3 Reaction Mechanisms Part (i) Aromatic Compounds By A. R. BUTLER Department of Chemistry University of St. Andrews St. Andrews 1 Electrophilic Aromatic Substitution Recent work on this subject has been reviewed by Taylor’ in an admirable manner. Predictions of the effect of substituents on aromatic reactivity by MO calculations are difficult to make but semi-empirical models have been proposed which give very accurate results.’ However there is an interesting report that lengthy and costly MIND0 calculations of certain indices of aromatic reactivity (electron densities localization energies) show no better correlation with suscepti- bility to electrophilic attack than the same quantities calculated by the simpler Hiickel method. It has been proposed that charge-transfer complexes play a part in the mechanism of electrophilic aromatic substitution (Scheme 1).The evidence is XH Scheme 1 that the order of reactivity of different positions in substituted benzenes follows the order of hyperfine coupling constants in the e.s.r. spectrum of the radical ~ation.~ It would be interesting to see this tested in a case where unexpected reaction products are obtained. The effect of the cyclopropyl substituent on aro-matic reactivity depends upon the nature of the transition state. When it is late (eg. bromination) reactivity depends upon whether or not a bisected conforma- tion can be adopted to give maximum stabilization of the Wheland intermediate. R. Taylor in ‘MTP International Review of Science Organic Chemistry Series One’ ed.H. Zollinger Butterworths London 1973 Vol. 3 p. 1 ; R. Taylor in ‘Aromatic and Heteroaromatic Chemistry’ ed. C. W. Bird and G. W. H. Cheeseman (Specialist Periodical Reports) The Chemical Society London 1973 Vol. 1 p. 176. D. A. Forsyth J. Amer. Chem. SOC.,1973,95 3594. J. N. Murrell W. Schmidt and R. Taylor J.C.S. Perkin If 1973 179. E. B. Pendersen T. E. Petersen K. Torsell and S.-0. Lawesson Tetrahedron 1973,29 579. 63 A. R.Butler Thus compound (1) reacts faster than (2)and attack is at thep-position. Nitration with an early transition state does not depend upon the conformation of the cyclopropyl group and (1) and (2) react at similar rates to give the o-substituted product.’ Sulphonation is a reaction one would imagine to be very susceptible to steric influences but Blackborow6 reports that with NN-dimethylanisidine sulphona- tion and hydrogen exchange show the same positional discrimination although the latter reaction is 100 times faster.On the other hand Olah7 has discussed varying substrate and positional selectivity in aromatic sulphonylation in terms of the position of the transition state along the reaction profile. A criticism of this analysis will be discussed later (p. 74). A simple study of the relative rates of nitration of benzene and toluene by nitronium tetrafluoroborate has established that substrate selectivity depends markedly upon the solvent and emphasizes the vital role of solvation in fixing the reaction rate. The low value originally reported by Olah was found for solvent like n-hexane but with more polar solvents higher values are obtained.8 Nitration may be effected by metal nitrates in acetic anhydride and the rate of reaction depends upon the metal ion ;other results show that titanium nitrate is an electrophilic nitrating agent.It is unlikely that free NO2+ is formed and the mechanism is thought to be attack of benzene on the nitrogen of the nitrate group (Scheme 2).’ The use of NaN0,-KNO in a pyrosulphate-sulphate melt at 250°C as a nitrating agent has been investigated in some detail. A kinetic study using benzenesulphonate as substrate indicates a mechanism involving an intermediate formed from NO and the benzenesulphonate ion which + Scheme 2 W. Kurtz P.Fischer and F. Effenberger Chem. Ber. 1973 106 525; P. Fischer W. Kurtz and F. Effenberger ibid. p. 549. J. R. Blackborow J.C.S. Perkin II 1973 2387. ’ G. A. Olah S. Kobayashi and J. Nishimura J. Amer. Chem. SOC.,1973 95 564. * S. Sekiguchi A. Hirose S. Kato and K. Matsui Bull. Chem. SOC. Japan 1973,46,646. K. Fukunaga and M. Kimura Nippon Kagaku Kaishi 1973 1306; D. W. Amos D. A. Baines and G. W. Flewett Tetrahedron Letters 1973 3191. Reaction Mechanisms-Part (i) Aromatic Compounds decomposes to give nitrobenzene and SO,. lo Dinitrogen tetroxide is an effective if inconvenient nitrating agent. Measurement of relative reactivities did not permit the effective species to be identified with certainty but it is clear that nitrosation plays a significant role with highly activated substrates.Nitric acid in acetic anhydride is an effective nitrating agent but exhibits com- plex kinetics and gives unusual products. This in part is due to the tendency for addition products to form and more of these have been reported during 1973. At room temperature reaction with 1,4-dimethylnaphthalene results in side- chain attack to give (3),but at -40 "Cthe adduct (4)is obtained. '' With toluene cis- and trans-forms of (5)are obtained and decompose to give p-tolyl acetate. ' (3) (4) Fischer has also isolated (6)and (7) from 2,3-and 3,4-dimethylbenz0nitrile'~ and (8) from 3,4-dimethylanisole. l5 The nitro-group in such adducts is mobile as has been shown by a study of the products of the action of acetic acid on (9).16 Me NO Me NO Me NO, 0 0:'.0'. AcO HQ:i2 H OAc H OAc Me0 OAc Another example of the action of acetyl nitrate giving unexpected products is its reaction with cyclotriveratrylene (lo) which results in a mixture of (1 1) and (12). lo J. M. Schlegel and J. J. Robinson J. Amer. Chem. SOC.,1973,95 665. ' G. R. Underwood R. S. Silverman and A. Vanderwalde J.C.S. Perkin II 1973 1 i 77. l2 A. Fischer and A. L. Wilkinson Canad. J. Chem. 1972 50 3988. l3 A. Fischer and J. N. Ramsay J.C.S. Perkin II 1973 237. l4 A. Fischer and C. C. Greig J.C.S. Chern. Comrn. 1973 396. Is A. Fischer and D. R. A. Leonard J.C.S. Chem. Comm. 1973 300. l6 R. C. Hahn and M. B. Groen J. Amer. Chem. SOC.,1973,95,6128. A. R. Butler The unsubstituted compound 10,15-dihydro-5H-tribenzo[u,d,g]cyclononene does not undergo cleavage so that reaction of (10)must be due to the stabilization of the veratryl cation by the methoxy-groups.17 Me0 OMe Me0 OMe Me0 OMe CH,OAc CH,OAc Challis has continued his study of aromatic nitrosation.With p-substituted phenol the rate-determining step is loss of a proton from the dienone intermediate (13) and there is subsequent oxidation to give the 2-nitro-compound. For this 0 reaction there is a low p value which is characteristic of rate-determining proton loss. * At high pH dienone formation becomes the slow step. With resorcinol and its 0-methyl derivative the product is an oxime and either proton loss or reaction of undissociated substrate and H,NO,+ is rate-determining depending on the pH.For 1,3-dimethoxybenzene the slow step is decomposition of the dienone intermediate to give nitrosomethoxybenzene.20Nitrosation of various indoles in dilute acid is brought about by a variety of species depending on the conditions. The rate-determining step depends on the basicity of the substrate for less basic ones it is proton loss but with others it may be either formation of T. Sato T. Akima and K. Uno J.C.S. Perkin I 1973 891. B. C. Challis and R. J. Higgins J.C.S. Perkin If 1972 2365. l9 B. C. Challis and R. J. Higgins J.C.S. Perkin II 1973 1597. 