Abstract
The structure and tautomeric equilibria of the Schiff base of gossypol with 3-amino-5-methylisoxazole were investigated by NMR spectroscopy and quantum chemical methods. It was established that in chloroform solution the compound exists exclusively in the dienamine tautomeric form.
The reasons why most Schiff bases of gossypol preferentially exist in the dienamine form are not yet fully understood. One factor influencing the tautomeric equilibrium may be the formation of an intramolecular hydrogen bond between the hydroxyl proton and the oxygen atom of the adjacent carbonyl group. Upon transition from chloroform to DMSO-d₆, intermolecular hydrogen bonding with solvent molecules occurs, leading to weakening of the intramolecular hydrogen bond. This may lead to a shift of the tautomeric equilibrium toward the diimine form.
According to ¹H NMR data, the Schiff base of gossypol with 3-amino-5-methylisoxazole in DMSO-d₆ exists in both dienamine and diimine tautomeric forms, as evidenced by the presence of characteristic proton signals corresponding to each form. The thermodynamic parameters of the tautomeric transition in DMSO-d₆ were determined. The equilibrium constants were calculated from the integral intensities of the C(11)-H proton signal, and the corresponding standard Gibbs free energy values (ΔG°) were obtained. From the temperature dependence of ΔG° (ΔG° = ΔH° − TΔS°), the standard enthalpy (ΔH°) and entropy (ΔS°) of the process were derived.
The ¹³C NMR data further confirm the coexistence of both tautomeric forms in DMSO-d₆ and reveal significant differences in the chemical shifts of the carbon atoms in the diimine and dienamine forms. DFT calculations at the B3LYP/6-31G(d) level were performed to establish the structural characteristics of both tautomers. The naphthyl fragments were found to be noncoplanar, with a dihedral angle of approximately 102°. It was established that in the gas phase the dienamine tautomeric form of the studied molecule is energetically more favorable.