Green Synthsis Of Barbiturate-fused Spirodihydrofurans By One-pot Three-component Reaction

Compounds containing barbituric acid have high medicinal value.As a calss of important medical intermediates,spirodihydrofuran barbiturates have made great contributions in the treatment of tumors,diabetes and Parkinson’s disease.After literature investigation,this paper studied the three-component reaction of barbituric acid,aromatic aldehydes and cyclic 1,3-dicarbonyls.Barbituric acid reacted with aromatic aldehyde and cyclic diketone in one-pot to afford uncyclized intermediate.NBS used as brominated reagent,the active CH on barbiturates was selectively brominated.Then,the enol hydroxyl group of the cyclic dicarbonyl compound on the intermediate initiates a nucleophilic attack while eliminating hydrogen bromide to form the spirodihydrofuran product.In this paper,the conditions of the reaction,including solvent,catalyst,halogen source,material ratio and temperature,were optimized.Two barbituric acids,eighteen aromatic aldehydes and three cyclic 1,3-dicarbonyl compounds were selected as substrates for combinatorial synthesis,and the reactions were carried out efficiently with ethanol-water as the environmentally friendly reaction solvent and L-proline as the catalyst at room temperature.Six series of products were designed and synthesized,and 103 compounds were obtained in this paper and their structures were determined by¹H-NMR,¹³C-NMR,IR、HR-MS and X-ray crystallographic diffraction.