Integration of Medium Engineering, Immobilization, and Rotating Bed Reactor for Intensifying Enzymatic Reduction of Halogenated Aryl Ketones

Enzymatic reduction of halogenated aryl ketones (HAKs) is an important reaction for the synthesis of pharmaceutical-related enantiopure halohydrins, but its preparative application remains restricted due to low substrate solubility and poor mass transfer in aqueous media. Herein, a multiengineering approach involving medium optimization, enzyme immobilization, and a rotating bed reactor was applied for intensifying the enzymatic reduction of HAKs. A deep eutectic solvent (DES) composed of betaine, glucose, and water (Bet-Glc-H2O) was demonstrated to be effective in improving enzymatic activity and stability, enabling efficient reduction of high-concentration HAKs (1.0 M, 85% conversion). In addition, enzyme immobilization was conducted using DES-modified resin supports, markedly enhancing the operational stability and reusability of the biocatalysts. Finally, a SpinChem rotating bed reactor (RBR) was implemented for further intensifying the enzymatic process, leading to dramatically shorter reaction times and increased overall productivity.