Kinetics of selective formation of ibuprofenamide by phase transfer catalyzed oxidation of 2-(4-isobutylphenyl)propionitrile with basic hydrogen peroxide

Abstract

Ibuprofenamide (benzeneacetamide-α-methyl-4-(2-methylpropyl)) is an ibuprofen analogue having anti-inflammatory activity itself and a precursor of many N-derivatives, all of which have good anti-inflammatory activities. The conventional process to prepare this amide is by the conversion of ibuprofen to acid chloride by thionyl chloride followed by ammonolysis or careful hydrolysis of the nitrile with H₂SO₄/CH₃COOH mixture. In this paper, the preparation of ibuprofenamide was achieved by the hydrolysis of 2-(4-isobutylphenyl)propionitrile with basic hydrogen peroxide under liquid−liquid phase transfer catalysis, under safe conditions with high conversion and selectivity. A systematic study was conducted to study the effects of various parameters such as different phase transfer catalysts, catalyst loading, substrate loading, and temperature on the conversion and rates of reaction. A kinetic model has been developed and validated against experimental data. With the 2-(4-isobutylphenyl)propionitrile to hydrogen peroxide mole ratio 1:4 at 60 °C, the conversion and selectivity were found to be 70% and 90%, respectively, in 2 h. This is a first report of its kind on mechanism and kinetics of PTC hydrolysis of nitriles. The results are novel.