Ordered mesoporous copper oxide nanostructures as highly active and stable catalysts for aqueous click reactions

Article abstract of DOI:10.1016/j.catcom.2016.04.002

We demonstrate that ordered mesoporous CuO with gyroid mesostructures can be used as highly efficient, stable, and recyclable self-supported catalysts for click reactions in aqueous media.

Full text of DOI:10.1016/j.catcom.2016.04.002

Ordered mesoporous copper oxide nanostructures as highly active and stable
catalysts for aqueous click reactions
Seongwan Jang, Young Jin Sa, Sang Hoon Joo, Kang Hyun Park
PII:
DOI:
Reference:
S1566-7367(16)30115-7
doi: 10.1016/j.catcom.2016.04.002
CATCOM 4625
To appear in:
Catalysis Communications
Received date:
Revised date:
Accepted date:
31 December 2015
31 March 2016
6 April 2016
Please cite this article as: Seongwan Jang, Young Jin Sa, Sang Hoon Joo, Kang
Hyun Park, Ordered mesoporous copper oxide nanostructures as highly active and
stable catalysts for aqueous click reactions, Catalysis Communications (2016), doi:
10.1016/j.catcom.2016.04.002
This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.

ACCEPTED MANUSCRIPT
Ordered mesoporous copper oxide nanostructures as highly
active and stable catalysts for aqueous click reactions
Seongwan Jang‡a, Young Jin Sa‡b, Sang Hoon Joob,c,*, Kang Hyun Parka,*
a Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National
University, Busan 609-735, Republic of Korea
b Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), 50 UNIST-
gil, Ulsan 689-798, Republic of Korea
c School of Energy and Chemical Engineering, Ulsan National Institute of Science and Technology
(UNIST), 50 UNIST-gil, Ulsan 689-798, Republic of Korea
Seongwan Jang‡a
E-mail address: swjang@chemistry.or.kr
Young Jin Sa‡b
E-mail address: youngjinsa@unist.ac.kr
Sang Hoon Joob,c,*
*Corresponding author. Tel: +82 52 217 2522, E-Mail address: shjoo@unist.ac.kr
Kang Hyun Parka,*
*Corresponding author. Tel: +82 51 510 2238, fax: +82 51 980 5200 E-mail address:
chemistry@pusan.ac.kr
‡These authors contributed equally to this work.

ACCEPTED MANUSCRIPT
Abstract: We demonstrate that ordered mesoporous CuO with gyroid mesostructures can be
used as highly efficient, stable, and recyclable self-supported catalysts for click reactions in
aqueous media.
Keywords: Nanostructures; Mesoporous materials; Copper; Click chemistry
1. Introduction
Click chemistry introduced by the work of Sharpless [1] and Meldal [2] is one of most
efficient cycloaddition methods. This approach has attracted tremendous interests in various
fields including material chemistry [3-5], combinatorial chemistry [6], and drug discovery [7].
The copper(I)-catalyzed azide-alkyne cycloaddition (ACC) reaction, one of the primary
examples of click chemistry, proceeds in different solvents and yields stable triazoles with
possible applications in DNA modification, as well as pharmaceutical and organic synthesis
[8]. However, the instability of the Cu(I) species as manifested by the easy aerial oxidation of
Cu(I) to Cu(II) has limited the application of Cu-catalyzed ACC reaction in other fields.
In the past years, many researches about AAC reactions catalyzed by Cu(II) catalyst have
been investigated. In 2002, Sharpless and co-workers used CuSO4 as catalyst for the ACC
reaction with reductant [9]. In 2009, Zhu and co-workers used Cu(OAc)2 catalyst in alcoholic
solvent without reductants [10]; these authors also proved the reduction of Cu(II) to Cu(I) by
alkynes during homocoupling reactions [11]. To improve catalytic activity of Cu(II) in ACC
reactions, Kaboudin and co-workers reported Cu(II)-β-cyclodextric complex and this
complex exhibited similar activity with previously reported Cu(I) catalyst in optimized
condition [12].
To overcome the limitations of homogeneous catalytic systems, such as difficult catalyst
recovery and low thermal stability, heterogeneous systems have been investigated as
alternative catalysts [13-21]. The fabrication of porous nanostructures represents a promising
approach to increase the catalytically active surface area and enhance the accessibility of the
surface sites to the reactants, thereby enhancing the performance of heterogeneous systems
[22,23]. Nanocasting represents one of the most successful strategies for fabricating ordered
nanoporous materials. The nanoporous materials fabricated by this method show good
thermal stability, high crystallinity, and highly ordered pore structures [24-26]. Particularly,
the nanoporous materials templated from mesoporous silica with cubic gyroid structure such

