First-principles insights into the halogen effect on enol-imine and keto-amine tautomerism in 4-halosalicylideneaniline derivatives

Density functional theory (DFT) calculations were carried out for N-(3,5-di-tert-butylsalicylidene)-4-halobenzene (DTBSA-X) derivatives to examine how halogen substitution (X = H, F, Cl, Br or I) modulates the enol-imine/keto-amine prototropic equilibrium and the associated intramolecular hydrogen bonding in the ground state. Across the series, the enol-imine form is predicted to be more stable than the keto-amine form at room temperature. In Br- and I-substituted derivatives, the tautomeric energy gap exhibits a high sensitivity to the basis set rather than the functional type. The more reliable def2-TZVP basis confirms a robust preference for the enol-imine form, with ∆ G values ranging from 4 to 6 kcal/mol, depending on the functional used. To quantify this halogen-series trend, thermochemical corrections, equilibrium constants, Boltzmann populations, and QTAIM descriptors at the relevant bond critical points were assessed. Noncovalent interaction analysis reveals that the weaker O-H···N hydrogen bonding in the Br/I enol-imine forms is compensated by stronger N-H···O interactions in the keto-amine species. Computed vibrational and electronic spectra indicate distinct halogen-dependent signatures, including wavenumber shifts and frontier-orbital gap modulation across the halogen series with smaller HOMO-LUMO gaps for Br/I than for H/F/Cl. Overall, these results provide a focused ground-state benchmark for halogen-dependent stabilization in DTBSA systems, interpreted using substituent electronic effects, thermochemical, and topological descriptors in related Schiff-base frameworks.