How does organic structure determine organic reactivity? Nucleophilic substitution and alkene-forming elimination reactions of α-carbonyl and α-thiocarbonyl substituted benzyl derivatives

The effect of α-(N,N-dimethylcarbamoyl) and α-(N,N-dimethylthiocarbamoyl) substituents on the rate constants for partitioning of α-substituted 1-(4-methoxyphenyl)ethyl carbocations between nucleophilic addition of 50:50 (v:v) MeOH/H₂0 (k(s), s^-1) and deprotonation by this solvent (k(e), s^-1) have been investigated. The data show that these α-amide and α-thioamide substituents result in 80-fold and ≤ 30000-fold decreases, respectively, in k(s) for capture of the 4-methoxybenzyl carbocation by solvent, but that they lead to much smaller changes in k(e), for deprotonation of the corresponding α-substituted 1-(4-methoxyphenyl)ethyl carbocations by solvent. The large effect of the α-thioamide substituent on the partitioning of α-substituted 1-phenylethyl carbocations between formation of the products of solvolysis and elimination is therefore due primarily to the effect of this α-substituent on k(s), for capture of the carbocation by solvent. The results of experimental and computational studies are consistent with the conclusion that the relative magnitude of the rate constants k(s) and k(e) for partitioning of α-substituted 1-phenylethyl carbocations is strongly controlled by the relative thermodynamic stabilities of the neutral products of these reactions.