Efficient synthesis of bis-coumarins using Isatin-N-sulfonic acid under solvent-free conditions

Coumarin derivatives are an important class of compounds in medicinal chemistry.These compounds possess several pharmacological properties such as anticancer,anti-HIV, anticoagulant, spasmolytic, antibacterial and anti-inflammatory activities. These compounds have been also used as fluorescent molecules, and laser dyes for the blue-green region (400–520 nm) [1]. Bis-coumarins, as an important member of coumarin derivatives, are prepared by the reaction of 4-hydroxycoumarin with arylaldehydes [2]. Although some catalysts have been introduced for the production of bis-coumarins; many of them are associated with at least one of these disadvantages: relatively long reaction times, moderate yields, utilization of volatile organic solvents as reaction media and poor compliance with the green chemistry protocols.Multicomponent reactions (MCRs) are powerful, versatile, and popular tools for the synthesis of novel and complex molecular structures that have advantages over a conventional multistep synthesis such as energy saving, lower cost, shorter reaction time, high atom economy and expensive purification [3]. In this research, we have introduced Isatin-N-sulfonic acid as a highly efficient and general solid-acid catalyst for the synthesis of bis-coumarins in high yields and short reaction times by the pseudo multicomponent reaction of 4-ydroxycoumarin with arylaldehydes (Scheme 1).