Thetrifluoromethyl group is afunctional group that has theformula−CF3. The naming of is group is derived from themethyl group (which has the formula−CH3), by replacing eachhydrogen atom by afluorine atom. Some common examples aretrifluoromethaneH−CF3,1,1,1-trifluoroethaneH3C−CF3, andhexafluoroacetoneF3C−CO−CF3. Compounds with this group are a subclass of theorganofluorines.
The trifluoromethyl group has a significantelectronegativity that is often described as being intermediate between the electronegativities of fluorine and chlorine.[1] For this reason, trifluoromethyl-substituted compounds are often strong acids, such astrifluoromethanesulfonic acid andtrifluoroacetic acid. Conversely, the trifluoromethyl group lowers the basicity of compounds liketrifluoroethanol.
The trifluoromethyl group occurs in certain pharmaceuticals, drugs, andabiotically synthesized naturalfluorocarbon based compounds. The medicinal use of the trifluoromethyl group dates from 1928, although research became more intense in the mid-1940s.[2] The trifluoromethyl group is often used as abioisostere to create derivatives by replacing a chloride or a methyl group. This can be used to adjust the steric and electronic properties of alead compound, or to protect a reactive methyl group from metabolic oxidation. Some notable drugs containing trifluoromethyl groups includeefavirenz (Sustiva), an HIV reverse transcriptase inhibitor;fluoxetine (Prozac), an antidepressant; andcelecoxib (Celebrex), anonsteroidal anti-inflammatory drug.
Sulfoxaflor is used as a systemic insecticide.Trifluralin, as with several dinitritroaniline herbicides, is a trifluoromethyl herbicide.Fluazifop is another, aphenoxy herbicide.
The trifluoromethyl group can also be added to change the solubility of molecules containing other groups of interest.
Trifluoromethylated arenes such asbenzotrifluoride andbis(trifluoromethyl)benzene are typically produced on scale fromtrichloromethyl precursors:[3]
Carboxylic acids can be converted to trifluoromethyl groups by treatment withsulfur tetrafluoride. Many specialized reagents have been developed in this area includingantimony trifluoride (theSwarts reaction),trifluoromethyl copper, andRuppert's reagent.[4]