Catalysis-free microwave-assisted synthesis of bis-coumarins with chromone group by a multicomponent process

Bis-coumarins, a widely studied group of compounds associated with coumarins, have been shown to be active as anticoagulants, antiseptics, and urease inhibitors. For its part, multicomponent reactions are convergent processes that combine three or more reactants in a single operation to form a single product. They are invaluable in drug development due to their high atom economy and lack of generation of harmless byproducts.

In this work, nine bis-coumarin molecules were obtained by multicomponent reaction, without catalysts, under thermal heating or microwave irradiation. First, optimization tests were performed using one mol benzaldehyde and two mol of 4‑hydroxycoumarin as starting substrates. The optimal temperature (100 ºC), solvent (n-propanol), and reaction time (4 h for conventional heating and 1 h for microwave irradiation) were then employed for the reaction between 4‑hydroxycoumarin and different 3-formylchromones to obtain bis-coumarins. Excellent yields and selectivity, which in most cases was greater than 65%, both with conventional thermal heating and microwave radiation were achieved. It is noteworthy that the products are insoluble in the reaction solvent; therefore, they precipitate from the reaction medium and are obtained almost pure (corroborated by ¹H‑NMR, melting point determination) without the need for other separation or purification methods such as recrystallization, which require the use of additional solvents.