Isotope effects in nucleophilic substitution reactions XI. The effect of ion-pairing, substituents, and the solvent on S N 2 transition states

The secondary alpha deuterium and primary leaving group nitrogen KIEs and Hammett ρ values found for the free ion and ion-pair S N 2 reactions between benzyldimethylphenylammonium ion and sodium para-substituted thiophenoxides in methanol at 20.000°C show how (i) ion-pairing of the nucleophile, (ii) a change in substituent in the nucleophile, and (iii) a change in solvent alters the structure of a Type II S N 2 transition state. Ion-pairing shortens the weaker sulfur - alpha carbon (S—C α ) transition state bond significantly but does not alter the stronger alpha carbon - leaving group (C α —N) transition state bond as the bond strength hypothesis predicts. However, the effect of ion pairing, i.e., the decrease in the S—C α bond on ion-pairing, decreases as a more electron-withdrawing substituent is added to the nucleophile, and the S—C α bond actually increases when the nucleophile is the p-chlorothiophenoxide ion. The identical Hammett ρ values of -0.85 and -0.84 for the free ion and ion-pair reactions, respectively, may be observed because, on average, the S—C α bonds are identical in the free ion and ion-pair transition states. When a more electron-donating substituent is added to the nucleophile, an earlier transition state is found in both the ion-pair and free ion reactions. However, the substituent effect is smaller in the ion-pair reactions, presumably because the change in the negative charge on the sulfur atom with substituent is greater in the free ion than in the ion-pair. The substituent effect on transition state structure suggested by the KIEs is not predicted by any of the theories that are used to predict substituent effects on S N 2 reactions. Both the secondary alpha deuterium and primary leaving group nitrogen KIEs and the Hammett ρ values indicate that the transition state is earlier when the solvent is changed from DMF to methanol as the "solvation rule for S N 2 reactions" predicts. This probably occurs because an earlier, more ionic, transition state is more highly solvated (more stable) in methanol.Key words: nucleophilic substitution, S N 2, isotope effect, transition state, substituent, ion-pair.