Selective hydrogenation of nitro compounds to amines by coupled redox reactions over a heterogeneous biocatalyst.

Sokolova, Daria; Lurshay, Tara C; Rowbotham, Jack S; Stonadge, Georgia; Reeve, Holly A; Cleary, Sarah E; Sudmeier, Tim; Vincent, Kylie A · Nat Commun · 2024

basic_science · Level V

Where this comes from

Abstract

Cleaner synthesis of amines remains a key challenge in organic chemistry because of their prevalence in pharmaceuticals, agrochemicals and synthetic building blocks. Here, we report a different paradigm for chemoselective hydrogenation of nitro compounds to amines, under mild, aqueous conditions. The hydrogenase enzyme releases electrons from H<sub>2</sub> 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 paracetamol (acetaminophen). 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 with a total turnover number over 1 million, indicating scope for direct translation to fine chemical manufacturing.