6758
I. Jlalia et al. / Tetrahedron Letters 49 (2008) 6756–6758
tion can be quite exothermic and should not be attempted on a lar-
ger scale, without being aware of explosion risks.
cycle yield (%)
PhthN
Ph
N
3
CuI
1
2
3
4
5
99
99
99
99
99
1a
Acknowledgments
N
N
+
Bn
N
NPhth
Sincere thanks to Pr. Frédéric Prima (Laboratoire de Métallurgie
Structurale, Pr. R. Portier’s group, UMR 7045) for small angle X-rays
analyses. This work was made possible with the help of Grants
CNRS 8151, INSERM U640, SESAME Program and CPER from
Ile-de-France. Ph. D. fellowship from Tunisia to Ibtissem Jlalia
and Hichem Elamari is greatly acknowledged.
5 cycles
1a2e
2e
PhthN : phthalimide
Scheme 4. Recycling stabilized WyÁCuI in the reaction of benzyl azide (1a) with
N-propargyl phthalimide (2e) to prepare triazole 1a2e.
temperature.8 While using CuI/Et3N, the reaction was complete in
3 h, with A-21ÁCuI in 5 h and with WyÁCuI in 15 h. Faster reactions
observed in the case of our reference systems can be attributed to
the presence of an amine (base) functionality helping the forma-
tion of the copper(I) acetylide. Our WyÁCuI system can, however,
be advantageously compared to other published heterogeneous
systems that are not easier to prepare, and for which longer reac-
tion times are required.6–11
References and notes
1. (a) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. 2001, 113, 2056–2075;
(b) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–
2021; (c) Kolb, H. C.; Sharpless, K. B. Drug Discovery Today 2003, 8, 1128–1137;
(d) Moses, J. E.; Moorhouse, A. D. Chem. Soc. Rev. 2007, 36, 1249–1262.
2. Huisgen, R. Angew. Chem. 1963, 75, 604–637; Huisgen, R. Angew. Chem., Int. Ed.
Engl. 1963, 2, 565–598.
3. (a) Tornøe, C. W.; Meldal, M. In 17th American Peptides Symposium Proceedings
Book Peptides: The Wave of the Future. In Copper(I)-Catalyzed 1,3-Dipolar
Cycloadditions on Solid phase; Lebl, M., Houghten, R. A., Eds.; American
Peptide Society and Kluwer Academic: San Diego, 2001; pp 263–264; (b)
Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002, 67, 3057–3064; (c)
Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem. 2002,
114, 2708–2711; (d) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596–2599; For reviews see: (e) Bock, V. D.;
Hiemstra, H.; van Maarseveen, J. H. Eur. J. Org. Chem. 2006, 51–68; (f) Wu, P.;
Fokin, V. V. Aldrichim. Acta 2007, 40, 7–17.
4. (a) Zhang, X.; Hsung, R. P.; Li, H. Chem. Commun. 2007, 2420–2422; (b)
Bertrand, P.; Gesson, J.-P. J. Org. Chem. 2007, 72, 3596–3599; (c) Peddibhotla, S.;
Dang, Y.; Liu, J. O.; Romo, D. J. Am. Chem. Soc. 2007, 129, 12222–12231.
5. (a) Beckmann, H. S. G.; Wittmann, V. Org. Lett. 2007, 9, 1–4; (b) Tao, C.-Z.; Cui,
X.; Li, J.; Liu, A.-X.; Liu, L.; Guo, Q.-X. Tetrahedron Lett. 2007, 48, 3525–3529; (c)
Barral, K.; Moorhouse, A. D.; Moses, J. E. Org. Lett. 2007, 9, 1809–1811.
6. Chassaing, S.; Kumarraja, M.; Sani Souna Sido, A.; Pale, P.; Sommer, J. Org. Lett.
2007, 9, 883–886.
We presented in this Letter the easy preparation of a new sup-
ported catalyst for the Huisgen’s cycloaddition. The Wyoming
montmorillonite-supported copper(I) iodide (WyÁCuI) was found
to catalyze efficiently the formation of several triazoles, starting
form organic azides and terminal alkynes. The catalyst can be recy-
cled without activity loss. All the reactions but a few gave very
good yields of triazoles that were isolated by simple filtration
work-up. We think that this catalyst based on a natural and non-
toxic clay can find many applications for the synthesis of triazole
derivatives. Further work on these systems will be reported in
due course.
Typical procedures. Preparation of the supported catalyst (WyÁCuI):
Purified Wyoming montmorillonite-Na (film) (170 mg) was added
to a solution of copper(I) iodide (1.4 g, 7.0 mmol) in acetonitrile
(50 ml), and gently shaken on an orbital stirrer for 3 h at room tem-
perature. The film was washed with actonitrile (2 Â 15 ml), CH2Cl2
(2 Â 15 ml) and dried at 50 °C. Elemental analyses gave a copper
content of 4.57%. Wy-Na was submitted to the same analysis and
copper was not detected below 50 ppm.
