Microwave-assisted enzymatic synthesis of citronellyl propionate in non-aqueous media: optimization, in-silico insights, and kinetic analysis

Abstract

Citronellyl propionate, a terpene ester, is widely used as a flavour and fragrance material. In this work, it was successfully synthesized under microwave irradiation via transesterification of β-citronellol (as nucleophile) with different acyl donors using dissimilar lipases with the same apolar support. Various reaction parameters were optimized, compared and screened for an optimum conversion and yield. Different organic solvents were compared to get the best catalytic activity. CALB (Candida antarctica lipase B)-Immobead 150 A lipase showed the highest activity among those studied, with up to 99 % conversion and selectivity in all reactions of vinyl propionate. The optimized reaction consisted of conditions: CALB-Immobead 150 A 0.26 % w/v loading, heptane solvent, 400 rpm agitation speed in a lab reactor, an equimolar ratio of citronellol and vinyl propionate, and 70 °C. Molecular docking indicated that CALB has more specificity for vinyl propionate than TL lipase. The initial reaction rate was further intensified by microwave irradiation. The Arrhenius frequency factor (A) of microwave irradiation was 1.6 fold more than that of conventional heating due to multiple factors like enhanced localized heating and non-thermal effects. To determine intrinsic kinetics, the optimum reaction system was studied to overcome mass transfer resistance and intra-particle diffusion limitations. It was found that the reaction is enzyme kinetic limited. A ping pong bi-bi non-sequential model was fitted and validated. Thus, a novel, scalable, and sustainable lab-scale process is presented that outperformed all previously reported citronellyl propionate syntheses.