A Continuous Kilogram-Scale Process for the Manufacture of o-Difluorobenzene

An expeditious and multikilogram-scale process for the Balz–Schiemann synthesis of o -difluorobenzene from o -fluoroaniline via two separate continuous flow reactors in 90.0% yield has been set up. The main steps involved the generation of stable diazonium fluoborate intermediate in situ via continuous diazotization reactor at 20 °C, and the choice of o -difluorobenzene as cosolvent to achieve the continuous flow fluorodediazoniation system. Reaction time of both steps could be brought down to within 10 s and 2 min, respectively, by increasing the reaction temperature and thereby taking advantage of improved mass and heat transfer of a continuous flow system.