Carboxymethylpullulan promoted Cu2O-catalyzed Huisgen-click reaction

Article abstract of DOI:10.1039/c4ra14813d

A combination of carboxymethylpullulan (CMP) and Cu₂O has been developed as a highly efficient catalytic system for the Huisgen-click reaction. Our results indicate that the acidic CMP could be used for 6 cycles without decreasing the activatin

Full text of DOI:10.1039/c4ra14813d

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Carboxymethylpullulans Promoted Cu2O-Catalyzed Huisgen-Click Reaction
Weiwei Zhang, Baoqi Ren, Yuqin Jiang*, Zhiguo Hu*
Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, Key
Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Che
mical Engineering, Henan Normal University, Xinxiang 453007, P. R. China.
Eꢀmail: jiangyuqin@htu.cn; zghu@htu.cn.
A combination of carboxymethylpullulans (CMP) and Cu2O has been developed as a highly efficient
catalytic system for Huisgenꢀclick reaction. Our results indicate that the acidic CMP could be used for 6
cycles without decreasing the activating efficiency for Cu2O.
Introduction
By now click chemistry has emerged as a prominent organic transformation. The copper(I)ꢀcatalyzed
azideꢀalkyne cycloaddition (CuAAC) reaction is one of the most popular reactions within the click
chemistry concept since discovered by the groups of Sharpless1 and Meldal2 independently. The CuAAC
reaction has attracted much attention and been applied in the synthesis of pharmaceuticals, agrochemicals,
dyes, corrosion inhibitors, biochemicals, polymers and functional materials due to its reliability, specificity
and biocompatibility.3
A plethora of copper catalytic systems have been utilized for CuAAC reaction including Cu(I) species,4
Cu(II) salts/reducing agents2,5 and metallic copper.6 Compared with other Cu(I) species, Cu2O is the most
readily available and practical catalyst. Efforts were made to enhance the catalytic efficiency of Cu2O7ꢀ11
because the directly used Cu2O powder in the CuAAC reaction showed very poor catalytic efficiency.12 To
date, the catalytic capability of Cu2O in CuAAC reactions has not been thoroughly exploited because of
lacking appropriate reaction conditions. Very recently, inspired by the reported PhCOOH/Cu2O catalytic
system by Hu et al., 8 we have reported Cu(OAc)2·H2O/NH2NH2·H2O as a highly efficient catalytic system
for the CuAAC reaction, which in situ generates Cu2OꢀNPs and HOAc in water at room temperature.13 Our
results indicate that the in situ generated HOAc plays an important role in the CuAAC reaction. While not
only the PhCOOH/Cu2O catalytic system, but also the Cu(OAc)2·H2O/NH2NH2·H2O catalytic system has
drawbacks due to the unrecoverable and unreusable properties of the used small molecular organic acid in
the processes, which both show better activating efficiency for Cu2O.
Until now, polymers, as important supports, have been employed for immobilization of copper species
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for CuAAC reaction and resulted in easy removal, recovery and reusability of the copper catalyst.14 To
solving the recyclability problem of small organic acid mentioned above, a waterꢀsoluble polymer linked
with such kind of small molecular organic acid could be considered, which usually should not dissolve in
common organic solvents, such as ethyl acetate, CHCl3, CH2Cl2. Therefore, after the 1,2,3ꢀtriazoles
precipitated from the reaction mixture or extracted by waterꢀinsoluble organic solvents, the waterꢀsoluble
polymers could still remain in the water phase for reusing. Carboxymethylpullulan (CMP), which has been
widely studied in polymer chemistry,15 is a waterꢀsoluble, nontoxic derivative of pullulan with carboxylic
acid groups linked to the main chain. The main aim of this work is to investigate the activated efficiency
and the recyclability ability of CMP in the Cu2Oꢀcatalyzed CuAAC reaction. To the best of our knowledge,
there is still no report of CMP as the activator for Cu2O on the CuAAC reaction. The work described in this
paper selected Cu2O/CMP as a catalyst system for the CuAAC reaction in water and demonstrated that the
CMP showed better recyclability ability for Cu2O than the reported PhCOOH and HOAc.
