3 Reaction Mechanisms Part (i) Aromatic Compounds By A. R. BUTLER Department of Chemistry University of St. Andrews St. Andrews 1 Electrophilic Aromatic Substitution During 1971 there have been two excellent reviews of this subject covering the main areas of controversy.’?’ Nitration by nitronium salts has been shown by Olah and his co-workers to have low relative reactivity between arenes but high positional selectivity and this has been explained by initial formation of a 7c-complex followed by rate-determining conversion to a o-c~mplex.~ In his review Olah’ defends this interpretation against the view that the results are better explained in terms of inadequate mixing of the reactants. He also suggests that in electrophilic substitution the transition state may be early and resemble the reactants (n-complex) or late and resemble the products (a-complex).In contrast Ridd’ reviews the evidence in favour of regarding Olah’s results as due to inadequate mixing and gives a summary of investigations into the mechan- ism of aromatic nitration. Further support for inadequate mixing comes from a study of the nitration of some polymethylbenzenes by Zollinger et aL4 In spite of wide synthetic use nitration by nitric acid in acetic anhydride is still a mechanistic puzzle. Hartshorn Moodie and Schofield’ report that a different value is obtained for the relative reactivity of benzene and toluene from that obtained with nitrating agents known to contain NOz+ as the active species indicating a unique mechanism for nitration by this reagent.Relative reactivity and isomer ratios may be influenced by solvation effects but two systems have been described which avoid this complication an intermediate similar to a a-complex has been detected in the gas phase by ion cyclotron resonance,6 and the helium tritide ion (HeT’) is a powerful electrophile effecting hydrogen exchange on halogenobenzenes in the gas phase.7 * G. A. Olah Accounts Chem. Res. 1971 4 240. J. H. Ridd Accounts Chem. Res. 1971 4 248. S. J. Kuhn and G. A. Olah J. Amer. Chem. SOC. 1961,83,4564. E. Hunziker J. R. Penton and H. Zollinger Helv. Chim. Acta 1971 54 2043. S. R. Hartshorn R. B. Moodie and K. Schofield J. Chem. SOC.(B) 1971 1256. S. A. Benezra M. K. Hoffman and M. M. Bursey J. Amer. Chem.SOC.,1970 92 7501. ’ F. Cacace and G. Perez J. Chem. SOC.(B) 1971 2086; F. Cacace R. Cipollini and G. Ciranni ibid. 1971 2089. 129 130 A. R.Butler In an interesting study Perrin* has assessed the leaving ability of some electro- philes by a study of the reactions of model compounds. For example reaction of (1) with HCl results in migration or loss of NOz+ rather than Cl'. However with the bromo-analogue it is Br' which is lost. As well as being an intrinsic C1 NO characteristic of the electrophile leaving ability depends on whether the electro- phile is lost from the a-complex in a unimolecular process or removed by a nucleophile. In the former case the order is NO2+ < i-Pr+ -SO < t-Bu+ -ArN,' < ArCHOH' < NO+ < CO < B(OH), and in the latter case Me' < CI+ < Br+ < D' < RCO' < H+< I' < Hg2+ < Me,Si+.Data from a variety of other sources are used to establish these orders. In some related work Perrin and Skinner' have measured ips0 partial rate factors i.e. the activating or deactivating effect of a substituent on electrophilic attack at the carbon atom bearing the substituent. The reaction used was nitration of phalogenoanisoles which results in partial replacement of the halogen. For H I Br and C1 the values are 1,0.119,0.077,and 0.069 respectively values which show surprisingly little variation. The situation is somewhat complicated by the occurrence of demethylation particularly with the chloro-compound. The importance of the direct field effect in the deactivating properties of positive poles has been demonstrated by comparing the rates of nitration of (2) and (3).The inductive effects along the a-bonds are the same in both cases but (3) nitrates 200 times slower than (2) owing to the different positions of the positive poles." If the positive pole is attached directly to the ring then the inductive effect is relatively more important although the field effect is still operative.' There is evidence of d,-p interaction between the aromatic ring and positive poles con- s C. L. Perrin J. Org. Chem. 1971 36 420. C. L. Perrin and G. A. Skinner J. Amer. Chem. SOC.,1971 93 3389. lo ' G. Mossa A. Ricci and J. H. Ridd J. Chem. SOC.