Trifluoroacetic acid


Trifluoroacetic acid 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. TFA is a stronger acid than acetic acid, having an acid ionisation constant 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 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:
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.
TFA occurs naturally in sea water, but only in small concentrations.

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.
TFA is popularly used as a strong acid to remove t-butyl derived side-chain protecting groups in Fmoc peptide synthesis, and in other organic syntheses to remove the t-butoxycarbonyl protecting group.
At a low concentration, TFA is used as an ion pairing agent in liquid chromatography of organic compounds, particularly peptides and small proteins. TFA is a versatile solvent for NMR spectroscopy. It is also used as a calibrant in mass spectrometry.
TFA is used to produce trifluoroacetate salts.

Implication in anaesthesia

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

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 results in an explosion.

Environment

TFA is not readily biodegradable and is toxic to aquatic life - although it does not bioaccumulate, prevention of release into waterways is of extreme importance when using TFA.