7. Lipshutz, B. H.; Taft, B. R. Angew. Chem., Int. Ed. 2006, 45, 8235–8238.
8. Girard, C.; Önen, E.; Aufort, M.; Beauvière, S.; Samson, E.; Herscovici, J. Org. Lett.
2006, 8, 1689–1692.
9. Chan, T. R.; Fokin, V. V. QSAR Comb. Sci. 2007, 26, 1274–1279.
10. (a) Appukkuttan, P.; Dehaen, W.; Fokin, V. V.; Van der Eycken, E. Org. Lett. 2004,
6, 4223–4225; (b) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.; Noodleman,
L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210–216; (c) David,
O.; Maisonneuve, S.; Xie, J. Tetrahedron Lett. 2007, 48, 6527–6530.
11. (a) Durán Pachón, L.; van Maarseveen, J. H.; Rothenberg, G. Adv. Synth. Catal.
2005, 347, 811–815; (b) Molteni, G.; Bianchi, C. L.; Marinoni, G.; Santo, N.;
Ponti, A. New J. Chem. 2006, 30, 1137–1139.
12. (a) Clark, G. L. J. Am. Chem. Soc. 1959, 81, 1268; (b) Cadène, A.; Rotenberg,
B.; Durand-Vidal, S.; Badot, J. C.; Turq, P. Phys. Chem. Earth 2006, 31, 505–
510; (c) Lantenois, S.; Champallier, R.; Bény, J.-M.; Muller, F. Appl. Clay Sci.
2008, 38, 165–178; (d) Su, P. G.; Chen, C.-Y. Sens. Actuators, B Chel 2008, 129,
380–385.
13. Sohn, J. R.; Han, J. S.; Lim, J. S. Appl. Surf. Sci. 2005, 252, 858–865.
14. Small angle X-rays diffraction was conducted on both purified Wyoming
montmorillonite-Na and Wyoming-CuI. Comparative studies did not give a
clear clue on the localisation of the copper (see supplementary data).
15. (a) Carrado, K. A.; Wasserman, S. R. Chem. Mater. 1996, 8, 219–225; (b) Morillo,
E.; Undabeytia, T.; Maqueda, C. Environ. Sci. Technol. 1997, 31, 3588–3592; (c)
Undabeytia, T.; Nir, S.; Rytwo, G.; Serban, C.; Morillo, E.; Maqueda, C. Environ.
Sci. Technol. 2002, 36, 2677–2683; (d) Krishna, G. B.; Susmita, S. G. J. Colloid
Interface Sci. 2007, 310, 411–424; (e) Krishna, G. B.; Susmita, S. G. Chem. Eng. J.
2008, 136, 1–13.
16. Teng, Y. W.; Chang, I. J.; Wang, C. M. J. Phys. Chem. B 1997, 101, 10386–10389.
17. Jlalia, I.; Meganem, F.; Herscovici, J.; Girard, C. Unpublished results.
18. Very reactive alkynes can react without copper even at room temperature, see:
Baskin, J. M.; Prescher, J. A.; Laughin, S. T.; Agard, N. J.; Chang, P. V.; Miller, I. A.;
Lo, A.; Codelli, J. A.; Bertozzi, C. R. PNAS 2007, 104, 16793–16797.
19. 20% yield in isomeric mixture after 20 h. See: Reddy, K. R.; Rajgopal, K.;
Kantam, M. L. Synlett 2006, 957–959.
Synthesis of 1-benzyl-4-phthalimidomethyl-1,2,3-triazole (1a2e): Ben-
zyl azide (1a, 73 mg, 0.55 mmol) and N-propargyl phthalimide (2e,
93 mg, 0.50 mmol) were dissolved in CH2Cl2 (2 mL). WyÁCuI
(55 mg, 0.04 mmol, 8 mol %) was added and the mixture was stir-
red at room temperature for 18 h. The reaction mixture was fil-
tered on sintered glass, and the catalyst was washed with CH2Cl2
(3 Â 2 mL). Evaporation of the solvent gave the product 1a2e as a
white solid (158 mg, 99%). mp = 179–181 °C. FTIR:
m
3110, 3076,
1H NMR
3038, 2849, 1771, 1708, 1432, 1402 and 1097 cmÀ1
.
(300 MHz, CDCl3) d 4.97 (s, 2H), 5.49 (s, 2H), 7.25–7.37 (m, 5H),
7.51 (s, 1H), 7.70–7.85 (m, 4H) ppm. 13C NMR (75.5 MHz, CDCl3) d
33.1, 54.2, 122.7, 123.4, 128.1, 128.7, 129.1, 132.0, 134.1, 134.5,
143.1, 167.6 ppm. LC–MS: ELSD 98%, Rt = 9.10 min, m/z 319 [M+H]+.
For the solvent-free version on the same scale, the azide
(0.55 mmol) and alkyne (0.55 mmol) were mixed in a small test
tube. The catalyst was added at once and the reaction was left to
stand overnight. The products were recuperated with CH2Cl2
(3 Â 2 mL), filtration, and evaporation.
Caution: Even if no noticeable temperature rise was detected in
the solvent-free reaction with WyÁCuI on this scale, the cycloaddi-