9‐Fluoro‐18‐hydroxy‐[3.3]metacyclophane: Synthesis and Estimation of a C−F···H−O Hydrogen Bond

Abstract

A cyclophane composed of fluorobenzene and phenol units was synthesized in order to observe the C−F···H−O hydrogen bond. In the crystal structure, 20% of the molecule clearly shows the intramolecular hydrogen bond and the other 80% is free from hydrogen bonding. On the other hand, a distinct low-field shift of the phenolic OH proton was observed in the 1 H NMR spectrum compared to that of the F-free analog.

C–F⋯HO hydrogen bond in 8-fluoro-4-methyl-1-naphthol

“…The shifts of these bands were the same in the concentration range of 1.0 Â 10 À3 to 2.0 Â 10 À4 mol dm À3 . As well as in previous studies of the 9-fluoro-18-hydroxy-[3.3]metacyclophane [10] or 2-fluorophenyldiphenylmethanol [11], the IR spectra in solution were not useful for determining the C-FÁ Á ÁHO HB.…”

“…We tried to detect such weak interactions by simple techniques, which are familiar to organic chemists, and succeeded in observing the C-FÁ Á ÁHO HB of 9-fluoro-18-hydroxy-[3.3]metacyclophane using the NMR and IR spectra, and X-ray crystallographic analysis [10]. The cyclophane system is a good model for this purpose because the geometry of the F and O atoms is adequate and these atoms are spatially close to each other but are separated by many s bonds.…”

Binding Properties of Aromatic Carbon-Bound Fluorine

“…The results in Table 1 (MP2) clearly indicate that aromatic fluorine can participate in significantly energetic hydrogen bonds with water (entries [10][11][12][13][14][15][16][17][18][19]. The most energetic hydrogen bond is found between water and the fluorine in monofluorobenzene (10).…”

“…Interestingly, the ortho (11, -2.4 kcal/mol), meta (12, -2.2 kcal/mol), and para (13, -2.3 kcal/ mol) substitution patterns yield similar binding energies within the BSSE error. The additional fluorine in the trifluorobenzene series (14)(15)(16)(17)(18)(19) yields complexes with water characterized by even smaller energies (1.9-2.0 kcal/mol). The binding of the aromatic fluorine in monofluorobenzene to cations such as lithium, sodium, and ammonium reserves some surprises.…”

Immunomodulatory α‐Galactoglycosphingolipids: Synthesis of 2'‐Fluoro‐2'‐deoxy‐α‐galactosylceramide and an Evaluation of Its Immunostimulating Properties

“…The capacity of organically bound fluorine to act as an OH mimic and enter into hydrogen bonding as an acceptor has been widely discussed, and it is now generally acknowledged that the fluorine atom can indeed act as hydrogen-bond acceptor, although the resulting F···H hydrogen bonds are clearly weaker (about half as much) than O···H hydrogen bonds. [10] We report below the first total synthesis of 2Ј-fluoro-2Ј-deoxy-α-d-galactopyranosylceramide (1), and a preliminary evaluation of its biological activity using lymphocyte proliferation tests (Scheme 1). Scheme 1.…”