Trifluoroacetic acid

Trifluoroacetic acid
Names
Preferred IUPAC name
trifluoroacetic acid
Other names
2,2,2-trifluoroacetic acid
2,2,2-trifluoroethanoic acid
perfluoroacetic acid
trifluoroethanoic acid
TFA
Identifiers
3D model (JSmol)
742035
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.000.846
2729
RTECS number
  • AJ9625000
UNII
  • InChI=1S/C2HF3O2/c3-2(4,5)1(6)7/h(H,6,7) checkY
    Key: DTQVDTLACAAQTR-UHFFFAOYSA-N checkY
  • InChI=1/C2HF3O2/c3-2(4,5)1(6)7/h(H,6,7)
    Key: DTQVDTLACAAQTR-UHFFFAOYAP
  • FC(F)(F)C(=O)O
Properties
C2HF3O2
Molar mass 114.023 g·mol−1
Appearance colorless liquid
Odor strong and vinegar-like
Density 1.489 g/cm3, 20 °C
Melting point −15.4 °C (4.3 °F; 257.8 K)
Boiling point 72.4 °C (162.3 °F; 345.5 K)
miscible
Vapor pressure 0.0117 bar (1.17 kPa) at 20 °C[1]
Acidity (pKa) 0.03 ± 0.08[2]
Conjugate base trifluoroacetate
−43.3·10−6 cm3/mol
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 highly corrosive, persistent groundwater pollutant
GHS labelling:
GHS05: CorrosiveGHS07: Exclamation mark
Danger
H314, H332, H412
P260, P264, P271, P273, P280, P301+P330+P331, P303+P361+P353, P304+P312, P304+P340, P305+P351+P338, P310, P312, P321, P363, P405, P501
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 3: Short exposure could cause serious temporary or residual injury. E.g. chlorine gasFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 1: Normally stable, but can become unstable at elevated temperatures and pressures. E.g. calciumSpecial hazards (white): no code
3
1
1
Safety data sheet (SDS) External MSDS
Related compounds
Related perfluorinated acids
 heptafluorobutyric acid
perfluorooctanoic acid
perfluorononanoic acid
Related compounds
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It belongs to the subclass of per- and polyfluoroalkyl substances (PFASs) known as ultrashort-chain perfluoroalkyl acids (PFAAs).[3] TFA, which is only produced industrially, is commonly used in organic chemistry.[4] In the form of its conjugate base trifluoroacetate, it is the most abundant PFAS found in the environment.[3]

It is a haloacetic acid, with all three of the acetyl group's hydrogen atoms replaced by fluorine. It is a colorless liquid with a vinegar-like odor. TFA is a stronger acid than acetic acid is, having an acid ionisation constant, Ka, that is approximately 50000 times higher,[5] 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.

History

In 1922, Frédéric Swarts synthesised trifluoroacetic acid, or rather its sodium salt, and investigated its physicochemical properties.[6]

Formation

TFA is prepared industrially by the electrofluorination of acetyl chloride or acetic anhydride, followed by hydrolysis of the resulting trifluoroacetyl fluoride:[7]

CH
3COCl + 4 HF → CF
3COF + 3 H
2 + HCl
CF
3COF + H
2O → CF
3COOH + HF

Wet samples can be dried by addition of trifluoroacetic anhydride.[8]

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.[9]

Via biodegradation of trifluomethyl compounds

Trifluoroacetic acid is not produced biologically,[4] but it is a breakdown product of various organofluorine compounds, e.g., the volatile anesthetic agent halothane. It also may be formed by hydroxyl radical-initiated atmospheric oxidation of the commonly used refrigerant 1,1,1,2-tetrafluoroethane (R-134a).[10][11] 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 is also formed by the degradation of some pesticides that contain a trifluoromethyl group (-CF3), such as flufenacet.[14] The German Environment Agency estimated that pesticide use releases approximately 500 metric tonnes of TFA annually in Germany alone, while refrigerants account for around 1170 metric tonnes per year.[15]

Reactions

Having a pKa value of around 0, TFA does not exist as such at concentrations found in natural waters. Instead TFA converts to trifluoroacetate, concomitant with the protonation of water.

