Trifluoroacetic acid
One of the lightest perfluoro compounds From Wikipedia, the free encyclopedia
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,[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 commonly used in organic chemistry for various purposes.
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| Names | |||
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| 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) |
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| 742035 | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider | |||
| ECHA InfoCard | 100.000.846 | ||
| 2729 | |||
PubChem CID |
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| RTECS number |
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| UNII | |||
CompTox Dashboard (EPA) |
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| 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: | |||
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| 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) | |||
| 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).
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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.[6]
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.[7] 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.[8][9]
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.[10]
TFA is used to produce trifluoroacetate salts.[11]
Safety
Trifluoroacetic acid is a strong acid.[12] 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. [13]
Environment
Summarize
Perspective
Although trifluoroacetic acid is not produced biologically or abiotically,[14] it is a metabolic breakdown product of the volatile anesthetic agent halothane. It is also thought to be responsible for halothane-induced hepatitis.[15] It also may be formed by photooxidation of the commonly used refrigerant 1,1,1,2-tetrafluoroethane (R-134a).[16][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.[18][19]
Trifluoroacetic acid is also formed by the degradation of pesticides that contain a CF3 group, like Flufenacet.[20] The German Umweltbundesamt has identified pesticides as the main source of TFA in water in agricultural areas. In November 2024, the Swiss authorities presented an overview of widespread groundwater contamination with TFA.[21]
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.[22] Median concentrations of a few micrograms per liter have been found in beer and tea.[23] Seawater can contain about 200 ng of TFA per liter.[24][25][26] Biotransformation by decarboxylation to fluoroform has been discussed.[27] In October 2024, a publication proposed classifying TFA as a planetary boundary threat, similar to how CFCs are treated.[28]
Toxicology
Trifluoroacetic acid is mildly phytotoxic.[29] 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.[30]
See also
- Fluoroacetic acid – highly toxic but naturally occurring rodenticide CH2FCOOH
- Difluoroacetic acid
- Trichloroacetic acid, the chlorinated analog
- Trifluoroacetone – also abbreviated TFA
References
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