Batch and Continuous Flow Mechanochemical Selective Oxidation of Benzyl Alcohol in Deep Eutectic Solvent Starting Exclusively from Solids

Reline, a deep eutectic solvent (DES), was employed as the reaction medium for the selective catalytic oxidation of phenylmethanol derivatives using either N-bromosuccinimide (NBS) or a combination of 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) and [bis(acetoxy)iodo]benzene (PIDA). Various reactor setups, including a stirred glass tank reactor, a planetary ball mill, and the impact in continuous flow heated mechanochemistry (ICHeM) system, were evaluated for the selective synthesis of 4-bromobenzaldehyde. Starting from solid components─primary or secondary alcohols, NBS or TEMPO/PIDA oxidizing agents, choline chloride, and urea─the ICHeM technology simultaneously enabled the in situ formation of the reline DES medium and the synthesis of 12 different aldehydes and ketones in yields ranging from 11% to 97% with 100% selectivity. The reactions were completed within a residence time of 9.4 to 10.9 min, achieving space-time yields of 0.750 kg h–1 L–1 for 4-bromobenzaldehyde, 0.780 kg h–1 L–1 for 4-iodobenzaldehyde, and 0.470 kg h–1 L–1 for p-tolualdehyde.