Study of stereoelectronic effects in saturated heterocycles containing nitrogen and their relation with intermolecular and intramolecular interactions

This study describes the synthesis of imidazolidines, hexahydropyrimidines, and 1,5-diazabicyclo[3.2.1]octane. These compounds are used as models to study the hyperconjugation using nuclear magnetic resonance (NMR) spectroscopy through the 13 C - 1 H one-bond coupling constants ( 1 J C,H ) and the 1 H chemical shifts. The molecular structures are corroborated by single-crystal X-ray diffraction, and the electron distribution is studied through electron mapping obtained by using Hirshfeld surface analysis to determine intermolecular and intramolecular interactions. The NMR data show that the 1 J C,H ax are lower than 1 J C,H eq as a consequence of the n N -> sigma* C - H interaction, while the 1 J C,H ax are very similar to 1 J C,H eq in the beta -carbon to the nitrogen. This is mainly due to the stabilization energy (E int 18 - 19.2 kJ/mol) by the hyperconjugative sigma C beta-H eq -> sigma * C - N interactions. This effect is marked in the chemical shift of 1 H, where H eq shifts to a lower frequency than H ax . Finally, the Hirshfeld surface analysis shows that the atoms involved in hyperconjugation play an important role in the intermolecular and intramolecular interactions. The obtained results can support new study models that would afford an accurate determination of interactions in molecular recognition and predict interactions between drugs and proteins, which in turn will help the design and development of new drugs.