ACCEPTED MANUSCRIPT
as KIT-6 are highly appealing, as their 3D-interconnected pore structure can provide highly
accessible catalytically active surfaces, as well as structural stability during catalytic reactions.
However, to our knowledge, no previous studies have investigated the use of copper(II) oxide
nanoporous structures for click reactions.
Here we report for the first time high-performance heterogeneous catalysts for click
reactions, based on ordered mesoporous copper(II) oxide (m-CuO) with 3D double gyroid
mesostructure. The m-CuO catalysts showed high activity, recyclability, and excellent
stability in the azide-alkyne cycloaddition reactions in aqueous media.
2. Experimental
2.1. Synthesis of ordered mesoporous copper(II) oxide nanostructures
Ordered mesoporous copper(II) oxide replica was synthesized by nitrate combustion
method [27]. 1.9 g of Cu(NO3)2・3H2O (Aldrich) was dissolved into 2.0 g of DI water, and
1.0 g of KIT-6 was added to the blue-coloured solution. The slurry was dried at 100 °C for 1
h. The silica-copper nitrate composite was placed with ammonia solution (28%, Samchun
chemical) in a separate container, with a cover to prevent ammonia solution vapour dispersed
through the atmosphere. Colour change was observed during this combustion step. After 1 h,
the ammonia-treated composite was dried at 100 °C for 1 h, and subsequently added into a
solution composed of 1.9 g of Cu(NO3)2・3H2O and 3.0 g of DI water, and dried. Then,
ammonia vapour treatment and drying were conducted. The dried powder was calcined at
400 °C for 6 h. (Caution: This calcination process explosively occurs, so using a wide
crucible is highly recommended.) The resulting dark-grey compound was mixed with 0.1 M
NaOH aqueous solution, and kept at 90 °C for 1 h to remove the silica template, then
centrifuged at 4000 rpm for 10 min. These etching-centrifuging processes were repeated
twice more, and the product was filtered, washed with DI water and ethanol, then dried at
60 °C.
2.2. General Procedure for Click Reactions
1.0 mg of m-CuO NPs (0.013 mmol, 1 mol%), benzylazide (0.15 mL, 1.26 mmol),
phenylacetylene (0.195 mL,1.77 mmol), and 3.6 mL H2O were placed in a 10 mL pressure