2o J. Jahelka V. Sttrba and K. Valter Coll. Czech. Chem. Comm. 1973 38 877. Reaction Mechrmisrns-Part (i)Aromatic Compounds reagent or diffusion of reactants.* The transfer of a nitroso-group from N-nitro- sodiphenylamine to N-methylaniline and other nucleophiles is acid catalysed.In some cases nitrous acid is an intermediate but protonation is not the slow step.22 The reactivity of diazonium ions has been reviewed.23 In general bases react with benzenediazonium ions in the unprotonated form,24although at high pH pyrrole reacts as the conjugate base.25 Several studies of coupling with phenols have been reported.26 Attack of benzene on the benzenediazonium ion may result in displacement of the azo-group as molecular nitrogen and formation of di~henyl.~’ Reid has shown that Ga-thiathiophthen generally undergoes normal electrophilic substitution but in its reaction with benzenediazonium tetrafluoro- borate there is rearrangement and a hypervalent heterocyclic system results.28 For some time there has been doubt concerning the role of positive halogen in halogenation by acidified hypohalous acid.It is not formed in acidified hypo- bromous acid and the active electrophile is H20Br+. However this is not formed from hypobromous acid but by protonation of a substrate-HOBr complex formed in a pre-equilibrium step.29 A study of the variation of the kinetic hydro- gen isotope effect with bromide ion concentration in the bromination of naph-thalene by Ehrlich and Berliner3’ gives further proof of the two-step mechanism. Studies of brom~desilylation~~ have been reported. and brom~degermylation~~ There has been one further important study of the mechanism of aromatic iodination.At low iodide concentration in the acid-catalysed iodination of phenol the slow step is attack of molecular iodine on the substrate to give (14) but at higher concentrations compound (14) is formed in a reversible process 5.C. Challis and A. J. Lawson J.C.S. Perkin 11 1973 918. *’B. C. Challis and M. R. Osborne J.C.S. Perkin 11 1973 1526. 23 H. Zollinger Accounts Chem. Res. 1973 6 335. 24 M. RemeS J. DiviS V. Zvttina and M. Matrka Coll. Czech. Chem. Comm. 1973 38 1049. ’’ K. Mitsumura Y. Hashida S. Sekiguchi. and K. Matsui Bull. Chem. SOC.Japan. 1973 46 1770. 26 S. Kishirnoto 0. Manabe H. Hachiro and N. Hirao Nippon Kagaku Kaishi 1972. 2132 B. Demian Bull. SOC.chim. France 1973. 796; Z. V. Belitskaya M. V. Plakidina and T.L. Bagal Org. Reactivity (U.S.S.R.) 1971,8 1046. z’ P. Burri and H. Zollinger Helv. Chim. Acra 1973 56 2204. R. M. Christie A. S. Ingram D. H. Reid and R. G. Webster J.C.S. Chem. Comm.. 1973 92. 29 H. M. Gillon and J. H. Ridd J.C.S. Perkin 11 1973 1321. 30 A. Ehrlich and E. Berliner J. Org. Chem. 1972 37 4186. ’‘ J. Vklak and V. Chvalovsky Coll. Czech. Chem. Comm. 1973 38 1055. 32 J. VEelak and V. Chvalovsky Coil. Czech. Chem. Comm. 1972,37 3615. 68 A. R. Butler and the slow step is depr~tonation.~~ This is also true for iodination by iodine in concentrated sulphuric acid,34 where the electrophile is 13+. Inoue et al. have reported3' a method of electrochemical fluorination a general technique of increasing importance in synthetic organic chemistry.There .is a curious differ- ence between the reactions of cyanogen chloride and bromide with phenyltrim- ethylstannane. With the former benzonitrile results whereas the latter gives br~mobenzene.~~ There have been studies of electrochemical cyanation3' and thi~cyanation.