Reactions of N-(o-carboxybenzoyl)-L-leucine: intramolecular catalysis of amidehydrolysis and imide formation by two carboxy groups

Abstract

The intramolecular reactions of N-(o-carboxybenzoyl)-L-leucine (1) were studied in aqueous solution, as a function of the hydrogen ion concentration. Two competing reactions were observed: i) cyclization to form the imide N-phthaloylleucine, and ii) hydrolysis of (1) to phthalic acid and leucine. Individual rate constants for cyclization and hydrolysis were obtained from the overall rate constants and product distributions. Imide formation predominates under highly acidic conditions (H₀ < −1) and hydrolysis in the H₀ > −1 to pH 5 range. In the hydrolysis reaction, the neighbouring carboxy group participates nucleophilically and in the pH 3–5 range there is a requirement for participation of the second carboxy group as a general acid. Imide formation also requires participation of two carboxy groups in the pH 2–5 range, and shows a bell-shaped pH–rate constant profile. Possible mechanisms for these reactions are discussed.