Kilogram-Scale Synthesis of 2,4-Dichloro-5-fluorobenzoic Acid by Air Oxidation under the Continuous-Flow Process

A continuous-flow process for the preparation of 2,4-dichloro-5-fluorobenzoic acid (BA) has been reported. We chose 2,4-dichloro-5-fluoroacetophenone (AP) as starting material and acetic acid as cosolvent to achieve the excellent results in the continuous-flow oxidization system. The nitric acid oxidation of BA is a violent exothermic reaction. However, the continuous-flow system includes advantages such as good mass and heat transfer to ensure the safety of the reaction. The influences of different factors, including reactant ratio, temperature, and residence time, were investigated based on single factor tests. The optimal reaction conditions were obtained, in which the yield reached up to 100%. Compared with the traditional tank reactor process, less nitric acid consumption, a higher product yield, less reacting time, being more environmental friendly, and process continuity ensuring higher operation safety are achieved in the continuous-flow system.