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 anti-inflammatory 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-2-naphthaldehyde (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 H2 in 8 h. All catalysts were characterized using CO2 temperature-programmed 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.