Trifluoroacetic acid (TFA) is a synthetic
organofluorine
Organofluorine chemistry describes the chemistry of organofluorine compounds, organic compounds that contain a carbon–fluorine bond. Organofluorine compounds find diverse applications ranging from Lipophobicity, oil and hydrophobe, water repell ...
compound with the
chemical formula
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, such as pare ...
CF
3CO
2H. It belongs to the subclass of
per- and polyfluoroalkyl substances
Per- and polyfluoroalkyl substances (also PFAS, PFASs, and informally referred to as "forever chemicals") are a group of synthetic organofluorine chemical compounds that have multiple fluorine atoms attached to an alkyl chain; there are 7 milli ...
(PFASs) known as ultrashort-chain perfluoroalkyl acids (PFAAs).
TFA is not produced biologically or abiotically and is commonly used in
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the science, scientific study of the structure, properties, and reactions of organic compounds and organic matter, organic materials, i.e., matter in its various forms that contain ...
for various purposes. It is the most abundant PFAS found in the environment.
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
Vinegar () is an aqueous solution of diluted acetic acid and trace compounds that may include flavorings. Vinegar typically contains from 5% to 18% acetic acid by volume. Usually, the acetic acid is produced by a double fermentation, converting ...
-like odor. TFA is a stronger acid than
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 compone ...
, 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 . The naming of is group is derived from the methyl group (which has the formula ), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluoromethane ...
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 conven ...
ic
conjugate base
A conjugate acid, within the Brønsted–Lowry acid–base theory, is a chemical compound formed when an acid gives a proton () to a base—in other words, it is a base with a hydrogen ion added to it, as it loses a hydrogen ion in the reve ...
.
Synthesis
TFA is prepared industrially by the
electrofluorination Electrochemical fluorination (ECF), or electrofluorination, is a foundational organofluorine chemistry method for the preparation of fluorocarbon-based organofluorine compounds.G. Siegemund, W. Schwertfeger, A. Feiring, B. Smart, F. Behr, H. Vogel ...
of
acetyl chloride
Acetyl chloride () 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 an ...
or
acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the chemical formula, formula . Commonly abbreviated , it is one the simplest organic acid anhydride, anhydrides of a carboxylic acid and is widely used in the production of c ...
, 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
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
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, which dissolves in water as K+ and ions to give an intensely pink to purple solution.
Potassium permanganate is widely us ...
. 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 of ...
of
hexachloropropene
Hexachloropropene is a compound of chlorine and carbon with the linear formula CCl3CCl=CCl2. It is a colourless liquid at room temperature. It is toxic for humans.
Hexachloropropene can be produced by the dehydrochlorination reaction of 1,1,1, ...
.
Reactions
Being a strong acid, TFA does not exist as such in water. Instead TFA fully converts to
trifluoroacetate
Trifluoroacetic acid (TFA) is a synthetic organofluorine compound with the chemical formula CF3CO2H. It belongs to the subclass of per- and polyfluoroalkyl substances (PFASs) known as ultrashort-chain perfluoroalkyl acids (PFAAs). TFA is not p ...
, concomitant with the protonation of water.
It protonates several weakly basic anions, e.g. azide to give
hydrazoic acid
Hydrazoic acid, also known as hydrogen azide, azic acid or azoimide, This also contains a detailed description of the contemporaneous production process. is a compound with the chemical formula . It is a colorless, volatile, and explosive liquid ...
.
It is a precursor to
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 ...
.

TFA is the precursor to many other fluorinated compounds such as
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 ...
,
trifluoroperacetic acid, 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 branch of chemical synthesis concerned with the construction of organic compounds. Organic compounds are molecules consisting of combinations of covalently-linked hydrogen, carbon, oxygen, and nitrogen atoms. Within the gen ...
because of a combination of convenient properties: volatility, solubility
In chemistry, solubility is the ability of a chemical substance, substance, the solute, to form a solution (chemistry), solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form su ...
in organic solvent
A solvent (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for p ...
s, and its strength as an acid. TFA is also less oxidizing
Redox ( , , reduction–oxidation or oxidation–reduction) is a type of chemical reaction in which the oxidation states of the reactants change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is ...
than sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...
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 changed by simple distillation.Moore, Walter J. ''Physical Chemistry'', 3rd e Prentice-Hall 1962, pp. 140–142 This happens beca ...
with water (b. p. 105 °C).
TFA is used as a strong acid to remove protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In man ...
s such as Boc used in organic chemistry and 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 ...
.
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 ...
(HPLC
High-performance liquid chromatography (HPLC), formerly referred to as high-pressure liquid chromatography, is a technique in analytical chemistry used to separate, identify, and quantify specific components in mixtures. The mixtures can origina ...
