Trifluoroacetic acid (TFA) is an organofluorine compound with the

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbol ...

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, ''K''_a, that is approximately 34,000 times higher, as the highly electronegative fluorine atoms and consequent electron-withdrawing nature of the

trifluoromethyl The trifluoromethyl group is a functional group that has the formula -CF3. The naming of is group is derived from the methyl group (which has the formula -CH3), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluoro ...

group weakens the oxygen-hydrogen bond (allowing for greater acidity) and stabilises the anionic conjugate base. TFA is widely used in

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...

for various purposes.

Synthesis

TFA is prepared industrially by the electrofluorination of

acetyl chloride Acetyl chloride (CH3COCl) is an acyl chloride derived from acetic acid. It belongs to the class of organic compounds called acid halides. It is a colorless, corrosive, volatile liquid. Its formula is commonly abbreviated to AcCl. Synthesis On a ...

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 Trifluoroacetic anhydride (TFAA) is the acid anhydride of trifluoroacetic acid. It is the perfluorinated derivative of acetic anhydride. Preparation Trifluoroacetic anhydride was originally prepared by the dehydration of trifluoroacetic acid with ...

. An older route to TFA proceeds via the oxidation of 1,1,1-trifluoro-2,3,3-trichloropropene with

potassium permanganate Potassium permanganate is an inorganic compound with the chemical formula KMnO4. It is a purplish-black crystalline salt, that dissolves in water as K+ and , an intensely pink to purple solution. Potassium permanganate is widely used in the c ...

. The trifluorotrichloropropene can be prepared by Swarts fluorination of hexachloropropene.

Uses

TFA is the precursor to many other fluorinated compounds such as

trifluoroperacetic acid Trifluoroperacetic acid (trifluoroperoxyacetic acid, TFPAA) is an organofluorine compound, the peroxy acid analog of trifluoroacetic acid, with the condensed structural formula . It is a strong oxidizing agent for organic oxidation reactions, such ...

, 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 An azeotrope () or a constant heating point mixture is a mixture of two or more liquids whose proportions cannot be altered or changed by simple distillation.Moore, Walter J. ''Physical Chemistry'', 3rd e Prentice-Hall 1962, pp. 140–142 This ...

with water (b. p. 105 °C). TFA is popularly used as a strong acid to remove t-butyl derived side-chain protecting groups in Fmoc

peptide synthesis In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl ...

, 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 In chemical analysis, chromatography is a laboratory technique for the separation of a mixture into its components. The mixture is dissolved in a fluid solvent (gas or liquid) called the ''mobile phase'', which carries it through a system (a ...

(HPLC) of organic compounds, particularly peptides and small

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s. 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 acid but it does not pose the hazards associated with hydrofluoric acid because the carbon-fluorine bond is not

labile Lability refers to something that is constantly undergoing change or is likely to undergo change. Biochemistry In reference to biochemistry, this is an important concept as far as kinetics is concerned in metalloproteins. This can allow for th ...

. 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.Safety data sheet fo
Trifluoroacetic acid
(PDF) from EMD Millipore, revision date 10/27/2014. TFA is a metabolic breakdown product of the volatile anaesthetic agent halothane. It is thought to be responsible for halothane induced hepatitis.

Environment

TFA was claimed to occur naturally in sea water, but only in small concentrations at about 200 ng per liter. However, a review paper from 2021 concludes that there is insufficient evidence that TFA occurs naturally, especially without a reasonable mechanism of formation. In the environment, it is also formed, among other things, by photooxidation of the commonly used refrigerant 1,1,1,2-tetrafluoroethane (R-134a).E.H. Christoph
''Bilanzierung und Biomonitoring von Trifluoracetat und anderen Halogenacetaten''
Dissertation, 2002, Universität Bayreuth. 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. TFA is toxic to aquatic lifealthough it does not

bioaccumulate Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance at a rate faster than that at which the substance is lost or eliminated ...

, prevention of release into waterways is of extreme importance when using TFA.

References

{{DEFAULTSORT:Trifluoroacetic Acid Perfluorocarboxylic acids * Reagents for organic chemistry Organic compounds with 2 carbon atoms

Synthesis

Uses

Safety

Environment

See also

References