Synthesis of coumarin derivatives in a microfluidic flow system employing the Pechmann condensation: A case study

Abstract

AbstractFor the synthesis of coumarin derivatives using the Pechmann condensation scheme, an acidic ionic liquid catalyst, abbreviated as [EBsImH][HSO4], was prepared from the ring opening of 1,4‐butanesultone by 1‐ethylimidazole, followed by the addition of 1 equiv. H2SO4(c). The [EBsImH][HSO4]‐catalyzed Pechmann condensation reactions proceeded smoothly in a batch setup, with recyclable [EBsImH][HSO4] showing great catalytic activity. The acidic ionic liquid catalyst [EBsImH][HSO4] was recovered from EtOAc/H2O extraction of the product mixture, where the H2O layer was worked up and dried for reuse in consecutive runs of the Pechmann condensation reactions, maintaining >85% conversion for four times. The catalytic reactions were also carried out in a microfluidic flow setup. The flow parameters, the reactant molar amounts, and the additional H2SO4 as a modifying acid catalyst were optimized in the current case study. A minimum conversion rate of 2.8 g/hr of coumarin derivatives was demonstrated.