Hexafluoroacetone Explained

Hexafluoroacetone (HFA) is a chemical compound with the formula (CF3)2CO. It is structurally similar to acetone; however, its reactivity is markedly different. It a colourless, hygroscopic, nonflammable, highly reactive gas characterized by a musty odour.[1] According to electron diffraction, HFA and acetone adopt very similar structures, the C-O distance being only longer in the fluorinated compound (124.6 vs 121.0 pm), possibly due to steric effects.[2]

The term "hexafluoroacetone" can refer to the sesquihydrate (1.5 H2O), which is a hemihydrate of hexafluoropropane-2,2-diol, a geminal diol. Hydrated HFA behaves differently from the anhydrous material.

Synthesis

The industrial route to HFA involves treatment of hexachloroacetone with HF (a Finkelstein reaction):[3]

(CCl3)2CO + 6 HF → (CF3)2CO + 6 HCl

Laboratory methods

Hydrated HFA can be converted to HFA by treatment with hot sulfuric acid.[4]

It has also be prepared from hexafluoropropylene oxide, which will rearrange to give HFA when heated in the in the presence of a Lewis acid such as AlCl3.[5] The Lewis acid catalysed oxidation of hexafluoropropylene will also produce HFA, via a similar mechanism.

Although it is commercially available, HFA can be prepared on the laboratory-scale from hexafluoropropylene.[6] In the first step KF catalyzes the reaction of the alkene with elemental sulfur to give the 1,3-dithietane dimer of hexafluorothioacetone. This species is then oxidized by potassium iodate to give HFA.

Uses

Hexafluoroacetone is used in the production of hexafluoroisopropanol:

(CF3)2CO + H2 → (CF3)2CHOH

It is also used as a precursor to hexafluoroisobutylene,[3] a monomer used in polymer chemistry, and as a building block in the synthesis of midaflur, bisphenol AF, 4,4′-(hexafluoroisopropylidene)diphthalic anhydride, and alitame.

Reactivity

With water, hexafluoroacetone converts to the hydrate. The equilibrium constant (Keq) for the formation of this geminal diol is 106 M−1. The analogous equilibrium for acetone is an unfavorable 10−3 M−1.[7] Hexafluoroacetone-hydrates are acidic. In an analogous reaction, ammonia adds to hexafluoroacetone to give the hemiaminal (CF3)2C(OH)(NH2) which can be dehydrated with phosphoryl chloride to give the imine (CF3)2CNH.[8]

Nucleophiles attack occurs at the carbonyl carbon of Hexafluoroacetone, as illustrated above. Thus, HFA readily forms lactones when treated with hydroxy- and amine-substituted carboxylic acids. In such reactions, HFA serves both as electrophile and dehydrating agent:[4]

See also

Notes and References

  1. https://www.cdc.gov/niosh/npg/npgd0319.html CDC - NIOSH Pocket Guide to Chemical Hazards
  2. 10.1021/j100702a030 . Electron diffraction investigation of hexafluoroacetone, hexafluoropropylimine, and hexafluoroisobutene . 1970 . Hilderbrandt . R. L. . Andreassen . A. L. . Bauer . Simon Harvey . The Journal of Physical Chemistry . 74 . 7 . 1586–1592 .
  3. Encyclopedia: Günter Siegemund. Werner Schwertfeger. Andrew Feiring. Bruce Smart. Fred Behr. Herward Vogel. Blaine McKusick. Fluorine Compounds, Organic. Ullmann's Encyclopedia of Industrial Chemistry. Wiley-VCH. Weinheim. 2002. 10.1002/14356007.a11_349.
  4. 10.1021/cr0509962 . Hexafluoroacetone as Protecting and Activating Reagent: New Routes to Amino, Hydroxy, and Mercapto Acids and Their Application for Peptide and Glyco- and Depsipeptide Modification . 2006 . Spengler . Jan . Böttcher . Christoph . Albericio . Fernando . Burger . Klaus . Chemical Reviews . 106 . 11 . 4728–4746 . 17091933 .
  5. Millauer . Hans . Schwertfeger . Werner . Siegemund . Günter . Hexafluoropropene Oxide — A Key Compound in Organofluorine Chemistry . Angewandte Chemie International Edition in English . March 1985 . 24 . 3 . 161–179 . 10.1002/anie.198501611.
  6. Anello . Louis G. . Van der Puy . Michael . A convenient synthesis of hexafluoroacetone . The Journal of Organic Chemistry . January 1982 . 47 . 2 . 377–378 . 10.1021/jo00341a046.
  7. 10.1021/jo0302556 . Perspective on Fluorocarbon Chemistry . 2004 . Lemal . David M. . The Journal of Organic Chemistry . 69 . 1–11 . 14703372 . 1.
  8. W. J. Middleton. H. D. Carlson . Hexafluoroacetone imine . Org. Syntheses . 50. 1970. 81–3. 10.15227/orgsyn.050.0081. .