trifluorotoluene
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 444991574
| Name = Trifluorotoluene
| ImageFileL1 = benzotrifluoride.png
| ImageFileR1 = Trifluorotoluene-3D-balls.png
| PIN = (Trifluoromethyl)benzene
| OtherNames = Benzotrifluoride (BTF)
α,α,α-Trifluorotoluene
CF3Ph
PhCF3
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 98-08-8
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 49R6421K89
| PubChem = 7368
| EINECS = 202-635-0
| InChI = 1S/C7H5F3/c8-7(9,10)6-4-2-1-3-5-6/h1-5H
| InChIKey = GETTZEONDQJALK-UHFFFAOYSA-N
| SMILES = C1=CC=C(C=C1)C(F)(F)F
| ChemSpiderID = 7090
}}
|Section2={{Chembox Properties
| Formula = C6H5CF3
| MolarMass = 146.11 g/mol
| Appearance = colorless liquid
| Odor = aromatic
| Density = 1.19 g/mL at 20 °C
| MeltingPtC = -29.05
| BoilingPtC = 103.46
| Solubility = <0.1 g/100 mL at 21 °C
| SolubleOther = soluble in ether, benzene, ethanol, acetone
miscible in n-heptane, CCl4
| RefractIndex = 1.41486 (13 °C)
}}
|Section7={{Chembox Hazards
| FlashPtC = 12
| NFPA-H = 0 | NFPA-F = 3 | NFPA-R = 0
}}
}}
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.Banks, R.E. Organofluorine Chemicals and their Industrial Applications, Ellis Horwood LTD, Chichester, 1979.
Synthesis
For small-scale laboratory preparations, trifluorotoluene is synthesized by coupling an aromatic halide and trifluoromethyl iodide in the presence of a copper catalyst: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}}
:PhX + CF3I → PhCF3 (where X = I, Br)
Industrial production is done by reacting benzotrichloride with hydrogen fluoride in a pressurized reactor.Siegemund, Günter "Aromatic Compounds with Fluorinated Side-Chains" in Ullmann’s Encyclopedia of Industrial Chemistry 2005, Wiley-VCH. {{doi|10.1002/14356007.a11_349}}.
: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.{{cite journal | last1 = Ogawa | first1 = Akiya | author-link2 = Dennis Patrick Curran | last2 = Curran | first2 = Dennis P. | year = 1997 | title = Benzotrifluoride: A Useful Alternative Solvent for Organic Reactions Currently Conducted in Dichloromethane and Related Solvents | journal = Journal of Organic Chemistry | volume = 62 | issue = 3| pages = 450–451 | doi = 10.1021/jo9620324 | pmid = 11671431 }} 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. 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.
Analytics
Trifluorotoluene appears in 19F NMR as a singlet at -63.2 ppm.{{cite journal|last1=Denmark|first1=Scott E.|last2=Smith|first2=Russell C.|title=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=Journal of the American Chemical Society|date=3 February 2010|volume=132|issue=4|pages=1243–1245|doi=10.1021/ja907049y|pmc=2812642|pmid=20058920}}