L-Pyrrolidine-2-Carboxylic Acid Sulfate: A New Ionic Liquid for the Synthesis of Bioactive Tetrahydrobenzo[b]pyrans

Abstract

Multicomponent reactions (MCRs), a significant subclass of reac tions, are one-pot processes in which three or four easily-approachable components react to form a single product. The methodology is a powerful synthetic tool for the preparation of important drugs and other biologically active compounds. 1 MCRs have been useful in the development of environ- mentally-friendly and less expensive procedure s for the generation of libraries of heterocy- clic compounds 2 and the development of MCRs can le ad to new, efficient, synthetic methodologies. Tetrahydrobenzo[b]pyrans an d their derivatives are an important class of heterocyclic compounds with antic oagulant, antitumor, spasmoly tic, antibacterial, diuretic, potassium channel activating and insulin-sensitizing activities. 3–6 4H-Benzo[b]pyrans are usually synthesized from a -cyano cinnamonitrile derivatives with dimedone catalyzed by acid or base. 7 Recently MCRs have been used for their preparation. As compared to the conventional linear step synthesis, they can make the process easier, reduce time, save money, energy, and raw materials, resulting in both economic and environmental bene- fits. 8–9 A number of methods have been reported using dimedone, aromatic aldehydes and malononitrile in the presence of catalysts, such as CeCl 3 ¢ 7H 2 O, 10 N-methylimidazole, 11 tet- ramethyl ammonium hydroxide, 12 MgO, 13 amines, 14 2,2,2-trifluoroethanol, 15 and TiO 2 . 16 Other methods have involved microwave heating, 17 ultrasonic irradiation, 18 electrosynthe- sis, 19 hexadecyldimethylbenzylammonium bromide (HDMBAB), 20 Na 2 SeO 4 , 21 DABCO, 22