Endocyclic oxygen in 3-fluorodihydro-2H-pyran-4(3H)-one that does not induce the gauche effect.

2-Fluorocyclohexanone undergoes chair inversion, giving rise to axial and equatorial conformers, with the equatorial form being highly preferred in solution, for example, 87% in chloroform and 93% in methylene chloride. Modifications in the conformational preferences can modify macroscopic properties of 2-fluoro ketones. The introduction of an endocyclic oxygen in 2-fluorocyclohexanone to give 3-fluorodihydro-2H-pyran-4(3H)-one would be expected to create a gauche effect in the axial conformer along with the O-C-C-F moiety, inducing an increase of its population.

Conformational analysis of 2,2-difluoroethylamine hydrochloride: double gauche effect.

The gauche effect in fluorinated alkylammonium salts is well known and attributed either to an intramolecular hydrogen bond or to an electrostatic attraction between the positively charged nitrogen and the vicinal electronegative fluorine atom. This work reports the effect of adding a fluorine atom in 2-fluoroethylamine hydrochloride on the conformational isomerism of the resulting 2,2-difluoroethylamine chloride (2). The analysis was carried out using NMR coupling constants in D2O solution, in order to mimic the equilibrium conditions in a physiological medium, in the gas phase and in implicit water through theoretical calculations.

The preferred all-gauche conformations in 3-fluoro-1,2-propanediol.

A competition between the terminal fluorine and hydroxyl groups by the central hydroxyl group as hydrogen bond donor in 3-fluoro-1,2-propanediol would be expected to dictate the conformational isomerism of this compound, but also the repulsion between the electronegative and bulky vicinal substituents. Indeed, an intramolecular hydrogen bond has been verified only for a local minimum using QTAIM calculations, while the most stable conformer exhibits an all-gauche conformation with a small stabilizing contribution from the nF→σ interaction. The preferred orientation of the OH and F substituents was confirmed from the chemical shifts and coupling constants of the diastereotopic hydrogens.

Alkyl group effect on the conformational isomerism of trans-2-bromoalkoxycyclohexanes analyzed by nmr spectroscopy and theoretical calculations.

Suitable (3)J(H,H) coupling constants and theoretical calculations were used to define the conformational preferences of trans-2-bromoalkoxycyclohexanes (alkoxy = OMe, OEt, O(i)Pr, and O(t)Bu) for the isolated molecule and as a function of the medium. The diaxial conformer was preponderant, or at least similarly populated to the diequatorial form, for the tert-butoxy derivative only, while the diequatorial conformer was prevalent for the remaining alkoxy derivatives (except for the OMe derivative in CCl(4) solution). The conformational behavior of these compounds was analyzed on the basis of classical steric effects and attractive electron delocalizations, by means of natural bond orbital analysis.

Theoretical and infrared studies on the conformational isomerism of trans-2-bromo-alkoxycyclohexanes.

The infrared spectra of trans-2-bromo-alkoxycyclohexanes (alcoxy = OMe, OEt, O(i)Pr and O(t)Bu) were obtained for the neat liquid, and the C-Br stretching mode was quantitatively analyzed to give insight about the conformational isomerism of these compounds. Frequency calculations supported the band assignments, and the relative band intensities suggest that the diaxial conformer is prevalent for the methoxy and tert-butoxy derivatives (51 and 56%, respectively), while the diequatorial form is preponderant for the ethoxy and isopropoxy derivatives (76 and 77%, respectively). Therefore, the size of the alkoxy group plays a determinant role in determining the conformational preferences of the title compounds.