C. Westaway Can. J. Chem. 1989 67,21. 29 K. C.Westaway and Z.G. Lai Can. J. Chem. 1989 67,345. 62 D. L. H. Williams namely that a change of solvent will not lead to a change in transition state structure if the charges on the two nucleophiles in the transition state are the same. Evidence has been presented that the metaphosphate monoanion is not an inter- mediate in the reaction of various oxygen nucleophile species with three phosphory- lated pyridine rnonoanion~.~~ The same authors discuss the nature of the transition state and electrostatic repulsions in phosphoryl transfer reactions to anionic oxygen nucleophiles and the implications for enzyme-catalysed phosphoryl transfer reac- tion~.~~ Catalysis by metal ions in nucleophilic displacement at phosphoryl centres (equation 6) has been interpreted in terms of reaction via the free nucleophile OEt- and also metal ion-OEt- ion pairs.32 0 0 I1 II OEt-+ Ph,POAr -+ Ph,POEt + OAr-Two theoretical accounts have been published one dealing with nucleophilic attack at cation radical and cation centres using the curve crossing the other with the analysis of solvent effects in SN2 reactions by different theoretical 4 Elimination Reactions Elimination reactions in the gas phase continue to attract attention from the mechanistic view point.Speranza and co-workers have published two paper^^',^^ which begin a series on base-induced eliminations in onium intermediates in the gas phase. In the first FT-ICR mass spectrometry is used to study the reaction of amines with diethylmethyloxonium ions (see equation 7) generated from diethyl HhR + C2H + MeOEt NR + CH,CH&Et -(7) I Me ether and dimethylchloronium ion (MeCIMe+).Both substitution and elimination takes place the latter being favoured with increasing base strength. At high encounter excitation energies other (novel) reactions occur involving one-electron transfers. In the second paper of the series a radiolytic method is used to investigate the stereochemistry and orientation in alkene formation from halonium ions in the gas phase. These high pressure studies allow comparisons to be made with solution studies. Other workers3’ have shown that methoxide ion reacts in the gas phase with 1-bromopropane to give only the products of elimination (equation 8) in contrast to the solution state reaction where substitution is the preferred pathway.Chuchani 30 D. Herschlag and W. P. Jencks J. Am. Chem. Soc. 1989 111 7579. 31 D. Herschlag and W. P. Jencks J. Am. Chem. SOC.,1989 111 7587. 32 E. J. Dunn and E. Buncel Can. J. Chem. 1989 67 1440. 33 S. S. Shaik and A. Pross J. Am. Chem. Soc. 1989 111 4306. 34 C. Aleman F. Maseras A. Lledos M. Duran and J. Bertran J. Phys. Org. Chem. 1989 611. 35 G. Occhiucci M. Speranza L. J. de Koning and N. M. M.Nibbering J. Am. Chem. Soc. 1989,111,7387. 36 G. Angelini G. Lilla and M. Speranza J. Am. Chem. SOC.,1989 111 7393. 37 M. E. Jones and G. B. Ellison J. Am. Chem. SOC.,1989 111 1645. Reaction Mechanisms -Part (ii) Polar Reactions 63 and co-workers have investigated the elimination of 2-chloropropionic acid38 and -0Me +CH,CH,CH,Br + MeOH +CH,CH=CH +Br-(8) primary alkyl methanes~lphonates,~~ again in the gas phase.Both reaction mechan- isms are discussed in terms of the formation of intimate ion-pair intermediates. In the case of the sulphonates steric factors are important and the data correlate with several steric parameters. In two papers Bunnett and Migda14* compare the reactivities of EtS- and MeO- in elimination reactions in DMSO-MeOH solvent mixtures. In the methanol-rich solvents EtS- is the more reactive species whilst in the DMSO-rich solvents the reverse is true. It is argued that these results are fully compatible with an E2 mechanism with a variable transition state structure and that there is no necessity to invoke an E2C mechanism.Another report41 examines the effect of the nature of the leaving group on the transition state structure of the E2 mechanism of the reaction of 1-phenylethylammonium ions with EtO- in EtOH. There is no linear correlation between reactivity and the basicity of the leaving group. The results together with those of KIE measurements suggest that leaving group ability is determined mainly by steric effects which in turn determines the transition state structure. For the poorer leaving groups the proton is more than half transferred in the transition state whereas it is less than this for the better leaving groups. 