5 The Ionization of Carbon Acids By J. R . JONES Department of Chemistry University of Surrey Guildford Surrey This topic is a subject of much interest not only because of the central position occupied by carbon acids in chemistry and the increasing synthetic use being made of carbanions but also because the process of ionization has so many distinguishing features not least being its inherent simplicity. Such a reaction seems therefore to be a good starting point for the study of reaction kinetics in solution. Systematic study would involve not only the determination of acidities but also the effect of different bases and of temperature on the rates of both forward and reverse reactions. This information may be supplemented by the results of isotopic substitution as many unknown or poorly known factors cancel in the ratio of the rates.The following account describes work published during the past twelve months which is relevant to the above considerations. Large numbers of kineticists will always be grateful to Guggenheim' and Swinbourne2 for their methods of analysing kinetic data for first-order reactions where the initial and infinity readings are not available. The disadvantages of both methods have been overcome3 by the development of a non-linear least squares procedure which enables the rate constant for a first-order process to be determined when data are recorded at irregular time intervals and when readings are taken for any length of time (although obviously the longer a reaction can be followed the more accurate the results).1 Rates of Ionization Methods.-With the development of techniques that enable very fast reaction rates to be measured it is now possible to study not only a wider range of reac-tions but also a particular reaction under more diverse conditions. Several modifications or improvements to existing and well-established methods have been reported. Thus to take full advantage of the potential of stopped-flow methods it is highly desirable to automate the sample handling and mixing operations as well as the data acquisition and evaluation steps. This has been done by Beckwith and C r ~ u c h . ~ A stopped-flow instrument in which the initial com-position of the reactant solution can be varied by mixing different volumes of ' E. A. Guggenheim Phil. Mag. 1926,2 538.E. S. Swinbourne J . Chem. SOC. 1960 2371. P. Moore J.C.S. Faraday I 1972,68 1890. P. M. Beckwith and S. R. Crouch Analyt. Chem. 1972,44221. 11 120 J . R. Jones two reactants at any of thirteen volume ratios has been described;' so also has a fully automatic instrument with the ability to prepare and mix samples to acquire kinetic data on the mixed solutions to process the results and to report them in one or more formats.6 In this way the manipulative operations are significantly reduced and extension of the method to more complex chemical reactions is facilitated. A vacuum-type stopped-flow instrument7 suitable for studying reac-tions of highly reactive anionic species has been developed and used to study the reaction between n-butyl-lithium and fluorene in tetrahydrofuran.For those with less money to spend a simple and inexpensive modification of a somewhat dated spectrophotometer is possible making it equally useful for monitoring enzymic reactions and chromatographic separations? Attention has been drawng to a potential source of error in measurements carried out at other than ambient temperatures using a commercially available stopped-flow instrument. The development of a rapid-mixing cell and stopped-flow nuclear magnetic resonance spectrometer has been reported" and the instrument has been used to study the reaction : Ni(NH,)(H,O):+ + H30+ --+ Ni(H,O)g+ + NH; A laser temperature-jump apparatus capable of measuring relaxation times in the 10-8-10-7 s range has been introduced.' ' This makes use of the simulated Raman effect in liquid nitrogen to shift the wavelength of the neodymium-glass laser radiation from 1.06 pm where the absorbance is very small to 1.41 pm, where water absorbs very strongly.A microwave temperature-jump method l 2 suitable for following reactions between neutral reagents in non-conducting solvents has been used to study the rate of formation of the donor-acceptor complex between tetracyanoethylene and hexamethylbenzene. The pressure-jump method13 has been used to study nickel malate complex formation. For investigating much slower reactions two methods one involving the use of selective ion electrode^,'^ and the other using the differential approach l5 seem destined to become more widely used. The high precision of the latter method is ideally suited for studying solvent isotope effectsI6 in media of varying deuterium composition.For measurements of hydrogendeuterium exchange a R. A. Harvey and W. 0. Barcherdt Analyt. Chem. 1972 44 1926. ' D. Sanderson J. A. Bittikofer and H. L. Pardue Analyt. Chem. 1972 44 1934. ' A. G. Evans N. H. Rees and A. Walker J.C.S. Perkin II 1972 1723. H. M. Rasmussen and J . R. Nielsen Analyr. Biochem. 