Trifluoromethyl group

Short description: Functional group

Chemical structure of the trifluoromethyl group

The trifluoromethyl group is a functional group that has the formula –CF
3. The naming of is group is derived from the methyl group (which has the formula –CH
3), by replacing each hydrogen atom by a fluorine atom. Some common examples are trifluoromethane H–CF
3, 1,1,1-trifluoroethane H
3C–CF
3, and hexafluoroacetone F
3C–CO–CF
3. Compounds with this group are a subclass of the organofluorines.

## Contents

* 1 Properties
* 2 Uses
* 3 Synthesis
* 4 See also
* 5 References

## Properties

The trifluoromethyl 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. Conversely, the trifluoromethyl group lowers the basicity of compounds like N-trifluoromethyl azoles.[2]

## Uses

The trifluoromethyl group occurs in certain pharmaceuticals, drugs, and abiotically synthesized natural fluorocarbon based compounds. The medicinal use of the trifluoromethyl group dates from 1928, although research became more intense in the mid-1940s.[3] 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 nonsteroidal anti-inflammatory drug.

Similar to pharmaceuticals, many pesticides also contain one or more trifluoromethyl groups.[4] Sulfoxaflor is used as a systemic insecticide. Trifluralin, as with several dinitritroaniline herbicides, is a trifluoromethyl herbicide. Fluazifop is another, a phenoxy herbicide. Fipronil, for example, contains two trifluoromethyl groups.

Hexafluoroisopropanol and trifluoroethanol have applications as specialist solvents. Compared to their non-fluorinated counterparts, they have reduced boiling points, increased polarity, reduced nucleophilicity, a greater propensity to donate hydrogen bonds, and a much weaker propensity to accept hydrogen bonds.[5][6]

## Synthesis

Main article: Chemistry:Trifluoromethylation

Trifluoromethylated arenes such as benzotrifluoride and bis(trifluoromethyl)benzene are typically produced on scale from trichloromethyl precursors:[7]

5CCl
3 \+ 3 HF → C

5CF
3 \+ 3 HCl

4(CCl

2 \+ 6 HF → C

4(CF

2 \+ 6 HCl

Carboxylic acids can be converted to trifluoromethyl groups by treatment with sulfur tetrafluoride. Many specialized reagents have been developed in this area including antimony trifluoride (the Swarts reaction), trifluoromethyl copper, and Ruppert's reagent.[8]

## See also

* Trifluromethyl cation
* Trichloromethyl group
* Trifluoromethoxy group
* Fluoroethyl

## References

1. ↑ Jan E. True; T. Darrah Thomas; Rolf W. Winter; Gary L. Gard (2003). "Electronegativities from Core-Ionization Energies: Electronegativities of SF5 and CF3". Inorganic Chemistry 42 (14): 4437–4441. doi:10.1021/ic0343298. PMID 12844318.
2. ↑ Schiesser, Stefan; Chepliaka, Hanna; Kollback, Johanna; Quennesson, Thibaut; Czechtizky, Werngard; Cox, Rhona J. (12 November 2020). "N-Trifluoromethyl Amines and Azoles: An Underexplored Functional Group in the Medicinal Chemist’s Toolbox". Journal of Medicinal Chemistry 63 (21): 13076–13089. doi:10.1021/acs.jmedchem.0c01457.
3. ↑ Yale, Harry L. (1959). "The Trifluoromethyl Group in Medicinal Chemistry". Journal of Medicinal and Pharmaceutical Chemistry 1 (2): 121–133. doi:10.1021/jm50003a001. PMID 13665284.
4. ↑ Donley, Nathan; Cox, Caroline; Bennett, Kyla; Temkin, Alexis M.; Andrews, David Q.; Naidenko, Olga V. (July 2024). "Forever Pesticides: A Growing Source of PFAS Contamination in the Environment". Environmental Health Perspectives 132 (7). doi:10.1289/EHP13954.
5. ↑ Shuklov, Ivan; Dubrovina, Natalia; Börner, Armin (October 2007). "Fluorinated Alcohols as Solvents, Cosolvents and Additives in Homogeneous Catalysis". Synthesis 2007 (19): 2925–2943. doi:10.1055/s-2007-983902.
6. ↑ Colomer, Ignacio; Chamberlain, Anna E. R.; Haughey, Maxwell B.; Donohoe, Timothy J. (8 November 2017). "Hexafluoroisopropanol as a highly versatile solvent". Nature Reviews Chemistry 1 (11). doi:10.1038/s41570-017-0088.
7. ↑ Siegemund, Günter; Schwertfeger, Werner; Feiring, Andrew; Smart, Bruce; Behr, Fred; Vogel, Herward; McKusick, Blaine (2000). "Fluorine Compounds, Organic". Ullmann's Encyclopedia of Industrial Chemistry. doi:10.1002/14356007.a11_349. ISBN 978-3-527-30385-4.
8. ↑ Synthetic fluorine chemistry. John Wiley. 1992. ISBN 978-0-471-54370-1.

0.00

(0 votes)

Original source: https://en.wikipedia.org/wiki/Trifluoromethyl group. Read more

|

Retrieved from "https://handwiki.org/wiki/index.php?title=Chemistry:Trifluoromethyl_group&oldid=4437682"