New investigations of the reaction of epichlorohydrin with hindered amines: X-ray and NMR analyses

Abstract

During the synthesis of a series of new antiarhythmic drugs, the reaction between epichlorohydrin and hindered amines was reinvestigated. With primary amines, 3-azetidinols were formed in fair yields. The X-ray structure elucidation of one of these compounds (1: P21/n, a = 17.210, b = 6.665, c = 23.585, β = 102.29, and R = 0.064 for 2005 observed reflections) and NMR studies led to the conclusion that both the hydroxy group and the bulky nitrogen substituent are on the same side of the azetidine ring. With secondary amines, the reaction was very complex, leading to diamino dioxane, diamino alcohols, amino alcohol ethers, and one glycol. X-ray analysis and 1H and 13C NMR studies allowed complete assignments for all compounds. All but one exhibited a slow interconversion of the nitrogen visible in the 13C NMR spectra. Keywords: epichlorohydrin, hindered amines, azetidinol, adamantane, alkanol amines.