The trifluoromethyl group is a

functional group In organic chemistry, a functional group is any substituent or moiety (chemistry), moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions r ...

that has the

formula In science, a formula is a concise way of expressing information symbolically, as in a mathematical formula or a ''chemical formula''. The informal use of the term ''formula'' in science refers to the general construct of a relationship betwe ...

. The naming of is group is derived from the

methyl In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula (whereas normal methane has the formula ). In formulas, the group is often abbreviated as ...

group (which has the formula ), by replacing each

hydrogen Hydrogen is a chemical element; it has chemical symbol, symbol H and atomic number 1. It is the lightest and abundance of the chemical elements, most abundant chemical element in the universe, constituting about 75% of all baryon, normal matter ...

atom by a

fluorine Fluorine is a chemical element; it has Chemical symbol, symbol F and atomic number 9. It is the lightest halogen and exists at Standard temperature and pressure, standard conditions as pale yellow Diatomic molecule, diatomic gas. Fluorine is extre ...

atom. Some common examples are trifluoromethane , 1,1,1-trifluoroethane , and hexafluoroacetone . Compounds with this group are a subclass of the

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 ...

Properties

The trifluoromethyl group has a significant

electronegativity 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 ...

that is often described as being intermediate between the electronegativities of fluorine and chlorine. For this reason, trifluoromethyl-substituted compounds are often strong acids, such as trifluoromethanesulfonic acid and

trifluoroacetic acid 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 ...

. Conversely, the trifluoromethyl group lowers the basicity of compounds like trifluoroethanol.

Uses

The trifluoromethyl group occurs in certain pharmaceuticals, drugs, and abiotically synthesized natural

fluorocarbon Fluorocarbons are chemical compounds with carbon-fluorine bonds. Compounds that contain many C-F bonds often have distinctive properties, e.g., enhanced stability, volatility, and hydrophobicity. Several fluorocarbons and their derivatives are ...

based compounds. The medicinal use of the trifloromethyl group dates from 1928, although research became more intense in the mid-1940s. The trifluoromethyl group is often used as a

bioisostere In medicinal chemistry, bioisosteres are chemical substituents or groups with similar physical or chemical properties which produce broadly similar biological properties in the same chemical compound. In drug design, the purpose of exchanging one b ...

to create derivatives by replacing a chloride or a methyl group. This can be used to adjust the steric and electronic properties of a lead compound, or to protect a reactive methyl group from metabolic oxidation. Some notable drugs containing trifluoromethyl groups include efavirenz (Sustiva), an HIV reverse transcriptase inhibitor;

fluoxetine Fluoxetine, sold under the brand name Prozac, among others, is an Antidepressant, antidepressant medication of the selective serotonin reuptake inhibitor (SSRI) class used for the treatment of major depressive disorder, Anxiety disorder, anx ...

(Prozac), an antidepressant; and celecoxib (Celebrex), a

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents bl ...

. Sulfoxaflor is used as a systemic insecticide. Trifluralin, as with several dinitritroaniline herbicides, is a trifluoromethyl herbicide. Fluazifop is another, a

phenoxy herbicide Phenoxy herbicides (or "phenoxies") are two families of chemicals that have been developed as commercially important herbicides, widely used in agriculture. They share the part structure of phenoxyacetic acid. Auxins The first group to be discove ...

. The trifluoromethyl group can also be added to change the solubility of molecules containing other groups of interest.

Synthesis

Various methods exist to introduce this functionality.

Carboxylic acids In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an Substituent, R-group. The general formula of a carboxylic acid is often written as or , sometimes as with R referring to an organyl ...

can be converted to trifluoromethyl groups by treatment with sulfur tetrafluoride and trihalomethyl compounds, particularly trifluoromethyl ethers and trifluoromethyl aromatics, are converted into trifluoromethyl compounds by treatment with antimony trifluoride/ antimony pentachloride (the Swarts reaction). Another route to trifluoromethyl aromatics is the reaction of aryl iodides with trifluoromethyl copper. Finally, trifluoromethyl carbonyls can be prepared by reaction of

aldehydes In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...

and

esters In chemistry, an ester is a chemical compound, compound derived from an acid (either organic or inorganic) in which the hydrogen atom (H) of at least one acidic hydroxyl group () of that acid is replaced by an organyl group (R). These compounds c ...

with Ruppert's reagent.{{cite book , editor1=G.A. Olah , editor2=R.D. Chambers , editor3=G.K.S. Prakash , title = Synthetic fluorine chemistry , publisher = John Wiley , year = 1992 , isbn = 0-471-54370-5

References

Haloalkyl groups Functional groups

Properties

Uses

Synthesis

See also

References