5 Addition Reactions Bernasconi has produced a timely Tetrahedron Report42 on the kinetics and mechan- ism of nucleophilic addition to alkenes.In the past such reactions have been overshadowed particularly with regard to mechanistic studies by their electrophilic counterparts but recent work by a number of research groups (over the past 14 years) has shed much light in this area. The report discusses the addition of H20 OH- amines RS- CN- N3- F- RO- and carbanions and there is a chapter on structure-reactivity relationships that includes a discussion of Bernasconi’s own ‘principle of non-perfect synchronization’ together with factors affecting nucleophi- licity and nucleofugality. Intermediates are often deduced from kinetic and other measurements. Bernasconi and have now reported the first direct observation by its UV absorption spectrum of an intermediate in a nucleophilic addition reaction of thiolate ion with a nitrostilbene derivative (equation 9).Russian workersM have found a rate equation Ph NO2 Ph NO Ph NO \ ’+RS-& \/ -/c=c\w\ ’+MeO-(9) /Ic-c Me0 /c=c\w Me0 I \Ph RS SR 38 G. Chuchani and A. Rotinov Int. J. Chem. Kinet. 1989 21 367. 39 G. Chuchani S. Pekerar R. M. Dominguez A. Rotinov and I. Martin J. Phys. Chem. 1989 93 201. 40 J. F. Bunnett and C. A. Migdal J. Org. Chem. 1989 54 3037 3041. 41 P. J. Smith and M. Amin Can. J. Chem. 1989 67 1457. 42 C. F. Bernasconi Tetrahedron 1989 45 4017. 43 C. F. Bernasconi R. B. Killion J. Fassberg and Z. Rappoport J. Am. Chem. SOC.,1989 111 6862. 44 A. F. Popov 1. F. Perepichka and L.I. Kostenko J. Chem. Soc. Perkin Trans. 2 1989 395; I. F. Perepichka L. 1. Kostenko A. F. Popov and A. Yu. Chervinski Zh. Org. Khim. 1988 24 822. D. L. H. Williams (equation 10) for the reaction of a nitroethylene with amines in acetonitrile which includes a component representing a pathway catalysed by the reactant amine and also by added tertiary amines. There is a negative measured activation energy for this step which suggests the rapid equilibrium formation of an intermediate (with a negative AH") as outlined in equation 11. kobs= k + kb[Amine] (10) R'CH=CHNO + R,NH R'CH-CHNO I R,NH Uncatalysed The reaction of enolate ions with perfluoropropene in the gas phase shows a C vs. 0 regio~electivity.~~ Most enolates derived from aldehydes ketones esters and amides react at oxygen whilst those with a-acceptors of .rr-donor type central substituents react mainly via carbon.The excess acidity method has been used to analyse the kinetic results for the acid-catalysed hydration of alkenyl esters of the type CH,=C(OX)R for X = Bz and Ts!~ The results indicate the familiar A42 mechanism with rate-limiting proton transfer to the double bond. Toullec4' has examined the relation between the equilibrium and rate constants for H+ transfer to a-methoxystyrenes (equation 12). Slightly curved plots of log k us. pK are found; analysis using the Marcus relation gives results consistent with synchronous and concerted CH bond formation and OH bond cleavage. The correlation of alkene .rr-ionization potentials with relative rate constants for hydroboration bromination and oxymercuration show that hydroboration and oxymercuration behave in a similar fashion in which steric effects are dominant whereas this is not the case for br~mination.~~ Nitrosation of acetylacetone (8) and the two fluorinated derivatives (9) and (10) using either alkyl nitrites in acetonitrile or nitrous acid in water takes place via the enol form only for (8) simultaneously uia the enol and enolate anion for (9) and wholly via the enolate anion for (10).All of the results are consistent with the deactivating effect of the CF3 groups on electrophilic addition and the acid- strengthening property of the CF3 groups for enol i0nization.4~ 45 M. D. Brickhouse and R.R. Squires J. Phys. Org. Chem. 1989 389. 46 R. A. Cox M. McAllister K. A. Roberts P. J. Stang and T. T. Tidwell J. Org. Chern. 1989 54 4899. 47 J. Toullec J. Chern. SOC.,Perkin Trans. 2 1989 167. 48 D. J. Nelson P. J. Cooper and R. Soundararajan J. Am. Chern. SOC.,1989 111 1414. 49 M. J. Crookes P. Roy and D. L. H. Williams J. Chern. SOC.,Perkin Truns. 