1972 50 648. P. K. Chattopadhyay and J. F. Coetzee Analyt. Chem. 1972,44,2117. l o J . Grimaldi J. Baldo C. McMurray and B. D. Sykes J . Amer. Chem. SOC. 1972 94, 7641. ' I D. H. Turner G. W. Flynn N. Sutin and J. V. Beitz J . Amer. Chem. SOC. 1972 94, 1554. E. F. Caldin J. E. Crooks D. O'Donnell D. Smith and S. Toner J.C.S. Faraday I, 1972 68 849. l 3 S.Harada K. Amidaiji and T. Yasunaga Ber. Bunsengesellschaft phys. Chem. 1972, 76 1752. l 4 G. A. Rechnitz Analyt. Chem. 1972 44 300. l 5 W. J. Albery and A. N. Campbell-Crawford J.C.S. Perkin I I 1972 2190. l 6 W. J. Albery J. R. Bridgeland and J. S. Curran J.C.S. Perkin I I 1972 2203 The Ionization of Carbon Acids 121 facile and direct method” for isotopic analysis of hydrogen or deuterium content of water based on ultrasonic velocity measurements has been reported. The change in sound velocity in going from pure D20 to pure H 2 0 is 97.7 m s- (or some 7 % of the value for pure D20) and varies linearly with concentration. Results.-When carbon acids undergo ionization numerous modes of carbanion stabilization are known to be important. l 8 In the base-catalysed isotope exchange of a series ofpolyfluorinated hydrocarbons (2-hydro-2-phenylhexafluoropropanes) none is more important than the polarizability and induction contributions.l9 Fluorine hyperconjugation seems to be unimportant but a +R carbanion-destabilizing mechanism is important for nearly all substituents and especially fluoro and methoxy. For a series of 2-substituted 1,1,1,3,3,3-hexafluoropropanes, l,l,l-trifluoroethanes and some haloforms in the same solvent (50 50 dimethyl sulphoxide-methanol) with triethylamine as base the two main factors that determine fluorocarbanion and halogenocarbanion stabilities appear to be induction and destabilization by a +R mechanism.20 The effect of adjacent unshared electron pairs on ease of carbanion formation has also been studied.2i The generally accepted mechanism of racemization isotopic hydrogen ex-change and halogenation of carbonyl compounds is rate-determining enoliza-tion followed by fast reaction of the enol or enolate ion.Rappe’s finding22 that bromination of butan-2-one can result in a ratio of monohalides quite different from that predicted on the basis of relative exchange rates under similar con-ditions led to the suggestion that another mechanism involving direct reaction of bromine with unenolized ketone is important. Thorpe and Warkentin23 failed to observe such a term and a product analysis shows that there is no need for different rate-determining steps for alkaline halogenation and deuterium exchange. The relative rates of acetate-catalysed enolization of CH,COCH CH,-COCH,Br and CH,COCHBr are 1 2.2 x lo4 1.5 x lo5 so that the polar effect of the inserted bromine atoms outweighs the opposing steric effect.25 The effect of the two bromines is less than twice as much as one in enhancing the rate, but it can be correlated with the ionization constants of the corresponding a-bromo-acids.26 Tritium exchange from the C-8 position of several purines in nucleosides and in deoxyribonucleic acid27 involves hydroxide ion attack on the 7-protonated form of the purines to give an ylide intermediate which is then reprotonated at ” J.G. Mathieson and B. E. Conway Analyt. Chem. 1972,44 1517. D. J. Cram ‘Fundamentals of Carbanion Chemistry’ Academic Press New York, 1965 Ch. 2. l 9 K. J. Klabunde and D. J. Burton J . Amer.Chem. SOC. 1972,94,820. 2 o K. J. Klabunde and D. J. Burton J . Amer. Chem. SOC. 1972,94 5985. 2 2 C. Rappe Acta Chem. Scand. 1968,22,219; 1967,21 1823. 2 3 J. W. Thorpe and J. Warkentin Canad. J . Chem. 1972 50 3229. 2 4 C. G . Swain and R. P. Dunlap J . Amer. Chem. SOC. 1972,94 5540. 2 5 R. A. Cox and J. Warkentin Canad. J . Chem. 1972,50 3233. 2 6 R. A. Cox and J. Warkentin Canad. J . Chem. 1972,50 3242. 2 7 M. Tomasz J. Olson and C. M. Mercado Biochemistry 1972 11 1235, J . Hine J . Amer. Chem. SOC. 1972 94 6998 122 J. R. Jones C-8 by the medium. For the hydrogen isotope exchange of uridine 5'-phosphate at position 5 cysteine is reported to be a very efficient catalyst.28 The pH-rate profile for the exchange of l-methyl[5-2H]tetrazole in aqueous solution2' has been used as a control experiment to demonstrate that o-complex formation of a heteroaromatic substrate with a transition-metal cation (e.g.Cu2+ Zn2+) can have a major rate-enhancing effect on processes in which substrate ring sub-stituents are eliminated to produce formal sp2 carbanion intermediates. Hydrogen-deuterium exchange of the methyl protons of 1,4,5- and 1,3,5-tri-methyltetrazolium iodides in D20 solution has also been rep~rted,~' as has exchange in several 5-substituted pyrimidine N-~xides.