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

 

Autores. Cesar Garcias Morales, Alejandro Hernández-Tanguma, Armando Ariza-Castolo

Revista. Tetrahedron

https://doi.org/10.1016/j.tet.2024.134086

Resumen. 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 13C–1H one-bond coupling constants (1JC,H) and the 1H 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 1JC,Hax are lower than 1JC,Heq as a consequence of the nN→σ*C–H interaction, while the 1JC,Hax are very similar to 1JC,Heq in the β-carbon to the nitrogen. This is mainly due to the stabilization energy (Eint 18–19.2 kJ/mol) by the hyperconjugative σCβ–Heq→σ*C–N interactions. This effect is marked in the chemical shift of 1H, where Heq shifts to a lower frequency than Hax. 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.

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27/09/2024 01:56:53 p. m.