Trifluorotoluene Explained

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]

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]

PhX + CF3I → PhCF3 (where X = I, Br)

Industrial production is done by reacting benzotrichloride with hydrogen fluoride in a pressurized reactor.[3]

PhCCl3 + 3 HF → PhCF3 + 3 HCl

Uses

Trifluorotoluene has a variety of niche uses.

Low toxicity 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, indicating 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 at 103 °C it has a higher boiling point than dichloromethane, which has a boiling point of ~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]

Analytics

Trifluorotoluene appears in 19F NMR as a singlet at -63.2 ppm.[5]

References

  1. 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.
  3. Siegemund, Günter "Aromatic Compounds with Fluorinated Side-Chains" in Ullmann’s Encyclopedia of Industrial Chemistry 2005, Wiley-VCH. .
  4. Ogawa . Akiya . Dennis Patrick Curran . Curran . Dennis P. . 1997 . Benzotrifluoride: A Useful Alternative Solvent for Organic Reactions Currently Conducted in Dichloromethane and Related Solvents . Journal of Organic Chemistry . 62 . 3. 450–451 . 10.1021/jo9620324 . 11671431 .
  5. Denmark. Scott E.. Smith. Russell C.. Mechanistic Duality in Palladium-Catalyzed Cross-Coupling Reactions of Aryldimethylsilanolates. Intermediacy of an 8-Si-4 Arylpalladium(II) Silanolate (Supplementary Material, referenced as PhCF3) . Journal of the American Chemical Society. 3 February 2010. 132. 4. 1243–1245. 10.1021/ja907049y. 2812642. 20058920.