Amine catalyzed intramolecular imidization of alkyl and aryl phthalamates. Kinetics and mechanism in deuteriated chloroform

Abstract

The kinetics of the amine catalyzed intramolecular imidization of alkyl and phenyl phthalamates with a variety of amines were measured in deuteriated chloroform at 40.1 °C. An overall second-order kinetic rate law, rate =k_overall[amine][phthalamate], was obtained from our experiments. Although pre-association between the amides and the amines through hydrogen-bonding interaction was suggested by proton NMR spectroscopy, the catalytic ability of amines was found to be related to their basicity rather than to their hydrogen-bonding ability or nucleophilicity. This observation implies the involvement of proton transfer from the amide to the amine in the critical transition state. In addition, by changing the leaving group from phenoxy to butoxy group, the reaction rate constants decrease by a factor of 30 to 70. On the basis of these kinetic results, we propose that the intramolecular imidization proceeds through an amine assisted cyclization to a zwitterionic intermediate, followed by the expulsion of the alkoxy or phenoxy group to provide phthalimide and the corresponding alcohol.