A theoretical and experimental study of the formation mechanism of 4-X-chalcones by the Claisen–Schmidt reaction

Abstract

A theoretical and experimental study on the formation of 4-X-chalcones (X=H, Cl, F, OCH 3, N(CH 3) 2) was carried out by the Claisen–Schmidt reaction. The influence of pH and temperature was analyzed. Under the adopted experimental conditions 4-X-chalcones were the only reaction products. In the theoretical study, the thermodynamic magnitudes and the reactivity indexes calculated with the AM1 method were used. The mechanism of Nayak and Rout was analyzed critically and a new mechanism was proposed, characterized by: (1) rapid nucleophilic attack of the catalyst (OH −) on the carbon atom of the methyl group of acetophenone; (2) attacks of the acetophenonate ion on the carbon atom of the aldehyde group (slow step of the reaction); (3) a configurational equilibrium cis- s- cis⇔ trans- s- trans between intermediate compounds is achieved; (4) electrophilic attack of a molecule of water on the oxygen atom bound to C β of the intermediate anion, forming a neutral intermediate, with catalyst regeneration; and (5) intramolecular dehydration of the neutral intermediate to give the 4-X-chalcone trans-s-trans. The proposed mechanism explains satisfactorily the global rate of the third-order reaction, and the variation with substituents of the global reaction rate constants and the equilibrium constants of 4-X-chalcones formation.