Trifluoroacetic acid is the simplest stable
perfluorinated carboxylic acidPerfluorinated carboxylic acids , or perfluorocarboxylates are fully fluorinated organofluorine compounds—or perfluorinated compounds—with carboxylic acid or carboxylate functional groups. PFCAs are fluorocarbon derivatives...
chemical compoundA chemical compound is a pure chemical substance consisting of two or more different chemical elements that can be separated into simpler substances by chemical reactions. Chemical compounds have a unique and defined chemical structure; they consist of a fixed ratio of atoms that are held together...
, with the formula CF
3CO
2H. It is a strong
carboxylic acidCarboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...
due to the influence of the
electronegativeElectronegativity, symbol χ , is a chemical property that describes the tendency of an atom or a functional group to attract electrons towards itself. An atom's electronegativity is affected by both its atomic number and the distance that its valence electrons reside from the charged nucleus...
trifluoromethylTrifluoromethyl is a functional group in organofluorines that has the formula -CF3. The naming of is group is derived from the methyl group , by replacing each hydrogen atom by a fluorine atom. The trifluomethyl group has a significant electronegativity that is often described as being...
group. TFA is almost 100,000-fold more acidic than
acetic acidAcetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
. TFA is widely used in
organic chemistryOrganic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, composition, reactions, and preparation of carbon-based compounds, hydrocarbons, and their derivatives...
.
Synthesis
Trifluoroacetic acid is prepared industrially by the electrofluorination of
acetyl chlorideAcetyl chloride, CH3COCl, also known as ethanoyl chloride or acyl chloride, is an acid chloride derived from acetic acid. It belongs to the class of organic compounds called acyl halides. It is a colorless liquid. Acetyl chloride does not exist in nature, because contact with water would hydrolyze...
and
acetic anhydrideAcetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
, followed by hydrolysis of the resulting trifluoroacetyl fluoride:
- + 4 → + 3 +
- + → +
Where desired, this compound may be dried by addition of
trifluoroacetic anhydrideTrifluoroacetic anhydride is the acid anhydride of trifluoroacetic acid. In particular, trifluoroacetic anhydride is the perfluorinated derivative of acetic anhydride. Like many acid anhydrides, it may be used to introduce the corresponding trifluoroacetyl group. The corresponding trifluoroacetyl...
.
An older route to TFA proceeds via the oxidation of 1,1,1-trifluoro-2,3,3-trichloropropene with
potassium permanganatePotassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
. The trifluorotrichloropropene can be prepared by Swarts fluorination of hexachloropropene.
Uses
TFA is the precursor to many other fluorinated compounds such as
trifluoroacetic anhydrideTrifluoroacetic anhydride is the acid anhydride of trifluoroacetic acid. In particular, trifluoroacetic anhydride is the perfluorinated derivative of acetic anhydride. Like many acid anhydrides, it may be used to introduce the corresponding trifluoroacetyl group. The corresponding trifluoroacetyl...
and
2,2,2-trifluoroethanol2,2,2-Trifluoroethanol is the organic compound with the formula CF3CH2OH. Also known as TFE or trifluoroethyl alcohol, this colourless, water-miscible liquid has a smell reminiscent of ethanol. Due to the electronegativity of the trifluoromethyl group, this alcohol exhibits a stronger acidic...
. It is a
reagentA reagent is a "substance or compound that is added to a system in order to bring about a chemical reaction, or added to see if a reaction occurs." Although the terms reactant and reagent are often used interchangeably, a reactant is less specifically a "substance that is consumed in the course of...
used in
organic synthesisOrganic synthesis is a special branch of chemical synthesis and is concerned with the construction of organic compounds via organic reactions. Organic molecules can often contain a higher level of complexity compared to purely inorganic compounds, so the synthesis of organic compounds has...
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 acidSulfuric acid is a strong mineral acid with the molecular formula . Its historical name is oil of vitriol. Pure sulfuric acid is a highly corrosive, colorless, viscous liquid. The salts of sulfuric acid are called sulfates...
but more readily available in anhydrous form than many other acids. One complication to its use is that TFA forms an
azeotropeAn azeotrope is a mixture of two or more liquids in such a ratio that its composition cannot be changed by simple distillation. This occurs because, when an azeotrope is boiled, the resulting vapor has the same ratio of constituents as the original mixture....
with water (b. p. 105 °C).
TFA is popularly used as a strong acid in
peptide synthesisIn organic chemistry, peptide synthesis is the production of peptides, which are organic compounds in which multiple amino acids are linked via amide bonds which are also known as peptide bonds...
and other organic synthesis to remove the t-butoxycarbonyl protecting group.
At a low concentration, TFA is used as an ion pairing agent in liquid chromatography (HPLC) of organic compounds, particularly
peptidePeptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
s and small
proteinProteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. TFA is a versatile solvent for
NMR spectroscopyNuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
(for materials stable in acid). It is also used as a calibrant in mass spectrometry.
TFA is used to produce trifluoroacetate salts that serve as precursors to ceramic materials such as YBa
2Cu
3O
{7-x}.