Hexafluoro-2-propanol

Hexafluoroisopropanol, commonly abbreviated HFIP, is the organic compound with the formula (CF3)2CHOH. This fluoroalcohol finds use as solvent in organic chemistry.[1] Hexafluoro-2-propanol is transparent to UV light with high density, low viscosity and low refractive index. It is a colorless, volatile liquid with a pungent odor.

1,1,1,3,3,3-Hexafluoro-2-propanol
1,1,1,3,3,3-Hexafluoro-2-propanol
Names
Preferred IUPAC name
1,1,1,3,3,3-Hexafluoropropan-2-ol
Other names
Hexafluoroisopropanol,
Hexafluoroisopropyl alcohol,
HFIP
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.011.873
RTECS number
  • UB6450000
UNII
  • InChI=1S/C3H2F6O/c4-1(5)2(6,10)3(7,8)9/h1,10H checkY
    Key: NMFQPFSIPWZZMR-UHFFFAOYSA-N checkY
  • InChI=1S/C3H2F6O/c4-2(5,6)1(10)3(7,8)9/h1,10H
    Key: BYEAHWXPCBROCE-UHFFFAOYSA-N
  • C(C(F)(F)F)(C(F)(F)F)O
Properties
C3H2F6O
Molar mass 168.038 g·mol−1
Appearance Colorless liquid
Density 1.596 g/mL
Melting point −3.3 °C (26.1 °F; 269.8 K)
Boiling point 58.2 °C (136.8 °F; 331.3 K)
Miscible
Vapor pressure 16 kPa at 20 °C
Viscosity 1.65 cP at 20 °C
Hazards
GHS labelling:
GHS05: Corrosive GHS08: Health hazard
Danger
H314, H361fd, H373
P201, P280, P303+P361+P353, P305+P351+P338+P310, P308+P313
NFPA 704 (fire diamond)
NFPA 704 four-colored diamond
3
0
0
Flash point > 100 °C (212 °F; 373 K)
Safety data sheet (SDS) External MSDS
Related compounds
Hexafluoroacetone;
Isopropyl alcohol, 2,2,2-Trifluoroethanol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)
Infobox references

Production

Hexafluoro-propan-2-ol is prepared from hexafluoropropylene through hexafluoroacetone, which is then hydrogenated.[2]

(CF3)2CO + H2 → (CF3)2CHOH

Solvent properties

As a solvent, hexafluoro-2-propanol is polar and exhibits strong hydrogen bonding properties. Testament to the strength of its hydrogen-bonding tendency is the fact that its 1:1 complex with THF distills near 100 °C. It has a relatively high dielectric constant of 16.7. It is also relatively acidic, with a pKa of 8.3, comparable to that for phenol.[1] It is classified as a hard Lewis acid and its acceptor properties are discussed in the ECW model.[3][4]

Hexafluoro-propan-2-ol is a speciality solvent for organic synthesis, particularly for reactions involving oxidations and strong electrophiles. For example, HFIP enhances the reactivity of hydrogen peroxide as applied to Baeyer-Villiger oxidation of cyclic ketones.[1] In another illustration of its use, HFIP is used as the solvent for Lewis-acid catalyzed ring opening of epoxides.[5]

It has also found use in biochemistry to solubilize peptides and to monomerize β-sheet protein aggregates. Because of its acidity (pKa = 9.3), it can be used as acid in volatile buffers for ion pair HPLC - mass spectrometry of nucleic acids.[6] Recent studies[7] showed an ability of HFIP to activate allylic alcohols, stabilise an allylic cation, and further functionalize to allylic sulphides and sulfones.

Hexafluoro-propan-2-ol is a speciality solvent for some polar polymers.[8] It solubilizes polymers that are insoluble in common organic solvents, such as: polyamides, polyacrylonitriles, polyacetals, polyesters (e.g. polyglycolide), and polyketones. It has also been evaluated as a solvent for electrolysis.[9]

Medicine

It is both the precursor and the chief metabolite of the inhalation anesthetic sevoflurane. Sevoflurane gets metabolized within the body into HFIP and formaldehyde. HFIP is inactive, non-genotoxic and once formed, is rapidly conjugated with glucuronic acid and eliminated as a urinary metabolite.[10][11]

Safety

Toxicity

Hexafluoro-2-propanol has very low acute toxicity, hence its use as a precursor to anesthetics. Although it has low acute toxicity, it is a strong irritant to skin and eyes.[2] Animal experiments show possible adverse effects on fertility,[12] placing HFIP as a reproductive toxicity category 2 material.[13]

