Cu(II) mediated chalcone synthesis via α-bromocarbonyl intermediate: A one-step synthesis of echinatin

Background: Since introduction of chalcones in 1899, chalcones have been considered as precursors of flavones in the biosynthesis of flavonoids. However, because the chalcones include multi-functional groups on aromatic rings, developments of efficient synthetic methodologies as well as synthetic strategies involving protection/ deprotection should be considered. Objective: The primary objective of this study was to describe chalcone synthesis under mild condition and its mechanism study. Method: The chalcones synthesis is aldol condensation of acetophenones with aldehydes in the presence of catalytic mount of copper(II) bromide at 70 °C. Result: Proposed transformation of the chalcone synthesis is to proceed via catalytically generated abromocarbonyl intermediate by copper(II) bromide, aldol condensation of a-bromocarbonyl intermediate is promoted by HBr, while its byproducts, HOBr and HBr reconstitute the catalyst. Using this method, the natural product echinatin (1) was conveniently synthesized in a single step with yield of 82%. Conclusion: Cu(II) mediated aldol condensation via a-bromocarbonyl species involving Cu(II) catalyst reconstitution were noted in this study. It was thought that it has the potential for application as a simple and quick synthesis method for pharmaceutical ingredients.