~' It is common for aromatic metallation to occur ortho to a substituent containing oxygen or nitrogen. This is because co-ordination to the substituent occurs prior to attack of the aromatic ring3' Lead tetratrifluoroacetate will effect aromatic plumbylation which occurs para to a halogen ~ubstituent.~' Friedel-Crafts reactions continue to attract much attention but few of the studies reported in 1973 throw further light on the mechanism. For example partial orders were obtained in a kinetic study of acylation by acetic anhydride in concentrated sulphuric acid41 and another study indicates that a variety of factors control orientation in these reactiom4* Agranat and A~nir~~ have produced evidence to show that acylation reactions are reversible contrary to previously held beliefs.Utley and Yate~~~ have reported an electrochemical method of acylation using the anodic oxidation of 2,3,5,6-tetramethyloxyquinol diacetate which produces an acylium ion. Factors affecting the ease of cyclization under Friedel-Crafts conditions have been e~amined.~' The cyclization of cyclohept-4-ene- 1-carbonyl chloride to 2-endo-chlorobicyclo[ 3,2,1]octan-8-one is stereospecific suggesting formation of the non-classical ion (15) as an i~~termediate.~~ Cyclization of o-arylthiophenyl methanol occurs uia formation of a carbenium ion and there is a 1,2-sulphur shift following formation of the spiro-intermediate (16).33 E. Grovenstein N. S. Aprahamian C. J. Bryan N. S. Gnanapragasam D. C. Kilby J. M. McKelvey and R. J. Sullivan J. Amer. Chem. Soc. 1973 95 4261. 34 J. Arotsky A. C. Darby and J. B. A. Hamilton J.C.S. Perkin Il 1973 595. 35 Y. Inoue S. Nagase K. Kodaira H. Baba and T. Abe Bull. Chem. SOC.Japan 1973 46,2204. 36 E. H. Bartlett C. Eaborn and D. R. M. Walton J. Organometallic Chem. 1972 46 267. 37 K. Yoshida and T. Fueno J. Org. Chem. 1973,38 1045. 38 V. R. Kartashov E. V. Skorobogatova and I. V. Bodrikov Zhur. org. Khim. 1973,9 214. 39 D. W. Slocum and F. E.Stonemark J. Org. Chem. 1973,38 1677; D. W. Slocum and B. P. Koonsviteky ibid. p. 1675. 40 D. de Vos J. Wolters and A. van der Gen Rec. Trau. chim. 1973,92 701 ;D. de Vos J. Spierenburg and J. Wolters ibid. p. 701. '' A. Germain A. Commeyras and A. Casadevall Bull. SOC.chim. France 1973 2527 2537. '* J. P. Girault P. Scribe and G. Dana Tetrahedron 1973 29 413; L. J. Kricka and A. Ledwith J.C.S. Perkin I 1973 859. 43 I. Agranat and D. Avnir J.C.S. Chem. Comm. 1973 362. 44 J. H. P. Utley and G. B. Yates J.C.S. Chem. Comm. 1973 473. 45 A. A. Khalaf and R. M. Roberts J. Org. Chem. 1972,37 4227. 46 G. Capozzi G. Melloni and G. Modena J.C.S. Perkin I 1973 2250. Reaction Mechanisms-Part (i)Aromatic Compounds RH Jackson and his co-workers have reported further studies on indole com- pounds.Cyclization of(17)is known to occur via formation of the spiro-indolenine (18) and the tosylate has been found to react in the same way!' However although the main route in the cyclization of 4-(6-methoxyIndol-3-yl)butanol to 7-methoxy- tetrahydrocarbazole is the same there is a minor route involving direct attack at the 2-position owing to activation by the metho~y-group.~~ From a study of the rearrangement of isolated indolenines it is probable that this minor route is also operative in the simple alkylation of in dole^.