Jump to content

Trifluoroacetic acid

From Wikipedia, the free encyclopedia
(Redirected from CF3CO2H)
For the abbreviation TFA, or another perfluoro compound, see TFA and Trifluoroacetone.
On Wikipedia, TFA refers to Today's featured article.

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 Edit this at Wikidata
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 Pungent/Vinegar
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) 0.52 [2]
Conjugate base trifluoroacetate
−43.3·10−6 cm3/mol
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Highly corrosive
GHS labelling:
GHS05: CorrosiveGHS07: Exclamation mark
Danger
H314, H332, H412
P260, P261, 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
 Acetic acid
Trichloroacetic acid
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Trifluoroacetic acid (TFA) is a synthetic 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 is not produced biologically or abiotically and is commonly used in organic chemistry for various purposes.[4] It is the most abundant PFAS found in the environment.[5]

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,[6] 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.

Synthesis

[edit]

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

Where desired, this compound may 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]

Reactions

[edit]

Being a strong acid, TFA does not exist as such in water. Instead TFA fully converts to trifluoroacetate, concomitant with the protonation of water.

It protonates several weakly basic anions, e.g. azide to give hydrazoic acid.[10]

It is a precursor to trifluoroacetic anhydride.


Trifluoroacetic acid in a beaker

TFA is the precursor to many other fluorinated compounds such as 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.[11] 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.[12][13]

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.[14]

TFA is used to produce trifluoroacetate salts.[15]

Safety

[edit]

Trifluoroacetic acid is a strong acid.[16] 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.[17]

Toxicology

[edit]

Trifluoroacetic acid is mildly phytotoxic.[18] In July 2024, the German Chemical Agency submitted a proposal to the European Chemicals Agency (ECHA) to link trifluoroacetic acid and its salts to reproductive toxicity and as suspected of damaging fertility.[19]

Environment

[edit]

Uncertainties remain in our understanding of the potential impacts on the environment of TFA.[3][20][21] A debate is ongoing regarding its ecological risk due to its persistence, ubiquity in the environment and increasing concentrations globally.[20] 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]

Although trifluoroacetic acid is not produced biologically or abiotically,[22] it is a metabolic breakdown product of the volatile anesthetic agent halothane. It is also thought to be responsible for halothane-induced hepatitis.[23] It also may be formed by photooxidation of the commonly used refrigerant 1,1,1,2-tetrafluoroethane (R-134a).[24][25] 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.[26][27]

Trifluoroacetic acid is also formed by the degradation of pesticides that contain a CF3 group, like Flufenacet.[28] The German Umweltbundesamt has identified pesticides as the main source of TFA in water in agricultural areas.

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.[29] Median concentrations of a few micrograms per liter have been found in beer and tea.[30] Seawater can contain about 200 ng of TFA per liter.[31][32][33] Biotransformation by decarboxylation to fluoroform has been discussed.[34] In October 2024, a publication proposed classifying TFA as a planetary boundary threat, similar to how CFCs are treated.[35]

Water contamination in Europe

[edit]

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.[36] 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 dramatically since the 1990s. German studies documented a fivefold increase in TFA levels in rainfall since the 1990s, while Danish groundwater showed more than tenfold increases over the same period. 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.[36]

The German Environment Agency estimated that pesticide use releases approximately 500 metric tonnes of TFA annually in Germany alone, while refrigerants account for around 1,170 metric tonnes per year.[37] In November 2024, the Swiss authorities presented an overview of widespread groundwater contamination with TFA.[38]

Regulatory response

[edit]

In 2024, the German Federal Institute for Risk Assessment formally requested that the European Chemicals Agency (ECHA) reclassify TFA as "presumed" toxic to human reproduction, based on studies showing damage to animal fetuses. ECHA opened a public consultation on this reclassification request and is expected to make recommendations to the European Commission regarding labeling and control measures.[36]

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.[36]

See also

[edit]

