Hydrogen Bonds Involving Fluorine Atoms

The strongest hydrogen bond known is that in the hydrogen difluoride ion, HFi The enthalpy of formation of HF (g) from HF (g) and F (g) has been evaluated as 58 5 kcal/mole by Wadaington  

Evidence that the proton lies midway between the fluorine atoms in the crystal KHF has been provided by entropy measurements,28 study of the polarized infrared spectrum,29 neutron diffraction,80 and nuclear spin magnetic resonance.81 The uncertainty in the location of the proton at the midpoint between the fluorine atoms is reported to be 0.10 A for the neutron diffraction study and 0.06 A for the nuclear magnetic resonance study. 

17 The enthalpy of formation of HF, (aq) from HF (aq) and F (aq) is only about 4 kcal/mole. Hence the hydrogen bonds formed by F and HF with water molecules must be much stronger than those formed by HF. If we make the reasonable assumption that most of the difference is due to the four hydrogen bonds between F and ligated water molecules, each of these O—H F bonds is to be assigned bond energy about 13 kcal/mole. 

Crystalline hydrogen fluoride has been found38 to contain infinite zigzag chains with F—H -F distance 2.49 0.01 A and bond angle 120.1°. These values are more accurate than those for the gas phase. 

The F—H—F distance in NH4HF2 is 2.32 0.02 A, about 0.06 A greater than in KHF. This increase may be the effect of the N—N- -F hydrogen bonds in partially saturating the valence of the fluorine atom, and thus decreasing the strength of the F—H—F bonds. 

---

Dalvit D, Vulpetti A (2012) Intermolecular and intramolecular hydrogen bonds involving fluorine atoms implications for recognition, selectivity, and chemical properties. ChemMedChem 7 262-272... 

SiFl(C,H J POL, SiFlfCH ) NOL and SiFiC H NOL. The interaction of silicon tetrafluoride with methanol has been shown recently to involve strong hydrogen bonds between fluorine atoms and hydroxyl protons rather than octahedral coordination of silicon (3). We have now examined the relative tendency of silicon and germanium tetrafluoride to complex with simple ethers, acetone, and methanol. 

Hydrogen bond involving an acidic hydrogen atom borne by a fluorine-substituted or halogen-substituted carbon seems to contribute to the activity and the selectivity of volatile fluorinated anaesthetics (Table 2). These molecules, although non-functional, can bind stereoselectively with protein targets of the central nervous system [33,34]. 

Fig. 16 Crystal structure of the BA/PFBA cocrystal viewed along the stacking axis. Interstack hydrogen bonding involving the carboxylic acid groups is shown as dashed lines. Hydrogen atoms are not shown, and the fluorine atoms of the PFBA molecules are shown in green...

In some force fields the interaction sites are not all situated on the atomic nuclei. For example, in the MM2, MM3 and MM4 programs, the van der Waals centres of hydrogen atoms bonded to carbon are placed not at the nuclei but are approximately 10% along the bond towards the attached atom. The rationale for this is that the electron distribution about small atoms such as oxygen, fluorine and particularly hydrogen is distinctly non-spherical. The single electron from the hydrogen is involved in the bond to the adjacent atom and there are no other electrons that can contribute to the van der Waals interactions. Some force fields also require lone pairs to be defined on particular atoms these have their own van der Waals and electrostatic parameters. 

During electrochemical fluorination retention of important functional groups or atoms in molecules is essential. Acyl fluorides and chlorides, but not carboxylic acids and anhydrides (which decarboxylate), survive perfluorination to the perfluorinated acid fluorides, albeit with some cyclization in longer chain (>C4) species [73]. Electrochemical fluorination of acetyl fluoride produces perfluoro-acetyl fluoride in 36-45% yields [85]. Electrochemical fluorination of octanoyl chloride results in perfluorinated cyclic ethers as well as perfluorinated octanoyl fluonde. Cyclization decreases as initial substrate concentration increases and has been linked to hydrogen-bonded onium polycations [73]. Cyclization is a common phenomenon involving longer (>C4) and branched chains. a-Alkyl-substituted carboxylic acid chlorides, fluorides, and methyl esters produce both the perfluorinated cyclic five- and six-membered ring ethers as well as the perfluorinated acid... 

Xenon difluoride fluorinates adamantane in low yield [45] (equation 22) When the carbon-hydrogen bond is activated by an a-sulfur atom, fliiorination occurs readily The reactions involve intermediates that contain sulfur-fluorine bonds. At-Fluoropyridinium reagents behave similarly [99, 100, 101, 102] (equations 55-57)... 

---