ACCEPTED MANUSCRIPT
o
schlenk tube. The reaction mixture was stirred at 50 C. After 9 h, the reaction product
analyzed by 1H NMR using Varian Mercury Plus (300 MHz).
2.3. Recyclability Test
After the reaction, the catalyst particles were precipitated by centrifugation and washed
with dichloromethane and ethanol. The particles were vacuum dried at room temperature and
were used as a catalyst for another cycle of the reaction.
2.4. Catalyst characterization
X-ray diffraction (XRD) patterns of the samples were obtained by using a high-power X-
ray diffractometer (D/Max 2500V/PC, Rigaku) with a Cu Kα source at 40 kV and 200 mA.
Crystallite size of the framework particle of m-CuO was calculated by Scherrer equation.
Dhkl and λ, FWHM, and θ indicate crystallite size, wavelength of X-ray, full-width-half-
maximum of a peak in radian, and Bragg angle respectively.
The pore structure was observed with a transmission electron microscope (TEM) (JEM-2100,
JEOL) and high-resolution TEM (HR-TEM) (JEM-2100F, JEOL) at an acceleration voltage
of 200 kV. The textural properties of the samples were obtained by N2 physisorption analyzer
(BELSORP-MAX, BEL) at -196 °C. Before measurements, the samples were evacuated with
heating. Specific surface areas and total pore volumes were calculated by using the Brunauer-
Emmett-Teller z(BET) equation in the relative pressure range of from 0.05 to 0.2. The pore
size distributions were determined by the Barrett-Joyner-Halenda (BJH) method from the
adsorption branch of the isotherm. X-ray photoelectron spectra (XPS) of the samples were
collected by using K-alpha X-ray photoelectron spectrometer (Thermo Scientific).
3. Results and discussion
3.1. Structural characterization
The m-CuO nanostructures were synthesized by nanocasting with KIT-6 mesoporous
silica with cubic Ia3d mesostructure (Fig. S1) [27]. In short, copper nitrate was infiltrated
into the mesopores of KIT-6, and the nitrate was decomposed by vapor from the ammonia

ACCEPTED MANUSCRIPT
solution. A mesoporous CuO-silica composite was produced through calcination at 400 °C,
and the silica template was then removed with hot dilute NaOH solution. The final m-CuO
catalyst contained little amount of Si, which appears to be the residual silica template. The Si
content determined by inductively coupled plasma-optical emission spectrometer was 6.0
wt%.
The transmission electron microscope (TEM) image of m-CuO (Fig. 1a) revealed a 3D
double gyroid mesostructure, indicating the successful replication of the structure of the KIT-
6 mesoporous silica template. The m-CuO framework thickness was around 10 nm. The
lattice fringes clearly visible in the high resolution TEM (HRTEM) image of m-CuO (Fig. 1b)
indicated the high crystallinity of the m-CuO framework. The distance between the two
nearest lattices was 0.23 nm, commensurate with the d-spacing value between (111) planes of
monoclinic CuO.
The structural integrity of the m-CuO investigated by small-angle X-ray diffraction (XRD)
pattern (Fig. S2a) showed (211) and (220) reflections, indicating the preservation of cubic
Ia3d symmetry after the replication. The high-angle XRD pattern of m-CuO (Fig. S2b)
revealed that the CuO phase is consistent with monoclinic CuO (JCPDS 80-1268),
confirming the HRTEM result. The crystallite size of CuO nanoparticles (calculated by
applying the Scherrer equation to the (202) reflection) was 12.8 nm, in good agreement with
the TEM observations. The textural properties of m-CuO were analyzed by nitrogen
adsorption-desorption measurements. The isotherms in Fig. 2 clearly suggested the presence
of mesopores in m-CuO, as evidenced by the hysteresis loop in the relative pressure range of
0.45–0.9. The m-CuO exhibited a large BET surface area of 248 m2 g-1 and a total pore
volume of 0.24 cm3 g-1. The pore size distribution of m-CuO obtained by the BJH method
(Fig. 2, inset) revealed a predominant mesopore at 3.8 nm, along with a larger mesopore
around 10 nm (indicated by an inverted blue triangle in the figure). The bimodal pore size
distribution for m-CuO may facilitate mass transfer of reagents and products. The oxidation
state of Cu species in m-CuO was accessed with Cu 2p X-ray photoelectron spectrum (Fig. 3).
The strong satellite peak accompanying the 2p3/2 peak rules out the presence of the Cu2O
phase [28]. Interestingly, the binding energy of the Cu 2p3/2 peak in m-CuO (~937 eV) was
higher than that for bulk CuO (933–934 eV), and the peak was broader. The shift in the Cu
2p3/2 peak can be attributed to the nanoscale size of the m-CuO framework, which could
expose a large number of Cu atoms on its surface [29-30].

