Selectivity Engineering in One-Pot Selective Synthesis of Drug Nabumetone over Novel Ni-Promoted La-Mg Oxide/Mesoporous Cellular Foam as Catalyst and Kinetic Modeling

Abstract

One-pot synthesis of one of the popular non-steroidal antiinflammatory drugs nabumetone (NBM) was achieved by using a novel catalyst. A series of mesoporous cellular foam (MCF) supported lanthanum magnesium mixed oxide (x% LMMO, x = 10−50 wt %) catalysts, further modified with Ni, Cu, and Fe dopants via a sequential impregnation method, were evaluated for the one-pot synthesis of NBM from 6-methoxy-2naphthaldehyde (6MNAL) and acetone. Ni was the best metal, and thus various Ni loadings (2, 4, and 6 wt %) were tested for their efficacy. The 4% Ni-40%LMMO/MCF catalyst was thus optimized as the best candidate. 4% Ni-40%LMMO/MCF offered complete conversion of 6MNAL at a mole ratio of 6MNAL/acetone of 1:30 with 93% selectivity to NBM at 140 °C and 15 atm of H 2 in 8 h. All catalysts were characterized using CO 2 temperatureprogrammed desorption, X-ray diffraction, small-angle X-ray scattering, Fourier transform infrared, Brunauer−Emmett−Teller surface area analysis, temperature-programmed reduction, field emission scanning electron microscopy, energy-dispersive spectroscopy, high-resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and differential scanning calorimetry−thermogravimetric analysis. The reaction mechanism and kinetic model for condensation as well as the hydrogenation step were established. The catalyst was active, selective, and robust.