Screwing NaBH₄ through a Barrel without a Bang: A Kneaded Alternative to Fed-Batch Carbonyl Reductions

In this work the application of green chemistry principles such as process intensification and the replacement of reagents and solvents to more benign alternatives were coupled with the advantages of continuous manufacturing. The reduction of lipophilic aromatic aldehydes using an aqueous alkaline solution of NaBH₄ was achieved by means of mechanical shearing and kneading provided by a custom-made batch reactor at the lab scale and a twin screw extruder at the kilo scale. The process was run continuously for 17 min to yield 1.41 kg of product (89% purity). The benefits of running the process in a continuous manner instead a conventional fed-batch mode were discussed in terms of both environmental and economic factors