A Comparative Study on the Hydrolysis of Acetic Anhydride and N,N-Dimethylformamide: Kinetic Isotope Effect, Transition-State Structure, Polarity, and Solvent Effect

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Recent studies have shown that general-base assisted catalysis is a viable mechanistic pathway for hydrolysis of smaller anhydrides. Therefore, it is the central purpose of the present work to compare and contrast the number of hydrogen atoms in-flight and stationary in the transition state structure of the base-catalyzed mechanisms of 2 hydrolytic reactions as well as determine if any solvent effects occur on the mechanisms. The present research focuses on the hydrolytic mechanisms of N,N-dimethylformamide (DMF) and acetic anhydride in alkali media of varying deuterium oxide mole fractions. Acetic anhydride has been included in this study to enable comparisons with DMF hydrolysis. Comparative studies may give synergistic insight into the detailed structural features of the activated complexes for both systems. Hydrolysis reactions in varying deuterium oxide mole fractions were conducted in concentrations of 2.0M, 2.5M, and 3.0M for DMF and 0.10M for acetic anhydride at 25°C. Studies in varying deuterium mole fractions allow for proton inventory analysis, which sheds light on the number and types of hydrogen atoms involved in the activated complex. For these systems, this type of study can distinguish between direct nucleophilic attack of the hydroxide ion on the carbonyl center and general-base catalysis by the hydroxide ion to facilitate a water molecule attacking the carbonyl center. The numerical data are used to discuss 3 possible mechanisms in the hydrolysis of DMF.