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Synlett 2009(9): 1453-1456  
DOI: 10.1055/s-0029-1216745
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Convenient Synthesis of 1-Substituted 1,2,3-Triazoles via CuI/Et3N Catalyzed ‘Click Chemistry’ from Azides and Acetylene Gas

Lu-Yong Wua, Yong-Xin Xiea, Zi-Sheng Chena, Yan-Ning Niua, Yong-Min Liang*a,b
a State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, P. R. of China
b State Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Science, Lanzhou 730000, P. R. of China
Fax: +86(931)8912582; e-Mail: liangym@lzu.edu.cn;
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Publication History

Received 5 January 2009
Publication Date:
04 May 2009 (online)

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Abstract

Copper(I)-catalyzed ‘click chemistry’ using acetylene gas was successfully explored under mild conditions. 1-Substituted-1,2,3-triazoles were conveniently synthesized from the corresponding aromatic and aliphatic azides.

Key words

azides - copper(I) catalysis - click chemistry - acetylene gas - 1,2,3-triazoles

    References and Notes

  • Reviews on 1,2,3-triazoles, see:
  • 1a Fan W.-Q. Katritzky AR. In Comprehensive Heterocyclic Chemistry II   Vol. 4:  Katritzky AR. Rees CW. Scriven EFV. Elsevier; Oxford, UK: 1996.  p.1-126  
    Google Scholar
  • 1b Dehne H. In Methoden der Organischen Chemie (Houben-Weyl)   Vol. E8d:  Schumann E. Thieme; Stuttgart: 1994.  p.305 
    Google Scholar
  • 2a Kolb HC. Finn MG. Sharpless KB. Angew. Chem. Int. Ed.  2001,  40:  2004 
    Google Scholar
  • 2b Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed.  2002,  41:  2596 
    Google Scholar
  • 2c Tornøe CW. Christensen C. Meldal M.
    J. Org. Chem.  2002,  67:  3057 
    Google Scholar
  • For recent reviews, see:
  • 3a Bock VD. Hiemstra H. van Maarseveen JH. Eur. J. Org. Chem.  2006,  51 
    Google Scholar
  • 3b Fournier D. Hoogenboom R. Schubert US. Chem. Soc. Rev.  2007,  36:  1369 
    Google Scholar
  • 3c Moses JE. Moorhouse AD. Chem. Soc. Rev.  2007,  36:  1249 
    Google Scholar
  • 3d Wu P. Fokin VV. Aldrichimica Acta  2007,  40:  7 
    Google Scholar
  • 3e Tron GC. Pirali T. Billington RA. Canonico PL. Sorba G. Genazzani AA. Med. Res. Rev.  2008,  28:  278 
    Google Scholar
  • 3f Gil MV. Arévalo MJ. López . Synthesis  2007,  1589 
    Google Scholar
  • 3g Meldal M. Tornøe CW. Chem. Rev.  2008,  108:  2952 
    Google Scholar
  • For examples, see:
  • 4a Whiting M. Muldoon J. Lin Y.-C. Silverman SM. Lindstrom W. Olson AJ. Kolb HC. Finn MG. Sharpless KB. Elder JH. Fokin VV. Angew. Chem. Int. Ed.  2006,  45:  1435 
    Google Scholar
  • 4b Kolb HC. Sharpless KB. Drug Discov. Today  2003,  8:  1128 
    Google Scholar
  • 4c Ye CF. Gard GL. Winter RW. Syvret RG. Twamley B. Shreeve JM. Org. Lett.  2007,  9:  3841 
    Google Scholar
  • 4d Angelos S. Yang YW. Patel K. Stoddart JF. Zink JI. Angew. Chem. Int. Ed.  2008,  47:  2222 
    Google Scholar
  • 4e Fazio F. Bryan MC. Blixt O. Paulson JC. Wong C.-H. J. Am. Chem. Soc.  2002,  124:  14397 
    Google Scholar