CH2OCH2COOH
O
CH2OCH2COOH
O
CH2
OH
O
OH
O
OH
O
O
OH
n
OH
OH
OH
Scheme 1. Structure of carboxymethylpullulan (CMP)
Results and Discussion
CMP was prepared by reaction of alkaliꢀpullulan with sodium chloroacetate in a 2:1 isopropanolꢀwater
mixture according to the reported procedure.15a The Cu2O was prepared according our previous literature.13
The reaction between propargyl phenyl ether and azide benzyl was selected as the model reaction (Scheme
2) to test the catalytic efficiency of the Cu2O/CMP catalyst system. The reaction conditions were settled as
follows: propargyl phenyl ether (1.0 mmol), azide benzyl (1.0 mmol), Cu2O (2 mol%), CMP (10 mol%),
and water (2 mL). The influence of the amount of CMP on the isolated yields of the model reaction was
investigated.
reaction condition
O
O
+
N3
N
N
N
Scheme 2. Model reaction for screening the Cu2O/CMP catalytic system
Initially, the pH values of different amount of CMP in 2 mL water were measured and the pH value of
2

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the used water is 7.00. As shown in Figure 1, the pH value of the CMP solution greatly affected the
isolated yield of the model reaction. When the amounts of the CMP (based on the alkyne) increased from 2
mol% to 20 mol%, the pH value decreased from 3.40 to 2.78 (line a), which is easy to understand that the
more amount of acid the lower the pH value. The yields increased significantly over the concentration
range of 2 mol% to 10 mol% (yield from 24.6% to 98.0%) and decreased over the concentration range of
10 mol% to 20 mol% (yield from 98.0% to 15.6%). The yield over the concentration range of 2 mol% to 10
mol% increased with the decreased of the pH values, which is consistent with our previous results that is
the lower the pH value the faster the reaction rate.13 As we all known that Cu2O is almost insoluble in water,
while in acidic water it becomes soluble and the Cu(I) ions are released, which is ready to disproportionate
or be oxidized to copper (II). The lower the pH values, the faster the release rate. The CMP has two
important roles in the Huisgenꢀclick reaction. One is providing the needed protons, which promote the
release of Cu(I) ions. The other role of CMP is acting as a stabling agent to prevent the disproportionation
or oxidization of the released of Cu(I) ions. The in situ released Cu(I) in the reaction mixture catalyzed the
Huisgenꢀclick reaction between the added organic alkynes and azides. The more Cu(I) ions, the faster the
reaction rate. While the contrary results obtained from the yields over the concentration range of 10 mol%
to 20 mol%, which decreased from 98.0% to 15.6%. One reason is ascribed to the higher viscosity of the
aqueous CMP solutions at the high concentration. Another reason is ascribed to the strong copper chelation
ability of CMP. For proving this, special experiments were designed and carried out. To the round bottom
flask, Cu2O (2 mol%), CMP (10 mol%), and water (2 mL) were added. After stirred for 6 mins, propargyl
phenyl ether (1.0 mmol) and azide benzyl (1.0 mmol) were added and stirred for another 20 mins. After
working up, only 40% isolated yield was obtained. It is worthy to be mentioned that when Cu2O (2 mol%),
CMP (20 mol%), and water (2 mL) were put together and stirred for 6 mins, coagulation was observed. The
same experimental result was obtained when it was carried out under a nitrogen atmosphere. The above
experimental results confirmed the copper(I) chelation ability of CMP. Therefore the optimized reaction
was settled as follows: Cu2O (2 mol%), CMP (10 mol%), and water (2 mL) and the Cu2O (2 mol%) should
be the last one to be added.
