Isotope effects in nucleophilic substitution reactions XI.: The effect of ion-pairing, substituents, and the solvent on SN2 transition states

The secondary alpha deuterium and primary leaving group nitrogen KIEs and Hammett rho 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 degrees 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 LI SN2 transition state. Ion-pairing shortens the weaker sulfur - alpha carbon (S-C-alpha) transition state bond significantly but does not alter the stronger alpha carbon leaving group (C-alpha-N) transition state bond as the bond strength hypothesis predicts. However, the effect of ion pairing, i.e., the decrease in the S-C-alpha bond on ion-pairing, decreases as a more electron-withdrawing substituent is added to the nucleophile, and the S-C-alpha bond actually increases when the nucleophile is the p-chlorothiophenoxide ion. The identical Hammett rho 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-alpha 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 rho 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.