(B),1971 714. F. De Sarlo G. Grynkiewicz A. Ricci and J. H.Ridd J. Chem. SOC.(B) 1971 714. Reaction Mechanisms-Part (i) Aromatic Compounds + + taining -Me and -SeMe, as there is with positive poles of P As and Sb but not pn-pn overlap.12 Creation of a positive pole may change completely the position of nitration ModroI3 reports that in a non-acidic medium nitration of N-benzylaniline occurs on the aniline moiety but protonation of the nitrogen diverts attack to the benzyl ring. Aromatic nitrosation is an important reaction which has received very little attention. Challis and Lawson14 report full details of a study of the nitrosation of phenol and anisole in perchloric acid. For phenol the rate is constant below 1M-acid and then increases to reach a maximum in 7.5M-acid. For anisole there is no acid-independent region but with both loss of a proton is the slow step.For this reason acidity dependence studies are not diagnostic of the mechanism. Phenol reacts via a dienone intermediate not available to anisole and although demethylation occurs with the latter this follows nitrosation. Identification of the nitrosating species is difficult but above SM-acid it is probably NO'. Nitration via nitrosation and oxidation has been recognized as an important pathway and it appears that this is what occurs in the attempted nitration of thiophen. The high susceptibility of heterocycles towards nitrosation and the production of nitrous acid in an autocatalytic process results in the reaction being very vi01ent.l~ Nitrosation is thought to occur to some extent even in nitration by nitronium salts.4 There have been numerous studies of aromatic halogenation and one of the most interesting is an account by Taylor and McKillop16 of the use of thallic trifluoroacetate in effecting iodination.There is immediate reaction with the aromatic compound to give an organothallium intermediate (4) which may be isolated. Reaction of this with aqueous potassium iodide results in anion ex- change to give the intermediate (5) which loses thallous iodide and iodine enters the ring at the site of thallation. The method is simple yields are good and it has wide applicability including heterocycles. With o/p directing sub- stituents attack is normally at the p-position but if the reaction mixture is heated before addition of KI the rn-iodo-compound is obtained owing to a change from kinetic to thermodynamic control of the product.If there is a basic H. M. Gilow M. De Shazo and W. C. Van Cleve J. Org. Chem. 1971,36 1745. l3 T. A. Modro Roczniki Chem. 1971 45 825. l4 B. C. Challis and A. J. Lawson J. Chem. SOC.(B) 1971 770. A. R. Butler and J. B. Hendry J. Chem. SOC.(B) 1971 102. A. McKillop J. D. Hunt M. J. Zelesko J. S. Fowler E. C. Taylor G. McGillivray and F. Kienzle J. Amer. Chem. Soc. 1971 93 4841. 132 A. R.Butler site in the substituent the thallium salt complexes with this first and thallation occurs at the o-p~sition.’~ A mixture of iodine and nitric acid is a common iodinating agent. It is generally supposed that there is direct iodination in an equilibrium step and that nitric acid acts by removing the HI formed and the equilibrium position shifts in favour of the iodo-compound.This has been shown to be incorrect and some other mechanism must be found.I8 A detailed kinetic study by Butler and Sander- son,” using acetic acid as solvent has shown that the reaction is catalysed by nitrous acid and hydrogen ions and that the iodinating species is probably protonated NO,I which reacts with the aromatic substrate in a slow step. The rate-determining step in acid-catalysed decarboxylation depends upon the acidity. The reaction of pyrrole-2-carboxylic acid follows the same pattern as that reported by Long