Difluoroalkylation of styrene in the continuous-flow microreactor: Process performance and Reaction kinetics

Abstract

Fluoroalkylation compounds are vital in pharmaceutical and agricultural chemistry. However, conventional batch reactor usually suffers from poor mass transfer and long reaction times. Comparatively, microreactors offer substantial improvement in mass and heat transfer for high-efficient production. Especially, it could innovate the original batch operation mode into continuous production. In this work, a highly efficient continuous flow system is constructed for styrene difluoroalkylation using CuI as a catalyst and BrCF₂CO₂Et as fluorinating reagent. The influences of reactant ratios, catalyst content, alkali amount, reaction temperature and residence time on reaction performance were investigated systematically. Under optimal conditions, 80% yield was gained in only 0.5 h. The reaction time required is significantly shortened. Meanwhile, the usage of catalyst could also be reduced. Moreover, the kinetics of the styrene difluoroalkylation reaction in microreactor were studied, and the rate constant, activation energy and pre-exponential factor were obtained according to reaction kinetic model.