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Figure 1. Effects of the amount of CMP to alkyne on yields and pH values
Secondly, the affection of the Cu2Oꢀloading on the model reaction was investigated. The model reaction
was carried out in water at room temperature in 20 mins in presence of 10 mol% CMP. As shown in Table
1, it could be seen that the larger the catalyst loading, the faster the reaction rate (entry 1 to 6). The model
reaction could be finished in 20 mins by increasing the catalyst loading above 2 mol%. When decreasing
the catalyst loading to 1 mol%, it would take 2 h to complete the reaction. Further reducing the catalyst
loading to 0.5 mol% and 0.1 mol%, it would take 10 h and 17 h to finish the model reaction respectively.
Unfortunately, when the catalyst loading was reduced to 0.05 mol%, very poor yield (8%) was obtained
even after reacting for 24 h. For improving the reaction rate of the model reaction at lower catalyst loading,
heating is considered as a simple and direct way.16 Very encouraged, the model reaction could complete in
20 mins when catalyzed by 0.5 mol% Cu2O at 80 ºC (entry 9). At the same condition mentioned above, the
reaction could complete smoothly in 20 mins even the amount of CMP reducing to 5 mol%. It is worth to
mention that only 15% yield is obtained when catalyzed by 10 mol% Cu2O in absence of CMP (entry 8),
which indicated the importance of the CMP. The results above encouraged us to study the effect of the
reaction temperature on the model reaction with the relatively lower loading of Cu2O and CMP.
Table 1. The screening of the catalyst loading on the model reaction
Entry
Cu2O (mol%)
Times (min) a
Yield(%) b
1
2
3
4
5
6
7
10
5
20
20
98/15 c
98
98
24
16
5
2
20
1
20
0.5
0.1
0.05
20
20
24 h
8
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8
9
0.05 d
0.5 d
0.5 e
24 h
20
15
98
98
10
20
a
Reaction conditions: propargyl phenyl ether (1 mmol), azide benzyl (1 mmol), CMP (10 mol%), H2O (2 mL),
c
e
rt; b Isolated yields; In absence of CMP; d Reaction temperature is at 80 ºC; CMP (5 mol%), H2O (2 mL),
reaction temperature is at 80 ºC.
For investigating the effect of reaction temperature on the model reaction, the reaction conditions were
settled as follows: propargyl phenyl ether (1.0 mmol), azide benzyl (1.0 mmol), Cu2O (0.5 mol%), CMP (5
mol%), and water (2 mL). The model reaction was carried out in 20 mins at different temperature among
the temperature range from 30 ºC to 100 ºC. As shown in Figure 2, the higher the reaction temperature, the
faster the reaction rate from 30 ºC to 60 ºC. When the temperature is above 60 ºC, the yield obtained in 20
mins is almost the same. So the optimized reaction condition is as follows: propargyl phenyl ether (1.0
mmol), azide benzyl (1.0 mmol), Cu2O (0.5 mol%), CMP (5 mol%) and water (2 mL) at 60 ºC.
