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

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

• 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.