Chemoselective Acetylation of 2-Aminophenol Using Immobilized Lipase: Process Optimization, Mechanism, and Kinetics

Abstract

N-(2-Hydroxyphenyl)acetamide is an intermediate for the complete natural synthesis of antimalarial drugs. Chemoselective monoacetylation of the amino group of 2-aminophenol to N-(2-hydroxyphenyl)acetamide was carried out by employing Novozym 435 as the catalyst. Different acyl donors such as vinyl acetate, vinyl butyrate, acetic anhydride, and ethyl acetate were studied. The effect of various parameters such as different acyl donors, speed of agitation, solvent, catalyst loading, mole ratio, and temperature was studied. Vinyl acetate was found to be the best acyl donor among the studied acyl donors since it leads to an irreversible reaction. It is a kinetically controlled synthesis since vinyl acetate was used as the activated acyl donor. The substrate to acyl donor ratio was 1:3. The mechanism for the given reaction system was predicted based on the observations of Lineweaver-Burk plots. It was observed that the reaction followed a ternary complex model with inhibition by vinyl acetate, and kinetic constants were estimated using the Polymath 6.0 software. Under the final optimized conditions, the conversion for the reaction was found to be 74.6% in 10 h.