Figure 2. Effects of the reaction temperature on the model reaction
Figure 3. Recyclability of CMP for the model reaction
There is an interesting thing happened during working up the model reaction. When the reaction was
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extracted by ethyl acetate, a yellow organic phase and an almost colorless water phase were obtained
(Figure 4). It could be imaged that the in situ formed copper(I) ion might be coordinated with the obtained
triazoles.17 The bright yellow organic phase could maintain for several weeks without changes. When the
propargyl phenyl ether was replaced by phenylacetylene, the extracting phenomenon was the same, even
using CH2Cl2 or chloroform as the extracting solvents. It was very interesting that when the pure obtained
triazoles from the model reaction were stirred with CMP and Cu2O for 20 mins and the mixture were
extracted by ethyl acetate, the organic phase was colorless. This indicated that chelation of triazoles with
copper(I) happened in the Huisgenꢀclick reaction cycles, which should be responsible for the leaching of
Cu(I) from the catalytic system. When the yellow organic phase was washed by aqueous ammonia, it
became colorless and the water phase became blue. The results mentioned above proving that the copper
almost transferred to the organic phase, thus the catalysis copper could not be recycled. Therefore the
recyclability of the CMP was investigated. The model reactions were carried out at 60 ºC in a relatively
large scale: propargyl phenyl ether (10 mmol), azide benzyl (10 mmol), Cu2O (0.5 mol%), CMP (5 mol%),
and water (20 mL). After the reaction mixture extracting by ethyl acetate, the remaining water phase was
added the same amount of starting alkyne, azide and Cu2O. As shown in Figure 3, after the model reaction
carried out for 6 cycles, the yield showed slowly decreasing. In the ninth cycle, the yield decreased sharply
to 50 % and the pH values of the remaining water phase is 4.36. It could be imaged that the hydrogen ions
were slowly consumed by Cu2O. When the Cu2O was replaced by CuOH (1 mol%), the same trend of pH
and catalytic efficiency changes could be obtained. It was very interesting that after the remaining water
phase was acidified by HCl to 2.82, the catalytic efficiency of CMP was recovered. The remaining water
phase could be reused for another 6 times without notable yields changes. It is worth to mention that when
the pure water in the absence of CMP was acidified by HCl to 2.82, the obtained yield is only 25.6% even
if the reaction temperature is at 60 ºC. It should attribute to the stable ability of CMP for copper(I) ion and
the importance of CMP for Cu2OꢀAAC reaction.
Figure 4. The picture of before the reaction (left) and after the reaction (right)
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A wide range of diversely substituted terminal alkynes and azides were carried out under the optimized
conditions in water at 60 ºC. As shown in Table 2, the reactions work well not only with alkyl azides, but
also with aryl azides. All reactions were highly regioselective towards the 1,4ꢀdisubstituted triazoles within
20 mins.
Table 2. Synthesis of triazoles using CMP/Cu2O system
N
R
1
Cu O(0.5 mol%) / CMP(5 mol%)
N
N
2
+
R
N
R
2
1
3
H O
2
2
3a-t
1
R
2
NO
Cl
2
O
O
O
O
O
O
O
O
N
N
N
N
N
N
N
N
N
N
N
N
N
N
O
N
O
O
O
O
3e (20 min, 90%)
3d (20 min, 92%)
3b20 min, 95%)
3c (20 min, 96%)
3a (20 min, 98%)
NO
2
Cl
O
N
N
O
O
N
N
N
N
N
N
N
N
N
N
N
N
N
3j (20 min, 96%)
3i (20 min, 95%)
3g (20 min, 91%)
3h (20 min, 95%)
3f (20 min, 98%)
Cl
Cl
O
O
N
N
N
O
N
N
N
N
N
2
N
N
N
N
N
N
N
N
O N
O
N
2
2
3o (20 min,89%)
3n (20 min, 94%)
3l (20 min, 92%)
3m (20 min, 94%)
3k (20 min, 90%)
NO
2
NO
2
NO
2
O
O
N
N
O N
2
N
O N
O
N
N
N
N
N
N
2
N
N
N
N
N
N
3t (20 min, 91%)
3s (20 min, 90%)
3q (20 min, 90%)
3r (20 min, 87%)
3p (20 min, 98%)
The proposed mechanism (Scheme 3) for the reaction will be the same as established mechanism shown
in earlier report.18 The CMP played important roles in the reaction:8, 19ꢀ21 (a) CMP breaks the crystal
structure of Cu2O to allow the formation of copper(I) speciesꢀhighly efficient catalysts for CuAAC reaction
assisted by the its acidity; (b) CMPꢀ as a ligand coordinated Cu(I) of monomer to promote the formation of
alkynylꢀcopper(I) intermediate (3) (step 2); (c) it had active effect on cycloaddition (step 3) and
protonation of CꢀCu bond (step 4); (d) the CMP comes into another cycle.
