Facile and One-Pot Access to Diverse and Densely Functionalized 2-Amino-3-cyano-4 H -pyrans and Pyran-Annulated Heterocyclic Scaffolds via an Eco-Friendly Multicomponent Reaction at Room Temperature Using Urea as a Novel Organo-Catalyst

A simple, straightforward, and highly efficient multicomponent one-pot synthesis of a pharmaceutically interesting diverse kind of functionalized 2-amino-3-cyano-4 H -pyrans and pyran-annulated heterocycles has been developed based on a low-cost and environmentally benign commercially available urea as a novel organo-catalyst. The reaction occurs via tandem Knoevenagel–cyclocondensation of aldehydes, malononitrile, and C–H-activated acidic compounds in aqueous ethanol at room temperature. Following this protocol, it was possible to synthesize 2-amino-3-cyano-pyrano[3,2- c ]chromen-5(4 H )-ones ( 4aa – 4al ), 2-amino-3-cyano-pyrano[4,3- b ]pyran-5(4 H )-ones ( 4ba – 4be ), 2-amino-3-cyano-7,8-dihydro-4 H -chromen-5(6 H )-one ( 4ca – 4cr ), 1 H -pyrano[2,3- d ]pyrimidine-2,4(3 H,5 H )-diones ( 4da – 4dd ), 2-amino-3-cyano-5,10-dioxo-5,10-dihydro-4 H -benzo[ g ]chromenes ( 4ea – 4ec ), 2-amino-3-cyano-4 H -pyrans ( 4fa – 4fh ), and 1,4-dihydropyrano[2,3- c ]pyrazoles ( 4ga – 4gb ). The salient features of the present protocol are mild reaction conditions, excellent yields, high atom-economy, eco-friendly standards, easy isolation of products, no column chromatographic separation, and reusability of reaction media. Bis-pyranization has also been observed in the reactions of terephthaldehyde.