One-pot synthesis of aldimines via single screw extrusion: a mechanochemical approach

Abstract

We report a continuous, solvent-free method for aldimine synthesis using single-screw extrusion (SSE) that achieves high yields with water as the sole byproduct. Under optimized conditions, SSE delivered aldimines in high to near-quantitative yields (>99% for selected derivatives) across diverse substrate classes including cyclohexanol amines, L-phenylalaninate methyl esters and ethylenediamine-derived bis-aldimines without requiring product purification. Furthermore, an optimized process is demonstrated, with a throughput rate of 6740 g day⁻¹, corresponding to a space-time yield of 1716 kg m⁻³ day⁻¹. The extrusion process outperformed mechanochemical grinding and batch methods in efficiency and crystallinity, as evidenced by the DSC endothermic peak. The synthesized compounds were characterized using various analytical tools like IR, GC-MS, NMR, single crystal XRD and HRMS. By leveraging mechanochemistry in a continuous flow system, SSE provides a simple yet powerful platform that significantly expands the possibilities for sustainable organic synthesis.