Step-by-step synthetic route to access eugenol-1,2,3-triazole-chalcone hybrid

Abstract

Molecular hybridization represents a strategic approach in drug design, where two or more pharmacophoric elements from distinct bioactive molecules are integrated into a single hybrid compound. In this study, we synthesized hybrid compounds of chalcone, triazole, and eugenol through straightforward reactions using 4-hydroxyacetophenone as the starting material. Initially, 4-hydroxyacetophenone (1) underwent alkylation with 1,4-dibromobutane to produce compound 2 with an 84 % yield. Compound 2 was then subjected to azidation, resulting in azidobutoxyacetophenone 3 with a 71 % yield. Subsequently, compound 3 was reacted with either benzaldehyde or 4-methoxybenzaldehyde via base-catalyzed aldol condensation, yielding azidobutoxychalcones 4a (69 %) and 4b (84 %). Finally, azide-alkyne [3+2] cycloaddition between 4a/4b and propargylated eugenol afforded chalcone derivatives bearing eugenol-1,2,3-triazole hybrids 5a and 5b, each with a 90 % yield.•Synthesized chalcones featuring an eugenol-1,2,3-triazole scaffold using 4-hydroxyacetophenone as the starting material.•Synthesis was accomplished through a four-step reaction sequence.•Products were obtained in good yield.

Keywords: 1,2,3-Triazole; 4-Hydroxyacetophenone; Chalcone; Eugenol; Molecular hybrid; Synthesis of chalcone containing an eugenol-1,2,3-triazole scaffold by aldol condensation and cycloaddition reactions.

Graphical abstract

Scheme 1

Synthetic route to produce eugenol-1,2,3-triazole-chalcones.

Fig. 1

¹H NMR spectrum of 5b.