^^ There is now considerable evidence that positional selectivity of ionic reactions in the gas phase depends upon the pressure." These reactions are characterized in general by low substrate selectivity but this does not apply to t-butylation since a much weaker electrophile is involved.' Taylor and Tewson' have shown that hydrogen exchange in superacids is 10" times faster than in trifluoroacetic acid. This enormous increase is due to enhanced reactivity of the electrophile and is not a medium effect. All available data for aromatic hydrogen exchange has been collected and standardized at 100 "Cand pH 0.53This permits an exact comparison to be made of the suscepti- bilities of many aromatic compounds to electrophilic attack. Using only substi- tuted benzenes there is an excellent correlation between the standardized rate constants and oP+values but if all the data are included the correlation is not as good.54 47 A.H. Jackson and B. Naidoo J.C.S. Perkin II 1973 548. 48 R. Iyer A. H. Jackson P. V. R. Shannon and B. Naidoo J.C.S. Perkin II 1973,872; R. Iyer A. H. Jackson and P. V. R. Shannon ibid. p. 878. 49 G. Casnati A. Dossena and A. Pochini Tetrahedron Letters 1972 5277. F. Cacace and E. Possagno J. Amer. Chem. SOC.,1973,95 3397. 51 F. Cacace and P. Giacomello J. Amer. Chem. SOC.,1973 95 5851. 52 R. Taylor and T. J. Tewson J.C.S. Chem. Comm. 1973 836. 53 A. El-Anani J. Banger G. Bianchi S. Clementi C. D. Johnson and A. R. Katritzky J.C.S. Perkin II 1973 1065. 54 S. Ciementi and A. R. Katritzky J.C.S. Perkin II 1973 1077. A. R.Butler 2 Nucleophilic Aromatic Substitution Crampton and Khan55 have shown that there is only a small energy difference between the 4- and 2-complexes formed from l-substituted 3,5-dinitrobenzenes and methoxide ion although the former is greatly increased by addition of bivalent metals ions.56 A spiro a-complex (19)has been reported.57 Aza-groups H2C -CH II 0 NMe (19) activate the ring towards nucleophilic attack as much as nitro-gr~ups.~' There have been several studies of the reaction of ketone anions with polynitrobenzenes to give a-complexes.With l-substituted 2,4-dinitrobenzene attack occurs at both the 3-and 5-positions to give (20) and (21).59 The hydrogen atoms of the X X Hoo2 MeCOCH NO NO CHJOMe methyl group of trinitrotoluene are sufficiently acidic to form an anion in alkaline solution and this will form a a-complex with trinitrobenzene.60 A transient a-complex has been detected in the reaction of the sodium salt of diethyl malonate with 2,4-dinitrofluorobenzene in DMSO to give diethyl 2,4-dinitrophenyl- malonate.6' Decomposition of the a-complex is the slow step in the reaction of substituted N-methylanilines with 2,4-dinitrochlorobenzene and 2,4-dinitro- fluorobenzene but no evidence for base catalysis was found.62 Reactions of 4-substituted 2-nitrochlorobenzenes with toluene-p-thiolate in DMF gives a 55 M.R. Crampton and H. A. Khan J.C.S. Perkin 11 1973 710. " M. R. Crampton and H. A. Khan J.C.S. Perkin ZZ 1973 1103. 57 S. Sekiguchi and T. Shiojima Bull. Chem. SOC. Japan 1973,46 693. J. Kavalek T. M. Chinh V. Mikan V. Sttrba and M. VeEeta COIL Czech. Chem. Comm. 1973,38 1935.59 N. Obi H. Kakizaki and M. Kimura Chem. and Pharm. Bull. (Jupan) 1973,21,235; N. Obi and M. Kimura ibid. 1972,20,2295; E. E. Gol'teuzen S. S. Gitis and A. Ya. Kaminskii Sin. Anal. Struckt. Org. Soedinenii 1971 121. " E. E. Gol'teuzen Yu. D. Grudtsyn S. S. Gitis and A. Ya. Kaminskii Zhur. org. Khim. 1972 8 1916; S. S. Gitis A. Ya. Kaminskii Yu. D. Grudtsyn and E. E. Gol'teuzen Doklady Akad. Nuuk S.S.S.R. 1972 205 102. 61 K. T. Leffek and P. H. Tremaine Canad. J. Chem. 1973,51 1659. '' J. Kavalek J. Kubias and V. Sterba Coll. Czech. Chem. Comm.. 1972 37 4041. Reaction Mechanisms-Part (i) Aromatic Compounds good Hammett plot (p = 6.65).63Taylor and vat^^^ report that the base- catalysed decomposition of (22) is greatly enhanced by addition of bovine serum albumin which acts as a macromolecular catalyst ;the product is (23).N The fascinating transformations brought about by reaction of the amide ion with heterocycles have been reviewed in a book by van der Plas6’ and new examples described e.g. chloropyrazine (24)is converted into 2-cyanoimidazole (27).The mechanism involves attack at C-3 and fisson of the C-3-N-4 bond to give (25) loss of HC1 and recyclization to (26);the final step is loss of hydrogen.66 Reaction of 4-bromo-2,6-diphenylpyrimidine with amide ion at -33 “C results in substitution by a benzyne mechanism but a minor route may involve an ANRORC me~hanism.