Flow Chemistry as an Enabling Technology for Process-Intensified Amination Reactions: A Decadal Review

Abstract

Amines are indispensable structural motifs in pharmaceuticals, agrochemicals, functional materials, and beyond, driving continuous demand for efficient synthetic methods. While established strategies like cross-coupling and reductive amination are prevalent, traditional batch processes often suffer from limitations in mixing, heat/mass transfer, safety, and scalability. Flow chemistry emerges as a powerful process intensification technology, offering enhanced transport properties, precise parameter control, and improved safety profiles, thereby presenting a highly efficient approach for amine synthesis. This review systematically summarizes representative advances in flow chemistry for amination reactions from 2015 onward. It encompasses a broad range of enabling scenarios (e.g., heterogeneous, thermally activated, and enzymatic amination, among others), analyzed through the lens of process intensification. This review also examines the development of novel continuous-flow amination processes and the study of reaction kinetics leveraging flow chemistry. By providing a consolidated reference on the field’s evolution over the past decade, this review aims to guide researchers toward developing more efficient, sustainable, and scalable flow-based amination processes.