A catalyst- and solvent-free protocol for the sustainable synthesis of fused 4 H-pyran derivatives

Abstract

An efficient and cost-effective method was developed for the synthesis of two kinds of fused 4H-pyran derivatives, namely, dihydropyrano[2,3-c]pyrazole 4 and pyrano[3,2-c]chromenone 6. The reactions of 3-methyl-1-phenyl-5-pyrazolone/4-hydroxycoumarin with aromatic aldehydes and (E)-N-methyl-1-(methylthio)-2-nitroethenamine (NMSM), involving the Knoevenagel, Michael-addition, O-cyclization and elimination reactions under thermal heating, afforded the desired products. The synthesized compounds were characterized by standard spectroscopic techniques. Further, the structures of pyrazole-fused 4H-pyran 4a and coumarin-fused 4H-pyran 6b were confirmed by single-crystal XRD analysis. The short reaction time, good-to-excellent yields, elimination of the use of expensive, metallic and toxic catalysts or hazardous organic solvents and high atom-economy are some noteworthy features of this protocol.

Fig. 1. Some representative examples of biologically active fused 4H-pyrans.

Scheme 1. Synthesis of pyrazole- and coumarin-fused 4H-pyrans under neat conditions.

Fig. 2. ORTEP representation of compound 4a (CCDC 1901104).

Fig. 3. ORTEP representation of compound 6b (CCDC 1901105).

Scheme 2. Plausible mechanism for the synthesis of the pyrazole- and coumarin-fused 4H-pyrans.