Catalytic Continuous Reductive Amination with Hydrogen in Flow Reactors

Abstract

Reductive amination with hydrogen is a green and atom‐efficient method to construct amines from accessible aldehydes and ketones. Flow reactors, with superior mass and heat transfer rate because of higher specific surface area, have emerged as a powerful tool to conduct reductive amination with high efficiency and selectivity. This article discusses the influence of catalysts, solvents, temperatures, additives, and substrate properties on reductive amination. Following this, a summary of research on reductive amination with hydrogen in flow reactors is provided. The investigations were classified based on distinct nitrogen sources, encompassing the use of ammonia, amines, and nitro compounds. Based on the influencing factors and reaction cases, the article analyzes the enhancement effects of temperature control, mass transfer intensification, and residence time distribution in flow reactors on the reductive amination. Finally, the article gives a conclusion by addressing challenges and prospects for further developments in this field.

Reductive N-Alkylation of Amines with Ketones Using Heterogeneous Polysilane–Palladium Catalysts under Continuous-Flow Conditions

“…Continuous-flow hydrogenation reactions with heterogeneous catalysts enhance reactivity due to the efficient and direct contact between the solid catalyst and H 2 gas. − While flow methods have been applied in reductive N-alkylation with H 2 and heterogeneous catalysts for ketones, including an asymmetric reaction, − harsh conditions and/or additives were often required to promote intermediate formation, and applicable substrates were limited. Our group previously established continuous-flow reductive N-alkylation using a heterogeneous Pt/C catalyst under relatively mild conditions; however, a high reaction temperature was still necessary when using a ketone substrate .…”