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 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 diamond
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).
☒N verify (what is checkY☒N ?)
Infobox references

Trifluoroacetic acid (TFA) is an organofluorine compound with the chemical formula CF3CO2H. It is a structural analogue of acetic acid with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with a vinegar-like odor.

Trifluoroacetic acid in a beaker

TFA is a stronger acid than acetic acid, having an acid ionisation constant, Ka, that is approximately 34,000 times higher,[3] 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 widely 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]

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.[5]

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.

Uses

TFA is the precursor to many other fluorinated compounds such as trifluoroacetic anhydride, trifluoroperacetic acid, and 2,2,2-trifluoroethanol.[4] 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.[6] 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 popularly used as a strong acid to remove protecting groups such as Fmoc and BOC used in organic chemistry and peptide synthesis.[7][8]

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.[9]

TFA is used to produce trifluoroacetate salts.[10]

Safety

Trifluoroacetic acid is a corrosive acid but it does not pose the hazards associated with hydrofluoric acid because the carbon-fluorine bond is not labile. Only if heated or treated with ultrasonic waves will it decompose into hydrofluoric acid. TFA is harmful when inhaled, causes severe skin burns and is toxic for aquatic organisms even at low concentrations.

TFA's reaction with bases and metals, especially light metals, is strongly exothermic. The reaction with lithium aluminium hydride (LAH) results in an explosion.[11]

TFA is a metabolic breakdown product of the volatile anaesthetic agent halothane. It is thought to be responsible for halothane induced hepatitis.[12]

Environment

TFA was claimed to occur naturally in sea water, but only in small concentrations at about 200 ng per liter.[13][14][15] However, a review paper from 2021 concludes that there is insufficient evidence that TFA occurs naturally, especially without a reasonable mechanism of formation.[16]

In the environment, it is also formed, among other things, by photooxidation of the commonly used refrigerant 1,1,1,2-tetrafluoroethane (R-134a).[17] 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.

TFA is virtually non-degradable (persistent) in the environment. Median concentrations of a few micrograms per liter have been found in beer and tea.[18] TFA is toxic to aquatic life – although it does not bioaccumulate, prevention of release into waterways is of extreme importance when using TFA.[19]

See also

References
  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. pp. 954–963. ISBN 978-1-4987-5429-3.
  3. Note: Calculated from the ratio of the Ka values for TFA (pKa = 0.23) and acetic acid (pKa = 4.76)
  4. 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.
  5. 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 9781856175678.
  6. 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 9780471936237.
  7. 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.
  8. 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 9783527631827.
  9. 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.
  10. 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.
  11. Safety data sheet for Trifluoroacetic acid (PDF) from EMD Millipore, revision date 10/27/2014.
  12. "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
  13. 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.
  14. 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.
  15. 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.
  16. 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.
  17. E.H. Christoph: Bilanzierung und Biomonitoring von Trifluoracetat und anderen Halogenacetaten, Dissertation, 2002, Universität Bayreuth.
  18. 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.
  19. "GPS Safety Summary: Trifluoroacetic Acid" (PDF). Retrieved 18 October 2016.
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