An Experimental and Computational Approach to The Microwave‐Assisted Synthesis of 2’‐Hydoxychalcone Derivatives in 1‐Dodecyl‐3‐Methylimidazolium Bromide ([DDMIm]Br) Ionic Liquids

Abstract

Four derivatives of 2’‐hydoxychalcone were synthesized through Claisen‐Schmidt condensation by combining 2’‐hydroxyacetophenone and four different benzaldehyde derivatives (o‐vanillin, salicylaldehyde, p‐anisaldehyde, and benzaldehyde) in the presence of a base. The reactions took place in an ionic liquid, 1‐dodecyl‐3‐methylimidazolium bromide ([DDMIm]Br), and were facilitated by microwave irradiation. The reactions were completed within 10 to 15 minutes, yielding products with chemical yields ranging from 52.64 % to 83.42 %. The structures of the synthesized products were confirmed using 1H NMR and 13C NMR spectroscopy. Additionally, antimicrobial activity tests demonstrated the effectiveness of specific derivatives against Staphylococcus aureus and Escherichia coli, underscoring the importance of hydroxy and methoxy groups on the aromatic ring in inhibiting microbial growth. These findings provide valuable knowledge for developing chalcone derivatives with improved properties and potential applications in drug discovery. Furthermore, the synthesized products′ reactivity was analyzed using Frontier Molecular Orbital (FMO) and their reactivity site was mapped using Molecular Electrostatic Potential (MEP). Lastly, molecular docking analysis was attempted to explain antibacterial activities from all products. Nonetheless, the molecular docking simulations conducted in this study were inadequate to fully account for the antimicrobial activity observed in all the products.