The continuous kilogram-scale process for the synthesis of 2,4,5-trifluorobromobenzene via Gattermann reaction using microreactors

2,4,5-Trifluorobromobenzene is a valuable synthetic intermediate with important applications in pharmaceutical industry. We report a continuous microflow process for the synthesis of 2,4,5-trifluorobromobenzene via Gattermann reaction in this paper. The microflow system is easily assembled by a simple T-micromixer, microchannel reactors and several pumps. The use of this system facilitated the diazotization reaction of 2,4,5-trifluoroaniline with HBr and NaNO 2 to produce the thermally unstable 2,4,5-trifluorophenyl diazonium salts in seconds, which then react with HBr at the catalysis of copper powder to obtain 2,4,5-trifluorobromobenzene. The aqueous HBr containing copper powder was added and stirred for 30 min at 70 °C in the stirred vessel. And then, the CuBr in situ was given and performed a quench-type reaction as catalyst. The influence of the reaction parameters on the diazotization reaction steps was examined and discussed in microreactors. The microflow system had the capacity to promote efficient mass- and heat-transfer and shorten the reaction time. On this basis, the kilogram-scale production of 2,4,5-trifluorobromobenzene was realized in a self-made scale-up microreactor by numbering-up of micromixers and microchannels.