Trifluorotoluene

Trifluorotoluene
Other names Benzotrifluoride α,α,α-Trifluorotoluene
Identifiers
CAS number	98-08-8 Y
Properties
Molecular formula	C6H5CF3
Molar mass	146.11 g/mol
Appearance	colorless liquid
Density	1.19 g/mL at 20 °C
Melting point	-29 °C
Boiling point	102 °C
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Infobox references

Trifluorotoluene is an organic compound with the formula of C₆H₅CF₃. This colorless fluorocarbon is used as a specialty solvent in organic synthesis and an intermediate in the production of pesticides and pharmaceuticals.^[1]

Contents 1 Synthesis 2 Uses 2.1 Solvent alternative to dichloromethane 2.2 Synthetic intermediate 3 References

Synthesis

For small-scale laboratory preparations, trifluorotoluene is synthesized by coupling an aromatic halide and trifluoromethyl iodide in the presence of a copper catalyst:^[2]

ArX + CF₃I → Ar-CF₃ + CuXI (where X = I, Br, Cl)

For large scale preparations using batch or continuous processes, benzotrichloride is treated with hydrogen fluoride under pressure.^[3]

C₆H₅CCl₃ + 3 HF → C₆H₅CF₃ + 3 HCl

Uses

Trifluorotoluene has a variety of niche uses.

Solvent alternative to dichloromethane

According to Ogawa and Curran, trifluorotoluene is similar to dichloromethane in standard acylation, tosylation, and silylation reactions.^[4] The dielectric constants for dichloromethane and trifluorotoluene are 9.04 and 9.18, respectively, indicative similar solvating properties. Dipole moments compare less favorably: 1.89 and 2.86 D for dichloromethane and trifluorotoluene, respectively. Replacing dichloromethane is advantageous when conditions require higher boiling solvents since trifluorotoluene boils 62 °C higher than dichloromethane (b.p. 40 °C).

As a solvent, trifluorotoluene is useful in mild Lewis-acid catalyzed reactions, such as the Friedel-Crafts preparations. The most common catalyst, aluminium trichloride reacts with trifluorotoluene at room temperature; however, zinc chloride does not.

Synthetic intermediate

A second and perhaps more valuable use of trifluorotoluene is as a synthetic intermediate. A derivative of trifluorotoluene, 3-aminobenzotrifluoride, is the precursor to the herbicide fluometuron.^[3] It is synthesized via nitration followed by reduction to meta-H₂NC₆H₄CF₃. This aniline is then converted to the urea.

Flumetramide (6-[4-(trifluoromethyl)phenyl]morpholin-3-one), a skeletal muscle relaxant, is also prepared from trifluorotoluene.^[1]

References

1. ^ ^{a b} Banks, R.E. Organofluorine Chemicals and their Industrial Applications, Ellis Horwood LTD, Chichester, 1979.
2. ^ Ogawa, Akiya; Tsuchii, Kaname “α,α,α-Trifluorotoluene” in Encyclopedia of Reagents for Organic Synthesis 2005, John Wiley and Sons. doi: 10.1002/047084289X.rn00653
3. ^ ^{a b} Siegemund, Günter “Aromatic Compounds with Fluorinated Side-Chains” in Ullmann’s Encyclopedia of Industrial Chemistry 2005, Wiley-VCH. doi:10.1002/14356007.a11_349.
4. ^ Ogawa, Akiya; Curran, Dennis P. “Benzotrifluoride: A Useful Alternative Solvent for Organic Reactions Currently Conducted in Dichloromethane and Related Solvents” Journal of Organic Chemistry 1997, volume 62, pp. 450-451. doi:10.1021/jo9620324