Synthesis 2012; 44(13): 1974-1976
DOI: 10.1055/s-0031-1290295
practical synthetic procedures
© Georg Thieme Verlag Stuttgart · New York

A Facile Synthesis of Isomeric C-(2,2,2-Trifluoroethyl)anilines

Sergii Trofymchuk
a  Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska St. 5, 02660 Kiev-94, Ukraine
,
Andrii V. Bezdudny
a  Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska St. 5, 02660 Kiev-94, Ukraine
b  Enamine Ltd., Alexander Matrosov St. 23, 01103 Kiev, Ukraine
,
Yurii M. Pustovit
a  Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska St. 5, 02660 Kiev-94, Ukraine
b  Enamine Ltd., Alexander Matrosov St. 23, 01103 Kiev, Ukraine
,
Oleg Lukin*
c  ChemBioCenter, Kiev National Taras Shevchenko University, Volodymyrska St. 62, 01033 Kiev, Ukraine, Fax: +380(44)2351273   Email: oleg.lukin@univ.kiev.ua
,
Alexander N. Boyko
c  ChemBioCenter, Kiev National Taras Shevchenko University, Volodymyrska St. 62, 01033 Kiev, Ukraine, Fax: +380(44)2351273   Email: oleg.lukin@univ.kiev.ua
,
Alexey Chekotylo
c  ChemBioCenter, Kiev National Taras Shevchenko University, Volodymyrska St. 62, 01033 Kiev, Ukraine, Fax: +380(44)2351273   Email: oleg.lukin@univ.kiev.ua
,
Andrei A. Tolmachev
b  Enamine Ltd., Alexander Matrosov St. 23, 01103 Kiev, Ukraine
c  ChemBioCenter, Kiev National Taras Shevchenko University, Volodymyrska St. 62, 01033 Kiev, Ukraine, Fax: +380(44)2351273   Email: oleg.lukin@univ.kiev.ua
,
Pavel K. Mykhailiuk*
d  Department of Chemistry, Kiev National Taras Shevchenko University, Volodymyrska St. 64, 01033 Kiev, Ukraine, Email: pavel.mykhailiuk@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 04 January 2012

Accepted after revision: 25 January 2012

Publication Date:
03 April 2012 (eFirst)

In memory of Prof. L. M. Yagupolskii - a father of modern fluoroorganic chemistry

Abstract

Three isomers of C-(2,2,2-trifluoroethyl)aniline were prepared on a multigram scale from readily available nitrophenylacetic acids­ in two steps. First, the carboxy groups of the latter were converted into the trifluoromethyl moieties by treatment with sulfur tetra­fluoride. The obtained 2,2,2-trifluoroethyl-substituted nitrobenzenes were reduced catalytically into the corresponding anilines.

 
  • References

    • For recent reviews and relevant reports, see:

    • 1a Mikami K, Fustero S, Sánchez-Roselló M, Aceña JL, Soloshonok VA, Sorochinsky AE. Synthesis 2011; 3045
    • 1b Sorochinsky AE, Soloshonok VA. J. Fluorine Chem. 2010; 131: 127
    • 1c O’Hagan D. J. Fluorine Chem. 2010; 131: 1071
    • 1d Artamonov OS, Mykhailiuk PK, Voievoda NM, Volochnyuk DM, Komarov IV. Synthesis 2010; 443
    • 1e Purser S, Moore PR, Swallow S, Gouverneur V. Chem. Soc. Rev. 2008; 37: 320
    • 1f Hagmann WK. J. Med. Chem. 2008; 51: 4360
    • 1g Müller K, Faeh C, Diederich F. Science 2007; 317
    • 1h Kirsch P. Modern Fluoroorganic Chemistry . Wiley-VCH; Weinheim: 2004
  • 2 Of ca. 1350 small-molecule FDA-approved drugs, 43 contain the trifluoromethyl group. See: Wishart DS, Knox C, Guo AC, Cheng D, Shrivastaya S, Tzur D, Gautam B, Hassanali M. Nucleic Acids Res. 2008; 36: D901
    • 3a Zhu G.-D, Gong J, Gandhi VB, Woods K, Luo Y, Liu X, Guan R, Klinghofer V, Johnson EF, Stoll VS, Mamo M, Li Q, Rosenberg SH, Giranda VL. Bioorg. Med. Chem. 2007; 15: 2441
    • 3b Gujjar R, Mazouni FE, White KL, White J, Creason S, Shackleford DM, Deng X, Charman WN, Bathurst I, Burrows J, Floyd DM, Matthews D, Buckner FS, Charman SA, Phillips MA, Rathod PK. J. Med. Chem. 2011; 54: 3935
    • 3c Jimonet P, Audiau F, Barreau M, Blanchard J.-C, Boireau A, Bour Y, Coléno M.-A, Doble A, Doerflinger G, Huu DH, Donat M.-H, Duchesne JM, Ganil P, Guérémy C, Honoré E, Just B, Kerphirique R, Gontier S, Hubert P, Laduron PM, Le Blevec J, Meunier M, Miquet J.-M, Nemecek C, Pasquet M, Piot O, Pratt J, Rataud J, Reibaud M, Stutzmann J.-M, Mignani S. J. Med. Chem. 1999; 42: 2828
    • 3d Xu H, Maga J, Focher F, Smith ER, Spadari S, Gambino J, Wright GE. J. Med. Chem. 1995; 38: 39
    • 3e Audiau F, James C. US 5,236,940, 1993
  • 4 Dupré VM, Pechmèze JP. E, Sureau RF. M. FR 2,265,739, 1974
  • 5 Fuqua SA, Duncan WG, Silverstein RM. J. Org. Chem. 1965; 30: 1027
  • 6 Kondratenko NV, Vechirko EP, Yagupolskii LM. Synthesis 1980; 932
  • 7 Kremlev MM, Tyrra W, Mushta AI, Naumann D, Yagupolskii YL. J. Fluorine Chem. 2010; 131: 212
  • 8 Nguyen BV, Burton DJ. J. Org. Chem. 1997; 62: 7758
  • 9 Duan J.-X, Chen Q.-Y. J. Chem. Soc., Perkin Trans. 1 1994; 725
  • 10 Clark JH, McClinton MA, Blade RJ. J. Fluorine Chem. 1992; 59: 257
  • 11 Ando A, Miki T, Kumadaki I. J. Org. Chem. 1988; 53: 3637
  • 12 Kawai H, Furukawa T, Nomura Y, Tokunaga E, Shibata N. Org. Lett. 2011; 13: 3596

    • Our contributions in this field:
    • 14a Radchenko DS, Mykhailiuk PK, Bezdudny AV, Komarov IV. Synlett 2009; 1827
    • 14b Sibgatulin DA, Bezdudny AV, Mykhailiuk PK, Voievoda NM, Kondratov IS, Volochnyuk DM, Tolmachev AA. Synthesis 2010; 1075
    • 14c Bezdudny AV, Klukovsky D, Mykhailiuk PK, Shishkin OV, Pustovit YM. Synthesis 2011; 119
    • 14d Bezdudny AV, Alekseenko AN, Mykhailiuk PK, Manoilenko OV, Shishkin OV, Pustovit YM. Eur. J. Org. Chem. 2011; 1782
    • 14e Gerus II, Mironetz RX, Kondratov IS, Bezdudny AV, Dmytriv YV, Shishkin OV, Starova VS, Zaporozhets OA, Tolmachev AA, Mykhailiuk PK. J. Org. Chem. 2012; 77: 47