Open Access Research article

Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference

Manuel Velázquez-Ponce1, Héctor Salgado-Zamora2*, Hugo A Jiménez-Vázquez2, Maria Elena Campos-Aldrete2, Rogelio Jiménez2, Humberto Cervantes3 and Taibi Ben Hadda4

Author Affiliations

1 Departamento de Formación Básica Disciplinaria, Unidad Profesional Interdisciplinaria de Ingeniería Campus Guanajuato, Instituto Politécnico Nacional, Silao de la Victoria-Guanajuato, 36275, Mexico

2 Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Mexico, DF, 11340, Mexico

3 Área de Química, Universidad Autónoma Metropolitana-Unidad Azcapotzalco, Mexico, DF, 02200, México

4 Université Mohammed Premier, Faculté des Sciences, Laboratoire Chimie Matériaux, Oujda, 60000, Morocco

For all author emails, please log on.

Chemistry Central Journal 2013, 7:20  doi:10.1186/1752-153X-7-20

Published: 31 January 2013

Abstract

Background

The proton at position 5 of imidazo[1,2-a]pyridines substituted with an angular electron withdrawing group (EWG) at position 3, shows an unusual downfield chemical shift, which is usually explained in terms of a peri effect. However usage of this term is sometimes confusing. In this investigation, it is proposed that the aforementioned shift is in fact a combination of several factors: Anisotropy, long-distance mesomerism and an attractive intramolecular interaction of the electrostatic hydrogen bond type.

Results

Theoretical calculations were performed aimed to obtain evidence of the existence of an intramolecular non-bonding interaction between H-5 and the oxygen atom of the EWG. Results derived from conformational and vibrational analysis at the DFT B3LYP/6-311++G(d,p) level of theory, the determination of Bond Critical Points derived from AIM theory, and the measurement of some geometrical parameters, support the hypothesis that the higher stability of the prevailing conformation in these molecules (that in which the oxygen of the EWG is oriented towards H-5) has its origin in an intramolecular interaction.

Conclusion

Computational calculations predicted correctly the conformational preferences in angular 3-π-EWG-substituted imidazo[1,2-a]pyridines. The existence of an electrostatic hydrogen bond between H-5 and the oxygen atom of the π-EWG was supported by several parameters, including X-ray crystallography. The existence of such structural array evidently impacts the H-5 chemical shift.

Keywords:
Imidazo[1,2-a]pyridine; Peri effect; Hydrogen bonding; Conformational preference

Graphical abstract