Ei. Gasull et al., A theoretical and experimental study of the formation mechanism of 4-X-chalcones by the Claisen-Schmidt reaction, J MOL ST-TH, 503(3), 2000, pp. 131-144
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.