It protonates several weakly basic anions, e.g. azide to give hydrazoic acid.[16]

Trifluoroacetic acid in a beaker

TFA is the precursor to trifluoroacetic anhydride, trifluoroperacetic acid, and 2,2,2-trifluoroethanol.[7] 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.[17] 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.[18][19]

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.[20]

TFA is used to produce trifluoroacetate salts.[21]

Health effects

Trifluoroacetic acid is a strong acid.[22] 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.[23]

TFA is also thought to be responsible for halothane-induced hepatitis.[24]

In 2024, the German Federal Institute for Risk Assessment (BfR) formally requested that the European Chemicals Agency (ECHA) reclassify TFA as "presumed" toxic to human reproduction, based on studies showing damage to animal fetuses.[25][26] In June 2026, ECHA's Risk Assessment Committee (RAC) concluded that TFA fulfils the criteria for toxic to the reproduction class 1B, persistent, mobile and toxic (PMT) as well as very persistent and very mobile (vPvM).[27]

In July 2026, the European Food Safety Authority (EFSA) reduced the acceptable daily intake for TFA by 72%, from 0.05 mg/kg body weight/day down to 0.014. It also set the acute reference dose (ARfD) to 0.07 mg/kg body weight.[28][29] These reductions were based on an assessment of new evidence, including changes in levels of the hormone thyroxine.[28]

Environmental impacts

Trifluoroacetic acid is mildly phytotoxic.[30]

Uncertainties remain in our understanding of the potential impacts on the environment of TFA.[3][31][32] A debate is ongoing regarding its ecological risk due to its persistence, ubiquity in the environment and increasing concentrations globally.[31][3] TFA exposure is widespread and increasing and it is the most abundant PFAS found in the environment.[3] TFA does not have well-established health advisories or regulatory limits as other PFAAs.[3]

Trifluoroacetic acid is also formed by the degradation of pesticides that contain a trifluoromethyl group (-CF3), such as flufenacet.[33] Pesticides have been identified as the main source of TFA in water in agricultural areas.[34]

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.[35] Median concentrations of a few micrograms per liter have been found in beer and tea.[36] Seawater can contain about 200 ng of TFA per liter.[37][38] Biotransformation by decarboxylation to fluoroform has been discussed.[39] In October 2024, a publication proposed classifying TFA as a planetary boundary threat, similar to how CFCs are treated.[3]

Water contamination in Europe

TFA has emerged as a significant environmental contaminant across European waterways since its discovery in 2016 by researchers at the Karlsruhe Water Technology Center in Germany.[40] Unlike other PFAS compounds, TFA's high water solubility allows it to spread rapidly through rivers and precipitation rather than binding to soil or organic matter.

TFA concentrations in European water sources have increased markedly since the 1990s. German and Swiss studies documented an approximately fivefold increase in TFA levels in rainfall since the 1990s[41][34], while Danish groundwater showed more than tenfold increases over the same period.[42] Research by the anti-pesticide network PAN Europe found that TFA accounted for 98 percent of all PFAS detected in water samples from 10 EU countries.[40] Groundwater contamination with TFA is also widespread in Switzerland.[43]

The contamination has proven extremely difficult to address due to TFA's resistance to conventional water treatment methods. The only effective removal technique is reverse osmosis, which is prohibitively expensive and wastes up to 25 percent of treated water while producing concentrated brine that requires indefinite containment.[25][44]

