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

A theoretical and experimental study on the formation of 4-X-chalcones (X = H, Cl, F, OCH3, N(CH3)(2)) was carried out by the Claisen-Schmidt reaction . The influence of pH and temperature was analyzed. Under the adopted exper imental conditions 3-X-chalcones were the only reaction products. In the th eoretical study, the thermodynamic magnitudes and the reactivity indexes ca lculated 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 confi gurational equilibrium cis-s-cis double left right arrow trans-s-trans betw een intermediate compounds is achieved; (4) electrophilic attack of a molec ule of water on the oxygen atom bound to C-beta of the intermediate anion, forming a neutral intermediate, with catalyst regeneration: and (5) intramo lecular dehydration of the neutral intermediate to give the 4-X-chalcone tr ans-s-trans. The proposed mechanism explains satisfactorily the global rate of the third-order reaction, and the variation with substituents of the gl obal reaction rate constants and the equilibrium constants of 4-X-chalcones formation. (C) 2000 Elsevier Science B.V. All rights reserved.