Multi-functional Fe-Al0.66DTP/MCF catalyst in cascade engineered synthesis of the drug butamben: Novelty of catalyst, reaction kinetics and mechanism

Abstract

Cascade engineered synthesis of the drug butamben (n-butyl-p-aminobenzoate), a local anaesthetic, which is used for the treatment of chronic pain, is presented here. A new multifunctional heterogeneous catalyst was synthesized, characterized and used for the direct synthesis of n-butyl-p-aminobenzoate by hydrogenation and esterification. A mixture of p-nitrobenzoic acid, n-butanol, hydrogen, acetonitrile as solvent and catalyst was used and hydrogenated in which hydrogenation precedes esterification. A series of aluminum exchanged dodecatungstophosphoric acids (DTP) (Alx-DTP; x = 0.33–1) (5–20% w/w) supported on mesocellular foam silica (MCF) were prepared. 2% Fe loaded on 15% Al0.66DTP/MCF showed the best activity for one-pot synthesis because the metal and acid sites had proper strength and distribution on MCF. Reaction mechanism and kinetic model were developed. The catalyst 2%Fe-15% Al0.66DTP/MCF was found reusable for four catalytic cycles. This work presents an interesting case of reaction engineering using multi-functional catalyst useful in synthesis of a pharmaceutical drug butamben and has potential applications in other areas.