N
R1
N
N
N
R1
R
(5)
N
N
Step 3
R
Cu
R1N3
(4)
Step 4
Cu(I)+ -OOC-CH2-Pullulan
Cu2O
H+
R
C C Cu(I)CMP
(3)
Cu(I)
HOOC-CH2-Pullulan
Step 1
Step 2
Cu(I)CMP
R C CH
(1)
R
C
C H
(2)
Scheme 3. Proposed mechanism for the CuAAC reaction
Conclusions
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In summary, we presented a novel and high yield Cu2O/CMP catalyst system in water with a relatively
short reaction time. Such a method will be interesting as the remaining water phase containing CMP could
be reused for several runs and could be recovered by simply acidified by hydrochloride acid.
Acknowledgements
This work was supported financially by the Natural Science Foundation of China (No. 21172058),
Scientific Research Foundation for Doctors (No. 01036500508), Youth Foundation (2012QK11) of Henan
Normal University, Foundation of Henan Educational Committee (No. 14A350005).
Notes and references
1
V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless, Angew. Chem., Int. Ed., 2002, 41,
2596.
2
3
C. W. Tornøe, C. Christensen and M. Meldal, J. Org. Chem., 2002, 67, 3057.
(a) M. Whiting, J. Muldoon, Y.ꢀC. Lin, S. M. Silverman, W. Lindstrom, A. J. Olson, H. C. Kolb, M. G.
Finn, K. B. Sharpless, J. H. Elder and V. V. Fokin, Angew. Chem., Int. Ed., 2006, 45, 1435; (b) H. C.
Kolb and K. B. Sharpless, Drug Discovery Today, 2003, 8, 1128; (c) M. J. Giffin, H. Heaslet, A. Brik,
Y. C. Lin, G. Cauvi, C.ꢀH. Wong, D. E. McRee, J. H. Elder, C. D. Stout and B. E. Torbett, J. Med.
Chem., 2008, 51, 6263; (d) H. Rajaram, M. K. Palanivelu, T. V. Arumugam, V. M. Rao, P. Nicholas
Shaw, R. P. McGeary and B. P. Ross, Bioorg. Med. Chem. Lett., 2014, 24, 4523; (e) H. Nandivada, X.
W. Jiang and J. Lahann, Adv. Mater., 2007, 19, 2197; (f) C. F. Ye, G. L. Gard, R. W. Winter, R. G.
Syvret, B. Twamley and J. M. Shreeve, Org. Lett., 2007, 9, 3841; (g) P. Wu, A. K. Feldman, A. K.
Nugent, C. J. Hawker, A. Scheel, B. Voit, J. Pyun, J. M. J. Frechet, K. B. Sharpless and V. V. Fokin,
Angew. Chem., Int. Ed., 2004, 43, 3928; (h) E.ꢀH. Ryu and Y. Zhao, Org. Lett., 2005, 7, 1035; (i) G. K.
Such, J. F. Quinn, A. Quinn, E. Tjipto and F. Caruso, J. Am. Chem. Soc., 2006, 128, 9318; (j) C. H.
Wong, S. C. Zimmerman, Chem. Commun., 2013, 49, 1679; (k) W. P. Zhu, M. J. Zhong, W. W. Li,
H.C. Dong and K. Matyjaszewski, Macromolecules, 2011, 44, 1920; (l) Z. J. Zheng, F. Ye, L. S.
Zheng, K. F. Yang, G. Q. Lai and L. W. Xu, Chem. Eur. J., 2012, 18, 14094; (m) X. B. Yao, Y. Gong,
R. Mamuti, W. W. Xing, H. Zheng, X. Y. Tang and Y. Wang, RSC Adv., 2014, 4, 30492; (n) J. L.
Huang, C. J. Li and D. G. Gray, RSC Adv., 2014, 4, 6965.
