Hydrogen and Halogen Bond Interactions with 2,6-Dimethoxypyridine

Raman spectroscopy and computational chemistry are used to explore the effects of noncovalent interactions with the nitrogen-containing building block 2,6-dimethoxypyridine (DMOP). Previously, we have shown that hydrogen and halogen bonding with simple nitrogen containing heterocycles lead to partial charge transfer and evolving vibrational spectroscopic properties. Adding electron-donating or electron-withdrawing groups to azabenzenes should allow us to tune these interactions. Here, DMOP, with its two methoxy substituents, offers an excellent opportunity to study the effect of electron withdrawal on spectroscopic properties. Unlike in previous studies, hydrogen bonding does not lead to any discernible experimental spectroscopic changes in varying mixtures of DMOP and water. Computational results suggest that water preferentially binds to itself or to the two oxygen atoms of the methoxy groups rather than to the lone nitrogen atom. This competition for binding and steric effects is possibly the origin of the lack of experimental changes. Halogen bonding interactions between DMOP and heptafluoro-2-iodopropane (HFIP), however, resulted in experimental vibrational red shifts (shifts to lower energy) in both the C-I stretching and the C-C-C symmetric stretching modes of HFIP, as predicted by computations and previous studies. Natural bond orbital (NBO) calculations indicate greater charge transfer in halogen versus hydrogen bonding interactions. Collectively, these results suggest that the addition of competitive binding sites and bulky functional groups may prevent access to the lone pair electrons on the nitrogen atoms of azabenzenes, but also that the halogen bond interaction between iodine and either nitrogen or oxygen is a resilient binding motif in solution that can be exploited for molecular self-assembly.