References

[edit]
  1. ^ Kreglewski, A. (1962). "Trifluoroacetic acid". Welcome to the NIST WebBook. 10 (11–12): 629–633. Retrieved 1 March 2020.
  2. ^ W. M. Haynes.; David R. Lide; Thomas J. Bruno, eds. (2016–2017). CRC Handbook of Chemistry and Physics. CRC Press. pp. 954–963. ISBN 978-1-4987-5429-3.
  3. ^ a b c d 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. ISSN 0013-936X. PMC 11562725. PMID 39475534.
  4. ^ 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. doi:10.1039/D1EM00306B. hdl:10315/40884. ISSN 2050-7887. PMID 34693963. S2CID 239768006.
  5. ^ 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. ISSN 0013-936X. PMC 11562725. PMID 39475534.
  6. ^ Note: Calculated from the ratio of the Ka values for TFA (pKa = 0.23) and acetic acid (pKa = 4.76)
  7. ^ a b 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. ^ Asher Kalir, David Balderman (1981). "2-Phenyl-2-Adamantanamine Hydrochloride". Organic Syntheses. 60: 104. doi:10.15227/orgsyn.060.0104.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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. doi:10.1021/ac00193a027.
  15. ^ 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.
  16. ^ 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.
  17. ^ "Safety Data Sheet - Trifluoroacetic Acid - Version 6.8". Sigma-Aldrich. Retrieved 25 November 2024.
  18. ^ 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.
  19. ^ Garry, Michael (1 July 2024). "German Chemicals Office Submits Proposal to EU Linking TFA to Reproductive Toxicity". Natural Refrigerants. Retrieved 5 February 2025.
  20. ^ a b 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.
  21. ^ Nilsson, Müller and Hancock (2 June 2025). "Europe's fight to get rid of 'forever chemicals'". Financial Times. Retrieved 2 June 2025.
  22. ^ 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. doi:10.1039/D1EM00306B. hdl:10315/40884. ISSN 2050-7887. PMID 34693963. S2CID 239768006.
  23. ^ "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
  24. ^ Scientific Assessment of Ozone Depletion: 2010 (PDF). Global Ozone Research and Monitoring Project. World Meteorological Organization.
  25. ^ 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. doi:10.1021/jp9624764.
  26. ^ "Degradation products of fluorinated greenhouse gases". Umweltbundesamt. 19 June 2023. Retrieved 27 September 2024.
  27. ^ "TFA as an atmospheric breakdown product". Fluorocarbons. European FluoroCarbons Technical Committee, (Cefic sector group). 6 December 2023. Retrieved 27 September 2024.
  28. ^ 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.
  29. ^ 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.
  30. ^ Marco Scheurer, Karsten Nödler (2021). "Ultrashort-chain perfluoroalkyl substance trifluoroacetate (TFA) in beer and tea – An unintended aqueous extraction". Food Chemistry. 351: 129304. doi:10.1016/j.foodchem.2021.129304. ISSN 0308-8146. PMID 33657499. S2CID 232115008.
  31. ^ 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.
  32. ^ 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.
  33. ^ Frank, Hartmut; Christoph, Eugen H.; Holm-Hansen, Osmund; Bullister, John L. (2002). "Trifluoroacetate in Ocean Waters". Environmental Science & Technology. 36 (1): 12–15. Bibcode:2002EnST...36...12F. doi:10.1021/es0101532. ISSN 0013-936X. PMID 11811478.
  34. ^ 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.
  35. ^ 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.
  36. ^ a b c d "Forever chemicals pose growing threat to Europe's water". Financial Times. 2025.
  37. ^ "Forever chemicals pose growing threat to Europe's water". Financial Times. 2025.
  38. ^ FOEN, Federal Office for the Environment. "TFA in groundwater". www.bafu.admin.ch. Retrieved 5 February 2025.
Retrieved from "https://en.wikipedia.org/w/index.php?title=Trifluoroacetic_acid&oldid=1293686765"