Safe, scalable and solvent-free acyl azide synthesis via continuous mechanochemistry

Abstract

Here we report a rapid, solvent- and additive-free, continuous-flow mechanochemical process for the synthesis of acyl azides (R–CO–N₃) using a custom single-screw reactor. The reaction operates under mild thermal conditions (0–50 °C) and achieves complete conversion with >95% selectivity within seconds of residence time. Efficient mixing, enhanced heat and mass transfer, precise residence-time control, and stable steady-state operation facilitates optimization leading to high yields and excellent reproducibility across a broad range of acyl chloride substrates. Product quenching, separation, and isolation were performed continuously. On laboratory scale, benzoyl azide was synthesized at throughputs of 180 g h⁻¹ without any operational interruption. This offers a safer, cost-effective and more sustainable platform for acyl azide synthesis.