4
(a) S. DíezꢀGonzález and S. P. Nolan, Angew. Chem., Int. Ed., 2008, 47, 8881; (b) S. DíezꢀGonzález, E.
D. Stevens and S. P. Nolan, Chem. Commun., 2008, 39, 4747; (c) B. W. T. Gruijters, M. A. C.
8

Page 9 of 11
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View Article Online
DOI: 10.1039/C4RA14813D
Broeren, F. L. Delft, R. P. Sijbesma, P. H. H. Hermkens and F. P. J. T. Rutjes, Org. Lett., 2006, 8,
3163; (d) S. Özçubukçu, E. Ozkal, C. Jimeno and M. A. Pericàs, Org. Lett., 2009, 11, 4680; (e) J.
GarcíaꢀÁlvarez, J. Díez and J. Gimeno, Green Chem., 2010, 12, 2127; (f) L. Li, P. S. Lopes, V. Rosa,
C. A. Figueira, M. A. Lemos, M. T. Duarte, T. Aviles and P. T. Gomes, Dalton Trans., 2012, 41, 5144;
(g) S. Lal, J. McNally, A. J. P. White and S. DıezꢀGonzález, Organometallics, 2011, 30, 6225.
́
5
6
7
(a) K. B. Sharpless, V. V. Fokin, L. G. Green and V. V. Rostovtsev, Angew. Chem., Int. Ed., 2002, 114,
2708; (b) F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless and V. V.
Fokin, J. Am. Chem. Soc., 2005, 127, 210.
(a) L. D. Pachón, J. H. Maarseveen and G. Rothenberg, Adv. Synth. Catal., 2005, 347, 811; (b) G.
Molteni, C. L. Bianchi, G. Marinoni, N. Santo and A. Ponti, New J. Chem., 2006, 30, 1137; (c) I. S.
Park, M. S. Kwon, Y. Kim, J. S. Lee and J. Park, Org. Lett., 2008, 10, 497.
Z. Zhang, C. Dong, C. Yang, D. Hu, J. Long, L. Wang, H. Li, Y. Chen and D. Kong, Adv. Synth. Catal.,
2010, 352, 1600.
8
9
C. Shao, R. Zhu, S. Luo, Q. Zhang, X. Wang and Y. Hu, Tetrahedron Lett., 2011, 52, 3782.
H. LópezꢀRuiz, J. E. D. L. CerdaꢀPedro, S. RojasꢀLima, I. PérezꢀPérez, B. V. RodríguezꢀSánchez, R.
Santillan and O. Coreño, Arkivoc, 2013, 139.
10 M. N. S. Rad, S. Behrouz, A. Movahedian, M. M. Doroodmand, Y. Ghasemi, S. RasoulꢀAmini, A.ꢀR.
A. Gandomani and R. Rezaie, Helv. Chim. Acta., 2013, 96, 688.
11 K. Wang, X. Bi, S. Xing, P. Liao, Z. Fang, X. Meng, Q. Zhang, Q. Liu and Y. Ji, Green Chem., 2011,
13, 562.
12 (a) F. Alonso, Y. Moglie, G. Radivoy and M. Yus, Eur. J. Org. Chem., 2010, 2010, 1875; (b) Please see
Supporting Information of the following report: E. J. Yoo, M. Ahlquist, S. H. Kim, I. Bae, V. V. Fokin,
K. B. Sharpless and S. Chang, Angew. Chem., Int. Ed., 2007, 46, 1730; (c) D. Wang, N. Li, M. Zhao,
W. Shi, C. Ma and B. Chen, Green Chem., 2010, 12, 2120.
13 Y. Q. Jiang, D. Y. Kong, J. L. Zhao, Q. H. Qi, W. Li and G. Q. Xu, RSC Adv., 2014, 4, 1010.
14 (a) C. Girard, E. Önen, M. Aufort, S. Beauvière, E. Samson, and J. Herscovici, Org. Lett., 2006, 8,
1689; (b) A. Sarkar, T. Mukherjee and S. Kapoor, J. Phys. Chem. C, 2008, 112, 3334; (c) S. Roy, T.
