Hexafluorobenzene

Summary

Hexafluorobenzene, HFB, C
6
F
6
, or perfluorobenzene is an organic, aromatic compound. In this derivative of benzene all hydrogen atoms have been replaced by fluorine atoms. The technical uses of the compound are limited, although it is recommended as a solvent in a number of photochemical reactions. In the laboratory hexafluorobenzene is used as standard in fluorine-19 NMR spectroscopy, solvent and standard in carbon-13 NMR, solvent in proton NMR, solvent when studying some parts in the infrared and solvent in ultraviolet–visible spectroscopy, as hexafluorobenzene itself hardly shows any absorbance in the UV region.

Hexafluorobenzene
Skeletal formula of hexafluorobenzene
Space-filling model of hexafluorobenzene
Names
Preferred IUPAC name
Hexafluorobenzene
Other names
Perfluorobenzene
Identifiers
  • 392-56-3 checkY
3D model (JSmol)
  • Interactive image
Abbreviations HFB
1683438
ChEBI
  • CHEBI:38589 checkY
ChemSpider
  • 13836549 checkY
ECHA InfoCard 100.006.252 Edit this at Wikidata
EC Number
  • 206-876-2
101976
  • 9805
UNII
  • CMC18T611K checkY
  • DTXSID5043924 Edit this at Wikidata
  • InChI=1S/C6F6/c7-1-2(8)4(10)6(12)5(11)3(1)9 checkY
    Key: ZQBFAOFFOQMSGJ-UHFFFAOYSA-N checkY
  • InChI=1/C6F6/c7-1-2(8)4(10)6(12)5(11)3(1)9
    Key: ZQBFAOFFOQMSGJ-UHFFFAOYAJ
  • Fc1c(F)c(F)c(F)c(F)c1F
Properties
C6F6
Molar mass 186.056 g·mol−1
Appearance Colorless liquid
Density 1.6120 g/cm3
Melting point 5.2 °C (41.4 °F; 278.3 K)
Boiling point 80.1 °C (176.2 °F; 353.2 K)
1.377
Viscosity cP (1.200 mPa•s) (20 °C)
0.00 D (gas)
Hazards[1]
GHS labelling:
GHS02: Flammable
Warning
H225
P210, P233, P240, P241, P242, P243
Flash point 10 °C (50 °F; 283 K)[2]
Related compounds
Related compounds
Benzene
Hexachlorobenzene
Polytetrafluoroethylene
Perfluorotoluene
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

Geometry of the aromatic ringEdit

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:[3]

Formula Name Calculated
inter-halogen
distance, aromatic ring assumed planar
Twice nonbonding radius Consequent symmetry of the benzene
C6F6 hexafluorobenzene 279 270 D6h
C6Cl6 hexachlorobenzene 312 360 D3d
C6Br6 hexabromobenzene 327 390 D3d
C6I6 hexaiodobenzene 354 430 D3d

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 C6F6 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.

SynthesisEdit

The direct synthesis of hexafluorobenzene from benzene and fluorine is not possible. The synthetic route proceeds via the reaction of alkali-fluorides with halogenated benzene:[4]

C6Cl6 + 6 KF → C6F6 + 6 KCl

ApplicationsEdit

In the laboratory hexafluorobenzene is used for several purposes:[citation needed]

ReactionsEdit

Most reactions of hexafluorobenzene proceed with displacement of fluoride. One example is its reaction with sodium hydrosulfide to afford pentafluorothiophenol:[5]

C6F6 + NaSH → C6F5SH + 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 applicationsEdit

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.[6] 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.[7] MRI measurements of HFB based on 19F relaxation have been shown to correlate with radiation response of tumors.[8] HFB has been used as a gold standard for investigating other potential prognostic biomarkers of tumor oxygenation such as BOLD (Blood Oxygen Level Dependent),[9] TOLD (Tissue Oxygen Level Dependent) [10] and MOXI (MR oximetry) [11] A 2013 review of applications has been published.[12]

ToxicityEdit

Hexafluorobenzene may cause eye and skin irritation, respiratory and digestive tract irritation and can cause central nervous system depression per MSDS.[13] The National Institute for Occupational Safety and Health (NIOSH) lists it in its Registry of Toxic Effects of Chemical Substances as neurotoxicant.

