Alkaline hydrolysis of N-methylazetidin-2-one. Hydration effects

Abstract Semiempirical calculations (PM3) have been used to investigate the reaction mechanism (B AC2 ) of the alkaline hydrolysis of N -methylazetidin-2-one. This mechanism involves the nucleophilic attack of a hydroxyl ion on the carbonyl carbon to give a tetrahedral complex followed by cleavage of the CN bond and proton transfer to form the final product. The influence of the solvent in this process has been analyzed using the supermolecular approach with a water solvation sphere of 20 molecules around the solute. The results obtained have been compared with those based on a continuum treatment of the solvent with semiempirical and ab initio methodology. The potential barrier of 17.5 kcal mol −1 due to the attack of the nucleophile is very close to the experimental value (16.1 kcal mol −1 ) and the final product is about 52 and 27 kcal mol −1 more stable than the reactives and the tetrahedral intermediate, respectively.