One‑Pot, Efficient, Microwave Assisted Multi-Component Synthesis of Substituted Pyrano[2,3-c]pyrazole derivatives in Aqueous Medium and Evaluation of its Antioxidant Activity

Abstract

A green and efficient microwave-assisted protocol was developed for the synthesis of substituted pyrano[2,3-c]pyrazole derivatives (5a-f) through a one-pot multicomponent condensation reaction involving hydrazine hydrate, ethyl acetoacetate, malononitrile and substituted aromatic aldehydes in the presence of tetrabutylammonium bromide (TBAB) as a phase-transfer catalyst/base under aqueous conditions. Microwave irradiation significantly reduced the reaction time (3-6 min) and afforded the desired products in high yields under mild and environmentally benign conditions. TBAB facilitated deprotonation of malononitrile and activation of the aldehyde carbonyl group, thereby accelerating the Knoevenagel condensation and subsequent cyclisation process. The synthesized compounds were characterised by FTIR, ¹H NMR and ¹³C NMR spectral analyses, which confirmed the successful formation of the pyrano[2,3-c]pyrazole framework. Spectral studies revealed characteristic absorption bands for –NH and –CN functionalities along with corresponding proton and carbon resonances. Electron-withdrawing substituents on aromatic aldehydes exhibited shorter reaction times and improved yields compared with electron-donating substituents. The antioxidant activity of all synthesized derivatives was evaluated using the DPPH free radical scavenging assay with ascorbic acid as the reference standard. Among the synthesized compounds, derivative 5a exhibited the highest antioxidant activity, while compounds containing substituted aromatic groups also demonstrated appreciable free radical scavenging potential. The developed methodology provides a rapid, sustainable and high-yielding synthetic approach for biologically important pyrano[2,3-c]pyrazole derivatives with promising antioxidant activity.