Hexafluorobenzene, HFB or perfluorobenzene is an

organofluorine compound Organofluorine chemistry describes the chemistry of organofluorine compounds, organic compounds that contain a carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, ...

with the

chemical formula A chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, such as pare ...

. In this derivative of

benzene Benzene is an Organic compound, organic chemical compound with the Chemical formula#Molecular formula, molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar hexagonal Ring (chemistry), ring with one hyd ...

, all

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

atoms have been replaced by fluorine atoms. The technical uses of the compound are limited, although it has some specialized uses in the laboratory owing to distinctive spectroscopic properties.

Geometry of the aromatic ring

Hexafluorobenzene stands somewhat aside in the perhalogenbenzenes. If a perhalogenated benzene ring were to remain planar, then geometric constraints would force adjacent halogens closer than their associated nonbonding radius. Consequently the benzene ring buckles, reducing ''p''-orbital overlap and aromaticity to avoid the steric clash. Perfluorobenzene is an exception: as shown in the following table, two fluorines are small enough to avoid collision, retaining planarity and full aromaticity.

Synthesis

The direct synthesis of hexafluorobenzene from

and

fluorine Fluorine is a chemical element; it has Chemical symbol, symbol F and atomic number 9. It is the lightest halogen and exists at Standard temperature and pressure, standard conditions as pale yellow Diatomic molecule, diatomic gas. Fluorine is extre ...

has not been useful. Instead it is prepared via the

Finkelstein reaction The Finkelstein reaction, named after the German chemist Hans Finkelstein, is a type of SN2 reaction (substitution nucleophilic bimolecular reaction) that involves the exchange of one halogen atom for another. It is an equilibrium reaction, bu ...

of perchlorobenzene: : C₆Cl₆ + 6 KF → C₆F₆ + 6 KCl Antimony fluoride instead adds to the ring, breaking aromaticity. In principle, various halofluoromethanes pyrolyze to hexafluorobenzene, but commercialization was still in the initial stages in 2000.

Reactions

Hexafluorobenzene easily undergoes

nucleophilic aromatic substitution A nucleophilic aromatic substitution (SNAr) is a substitution reaction in organic chemistry in which the nucleophile displaces a good leaving group, such as a halide, on an aromatic ring. Aromatic rings are usually nucleophilic, but some aromatic c ...

. One example is its reaction with sodium hydrosulfide to afford

pentafluorothiophenol Pentafluorothiophenol is an organosulfur compound with the formula . It is a colorless volatile liquid. The compound is prepared by the reaction of sodium hydrosulfide and hexafluorobenzene. With a p''K''a of 2.68, it is one of the most acidic th ...

: :C₆F₆ + NaSH → C₆F₅SH + NaF The further reaction of pentafluorophenyl derivatives has long been puzzling, because the non-fluorine substituent has no effect. The second new substituent is always directed ''para'', to form a 1,4-disubstituted-2,3,5,6-tetrafluorobenzene. Hexafluorobenzene is thus a

comonomer In polymer chemistry, a comonomer refers to a polymerizable precursor to a copolymer aside from the principal monomer. In some cases, only small amounts of a comonomer are employed, in other cases substantial amounts of comonomers are used. Furt ...

in certain heavily fluorinated heat-resistant

polyether In organic chemistry, ethers are a class of compounds that contain an ether group, a single oxygen atom bonded to two separate carbon atoms, each part of an organyl group (e.g., alkyl or aryl). They have the general formula , where R and R� ...

s' synthesis. UV light causes gaseous HFB to isomerize to hexafluoro derivative of

Dewar benzene Dewar benzene (also spelled ''dewarbenzene'') or bicyclo .2.0exa-2,5-diene is a bicyclic isomer of benzene with the molecular formula C6H6. The compound is named after James Dewar who included this structure in a list of possible C6H6 structures i ...

Laboratory applications

Hexafluorobenzene has been used as a reporter molecule to investigate tissue oxygenation in vivo. It is exceedingly hydrophobic, but exhibits high gas solubility with ideal liquid gas interactions. Since molecular oxygen is paramagnetic it causes ¹⁹F NMR spin lattice relaxation (R1): specifically a linear dependence R1= a + bpO₂ has been reported. HFB essentially acts as molecular amplifier, since the solubility of oxygen is greater than in water, but thermodynamics require that the pO2 in the HFB rapidly equilibrates with the surrounding medium. HFB has a single narrow ¹⁹F NMR signal and the spin lattice relaxation rate is highly sensitive to changes in pO₂, yet minimally responsive to temperature. HFB is typically injected directly into a tissue and ¹⁹F NMR may be used to measure local oxygenation. It has been extensively applied to examine changes in tumor oxygenation in response to interventions such as breathing hyperoxic gases or as a consequence of vascular disruption. MRI measurements of HFB based on 19F relaxation have been shown to correlate with radiation response of tumors. HFB has been used as a gold standard for investigating other potential prognostic biomarkers of tumor oxygenation such as BOLD (Blood Oxygen Level Dependent), TOLD (Tissue Oxygen Level Dependent) and MOXI (MR oximetry) A 2013 review of applications has been published. HFB has been evaluated as standard in

fluorine-19 NMR Fluorine-19 nuclear magnetic resonance spectroscopy (fluorine NMR or 19F NMR) is an analytical technique used to detect and identify fluorine-containing compounds. 19F is an important nucleus for NMR spectroscopy because of its receptivity and ...

spectroscopy.

Toxicity

Hexafluorobenzene may cause eye and

skin irritation Irritation, in biology and physiology, is a state of inflammation or painful reaction to allergy or cell-lining damage. A stimulus or agent which induces the state of irritation is an irritant. Irritants are typically thought of as chemical age ...

, respiratory and digestive tract irritation and can cause

central nervous system depression Central nervous system depression (or CNS depression) is a nervous system disorder characterized by a severely impaired physiological state in which patients may exhibit decreased rate of breathing, decreased heart rate, and loss of consciousnes ...

per

MSDS A safety data sheet (SDS), material safety data sheet (MSDS), or product safety data sheet (PSDS) is a document that lists information relating to occupational safety and health for the use of various substances and products. SDSs are a wide ...

. The

National Institute for Occupational Safety and Health The National Institute for Occupational Safety and Health (NIOSH, ) is the List of United States federal agencies, United States federal agency responsible for conducting research and making recommendations for the prevention of work-related occ ...

(NIOSH) lists it in its Registry of Toxic Effects of Chemical Substances as

neurotoxicant Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature ner ...

Geometry of the aromatic ring

Synthesis

Reactions

Laboratory applications

Toxicity

See also

References

Further reading