~’ No 2,5-didehydropyrazine is formed in the analogous reaction of 2-chlor0-6-phenylpyrazine.~~ Lithium isopropylamide reacts with 6-bromo-4phenylpyrimidine by a complex ANRORC me~hanism.~’ In strongly basic media bromopyrazoles and bromothiophens undergo ‘halogen dances’ ;’O the reactions are intermolecular.’ * 63 P.Carniti P. Beltrame and S. Cabiddu J.C.S. Perkin ff 1973 1430. 64 R.P. Taylor and J. B.Vatz J. Amer. Chem. SOC.,1973,95 5819. ’’ H.C. van der Plas ‘Ring Transformations of Heterocycles’ Academic Press London 1973. 66 P. J. Lont and H. C. van der Plas Rec. Truv. chim. 1973,92,311. 67 J. de Valk and H. C. van der Plas Rec. Truv. chim. 1973,92 145. 68 P. J. Lont H. C. van der Plas and A. van Veldhuizen Rec. Trav. chim. 1973,92 708. 69 H. C. van der Plas and A. Koudijs Rec. Trau. chim. 1973,92 71 1. ’O J. F.Bunnett and C. E. Moyer J. Amer.Chem. SOC.,1971,93 1183. D. A. de Bie H.C. van der Plas G. Geurtsen and K. Nijdam Rec. Trav. chim.,1973 92 245. 72 A. R.Butler 3 Acidity Functions Gillespie and Peel7' have determined H values for a number of superacids :the highest value is 19.35 for HS0,F containing 7% SbF, 3s0,. Values for per- chloric acid in aqueous acetic acid have been reported.73 The problem of the proliferation of acidity scales has been discussed by Yates and co-w~rkers.~~ The search for a measure of the inherent acidity of an acid appears to be futile and it is now clear that Wyatt's75 observation that acidity is a unique function of the water activity applies to only H values and is probably fortuitous. The activity coeffi- cients of various indicators have been measured by independent means and from these hydronium ion activity can be calculated.The values obtained are remark- ably independent of the method used to obtain them. The utility of this approach is not to establish an intrinsic scale of acidity as in any reaction the important matter is the extent to which any particular substrate is protonated but it will permit calculation of the free energies of solvation of various cations. It was considered impossible to draw any conclusion from the linear relationship between H and log k for the hydrolysis of cellulose.76 All the problems associated with describing the acidity of a concentrated acid are parallelled in strongly basic media. For instance different H-scales are obtained particularly at high DMSO concentration using the ionization of nitrogen and oxygen weak The acidities of such media have been measured kinetically78 and a new scale (J-) based on the addition of hydroxide ions to substituted benzaldehydes has been proposed.79 In an interesting study hydrogen ion activities in strongly basic media have been measured using glass and dropping mercury electrodes.*' The new acidity function HGc has values higher than those for H-and H -." Similar values were obtained using a ferrocene-ferricinium ion couple as a reference electrode. 82 In alkaline ethylene glycol and DMSO the H-scale was found not to correlate well with logk for the solvolysis of chl~roform.