Conformational preferences for 1,2- and 1,4-difluorocyclohexane

Area of Science:

• Organic Chemistry
• Computational Chemistry
• Physical Chemistry

Background:

• Conformational analysis of fluorinated cyclohexanes is crucial for understanding molecular behavior.
• Previous studies suggested differing conformational preferences based on phase.

Purpose of the Study:

• To experimentally and computationally investigate the conformational preferences of 1,2-difluorocyclohexane.
• To elucidate the influence of phase (gas vs. solution) on conformational stability.
• To re-examine the conformational preferences of 1,4-difluorocyclohexanes.

Main Methods:

• Nuclear Magnetic Resonance (NMR) spectroscopy for experimental analysis.
• Coupled Cluster Singles Doubles/6-311+G(2df,p) (CCSD/6-311+G(2df,p)) computational method for theoretical calculations.
• Self-Consistent Ion-Pair Interaction Model (SCIPCM) reaction field calculations to simulate solvent effects.

Main Results:

• Experimental and computational data confirm the diaxial conformer of trans-1,2-difluorocyclohexane is more stable in the gas phase.
• The diequatorial conformer of trans-1,2-difluorocyclohexane is more stable in solution.
• SCIPCM calculations accurately reproduced the observed solvent effects on conformational preference.
• Computational reexamination of 1,4-difluorocyclohexanes was also performed.

Conclusions:

• The conformational preference of 1,2-difluorocyclohexane is highly dependent on the phase.
• Solvent effects play a significant role in determining the preferred conformation of fluorinated cyclohexanes.
• Computational methods, including SCIPCM, are reliable for predicting conformational behavior in different environments.