Hexafluorobenzene, HFB, C
6
F
6
, or perfluorobenzene is an organofluorine 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 In this derivative of benzene, all hydrogen atoms have been replaced by fluorine atoms.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 has some specialized uses in the laboratory owing to distinctive spectroscopic properties.

Hexafluorobenzene
Skeletal formula of hexafluorobenzene
Space-filling model of hexafluorobenzene
Names
Preferred IUPAC name
Hexafluorobenzene
Other names
Perfluorobenzene
Identifiers
3D model (JSmol)
Abbreviations HFB
1683438
ChEBI
ChemSpider
ECHA InfoCard 100.006.252 Edit this at Wikidata
EC Number
  • 206-876-2
101976
UNII
  • 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 80.3 °C (176.5 °F; 353.4 K)[1]
1.377
Viscosity cP (1.200 mPa•s) (20 °C)
0.00 D (gas)
Hazards[2]
GHS labelling:
GHS02: Flammable
Warning
H225
P210, P233, P240, P241, P242, P243
Flash point 10 °C (50 °F; 283 K)[3]
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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Geometry of the aromatic ring

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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.[4]

Formula Name Inter-halogen distance (if planar) Nonbonding radius×2 Consequent symmetry
C6F6 Hexafluorobenzene 279 270 D6h
C6Cl6 Hexachlorobenzene 312 360 D3d
C6Br6 Hexabromobenzene 327 390 D3d
C6I6 Hexaiodobenzene 354 430 D3d

Synthesis

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The direct synthesis of hexafluorobenzene from benzene and fluorine has not been useful. Instead it is prepared by the reaction of alkali fluorides with halogenated benzene:[5]

C6Cl6 + 6 KF → C6F6 + 6 KCl

Antimony fluoride instead adds to the ring, breaking aromaticity.[6]: 861 

In principle, various halofluoromethanes pyrolyze to hexafluorobenzene, but commercialization was still in the initial stages in 2000.[7]: 21 [needs update]

Reactions

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Hexafluorobenzene easily undergoes nucleophilic aromatic substitution.[6]: 866 [7]: 19–21  One example is its reaction with sodium hydrosulfide to afford pentafluorothiophenol:[8]

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.[citation needed]

Hexafluorobenzene is thus a comonomer in certain heavily fluorinated heat-resistant polyethers' synthesis.[9]

UV light causes gaseous HFB to isomerize to hexafluoro derivative of Dewar benzene.[10]

Laboratory applications

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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.[11] 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.[12] MRI measurements of HFB based on 19F relaxation have been shown to correlate with radiation response of tumors.[13] HFB has been used as a gold standard for investigating other potential prognostic biomarkers of tumor oxygenation such as BOLD (Blood Oxygen Level Dependent),[14] TOLD (Tissue Oxygen Level Dependent) [15] and MOXI (MR oximetry) [16] A 2013 review of applications has been published.[17]

HFB has been evaluated as standard in fluorine-19 NMR spectroscopy.[18]

Toxicity

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Hexafluorobenzene may cause eye and skin irritation, respiratory and digestive tract irritation and can cause central nervous system depression per MSDS.[19] The National Institute for Occupational Safety and Health (NIOSH) lists it in its Registry of Toxic Effects of Chemical Substances as neurotoxicant.

See also

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References

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  1. ^ Siegemund, Günter; Schwertfeger, Werner; Feiring, Andrew; Smart, Bruce; Behr, Fred; Vogel, Herward; McKusick, Blaine; Kirsch, Peer (2016). "Fluorine compounds, organic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. p. 44. doi:10.1002/14356007.a11_349.pub2. ISBN 978-3527306732.{{cite encyclopedia}}: CS1 maint: multiple names: authors list (link)
  2. ^ "Hexafluorobenzene 99%". Sigma Aldrich.
  3. ^ Acros Organics:Catalog of fine Chemicals (1999)
  4. ^ 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.
  5. ^ 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.
  6. ^ a b Bajzer, William X., "Fluorine compounds, organic", Kirk-Othmer Encyclopedia of Chemical Technology, vol. 11, New York: John Wiley, doi:10.1002/0471238961.0914201802011026.a01.pub2, ISBN 9780471238966
  7. ^ a b Boudakian, Max M., "Fluorinated aromatic compounds", Kirk-Othmer Encyclopedia of Chemical Technology, New York: John Wiley, doi:10.1002/0471238961.0612211502152104.a01, ISBN 9780471238966
  8. ^ 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.
  9. ^ Cassidy, Patrick E.; Aminabhavi, Tejraj M.; Reddy, V. Sreenivasulu, "Heat-resistant polymers", Kirk-Othmer Encyclopedia of Chemical Technology, New York: John Wiley, p. 18, doi:10.1002/0471238961.0805012003011919.a01, ISBN 9780471238966
  10. ^ Lemal, David M. (2001). "Hexafluorobenzene Photochemistry: Wellspring of Fluorocarbon Structures". Accounts of Chemical Research. 34 (8): 662–671. doi:10.1021/ar960057j. PMID 11513574.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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.
  16. ^ 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.
  17. ^ 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.
  18. ^ Rosenau, Carl Philipp; Jelier, Benson J.; Gossert, Alvar D.; Togni, Antonio (2018). "Exposing the Origins of Irreproducibility in Fluorine NMR Spectroscopy". Angewandte Chemie International Edition. 57 (30): 9528–9533. doi:10.1002/anie.201802620. PMID 29663671.
  19. ^ "Material safety data sheet: Hexafluorobenzene, 99%". Fisher Scientific. Thermo Fisher Scientific. n.d. Retrieved 2020-02-08.

Further reading

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  • 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. Bibcode:1974JApCr...7...87B. 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.