ON THE SYNTHESIS OF MONO AMIDES OF 18-CROWN-6-TETRACARBOXYLIC ACID

The synthesis of monoamides of (R,R,R,R)-18-crown-6-2,3,11,12-tetracar boxylic acid via reaction of primary and secondary amines with the cro wn ether bis-anhydride is explored. One equivalent of benzylamine gave a quantitative yield of a diamide, and the recovered crown ether suff ered epimerization. The expected monoamide was prepared via initial pa rtial hydrolysis of the bis-anhydride followed by benzylamine addition . The initial hydrolysis method fails for secondary amines, as nucleop hilic attack is not competitive with epimerization. As a consequence, the stereochemical integrity of the starting material is lost and amid e ester derivatives of this important framework crown ether are inacce ssible by direct refunctionalization.