2 1989 1015. Reaction Mechanisms -Part (ii) Polar Reactions CH,C=CHCOCH CF,C=CHCOCH C F3C =C HCOC F3 I I I OH OH OH (8) (9) (10) 6 Aromatic Substitution and Rearrangements Effenberger" has reported the synthesis for the first time of 1,3,5-tris (dialkylamino) benzene derivatives (1 l) which are models for intermediates in electrophilic aro- matic substitution. The stabilization by three amino substituents is analogous to the stabilization of the corresponding anionic a-complexes by three nitro groups.The salts have been isolated and their structure established by X-ray crystallography. It is expected that the study of such ions will lead to a better understanding of energy profiles in electrophilic aromatic substitution. A nitrating agent has been produced by mixing Bu,NN03 and (CF3C0)20 and used to measure selectivity in a range of aromatic compounds in a number of organic solvents.51 This results in the following selectivity order MeN02 < MeCN d sulpholane < CH2ClCH2Cl < CHzC12 d EtOAc d Pr'Br = BuCl = BuBr d CHC13. Both products of electrophilic chlorination and nitration are obtained in competing processes when reaction of aromatics takes place with nitric acid and chlorine or hydrogen chloride in sulphuric acid or 01eum.~* Chlorination is the less selective process but it is not yet known what the effective chlorinating agent is.Further evidence has been given53 which shows that the mechanism of aromatic nitration in aqueous nitric acid is identical to that in aqueous sulphuric acid. The rate equation for the nitrous acid-catalysed nitration of naphthalene contains a term which is second order in the aromatic.54 All the evidence points to an electron transfer mechanism; the second-order term is thought to arise .from the formation and subsequent reaction with NO2 of the dimeric radical cation . The bromination of phenols in water in the pH range 0-7 involves reaction of both the phenol and the phenoxide ion.55 For 16 phenoxide ions values of the second-order rate constants are all in the range (1-9) x lo9dm3 mol-' s-l showing that the reactions are diffusion controlled.Kinetic and chemical trapping experiments with the highly selective chlorination of electron-rich aromatic compounds with N-chloroamines in CF3C02H fit with 50 F. Effenberger Acc. Chem. Res. 1989 22 27. 5' B. Masci Tetrahedron 1989 45 2719. 52 M. W. Melhuish and R. B. Moodie J. Chem. Soc. Perkin Trans. 2 1989 667. 53 D. J. Belson and A. N. Strachan J. Chem. SOC.,Perkin Trans. 2 1989 15. 54 J. R. Leis M. E. Peiia and J. H. Ridd Can. J. Chem. 1989 67,1677. 55 0. S. Tee M. Paventi and J. M. Bennett J. Am. Chem. Soc. 1989 111 2233.D. L. H. Williams the arenium ion mechanism for the majority of substrates but the reaction of 1,4-dimethoxybenzene may have an electron transfer chain reaction component to its reaction.56 The first example has been reported of a rate-limiting proton transfer in elec- trophilic substitution in pyrroles as witnessed by the observation of an amplified isotope effect in the chlorination of l-methylpyrr~le.~~ Substitution by aryldiazonium ions in imidazole takes place via the anion form present in very low concentration (see equation 13).58The product or product mixture was not fully described. The behaviour of imidazole contrasts with that of pyrrole which reacts via the nbutral form. These experiments bear out a suggestion made by Ridd and co-workers in 1953.59 N2Ar Nudelman6' has presented a review of the dimer mechanism for aromatic nucleophilic substitution by amines in aprotic solvents.The unusual experimental findings (compared with the same reactions in protic solvents) are explained in terms of simultaneous initial attack by the free amine and by its dimer. In water and aqueous DMSO (12) and (13) respectively give a-adducts with hydroxide ion at unsubstituted positions whilst attack at the C atom bearing X (X = halogen) leads to the formation of 2,4,6-trinitro- or 2,4-dinitrophenolate ions by nucleophilic substitution.61 No evidence was found for the previously reported r-complex or radical pair intermediates discussed in last year's Report. Shine in an article62 dedicated to Professor M.J. S. Dewar on the occasion of his 70th birthday has reviewed the current position regarding the mechanisms of the benzidine rearrangement. In particular he discusses the part played by Dewar most notably in the 1950s when he advanced his then revolutionary ?r-complex theory. The review stresses the value of these early ideas especially in stimulating research in this area and comments on their present-day relevance. 