A theoretical study supported by calculations at the B3LYP/6-31+G and B3LYP/6-311++G(d,p) levels demonstrated that an attractive interaction involving a hydrogen bond between a hydroxyl group and an acceptor halogen atom (O-H⋯Cl) is present in 2,3-dihydro-2-hydroxy-2-chloromethylimidazo[1,2-a] pyridinium salts, which have an hemiaminal structure. However, the conformers obtained from a dihedral angle analysis performed upon these hemiaminal structures showed relatively small differences in energy among them, indicating that the hydrogen bonding interaction is not entirely responsible for preventing the aromatization process. Calculations were carried out on the gas phase of the hemiaminal cation 6b and the corresponding fully aromatic heterocycle cation 8b. It was found that the difference in energy between the two species is rather small, suggesting that other factors must be contributing to the hemiaminal isolation. The fact that a hydrogen bond is a stabilizing element of the hemiaminal suggests that the formation process of this compound should be favored in aprotic solvents. Accordingly, the condensation of several 2-aminopyridines with 3-bromo-1,1,1-trifluoroacetone was revised. The reaction performed in dry acetone (a non-competing hydrogen bond solvent) proceeded to the hemiaminal derivative, thus confirming the prediction made by theoretical calculations. © 2010 Elsevier B.V. All rights reserved.
Velázquez, M., Salgado-Zamora, H., Pérez, C., Campos-A, M. E., Mendoza, P., Jiménez, H., & Jiménez, R. (2010). Intramolecular hydrogen bond stabilization of hemiaminal structures, precursors of imidazo[1,2-a]pyridine. Journal of Molecular Structure, 56-61. https://doi.org/10.1016/j.molstruc.2010.05.044