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.
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 spectrometryofnucleic 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]
It is both the precursor and the chief metabolite of the inhalation anestheticsevoflurane. 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]
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]
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]
^ abGünter 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
^Laurence, C.; Gal, J-F. (2010). Lewis Basicity and Affinity Scales, Data and Measurement. Wiley. p. 50-51. ISBN978-0-470-74957-9.{{cite book}}: CS1 maint: multiple names: authors list (link)
^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)
^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. S2CID236388357.