for the decarboxylation of azulene- 1-carboxylic acid i.e. rate-determining protonation of the anion to give (6) at low acidity and rate- determining decarboxylation of (6) at high acidity.20 Because of the ease with which it may be followed and the absence of com- plicating steric effects hydrogen-exchange reactions in acidic solution continue to be used for comparing the reactivities of different positions on aromatic rings.The effect of substituents on hydrogen exchange at the 2- 3- and 8-positions of fluoranthene (7) has been analysed in terms of atom-atom polarizabilities a-inductive effects and the direct field effect.’l Only the 6-position of the 2,3- dihydro-5,7-dimethyl- 1P-diazepinium ion (8) undergoes detectable hydrogen H H H 4 3 (7) exchange in strong acid as the positive charge in the intermediate may be located on the two nitrogen atoms., The relative reactivities of the 2- and 3-positions of pyrrole invert as the acidity is changed and it is suggested that this is due to an earlier transition state in a more acidic rnedi~rn.’~ Comparison of the relative reactivities of different positions in an aromatic system with the predictions of l7 E.C. Taylor F. Kienzle R. L. Robey A. McKillop and J. D. Hunt J. Amer. Chem. SOC.,1971 93 4845. la A. R. Butler J. Chem. Educ. 1971 48 508. l9 A. R. Butler and A. P. Sanderson J. Chem. SOC. (B) 1971 2265. G. E. Dunn and G. K. J. Lee Cunad. J. Chem. 1971,49 1032. K. C. C. Bancroft and G. R. Howe J. Chem. SOC. (B) 1971 400. 22 A. R. Butler D. Lloyd and D. R. Marshall J. Chem. SOC.(B) 1971 795. ’’ G. P. Bean Chem. Comm. 1971,421.Reaction Mechanisms-Part (i) Aromatic Compounds 133 MO calculations meets with some success but the same type of calculation does not always give the best prediction. For the non-equivalent positions of indoli- zine (9),n-electron densities give a better correlation than localization energies.24 In view of their inherent approximations and the neglect of solvation effects such simple calculations appear to be of little value in elucidating the exact mechanism of hydrogen exchange. In recent years there has been interest in the mechanism of electrophilic attack on aromatic side-chains and Eaborn and Wright2’ report a study of hydrogen exchange in trifluoroacetic acid of the methyl group of 2-methylbenzo[b]thiophen (10). The reaction appears to involve ring protonation and slow proton loss to give the olefinic compound (11) (Scheme 1).Scheme 1 Among unusual pathways in electrophilic aromatic substitution the formation of dienones is important. They are for example formed in the chlorination of 3,4dimethylphenol and related compounds.26 During work-up of the reaction mixture a dienone intermediate may be destroyed and the normal reaction pro- duct obtained. A study of such a conversion the acid-catalysed rearrangement of (12) to (13) has been reported. The rate of reaction is directly proportional to Ho and substitution of protium by deuterium at the 4-position depresses the rate by a factor of Nitration of 5-bromohemimellitene gave 2-nitro-3,4,5- trimethylphenol in 60% yield owing to decomposition of the dienone inter- mediate (14) formed during the reaction.28 A very full study has shown that formation of 2,4-dinitro-3,5-di-t-butyltoluene and 2,6-dinitro-3,5-di-t-butyl-24 W.Engewald M. Muhlstadt and C. Weiss Tetrahedron 1971 27 851 4171. 25 C. Eaborn and G. J. Wright J. Chem. SOC.(B) 1971 2262. 26 P. B. D. de la Mare and B. N. B. Hannan Chem. Comm. 1971 1324. ” P. B. D. de la Mare A. Singh J. G. Tillett and M. Zeltner J. Chem. SOC.(B) 1971 1122. 28 D. J. Blackstock M. B. Hartshorn A. J. Lewis K. E. Richards and J. Vaughan J. Gem. SOC.(B) 1971 1212. 