Electrostatic Effects on the Stability of 2,4,6-Trifluoromethylidenecyclohexanes, Cyclohexanones, and Cyclohexanethiones: Beyond Nonconventional Hydrogen Bonding.
- 1Department of Chemistry, Institute of Natural Sciences, Federal University of Lavras, Lavras, Minas Gerais, Brazil.
Abstract
Six-membered rings provide valuable frameworks for investigating intramolecular interactions, as their axial and equatorial bonds create distinct chemical environments governed by steric, electrostatic, and hyperconjugative effects. Fluorine is an especially suitable probe for such studies because the C─F bond is among the most polar in organic chemistry. In this context, 2,4,6-trifluoromethylidenecyclohexanes (1), cyclohexanones (2), and cyclohexanethiones (3) were investigated by quantum chemical calculations at the B3LYP/def2-TZVP level to evaluate the role of unconventional C─F···H─C hydrogen bonding and electrostatic effects on stereoisomer stability. For compounds 1 and 3, the eae stereoisomer is favored not only by unconventional hydrogen bonding but also by stabilizing electrostatic gauche interactions. Interestingly, the C─F···H─C interaction is weaker than in the monofluorinated counterparts because fluorination decreases the acidity of the α-hydrogens while simultaneously rendering the α-carbon atoms positively charged, thereby enhancing favorable F···C electrostatic interactions. Although this electrostatic effect is also present in compound 2, the eae stereoisomer is primarily stabilized by σC─H → π*C═O hyperconjugation, since the equatorial α-fluorine atoms at C2 and C6 experience dipolar repulsion with the C═O bond, diminishing the electrostatic stabilization. These electrostatic interactions persist in a high-dielectric medium (water), where increased solvent polarity further stabilizes the more polar stereoisomers.
Related
- Structure and Solvent Effects on Nonconventional Fluorescence in Choline-Carboxylic Acid Ionic Liquids Hybrid Solvents.
- Polarization Is Required to Model Electrostatic Preorganization: The Case of Chorismate Mutase
- Ensemble Molecular Surface Electrostatic Potential Descriptors as Informative Features for Active Learning
- Short-Rotation Coppice Pellets as Biofuels in a Modern Boiler with an Electrostatic Precipitator: Particulate Matter and Carbon Monoxide Emissions
- GPU infrastructure for ML/MM with electrostatic embedding for enzyme chemistry
BibTeX
@article{freitas2026electrostatic,
title = {{Electrostatic Effects on the Stability of 2,4,6-Trifluoromethylidenecyclohexanes, Cyclohexanones, and Cyclohexanethiones: Beyond Nonconventional Hydrogen Bonding.}},
author = {Matheus P Freitas},
journal = {Chemphyschem : a European journal of chemical physics and physical chemistry},
year = {2026},
month = oct,
doi = {10.1002/cphc.70619},
url = {https://europepmc.org/article/MED/42956277},
note = {CC BY},
}
RIS
TY - JOUR
TI - Electrostatic Effects on the Stability of 2,4,6-Trifluoromethylidenecyclohexanes, Cyclohexanones, and Cyclohexanethiones: Beyond Nonconventional Hydrogen Bonding.
AU - Matheus P Freitas
PY - 2026
DA - 2026/10/29
JO - Chemphyschem : a European journal of chemical physics and physical chemistry
DO - 10.1002/cphc.70619
UR - https://europepmc.org/article/MED/42956277
AB - Six-membered rings provide valuable frameworks for investigating intramolecular interactions, as their axial and equatorial bonds create distinct chemical environments governed by steric, electrostatic, and hyperconjugative effects. Fluorine is an especially suitable probe for such studies because the C─F bond is among the most polar in organic chemistry. In this context, 2,4,6-trifluoromethylidenecyclohexanes (1), cyclohexanones (2), and cyclohexanethiones (3) were investigated by quantum chemical calculations at the B3LYP/def2-TZVP level to evaluate the role of unconventional C─F···H─C hydrogen bonding and electrostatic effects on stereoisomer stability. For compounds 1 and 3, the eae stereoisomer is favored not only by unconventional hydrogen bonding but also by stabilizing electrostatic gauche interactions. Interestingly, the C─F···H─C interaction is weaker than in the monofluorinated counterparts because fluorination decreases the acidity of the α-hydrogens while simultaneously rendering the α-carbon atoms positively charged, thereby enhancing favorable F···C electrostatic interactions. Although this electrostatic effect is also present in compound 2, the eae stereoisomer is primarily stabilized by σC─H → π*C═O hyperconjugation, since the equatorial α-fluorine atoms at C2 and C6 experience dipolar repulsion with the C═O bond, diminishing the electrostatic stabilization. These electrostatic interactions persist in a high-dielectric medium (water), where increased solvent polarity further stabilizes the more polar stereoisomers.
SN - 1439-4235
SN - 1439-7641
ER -