) of organic compounds, particularly peptide
Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty am ...
s and small protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
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 based on re-orientation of atomic nuclei with non-zero nuclear spins in an external magnetic f ...
(for materials stable in acid). It is also used as a calibrant in mass spectrometry
Mass spectrometry (MS) is an analytical technique that is used to measure the mass-to-charge ratio of ions. The results are presented as a ''mass spectrum'', a plot of intensity as a function of the mass-to-charge ratio. Mass spectrometry is used ...
.
TFA is used to produce trifluoroacetate salts.
Safety
Trifluoroacetic acid is a strong acid. TFA is harmful when inhaled, causes severe skin burns and is toxic for aquatic organism
An aquatic ecosystem is an ecosystem found in and around a body of water, in contrast to land-based terrestrial ecosystems. Aquatic ecosystems contain communities of organisms—aquatic life—that are dependent on each other and on their environm ...
s even at low concentrations.
Skin burns are severe, heal poorly and can be necrotic
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. The term "necrosis" came about in the mid-19th century and is commonly attributed to German pathologist Rudolf Virchow, who is ...
. 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 oedema
Edema (American English), also spelled oedema (British English), and also known as fluid retention, swelling, dropsy and hydropsy, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may inclu ...
s in the respiratory tract. Exposure damages the kidneys.
Toxicology
Trifluoroacetic acid is mildly phytotoxic
Phytotoxins are substances that are poisonous or toxic to the growth of plants. Phytotoxic substances may result from human activity, as with herbicides, or they may be produced by plants, by microorganisms, or by naturally occurring chemical react ...
. In July 2024, the German Chemical Agency submitted a proposal to the European Chemicals Agency
The European Chemicals Agency (ECHA; ) is an agency of the European Union working for the safe use of chemicals. It manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, E ...
(ECHA) to link trifluoroacetic acid and its salts to reproductive toxicity and as suspected of damaging fertility.
Environment
Uncertainties remain in our understanding of the potential impacts on the environment of TFA. A debate is ongoing regarding its ecological risk due to its persistence, ubiquity in the environment and increasing concentrations globally. TFA exposure is widespread and increasing and it is the most abundant PFAS
Per- and polyfluoroalkyl substances (also PFAS, PFASs, and informally referred to as "forever chemicals") are a group of synthetic organofluorine chemical compounds that have multiple fluorine atoms attached to an alkyl chain; there are 7 millio ...
found in the environment. TFA does not have well-established health advisories or regulatory limits as other PFAAs.
Although trifluoroacetic acid is not produced biologically or abiotically, it is a metabolic breakdown product of the volatile anesthetic 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 ...
. It is also thought to be responsible for halothane-induced hepatitis
Hepatitis is inflammation of the liver parenchyma, 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), Anorexia (symptom), poor appetite ...
. It also may be formed by photooxidation of the commonly used refrigerant
A refrigerant is a working fluid used in the cooling, heating, or reverse cooling/heating cycles of air conditioning systems and heat pumps, where they undergo a repeated phase transition from a liquid to a gas and back again. Refrigerants are ...
1,1,1,2-tetrafluoroethane
1,1,1,2-Tetrafluoroethane (also known as norflurane ( INN), R-134a, Klea 134a, Freon 134a, Forane 134a, Genetron 134a, Green Gas, Florasol 134a, Suva 134a, HFA-134a, or HFC-134a) is a hydrofluorocarbon (HFC) and haloalkane refrigerant with th ...
(R-134a). Moreover, it is formed as an atmospheric degradation product of almost all fourth-generation synthetic refrigerants, also called hydrofluoroolefin
Hydrofluoroolefins (HFOs) are Saturated and unsaturated compounds, unsaturated organic compounds composed of hydrogen, fluorine and carbon. These organofluorine compounds are of interest as refrigerants. Unlike traditional hydrofluorocarbons (HFCs ...
s (HFO), such as 2,3,3,3-tetrafluoropropene.
Trifluoroacetic acid is also formed by the degradation of pesticides that contain a CF3 group, like Flufenacet
Flufenacet is an oxyacetanilide herbicide applied Preemergent herbicide, before crops have emerged. It was registered for use in the United States in 1998 and the European Union in 2004.
Mode of action
Flufenacet is related to the chloroacetami ...
. The German Umweltbundesamt
The Umweltbundesamt (; UBA, ) is the environment agency of the German government. Together with the Federal Agency for Nature Conservation, the Federal Office for the Safety of Nuclear Waste Management, and the Bundesamt für Strahlenschutz ( ...
has identified pesticides as the main source of TFA in water in agricultural areas.
