Selective Modification of Carboxylic Acids with Oximoyl Chlorides under Aqueous Conditions

A carboxy group-selective modification method using an oximoyl chloride has been developed. In aqueous conditions at neutral to basic pH, the oximoyl chloride efficiently generates a nitrile oxide that reacts with a carboxylic acid to form an <i>O</i>-acylhydroxamic acid. The reaction of the nitrile oxide with the carboxylic acid is accelerated in water. The resulting <i>O</i>-acylhydroxamic acid can be further modified through aminolysis or photochemical decarboxylation under these aqueous conditions. The reaction is selective for carboxy groups and largely unaffected by other nucleophilic functional groups such as hydroxy, amino, and imidazolyl groups. This reaction could be applied to selective modification of carboxy groups of biomolecules in aqueous buffer.