Hexafluoro-2-propanol explained

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.

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 9.3, 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

Sources

External links

Notes and References

  1. 10.1038/s41570-017-0088. Hexafluoroisopropanol as a Highly Versatile Solvent . 2017 . Colomer . Ignacio . Chamberlain . Anna E. R. . Haughey . Maxwell B. . Donohoe . Timothy J. . Nature Reviews Chemistry . 1 . 11 .
  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.
  3. Book: Laurence, C.; Gal, J-F.. Lewis Basicity and Affinity Scales, Data and Measurement. Wiley. 2010. 50-51. 978-0-470-74957-9.
  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. 10.1021/ed054p612.
  5. 10.15227/orgsyn.089.0009. Fluoride Ring-Opening Kinetic Resolution of Terminal Epoxides: Preparation of (S)-2-Fluoro-1-phenylethanol . Organic Syntheses . 2012 . 89 . 9 . Travis W.Shaw, Julia A.Kalow, Abigail G.Doyle. free .
  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. 10.1021/ac960916h. 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 . en . 33 . 17 . 1745–1750 . 10.1055/a-1915-8309 . 251303213 . 0936-5214.
  8. Lu . Le . Hua . Ruimao . A Monomer‐Polymer‐Monomer (MPM) Organic Synthesis Strategy: Synthesis and Application of Polybenzofuran for Functionalizing Benzene Ring of Benzofuran . Asian Journal of Organic Chemistry . 20 May 2021 . 10 . 8 . 2137–2142 . 10.1002/ajoc.202100208. 236388357 .
  9. 10.1149/1945-7111/abb83c. Review—Use of 1,1,1,3,3,3–hexafluoro–2–propanol (HFIP) Co-Solvent Mixtures in Organic Electrosynthesis . 2020 . Ramos-Villaseñor . José Manuel . Rodríguez-Cárdenas . Esdrey . Barrera Díaz . Carlos E. . Frontana-Uribe . Bernardo A. . Journal of the Electrochemical Society . 167 . 15 . 155509 . 224972047 . free .
  10. Web site: Baxter Healthcare Corporation . SEVOFLURANE- sevoflurane liquid DESCRIPTION . DailyMed . 12 March 2021 . June 2017.
  11. Web site: PubChem Compound Summary for CID 5206, Sevoflurane . PubChem . 12 March 2021 . 2021.
  12. Web site: 1,1,1,3,3,3-hexafluoropropan-2-ol Toxicity to Reproduction . ECHA . 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 . 31 December 2008 . 109 . 26 March 2021.
  14. Web site: Arp . Hans Peter H. . Hale . Sarah E. . REACH: Improvement of guidance and methods for the identification and assessment of PMT/vPvM substances . umweltbundesamt.de . Umweltbundesamt . 12 March 2021 . November 2019.
  15. Web site: United States Environmental Protection Agency . PFAS Master List of PFAS Substances (Version 2) . comptox.epa.gov/ . 12 March 2021.

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