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.