134 A. R.Butler toluene from the nitration of 2,4,6-tri-t-butylbenzeneis due to rearrangement of the intermediate cyclohexadienyl carbonium ion (15)and alkyl fragmentation of the 4-t-butyl 2 Nucleophilic Aromatic Substitution There is now convincing evidence that nucleophilic aromatic substitution occurs by a two step mechanism (S,Ar) involving formation of an intermediate (16) similar to a Meisenheimer complex (Scheme 2).Bowden and Cook3' report that in the alkaline hydrolysis of a number of substituted nitrobenzenes and 2,4- dinitrobenzenes in aqueous DMSO the rate-determining step depends upon the Scheme 2 composition of the medium. In cases where addition of hydroxide ion is slow the ratio k(H,O)/k(D,O) is ca. unity for those reactions with a transition state resembling the reactants but smaller for more advanced transition state^.^ Solvent effects in such reactions are complex and appear to be very specific.For example addition of methanol lowers the rate of reaction between thiocyan- ate ion and 2,4-dinitroiodobenzene owing to strong solvation of the thiocyanate ion by methanol.32 It is the presence of the nitro-groups which renders the aromatic ring susceptible to nucleophilic attack and picryl chloride reacts with as weak a base as imidazole to give 2,4,6-trinitrophenylimida~ole.~~ With only one nitro-group the reaction 2q P. C. Myhre M. Beug K. S. Brown and B. Ostman J. Amer. Chem. SOC.,1971 93 3452. 30 K. Bowden and R. S. Cook J. Chem. SOC.(B) 1971 1765 1771. 31 K. Bowden R. S. Cook and M. J. Price J. Chern. SOC.(B),1971 1778. 32 Y.Kondo K. Uosaki and N. Tokura Bull. Chetn. SOC. Japan 1971,44 2548. 33 R. Minetti and A. Bruylants Bull.Classe Sci. Acad. Roy. Belg. 1971 56 1047. Reaction Mechanisms-Part (i) Aromatic Compounds is much more difficult but the anions derived from various phenylalkylaceto- nitriles will displace chlorine from a number of chloronitr~benzenes.~~ Fluorine para to a nitro-group is replaced by methoxide ion in methanol faster than at the o-position but with 2,4-difluoronitrobenzene it is fluorine at the 2-position which is replaced first indicating that the effect of a second fluorine on a para activated system is different from that on an ortho activated system.35 Nucleophiles with a lone pair c1 to the site of nucleophilicity exhibit an enhanced reactivity and this shows up as a positive deviation in a Bransted plot. Bibbi and Pietra36 have looked for this a-effect in aromatic substitution but without success.In reaction with 2,4-dinitrochlorobenzene four primary amines give a linear Brernsted plot with a high p-value but the exalted positions of hydrazine and methoxylamine are not greater than those of other nucleophiles which have no lone pair c1 to the site of nucleophilicity (e.g.aniline and morpholine). As mentioned previously when discussing the direct field effect of positive poles in electrophilic aromatic substitution the importance of interactions through space is being increasingly recognized. Similar considerations apply in the reaction of hydrogen peroxide and the hydroperoxide ion with 3'-sub- stituted 3,4-benzotropolone- 1',2'-quinone monoanion (17) and the dianion of (17) purpurgalloquinone.Collier3' has concluded that charge repulsion decides which species is the more reactive. Comparison of the activating effects of nitro- and aza-groups in nucleophilic substitution has received considerable attention. A study of the reactions of hydroxide ion with various alkoxynitropyridines indicates the absence of steric factors with the a~a-group.~' Aza-activation is much smaller in five-membered rings than in six and in thiazoles all positions (2-,4- and 5-)are equally activated contrary to previously held views. There is no addition-elimination mechanism in the reactions of these compounds with methoxide ion.39 In the reactions of 2-chlorothiazole with benzenethiolate ion the 4- and 5-positions act as rn-and p-positions in benzene with respect to a Hammett plot and the high p value (+ 5.3) indicates how very sensitive thiazoles are to substituent effects4' 34 M.Makoszu J. M. Jaguoztyn-Grochowska and M. Jaurdosiuk Roczniki Chem. 1971 45 858. 35 T. L. Bamkole and J. Hirst Chem. Comm. 1971 69. 36 G. Bibbi and F. Pietra J. Chem. Soc. (B),1971 44. 31 P. D. Collier J. Chem. SOC.(B),1971 637. 38 J. Murto L. Nummela M. L. Hyvonen and I. Wartiovaara Suomen Kem. (B),1970 43 517. 39 M. Bosco L. Forlani P. E. Todesco and L. Troisi Chem. Comm. 1971 1093. 