~ Exchange at the 7-methyl group in 6,7,8-trimethyl-l~mazine~~ (l) which serves as a model com-pound for the naturally occurring 8-substituted 6,7-dimethyl-lumazines and for Me flavin nucleotides is both general-acid- and general-base-catalysed (a = 0.46, p = 0.45).of the kinetics of ionization of bromomalon-nitrile (pK = 7.81) shows that this acid behaves like other cyano-substituted carbon acids (p - 0.9-1.0) e.g. malononitrile whereas the behaviour of the much weaker p-nitrobenzyl cyanide (p = 0.61) is considerably different. It is suggested that withp-nitrobenzyl as the activating group several bond changes areassociated with the process of ionization and considerable activation energy is required, whereas with the cyano-group this process contributes negligibly to the activation energy with the result that the potential energy curves are very different. A of the water-catalysed detritiation of malononitrile and its t-butyl derivative in mixed solvents of water with dioxan ethanol and dimethyl sulph-oxide shows the rate to pass thiough a maximum but in the largely non-aqueous solutions the rate is reduced below its value in water.The results are interpreted in terms of medium effects on the activity of the ion-pair transition state and also on the effects these solvents have on the structure of water. A temperature-jump '' Y. Wataya H. Hayatsu and Y. Kawazoe J. Amer. Chem. SOC. 1972,94 8927. 2 9 H. Kohn S. J. Benkovic and R. A. Olofson J. Amer. Chem. SOC. 1972 94 5759. 30 T. Isida S. Fujimori K. Nabika K. Sisido and S. Kozima Ber. Bunsengesellschaft phys. Chem. 1972,76 1246. 3 1 S. A. Krueger and W. W. Pandler J . Org. Chem. 1972,37,4188. 32 R. Stewart and J. M. McAndless J.C.S. Perkin I I 1972 376. 3 3 F. Hibbert and F. A. Long J . Amer. Chem. SOC. 1972,94,2647.3 4 F. Hibbert and F. A. Long J. Amer. Chem. SOC. 1972,94,7637 The Ionization of Carbon Acids 123 Aromatic nitro-compounds react with bases in a variety of ways (see p. 129 for Meisenheimer complex formation). For the reaction between 2,4,6-tri-nitrotoluene and ethoxide ion3’ the rate-determining step is the transfer of a proton from the methyl group to the ethoxide ion. A second species probably a a-complex between TNT and base is also formed. Similarly hydrogen-deuterium exchange in 1,3-dinitrobenzene in sodium metho~ide-methanol~~ occurs by simple proton removal in an internal-return type mechanism ; the radical anion is also formed under these condition^.^' For the ethoxide- and isopropoxide-catalysed deprotonation of di-(4-nitropheny1)methane the activation parameters are nearly the same (10.2,10.4 kcal mol- I) but those for t-butoxide show a lower enthalpy of activation (7.1 kcal mol-I) which is compensated by a much more negative entropy of a c t i ~ a t i o n .~ ~ 2 Acidities of Carbon Acids The pK values of both keto and enol forms of a series of meta- and para-sub-stituted benzoylacetones have been measured by a spectrophotometric method3’ and correlated with the appropriate Hammett substituent constants. The acidities of some 1,1,1-trifluoromethyl-P-diketones in 46 % aqueous acetone have been reported:’ as well as those for a series of meta- and para-substituted 1-arylnitroethanes and arylnitromethanes in water.41 Continuing their extensive studies on the acidities of aromatic hydrocarbons, Streitwieser and co-workers have determined pK values of 19.8 and 18.2 in methanol for 1,3-diphenylindene and fluoradene (2) re~pectively.~~ The high acidity of the latter is usually ascribed to the high resonance stabilization of the anion compared with that of the parent hydrocarbon and relief of strain in (3) 3 5 E.Buncel A. R. Norris K. E. Russell and R. Tucker J. Amer. Chem. SOC. 1972 94, 1646. 36 I. R. Bellobono and G. Sala J.C.S. Perkin 11 1972 169. 3 7 I. R. Bellobono A. Gamba G. Sala and M. Tampieri J. Amer. Chem. SOC. 1972 94, 578 1. 3 8 A. Jacrzewski and K. T. Leffek Canad. J. Chem. 1972,50,24. 39 M. Bergon and J. P. Calmon Bull. SOC. chim. France 1972 1020. 40 K. Bowden G. M. Tanner and D. G. Tuck Canad. J. Chem. 1972,50,2622. 4 1 F. G. Bordwell and W. J.Boyle jun. J. Amer. Chem. SOC. 1972,94 3907. 4 2 A. Streitwieser jun. C. J. Chang and A. T. Young J. Amer. Chem. SOC. 1972 94, 4888 1 24 J . R. Jones changing from sp3 to sp2 hydridization. However the debenzo-analogues of fluoradene 2aH-cyclopent[cd]indene (3) and 9bH-cyclopenta~k]fluorene (4) are not as acidic as the parent compound presumably liecause the strain is not relieved to as great an extent as a n t i ~ i p a t e d . ~ ~ Dibenz[bgJoxocin (5) has been found to be a slightly stronger acid44 (pK - 27) in tetrahydrofuran than xan-thene (pK - 29). Taken in conjunction with the rates of detritiation of penta-fluorobenzene 1,2,3,4-tetrafluorobenzene and o-difluorobenzene the recently measured acidities of these compounds (pK 25.8 31.5 and 35 respectively) allow an estimate of 43 for the pK of benzene.45 Whilst the visible absorption spectra of fluorenylcaesium indenylcaesium and triphenylmethylcaesium in cyclohexylamine or cyclohexylamine-diethylamine change but little with temperature the spectra of fluorenyl-lithium and indenyl-lithium in cyclo hexylaminediethylamine are temperature-dependent and indicate an equilibrium between contact and solvent-separated ion pairs.46 At room temperature the proportion of solvent-separated ion pairs is 95 and 65%, respectively.The small differences between acidities of contact ion pairs and solvent-separated ibIi pairs for several hydrocarbons can be accounted for by a simple electrostatic treatment. The acidities of a number of relatively acidic hydrocarbons (pK - 13-18) have been determined47 in several solvent systems and the small differences that exist interpreted in terms of electrostatic interac-tions between cations and carbanions.These interactions are sensitive to the size of the cations the charge distribution of the carbanions and the polarity of the solvent. The pK values of several 9-alkylfluorenes have been measured4* using both caesium and lithium cyclohexylaniides. 