Reactivity of (E)-4-aryl-4-oxo-2-butenoic acid arylamides toward 2-mercaptoethanol. A LFER study

Abstract

The reactivity of fifteen (E)-4-aryl-4-oxo-2-butenoic (aroylacrylic) acid arylamides toward thiols was studied, measuring the rate constants of the addition of model thiol nucleophile, 2-mercaptoethanol. The influence of the variation of the substituents on the phenyl rings on the rate of reaction was quantified using the Hammett substituent constants and descriptors derived from ab initio or semiempirical calculations (atomic charges, HOMO, and LUMO). Statistically significant linear correlations between second-order rate constants and Hammett substituent constants, as well as energies of LUMO orbitals, were obtained. Substituents on both aroyl and arylamido moieties were shown to influence the reactivity of studied compounds toward thiols. The regioselectivity of reaction was confirmed by NMR spectroscopy. Exclusively β-addition product with respect to the aroyl keto group was obtained. The determined enthalpy and entropy of activation were found to be in agreement with the proposed reaction mechanism, which includes a highly ordered transition state. Graphical Abstract: [Figure not available: see fulltext.] © 2013 Springer-Verlag Wien.