40 M. Bosco L. Forlani V. Liturri P. Riccio and P. E. Todesco J. Chem. SOC.(B),1971 1373. 136 A. R.Butler As might be expected triazines are very susceptible to nucleophilic attack. The replacement of one chlorine on 2,4-dichloro-6-phenylamino-sym-triazine is catalysed by a tertiary amine and involves formation of (18) as the slow Zollinger et have reported a very interesting study of the kinetics of the alka- line hydrolysis of various chloro-sym-triazines.The initial reaction is attack by hydroxide ion and protonation to give the intermediate (19) formed in a non-steady equilibrium state which undergoes deprotonation and release of chloride ion. The kinetics were analysed by the use of an analog computer. The similarity between the intermediate formed in nucleophilic aromatic substitution and Meisenheimer complexes has led to a large number of studies of these complexes in recent years. This has been aided by the development of techniques for following very fast reactions such as stopped flow and temperature jump.These have been applied by Fendler et to the reaction between hydroxide ion and 1,3,5,8-tetranitronaphthalene.The equilibrium constant is reduced by a factor of 0.3 with deuteroxide in D,O. Although cyanide groups do activate the aromatic ring towards complex formation they are much less effective than nitro-gr~ups.~~ The first step in the reaction of methoxide ion and various nitro- and cyano-anisoles is formation of a 1,3-complex (20)and there is slow conversion to the thermodynamically more stable 1,l-complex (21).45 Also the initial reaction between 4-substituted 2,6-dinitrochlorobenzene and methoxide ion is formation of a 1,3-complex although there is eventual OMe CN CN 41 G.Ostrogovich E. Fliegl and R. Bacaloglu Tetrahedron 1971 27 2885. 42 P. Rys A. Schmitz and H. Zollinger Helv. Chim. Acta 1971 35 163. 43 J. M. Fendler E. J. Fendler and L. M. Casilo J. Org. Chem. 1971 36 1749. 44 E. J. Fendler W. Ernsberger and J. H. Fendler J. Org. Chem. 1971 36 2333. 45 C. Deaving F. Terrier and R.Schaal Compt. rend. 1970 271 C 349; F. Terrier J. C. Halle M. P. Simonnin and M. J. Lecourt Org. Mugn. Resonance 1971 3 361; F. Terrier and M. P. Simonnin Bull. Soc. chim. France 1971 677. Reaction Mechanisms-Part (i) Aromatic Compounds 137 replacement of the chlorine.46 In certain cases (e.g. N-t-butyl-2,4,6-trinitro-benzamide) Meisenheimer complex formation is followed by replacement of a nitro-gr~up.~ Bernasconi4* reports that the initial reaction between trinitrotoluene and methoxide ion is formation of the anion (22) and this then reacts with more trinitrotoluene to give a Meisenheimer complex of probable structure (23).02NooMe .-NHCHMeCONHMe NO2 (24) Anion formation does not occur however with 3,5,6,%tetranitroacenaphthene and the sodium salt of the complex may be isolated.49 The kinetics of the forma- tion of (24) from 2,4,6-trinitroanilino-N-methylpropionamide and methoxide ion have been studied. Acidification of an alcoholic solution of this complex gives the conjugated acid.50 There is hydrogen bonding between the amino- group and the ortho nitro-group which is maximized in the conformation adopted by the Meisenheimer complex but if the amido-group is alkylated and hydrogen bonding is not possible the anilino-group ionizes and no complex is formed.If the anilino-group is alkylated no 1,l-complex can form for steric reasons and instead a 1,3-complex results.51 Full details have been given of the formation of a Meisenheimer complex of thiophen (25) resulting from the interaction of 2-methoxy-3,5-dinitrothiophen and methoxide ion. This complex forms more readily than that from trinitro- anisole and related intermediates are formed during nucleophilic attack on " M. R. Crarnpton M. A. El Ghariani and H. A. Khan Chem. Comm. 1971 834. *' E. J. Fendler D. M. Camioni and J. H. Fendler J. Org. Chern. 1971 36 1544. '' C. F. Bernasconi J. Org. Chem. 1971 36 1671. '' C. H. J. Wells and J. A.Wilson Tetrahedron Letters 1971 4521. 50 J. J. K. Boulton and N. R. McFarlane J. Chem. Soc. (B),1971 925. 51 J. J. K. Boulton P. J. Jewess and N. R. McFarlane J. Chem. SOC.