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

Abstract

For the synthesis of coumarin derivatives using the Pechmann condensation scheme, an acidic ionic liquid catalyst, abbreviated as [EBsImH][HSO 4 ], was prepared from the ring opening of 1,4-butanesultone by 1-ethylimidazole, followed by the addition of 1 equiv. H 2 SO 4 (c). The [EBsImH][HSO 4 ]catalyzed Pechmann condensation reactions proceeded smoothly in a batch setup, with recyclable [EBsImH][HSO 4 ] showing great catalytic activity. The acidic ionic liquid catalyst [EBsImH][HSO 4 ] was recovered from EtOAc/H 2 O extraction of the product mixture, where the H 2 O 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 H 2 SO 4 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.

SnO2 nanoparticles: A recyclable and heterogeneous catalyst for Pechmann condensation of coumarins and Knoevenagel condensation–Michael addition of biscoumarins

“…Coumarin and its derivatives are natural and synthetic compounds having biological activity for example antifungal, anti-tubercular, antibacterial, antioxidant properties, anti-HIV agents, antiviral, anticoagulant, anticancer, anti-inflammatory, antibiotics, anti-malarial and so on [ [1] , [2] , [3] , [4] , [5] , [6] , [7] ]. Also, these compounds have been broadly applied in the parts of cosmetics, perfumes, medicine, fluorescent dyes, and microfluidic flow system [ [1] , [2] , [3] , [4] , [5] ]. Moreover, numerous coumarins have showed appropriate efficacy in the treatment of several categories of illnesses.…”

Visible‐Light‐Induced Regioselective Deaminative Alkylation of Coumarins via Photoredox Catalysis

“…Traditionally, coumarin derivatives can be prepared via classical pathway such as Perkin condensation, [3] Knoevenagel condensation [4] and Pechmann reaction. [5] In the past decade, direct CÀ H functionalization strategies [6] have emerged as forceful alternatives for the synthesis of diversified coumarin derivatives owing to their advantages of atom and step economy. Though tremendous progress have been made in CÀ H modification of coumarin, methods for the direct installation of alkyl onto coumarins with high regioselectivity were less been developed, [7] especially for the alkylation of furanocoumarins, only one example with moderate yield has been demonstrated.…”

“…As shown in Table 2, a broad range of cyclic and acyclic amine derived Katritzky salts were well tolerated by this photocatalyzed alkylation reaction. Some important function groups like oxa-, difluoromethyl and amide could be reserved in the process (3)(4)(5)(6)(7). Remarkably, the substrates bearing 5-, 6-, 7-, and 8-membered rings could deliver the corresponding cyclic alkylated products 8-11 efficiently.…”