A density functional theory study of keto-enol tautomerism in 1,2-cyclodiones: Substituent effects on reactivity and thermodynamic stability

This study systematically investigated the influence of substituents (NH 2 , CH 3 , CF 3 , and Cl) on the keto-enol tautomerism of 1,2-cyclodiones, focusing on reactivity and thermodynamic stability. Calculations were performed using the M06-2X/6-311G++** level of theory, with a solvation model through CPCM/M06-2X/6-311G++**. Results indicate ring-size dependent tautomerism, with three-, five-, and six-membered rings favouring the keto-enol form, while four- and seven-membered rings favour the diketo form. The NH 2 substituent uniquely stabilised the keto-enol form. Electron-donating groups generally stabilised the keto-enol form. Contrary to common expectations, a direct correlation between dipole moment and stability order was not universally observed within 1,2-cyclodione systems, with the NH 2 group demonstrating nuanced effects. Similarly, dipole moment and electrostatic potential variance did not exhibit consistent correlation under the influence of different substituents. The diketo tautomer was generally found to be more reactive than the keto-enol form, especially in non-polar solvents. Surprisingly, substituent groups decreased the reactivity of the diketo form relative to the unsubstituted compound.