56 J. R. Lindsay Smith L. C. McKeer and J. M. Taylor J. Chem. SOC.,Perkin Trans. 2 1989 1529. 57 M. De Rosa and M. Marquez J. Chem. SOC.,Chem. Commun. 1989 1466. 58 L. M. Anderson A. R. Butler C. Glidewell D. Hart and N. Isaacs J. Chem. SOC.,Perkin Trans. 2 1989 2055. 59 R. D. Brown H. C. Duffin J. C. Maynard and J.H. Ridd 1. Chem. SOC.,1953 3937. 6o N. S. Nudelman J. Phys. Org. Chem. 1989 1. 61 M. R. Crampton A. B. Davis C. Greenhalgh and J. A. Stevens J. Chem. SOC.,Perkin Trans. 2,1989,675. 62 H. J. Shine J. Phys. Org. Chem. 1989 491. Reaction Mechanisms -Part (ii) Polar Reactions 7 Proton Transfer and Carbanions The gas-phase acidities of 47 aliphatic carboxylic acids have been measured by pulsed electron high-pressure mass spectrometry calibrated with a reference com- pound.63 There is a good correspondence with earlier work for some of the acids measured by the ion cyclotron resonance technique. The results are discussed in terms of substituent effects. Similarlya the gas-phase acidities of 15 simple alkanes have been obtained in a flowing afterglow-selected ion flow tube using a kinetic method in which alkyltrimethylsilanes react with OH-.Generally methyl substitu- tion is found to stabilize the anion form. Han and Bra~man~~ have studied the gas-phase proton transfer from toluenes to benzyl anions (equation 14) and have established the energetics of the systems. PhCH,-+ ArCH + PhCH +ArCH,-(14) Literature data for the ionization in solution of a number of carbon acids with various bases have been analysed by the use of variable intrinsic barriers in the Marcus equation.66 This allows the prediction of Q and p Bransted values over a wide range of reactivity. Proton transfer from amides has not been much studied but a recent discusses the results of pK measurements and of kinetic studies (by the T-jump method) of the proton transfer reactions from l-benzoylaminonaph- thalenes (14) and related compounds to hydroxide ion in 70% DMSO-H20.The HNCOCtjHs rate constants are -lo2 smaller than expected possibly due to the formation of an intramolecular H-bond in the amide anion. The same group6* has examined the effect of substituents on the strength of the internal H-bond in salicylate ions. The H-bond is strengthened by electron-releasing substituents and by the change from H20 to 50% DMSO-H20 solvent. At high [OH-] the opening of the H-bond is partially rate-limiting. Hydrogen bromide in CBr2F2 is a powerful acid solvent for the protonation of weak bases.69 In a study with P-diketones NMR evidence shows that the proton is located between the two keto groups in a very strong intramolecular H-bond.Phenylynol (PhCECOH) has been generated and observed in solution for the first time as the first intermediate formed in the flash photolysis of phenylhydroxy- 63 G. Caldwell R. Renneboog and P. Kebarle Can. 1. Chem. 1989 67 611. 64 C. H. De Puy S. Gronert S. E. Barlow V. M. Bierbaum and R. Damrauer J. Am. Chem. SOC.,1989 111 1968. 65 C.-C. Han and J. I. Brauman J. Am. Chem. SOC.,1989 111 6491. 66 J. W. Bunting and D. Stefanidis 1. Am. Chem. Soc. 1989 111 5834. 67 N. E. Briffett and F. Hibbert J. Chem. SOC.,Perkin Trans. 2 1989 1261. F. Hibbert and K. J. Spiers J. Chem. SOC.,Perkin Trans. 2 1989 67. 69 D. R.Clark J. Emsley and F. Hibbert J. Chem. SOC., Perkin Trans.2 1989 1299. D. L. H. Williams cyclopr~penone.~~ It is more acidic than the corresponding enol PhCH=CHOH by at least 7 pK units. This is predicted to be true also in the gas phase,71 and is attributed both to the stabilization of the ynolate anion and the destabilization of the neutral ynol relative to the enol situation. The rate constants for detritiation of some common anaesthetics (CF3CHClBr CH30CF2CHC12 and CHF,OCF,CHFCl) in dilute hydroxide ion solution have been obtained. The Bransted plot suggests normal acid behaviour which prompts the thought that the H-bonding acceptor ability is an important factor governing the power of the anae~thetic.