Solvent Minimized Synthesis of Amides by Reactive Extrusion
Robert R. A. Bolt, Harry R. Smallman, Jamie A. Leitch, Gavin W. Bluck, Fabien Barreteau, Andrei V. Iosub, David J. C. Constable, Olivier Dapremont, Paul Richardson, Duncan L. Browne
Abstract
Herein, we report on the translation of a small scale ball-milled amidation protocol into a large scale continuous reactive extrusion process. Critical components to the successful translation were: a) understanding how the different operating parameters of a twin-screw extruder should be harnessed to control prolonged continuous operation, and b) consideration of the physical form of the input materials. The amidation reaction is applied to 36 amides spanning a variety of physical form combinations (liquid-liquid, solid-liquid and solid-solid). Following this learning process, we have developed an understanding for the translation of each physical form combination and demonstrated a 7-hour reactive extrusion process for the synthesis of an amide on 500 gram scale (1.3 mols of product).