Studies on the use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline for the synthesis of acylamino acid anilides and p-nitroanilides

Abstract

The use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) for coupling acyl-L-amino acids with aniline and p-nitroaniline has been investigated. Optically pure anilides are obtained in good yield but partial racemization occurred in one case. p-Nitroanilides cannot be obtained under similar conditions but if the reaction solvent is removed and the residue left for several days, coupling occurs giving a racemic product in moderate yields. Reaction mechanisms are proposed on the basis of isolated and characterized intermediates. It has been found that N-benzoylamino acid anilides and p-nitroanilides are cleaved within a few minutes by hydrogen bromide in acetic acid to give the N-benzoylamino acid and the amine.