Kinetics and mechanism of hydroxy group acetylations catalyzed by N-methylimidazole

The kinetics of acetylation of alcohols by acetyl chloride and acetic anhydride, with N-methylimidazole as the catalyst, were studied in acetonitrile solution at 25 degrees; some measurements were also made with 4-dimethylaminopyridine as the catalyst. The acetic anhydride-N-methylimidazole system proceeds entirely by a general base catalysis, whereas the acetyl chloride-N-methylimidazole system reacts entirely via a nucleophilic route, with the intermediate formation of the N-acylated catalyst. The reaction of this intermediate with the alcohol is general base catalyzed. The acetyl chloride-4-dimethylaminopyridine system also reacts via the nucleophilic route. In the acetic anhydride-4-dimethylaminopyridine system a small fraction of the intermediate was detected. The acetic anhydride-N-methylimidazole system was studied in n-propanol-acetonitrile solvent mixtures; no spectral evidence for intermediate formation was seen. However, the hydrolysis reaction in acetic anhydride-N-methylimidazole, studied over a wide range of water-acetonitrile mixtures, revealed a change in mechanism from general base in dry acetonitrile to a solely nucleophilic route at high water concentrations.