Hexafluorobenzene

Last updated
Hexafluorobenzene
Hexafluorobenzene.svg
Hexafluorobenzene 3D spacefill.png
Names
Preferred IUPAC name
Hexafluorobenzene
Other names
Perfluorobenzene
Identifiers
3D model (JSmol)
AbbreviationsHFB
1683438
ChEBI
ChemSpider
ECHA InfoCard 100.006.252 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 206-876-2
101976
PubChem CID
UNII
  • InChI=1S/C6F6/c7-1-2(8)4(10)6(12)5(11)3(1)9 Yes check.svgY
    Key: ZQBFAOFFOQMSGJ-UHFFFAOYSA-N Yes check.svgY
  • 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
AppearanceColorless 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:
GHS-pictogram-flamme.svg
Warning
H225
P210, P233, P240, P241, P242, P243
Flash point 10 °C (50 °F; 283 K) [3]
Related compounds
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Hexafluorobenzene, HFB or perfluorobenzene is an organofluorine compound with the chemical formula C
6
F
6
. In this derivative of benzene, all hydrogen atoms have been replaced by fluorine atoms.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.

Contents

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. [4]

FormulaNameInter-halogen distance (if planar)Nonbonding radius×2Consequent symmetry
C6F6Hexafluorobenzene279 pm 270 pmD6h
C6Cl6 Hexachlorobenzene 312 pm360 pmD3d
C6Br6 Hexabromobenzene 327 pm390 pmD3d
C6I6 Hexaiodobenzene 354 pm430 pmD3d

Synthesis

The direct synthesis of hexafluorobenzene from benzene and fluorine has not been useful. Instead it is prepared via the Finkelstein reaction of perchlorobenzene: [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

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

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

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

References

  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   978-3-527-30673-2.{{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. 1 2 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. 1 2 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