Catalytic reductive aminations using molecular hydrogen for synthesis of different kinds of amines.

Abstract

This review systematically examines catalytic reductive amination reactions that employ molecular hydrogen as the reducing agent. By coupling carbonyl substrates—aldehydes or ketones—with ammonia, amines, or nitro compounds under hydrogen pressure in the presence of appropriate catalysts, a broad spectrum of primary, secondary, tertiary, and N-methylamines can be accessed. Both homogeneous and heterogeneous catalytic systems are surveyed, with particular attention to selectivity challenges such as over-alkylation and undesired carbonyl reduction to alcohols. Mechanistic aspects governing product selectivity and side-reaction pathways are discussed in detail. The scope encompasses benzylic, heterocyclic, and aliphatic amine targets, including complex drug-like molecules relevant to pharmaceutical, agrochemical, and life-science applications. The review underscores the importance of developing efficient, selective catalysts for cost-effective and sustainable amine production at both laboratory and industrial scales.

Mechanism

Carbonyl compounds condense with amine sources on a catalyst surface to form imine intermediates, which are subsequently hydrogenated by molecular hydrogen to yield the target amine. Over-alkylation and direct carbonyl reduction to alcohols represent the principal competing side reactions.