One-pot Three-component Synthesis of Fully and Diversely Functionalized Pyrans and Spiropyrans Using Sodium Formate as Catalyst in Aqueous Ethanol at Room Temperature

Abstract

Abstract: A convenient and general method has been developed for the synthesis of fully and diversely functionalized pyrans via one-pot three-component reactions of various aryl or heteroaryl aldehydes, malononitrile, and 1,3-dimethyl/1,3-diethyl-acetonedicarboxylates in the presence of a catalytic amount of sodium formate as an efficient organocatalyst in aqueous ethanol at room temperature. All the scaffolds were synthesized in excellent yields within 2.5 hours. Under the same reaction conditions, fully and diversely functionalized spiro-pyrans were also synthesized in excellent yields from the reaction of isatin, malononitrile, and 1,3-dimethyl/1,3-diethylacetonedicarboxylates. All the products were isolated pure just by simple filtration. Synthesis of fully and diversely functionalized biologically promising pyrans, excellent yields, use of organocatalyst, less toxic solvent, no column chromatographic purification, and energy efficiency are some of the major advantages of this newly developed protocol. method: In a clean test tube a magnetic stir bar, 0.5 mmol of aldehydes (1a-1i), 0.5 mmol of malononitrile (2; 0.033 g) and 0.5 mmol of 1,3-dimethylacetonedicarboxylate (3a; 0.087 g) or 1,3-diethylacetonedicarboxylate (3b; 0.101 g), 4 ml aqueous ethanol (1:1 v/v) and 20 mol% sodium formate were taken sequentially. The whole reaction mixture was stirred at room temperature for the time mentioned in Table 2. The progress of reaction was monitored by TLC. By using the same amount of catalyst and solvent the synthesis of methyl/ethyl-2'-amino-3'-cyano-6'-(2-meth/ethoxy-2-oxoethyl)-2-oxospiro[indoline-3,4'-pyran]-5'-carboxylate (6a/6b) was achieved from the reactions of 0.5 mmol of isatin (5; 0.0735 g), 0.5 mmol of malononitrile (2; 0.033 g) and 0.5 mmol of 1,3-dimethylacetonedicarboxylate (3a; 0.0871 g) or 1,3-diethylacetonedicarboxylate (3b; 0.1011 g). After the completion of each reaction, the desired products were isolated simply by filtration and subsiquent washing with aqueous ethanol (EtOH:H2O = 1:1).