Intramolecular Imidazole-Promoted General-Base Catalysis of the Hydrolysis of an Acetylimidazole

Article abstract of DOI:10.1021/jo00383a007

Intramolecular general-base catalysis of the hydrolysis of an acetylimidazole by imidazole is assessed by studying the hydrolysis of 2-(imidazol-2-ylmethyl)-N-acetylimidazole (3).The pH vs. log k_obsd profile exhibits three major domains that consist of H2O attack on the protonated acetylimidazolium unit,OH^- attack on the neutral material, and an intramolecular general-base catalysis of H2O on the neutral species.Consistent with the latter is a plateau observed in the pH profile (k₃ = 1.02*10^-3 s^-1) at neutrality and a solvent kinetic isotope effect of k_H2O/k_D2O = 2.8 in that region.The effective molarity of the intramolecular imidazole in 3 can be assessed by comparing the value of k₃ with the second-order rate constant for 2-methylimidazole catalyzing the hydrolysis of 2-methyl-N-acetylimidazole (4).After the difference in the imidazole pK_a values is corrected for, the effective molarity of the intramolecular catalyst is 3 M.