Selective and sustainable nitro reduction and reductive N-alkylation using a recyclable V2O5/TiO2 catalyst for amine synthesis

Abstract

We present a sustainable and versatile catalytic platform for the synthesis of primary and secondary amines via the selective reduction of nitroarenes, employing a heterogeneous V₂O₅/TiO₂ catalyst. This methodology eliminates the use of stoichiometric metal hydrides, molecular hydrogen, and homogeneous catalytic systems, aligning with green chemistry principles. The catalyst exhibits excellent chemoselectivity across a diverse array of nitroarenes, including substrates bearing alkenes, alkynes, halogens, and functionalized heterocycles, demonstrating broad functional group tolerance. Furthermore, we extend this platform to a one-pot reductive alkylation of nitroarenes with alkyl halides (Br and I), affording N-alkylated amines in high yields under mild conditions. The catalytic system is recyclable over multiple cycles with minimal loss of activity or selectivity, showcasing its practical utility. The synthetic value of this approach is highlighted through the preparation of 47 (hetero)arylamines, 12 secondary amines, and 7 pharmaceutically relevant molecules, including paracetamol, phenacetin, and bromhexine. Mechanistic insights derived from DFT calculations and controlled experiments provide a molecular-level understanding of the selective nitro group activation on the V₂O₅/TiO₂ surface. This work contributes a green, efficient, and mechanistically informed catalytic solution for amine synthesis from abundant nitroarenes.