Monoselective Alkylation of Primary Amines Under Simple Conditions: Only Amine and Alkyl Bromide in the Reaction Vial

Abstract Selective alkylation of primary amines is an important chemical transformation because amines are constituents of natural products, pharmaceuticals, agrochemicals, and are important synthetic intermediates. We have shown that selective monoalkylation can be achieved using simple equipment and reaction conditions: amine and alkyl bromide in a 3:1 molar ratio in a reaction vial, heated in a laboratory oven if necessary. The scope of the reaction was investigated using various primary, secondary, and tertiary bromides and amines having nitrogen attached to primary, secondary, and tertiary carbon atoms. In the case of the aromatic amine, the reaction was carried out on silica gel in the solid state. Monoselectivity ranges from 53/47 to 100/0 and yield of secondary amines from 24%–87%.