9-Methylfluorene is more acidic than fluorene as is the case in other media; an explanation based on a-bond-strength changes on ionization is favoured. With the development of ion-cyclotron and flowing afterglow techniques, considerable interest is being expressed in gas-phase acidities and the following order has been determined4 at 300 K n-C,H,SH > CH3N02 > CSH6 2 OH i-C3H,0H > C2H,0H > CH30H > C3H4 C,H,CH(CH,) > C6H,-Likewise the basicities of amines which in solution have presented difficulties in CHCl3 > CH3COCH3 > CH3CN > CHZCl, CH3SOCH3 2 C2H2 t-C,H,-CH3 > C3H6 > H2O > C6H6 > H2 > NH3 > C2H4 C6H12 (CH2)3 CH4.J3 B. L. McDowell and H. Rapoport J. Urg. Chem. 1972,37 3261. 44 H. S. Kasmai and H. W. Whitlock jun. J. Org. Chem. 1972 37 2161. 4 5 A. Streitwieser jun. P. J. Scannon and 11. M. Niemeyer J. Amrr. Chc~tri 3To(, 1972, 94 7936. 46 A. Streitwieser jun. C. J. Chang W. B. Hollyhead and J . R. Murdoch. .I. Artwr. Chem. SOC. 1972,944. 5 2 8 8 . 4 7 H. Streitwieser. jun. C . .I. Chiing. and W B. Holljhead J . Amw. Chwz. SOC~. 1972, 94 5292. 4 8 A. Streitwieser jun.C. J . Chang and D. M. E. Reuben J. Amer. Chrnr. Soc. 1972, 94 5730. 49 D. K. Bohme E. Lee-Ruff and L. B. Young J. Amer. Chrm. Soc. 1972 94 5153 The Ionization of Carbon Acids 125 interpretation have been measured in the gas p h a ~ e . ~ O - ~ ~ The basicity order of simple aliphatic amines in aqueous solution (NH < primary < secondary > tertiary) stems from slight differences in the rate of change of the thermodynamic properties in response to progressive alkyl ~ubstitution.~~ The gas-phase basici-ties of the amines increase with increasing methyl substitution and can be inter-preted in terms of effects on the ionization potential of the amine and the hydrogen affinity of the amine radical anion.52 In the gas phase aniline and pyridine are stronger bases than ammonia whereas the reverse is true in aqueous solution.54 3 Aspects of Catalysis The Importance of the Solvent .-The most extensively studied and possibly least understood of solvents water continues to attract interest.Its structure has been further discussed55 and values of K up to 350°C have been rep~rted,'~ as well as in water-methanol mixture^.'^ Methanol appears to be a stronger acid than water over the entire range of solvent compositions the difference becoming larger as the methanol content of the solvent increases. Further com-parison of the relative acidities of water and methanol in the gas phase and in water shows that the hydroxide ions in water are more strongly solvated than methoxide ions.58 The dependence of the acidity and basicity of water on the extent of its hydrogen-bonded structure has been investigated by observing the 'H chemical shifts G(CHC1,) and G(DMS0) in water-solvent-R,NBr mixtures.The available evidence points strongly to enhanced water basicity as a con-sequence of enhanced water structure but the effect if any on water acidity is not clear.59 A calorimetric study of the enthalpies of reaction between water and dimethyl sulphoxide in dilute dioxan solution fails to confirm the existence of a 2H20,DMS0 adduct.60 The free energies of transfer of ionic solutes from H,O to D20 are usually small and despite their importance in the interpretation of kinetic salt effects and the study of aqueous electrolyte solutions relatively few values are available. Lowe and Smith61 report the first use of a cation-sensitive glass electrode for this purpose ; subsequently lanthanum fluoride single-crystal and sodium-responsive glass electrodes were used to obtain the free energies of transfer of 5" M.Taagepera W. G. Henderson R. T. C. Brownlee J. L. Beauchamp D. Holtz and R. W. Taft J . Amer. Chem. SOC. 1972 94 1369. 5 1 E. M. Arnett F. M. Jones M. Taagepera W. G. Henderson J. L. Beauchamp D. Holtz, and R. W. Taft J. Amer. Chem. Soc. 1972 94 4724. 5 2 D. H. Aue H. M. Webb and M. T. Bowers J. Amer. Chem. SOC. 1972,94,4728. 5 3 W. G. Henderson M. Taagepera D. Holtz R. T. McIver jun. J. L. Beauchamp and R. W. Taft J. Amer. Chem. Soc. 1972 94 4728. 5 4 J. P. Briggs R. Yamdagni and P. Kebarle J. Amer. Chem. Sac. 1972 94 5128. 5 5 A. T. Hagler H.A. Scheraga and G. Nemethy J. Phys. Chem. 1972 76 3229. 56 J. R. Fisher and H. L. Barnes J. Phys. Chem. 1972 76,90. 5 7 C. H. Rochester J.C.S. Dalton 1972 5 . 5 8 G. H. Parsons and C. H. Rochester J.C.S. Faraday I 1972 68 523. 5 9 J. E. Gordon J. Amer. Chem. Soc. 1972 94 650. 6 o F. Rallo and F. Rodante Ann. Chim. (Irafy) 1972 62 221. 