~~ The reaction of malononitrile with nitrous acid in aqueous acid buffers takes place uia the carbanion in a rate-limiting reatction with the nitrosating agent XNO (equation 15).73 For X=Br- SCN- and SC(NH2)* the reaction occurs at the encounter limit making the carbanion from malononitrile the most reactive species studied in a nitrosation reaction.I CH,(CN) CH(CN) HON=C(CN)2 (15) 8 Carbonyl Derivatives The Kresge group has determined for the first time the temperature dependence of the rate constants for the acid-catalysed enolization of acetone and the ketoniz- ation of the enol in aqueous solution and also in a~etonitrile.~~ This enables the AH* and AS* values along with the overall AH" and AS"values to be obtained. There is a remarkable similarity to the corresponding values of the parameters obtained in the gas phase for the keto eenol system.Acta Chemica Scandinauica is published from 1989 onwards as a single journal rather than in the familiar series A and B sections. In the first issue an article describes kinetic studies on the keto-enol system of 2-carboxycyclohexanone in aqueous solution using the bromi- nation method.75 Because of a fortuitous overlap of spectra and the values of the rate constants it turns out to be possible to follow the zero-order (in bromine) enolization at the start of each experiment and the restoration of the perturbed keto-enol equilibrium towards the end of the experiment. Thus rate and equilibrium constants can be obtained from a single experiment. There is a continuing interest (though not at the level of recent years) in the generation of unstable enol tautoders.Capon and Wu76 have observed and character- ized 2,5-dihydroxythiophene as an intermediate in the hydrolysis of 2,5-bis [(trimethylsilyl)oxy]thiophene (in a deuterated solvent) which finally yields thiosuc- cinic anhydride (see equation 16). The same has carried out a more extensive 70 Y. Chiang A. J. Kresge R. Hochstrasser and J. Wirz J. Am. Chem. SOC.,1989 111 2355. 71 B. J. Smith L. Radom and A. J. Kresge J. Am. Chem. SOC.,1989 111 8297. 72 A. L. Brown Y. Chiang A. J. Kresge Y.3. Tang and W.-H. Wang J. Am. Chem. SOC.,1989 111,4918. 73 E. Iglesias and D. L. H. Williams J. Chem. SOC.,Perkin Trans. 2 1989 343. 74 Y. Chiang A.-J. Kresge and N. P. Schepp J. Am. Gem. SOC.,1989 111 3977. 7s H. Groth-Andersen and P.E. Seirensen Acta Chem. Scand. 1989 43 32. 76 B. Capon and Z.-P. Wu J. Org. Chem. 1989 54 1211. 77 B. Capon and F. C. Kwok J. Am. Chem. SOC.,1989 111 5346. Reaction Mechanisms -Part (ii) Polar Reactions study of monohydroxy derivatives of five-membered 0 N and S (benzo) heterocycles such as 3-hydroxybenzofuran (15). Again the enols were generated by hydrolysis of their trimethylsilyl derivatives in DC1 and the kinetics of ketonization and the KE values determined. Ketonization is found to be both general acid and general base catalysed and mechanisms for both are discussed. The first report of a direct observation in solution of hydroxyacetylenes has a~peared.~' These are ynols the triple bond analogues of enols and are the tautomers of ketenes (see equation 17).The flash photolysis of phenylhydroxycyclopropenone yields pheny- lacetic acid uia two intermediates the first identified as phenylhydroxyacetylene and the second as phenylketene. Rate constants were obtained for the acid-catalysed ynol -* ketene reaction. RCrCOH RCH=C=O (17) Acid-catalysed proton exchange in amides has been studied by NMR techniques including the application of quantitative 2D exchange NMR.78 Two mechanisms have been established one involving the intermediate formationpf the imidic acid RC(OH)=NR' the other the N-protonated intermediate RCONH2R'. Generally amides with electron-donating substituents exchange via N-protonation whereas those with electron-withdrawing substituents (including peptides and proteins) involve the imidic acid.Experimental evidence has been presented for co-operative catalysis (or synergistic catalysis) well known in esters and amides containing the C02H group in amide hydrolysis by neighbouring C02- at moderately high pH.79 The case has been argued for a concerted pathway in acyl group transfer reactions in solution," as well as the stepwise (dissociative and associative) routes. It is believed that