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. Seawater
Seawater, or sea water, is water from a sea or ocean. On average, seawater in the world's oceans has a salinity of about 3.5% (35 g/L, 35 ppt, 600 mM). This means that every kilogram (roughly one liter by volume) of seawater has approximat ...
can contain about 200 ng of TFA per liter. Biotransformation
Biotransformation is the biochemical modification of one chemical compound or a mixture of chemical compounds. Biotransformations can be conducted with whole cells, their lysates, or purified enzymes. Increasingly, biotransformations are effected ...
by decarboxylation
Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is ...
to fluoroform
Fluoroform, or trifluoromethane, is the chemical compound with the formula . It is a hydrofluorocarbon as well as being a part of the haloforms, a class of compounds with the formula (X = halogen) with C3v symmetry. Fluoroform is used in divers ...
has been discussed. In October 2024, a publication proposed classifying TFA as a planetary boundary
Planetary boundaries are a framework to describe limits to the impacts of human activities on the Earth system. Beyond these limits, the environment may not be able to continue to self-regulate. This would mean the Earth system would leave th ...
threat, similar to how CFCs are treated.
Water contamination in Europe
TFA has emerged as a significant environmental contaminant across European waterways since its discovery in 2016 by researchers at the Karlsruhe Water Technology Center in Germany. Unlike other PFAS
Per- and polyfluoroalkyl substances (also PFAS, PFASs, and informally referred to as "forever chemicals") are a group of synthetic organofluorine chemical compounds that have multiple fluorine atoms attached to an alkyl chain; there are 7 millio ...
compounds, TFA's high water solubility allows it to spread rapidly through rivers and precipitation rather than binding to soil or organic matter.
TFA concentrations in European water sources have increased dramatically since the 1990s. German studies documented a fivefold increase in TFA levels in rainfall since the 1990s, while Danish groundwater showed more than tenfold increases over the same period. Research by the anti-pesticide network PAN Europe found that TFA accounted for 98 percent of all PFAS detected in water samples from 10 EU countries.
The German Environment Agency estimated that pesticide use releases approximately 500 metric tonnes of TFA annually in Germany alone, while refrigerants account for around 1,170 metric tonnes per year. In November 2024, the Swiss authorities presented an overview of widespread groundwater contamination with TFA.
Regulatory response
In 2024, the German Federal Institute for Risk Assessment formally requested that the European Chemicals Agency
The European Chemicals Agency (ECHA; ) is an agency of the European Union working for the safe use of chemicals. It manages the technical and administrative aspects of the implementation of the European Union regulation called Registration, E ...
(ECHA) reclassify TFA as "presumed" toxic to human reproduction, based on studies showing damage to animal fetuses. ECHA opened a public consultation on this reclassification request and is expected to make recommendations to the European Commission
The European Commission (EC) is the primary Executive (government), executive arm of the European Union (EU). It operates as a cabinet government, with a number of European Commissioner, members of the Commission (directorial system, informall ...
regarding labeling and control measures.
The contamination has proven extremely difficult to address due to TFA's resistance to conventional water treatment methods. The only effective removal technique is reverse osmosis, which is prohibitively expensive and wastes up to 25 percent of treated water while producing concentrated brine that requires indefinite containment.
See also
* Fluoroacetic acid
Fluoroacetic acid is an organofluorine compound with the chemical formula . It is a colorless solid that is noted for its relatively high toxicity. The conjugate base, fluoroacetate occurs naturally in at least 40 plants in Australia, Brazil, an ...
highly toxic but naturally occurring rodenticide
Rodenticides are chemicals made and sold for the purpose of killing rodents. While commonly referred to as "rat poison", rodenticides are also used to kill mice, woodchucks, chipmunks, porcupines, nutria, beavers, and voles.
Some rodenticides ...
CH2FCOOH
* Difluoroacetic acid
Difluoroacetic acid is a chemical compound with formula . It is a dihalogenocarboxylic acid, specifically a structural analog of acetic acid with two of three hydrogen atoms on the alpha carbon replaced with fluorine atoms. In solution, it dissoci ...
* Trichloroacetic acid
Trichloroacetic acid (TCA; TCAA; also known as trichloroethanoic acid) is an analogue of acetic acid in which the three hydrogen atoms of the methyl group have all been replaced by chlorine atoms. Salts and esters of trichloroacetic acid are cal ...
, the chlorinated analog
* Trifluoroacetone – also abbreviated TFA
References
{{DEFAULTSORT:Trifluoroacetic Acid
Perfluorocarboxylic acids
*
Reagents for organic chemistry
Organic compounds with 2 carbon atoms