A High-Output, Continuous Selective and Heterogeneous Nitration of p‑Difluorobenzene

A practical continuous nitration process for 2,5-difluoronitrobenzene via nitration of p-difluorobenzene with fuming nitric acid in 98% yield has been developed. The excellent yield of this liquid/liquid biphasic reaction resulted from the advantages of a continuous flow system. The 2.0 equiv sulfuric acid could be used three times directly with product yields in the range of 96–98%, and further recycling of waste acid could be partly achieved by adjusting the concentration of sulfuric acid. Reaction time could be brought down to 2 min by increasing the reaction temperature and thereby taking advantage of superior mass and heat transfer of this continuous flow system.