See also

References

  1. ↑ Kreglewski, A. (1962). "Trifluoroacetic acid". Welcome to the NIST WebBook. 10 (11–12): 629–633. Retrieved 1 March 2020.
  2. ↑ Damalka Balasuryia; Aina Queral-Beltran; Tristan Vic; Scott Simpson; Silvia Lacorte; Diana S. Aga; Alexander C. Hoepker (2025). "Experimental Determination of pKa for 10 PFAS, Mono-, Di-, and Trifluoroacetic Acid by 19F-NMR". Environmental Science & Technology Letters. 12 (9): 1238–1246. Bibcode:2025EnSTL..12.1238B. doi:10.1021/acs.estlett.5c00688. PMC 12424170. PMID 40951867.
  3. 1 2 3 4 5 6 7 Arp, Hans Peter H.; Gredelj, Andrea; Glüge, Juliane; Scheringer, Martin; Cousins, Ian T. (12 November 2024). "The Global Threat from the Irreversible Accumulation of Trifluoroacetic Acid (TFA)". Environmental Science & Technology. 58 (45): 19925–19935. Bibcode:2024EnST...5819925A. doi:10.1021/acs.est.4c06189. PMC 11562725. PMID 39475534.
  4. 1 2 Joudan, Shira; De Silva, Amila O.; Young, Cora J. (2021). "Insufficient evidence for the existence of natural trifluoroacetic acid". Environmental Science: Processes & Impacts. 23 (11): 1641–1649. Bibcode:2021ESPI...23.1641J. doi:10.1039/D1EM00306B. hdl:10315/40884. ISSN 2050-7887. PMID 34693963. S2CID 239768006.
  5. ↑ Note: Calculated from the ratio of the Ka values for TFA (pKa = 0.03) and acetic acid (pKa = 4.76)
  6. ↑ Frédéric Swarts (1922), "Sur l'acide trifluoracétique", Bulletin de la Classe des Sciences, vol. 8, pp. 343–370
  7. 1 2 G. Siegemund; W. Schwertfeger; A. Feiring; B. Smart; F. Behr; H. Vogel; B. McKusick. "Fluorine Compounds, Organic". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a11_349. ISBN 978-3-527-30673-2.
  8. ↑ Wilfred L.F. Armarego & Christina Li Lin Chai (2009). "Chapter 4 – Purification of Organic Chemicals". Purification of Laboratory Chemicals (6th ed.). pp. 88–444. doi:10.1016/B978-1-85617-567-8.50012-3. ISBN 978-1-85617-567-8.
  9. ↑ Gergel, Max G. (March 1977). Excuse me sir, would you like to buy a kilo of isopropyl bromide?. Pierce Chemical. pp. 88–90.
  10. ↑ Scientific Assessment of Ozone Depletion: 2010 (PDF). Global Ozone Research and Monitoring Project. World Meteorological Organization.
  11. ↑ Wallington, T. J.; Hurley, M. D.; Fracheboud, J. M.; Orlando, J. J.; Tyndall, G. S.; Sehested, J.; Møgelberg, T. E.; Nielsen, O. J. (1996). "Role of Excited CF3CFHO Radicals in the Atmospheric Chemistry of HFC-134a". The Journal of Physical Chemistry. 100 (46): 18116–18122. Bibcode:1996JPhCh.10018116W. doi:10.1021/jp9624764.
  12. ↑ "Degradation products of fluorinated greenhouse gases". Umweltbundesamt. 19 June 2023. Retrieved 27 September 2024.
  13. ↑ "TFA as an atmospheric breakdown product". Fluorocarbons. European FluoroCarbons Technical Committee, (Cefic sector group). 6 December 2023. Retrieved 27 September 2024.
  14. ↑ Joerss, Hanna; Freeling, Finnian; van Leeuwen, Stefan; Hollender, Juliane; Liu, Xingang; Nödler, Karsten; Wang, Zhanyun; Yu, Bochi; Zahn, Daniel; Sigmund, Gabriel (1 November 2024). "Pesticides can be a substantial source of trifluoroacetate (TFA) to water resources". Environment International. 193 109061. Bibcode:2024EnInt.19309061J. doi:10.1016/j.envint.2024.109061. ISSN 0160-4120. PMID 39442319.
  15. ↑ "Forever chemicals pose growing threat to Europe's water". Financial Times. 2025.