See alsoEdit

ReferencesEdit

  1. ^ "Hexafluorobenzene 99%". Sigma Aldrich.
  2. ^ Acros Organics:Catalog of fine Chemicals (1999)
  3. ^ Delorme, P.; Denisselle, F.; Lorenzelli, V. (1967). "Spectre infrarouge et vibrations fondamentales des dérivés hexasubstitués halogénés du benzène" [Infrared spectrum and fundamental vibrations of the hexasubstituted halogen derivatives of benzene]. Journal de Chimie Physique (in French). 64: 591–600. Bibcode:1967JCP....64..591D. doi:10.1051/jcp/1967640591.
  4. ^ Vorozhtsov, N. N., Jr.; Platonov, V. E.; Yakobson, G. G. (1963). "Preparation of hexafluorobenzene from hexachlorobenzene". Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science. 12 (8): 1389. doi:10.1007/BF00847820.
  5. ^ Robson, P.; Stacey, M.; Stephens, R.; Tatlow, J. C. (1960). "Aromatic polyfluoro-compounds. Part VI. Penta- and 2,3,5,6-tetra-fluorothiophenol". Journal of the Chemical Society (4): 4754–4760. doi:10.1039/JR9600004754.
  6. ^ Zhao, D.; Jiang, L.; Mason, R. P. (2004). "Measuring changes in tumor oxygenation". In Conn, P. M. (ed.). Imaging in Biological Research, Part B. Methods in Enzymology. Vol. 386. Elsevier. pp. 378–418. doi:10.1016/S0076-6879(04)86018-X. ISBN 978-0-12-182791-5. PMID 15120262.
  7. ^ Zhao, D.; Jiang, L.; Hahn, E. W.; Mason, R. P. (2005). "Tumor physiologic response to combretastatin A4 phosphate assessed by MRI". International Journal of Radiation Oncology, Biology, Physics. 62 (3): 872–880. doi:10.1016/j.ijrobp.2005.03.009. PMID 15936572.
  8. ^ Zhao, D.; Constantinescu, A.; Chang, C.-H.; Hahn, E. W.; Mason, R. P. (2003). "Correlation of tumor oxygen dynamics with radiation response of the Dunning prostate R3327-HI tumor". Radiation Research. 159 (5): 621–631. doi:10.1667/0033-7587(2003)159[0621:COTODW]2.0.CO;2. PMID 12710873.
  9. ^ Zhao, D.; Jiang, L.; Hahn, E. W.; Mason, R. P. (2009). "Comparison of 1H blood oxygen level–dependent (BOLD) and 19F MRI to investigate tumor oxygenation". Magnetic Resonance in Medicine. 62 (2): 357–364. doi:10.1002/mrm.22020. PMC 4426862. PMID 19526495.
  10. ^ Hallac, R. R.; Zhou, H.; Pidikiti, R.; Song, K.; Stojadinovic, S.; Zhao, D.; Solberg, T.; Peschke, P.; Mason, R. P. (2014). "Correlations of noninvasive BOLD and TOLD MRI with pO2 and relevance to tumor radiation response". Magnetic Resonance in Medicine. 71 (5): 1863–1873. doi:10.1002/mrm.24846. PMC 3883977. PMID 23813468.
  11. ^ Zhang, Z.; Hallac, R. R.; Peschke, P.; Mason, R. P. (2014). "A noninvasive tumor oxygenation imaging strategy using magnetic resonance imaging of endogenous blood and tissue water". Magnetic Resonance in Medicine. 71 (2): 561–569. doi:10.1002/mrm.24691. PMC 3718873. PMID 23447121.
  12. ^ Yu, J.-X.; Hallac, R. R.; Chiguru, S.; Mason, R. P. (2013). "New frontiers and developing applications in 19F NMR". Progress in Nuclear Magnetic Resonance Spectroscopy. 70: 25–49. doi:10.1016/j.pnmrs.2012.10.001. PMC 3613763. PMID 23540575.
  13. ^ "Material safety data sheet: Hexafluorobenzene, 99%". Fisher Scientific. Thermo Fisher Scientific. n.d. Retrieved 2020-02-08.

Further readingEdit

  • Pummer, W. J.; Wall, L. A. (1958). "Reactions of hexafluorobenzene". Science. 127 (3299): 643–644. Bibcode:1958Sci...127..643P. doi:10.1126/science.127.3299.643. PMID 17808882.
  • US patent 3277192, Fielding, H. C., "Preparation of hexafluorobenzene and fluorochlorobenzenes", issued 1966-10-04, assigned to Imperial Chemical Industries 
  • Bertolucci, M. D.; Marsh, R. E. (1974). "Lattice parameters of hexafluorobenzene and 1,3,5-trifluorobenzene at −17°C". Journal of Applied Crystallography. 7 (1): 87–88. doi:10.1107/S0021889874008764.
  • Samojłowicz, C.; Bieniek, M.; Pazio, A.; Makal, A.; Woźniak, K.; Poater, A.; Cavallo, L.; Wójcik, J.; Zdanowski, K.; Grela, K. (2011). "The doping effect of fluorinated aromatic solvents on the rate of ruthenium‐catalysed olefin metathesis". Chemistry—A European Journal. 17 (46): 12981–12993. doi:10.1002/chem.201100160. PMID 21956694.