Download PDF
Synlett 2003(2): 0187-0190
DOI: 10.1055/s-2003-36784
LETTER
© Georg Thieme Verlag Stuttgart · New York

Efficient Synthesis of 5-Fluoroalkylated 1H-1,2,3-Triazoles and Application of the Bromodifluoromethylated Triazole to Prepare New gem-Difluorinated Triazole Compounds

Weimin Peng, Shizheng Zhu*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Fax: +86(21)64166128; e-Mail: zhusz@pub.sioc.ac.cn;
Further Information

Publication History

Received 3 December 2002
Publication Date:
22 January 2003 (online)

    Permissions and Reprints All articles of this category

Abstract

A series of 5-fluoroalkylated 1H-1,2,3-triazoles was prepared in good yield by the regiospecific 1,3-dipolar cycloaddition reaction of the (Z) ethyl 3-fluoroalkyl-3-pyrrolidino-acrylates with aryl or benzyl azides. In the cases of benzyl azides, addition of Na2CO3 was crucial for a high yield of the triazoles. The tetrakis(dimethylamino)ethylene (TDAE) promoted reaction of the bromo-difluoromethylated 1H-1,2,3-triazole with aldehyde afforded a new class of novel gem-difluorinated triazole compounds.

Key words

acrylates - 1,3-dipolar cycloaddition - fluoroalkylated 1H-1,2,3-triazole - tetrakis(dimethylamino)ethylene - gem-difluorinated compound

    References

  • 1 Wamhoff H. In Comprehensive of Heterocyclic Chemistry   Vol. 5:  Katritzky AR. Rees CW. Elesevier; New York: 1996.  p.705 
    Search in Google Scholar
  • For review see:
  • 2a Finley KA. Triazoles: 1,2,3, In Heterocyclic Compounds   Vol. 29:  Montgomery JA. John Wiley and Sons Inc.; New York: 1980. 
    Search in Google Scholar
  • 2b Gilchrist TL. Gymer GE. In Advance in Heterocyclic Chemistry   Vol. 16:  Katritzky AR. Boulton AJ. Academic Press; New York: 1974.  p.33 
    Search in Google Scholar
  • 2c Gilchrist TL. Heterocyclic Chemistry   3rd ed.:  Addiso Wesley Longman; Beijing: 1997.  p.304 ; and ref. 1
    Search in Google Scholar
  • 3 Abu-Orabi ST. Al-Hamdany R. Shahateet S. Abu-Shandi K. Heterocycl. Commun.  2000,  6:  443 
    Search in Google Scholar
  • 4a Bertelli L. Biagi G. Calderone V. Giorgi I. Livi O. Scartoni V. Barili PL. J. Heterocycl. Chem.  2000,  37:  1169 
    CrossrefSearch in Google Scholar
  • 4b Lonning PE. Eur. J. Cancer  2000,  36 (Suppl. 4):  S81 
    CrossrefSearch in Google Scholar
  • 5 Kirk-Othmer Encycopedia of Chemical Technology   2nd ed.:  Wiley-Interscience; New York: 1964.  p.737 
  • 6 Itoh Y. Ma FH. Hoshi H. Oka M. Noda K. Ukai Y. Kojima H. Nagano T. Toda N. Anal. Biochem.  2000,  287:  203 
    CrossrefSearch in Google Scholar
  • 7 Mori Y, Osawa M, Hori M, and Nagashima T. inventors; Eur. Pat. Appl. EP  1081250.  ; Chem. Abstr. 2001, 134, 210398
  • 8 Philips D. Photochemistry  1971,  2:  795 
    Search in Google Scholar
  • 9a Yanase Y, Yoshikawa Y, Kawashima H, Takashi A, and Akase T. inventors; Jpn. Kokai Tokkyo Koho JP  2001072507.  ; Chem. Abstr. 2001, 134, 233062
  • 9b Yanase Y, Yoshikawa Y, and Takashi A. inventors; Jpn. Kokai Tokkyo Koho JP  2001072512.  ; Chem. Abstr. 2001, 134, 233064
  • For example see:
  • 10a Allessandro DI. Patrizia S. Anonella C. Laura B. Allessandro M. Gianna R. Tetrahedron Lett.  1995,  36:  9031 
    Search in Google Scholar
  • 10b Kobayashi Y. Yamashita T. Takahashi K. Kuroda H. Kumadaki I. Chem. Pharm. Bull.  1984,  32:  4402 
    Search in Google Scholar
  • 11 For example see: Kadaba PK. Stanovnik B. Tisler M. Advances in Heterocyclic Chemistry   Academic Press; New York, London: 1980.  p.219 ; see also ref.2b
  • 12a Filler R. Kobayashi Y. Yagupolskii LM. Organofluorine Compounds in Medical Chemistry and Biochemical Applications   Elesevier; Amsterdam: 1993. 
    Crossref
  • 12b Smart BE. , J. Fluorine Chem.  2001,  109:  3 
    CrossrefSearch in Google Scholar
  • 13a Carpenter W. Haymaker A. Moore DW. J. Org. Chem.  1966,  31:  789 
    Search in Google Scholar
  • 13b Saunier YM. Danion-Bougot R. Danoin D. Carrie R. Tetrahetron  1976,  32:  1995 
    Search in Google Scholar
  • 13c Kobayashi Y. Fujino S. Hamana H. Hanzawa Y. Morita S. Kumadaki I. J. Org. Chem.  1980,  45:  4683 
    Search in Google Scholar
  • 14 Peng WM. Zhu SZ. Jin GF. Tetrahedron  2001,  57:  5781 
    CrossrefSearch in Google Scholar
  • 15a Tozer MJ. Herpin T. Tetrahedron  1996,  52:  8619 
    Search in Google Scholar
  • 15b Burkholder CR. Dolbier WR. Medebielle M. J. Fluorine Chem.  2001,  109:  39 
    Search in Google Scholar
  • 16a Burkholder CR. Dolbier WR. Medebielle M. J. Org. Chem.  1998,  63:  5385 
    Search in Google Scholar
  • 16b Burkholder CR. Dolbier WR. Medebielle M. Ndedi A. Tetrahetron Lett.  1998,  39:  8853 
    Search in Google Scholar
  • 17 Metzger JO. Angew. Chem. Int. Ed.  1998,  37:  2975 
    CrossrefSearch in Google Scholar
  • 18 Balicki R. Pol. J. Chem.  1984,  58:  85 
    Search in Google Scholar
  • 19 Chen QY. Jiang XK. Chen BQ. Scientia Sinica  1966,  4:  498 
    Search in Google Scholar
  • 22 Norman SB. Plunkett AO. J. Chem. Soc., Chem. Commum.  1973,  188 
  • 23a Goldsmith D. Soria JJ. Tetrahetron Lett.  1991,  32:  2457 
    CrossrefSearch in Google Scholar
  • 23b Funicello M. Spagnolo D. Sanirato P. J. Chem. Soc., Perkin Trans. 1  1990,  2971 
    Crossref
  • 24a Burkholder C. Dolbier WR. Medebielle M. Aitmoliand S. Tetrahedron Lett.  2001,  42:  3077 
    CrossrefSearch in Google Scholar
  • 24b Burkholder C. Dolbier WR. Medebielle M. Tetrahedron Lett.  1997,  38:  821 
    CrossrefSearch in Google Scholar
20

