Theoretical Study of Tautomeric Equilibrium, the Stability, Polarizability, HOMO-LUMO Analysis and Acidity of 4,4-diméthyl-3,4-dihydroquinolin-2(1H)-one Derivatives

Abstract

Quinoline derivatives have several reactionnels sites conferring them a hight reactivity. This makes them excellent precursors in the synthesis of new bioactive compounds. Considering the interest of quinoline chemistry and diversity of their applications, a study based on a theoretical approach of reactivity of 4,4-dimethyl-3,4-dihydro-quinolin-2(1H)-one and derivatives is carried. This study determines interaction sites of these derivatives in order to understand the mechanisms involved. Calculations are carried in gaseous phase and solution in N, N-dimethylformamide (DMF). Density Functional Theory (DFT/B3LYP) method associated with 6-311G(d) and 6-311+G (d) bases is used to perform these calculations. Results of the thermodynamic parameters showed that there is a tautomeric equilibrium relationship between the different derivatives Reactivity analysis based on Frontier Molecular Orbitals theory revealed that tautomers ketone are less reactive than tautomers enol. Calculation of Fukui indices indicates that the carbon atoms C², C³, C⁵, C ⁷ and C⁸ of quinoline-2-one ring are sites favorable to nucleophilic attack. Atoms N¹, C⁴, C⁶ and O¹¹ are nucleophilic sites therefore favorable to an electrophilic attack. Methoxyl substituent (CH₃O) decreases the acidity of nitrogen and oxygen atoms of quinolin-2-one while bromine atom increases acidity of these same sites. These results predict a deprotonation of the nitrogen (N¹) of the brominated quinoline-2-ones less energetic than that of the methoxylated derivatives. Conclusively, this work provides data to elucidate the mechanisms to understand the reactivity of 4,4-diméthyl-3,4-dihydroquinolin-2(1H)-one derivatives.