Cofactor-free biocatalytic hydrogenation of nitro compounds for synthesis of amines

We report a new paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. Hydrogenase enzyme releases electrons from H2 to a carbon black support which facilitates nitro-group reduction. For 30 nitroarenes we demonstrate full conversion (isolated yields 78 – 96%), with products including pharmaceuticals benzocaine, procainamide and mesalazine, and 4-aminophenol – precursor to acetaminophen (paracetamol). We also showcase gram-scale synthesis of procainamide with 90% isolated yield. We demonstrate potential for extension to aliphatic substrates. The catalyst is highly selective for reduction of the nitro group over other unsaturated bonds, tolerant to a wide range of functional groups, and exhibits excellent stability in reactions lasting up to 72 hours and full reusability over 5 cycles, indicating scope for direct translation to fine chemical manufacturing.