  16. ↑ Asher Kalir, David Balderman (1981). "2-Phenyl-2-Adamantanamine Hydrochloride". Organic Syntheses. 60: 104. doi:10.15227/orgsyn.060.0104.
  17. ↑ Eidman, K. F.; Nichols, P. J. (2004). "Trifluoroacetic Acid". In L. Paquette (ed.). Encyclopedia of Reagents for Organic Synthesis. New York: J. Wiley & Sons. doi:10.1002/047084289X.rt236.pub2. hdl:10261/236866. ISBN 978-0-471-93623-7.
  18. ↑ Lundt, Behrend F.; Johansen, Nils L.; Vølund, Aage; Markussen, Jan (1978). "Removal of t-Butyl and t-Butoxycarbonyl Protecting Groups with Trifluoroacetic acid". International Journal of Peptide and Protein Research. 12 (5): 258–268. doi:10.1111/j.1399-3011.1978.tb02896.x. PMID 744685.
  19. ↑ Andrew B. Hughes (2011). "1. Protection Reactions". In Vommina V. Sureshbabu; Narasimhamurthy Narendra (eds.). Amino Acids, Peptides and Proteins in Organic Chemistry: Protection Reactions, Medicinal Chemistry, Combinatorial Synthesis. Vol. 4. pp. 1–97. doi:10.1002/9783527631827.ch1. ISBN 978-3-527-63182-7.
  20. ↑ Stout, Steven J.; Dacunha, Adrian R. (1989). "Tuning and calibration in thermospray liquid chromatography/mass spectrometry using trifluoroacetic acid cluster ions". Analytical Chemistry. 61 (18): 2126. Bibcode:1989AnaCh..61.2126S. doi:10.1021/ac00193a027.
  21. ↑ O. Castano; A. Cavallaro; A. Palau; J. C. Gonzalez; M. Rossell; T. Puig; F. Sandiumenge; N. Mestres; S. Pinol; A. Pomar & X. Obradors (2003). "High quality YBa2Cu3O7 thin films grown by trifluoroacetates metal-organic deposition". Superconductor Science and Technology. 16 (1): 45–53. Bibcode:2003SuScT..16...45C. doi:10.1088/0953-2048/16/1/309. S2CID 250765145.
  22. ↑ Henne, Albert L; Fox, Charles J (1951). "Ionization constants of fluorinated acids". Journal of the American Chemical Society. 73 (5): 2323–2325. Bibcode:1951JAChS..73.2323H. doi:10.1021/ja01149a122.
  23. ↑ "Safety Data Sheet - Trifluoroacetic Acid - Version 6.8". Sigma-Aldrich. Retrieved 25 November 2024.
  24. ↑ "Halothane", LiverTox: Clinical and Research Information on Drug-Induced Liver Injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases, 2012, PMID 31643481, retrieved 15 July 2021
  25. 1 2 "Forever chemicals pose growing threat to Europe's water". Financial Times. 2025.
  26. ↑ "Registry of CLH intentions until outcome: Trifluoroacetic acid". ECHA. Retrieved 23 July 2026.
  27. ↑ "Minutes of the 77th Meeting of the Committee for Risk Assessment (RAC-77)". ECHA. 5 June 2026. Retrieved 23 July 2026.
  28. 1 2 "EFSA lowers safe level for exposure to TFA". www.efsa.europa.eu. EFSA. 22 July 2026. Retrieved 23 July 2026.
  29. ↑ EFSA (European Food Safety Authority); Cavelier, Adeline; Coja, Tamara; Gall, Andrea; Hernández-Jerez, Antonio; Vleminckx, Christiane; Bergsma, Elodie; Binaglia, Marco; Crivellente, Federica; Colas, Mathilde; Lanzoni, Anna; Louisse, Jochem; De Jesus, Rafaela Rodrigues; Grillo, Annetta; Mangas, Iris (2026). "Scientific Report on consumer health-based guidance values for trifluoroacetic acid". EFSA Journal. 24 (7) e10227. doi:10.2903/j.efsa.2026.10227. PMC 13389894. PMID 42488728.
  30. ↑ 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. Bibcode:1999HERA....5...59B. doi:10.1080/10807039991289644.
  31. 1 2 Hanson, Mark L.; Madronich, Sasha; Solomon, Keith; Sulbaek Andersen, Mads P.; Wallington, Timothy J. (1 October 2024). "Trifluoroacetic Acid in the Environment: Consensus, Gaps, and Next Steps". Environmental Toxicology and Chemistry. 43 (10): 2091–2093. Bibcode:2024EnvTC..43.2091H. doi:10.1002/etc.5963. ISSN 0730-7268. PMID 39078279.