(B),1971 928. 138 A. R.Butler thiophen compounds but reactions other than displacement may occur subse- quently (e.g.ring opening).’* Reaction of octahydrotriborate and 2,4,6-trinitrochlorobenzeneresults in hydride transfer to give (26),the parent Meisenheimer complex. Hydride ion will also displace chlorine from this compound but no evidence could be obtained for formation of the l,l-~ornplex.~~ CI EtO C1 NO* PerkinsS4 has described a case where nucleophilic substitution occurs on a ring system not activated by an electron-withdrawing group. Ethoxide ion will displace chlorine from 5-chloroacenaphthylene and the addition intermediate may be stabilized by formation of a cyclopentadienide ion (27).There have been further studies on the effect of surfactants and electrolytes on the rate of formation and decomposition of Meisenheimer complexes. A complex pattern emerges which cannot be explained in terms of simple electrolyte the~ry.~’ The displacement of fluorine by nucleophiles displays a number of special features. A variety of products results from attack of polyfluoroalkyl anions on pentafluoropyridine and tetrafluoropyridazine. With CF,CF there is kinetic control of the products but with increasing bulk there is a gradual change to thermodynamic control and this is complete with (CF,),C-.56 3 Acidity Functions Work over the past few years has shown that the value of an acidity function depends very much on the indicator used to measure it.Now one can only talk about the acidity of a concentrated acid relative to a particular base. All this has lessened the value of acidity function dependence as a criterion of reaction mechanism. The whole matter is admirably discussed in Rochester’s’ mono-graph on the subject and during 1971 little has been reported to modify the 52 G. Doddi G.Illuminati and F. Stegel J. Org. Chem. 1971 36 1918. 53 L. A. Kaplan and A. R. Siedle J. Org. Chem. 1971 36 937. 54 M. J. Perkins Chern. Comrn. 1971 231. 55 J. H. Fendler E. J. Fendler and M. V. Merritt J. Org. Chem. 1971 36 2172; L. M. Casilio E. J. Fendler and J. H.Fendler J. Chem. SOC.(B) 1971 1337. 56 R. D. Chambers R. P. Corbally M. Y.Gribble and W. K. R. Musgrave Chem. Cornrn. 1971 1345. 57 C. H. Rochester ‘Acidity Functions,’ Academic Press London 1970; Progr. Reaction Kinetics 197 1 6 143. Reaction Mechanisms-Part (i) Aromatic Compounds 139 position. However Kresge et a1.58 have reported a very full and important study of the acidity dependence of hydrogen exchange. In concentrated acid 1,3,5-trihydroxybenzene its methyl and ethyl ethers and a number of related com- pounds are protonated giving benzenonium ions which may be considered the same as the a-complexes occurring in electrophilic aromatic substitution. With the ethers protonation occurs para to the hydroxy-group rather than para to the alkoxy-group.Even anisole is C-protonated in perchloric acid more concentrated than 70%. When studied as a function of acid concentration the concentration of the conjugate acid depends linearly upon the acidity function H (based on the protonation of carbon59) and not H, but the slopes of the plots vary and are not unity. The superiority of H over Ho is not surprising as the latter is based on the protonation of nitrogen. Extrapolation to dilute acid gives a set of pK values and assuming that substituent effects are additive the pK of the conjugate acid of benzene is estimated to be -23. Studies of the behaviour of these compounds in concentrated acid have been extended to include the rates of hydrogen exchange. The rates give a linear correlation with both Ho and H and with both the slopes vary from compound to compound.The authors argue from this that there is no unique relationship between kinetic acidity dependence and reaction mechanism. By comparing the acidity de- pendence of equilibrium protonation and hydrogen exchange it is possible to estimate the degree of proton transfer in the transition state of the latter reaction. The results agree well with similar estimates made from the size of the exponent in the Brransted