Hexafluoro-2-propanol

Last updated
1,1,1,3,3,3-Hexafluoro-2-propanol
Hexafluoroisopropanol.svg
Hexafluoroisopropanol 3D.png
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 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
RTECS number
  • UB6450000
UNII
  • InChI=1S/C3H2F6O/c4-1(5)2(6,10)3(7,8)9/h1,10H Yes check.svgY
    Key: NMFQPFSIPWZZMR-UHFFFAOYSA-N Yes check.svgY
  • 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
AppearanceColorless 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:
GHS-pictogram-acid.svg GHS-pictogram-silhouette.svg
Danger
H314, H361fd, H373
P201, P280, P303+P361+P353, P305+P351+P338+P310, P308+P313
NFPA 704 (fire diamond)
NFPA 704.svgHealth 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 0: Will not burn. E.g. waterInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
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).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

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.

Contents

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 HPLCmass 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]

Related Research Articles

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References

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  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)
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  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)
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  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.
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Sources