  • 4f Lutz J.-F. Angew. Chem. Int. Ed.  2007,  46:  1018 
    Google Scholar
  • 5a Krasinski A. Fokin VV. Sharpless KB. Org. Lett.  2004,  6:  1237 
    Google Scholar
  • 5b Rasmussen LK. Boren BC. Fokin VV. Org. Lett.  2007,  9:  5337 
    Google Scholar
  • 5c Zhang L. Chen X. Xue P. Sun HHY. Williams ID. Sharpless KB. Fokin VV. Jia G. J. Am. Chem. Soc.  2005,  127:  15998 
    Google Scholar
  • 5d Ackermann L. Potukuchi HK. Landsberg D. Vicente R. Org. Lett.  2008,  10:  3081 
    Google Scholar
  • 5e Boren BC. Narayan S. Rasmussen LK. Shang L. Zhao H. Lin Z. Jia G. Fokin VV. J. Am. Chem. Soc.  2008,  130:  8923 
    Google Scholar
  • 5f Chuprakov S. Chernyak N. Dudnik AS. Gevorgyan V. Org. Lett.  2007,  9:  2333 
    Google Scholar
  • 6a Fletcher JT. Walz SE. Keeney ME. Tetrahedron Lett.  2008,  49:  7030 
    Google Scholar
  • 6b Song R.-J. Deng C.-L. Xie Y.-X. Li J.-H. Tetrahedron Lett.  2007,  48:  7845 
    Google Scholar
  • 6c Taillefer M. Xia N. Ouali A. Angew. Chem. Int. Ed.  2007,  46:  934 
    Google Scholar
  • 6d Cristau HJ. Cellier PP. Spindler J.-F. Taillefer M. Chem. Eur. J.  2004,  10:  5607 
    Google Scholar
  • 6e Taillefer M, Cristau H.-J, Cellier PP, and Spindler J.-F. inventors; FR  2833947. 
  • 6f Taillefer M, Cristau H.-J, Cellier PP, and Spindler J.-F. inventors; WO  0353225.  ; Pr. Nb. Fr 2001 16547
  • 6g Taillefer M, Cristau H.-J, Cellier PP, Spindler J.-F, and Ouali A. inventors; FR  2840303. 
  • 6h Taillefer M, Cristau H.-J, Cellier PP, Spindler J.-F, and Ouali A. inventors; WO  03101966.  ; Pr. Nb. Fr 200206717
  • 7a Fan H. Xu G. Chen Y. Jiang Z. Zhang S. Yang Y. Ji R. Eur. J. Med. Chem.  2007,  42:  1137 
    Google Scholar
  • 7b Kauer JC. Carboni RA. J. Am. Chem. Soc.  1967,  89:  2633 
    Google Scholar
  • 8a Yan Z.-Y. Zhao Y.-B. Fan M.-J. Liu W.-M. Liang Y.-M. Tetrahedron  2005,  61:  9331 
    Google Scholar
  • 8b Zhao Y.-B. Yan Z.-Y. Liang Y.-M. Tetrahedron Lett.  2006,  47:  1545 
    Google Scholar
  • 8c Yan Z.-Y. Niu Y.-N. Wei H.-L. Wu L.-Y. Zhao Y.-B. Liang Y.-M. Tetrahedron: Asymmetry  2006,  17:  3288 
    Google Scholar
  • 8d Wu L.-Y. Yan Z.-Y. Xie Y.-X. Niu Y.-N. Liang Y.-M. Tetrahedron: Asymmetry  2007,  18:  2086 
    Google Scholar
  • 8e Niu Y.-N. Yan Z.-Y. Li G.-Q. Wei H.-L. Gao G.-L. Wu L.-Y. Liang Y.-M. Tetrahedron: Asymmetry  2008,  19:  912 
    Google Scholar
  • 9 Sonogashira K. Tohda Y. Hagihara N. Tetrahedron Lett.  1975,  16:  4467 
    CrossrefGoogle Scholar
10

The present reaction exhibited strong solvent effect, which is greatly different from the typical ‘click chemistry’. The discrepancy was presumed to cause by the acetylene gas. In the reactions, abundant reddish-brown precipitate was formed.

11

Acetonitrile and DMSO-H2O both gave excellent results in the template reaction. But when other azides used, the yields decreased significantly. In MeCN, 2b and 2c were obtained, respectively, in 52% and 63% after 24 h. In DMSO-H2O (4:1), 4-methylphenyl azide was tried, but the yield was only poor 40%. Therefore, we chose DMSO as typical solvent in subsequent experiments. The reason of the discrepancy is unknown.