ACCEPTED MANUSCRIPT
3.2. Catalytic activity of the catalysts
We next explored the catalytic properties of m-CuO in the AAC reactions. In order to
assess the effect of the solvent, we carried out the AAC reaction of benzyl azide and
phenylacetylene in various solvents (entries 1–5, Table 1). The conversion of benzyl azide
was much higher in protic than in aprotic solvents. Generally, water is a poor solvent for most
click reactions. To improve catalytic activity of nanoparticles in aqueous media, supporting
material and/or surfactant were extensively used [28]. Xia groups reported the CuO catalyst
supported by polymeric ionic liquid material for AAC reactions in water [31]. Also, Kong
groups reported the Cu2O catalyst coated by water-soluble polymer such as
polyvinylpyrrolidone [32]. Very similarly, the obtained our m-CuO exhibited remarkably
enhanced AAC catalytic activity in water.
Therefore, we used water as solvent in the subsequent reactions, for both economic and
environmental reasons. The catalytic activity of the m-CuO catalyst was almost six times
higher than that of a commercial catalyst used for comparison, and 20 times higher than
without catalyst (entries 5–7, Table 1). This difference can probably be attributed to the large
specific surface area and pore volume of m-CuO. The AAC reactions carried out with m-CuO
as catalyst showed increased reactivity with increasing temperature (entries 5 and 8–9, Table
1). The recovered catalyst could be reused at least three times without loss of catalytic
activity and selectivity (entries 10–11, Table 1). Compared to the original mesoporous
nanostructure, the catalyst did not show significant structural damage after recycling three
times (Fig. S3a). Furthermore, the original lattice fringes were maintained in the recycled
nanoparticles (Fig. S3b).
The accepted reaction mechanism for the AAC reaction catalyzed by copper ions is
depicted in Fig. S4. [33] In the first step, one of copper ion forms a π-complex with the
alkyne. Then, copper acetylide is generated by replacing the proton with another copper ion.
The scope of the reaction was examined for various alkynes and azides (Table 2).
Moderate conversions of these substrates were obtained under the optimized conditions. As
shown in entries 1–6 of Table 2, the electronic properties of both azides and alkynes
significantly influenced the consequence of the reaction. For example, 4-bromophenyl
acetylene (entry 1, Table 2) and 4-fluorobenzyl azide (entry 4, Table 2) substituted with an
electron-withdrawing group showed lower reactivity than compounds substituted with an
electron-donating group (entries 2–3 and 5–6, Table 2). This is deemed the results of
decreasing of nucleophilicity of the acetylide anion and efficiency of cyclization step with

ACCEPTED MANUSCRIPT
triazenide decreased by substitution with electron-withdrawing groups. The reactivity of
methoxyphenyl azides substituted in para-, meta-, and ortho- position was also assessed
(entries 6–8, Table 2). The ortho- substituent yielded the lowest conversion, due to
interference with the ring closure of the intermediate [34]. Unexpectedly, the para-
substituent showed lower reactivity than the meta- one, even though it represents the best
activating site in a number of click reactions. We also examined the reactivity in relation to
the length of the chain directly linked to the reactive azide (entries 9–10, Table 2). While
phenyl and benzyl azides showed high conversion within 9 h, 2-phenylethyl azide required
more than 18 h for achieving a similar conversion. This result seems to reflect the rapidly
increasing interference with increasing steric hindrance.
4. Counclusions
In conclusion, m-CuO nanostructures were synthesized through nanocasting from KIT-6
mesoporous silica with cubic Ia3d mesostructure, and employed as self-supported catalysts
for the ACC reactions. The m-CuO catalysts showed high catalytic activity in water, and
were suitable for multiple reuses. Therefore, m-CuO catalysts are able to balance reactivity,
robustness, and environmental compatibility of aqueous click reactions.
Acknowledgements
This research was supported by Basic Science Research Program through the National
Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future
Planning (NRF-2015R1D1A1A02060684 and NRF-2013R1A1A2012960).
References
[1] H.C. Kolb, M.G. Finn, K.B. Sharpless, Angew. Chem. Int. Ed. 40 (2001) 2004-2021.
[2] C.W. Tornoe, C. Christensen, M. Meldal, J. Org. Chem. 67 (2002) 3057-3064.
[3] N.K. Devaraj, G.P. Miller, W. Ebina, B. Kakaradov, J.P. Collman, E.T. Kool, C.E.D. Chidsey, J. Am. Chem. Soc. 127
(2005) 8600-8601.
[4]
K. Kempe, A. Krieg, C.R. Becer, U.S. Schubert, Chem. Soc. Rev. 41 (2012) 176-191.