relation. Differences in substrate structure and in the degree of proton transfer in the transition state will explain the variation of kinetic acidity dependence for different compounds. A book by Liler6' contains a detailed account of the acidity functions of sulphuric acid and also discusses activity coefficients and the hydration treatment of acidity functions.Values of Ho are very sensitive to changes in the ionic strength.6 Values of H-for various alkali-metal glycoxides in ethylene and propylene glycols have been reported62 and the H-function in aqueous DMF has been measured.63 4 Linear Free Energy Relationships The various forms of the simple Hammett equation are difficult to substantiate on theoretical grounds but from a practical point of view they are able to 58 A. J. Kresge Y. Chiang and L. E. Hakka J. Amer. Chem. SOC.,1971 93 6167; A. J. Kresge H. J. Chen L. E. Hakka and J. E. Kouba ibid. 1971 93 6174; A. J. Kresge S. G. Mylonakis Y. Sato and V. P. Vitullo ibid. 1971 93 6181; A. J. Kresge Y. Chiang and S.A. Shapiro Canad. J. Chem. 1971 49 2777. 59 M. Reagan J. Amer. Chem. SOC.,1969 91 5506. 'O M. Liler 'Reaction Mechanisms in Sulphur Acid,' Academic Press London 1971. '' P. J. Staples and E. Hogfeldt J. Chem. SOC.(A) 1971 2074. 62 N. Chattanathan and C. Kalidas Austral. J. Chem. 1971 24 83; N. Chattanathan and C. Kalidas Bull. Chem. SOC.Japan 1971 44 1004; K. K. Kundu and L. Aiyar J. Chem. SOC.(B) 1971 40. 63 E. Buncel E. A. Symons D. Dolman and R. Stewart Canad. J. Chem. 1970 48 3354. 140 A. R.Butler correlate a wide variety of phenomena the basicity of pyridine~,~~ the deoxy- genation reaction of nitrobenzenes and triethyl ph~sphite,~~ the dissociation constants of 5-~tyryltropolones,~~ the syn-anti topomerization of N-arylimino-carb0nateq.6~ the Hofmann rearrangement,68 13C I4N and 'H shifts in n.m.r.spectro~copy,~~ the rate of interaction of the fluorenone triplet and substituted aniline~,~' and the pyrimidal inversion of nitrogen71 are a selection from papers appearing in 1971. The main theoretical interest comes in analysing the various modes of transmission of substituent effects to different sites in the molecule. The prominence given recently to field effects (as in the Dewar-Grisdale treat- ment72) has been questioned by Eaborn Eastmond and Walt~n~~ from a study of the alkaline cleavage Of XC,&C-C-c-CSiEt3 where the substituent X was found to have a considerable effect on the rate in spite of its distance from the reactive site. However the Dewar-Grisdale treatment which was sur-prisingly successful in spite of its simplicity has been extended to include the mesomeric field effect (e.g.in aniline mesomeric interaction between -NH2 and the ring leads to charge transfer from nitrogen to the 0-and p-positions and the resulting negative charge can then influence a reaction centre by a field effect) and to consider neutral substituents as finite dipoles rather than point charges. This treatment has been applied successfully to the reactions of a number of ring systems but not to "F chemical shifts.74 G~dfrey~~ has given an extensive analysis of substituent effects and has applied MO theory to field effects. This treatment has been applied successfully to the ionization poten- tials and some reactions of benzene compounds.It predicts the observed non- additivity of substituent effects in electrophilic aromatic substitution. The formation of complexes between Ag' and exo- and endo-substituted norbornenes has been analysed on the basis of the Kirkwood-Westheimer-Tanford The pyrolysis of substituted 1-phenylethyl acetates by Taylor7 has again proved to be a very powerful method of examining substituent effects and a new value of CT' for the rn-CF group has been proposed (+0.565).78 An angular dependence of a substituent effect has been observed reversing the positions of 64 C. D. Johnson and G. B. Ellam J. Org. Chem. 1971,36,2284. 65 R. J. Sundberg and C.-C. Lang J. Org. Chem. 1971 36 300. 66 K. Hamada S. Nakama K. Imafuku K. Kurosawa and H. Matsumura Tetrahedron 1971 27 337.67 H. Kessler P. F. Bley and D. Leibfritz Tetrahedron 1971 27 1687. 