trifluoromethyl

The trifluoromethyl group, abbreviated as CF3, is a functional group consisting of a carbon atom bonded to three fluorine atoms. When attached to an organic scaffold, it forms a CF3 substituent or a trifluoromethylated moiety. The group is small, electronically distinct, and typically acts as a strong electron-withdrawing element.

electronically, the CF3 group exerts a powerful inductive effect and low polarizability due to the high electronegativity of fluorine. As a result, it stabilizes adjacent negative charge and reduces basicity, while often increasing the lipophilicity of a molecule. The C–F bonds are among the strongest in organic chemistry, contributing to the chemical stability of trifluoromethylated compounds. The presence of CF3 can raise metabolic stability in pharmaceutical agents and alter pharmacokinetic properties, including distribution and clearance. It also tends to influence acidity of neighboring C–H bonds and can modify conformational preferences.

Methods for introducing CF3 groups are diverse. The Ruppert–Prakash reagent, trimethylsilyl trifluoromethyl (Me3SiCF3) with fluoride sources, enables nucleophilic trifluoromethylation of carbon centers. Electrophilic trifluoromethylation employs reagents such as Togni or Umemoto reagents to install CF3 onto arenes, alkenes, or heteroatoms. Other methods include photoredox or radical approaches that deliver CF3 groups under mild conditions.

In applications, CF3-containing compounds are prevalent in medicinal chemistry and agrochemistry. The group is used to tune potency, selectivity, and metabolic stability, as well as to adjust lipophilicity and oral bioavailability. Notable examples appear across drugs, agrochemicals, and materials where the CF3 group modulates physicochemical properties without introducing large steric changes.