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. 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.

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

(CF₃)₂CO + H₂ → (CF₃)₂CHOH

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. It is classified as a hard Lewis acid and its acceptor properties are discussed in the ECW model.

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. In another illustration of its use, HFIP is used as the solvent for Lewis-acid catalyzed ring opening of epoxides.

It has also found use in biochemistry to solubilize peptides and to monomerize β-sheet protein aggregates. Because of its acidity (pK_a = 9.3), it can be used as acid in volatile buffers for ion pair HPLC – mass spectrometry of nucleic acids. Recent studies 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. 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.

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.

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. Animal experiments show possible adverse effects on fertility, placing HFIP as a reproductive toxicity category 2 material.

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. HFIP also belongs to per- and polyfluorinated alkyl substances (PFAS).

• Application note on quantification of HFIP in polymers

1. Acrinathrin
2. Nonafluoro-tert-butyl alcohol
3. HFIP
4. Hexafluoroacetone
5. Nazarov cyclization reaction
6. 1-Tetralone
7. C3H2F6O
8. 2,2,2-Trifluoroethanol
9. Hexafluoropropylene
10. Self-assembling peptide
11. Isoflurothyl