Development of an Optimized Process for 2,4-Dichloro-5-fluoroacetophenone: A Key Intermediate of Ciprofloxacin

Herein, we report an optimized process for 2,4-dichloro-5-fluoroacetophenone, a key intermediate of ciprofloxacin. In the nitration step, the traditional mixed acid process was replaced by a microchannel continuous reaction technology. For the fluorination reactions, the traditional quaternary ammonium salt catalyst was replaced by a novel CNC+ catalyst, which led to improved catalytic efficiency, lowered reaction temperatures, and increased product yields. Furthermore, a cost-effective method for utilizing waste gases with high concentrations of nitrogen oxides was developed for the nitrochlorination reaction. In the acetylation step, magnetic materials featuring both Bronsted and Lewis acid sites were utilized to immobilize the bisacid site catalyst [HPhIm][FeCl4]/MPNs, replacing the traditional AlCl3 approach. The overall yield of this new sustainable process across all four steps reached 86.4%, marking a significant improvement of over 10% compared to the traditional method. Moreover, the new process has resulted in an 87% reduction in waste acid emissions and a remarkable 96% reduction in exhaust emissions.