6 1 B. M. Lowe and D. G. Smith J.C.S. Chem. Comm. 1972,989 126 J. R. Jones sodium fluoride from H 2 0 to H202-H20 mixtures.62 The free energy of transfer of various solutes in H,O-D20 mixtures as determined from solubility measure-ments varies linearly with the deuterium concentration of the solvent.63 In evaluating single-ion solvent activity coefficients O r > + and for transfer of cations A' or of anions B- from a reference solvent (superscript 0) to another solvent (superscript s) experience shows that different groups of extra-thermodynamic assumptions give much the same values as for example in the transfer of silver cation from acetonitrile to 14 other solvents at 25 "C.Parker and c o - ~ o r k e r s ~ ~ strongly recommend that the simplest of these namely the assumption of negligible liquid-junction potential between Ag I AgClO (0.01 moll- l ) half-cells in different solvents when linked by a salt bridge of tetra-ethylammonium picrate (0.01 moll- ') be adopted as the standard procedure. hem me^^^ has speculated on the possibility of there being strong cation-cation interactions in water the lifetime of these cation pairs being comparable with that of the more usual ion-pairs.In solvents of lower polarity salts contain-ing a carbanion e.g. fluorensylsodium or a radical anion e.g. coronenesodium, can exist as contact or solvent-separated ion pairs. In the proton-transfer reaction between triphenylmethane and polystyryl anion in ethereal solvents the free ions are much more reactive than the ion pairs.66 Advantage may be taken of the fact that macrocyclic polyethers are able to form complexes with alkali-metal salts. In this way the solubilities of the salts may be increased as well as the dissociation of the ion pairs leading to the formation of highly reactive unsolvated anions ; in a more subtle way contact ion-pairs may be converted into solvent-separated ion-pairs. This interesting work has been reviewed both by P e d e r ~ e n ~ ~ and Smid.68 N.m.r.studies of the influence of the solvent on ion association have also been reported.69 Linear Free-energy Relationships.-The Hammond postulate 70 that extremely exothermic reactions with small activation energies will have transition states that closely resemble the reactants whereas the transition states of strongly endothermic reactions with large activation energies will bear a close relationship to the products has been put on a more quantitative basis.71 The derived equa-tions are identical with those originally developed by Marcus72 for electron-transfer reactions and the results show that the Bronsted exponent is not always a reliable guide for predicting the position of the transition state along the reac-6 2 A. K. Covington K.E. Newman and M. Wood J.C.S. Chem. Comm. 1972 1234. 6 3 H. Selander and J. L. G. Nilsson Acta Chem. Scand. 1972 26 2433. 6 4 R. Alexander A. J. Parker J. H. Sharp and W. E. Waghorne J. Amer. Chem. SOC., 6 5 P. Hemmes J . Amer. Chem. SOC. 1972 94 75. 6 6 L. L. Chan and J. Smid J. Phys. Chem. 1972,76 695. 6 7 C. J. Pedersen and H. F. Krensdorff Angew. Chem. Internat. Edn. 1972 11 16. 6 8 J. Smid Angew. Chem. Internat. Edn. 1972 11 112. 6 9 Y . Y . Lim and R. S. Drago J. Amer. Chem. SOC. 1972,94 84. ' O G. S. Hammond J. Amer. Chem. SOC. 1955 77 334. 7 1 J. R. Murdoch J. Amer. Chem. SOC. 1972,94,4410. 7 2 R. A. Marcus J. Phys. Chem. 1968,72 891. 1972 94 1148 The Ionization of Carbon Acids 127 tion co-ordinate a point forcefully made by Bordwell and Boyle4’ in their studies on aliphatic nitro-compounds.The non-linear Bronsted plots observed for general acid-base catalysis of several acyl aminolysis reactions with nitrogen or oxygen leaving-groups have been interpreted as evidence of a change in mechanism.73 The deviation of the point for HF in the acid-catalysed hydrolysis of vinyl ethers is due to the fact that all of the negative charge remains localized on the fluorine atom whereas part of the charge formed on proton removal from carboxylic acids is dispersed on to the more distant oxygen.74 A semi-empirical approach to the problem of calculating the potential energy surface and hence of predicting the configuration and energies of transition states has been developed.75 The model is tested by comparing predicted and observed structure-reactivity relations ; for carbonyl hydration reactions it is suggested that nucleophilic attack occurs synchronously with a single proton transfer.Jencks7 has examined various aspects of complex general acid-base-catalysed reactions in which one or more proton transfers accompany another more difficult process using the three-dimensional reaction co-ordinate contour diagrams used by More O’Ferral17 for studying carbon elimination reactions. It is suggested that such reactions can only occur in aqueous solution (a) when the change in pK converts an unfavourable proton transfer into a favourable one and (b) at sites that undergo a large change in pK during the course of the reaction. The driving force of the reaction is the free energy of the proton-transfer process itself rather than stabilization of the transition state by hydrogen-bonding to the The Bronsted p exponent gives a positive correlation with the magnitude of the a effect so that a study of proton transfer from t-butylmalononitrile (p - 0.9) is a good choice for investigating its importance in the ionization of carbon acids.Detritiation studies in a-effective (methoxylamine hydrazine) and non-a-effective buffers however lead to no significant deviations from the Bronsted r e l a t i ~ n s h i p . ~ ~ The past year has witnessed an increasing number of studies in highly basic media and correlations with the appropriate acidity functions. The simple but nevertheless very important reaction between molecular hydrogen (or deuterium) and hydroxide ion in aqueous solution leading to ortho-para conversion (or isotopic exchange) has been studied” in dimethyl sulphoxide-water mixtures.The rates of exchange increase by a factor of lo4 as the medium composition is changed from 0 to 99.5 % dimethyl sulphoxide the plot of log k versus H - having 7 3 J. P. Fox M. I. Page A. Satterthwait and W. P. Jencks J . Amer. Chem. SOC. 1972, 7 4 A. J. Kresge and Y. Chiang J . Amer. Chem. SOC. 1972,94,2815. ” J. E. Critchlow J.C.S. Furuduy I 1972 68 1774. ” W. P. Jencks Chem. Rev. 1972 72 705. ” R. A. More O’Ferrall J . Chem. SOC. (B) 1970 274. 7 8 W. P. Jencks J . Amer. Chem. SOC. 1972 94 4731. 7 9 R. F. Pratt and T. C. Bruice J . Org. Chem. 1972 37 3563. *’ E. A. Symons and E. Buncel J . Amer. Chem. SOC. 1972,94 3641.94 4729 128 J. R. Jones an initial slope of 0.23 which increases to 0.36 in the more basic solutions. The corresponding plot (although over a much narrower H - range) for the detritiation of chloroform" has a slope of unity compared with 0.7 for 1,6dicyanobutene. This result explains why general-base catalysis was only observed for the latter and is consistent with the primary isotope effects observed (kJkD)OH- = 3.5 for the cyanocarbon and 1.4 for chloroform. Bowden and Cookg2 have correlated the rates of hydroxide-catalysed iso-merization of a series of 3- and 4-substituted allylbenzenes as well as 1,3,3-triphenylprop-1-yne in aqueous dimethyl sulphoxide solutions with the H -values. The results of substituent effects kinetic hydrogen isotope effects and the slopes of the log k versus H - plots are all consistent with the proposed mechan-ism involving rate-determining proton abstraction.Several reactions in concen-trated sodium methoxide-methanol solutions however provide no example of a direct correlation between reaction rate and either the H - function orstoicheio-metric base con~entration.~~ In fact the best relationship is between log k and H - - pKMeoH - log (CMeO-/CMeOH) the slopes being related to the transition-state structure for the particular reaction. Large increases in the rates of hydrolysis and methanolysis of cyclic sulphate and sulphonate esters in highly basic media have been reported.84 Such findings have usually been ascribed to either the desolvation of the hydroxide ion or to the superior ability of the dipolar aprotic solvent to solvate the transition state.As the rate enhancements are generally accompanied by large decreases in the enthalpy of activation in the dipolar aprotic solvent relative to the polar protic solvent the two explanations can be subjected to an experimental test.85 The difference in the enthalpies of the reactants in the two kinds of solvents (6 AH;) can be determined calorimetrically and if the first explanation is correct this should then be equal to the difference in the enthalpies of activation (AH*) in the two solvents. In a particular example it turns out that the enthalpy of transfer of the reactants from the dipolar solvent to the protic solvent is three times as great as the differences in the AH* values in the two kinds of solvent.The H - values for sodium glycoxide-thylene glycol solutions using t-butyl-phenols as indicators are lower than when nitroanilines and diphenylamines are used,86 and an attempt has been made to explain the different activity-coefficient behaviour of the indicators. The effect of adding some protic and dipolar aprotic solvents to this system is to increase the H - values the order of effectiveness being DMSO > Me,CHO > Bu'OH > Me,CO > MeCN > MeOH.87 An H-scale for methanolic sodium methoxide solutions (up to 3 moll- ') has been con-structed from the ionization of 1,3-di~henylindene~~ and a J acidity function '' Z . Margolin and F. A. Long J . Amer. Chem. SOC. 1972 94 5108. 8 2 83 84 J . H. Smith T. Inone and E. T. Kaiser J .Amer. Chem. SOC. 1972,94 3098. 8 5 P. Haberfield J. Friedman and M. F. Pinkston J . Amer. Chem. SOC. 1972 94 71. 8 6 L. Aiyar A. N. Datta and K. K. Kundu J . C . S . Perkin ZZ 1972 1046. '' K. K. Kundu and L. Aiyar J . C . S . Perkin ZI 1972 715. K. Bowden and R. S. Cook J . C . S . Perkin / I 1972 1407. R. A. More O'Ferrall J . C . S . Perkin IZ 1972 976 The Ionization of Carbon Acids 129 for methanol4imethyl sulphoxide mixtures containing NaOMe (0.1 moll- ) in respect of methoxide addition to substituted anisoles.88 Meisenheimer Complex Formation.