Chatterjee and Sk. M. Islarm, Green Chem., 2013, 15, 2532; (d) R. B. Nasir Baig and R. S. Varma,
Green Chem., 2013, 15, 1839; (d) T. R. Chan and V. V. Fokin, QSAR Comb. Sci., 2007, 11-12, 1274; (e)
M. Chtchigrovsky, A. Primo, P. Gonzalez, K. Molvinger, M. Robitzer, F. Quignard and F. Taran,
9

RSC Advances
Page 10 of 11
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Angew. Chem., Int. Ed., 2009, 48, 5916; (f) M. N. Tahir, R. Qamar, A. Adnan, E. Cho and S. Jung,
Tetrahedron Lett., 2013, 54, 3268; (g) L. Bonami, W. van Camp, D. van Rijckegen and F. E. Du Prez,
Macromol. Rapid Commun., 2009, 30, 34; (h) K. R. Reddy, K. Rajgopal and M. L. Kantam, Catal.
Lett., 2007, 114, 36; (i) U. Sirion, Y. J. Bae, B. S. Lee and D. Y. Chi, Synlett., 2008, 2326.
15 (a) I. Bataille, J. Huguet, G. Muller, G. Mocanu and A. Carpov, Int. J. Biol. Macromol., 1997, 20,179;
(b) G. Ali, C. Rihouey, D. Le Cerf, and L. Picton, Carbohyd. Polym., 2013, 93, 109; (c) G. Mocanu, Z.
Souguir, L. Picton and D. Le Cerf, Carbohyd. Polym., 2012, 89, 578; (d) M. Legros, P. Cardinael, V.
Dulong, L.Picton, D.Le Cerf, Polym. J., 2008, 40, 1132; (e) K. Horie, M.Sakagami, K. Masuda, M.
Notoya, H. Hamana, T. Yoshikawa and K. Hirano, Biol. Pharm. Bull., 2004, 27, 1275.
16 Y. Q. Jiang, D. Y. Kong, J. L. Zhao, W. W. Zhang, W. J. Xu, W. Li and G. Q. Xu, Tetrahedron Lett.,
2014, 55, 2410.
17 (a) D. MendozaꢀEspinosa, G. E. NegrónꢀSilva, D. ÁngelesꢀBeltrán, A. ÁlvarezꢀHernández, O. R.
SuárezꢀCastillo and R. Santillán, Dalton Trans., 2014, 43, 7069; (b) D. Schweinfurth, K. I. Hardcastle
and Uwe H. F. Bunz, Chem. Commun., 2008, 2203; (c) C. Deraedt, N. Pinaud and D. Astruc, J. Am.
Chem. Soc., 2014, 136,12092.
18 F. Himo, T. Lovell, R. Hilgraf, V. V. Rostovtsev, L. Noodleman, K. B. Sharpless and V. V. Fokin, J. Am.
Chem. Soc., 2005, 127, 210.
19 N. Balcioglu, I. Uraz (Unalan), C. Bozkurt and F. Sevin, Polyhedron, 1997, 16, 327.
20 C. Shao, X. Wang, J. Xu, J. Zhao, Q. Zhang and Y. Hu, J. Org. Chem., 2010, 75, 7002.
21 C. Shao, G. Cheng, D. Su, J. Xu, X. Wang and Y. Hu, Adv. Synth. Catal., 2010, 352, 1587.
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Page 11 of 11
RSC Advances
View Article Online
DOI: 10.1039/C4RA14813D
Graphical abstract
N
N
3
R
1
Cu O(0.5 mol%) / CMP(5 mol%)
N
N
2
+
O
H O
2
R
2
Cu2O/CMP has been developed as a highly efficient catalytic system for Huisgenꢀclick reaction in
water at 60 ºC.
11