STERIC EFFECTS IN THE HYDROLYSIS REACTIONS OF N-ACYLIMIDAZOLES - EFFECT OF ARYL SUBSTITUTION IN THE LEAVING GROUP

The kinetic and mechanistic effects of aryl substitution in the leavin g group have been determined in the hydrolysis reactions of N-acylimid azoles. N-Acyl derivatives of 2,4,5-triphenylimidazole hydrolyze rapid ly in OH- and water reactions. The latter reactions are pH independent from pH 4 to 9. The N-acetyl derivative hydrolyzes with rate constant s similar to those of N-acetylimidazole in the OH- reaction but 40-fol d larger in the pH-independent re action. N-(trimethylacetyl)-2,4,5-tr iphenylimidazole hydrolyzes at 15 degrees C with k(OH), the second-ord er rate constant for the OH- reaction, 26-fold larger than the rate co nstant for alkaline hydrolysis of the corresponding N-acetyl derivativ e, even though steric hindrance to approach of a nucleophile is extrem e in the former reaction. The pH-independent reaction of the N-trimeth ylacetyl compound is 4-fold faster than that of the N-acetyl derivativ e and is characterized by a D2O solvent isotope effect (k(H2O)/k(D2O)) of 2.0. A phenyl substituent in the 2-position of the imidazole ring exerts a small rate-retarding effect in the hydrolysis reactions. N-(T rimethylacetyl)-4,5-diphenylimidazole hydrolyzes 10- and 55-fold faste r in the OH- and water reactions, respectively, at 15 degrees C, than N-(trimethylacetyl)benzimidazole at 30 degrees C, although the pK(a) o f the leaving group is identical in the two cases. The additive nature of the steric rate-accelerating effects in the acyl group and the lea ving group indicates an effect on the ease of C-N bond breaking; the h ydrolysis reactions very Likely proceed in a concerted manner without the formation of a stable tetrahedral intermediate.