Trifluoroacetic acid

Trifluoroacetic acid (TFA) is an 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, 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 →  + 3  +

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

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. 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. 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 Boc used in organic chemistry and peptide synthesis.

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.

TFA is used to produce trifluoroacetate salts.

Safety
Trifluoroacetic acid is a corrosive strong acid but it does not pose the hazards associated with hydrofluoric acid because the carbon-fluorine bond is not labile. 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.

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

Environment
No known natural processes generate trifluoroacetic acid. In the environment, trifluoroacetic acid 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.

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. Median concentrations of a few micrograms per liter have been found in beer and tea. Sea water contains about 200 ng of TFA per liter. No biodegradation mechanism for the compound is known in water, although biotransformation apparently decarboxylates the acid to fluoroform.

Trifluoroacetic acid is mildly phytotoxic.