Month 2014 Sodium Formate-Catalyzed One-Pot Synthesis of Benzopyranopyrimidines and 4-Thio-substituted 4H-Chromenes via Multicomponent Reaction at Room Temperature Goutam Brahmachari* and Suvankar Das Laboratory of Natural products & Organic Synthesis, Department of Chemistry, Visva-Bharati University, Santiniketan, 731 235, West Bengal, India * E-mail: brahmg2001@yahoo.co.in; brahmg2001@gmail.com Received May 30, 2013 DOI 10.1002/jhet.2123 Published online 00 Month 2014 in Wiley Online Library (wileyonlinelibrary.com). A simple, straightforward and highly efficient multicomponent one-pot synthesis of a series of pharmaceutically interesting benzopyranopyrimidine and 4H-chromene derivatives has been developed on the basis of low-cost and environment-friendly sodium formate catalyst via tandem reactions of salicylic aldehydes, malononitrile, and cyclic secondary amines in ethanol at room temperature. Nature of nucleophile used in this reaction directs the course of the reaction; cyclic secondary amines result in the formation of benzopyrano[2,3-d]pyrimidines, whereas thiophenol furnish corresponding 4-thio-subtituted 4H-chromenes under the same reaction conditions. High atom-economy, good yields, eco-friendly, and mild reaction conditions are some of the important features of this protocol. J. Heterocyclic Chem., 00, 00 (2014). INTRODUCTION Due to a handful of benefits such as procedural simplicity, shorter reaction times, high atom-economy, lower costs, and avoidance of time-consuming expensive purification pro- cesses [1], multicomponent reactions (MCRs) have emerged in recent times as fascinating and well-accepted strategies to the scientific community at large for the construction of novel and complex molecular structures in comparison to conventional multi-step synthesis [2]. In addition, MCRs have appeared to be much more environment-friendly, and also capable of offering rapid access to combinatorial libraries of complex organic molecules finding applications in the field of drug discovery and development [3]. It has already been demonstrated from earlier works that an MCR protocol involving eco-friendly solvents and catalytic systems can serve as one of the most suitable strategies and meets the requirements of green aspects of synthetic chemis- try for developing libraries of medicinal scaffolds [2,4]. Hence, development of new MCRs and improving the known MCR strategies in these directions are of consider- able interest in modern organic synthesis. In recent years, benzopyrano[2,3-d]pyrimidines have gained much attention as significant medicinal scaffolds due to their inherent and multidirectional pharmaceutical potentials that include anti-inflammatory, analgesic, and anti- aggregating activities [5]; more importantly, such chemical entities have been found to exhibit potent in vivo antitumor as well as in vitro cytotoxic activity against various cancer cell lines causing considerable degree of perturbation in cell cycle kinetics [6]. Benzopyrano[2,3-d]pyrimidine core was first synthesized by O’Callaghan from the condensation reaction of 2-iminocoumarin-3-carboxamides with aldehydes following a complex multi-step protocol [7]. Later on, a few more reports appeared describing the synthesis of benzopyranopyrimidine derivatives with a limited substitution pattern via multi-step complex reaction procedures [5,8]. However, one-pot multicomponent synthetic protocols for such scaffolds have recently been reported based on the use of microwave irradiation [9a] or catalysts such as lithium per- chlorate [9b,c] and the ionic liquid [Bmim]BF 4 [9d]; despite such sincere attempts to overcome the existing drawbacks, no one of these three procedures is sufficient enough to attain © 2014 HeteroCorporation