Yanxing Li

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.

While organolithium reactions hold great promise in synthetic chemistry, their high reactivity, strong exothermicity, and the instability of intermediates often limit their application, making the effective control of reaction processes difficult in traditional batch reactors. This review systematically summarizes the latest advances in utilizing flow chemistry technology to address process challenges related to organolithium reactions from 2014 to 2025. From a process perspective, we systematically discuss the literature cases regarding three key themes: the synthesis of organic compounds applied in the pharmaceutical field, the development of novel methods centered on effective process control (reaction temperature, residence time, phase state, multi-step reaction sequence, and safety), and fundamental process research on continuous flow organolithium reactions. Analysis shows that continuous flow systems provide a powerful platform for fully realizing the potential of organolithium chemistry by enhancing heat/mass transfer and precisely controlling reaction parameters. This review emphasizes how flow chemistry technology not only improves process safety and efficiency but also enables transformations and process scaling that are difficult or impossible in batch modes, thus providing a novel process intensification method for modern synthetic chemistry.

Anthraquinone dyes are the second most important type of dyes after azo dyes. In particular, 1-aminoanthraquinone has been extensively utilized in the preparation of diverse anthraquinone dyes. This study employed a continuous-flow method to synthesize 1-aminoanthraquinone safely and efficiently through the ammonolysis of 1-nitroanthraquinone at high temperatures. Various conditions (reaction temperature, residence time, molar ratio of ammonia to 1-nitroanthraquinone (M-ratio), and water content) were investigated to explore the details of the ammonolysis reaction behavior. Operation conditions for the continuous-flow ammonolysis were optimized using Box–Behnken design in the response surface methodology, and ~88% yield of 1-aminoanthraquinone could be achieved with an M-ratio of 4.5 at 213 °C and 4.3 min. The developed process’s reliability was evaluated by performing a 4 h process stability test. The kinetic behavior for the preparation of 1-aminoanthraquinone was investigated under continuous-flow mode to guide the reactor design and to gain a deeper understanding of the ammonolysis process.

An efficient and practical catalytic system for the oxidation of alcohols to aldehydes/ketones using catalytic amounts of Bi(NO₃)₃ and Keto-ABNO (9-azabicyclo [3.3.1]nonan-3-one N-oxyl) with air as the environmentally benign oxidant was developed. Various primary and secondary alcohols were smoothly oxidized to the corresponding products under mild conditions, and satisfactory yields were achieved. Moreover, this methodology avoids the use of a ligand and base. The gram-scale reaction was demonstrated for the oxidation of 1-phenyl ethanol, and the product of acetophenone was obtained at an isolated yield of about 94%.