The trifluomethyl group has a significant electronegativity 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 as trifluoromethanesulfonic acid and trifluoroacetic acid. In other cases, the trifluoromethyl group is employed to lower the basicity of organic compounds or to confer distinctive solvation properties (e.g. trifluoroethanol).
The trifluoromethyl group occurs in certain pharmaceuticals, drugs, and abiotically synthesized natural fluorocarbon based compounds. The medicinal use of the trifloromethyl group dates from 1928, although research became more intense in the mid-1940s.[2] The trifluoromethyl group is often used as a bioisostere 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 (Prozac), an antidepressant; and celecoxib (Celebrex), a non-steroidal anti-inflammatory.
