Trifluoroacetic acid (TFA) is an

organofluorine Organofluorine chemistry describes the chemistry of the organofluorines, organic compounds that contain the carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from oil and water repellents to pharmaceuticals, ref ...

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 symbols, ...

CF₃CO₂H. It is a structural analogue of

acetic acid Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...

with all three of the acetyl group's hydrogen atoms replaced by fluorine atoms and is a colorless liquid with a

vinegar Vinegar is an aqueous solution of acetic acid and trace compounds that may include flavorings. Vinegar typically contains 5–8% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting simple sugars to et ...

-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 Electronegativity, symbolized as , is the tendency for an atom of a given chemical element to attract shared electrons (or electron density) when forming a chemical bond. An atom's electronegativity is affected by both its atomic number and the d ...

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

anion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

conjugate base A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid donates a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as in the reverse reaction it loses a ...

. 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, J.; ...

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 ...

acetic anhydride Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula (CH3CO)2O. Commonly abbreviated Ac2O, it is the simplest isolable anhydride of a carboxylic acid and is widely used as a reagent in organic synthesis. It is a col ...

, 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 Swarts fluorination is a process whereby the chlorine atoms in a compound – generally an organic compound, but experiments have been performed using silanes – are replaced with fluorine, by treatment with antimony trifluoride in the presence o ...

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 In chemistry, a reagent ( ) or analytical reagent is a substance or compound added to a system to cause a chemical reaction, or test if one occurs. The terms ''reactant'' and ''reagent'' are often used interchangeably, but reactant specifies a ...

used in

organic synthesis Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...

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 Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular formu ...

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

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

s 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, respo ...

s. TFA is a versatile solvent for

NMR spectroscopy Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy or magnetic resonance spectroscopy (MRS), is a spectroscopic technique to observe local magnetic fields around atomic nuclei. The sample is placed in a magnetic fiel ...

(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 Hydrofluoric acid is a Solution (chemistry), solution of hydrogen fluoride (HF) in water. Solutions of HF are colourless, acidic and highly Corrosive substance, corrosive. It is used to make most fluorine-containing compounds; examples include th ...

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 metal A light metal is any metal of relatively low density. More specific definitions have been proposed; none have obtained widespread acceptance. Magnesium, aluminium and titanium are light metals of significant commercial importance. Their densities ...

s, is strongly exothermic. The reaction with

lithium aluminium hydride Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...

(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 Halothane, sold under the brand name Fluothane among others, is a general anaesthetic. It can be used to induce or maintain anaesthesia. One of its benefits is that it does not increase the production of saliva, which can be particularly useful i ...

. It is thought to be responsible for halothane induced

hepatitis Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pa ...

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 In polymer chemistry photo-oxidation (sometimes: oxidative photodegradation) is the degradation of a polymer surface due to the combined action of light and oxygen. It is the most significant factor in the weathering of plastics. Photo-oxidatio ...

of the commonly used

refrigerant A refrigerant is a working fluid used in the heat pump and refrigeration cycle, refrigeration cycle of air conditioning systems and heat pumps where in most cases they undergo a repeated phase transition from a liquid to a gas and back again. Ref ...

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 2,3,3,3-Tetrafluoropropene, HFO-1234yf, is a hydrofluoroolefin (HFO) with the formula CH2=CFCF3. It is also designated R-1234yf as the first of a new class of refrigerants: it is marketed under the name Opteon YF by Chemours and as Solstice YF b ...

. 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