Formation of carboxamides by direct condensation of carboxylic acids and amines in alcohols using a new alcohol- and water-soluble condensing agent: DMT-MM

Selective formation of carboxamides in an alcohol or water by an exceptiona lly convenient one-step procedure in which a condensing agent is simply add ed to a mixture of acids and amines has been achieved successfully by using a new condensing agent, 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorph olinium chloride (DMT-MM). Activation of carboxylic acids by DMT-MM in the presence of amines and subsequent aminolysis of the resulting acyloxytriazi ne in alcoholic solvents occurred selectively and led to the formation of c arboxamides in excellent yields. The rate of aminolysis of the acyloxytriaz ine intermediate can be estimated to be about 2x10(4) times greater than th at of methanolysis. The amide/ester selectivity observed using DMT-MM was m uch larger than that obtained with DCC or EDC. Condensation of polar substr ates, such as amino acid esters and their hydrochlorides, glucosamine hydro chloride, sodium acetate and dicarboxylic acids, proceeded successfully in MeOH, water or aqueous MeOH in good yields. The present reaction is technic ally quite simple and easy to achieve. It proceeds by simple mixing of acid s, amines and DMT-MM without any additives, and the MeOH is readily removab le by a rotary evaporator after completion of the reaction. (C) 2001 Elsevi er Science Ltd. All rights reserved.