the concerted pathway is more common than previously supposed. The full paper has been published" on AM1 calculations for reactions of a number of anions with eight carboxylic acid derivatives. The formation of tetrahedral intermediates are computed to occur without activation in an exothermic reaction. In solution therefore the energy barriers must arise from the energy of desolvation of the anion before the reactant can approach.9 Other Reactions The diazotization (and protonation) of 2-aminothiazole (16) at high acidity takes place by NO+ (or H+) attack at the ring nitrogen.82 In this case the overall reaction 78 C. L. Perrin Acc. Chem. Res. 1989 22 268. 79 M. N. Khan J. Chem. Soc. Perkin Trans. 2 1989 233. 80 A. Williams Acc. Chem. Res. 1989 22 387. 81 M. J. S. Dewar and D. M. Storch J. Chem. SOC. Perkin Trans. 2 1989 871. 82 H. Diener B. Gulec P. Skrabal and H. Zollinger Helu. Chim. Acta 1989 72 800. 70 D. L. H. Williams is reversible and these results present the first quantitative evidence for reversibility in diazotization reactions. It is known that diazotization of 1,2-diamino aromatic systems lead to triazole formation.Kinetic experiments have shown that 2,3- diaminonaphthalene reacts via the unprotonated and also the monoprotonated forms of the diamine (equation 18).83Nucleophilic catalysis is well established in t-rnN% .+It \ / " I H diazotization (and nitrosation generally). The most recently discovered catalyst is thiosulphate ion,84 from which the NOS203-species is thought to be the effective reagent. Its reactivity towards anilines has now been e~tablished;~~ the results confirm that NOS203-is significantly less reactive than the other well-known NOX species. In dilute acid solution P-aminopyridines (17) react directly with acidified nitrous acid at the exocyclic nitrogen atom whereas y-aminopyridines (18) react initially at the aromatic nucleus (cJ anilines at high acidity) probably owing to substantial positive charge on the exocyclic nitrogen atom in the latter case.86 NHR I;HR H (17) A range of alkyl nitrites8' react readily with cysteine and other thiols in water at pH 6-12 to give the corresponding thionitrites (or nitrosothiols) by a direct reaction with the thiolate anion.Another example has been published88 of initial attack at 83 S. M.N. Y. F. Oh and D. L. H. Williams J. Chem. Res. (S) 1989 264. 84 T. Bryant D. L. H. Williams M. H. A. Mi and G. Stedman J. Chem. SOC.,Perkin Trans. 2 1986 193. 85 L. Abia A. Castro E. Iglesias J. R. Leis and M. E. Peha J. Chem. Res. (S) 1989 106. 86 E. Kalatzis and L.Kiriazis J. Chem. SOC. Perkin Trans. 2 1989 179. 87 H. M. S. Pate1 and D. L. H. Williams J. Chem. Soc. Perkin Trans. 2 1989 339. 88 A. Coello F. Meijide and J. V. Tato J. Chem. SOC.,Perkin Trans. 2 1989 1677. Reaction Mechanisms -Part (ii) Polar Reactions 71 sulphur in nitrosation followed by an intramolecular rearrangement of the nitroso group to nitrogen in this case in the reaction of thiomorpholine. It is suggested that rearrangement occurs in a boat conformation of an intermediate. Two papers have been published describing reactions of N-methyl-N-nitrosotoluene-p- sulphonamide with nucleophiles in basic solution. The fird9 shows that a direct reaction occurs with cysteine and other thiols in their thiolate anion forms resulting in thionitrite formation.The second” discusses the reaction with a number of nitrogen-containing nucleophilic species; ammonia hydroxylamine hydrazine and amines. Again reactions occur at the nitroso nitrogen atom resulting in a transnitrosation reaction. This contrasts with the reaction of hydroxide ion which attacks the sulphur atom and gives products of hydrolysis. The reactions of the related N-nitroamides in aqueous buffer solution (equation 19) have also been RCON(Me)N02 + H20 + RC02H + MeNHN02 (19) studied.” The kinetic results and the observation of an absence of I80-exchange during the reaction are all consistent with a mechanism involving rate-limiting nucleophilic attack at the carbonyl carbon atom to give a tetrahedral intermediate which then breaks up rapidly.This is different from the common hydrolysis mechan- ism for amides and must arise because of the enhanced leaving group ability of -N(Me)NO; . Cyclization of N-substituted hydantoic acids (equation 20) has been examined as part of model studies of biotin action.92 It is an example of attack by ureido anion nitrogen on the carboxylate anion which is general acid/ base catalysed. 