Revisiting the Conformational Equilibrium of 1,1,2-Trifluoroethane and 1,1,2,2-Tetrafluoroethane: An NBO Study
Year: 2025
Type: article
Abstract: High Resolution Image Download MS PowerPoint Slide Organofluorine compounds are key to pharmaceutical, agrochemical, and high-performance material applications, where C–F bond conformations influence critical properties such as solubility, lipophilicity, and biological activity. While the conformational behavior of 1,2-difluoroethane and its characteristic gauche effect is well understood, the structural preferences of 1,1,2-trifluoroethane and 1,1,2,2-tetrafluoroethane have remained less explored, particularly in light of hyperconjugation theory. In this quantum-chemical study, the conformational equilibria of these two model fluoroalkanes were investigated using density functional theory and Natural Bond Orbital (NBO) analysis, with complementary NMR coupling constant calculations. The results reveal that Lewis-type interactions govern conformational stability, favoring the anti-gauche conformer in 1,1,2-trifluoroethane and the double antigauche conformer in 1,1,2,2-tetrafluoroethane. Nevertheless, electron delocalization plays an essential role in ensuring that staggered conformations remain energy minima, as fully localized electronic structures would yield only a single conformer for each compound. These findings refine our understanding of hyperconjugative and electrostatic effects in fluorinated ethanes and provide a more nuanced framework for predicting conformational preferences in difluoromethyl-containing systems.
Author: Matheus P. Freitas
Institutions: Universidade Federal de Lavras, Institute of Natural Sciences
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Award: G1862978056
OpenAlex ID: W4415478258