Trifluoroacetic acid explained

Trifluoroacetic acid (TFA) is a synthetic organofluorine compound with the chemical formula CF3CO2H. It is a haloacetic acid, with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms. It is a colorless liquid with a vinegar-like odor. TFA is a stronger acid than acetic acid, having an acid ionisation constant, Ka, that is approximately 34,000 times higher,[1] as the highly electronegative fluorine atoms and consequent electron-withdrawing nature of the trifluoromethyl group weakens the oxygen-hydrogen bond (allowing for greater acidity) and stabilises the anionic conjugate base. TFA is commonly used in organic chemistry for various purposes.

Synthesis

TFA is prepared industrially by the electrofluorination of acetyl chloride or acetic anhydride, followed by hydrolysis of the resulting trifluoroacetyl fluoride:

+ 4 → + 3 +

+ → +

Where desired, this compound may be dried by addition of trifluoroacetic anhydride.[2]

An older route to TFA proceeds via the oxidation of 1,1,1-trifluoro-2,3,3-trichloropropene with potassium permanganate. The trifluorotrichloropropene can be prepared by Swarts fluorination of hexachloropropene.[3]

Uses

TFA is the precursor to many other fluorinated compounds such as trifluoroacetic anhydride, trifluoroperacetic acid, and 2,2,2-trifluoroethanol. It is a reagent used in organic synthesis because of a combination of convenient properties: volatility, solubility in organic solvents, and its strength as an acid.[4] TFA is also less oxidizing than sulfuric acid but more readily available in anhydrous form than many other acids. One complication to its use is that TFA forms an azeotrope with water (b. p. 105 °C).

TFA is used as a strong acid to remove protecting groups such as Boc used in organic chemistry and peptide synthesis.[5] [6]

At a low concentration, TFA is used as an ion pairing agent in liquid chromatography (HPLC) of organic compounds, particularly peptides and small proteins. TFA is a versatile solvent for NMR spectroscopy (for materials stable in acid). It is also used as a calibrant in mass spectrometry.[7]

TFA is used to produce trifluoroacetate salts.[8]

Safety

Trifluoroacetic acid is a strong acid.[9] TFA is harmful when inhaled, causes severe skin burns and is toxic for aquatic organisms even at low concentrations.

Skin burns are severe, heal poorly and can be necrotic. Vapour fumes have an LC50 of 10.01 mg/L, tested on rats over 4 hours. Inhalation symptoms include mucus irritation, coughing, shortness of breath and possible formation of oedemas in the respiratory tract. Exposure damages the kidneys.[10]

Environment

Although trifluoroacetic acid is not produced biologically or abiotically,[11] it is a metabolic breakdown product of the volatile anesthetic agent halothane. It is also thought to be responsible for halothane-induced hepatitis. It also may be formed by photooxidation of the commonly used refrigerant 1,1,1,2-tetrafluoroethane (R-134a). Moreover, it is formed as an atmospheric degradation product of almost all fourth-generation synthetic refrigerants, also called hydrofluoroolefins (HFO), such as 2,3,3,3-tetrafluoropropene.[12] [13]

Trifluoroacetic acid degrades very slowly in the environment and has been found in increasing amounts as a contaminant in water, soil, food, and the human body.[14] Median concentrations of a few micrograms per liter have been found in beer and tea.[15] Seawater can contain about 200 ng of TFA per liter.[16] [17] [18] Biotransformation by decarboxylation to fluoroform has been discussed.[19]

Trifluoroacetic acid is mildly phytotoxic.[20]

