Substituent Effects on the Relative Stabilities of Tautomers of 2-Butanone in the Gas Phase: A Theoretical PM3 and DFT Study

Abstract

This work presents a comprehensive theoretical study of the effects of substituents (X = F, OH, NH₂, CH₃, CN, CF₃) on the keto–enol tautomerism of 2-butanone. Using semiempirical PM3 and DFT (B3LYP/6-31G(d,p)) methods, we evaluated the relative stabilities of 2-butanone and its enol form, 2-buten-2-ol, in the gas phase. Thermodynamic parameters (ΔH, ΔG), isodesmic reaction enthalpies, and frontier molecular orbital (FMO) analyses were employed to investigate the influence of electron-donating and electron-withdrawing substituents at the α-carbon position. Our results indicate that 2-butanone is thermodynamically more stable than 2-buten-2-ol across all substituents. Electron-donating groups (EDGs) such as CH₃ and NH₂ exert a minor destabilization of the keto form, while electron-withdrawing groups (EWGs) like CN and CF₃ significantly reduce keto stability, favoring enolization. FMO analysis revealed that EWGs lower the HOMO-LUMO gap, indicating increased reactivity and a tendency to stabilize the enol tautomer. These insights provide a valuable framework for understanding substituent effects on tautomerism in aliphatic ketones.