-In the reaction of aromatic nitro-compounds with bases proton abstraction is the least well-characterized process. The formation of covalently bonded adducts (Meisenheimer or o-complexes) is far more common and several papers bearing on both the kinetic and equilibrium aspects have been published.The stopped-flow method has been used to study the interaction of 4-methoxy-3,5-dinitr~pyridine'~ and 2-chloro-4,6-dinitro-anisole" with methoxide ions in methanol-dimethyl sulphoxide solutions. The equilibrium constant between 1,3,5-trinitrobenzene and hydroxide ions has been studied as a function of medium composition for the dimethylformamide-water system and found to vary from 3 1 mol- ' in purely aqueous solution to greater than lo5 1 mol- in 50 mol % dimethylformamide mainly because of the increasing desolvation of the hydroxide ion.' ' Equilibrium constants between several substituted anisoles and methoxide ion have also been determined,92 and in the case of 3,5-dinitropyridineg3 the Meisenheimer complex is more stable than that formed between trinitrobenzene and methoxide ion.Further aspects of the stabilities of these complexes have also been discussed9L96 and in one case97 the heat of formation has been determined. The first case of Meisenheimer complex formation involving an aromatic rather than an aliphatic amine has also been rep~rted.'~ Miscellaneous.-In the hydration of chloral in methan01:~ the order with respect to the solvent is three similar to that previously estimated for addition of water to various carbonyl compounds. Thermodynamic and activation parameters have been reported loo for the reversible hydration of 1,3-dichloroacetone in dioxan and in the corresponding reaction of a series of ring-substituted tri-fluoroacetophenones in dimethyl sulphoxide-water and sulpholane-water mix-tures"' the latter have a dehydrating effect relative to water.In mixtures of water and dimethyl sulphoxide down to 15 mol % water they are more hydrating with respect to the carbonyl group than is pure water. The rate of the uncatalysed hydration of 4-methoxytrifluoroacetophenone in aqueous sulpholane drops drastically as the water content of the medium decreases. 8 8 M. R. Crampton M. A. E. Ghariani and H . A. Khan J.C.S. Perkin ZZ 1972 1178. 8 9 F. Terrier A. P. Chatrousse and R. Schaal J . Org. Chem. 1972 37 3010. 90 F. Terrier F. Millot and R. Schaal J.C.S. Perkin ZZ 1972 1192. 9 L E. A. Symons and E. Buncel Canad. J . Chem. 1972,50 1729. 9 2 M. R. Crampton and H. A. Khan J.C.S. Perkin ZZ 1972 1173.9 3 A. P. Chatrousse and F. Terrier Bull. SOC. chim. France 1972 4549. 9 4 M. P. Simonin M. L. Lecourt F. Terrier and C. A. Dearing Canad. J . Chem. 1972, 9 5 9 6 M. R. Crampton and H. A. Khan J.C.S. Perkin ZZ 1972 2286. 9 7 J. W. Larsen K. Amin S. Ewing and L. L. Magid J . Org. Chem. 1972,37 3857. 99 R. P. Bell and D. G. Horne J.C.S. Perkin IZ 1972 1371. l o o R. P. Bell and P. E. Sorensen J.C.S. Perkin 11 1972 1740. l o ' R. Stewart and J. D. Van Dyke Canad. J . Chern. 1972,50 1992. 50 3558. M. R. Crampton and H. A. Khan J.C.S. Perkin ZZ 1972 733. E. Buncel and J. G. K. Webb Canad. J . Chem. 1972,50 129 130 J . R. Jones When the iodination of o-carboxyacetophenone is carried out in self-buffered solutions the rate can be attributed solely to intramolecular proton transfer from the acetyl group to the carboxylate group.'02 In the mutarotation of 2,3,4,6-tetramethyl a-D-glucose in benzene and cyclohexane micellar catalysis leads to a considerable rate enhan~ernent,"~ as has been found in other ' 0 5 4 Kinetic Isotope Effects The theoretical interpretation of isotope effects in such diverse fields as vibrational spectroscopy gas-phase equilibrium constants and reaction kinetics has been reviewed.'06 An increasing use is being made of models in calculating isotope effects e.g. in SN2 displacement reactions :lo' Y + REH,X -+ Ty . ? a REH .? XI' -+ R?H,Y + X, The carbon isotope effect goes through a maximum as a function of n the bond order of the Y - . . C bond supporting the qualitative suggestion made previously by Fry'08 that a reaction of this type can be viewed as an 'RCH,' group transfer from X to Y with mechanistic implications similar to those of hydrogen-transfer reactions.The chlorine isotope effect on the other hand increases continuously as one goes from a reactant-like to a product-like transition state. Model calculations log indicate that for reactions exhibiting reasonable primary hydrogen isotope effects the effective lower limit to the pre-exponential ratio A d A is -0.7-0.5 thereby lending support to the common procedure of inter-preting experimental values lower than this to the operation of tunnelling effects. Calculations of primary hydrogen isotope effects in the racemization of 2-methyl-3-phenylpropionitrile show that very low values may be obtained for highly unsymmetrical transition states in line with the experimental results and the product-like transition state.' lo The kinetic hydrogen isotope effect for the hydroxide-catalysed ionization of (d)-phenylmethylacetophenone has been studied' ' ' as a function of changing medium basicity by increasing the proportion of dimethyl sulphoxide in the solvent; kJkT passes through a clearly defined maximum at an H - of 16.5, corresponding to ApK = 0.The Bronsted exponent /? is 0.49 for both isotopes and the activation energy difference E - E reaches a maximum value at an * l o ' R. P. Bell B. G. Cox and J. B. Henshall J.C.S. Perkin IZ 1972 1232. J. H. Fendler E. J. Fendler R. T. Medary and V. A. Woods J. Amer. Chem. SOC., 1972,94 7288. J.H. Fendler and R. R. Liechti J.C.S. Perkin IZ 1972 1041. C. A. Bunton and S. K. Huang J. Org. Chem. 1972,37 1790. I o 6 M. Wolfsberg Accounts Chem. Res. 1972 5 225. l o ' L. B. Sims A. Fry L. T. Netherton J. C. Wilson K. D. Reppond and S. W. Crook, J. Amer. Chem. SOC. 1972,94 1364. ''* A. Fry Pure. Appl. Chem. 1964 8 409. M. E. Schneider and M. J. Stern J . Amer. Chem. SOC. 1972 94 1517. ' l o N A. Bergman W. H. Saunders jun. and L. Melander Actu Chem. Scund. 