Environment and toxicity

HFIP is a specialty chemical that is produced in small quantities, thus it is not of significant environmental concern. Its environmental implications have been assessed.[14] HFIP also belongs to per- and polyfluorinated alkyl substances (PFAS).[15]

References
  1. Colomer, Ignacio; Chamberlain, Anna E. R.; Haughey, Maxwell B.; Donohoe, Timothy J. (2017). "Hexafluoroisopropanol as a Highly Versatile Solvent". Nature Reviews Chemistry. 1 (11). doi:10.1038/s41570-017-0088.
  2. Günter Siegemund, Werner Schwertfeger, Andrew Feiring, Bruce Smart, Fred Behr, Herward Vogel, Blaine McKusick “Fluorine Compounds, Organic” in Ullmann's Encyclopedia of Industrial Chemistry, John Wiley & Sons, 2007. doi:10.1002/14356007.a11_349
  3. Laurence, C.; Gal, J-F. (2010). Lewis Basicity and Affinity Scales, Data and Measurement. Wiley. p. 50-51. ISBN 978-0-470-74957-9.{{cite book}}: CS1 maint: multiple names: authors list (link)
  4. Cramer, R. E.; Bopp, T. T. (1977). "Great E and C Plot. Graphical Display of the Enthalpies of Adduct Formation for Lewis Acids and Bases". Journal of Chemical Education. 54 (10): 612-613. doi:10.1021/ed054p612.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  5. Travis W.Shaw, Julia A.Kalow, Abigail G.Doyle (2012). "Fluoride Ring-Opening Kinetic Resolution of Terminal Epoxides: Preparation of (S)-2-Fluoro-1-phenylethanol". Organic Syntheses. 89: 9. doi:10.15227/orgsyn.089.0009.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. Apffel, A.; Chakel, J.A.; Fischer, S.; Lichtenwalter, K.; Hancock, W.S. (1997). "Analysis of oligonucleotides by HPLC-electrospray ionization mass spectrometry". Anal. Chem. 69 (7): 1320–1325. doi:10.1021/ac960916h. PMID 21639339.
  7. Lu, Maojian; Zhang, Rong-Jin; Zhu, Can-Ming; Xiao, Yonghong; Chen, Jian-Rui; Zhao, Lei-Min; Tong, Qing-Xiao; Zhong, Jian-Ji (October 2022). "HFIP-Induced Allylation Reaction of Tertiary Allylic Alcohols with Thiols or Sulfonyl Hydrazines to Access Allylic Organosulfurs". Synlett. 33 (17): 1745–1750. doi:10.1055/a-1915-8309. ISSN 0936-5214. S2CID 251303213.
  8. Lu, Le; Hua, Ruimao (20 May 2021). "A Monomer‐Polymer‐Monomer (MPM) Organic Synthesis Strategy: Synthesis and Application of Polybenzofuran for Functionalizing Benzene Ring of Benzofuran". Asian Journal of Organic Chemistry. 10 (8): 2137–2142. doi:10.1002/ajoc.202100208. S2CID 236388357.
  9. Ramos-Villaseñor, José Manuel; Rodríguez-Cárdenas, Esdrey; Barrera Díaz, Carlos E.; Frontana-Uribe, Bernardo A. (2020). "Review—Use of 1,1,1,3,3,3–hexafluoro–2–propanol (HFIP) Co-Solvent Mixtures in Organic Electrosynthesis". Journal of the Electrochemical Society. 167 (15): 155509. doi:10.1149/1945-7111/abb83c. S2CID 224972047.
  10. Baxter Healthcare Corporation (June 2017). "SEVOFLURANE- sevoflurane liquid DESCRIPTION". DailyMed. Retrieved 12 March 2021.
  11. "PubChem Compound Summary for CID 5206, Sevoflurane". PubChem. 2021. Retrieved 12 March 2021.
  12. "1,1,1,3,3,3-hexafluoropropan-2-ol Toxicity to Reproduction". ECHA. Retrieved 26 March 2021.
  13. "REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006". Official Journal of the European Union: 109. 31 December 2008. Retrieved 26 March 2021.
  14. Arp, Hans Peter H.; Hale, Sarah E. (November 2019). "REACH: Improvement of guidance and methods for the identification and assessment of PMT/vPvM substances". umweltbundesamt.de. Umweltbundesamt. Retrieved 12 March 2021.
  15. United States Environmental Protection Agency. "PFAS Master List of PFAS Substances (Version 2)". comptox.epa.gov/. Retrieved 12 March 2021.

Sources
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