~~ 4 Linear Freeenergy Relationships Various aspects of linear free-energy relationships have been reviewed by workers prominent in this field.84 It has been obvious for some time that the Hammett 72 R.J. Gillespie and T. E. Peel J. Amer. Chem. SOC.,1973 95 5173. 73 M. Godel A. Jussiaume and F. Coussemant Tetrahedron 1973 29 2889. 74 K. Yates H. Wai G. Welch and R. A. McClelland J. Amer. Chem. SOC.,1973 95 418. 75 P. A. H. Wyatt Discuss. Faraday SOC.,1957 No. 24 p. 162. 76 A. Mohn-Wehner H. K. Rouette and H. Zollinger Helv. Chim. Acta 1973 56 323. 71 A. Albagli A. Buckley A. M. Last and R. Stewart J. Amer. Chem. SOC.,1973 95 471 1. 78 M. F. Semmelhack R. J. DeFranco Z. Margolin and J. Stock J. Amer. Chem. SOC. 1973 95,426. 79 W. J. Bover and P. Zuman J. Amer. Chem. SOC.,1973,952531. 80 J. Janata and R.D. Holtby-Brown J. Electroanalyt. Chem. Interfacial Electrochem. 1973,44 137. 81 J. Janata and R. D. Holtby-Brown J.C.S. Perkin II 1973 991. 82 K. Yates and R. A. McClelland J. Amer. Chem. SOC.,1973,95 3055. 83 K. K. Kundu and L. Aiyar J.C.S. Perkin ?I 1973 143. 84 'Advances in Linear Free Energy Relations' ed. N. B. Chapman Plenum London 1972. Reaction Mechanisms-Part (i) Aromatic Compounds 73 equation is too simple to give an accurate measure of substituent effects and another two-parameter equation has been proposed which has better predictive powers.85 Wepstera6 has shown that the Yakawa-Tsuno equation is implicit in Hine's generalized equation.87 Transmission of substituent effects through the thiazole ring,88 pyridine ring,89 imidazole ring," furan and thiophen,' ' carbon-carbon double and triple bonds,92 and cyclopropane rings93 has been examined.From a study of the pK values ofa series ofcompounds ArXCH,CO,H (X = CH, CMe, NH 0,S or NHCH,) it was found that -M substituents in the p-position deviate from the Hammett equation.94 Because of such deviations insulated systems of this type are unsuitable for the determination of o" con-stant~.~~ The effect of substituents on the fluorine n.m.r. in compounds (28) (28) G = -CH2-or -HC=N-supports96 a two-parameter equation proposed elsewhere.97 A study of pK values of 4-substituted quinuclidines suggests that the substituent effect is trans- ferred along the o-bonds and is not a direct field effect.98 There is a linear rela- tionship with the Taft constant o*,provided the unsubstituted compound is excluded.The reason for this is not under~tood.~~ The nature of the Taft steric constant E has been considered"' and it is clear that this constant is successful only if the substituent does not adopt a preferred conformation."' It is important that further examples of this are found. A good correlation has been found between carbonyl stretching frequencies and o+ constants.lo2 This applies to phenyl esters but o' constants are used. This is also the appropriate constant for the reaction of various nucleophiles R. T. C. Brownlee and R. D. Topsom Terrahedron Letters 1972 5187. B. M. Wepster J. Amer. Chem. SOC., 1973,95 102. J. Hine J. Amer. Chem. SOC.,1959 81 1126; ibid. 1960 82 4877.D. S. Noyce and S. A. Fike J. Org. Chem. 1973,38,2433 3316 3318 3321. 89 D. S. Noyce J. A. Virgilio and B. Bartman J. Org. Chem. 1973,38,2657; D. S. Noyce and J. A. Virgilio ibid. p. 2660. 90 D. S. Noyce and G. T. Stowe J. Org. Chem. 1973 38 3762. 91 A. BeAo A. KrutoSikova L. FiSera and R. Frimm Coll. Czech. Chem. Comm. 1973 38 2734. 92 K. Izawa T. Okuyama and T. Fueno Bull. Chem. SOC.Japan 1973,46,2880. 93 G. Montando and C. G. Overberger J. Org. Chem. 1973,38 804. 94 A. J. Hoefnagel J. C. Monshouwer E. C. G. Snorn and B. M. Wepster J. Amer. Chem. SOC.,1973 95 5350. 95 A. J. Hoefnagel and B. M. Wepster J. Amer. Chem. SOC. 1973 95 5357. 96 S. K. Dayal S. Ehrenson and R. W. Taft J. Amer. Chem. Suc. 1972,94 91 13. 