pKa-Dependent Formation of Amides in Water from an Acyl Phosphate Monoester and Amines

Acyl phosphate monoesters are readily prepared biomimetically activated anionic derivatives of carboxylic acids that react rapidly with amines in water to form amides. A plot of the logarithms of the rate constants for the reactions of a series of primary amines with benzoyl methyl phosphate depends on the pKa of the conjugate acids of the amines (beta(nuc) approximately 0.9). This provides a simple and quantitative basis for regioselective acylation with these reagents.