ACCEPTED MANUSCRIPT
[5] W. Xi, T.F. Scott, C.J. Kloxin, C.N. Bowman, Adv. Funct. Mater. 24 (2014) 2572-2590.
[6] D.B. Ramachary, C.F. Barbas, III, Chem. - Eur. J. 10 (2004) 5323-5331.
[7] H.C. Kolb, K.B. Sharpless, Drug Discovery Today 8 (2003) 1128-1137.
[8] J.E. Moses, A.D. Moorhouse, Chem. Soc. Rev. 36 (2007) 1249-1262.
[9] V.V. Rostovtsev, L.G. Green, V.V. Fokin, K.B. Sharpless, Angew. Chem. Int. Ed. 41 (2002) 2596-2599.
[10] W.S. Brotherton, H.A. Michaels, J.T. Simmons, R.J. Clark, N.S. Dalal, L. Zhu, Org. Lett. 11 (2009) 4954-4957.
[11] G.-C. Kuang, P.M. Guha, W.S. Brotherton, J.T. Simmons, L.A. Stankee, B.T. Nguyen, R.J. Clark, L. Zhu, J. Am.
Chem. Soc. 133 (2011) 13984-14001.
[12] B. Kaboudin, Y. Abedi, T. Yokomatsu, Org. Biomol. Chem. 10 (2012) 4543-4548.
[13] Z.-c. Zhang, B. Xu, X. Wang, Chem. Soc. Rev. 43 (2014) 7870-7886.
[14] Y. Zhang, X. Cui, F. Shi, Y. Deng, Chem. Rev. (Washington, DC, U. S.) 112 (2012) 2467-2505.
[15] J. Shi, Chem. Rev. (Washington, DC, U. S.) 113 (2013) 2139-2181.
[16] H. Woo, H. Kang, A. Kim, S. Jang, J.C. Park, S. Park, B.-S. Kim, H. Song, K.H. Park, Molecules 17 (2012) 13235-
13252.
[17] G. Zhao, J. Wang, X. Peng, Y. Li, X. Yuan, Y. Ma, Chem. - Asian J. 9 (2014) 546-553.
[18] M. Biswas, A. Saha, M. Dule, T.K. Mandal, J. Phys. Chem. C 118 (2014) 22156-22165.
[19] A. Berrichi, R. Bachir, M. Benabdallah, N. Choukhou-Braham, Tetrahedron Lett. 56 (2015) 1302-1306.
[20] A. Saha, D. Saha, B. Ranu, Org. Biomol. Chem. 7 (2009) 1652-1657.
[21] J. Chen, J. Qi, G. Li, F. Zheng, S. Li, Z. Tang, Chem. – Asian J. 8 (2013) 694-699.
[22] N. Linares, A.M. Silvestre-Albero, E. Serrano, J. Silvestre-Albero, J. Garcia-Martinez, Chem. Soc. Rev. 43 (2014)
7681-7717.
[23] V. Valtchev, L. Tosheva, Chem. Rev. (Washington, DC, U. S.) 113 (2013) 6734-6760.
[24] B. Tian, X. Liu, H. Yang, S. Xie, C. Yu, B. Tu, D. Zhao, Adv. Mater. (Weinheim, Ger.) 15 (2003) 1370-1374.
[25] D. Han, D. Li, T. Zheng, Adv. Mater. Res. (Zuerich, Switz.) 15-17 (2007) 53-58.
[26] K. Jiao, B. Zhang, B. Yue, Y. Ren, S. Liu, S. Yan, C. Dickinson, W. Zhou, H. He, Chem. Commun. (Cambridge, U.
K.) (2005) 5618-5620.
[27] Y. Ren, Z. Ma, L. Qian, S. Dai, H. He, P.G. Bruce, Catal. Lett. 131 (2009) 146-154.
[28] D. Barreca, A. Gasparotto, E. Tondello, Surf. Sci. Spectra 14 (2008) 41-51.
[29] K. Borgohain, J.B. Singh, M.V. Rama Rao, T. Shripathi, S. Mahamuni, Phys. Rev. B: Condens. Matter Mater. Phys.
61 (2000) 11093-11096.
[30] Z.-s. Hong, Y. Cao, J.-f. Deng, Mater. Lett. 52 (2002) 34-38.
[31] Y. Wang, J. Liu, C. Xia, Adv. Synth. Catal. 353 (2011) 1534-1542.
[32] Z. Zhang, C. Dong, C. Yang, D. Hu, J. Long, L. Wang, H. Li, Y. Chen, D. Kong, Adv. Synth. Catal. 352 (2010) 1600-
1604.
[33] B. T. Worrell, J. A. Malik and V. V. Fokin, Science 340 (2013) 457–460.
[34] S.W. Kwok, J.R. Fotsing, R.J. Fraser, V.O. Rodionov, V.V. Fokin, Org. Lett. 12 (2010) 4217-4219.

