Nucleophilic Reactivities Toward Substituted Aryl Trimethylacetates: Conflicting Steric Effects of Ground-State Activation and Transition-State Crowding

The hydroxide ion and imidazole catalyzed hydrolyses of a series of leaving-group-substitued aryl trimethylacetates have been studied at 25 °C in 10% (v/v) acetonitrile-water. The p value for hydroxide ion catalysis (vs. σ) is 0.99, with a low correlation coefficient (r = 0.962). The Brønsted plot for dependence of log K_ho^- on the pK_a of the conjugate acid (slope, β_lg) indicates that 2,3-dimethylphenyl trimethylacetate is some 25-fold less reactive than predicted; 2-chloro-4-nitro- and 2,4-dinitrophenyl esters are 3.5- and 5-fold inhibited, respectively. These deviations are ascribed to steric hindrance. Imidazole catalysis is nucleophilic even for esters with ortho substituents and the β_lg value was −1.16, indicating a high dependence on leaving group pK_a. The transition state for imidazole catalysis is suggested to incorporate some degree of bond cleavage between the acyl and leaving groups. The unusually high reactivity of trimethylacetylimidazole toward imidazole is suggested to be caused by steric destruction of resonance in the ground state.