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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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Publikationsverlauf

Received 5 January 2009
Publikationsdatum:
04. Mai 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

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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+].