  32. ↑ Nilsson, Müller and Hancock (2 June 2025). "Europe's fight to get rid of 'forever chemicals'". Financial Times. Retrieved 2 June 2025.
  33. ↑ Joerss, Hanna; Freeling, Finnian; van Leeuwen, Stefan; Hollender, Juliane; Liu, Xingang; Nödler, Karsten; Wang, Zhanyun; Yu, Bochi; Zahn, Daniel; Sigmund, Gabriel (1 November 2024). "Pesticides can be a substantial source of trifluoroacetate (TFA) to water resources". Environment International. 193 109061. Bibcode:2024EnInt.19309061J. doi:10.1016/j.envint.2024.109061. ISSN 0160-4120. PMID 39442319.
  34. 1 2 Henne, Stephan; Storck, Florian R.; Wöhrnschimmel, Henry; Leuenberger, Markus; Vollmer, Martin K.; Reimann, Stefan (16 December 2025). "Trifluoroacetate (TFA) in precipitation and surface waters in Switzerland: trends, source attribution, and budget". Atmospheric Chemistry and Physics. 25 (23): 18157–18186. Bibcode:2025ACP....2518157H. doi:10.5194/acp-25-18157-2025.
  35. ↑ Hosea, Leana; Salvidge, Rachel (1 May 2024). "Rapidly rising levels of TFA 'forever chemical' alarm experts". The Guardian. ISSN 0261-3077. Retrieved 29 May 2024.
  36. ↑ Marco Scheurer, Karsten Nödler (2021). "Ultrashort-chain perfluoroalkyl substance trifluoroacetate (TFA) in beer and tea – An unintended aqueous extraction". Food Chemistry. 351 129304. Bibcode:2021FoodC.35129304S. doi:10.1016/j.foodchem.2021.129304. ISSN 0308-8146. PMID 33657499. S2CID 232115008.
  37. ↑ Frank, H.; Christoph, E. H.; Holm-Hansen, O.; Bullister, J. L. (January 2002). "Trifluoroacetate in ocean waters". Environ. Sci. Technol. 36 (1): 12–5. Bibcode:2002EnST...36...12P. doi:10.1021/es0221659. PMID 11811478.
  38. ↑ Scott, B. F.; MacDonald, R. W.; Kannan, K.; Fisk, A.; Witter, A.; Yamashita, N.; Durham, L.; Spencer, C.; Muir, D. C. G. (September 2005). "Trifluoroacetate profiles in the Arctic, Atlantic, and Pacific Oceans". Environ. Sci. Technol. 39 (17): 6555–60. Bibcode:2005EnST...39.6555S. doi:10.1021/es047975u. PMID 16190212.
  39. ↑ Visscher, Pieter T.; Culbertson, Charles W.; Oremland, Ronald S. (June 1994). "Degradation of trifluoroacetate in oxic and anoxic sediments". Nature. 369 (6483): 729–731. Bibcode:1994Natur.369..729V. doi:10.1038/369729a0.
  40. 1 2 "Forever chemicals pose growing threat to Europe's water". Financial Times. 2025.
  41. ↑ Freeling, Finnian; Behringer, David; Heydel, Felix; Scheurer, Marco; Ternes, Thomas A.; Nödler, Karsten (2020). "Trifluoroacetate in Precipitation: Deriving a Benchmark Data Set". Environmental Science & Technology. 54 (18): 11210–11219. Bibcode:2020EnST...5411210F. doi:10.1021/acs.est.0c02910. PMID 32806887.
  42. ↑ Albers, Christian N.; Sültenfuss, Jürgen (2024). "A 60-Year Increase in the Ultrashort-Chain PFAS Trifluoroacetate and Its Suitability as a Tracer for Groundwater Age". Environmental Science & Technology Letters. 11 (10): 1090–1095. Bibcode:2024EnSTL..11.1090A. doi:10.1021/acs.estlett.4c00525.
  43. ↑ FOEN, Federal Office for the Environment. "TFA in groundwater". www.bafu.admin.ch. Retrieved 6 September 2025.
  44. ↑ "Position Paper – TFA in Drinking Water Resources" (PDF). EurEau. March 2025. Retrieved 23 July 2026.
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