68 T. Imamoto Y. Tsuno and Y. Yukawa Bull. Chem. SOC.Japan 1971,44 1632 1639. 69 F. W. Wehrli W. Giger and S. Wilhelm Helu. Chim. Acta 1971 54 229; A. Mathias P. Hampson and R. Westhead J. Chem. SOC.(B),1971 397; R. R. Fraser and R. N. Renaud Canad. J. Chem. 1971,49 755 800. 70 S. G. Cohen and G. Parsons J. Amer. Chem. SOC.,1970,92 7603. " J. Stackhouse R. D. Baechler and K. Mislow Terrahedron Lerters 1971 3441. 72 M. J. S. Dewar and P. Grisdale J. Amer. Chem. SOC.,1962 84 3548. 73 C. Eaborn R. Eastmond and D. R. M. Walton J. Chem. SOC.(B) 1971 127. 74 M. J. S. Dewar R.Golden and J. M. Harris J. Amer. Chem. SOC.,1971 93 4187. '' M. Godfrey J.Chem. SOC.(B) 1971 1534 1537 1540 1545. 76 C. F. Wilcox and W. Gaal J. Amer. Chern. SOC.,1971 93 2453. 77 R. Taylor J. Chem. SOC.(B) 1971 255 1450. '* R. Taylor J. Chem. SOC.(B) 1971 622. Reaction Mechanisms-Part (i)Aromatic Compounds the hydrogen and chlorine in the acid (28) has an effect on the pK value.79 Bentley and Johnstone" have proposed a new set of 0 values based on ionization potentials determined by mass spectrometry. Non-linear Hammett plots have been discussed8 and Ostrogovich Csunderlik and Bacaloglu82 provide a good example of this phenomenon in the reaction of substituted anilines with ethyl chloroformate. The value of p for a reaction varies with the temperature according to the equation p = p,(l -PJT)where pi is the isokinetic temperature providing that 6AH" and 6AS" are temperature inde~endent.~~ Matsui and Tokura have considered the effect of changing solvent on p.84 The significance which may be attached to the coefficients in the Brransted equation is now a matter of contention.Linearity applies only within a family of catalysts and the value of aor P may vary from family to family. For the reaction of p-nitrophenyl triphenylmethanesulphenatewith a number of amines P has the following values 1.5 (anilines) 0.84 (pyridine) 0.75 (heterocyclic amines) and 0.58 (primary aliphatic amine~).~' The size of p was thought to represent the degree of proton transfer in the transition state and this view is maintained by Hibbert Long and Waters86 in a study of hydrogen exchange on malonitrile and t-butylmalononitrile.However this view is doubted by Bordwell and Boyles7 who found no trend relating the size of for the ionization of phenylnitromethanes and the relative basicity of the catalyst and the reactive site which should decide the position of the proton in the transition state. These authors give the following assessment of the situation 'the hope which at one time seemed bright for a simple general correlation of Brransted coefficients kinetic isotope effects and solvent isotope effects with the extent of proton transfer in the transition state has proven vain'. A similar position on this matter is adopted by Kresge et d8' who from a study of the hydrolysis of vinyl ethers conclude that the size of the '9 E. J.Grubbs R. Fitzgerald R. E. Phillips and R. Petty Tetrahedron 1971 27 935. T. W. Bentley and R. A. W. Johnstone J. Chem. SOC.(B) 1971 263. " J. 0. Schreck J. Chem. Educ. 1971 48 102. " G. Ostrogovich C. Csunderlik and R. Bacaloglu J. Chern. SOC.(B) 1971 18. 83 L. G. Hepler Canad. J. Chem. 1971 49 2803. 84 T. Matsui and N. Tokura Bull. Chem. Soc. Japan 1971 44 756. 85 E. Ciuffarin L. Senatore and M. Isola J. Chem. SOC.(B) 1971 2187. 86 F. Hibbert F. A. Long and E. A. Waters J. Amer. Chern. SOC.,1971 93 2829. " F. G. Bordwell and W. J. Boyle J. Amer. Chern. SOC.,1971 93 512 514. *' A. J. Kresge H. L. Chen Y. Chiang E. Murrill M. A. Payne and D. S. Sagatys J. Amer. Chem. Soc. 1971 93 413. 142 A. R.Butler Brsnsted exponent may be affected by intermolecular effects such as interactions between substrate and catalyst in the transition state.Dixon and BruiceE9 report that the enhanced nucleophilicity of nucleophiles with a lone pair o! to the site of attack is not explained by the high stability of the products and large amount of bond formation in the transition state. 89 J. E. Dixon and T. C. Bruice J. Amer. Chem. Sac. 1971 93 3248.