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

Abstract

A simple, straightforward, and highly efficient multicomponent one-pot synthesis of a pharmaceutically interesting diverse kind of functionalized 2-amino-3-cyano-4H-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(4H)-ones (4aa–4al), 2-amino-3-cyano-pyrano­[4,3-b]­pyran-5­(4H)-ones (4ba–4be), 2-amino-3-cyano-7,8-dihydro-4H-chromen-5­(6H)-one (4ca–4cr), 1H-pyrano­[2,3-d]­pyrimidine-2,4­(3H,5H)-diones (4da–4dd), 2-amino-3-cyano-5,10-dioxo-5,10-dihydro-4H-benzo­[g]­chromenes (4ea–4ec), 2-amino-3-cyano-4H-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.

Efficient tandem synthesis of a variety of pyran-annulated heterocycles, 3,4-disubstituted isoxazol-5(4H)-ones, and α,β-unsaturated nitriles catalyzed by potassium hydrogen phthalate in water

“…Several synthetic methods have been widely applied for synthesis of pyran-based heterocyclic compounds, using many homogeneous or heterogeneous organic, inorganic, and nanomaterial catalysts, for example hexamethylenetetramine (HMT) [40], heteropolyacid [41], diammonium hydrogen phosphate [42], DBU [43], piperidine [44][45][46][47], tetrabutylammonium bromide (TBAB) [48], ionic liquids [49], morpholine [50], 4-(dimethylamino)pyridine (DMAP) [51], urea [52], 3-hydroxypropanaminium acetate (HPAA) [53], N-propylpiperazine sodium n-propionate (SBPPSP) [54], silica gel [55], sulfonic acid-functionalized silica [ [60], meglumine [61], I 2 /K 2 CO 3 [62], cetyltrimethylammonium bromide (CTABr) [63], nano-sized MgO [64], nano-structured Na 2 CaP 2 O 7 [65], NaHCO 3 [66], Na 2 CO 3 [67], triazine-functionalized ordered mesoporous organosilica [68], potassium phosphate tribasic trihydrate [69], Mg/Al hydrotalcite [70], Amberlyst A21 [71], DABCO [72], CeO 2 /CaO nanocomposite oxide [73], triton B [74], tetrabutylammonium chloride (TBAC) [75], nano-eggshell powder [76], basic alumina [77], [bmim]OH [78,79], LiBr [80], glycine [81], silica nanoparticles [82], ionic liquid choline chlorid...…”

Recent developments on nano-ZnO catalyzed synthesis of bioactive heterocycles

“…Pyrans and pyran-annulated heterocyclic scaffolds possess a broad spectrum of significant biological activities that include anticancer, cytotoxic, anti-HIV, anti-inflammatory, antimalarial, antimicrobial activity [105][106][107]. Das and his group reported a simple, efficient, environmentally benign protocol for the synthesis of 2-amino-3-cyano-4H-pyran derivatives via a one-pot three-component coupling reaction between a series of aromatic aldehydes (5), malononitrile (18) and 1,3-dicarbonyl compounds (17,50) using nano-ZnO as the catalyst in water at room temperature [108] (Scheme 6).…”

Facile One-Pot Synthesis of Amidoalkyl Naphthols and Benzopyrans Using Magnetic Nanoparticle-Supported Acidic Ionic Liquid as a Highly Efficient and Reusable Catalyst

“…In addition, most of them are limited to only aromatic aldehydes and the reactions with aliphatic aldehydes were reported to suffer from low yields and harsh reaction conditions. Meanwhile, the benzopyrans could also be prepared by multicomponent condensation of dimedone with aldehyde and malononitrile in the presence of newly reported catalysts such as SO4 2− /MCM-41 [22], NH4H2PO4/Al2O3 [23], THAM [24], urea [25], ionexchange resin [26], SO3H-functionalized nano-TiO2 [27], immobilized HPA [28,29], ionic liquid [30] and MWCNT@Co-complex [19]. Many of the reported procedures suffer from limitations yet, for example use of volatile organic solvent, prolonged reaction time, tedious work-up and additional ultrasonic irradiation.…”