The analytical and spectroscopic data for triazole 3aa was demonstrated as an example. 5-Chlorodifluoromethyl-1-phenyl-1 H -1,2,3-triazole-4-carboxylic Acid, Ethyl Ester(3aa): Mp: 69.5-70.5 °C. [Found: C, 47.80; H, 3.35; N, 14.24. C12H10ClF2N3O2 requires C, 47.78; H, 3.34; N, 13.93%]. IR(film): 2982, 1723, 1593, 1560, 1497, 1375, 1296, 1254, 1238, 1153, 1094, 1058, 1008, 906, 771 cm-1. 1H NMR (60 MHz, CDCl3): δ = 1.47 (3 H, t, J = 7.0 Hz), 4.52 (2 H, q, J = 7.0 Hz), 7.34-7.74 (5 H, m). 19F NMR (56.4 MHz, CDCl3): δ = -44.5; EI-MS: m/z (%) = 302/304 (10/3) [M+ + 1], 256/258 (12/4), 245/247 (10/3), 189 (42), 170 (33), 144 (19), 77 (100) [Ph+].

21

Crystallographic data (excluding structure factors) for the structures in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publication numbers CCDC 196350. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [Fax:+44(1223)336033 or e-mail: deposit@ccdc.cam. ac.uk].

25

5-(1,1-Difluoro-2-hydroxy-2-phenyl-ethyl)-1-pheny-l-1 H -1,2,3-triazole-4-carboxylic Acid, Ethyl Ester(7a): Mp: 146.0-148.0 °C. Found: C, 61.41; H, 4.78; N, 10.97. C19H17F2N3O3 requires C, 61.12; H, 4.59; N, 11.25. IR(film): 3445, 3065, 2984, 1778, 1717, 1595, 1546, 1497, 1249, 1231, 1170, 1077, 1014, 766, 738, 693 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.51 (3 H, t, J = 7.2 Hz), 4.01 (1 H, d, J = 3.9 Hz), 4.55 (2 H, q, J = 7.2 Hz), 5.63 (1 H, ddd, J = 12.7, 8.7, 3.9 Hz), 6.89-7.49 (10 H, m). 19F NMR (282 MHz, CDCl3): δ = -100.3 (AB-d, J = 273.0, 12.7, 8.7 Hz); EI-MS: m/z (%) = 373 (8) [M+], 353 (15), 328 (1), 300 (3), 281 (1), 104 (25), 77 (100) [Ph+], 51 (20).