Hexafluorobenzene, HFB, , or perfluorobenzene is an
organic,
aromatic
In chemistry, aromaticity is a chemical property of cyclic ( ring-shaped), ''typically'' planar (flat) molecular structures with pi bonds in resonance (those containing delocalized electrons) that gives increased stability compared to satur ...
compound
Compound may refer to:
Architecture and built environments
* Compound (enclosure), a cluster of buildings having a shared purpose, usually inside a fence or wall
** Compound (fortification), a version of the above fortified with defensive struc ...
. In this derivative of
benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
all
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
atoms have been replaced by fluorine atoms. The technical uses of the compound are limited, although it is recommended as a
solvent
A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...
in a number of
photochemical
Photochemistry is the branch of chemistry concerned with the chemical effects of light. Generally, this term is used to describe a chemical reaction caused by absorption of ultraviolet (wavelength from 100 to 400 nm), visible light (400–7 ...
reactions. In the laboratory hexafluorobenzene is used as
standard in
fluorine-19
Fluorine (9F) has 18 known isotopes ranging from to (with the exception of ) and two isomers ( and ). Only fluorine-19 is stable and naturally occurring in more than trace quantities; therefore, fluorine is a monoisotopic and mononuclidic elem ...
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fie ...
, solvent and standard in
carbon-13 NMR, solvent in
proton NMR
Proton nuclear magnetic resonance (proton NMR, hydrogen-1 NMR, or 1H NMR) is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 nuclei within the molecules of a substance, in order to determine the struct ...
, solvent when studying some parts in the
infrared
Infrared (IR), sometimes called infrared light, is electromagnetic radiation (EMR) with wavelengths longer than those of visible light. It is therefore invisible to the human eye. IR is generally understood to encompass wavelengths from around ...
and solvent in
ultraviolet–visible spectroscopy
UV spectroscopy or UV–visible spectrophotometry (UV–Vis or UV/Vis) refers to absorption spectroscopy or reflectance spectroscopy in part of the ultraviolet and the full, adjacent visible regions of the electromagnetic spectrum. Being relative ...
, as hexafluorobenzene itself hardly shows any absorbance in the UV region.
Geometry of the aromatic ring
Hexafluorobenzene stands somewhat aside in the perhalogenbenzenes. When counting for bond angles and distances it is possible to calculate the distance between two ortho fluorine atoms. Also the non bonding radius of the halogens is known. The following table presents the results:
The conclusion of the table is hexafluorobenzene is the only perhalobenzene being planar, the others all are buckled more or less. As a consequence in C
6F
6 the overlap between the
''p''-orbitals is optimal, while in the others it is less, also giving rise to a lower aromaticity in those compounds.
Synthesis
The direct synthesis of hexafluorobenzene from
benzene
Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
and
fluorine is not possible. The synthetic route proceeds via the reaction of
alkali-
fluorides
Fluoride (). According to this source, is a possible pronunciation in British English. is an inorganic, monatomic anion of fluorine, with the chemical formula (also written ), whose salts are typically white or colorless. Fluoride salts typi ...
with
halogenated benzene:
: C
6Cl
6 + 6 KF → C
6F
6 + 6 KCl
Applications
In the laboratory hexafluorobenzene is used for several purposes:
* 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 ...
* solvent and standard in
carbon-13 NMR
* solvent in
proton NMR
Proton nuclear magnetic resonance (proton NMR, hydrogen-1 NMR, or 1H NMR) is the application of nuclear magnetic resonance in NMR spectroscopy with respect to hydrogen-1 nuclei within the molecules of a substance, in order to determine the struct ...
* solvent when studying some parts in the
IR spectrum
* solvent in
UV spectra, as hexafluorobenzene itself hardly shows any absorbance in the UV region.
Reactions
Most reactions of hexafluorobenzene proceed with displacement of fluoride. One example is its reaction with sodium hydrosulfide to afford
pentafluorothiophenol
Pentafluorothiophenol is an organosulfur compound with the formula C6F5SH. It is a colorless volatile liquid. The compound is prepared by the reaction of sodium hydrosulfide and hexafluorobenzene. With a pKa of 2.68, it is one of the most acid ...
:
:C
6F
6 + NaSH → C
6F
5SH + NaF
The reaction of pentafluorophenyl derivatives has been long puzzling for its mechanism. Independent of the substituent, they all exhibit a
para directing effect. The new introduced group too has no effect on the directing behaviour. In all cases, a 1,4-disubstituted-2,3,5,6-tetrafluorobenzene derivative shows up. Finally, the clue is found not in the nature of the non-fluorine substituent, but in the fluorines themselves. The π-electropositive effect introduces electrons into the aromatic ring. The non-fluorine substituent is not capable of doing so. As charge accumulates at the ''ortho'' and ''para'' positions relative to the donating group, the ''ortho'' and ''para''-positions relative to the non-fluorine substituent receive less charge, so are less negative or more positive. Furthermore, the non-fluorine substituent in general is more bulky than fluorine, so its ''ortho''-positions are sterically shielded, leaving the ''para''-position as the sole reaction site for anionic entering groups.
Biomedical 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 + bpO
2 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 pO
2, 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.
Toxicity
Hexafluorobenzene may cause eye and skin irritation, respiratory and digestive tract irritation and can cause central nervous system depression per MSDS.
The
National Institute for Occupational Safety and Health
The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
(NIOSH) lists it in its
Registry of Toxic Effects of Chemical Substances
Registry of Toxic Effects of Chemical Substances (RTECS) is a database of toxicity information compiled from the open scientific literature without reference to the validity or usefulness of the studies reported. Until 2001 it was maintained by U ...
as
neurotoxicant
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...
.
See also
*
Pentafluorobenzene
References
Further reading
*
*
*
* {{cite journal , last1=Samojłowicz , first1=C. , last2=Bieniek , first2=M. , last3=Pazio , first3=A. , last4=Makal , first4=A. , last5=Woźniak , first5=K. , last6=Poater , first6=A. , last7=Cavallo , first7=L. , last8=Wójcik , first8=J. , last9=Zdanowski , first9=K. , last10=Grela , first10=K. , date=2011 , title=The doping effect of fluorinated aromatic solvents on the rate of ruthenium‐catalysed olefin metathesis , journal=Chemistry: A European Journal , volume=17 , issue=46 , pages=12981–12993 , doi=10.1002/chem.201100160, pmid=21956694
Fluoroarenes
Aromatic solvents
Neurotoxins
Perfluorinated compounds
Solvents