Fluoromethanol, conformations

This is simply the anomeric effect viewed in a different way Consider fluoromethanol (32). It has an HOCF dihedral angle of 60°,26 so the CF bond will be perfectly antiparallel to one of the lone pairs if the oxygen atom is represented by 22. However, care is needed if we depict the oxygen by 21. Conformation 33 is not the best the p-o CF... 

Fluoromethanol also shows a preference for the gauche conformation. At the HF/6-31G level it is 4.8 kcal/mol more stable than the anti conformation and 2.4 kcal/mol more stable than the eclipsed conformation. Only the gauche conformation aligns an unshared pair anti to the C-F bond. 

The Fj constant is strongly negative (Fj =—20.3 kJ/mol) for fluoromethylamine (4) but strongly positive (Fi = + 21.9 kJ/mol) for fluoromethanol (121). A negative Fj constant indicates that the most stable conformation (from the F, term point of view) is ap and the least stable is sp. If Fj is positive, on the other hand, the most stable conformation (from the F term point of view) is sp. This finding is consistent with stabilization (or destabilization) of these molecules by intramolecular dipolar interactions as pictured in Figure 20. For 121, the ap form is less stabilized (or more destabilized), whereas attractive, dipolar interactions in 121 are present predominantly in the sp conformation. ... 

Thus the synclinal conformer of fluoromethanol (121) appears to be preferred due to overlap repulsion as well. This conclusion is of significance, since it provides additional proof for the role of destabilizing interactions in the origin of the anomeric effect. Though the importance of destabilizing interactions involving lone electron pairs seems to be well established even in the... 

The validity of the Lemieux-Chii interpretation was entirely supported, and the picturesque rabbit-ear idea shown untenable, by a theoretical study that used an ab initio (Hartree-Fock) calculation, with fluoromethanol as the model compound. The calculations showed that the stable conformation has the C-F bond trans to one electron pair and gauche to another, whereas the conformation in which the C-F bond bisects the electron pairs is the energy maximum. Similar interpretations were established for hydrazine, hydroxylamine, and hydrogen peroxide. The concept can be stated in general terms as a destabilization of a conformation that places a polar (C-X) bond eclipsed between two electron pairs. 

If these two conformations are presented pictorially in a different perspective, it becomes clear that the most stable conformation corresponds to axial fluoro-substitution in a tetrahydropyran ring, and the least stable conformation to equatorial fluoro-substitution. The calculated conformational preferences for fluoromethanol then mimic the anomeric effect seen in heterocyclic systems, where electronegative substituents are more stable in the axial than in the equatorial orientation. 

The stereochemical requirements of adjacent lone electron pairs and polar bonds have been discussed in an important paper which analysed the considerable volume of available data, including those pertaining to 1,4-dithians and similar systems. The Edwards-Lemieux effect in substituted 1,4-dithians was accounted for satisfactorily by calculations using fluoromethanol as a model compound. The temperature-dependence of the F n.m.r. spectrum of perfluoro-1,4-dithian indicated a barrier to ring-inversion of 10.05 0.10 kcalmol. The fluorine chemical-shift differences at — 90 °C appeared to be consistent with a preferred chair conformation, possibly strongly puckered as in 1,4-dithian. The i.r. and Raman spectra of 1,4-dithian and 1,4-diselenan have received detailed attention, and the crystal and molecular structures of... 

Predict the preferred conformation of fluoromethanol, FCH2OH, around the C-O bond and briefly rationalize your choice. 

The case of fluoromethanol is also illustrative. There is a substantial barrier to rotation of the hydroxyl hydrogen with respect to the fluoromethyl group, with the preferred orientation having the hydroxyl hydrogen gauche to the fluorine. This conformation is 12.6 kcal/mol more stable than that having the fluorine anti to the hydroxyl hydrogen. 

If these two conformations are shown from a different perspective it becomes clear that fluoromethanol is another example of the anomeric (or gauche) effect discussed in Section 3.5. The gauche arrangement permits a lone pair on oxygen to be in an anri-periplanar relationship to the C-F bond. 

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