ACCEPTED MANUSCRIPT
Figure Captions
Fig. 1. (a) TEM and (b) HRTEM images of m-CuO nanostructures
Fig. 2. N2 adsorption-desorption isotherms of m-CuO and the corresponding pore size
distribution (inset).
Fig. 3. Cu 2p XPS spectrum of m-CuO sample.

ACCEPTED MANUSCRIPT
Table 1. Optimization of click reactions catalyzed by m-CuO.
Temp.
(oC)
Time
(h)
Entry
1
Cat. (mol%)
5
Solvent
Yield[a](%)
56
H2O/t-
BuOH(2:1)
50
12
2
5
t-BuOH
DMSO
CH3CN
H2O
50
50
50
50
50
50
25
40
50
50
12
12
12
9
8
15
3
5
4
5
85
5
1
>99
16
6
1 [b]
H2O
9
7
-
H2O
9
5
8
1
H2O
9
24
9
1
H2O
9
65
10
11
Recovered #5
Recovered #12
H2O
9
>99
>99
H2O
9
Reagents and conditions: benzyl azide, 1.26 mmol; phenylacetylene, 1.77 mmol. [a]
Determined by 1H-NMR. Yields are based on the amount of benzyl azide used. [b]
Commercial CuO purchased from Aldrich (cat. no. 544868).

ACCEPTED MANUSCRIPT
Table 2. Click reactions of various azides with terminal alkynes catalyzed by m-CuO.
Entry
1
Azide
Alkyne
Time (h)
9
Yield[a] (%)
62
2
3
4
9
9
9
97
100
72
5
9
98
6
7
9
9
85
96
8
9
9
72
98
85
9
10
18
Reagents and conditions: azide, 1.26 mmol; alkyne, 1.77 mmol; water, 3.6 mL;
catalyst, 1 mol %; temperature, 323 K. [a] Determined by 1H-NMR. Yields are
based on the amount of azide used.

ACCEPTED MANUSCRIPT
Fig. 1

ACCEPTED MANUSCRIPT
Fig. 2

ACCEPTED MANUSCRIPT
Fig. 3

ACCEPTED MANUSCRIPT
Graphical abstract

ACCEPTED MANUSCRIPT
Highlights



The m-CuO catalysts were synthesized by nanocasting with KIT-6 mesoporous silica.
The m-CuO showed high catalytic activity for click reactions in aqueous media.
The recovered catalyst could be reused without loss of the activity and selectivity.