Novel and efficient method for esterification, amidation between carboxylic acids and equimolar amounts of alcohols, and amines utilizing Me 2NSO 2Cl and N, N-dimethylamines; its application to the synthesis of coumaperine, a natural chemopreventive dieneamide

Abstract

Various carboxylic esters or amides were prepared in good to excellent yield between carboxylic acids and equimolar amounts of alcohols or amines under very mild conditions (0–45°C; within 3 h) using dimethylsulfamoyl chloride (Me 2NSO 2Cl; 1 ) combined with N, N-dimethylamines (Me 2NR: 2a ; R=Me, 2b ; R=Bu). The choice of the sulfamoyl chloride and the amine is crucial for the reaction; that is, sterically uncrowded amines accelerated the present esterification and amidation. This agent had some advantages over methanesulfonyl chloride ( 3 )/amines as for the atom-economy, avoidance of side reactions, and had very high chemoselectivity toward the carboxyl group vs the hydroxyl group; the experiment was performed by the addition of 1 to the mixture of carboxylic acids and alcohols. Application of this method to the synthesis of coumaperine, a chemopreventive natural product, was performed using the present amidation as a key step.