Base strength isotope effects

The log rate versus acid strength curve for the latter compound is of the exact form expected for reactions of the free base, whilst that of the former compound is intermediate between this form and that obtained for the nitration of aniline and phenyltrimethylammonium ion, i.e. compounds which react as positive species. That these compounds react mainly or entirely via the free base is also indicated by the comparison of the rate coefficients in Table 8 with those in Table 5, from which it can be seen that the nitro substituent here only deactivates weakly, whilst the chloro substitutent appears to activate. In addition, both compounds show a solvent isotope effect (Table 9), the rate coefficients being lower for the deuterium-containing media, as expected since the free base concentration will be lower in these. 

Methods for determining permanent dipole moments and polarizabilities can be arbitrarily divided into two groups. The first is based on measuring bulk phase electrical properties of vapors, liquids, or solutions as functions of field strength, temperature, concentration, etc. following methods proposed by Debye and elaborated by Onsager. In the older Debye approach the isotope effects on the dielectric constant and thence the bulk polarization, AP, are plotted vs. reciprocal temperature and the isotope effect on the polarizability and permanent dipole moment recovered from the intercept and slope, respectively, using Equation 12.5. 

The ratio of products (36) and (37) from VNS of hydrogen (Pe) and substimtion of halogen (Px), respectively (Scheme 4), will depend on the strength and concentration of base, provided that the elimination is a kinetically important step in the VNS reaction, namely Pr/Px = kikE[B]/k-ikx. The influence of base will decrease until a constant value Ph/Px = k /kx is reached as kslB] k i. This has been demonstrated for 4-chloronitrobenzene, which undergoes exclusive substimtion of chlorine unless strong base is present to favour the VNS process. The deuterium isotope effect for VNS hydroxylation by Bu OOH, determined as me ratio of H versus D substitution of l-deutero-2,4-dinitrobenzene, varied from 7.0 0.3 to 0.98 0.01 as the base in NH3 was changed from NaOH to Bu OK me former value is consistent with a rate determining E2 process. 

In the framework of equation 41, it may be observed that the desilylation of the intermediate arenium ion competes with the deprotonation process, so that a H/D kinetic isotope effect (KIE) is expected to arise when the MejSi"1" transfer competes with either H+ or D+ transfer. Indeed, kinetic isotope effects for the formation of silylated products arising from the different rates of H+ vs D+ transfer have been reported from the reaction of selectively D-labelled toluene and 1,2-diphenylethane or from mixtures of unlabelled and labelled substrates (Table l)121 —123. The kinetic isotope effects listed in Table 1 are the ones reported when the base used is Et3N. The use of bases of different strength to effect the H+ or D+ transfer should have an influence on the observed kinetic isotope effect. The role of the base on the values of the KIE was indeed verified in the competitive silylation of CH3C6H5/CD3C6D5 mixtures122. 

Only few authors discuss the really essential part of that work, namely a) the dependence of the measured overall values of k /kj> on the structure of the o-complex (steric crowding by neighbouring groups, C—N bond and C—H bond strength changes influenced by the electrophilidty of the benzenediazonium ion) and on the base B (concentration and structure of B). The intrinsic isotope effect, i.e. k n/kjo (isotope effect of the second step, i.e. equation 51) is, however, almost independent of these parameters. 

The characteristics of this mechanism are that (i) the attacking base and the substrate both take part in the rate-determining step, which has second-order kinetics overall (first-order in base and first-order in substrate) (ii) a large primary isotope effect is usually observed (iii) since the mechanisms of 5n2 and E2 differ much more than those of 5n1 and 1 reactions, the substitution/elimination ratio can be controlled in most cases by choosing appropriate conditions (iv) no rearrangement reactions are observed (v) the rate of elimination depends upon the strength of the base (vi) the stereospecificity of an E2 reaction depends on the conditions (see Section 5.1.2.4). 

With aqueous dimethyl sulphoxide (19-22, Table 9) the sudden increase in p, when considered in conjunction with the decrease in the sulphur isotope effect (Table 7, p. 204) suggests an increase in carbanion character. Further addition of dimethyl sulphoxide has little influence and the constancy ofp may reflect a delicate balance between the solvent effect on p and a gradual decrease in the extent of proton transfer as the strength of the base increases (Fig.4,p. 191)8" " . 

In the rearrangement of 1-protio- and I-deuterio-l,3-dimethylindene, the isotope effect tended to increase with increasing base strength of the catalyst. At 30°C, potassium / r/.-butoxide in tert,-buty alcohol, sodium methoxide in methanol and DABCO in methanol gave k lko ratios of 8.1, 6.7, and 4.8,... 

Many other examples could be cited which show a smooth variation of k /kP with the strength of the base, and in a few cases some indication of a maximum isotope effect when ApK (and hence the standard free energy change of the reaction) is close to zero. Such a maximum may well be concealed in the results for sodium propan-2-one-l-sulphonate in Table 25, since kP/k has almost the same value for reaction with 2,6-lutidine and hydroxide, for which ApK is -h7.4 and —2.0 respectively. One way of changing the value of Api is to modify the nature of the solvent, and in particular the addition of dimethyl sulphoxide to aqueous solutions containing hydroxide ions will displace the equilibrium SH-hOH"... 

Some areas which are not covered are isotope effects on proton and deuterium exchange with solvent, for example, the water-hydronium ion system (Saunders et al., 1984), deuterium isotope effects on acid and base strength (Halevi et al., 1979), on amino acids (Petersen and Led, 1979) and on hydration of cobalt (II) (Saunders and Evilia, 1985). Solvent-dependent isotope effects on equilibria involving hydrogen bonds in carbohydrates and... 

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