See also

Notes and References

  1. Note: Calculated from the ratio of the Ka values for TFA (pKa = 0.23) and acetic acid (pKa = 4.76)
  2. Book: 10.1016/B978-1-85617-567-8.50012-3 . Chapter 4 – Purification of Organic Chemicals . Purification of Laboratory Chemicals . 6th . Wilfred L.F. Armarego . Christina Li Lin Chai . 2009 . 88–444 . 978-1-85617-567-8 . amp .
  3. Book: Gergel, Max G.. Excuse me sir, would you like to buy a kilo of isopropyl bromide?. Max Gergel. March 1977. Pierce Chemical. 88–90.
  4. Encyclopedia: 2004. Encyclopedia of Reagents for Organic Synthesis. J. Wiley & Sons. New York. L. Paquette. 10.1002/047084289X.rt236.pub2. 978-0-471-93623-7. Nichols, P. J.. Eidman, K. F.. Trifluoroacetic Acid. 10261/236866. free.
  5. 10.1111/j.1399-3011.1978.tb02896.x . Removal of t-Butyl and t-Butoxycarbonyl Protecting Groups with Trifluoroacetic acid . 1978 . Lundt . Behrend F. . Johansen . Nils L. . Vølund . Aage . Markussen . Jan . International Journal of Peptide and Protein Research . 12 . 5 . 258–268 . 744685.
  6. Book: 10.1002/9783527631827.ch1 . 1. Protection Reactions . Andrew B. Hughes . Vommina V. Sureshbabu . Narasimhamurthy Narendra . 4 . Amino Acids, Peptides and Proteins in Organic Chemistry: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis. 2011 . 1–97 . 978-3-527-63182-7.
  7. 10.1021/ac00193a027 . Tuning and calibration in thermospray liquid chromatography/mass spectrometry using trifluoroacetic acid cluster ions . 1989 . Stout . Steven J. . Dacunha . Adrian R. . Analytical Chemistry . 61 . 2126 . 18.
  8. O. Castano . A. Cavallaro . A. Palau . J. C. Gonzalez . M. Rossell . T. Puig . F. Sandiumenge . N. Mestres . S. Pinol . A. Pomar . X. Obradors . amp . High quality YBa2Cu3O7 thin films grown by trifluoroacetates metal-organic deposition . Superconductor Science and Technology . 2003 . 16 . 1 . 45–53 . 10.1088/0953-2048/16/1/309 . 2003SuScT..16...45C . 250765145 .
  9. Henne . Albert L . Fox . Charles J . 1951 . Ionization constants of fluorinated acids . . 73 . 5 . 2323–2325 . 10.1021/ja01149a122.
  10. Web site: Safety Data Sheet - Trifluoroacetic Acid - Version 6.8 . Sigma-Aldrich . 25 November 2024.
  11. Joudan . Shira . De Silva . Amila O. . Young . Cora J. . 2021 . Insufficient evidence for the existence of natural trifluoroacetic acid . Environmental Science: Processes & Impacts . en . 23 . 11 . 1641–1649 . 10.1039/D1EM00306B . 34693963 . 2050-7887. 10315/40884 . 239768006 . free .
  12. Web site: Degradation products of fluorinated greenhouse gases . . 2023-06-19 . 2024-09-27.
  13. Web site: TFA as an atmospheric breakdown product . Fluorocarbons . 2023-12-06 . European FluoroCarbons Technical Committee, (Cefic sector group). 2024-09-27.
  14. News: Hosea . Leana . Salvidge . Rachel . 2024-05-01 . Rapidly rising levels of TFA 'forever chemical' alarm experts . 2024-05-29 . The Guardian . en-GB . 0261-3077.
  15. Marco Scheurer, Karsten Nödler. 2021. Ultrashort-chain perfluoroalkyl substance trifluoroacetate (TFA) in beer and tea – An unintended aqueous extraction. Food Chemistry. 351. 129304. 10.1016/j.foodchem.2021.129304. 33657499. 232115008. 0308-8146.
  16. 11811478 . 36 . 1 . Trifluoroacetate in ocean waters . January 2002 . Environ. Sci. Technol. . 12–5. 2002EnST...36...12P . 10.1021/es0221659 . Frank . H. . Christoph . E. H. . Holm-Hansen . O. . Bullister . J. L. .
  17. 16190212 . 39 . 17 . Trifluoroacetate profiles in the Arctic, Atlantic, and Pacific Oceans . September 2005 . Environ. Sci. Technol. . 6555–60. 2005EnST...39.6555S . 10.1021/es047975u . Scott . B. F. . MacDonald . R. W. . Kannan . K. . Fisk . A. . Witter . A. . Yamashita . N. . Durham . L. . Spencer . C. . Muir . D. C. G. .
  18. Frank. Hartmut. Christoph. Eugen H.. Holm-Hansen. Osmund. Bullister. John L.. 2002. Trifluoroacetate in Ocean Waters. Environmental Science & Technology. 36. 1. 12–15. 10.1021/es0101532. 11811478. 2002EnST...36...12F. 0013-936X.
  19. Visscher . Pieter T. . Culbertson . Charles W. . Oremland . Ronald S. . June 1994 . Degradation of trifluoroacetate in oxic and anoxic sediments . Nature . 369 . 6483 . 729–731 . 10.1038/369729a0. 1994Natur.369..729V .
  20. Boutonnet . Jean Charles . Bingham . Pauline . Calamari . Davide . Rooij . Christ de . Franklin . James . Kawano . Toshihiko . Libre . Jean-Marie . McCul-Loch . Archie . Malinverno . Giuseppe . Odom . J Martin . Rusch . George M . Smythe . Katie . Sobolev . Igor . Thompson . Roy . Tiedje . James M . 1999 . Environmental risk assessment of trifluoroacetic acid . International Journal of Human and Ecological Risk Assessment . 5 . 1 . 59–124 . 1999HERA....5...59B . 10.1080/10807039991289644.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Trifluoroacetic acid".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2025, A B Cryer, All Rights Reserved. Cookie policy.