0 Me N NR Sulphonyl transfer reactions (equation 21) have been reviewed.93 The evidence is very much in favour of mechanisms which are concerted bimolecular displacements at the sulphonyl group. RS02X + Y-(or HY) + RS02Y + X-(or HX) (21) 10 Some Probes of Polar Mechanisms Activation volumes and reaction volumes are increasingly used as mechanistic probes.We now have a review of the complete listings of A V’ and A V values for reactions in solution covering the span January 1977 to the end of 1986.94 (This updates an earlier review by two of the authors which was published in 1978.) The a9 S. M. N. Y. F. Oh and D. L. H. Williams J. Chem. SOC.,Perkin Trans. 2 1989 755. 90 A. Castro J. R. Leis and M. E. Pefia J. Chem. SOC.,Perkin Trans. 2 1989 1861. 91 B. C. Challis E. Rosa F. Norberto and J. Iley J. Chem. SOC.,Perkin Trans. 2 1989 1823. 92 I. B. Blagoeva 1. G. Pojarlieff D. T. Tashev and A. J. Kirby J. Chem. SOC.,Perkin Trans. 2 1989 347. 93 I. M. Gordon M. Maskill and M.-F. Ruasse Chem. SOC.Rev. 1989 18 123. 94 R. Van Eldick T. Asano and W. J. LeNoble Chem. Rev. 1989 89 549. D.L. H. Williams extensive list is presented in tabular form for both inorganic and organic reactions. Over 1000 organic reactions are listed. The isokinetic relationship (IKR) has been reviewed.95 The subject is examined historically and the authors emphasize the problem that generally E and 1nA values are derived from the same set of data and are therefore not statistically independent and suggest how this may be overcome. The connection between IKR and linear free energy relationships is brought out. It is clear that more experimental results are needed on the IKR itself and on the measurement and interpretation of far-IR spectra since an isokinetic temperature can only be found within discrete regions corresponding to the absorbance bands of the vibrational spectra of the solvent.Buncel and co-~orkers~~ have developed a new approach for obtaining Brdnsted correlations. Instead of varying the pK of the nucleophile by changing the sub- stituents the effect is achieved by changing the solvent composition of DMSO-water mixtures. This procedure it is claimed allows a greater range of pK values and more data points to be obtained. Pross and S~haik~~ have questioned the value of Brflnsted coefficients as quantitative measures of transition state structure. They conclude that they cannot provide a quantitative measure since inter alia (a) some factors govern the energetics of the transition state but do not operate on equilibrium processes (e.g. solvent effects and energies of excited configurations which are important in rate processes but absent in equilibrium processes) and (b) giving a single Brflnsted coefficient to a single transition state is unsatisfactory since it is derived from a reaction series with varying transition state structures.Pearson9* has reviewed the application of the concepts of absolute electronega- tivity and absolute hardness to well-known chemical reactions. Good agreement is claimed with the experimentally known behaviour of common reactions in terms of electrophilic and nucleophilic reagents; the treatment also allows predictive power. A new scale of solvent polarity (+&,) has been obtained from measured solvato- chromic changes of six new merocyanine dyes in 29 solvents.99 The T& values are similar to the T*values of Kamlet et a1.l'' Finally the application of the Savage- Wood additivity of group interactions procedure to reaction mechanisms has been used to yield quantitative data which allow mechanistic interpretation based on medium effects for organic reactions in water-rich solvents."' 95 W.Linert and R. F. Jameson Chem. SOC.Rev. 1989 18 47. 96 E. Buncel I. H. Um and S. Hoz,J. Am. Chem. SOC.,1989 111 971. 97 A. Pross and S. S. Schaik Now. J. Chim. 1989 13 427. 98 R. G. Pearson J. Org. Chem. 1989 54 1423. 99 E. Buncel and S. Rajagopal J. Org. Chem. 1989 54,798. loo M. J. Kamlet J.-L. M. Abboud and R. W. Taft J. Am. Chem. SOC.,1977 99 6027. S. A. Galema M. J. Blandamer and J. B. F. N. Engberts J. Org. Chem. 1989 54 1227.