97 S. Ehrenson R.T. C. Brownlee and R. W. Taft Progr. Phys. Org. Chem. 1973,10 1. 98 J. Paleeek and J. Hlavaty CON. Czech. Chem. Comm. 1973 38 1985. 99 C. A. Grob W. Simon and D. Treffert Angew. Chem. Internat. Edn. 1973 12 319. loo T. Fujita C. Takayama and M. Nakajima J. Org. Chem. 1973 38 1623. A. Babadjamian M. Chanon R. Gallo and J. Metzger J. Amer. Chem. SOC.,1973,95 3807. A. Perjessy Tetrahedron 1973 29 2189 3207. A. R.Butler with esters indicating that during reaction there is uncoupling of resonance between the phenolic oxygen and the aromatic mystem. '03 In a very important paper Johnson and Schofield''" have analysed common interpretations of p as it reflects the nature (particularly charge distribution) of the transition state. They suggest that p should be the same whatever the substrate and that different values merely reflect different abilities to transmit substituent effects.A more rigorous approach would be to use the standard reactions (e.g. ionization of carboxylic acids) to define CT and CT' constants for each ring system (as Noyce is doing for a') and use these to obtain unique p values. In the present state of our knowledge of the transition state it might not be very profitable to compare p values obtained with different ring systems. Johnson and Schofield continue with an analysis of Olah's results where p values are used to designate early and late transition states. They contend that Olah's interpretation leads to a situation where reaction with a less reactive electrophile (high negative p) would be faster than reaction with a highly reactive electrophile (low negative p).Further analyses of the situation are awaited with interest. However this Reporter agrees with the closing remark 'linear free energy relationships (are) by definition incompatible with structure-reactivity correlations invoking variable transition states'. Jencks' O5 has reviewed the relation between mechanism and structure-reactivity relationships and there has been an analysis of the Marcus theory in terms of a model for a simple proton transfer. ' O6 There is now some confusion concerning the linearity of Brnrnsted plots. Kreevoy and Oh'" report that the plot for the hydrolysis of the diazoacetate ion catalysed by trialkylammonium ions is curved and account for this in terms of the Marcus theory.The kinetic isotope effect is also consistent with this. A very detailed and elegant analysis of the results permits the separation of the free-energy change into that part involved in the rate-determining step and that associated with preliminary steps. On the other hand Kemp and Casey"' found that the Brernsted plot for the base- catalysed reaction of benzisoxazoles to give salicyclonitrile over a very wide range of pK values is completely linear and conclude that curvature is always due to extraneous factors. The constancy of the /Ivalue reflects a transition state in proton-transfer reactions which has a uniform sensitivity to substituent effects over an appreciable range of transition-state energies.An attempt has been made to deal with the confusion surrounding the enthalpy-entropy or isokinetic relationship by using an extended Arrhenius equation. log lo' L. A. Cohen and S. Takahashi J. Amer. Chem. SOC.,1973,95,443. Io4 C. D. Johnson and K. Schofield J. Amer. Chem. SOC.,1973,95,270. W. P. Jencks Chem. Rev. 1972.12 705. lo' G. W. Koeppl and A. J. Kresge J.C.S. Chem. Comm. 1973 371. lo' M. Kreevoy and S. Oh J. Amer. Chem. SOC.,1973,95,4805. lo* D. S. Kemp and M. L. Casey J. Amer. Chem. SOC.,1973,95,6670. S. Wold and 0.Exner Chem. Scripta 1973 3 5.