12

Typical Procedure for Compound 2.
To a 5 mL flask with Et3N (0.4 mmol), azides 1 (1.0 mmol), and solvent (1.5 mL), CuI (0.1 mmol) was added into the mixture under N2 atmosphere. The flask was purged with acetylene for several times. Then the mixture was stirred under a balloon pressure of acetylene at r.t. After the designed time, the mixture was diluted with 25 mL EtOAc, and washed by 10 mL H2O for four times then by brine. The organic phase dried over anhyd Na2SO4. After removal of the solvent under reduced pressure, the residue was purified on SiO2 with PE-EtOAc (4:1 to 1:2). Caution: Azides are potentially explosive compounds and should be handled with great care.

13

Analytical Data of Selected Products
Compound 2a: white solid, mp 51-53 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.71 (s, 1 H), 7.48 (s, 1 H), 7.37 (m, 3 H), 7.27 (m, 2 H), 5.57 (s, 2 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 134.6, 134.0, 128.9, 128.5, 127.8, 123.3, 53.7 ppm. MS (EI): m/z = 159 [M+], 130, 104, 91, 77.
Compound 2b: pale yellow solid, mp 52-53 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.04 (s, 1 H), 7.88 (s, 1 H), 7.77 (m, 2 H), 7.56 (m, 2 H), 7.47 (m, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 137.5, 135.7, 130.0, 129.0, 122.8, 121.0 ppm. MS (EI): m/z = 145 [M+].
Compound 2c: ¹H NMR (400 MHz, CDCl3): δ = 7.99 (s, 1 H), 7.80 (s, 1 H), 7.59 (d, J = 6.8 Hz, 2 H), 7.28 (d, J = 6.8 Hz, 2 H), 2.39 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3):
δ = 138.6, 134.5, 134.0, 130.0, 121.6, 120.2, 20.8 ppm.
MS (EI): m/z = 159 [M+].
Compound 2d: yellow oil. ¹H NMR (400 MHz, CDCl3): δ = 7.98 (s, 1 H), 7.79 (s, 1 H), 7.54 (s, 1 H), 7.47 (d, J = 8.0 Hz, 1 H), 7.35 (d, J = 7.6 Hz, 1 H), 7.20 (d, J = 7.2 Hz, 1 H), 2.40 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 139.8, 136.8, 134.2, 129.34, 129.33, 121.7, 121.1, 117.5, 21.2 ppm.
MS (EI): m/z = 159 [M+].
Compound 2f: white solid, mp 78-80 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 7.94 (s, 1 H), 7.85 (s, 1 H), 7.65 (dd, J 1 = 6.9 Hz, J 2 = 2.1 Hz, 2 H), 7.03 (dd, J 1 = 6.9 Hz, J 2 = 2.1 Hz, 2 H), 3.88 (s, 3 H) ppm. ¹³C NMR (100 MHz, CDCl3):
δ = 160.1, 135.7, 131.1, 123.0, 122.6, 115.1, 55.9 ppm.
MS (EI): m/z = 175 [M+].
Compound 2g: pale yellow solid, mp 111-113 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.01 (s, 1 H), 7.85 (s, 1 H), 7.70 (d, J = 8.8 Hz, 2 H), 7.50 (d, J = 8.8 Hz, 2 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 138.6, 134.5, 134.0, 130.0, 121.6, 120.2, 20.8 ppm. MS (EI): m/z = 179 [M+].
Compound 2h: pale yellow solid, mp 91-93 ˚C. ¹H NMR (400 MHz, CDCl3): δ = 8.05 (s, 1 H), 7.85 (s, 1 H), 7.79 (s, 1 H), 7.65 (d, J = 7.6 Hz, 1 H), 7.46 (d, J = 8.0 Hz, 1 H), 7.41 (d, J = 8.0 Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl3): δ = 137.7, 135.4, 134.6, 130.8, 128.7, 121.7, 120.7, 118.5 ppm. MS (EI): m/z = 179 [M+].