Alkylation of amines. New method for the synthesis of quaternary ammonium compounds from primary and secondary amines

A new method for the preparation of quaternary ammonium compounds by complete alkylation of primary or secondary amines to their quaternary stage in a one-step procedure is described. The observation that protonation of sterically hindered amines is only slightly affected by steric hindrance, whereas nucleophilicity as measured by the rate of alkylation is considerably decreased, is synthetically utilized. An organic base of greater base strength than the reactant amines is employed to bind the acid generated inalkylation reactions. Thus, a number of aniline derivatives are methylated in the presence of the stronger, but sterically hindered base 2,6-lutidine. The mild and homogenous reaction conditions result in good yields with minimal laboratory manipulations and effort. The method is particularly of importance in reactions where the amines and the alkylating agents possess labile functions.