A Catalyst-free Approach to Synthesis of Polysubstituted Pyrano[3,2- c]chromene and Benzo[g]chromene Derivatives

Nowadays, the rapid development of new drugs with diverse and unique structures and with novel mechanisms of action from that of existing widely used drugs seemsessential. In the meantime, the development of heterocycles for drug design continues to be crucial in addressing this phenomenon [1]. Two class of the most important oxygen-containing heterocyclic compounds are pyrano[3,2-c]chromene and benzo[g]chromenes derivatives with a wide range of biological properties and applications in pigments and agrochemicals [2,3]. Hence, Because of their importance in pharmaceuticals and materials sciences, we were interested to synthesize a new library of pharmacologically relevant pyrano[3,2- c]chromene and benzo[g]chromene via the one-pot, multicomponent reaction of phenylglyoxal monohydrate, malononitrile/ethyl cyanoacetate/methyl cyanoacetate/cyanoacetamide and 4-hydroxycumarine or 2-hydroxy-1,4- naphthoquinone, at reflux in ethanol without the use of any catalyst (Scheme 1). These polysubstituted heterocyclic ring systems substituted with an amino group at C-2, carbonitrile group at C-3 and aroyl or acetyl group at C-4, which highlighted theeffect of the substituents on the biological activity. This protocol is distinguished by its high atom-economy, good to high yields, mild condition without the use of anyactivator or metal promoters, simple workup and easy purification