Scalable Electrochemical Reduction of Nitrobenzotrifluorides to 3-Trifluoromethylanilines

The scalability of electrochemical methods remains one of the biggest reasons for their scarce implementation in manufacturing synthetic routes as well as pharmaceutical and agrochemical industry. To bridge this gap, we designed a robust and safe electrochemical workflow route for the synthesis of a collection of various 3-trifluoromethylanilines. The 3-trifluoromethylanilines are important intermediates for preparing agrochemicals and active pharmaceutical ingredients. The agent-free conversion could be easily scaled beyond the decagram scale. The cathodic conversion of nitroarenes in sulfuric acid/methanolic media was used to generate the 3-trifluoromethylanilinium bisulfates. During the reductive process, H2SO4 formed the corresponding bisulfates, which precipitated and facilitated downstream processing. The translation of a small-scale batch electrochemical reduction to forge the 3-trifluoromethylanilinium bisulfates in a continuous flow electrolysis allowed the target compound to be obtained in quantities of up to 107 g per run. The molecular composition of 3-trifluoromethylanilinium bisulfate was confirmed by elemental analysis. In addition, we demonstrated that the methodology can be extended to a broader scope. In total, eight different 3-trifluoromethylnitrobenzenes were applicable in batch, and six of them were translated to flow conditions.