An Expedient Synthesis of 2,4,6-Tris(trifluoromethyl)aniline

Brian L. Edelbach; Blaze M. Pharoah; Sarina M. Bellows; Peter R. Thayer; Charles N. Fennie; Ryan E. Cowley; Patrick L. Holland

doi:10.1055/s-0032-1316809

Synthesis, Table of Contents

Synthesis 2012; 44(23): 3595-3597
DOI: 10.1055/s-0032-1316809

short paper

An Expedient Synthesis of 2,4,6-Tris(trifluoromethyl)aniline

Brian L. Edelbach

^aMonroe Community College, 1000 East Henrietta Rd., Rochester, NY 14623, USA

,

Blaze M. Pharoah

^aMonroe Community College, 1000 East Henrietta Rd., Rochester, NY 14623, USA

,

Sarina M. Bellows

^bDepartment of Chemistry, University of Rochester, Rochester, NY 14627, USA Fax: +1(585)2760205 Email: holland@chem.rochester.edu

,

Peter R. Thayer

^aMonroe Community College, 1000 East Henrietta Rd., Rochester, NY 14623, USA

,

Charles N. Fennie

^aMonroe Community College, 1000 East Henrietta Rd., Rochester, NY 14623, USA

,

Ryan E. Cowley

^bDepartment of Chemistry, University of Rochester, Rochester, NY 14627, USA Fax: +1(585)2760205 Email: holland@chem.rochester.edu

,

Patrick L. Holland*

^bDepartment of Chemistry, University of Rochester, Rochester, NY 14627, USA Fax: +1(585)2760205 Email: holland@chem.rochester.edu

› Author Affiliations

Abstract

All articles of this category

Abstract

A simple two-step synthetic route leads to 2,4,6-tris(trifluoromethyl)aniline. It proceeds through deprotonation and iodination of 1,3,5-tris(trifluoromethyl)benzene, followed by copper-catalyzed amination.

Key words

fluorination - aniline - ligand precursor

Full Text

References

References
1 Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320

2a Bennett BL, Hoerter JM, Houlis JF, Roddick DM. Organometallics 2000; 19: 615
2b Sadighi JP, Henling LM, Labinger JA, Bercaw JE. Tetrahedron Lett. 2003; 44: 8073
2c Hamilton CW, Laitar DS, Sadighi JP. Chem. Commun. 2004; 1628
2d Dias HV. R, Singh S. Inorg. Chem. 2004; 43: 5786
2e Despagnet-Ayoub E, Jacob K, Vendier L, Etienne M, Álvarez E, Caballero A, Díaz-Requejo MM, Pérez PJ. Organometallics 2008; 27: 4779

3a Burmakov AI, Alekseeva LA, Yagupolskii LM. Zh. Org. Khim. 1970; 6: 144 ; Chem. Abstr. 1970, 89975
3b Synthesis of Fluoroorganic Compounds . Knunyants IL, Yacobson GG. Springer; Berlin: 1985

4 Ahlemann J.-T, Roesky HW, Noltemeyer M, Schmidt H.-G, Markovsky LN, Shermolovich YG. J. Fluorine Chem. 1998; 87: 87
5 Kino T, Nagase Y, Ohtsuka Y, Yamamoto K, Uraguchi D, Tokuhisa K, Yamakawa T. J. Fluorine Chem. 2010; 131: 98

6a Carr GE, Chambers RD, Holmes TF. J. Organomet. Chem. 1987; 325: 13
6b Cornet SM, Dillon KB, Entwistle CD, Fox MA, Goeta AE, Goodwin HP, Marder TB, Thompson AL. Dalton Trans. 2003; 4395

7 Markiewicz JT, Wiest O, Helquist P. J. Org. Chem. 2010; 75: 4887
8 This solid can be used in the synthesis of compound 2 directly, and passes elemental analysis. It can also be resublimed from CaO after adding a few drops of water, to give a white solid.
9 If the emulsion after the first wash with water does not clear up, 20 mL of brine can be added to the separatory funnel and the mixture can be reshaken. It may take some time (~40 min) for the first emulsion to clear.
10 When the aqueous layers and the brine layers were combined and extracted with Et₂O, no aniline 2 was observed in the organic extracts, indicating that the desired product was not water soluble.