1972, 26 1130. "' D. W. Earls J. R. Jones and T. G. Rumney J.C.S. Furuduy I 1972 68 925 The Ionization of Carbon Acids 131 H - of 16.8. The pre-exponential ratios AH/AT reflect the importance of solvent-reorganization contributions. A quantitative model ' I 2 that was developed in order to investigate the importance of such factors in proton-transfer processes predicts that reactions in which the activated complex has a non-equilibrated environment should be rare and that when they do occur the deviation of solvent configuration from its equilibrium state is expected to be toward that configuration which is appropriate for an internal structure in which the proton is half transferred.Although tunnelling seems to be unimportant in the hydroxide-catalysed ionization of both 2,4-dimethylpentan-3-one and 3,5-dimethylheptan-4one,' l3 the rate of hydrogen-atom abstraction from solid acetonitrile at 77-47 K pro-ceeds almost totally via quantum-mechanical tunnelling.' l4 From a mass spectral study of the dedeuteriation of [2H6]acetone it is claimed'15 that the primary hydrogen isotope effect is considerably lower than a previously determined value.Isotope effects have been measured in the pyrolysis of esters,l16 in the acid-catalysed exchange of several indoles ' '* ' and in the protonation of olefinic substrates.' Schowen'20 has considered at length the mechanistic deductions that may be made from a study of solvent isotope effects. Similarly Albery and Davies12' have discussed what mechanistic conclusions may be drawn from the curvature of solvent isotope effects as obtained from studies in H20-D20 mixtures. Their findings should facilitate the interpretation of the curvature and may be parti-cularly useful in distinguishing single parallel and consecutive transition states. The observed hydroxide ion isotope effect kgho/kD,&o = 0.72 for the detritia-tion of 1,4-dicyanobut-2-ene1 22 has been separated into a secondary kinetic isotope effect kEfP_/kg&o = 0.57 and a secondary solvent isotope effect kg&o/ gho = 1.27.The effect of changing the solvent from H 2 0 to D20 on the rates of ionization of 2-nitropropane as well as the change in K have been quanti-tatively explained'23 on the basis of the formula OH;(H,OH,) for the aqueous hydroxide ion in which b and c denote non-equivalent positions and where it is assumed that different fractionation factors apply to the three hydrogen sites (4a z 1.2-1.5 +, N 0.654.7 4c z 1). ' l 2 J. L. Kurz and L. C. Kurz J . Amer. Chem. SOC. 1972 94 4451. l ' ' R. A. Lynch S. P. Vincent Y . T. Lin L. D. Smucker and S. C. Subba Rao J. Amer.Chem. SOC. 1972,94,8351. R. J. Le Roy E. D. Sprague and F. Williams J. Phys. Chem. 1972 76 546. 'I5 J. Hine J. C. Kaufmann and M. S. Cholod J . Amer. Chem. SOC. 1972,94,4590. R. Taylor J. C.S. Perkin ZI 1972 165. B. C. Challis and E. M. Millar J.C.S. Perkin IZ 1972 11 16. B. C. Challis and E. M. Millar J.C.S. Perkin 11 1972 1618. Phys. Chem. 1972,76,295 1. * ' W. J. Albery and M. H. Davies J.C.S. Furuduy I 1972 68 167. E. A. Walters and F. A. Long J . Phys. Chem. 1972,76 362. V. Gold and S. Grist J.C.S. Perkin 11 1972 89. ' I 9 M. M. Kreevoy R. Eliason R. A. Landholm T. S. Straub and J. L. Melquist J. ' 2 o R. L. Schowen. Progr. Phys. Org. Chem. 1972 9 275 132 J. R. Jones 5 Labelled Carbon Acids With the increasing use being made of labelled compounds any improvements in existing methods of preparation or the discovery of new ones are to be greatly welcomed.It is frequently the case that conventional homogeneous and hetero-geneous catalysts require elevated temperatures and reaction times of hours before equilibrium is reached. However it has been reported'24 that a new range of highly active catalysts - metal halides of the type MoCl WCl AlCl,, and SbCl - readily catalyse the exchange between two aromatic molecules such as C,D and toluene. The reaction is characterized by the apparent absence of steric effects and complicating side-reactions. The discovery that organo-aluminium dihalides such as ethylaluminium dichloride catalyse very rapid exchange of hydrogen atoms between aromatic nuclei is an attractive alternative method of deuteriation. 2 5 The same organoaluminium dihalide catalysts with tritiated water as the isotope source and catalyst promoter may be used for instantaneous tritium labelling.' 26 12' J. L. Garnett M. A. Long R. F. W. Vining and T. Mole J.C.S. Chem. Cornm. 1972, 1172. J. L. Garnett M. A. Long R. F. W. Vining and T. Mole J . Amer. Chem. Sac. 1972, 94 5913. M. A. Long J. L. Garnett R. F. W. Vining and T. Mole J . Amer. Chem. SOC. 1972, 94 8632