Synthesis of Curcumin Inspired Chalcone and Corresponding Dihydropyrazole Derivatives

Abstract

Molecular hybridization has emerged as a promising strategy for the development of multifunctional therapeutic agents with improved pharmacological profiles. In the present work, a series of curcumin-inspired chalcone and dihydropyrazole were synthesized by integrating the bioactive pharmacophoric features of curcumin and chalcone scaffolds. Initially, aminoalkyl and propargyl substituted benzaldehyde derivatives were prepared from 4-hydroxybenzaldehyde through alkylation reactions. These intermediates were further reacted with dehydroacetic acid under piperidine-catalyzed conditions to afford curcumin-inspired chalcone derivatives in good yields. The synthesized chalcones were subsequently cyclized with phenylhydrazine hydrochloride to obtain corresponding dihydropyrazole derivatives. In addition, propargyl-functionalized chalcones were transformed into triazole analogues through Cu(I)-catalyzed azide–alkyne cycloaddition reactions. All synthesized compounds were characterized using IR, 1H NMR, 13C NMR, elemental analysis, melting point determination, and spectral interpretation. The developed synthetic approach provided structurally diverse hybrid molecules with satisfactory yields and straightforward purification protocols. The study demonstrates an efficient route for the preparation of curcumin-inspired multifunctional scaffolds that may serve as promising candidates for further biological investigations.