Nanoscrystalline CuO: Synthesis and application as an efficient catalyst for the preparation of 1,2,3-triazole acyclic nucleosides via 1,3-dipolar cycloaddition

Article abstract of DOI:10.1016/j.catcom.2012.05.016

Nanowire CuO particles with an average diameter range of 2.5-3.7 nm were examined as catalysts for the 1,3-dipolar cycloadditions of organic azides to terminal alkynes. The material was successfully synthesized at room temperature from metallic copper powder by a facile solution-phase method in the presence of nitric acid, sodium hydroxide (NaOH) and ethylene glycol (EG) as growth-directing agent. The crystallinity, purity, morphology, specific surface areas and structural features of the as-prepared nanowires were characterized by powder X-ray diffraction, Brunauer-Emmett-Teller (BET) method and high-Transmission Electron Microscopy. Under mild reaction conditions, the addition of organic azides to terminal alkynes gives 1,4-disubstituted 1,2,3-triazole as a single regioisomer in good yields with reusability of the catalyst. The present click reaction protocol of terminal alkynes, via 1,3-dipolar cycloaddition with various organic azides allows the regioselective synthesis of 1,2,3-triazole acyclic nucleosides in good yields. We have then initiated the one-pot tandem [3 + 2] cycloaddition where benzylchloride was reacted with propargyl derivatives and sodium azide in the presence of CuO nanoparticles as catalyst.

Full text of DOI:10.1016/j.catcom.2012.05.016

Catalysis Communications 26 (2012) 155–158
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Catalysis Communications
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Short Communication
Nanoscrystalline CuO: Synthesis and application as an efficient catalyst for the
preparation of 1,2,3-triazole acyclic nucleosides via 1,3-dipolar cycloaddition
c
a,
Hanane Elayadi a, Mustapha Ait Ali b, , Ahmad Mehdi , Hasan Bihi Lazrek
⁎
⁎
a
Laboratoire de Chimie Bio-Organique, Faculté des Sciences Semlalia Université Cadi Ayyad, PB 2390, 40001 Marrakech, Morocco
Equipe de Chimie de Coordination et Catalyse, Université Cadi Ayyad, Faculté des Sciences-Semlalia PB 2390, 40001 Marrakech, Morocco
Université Montpellier, Institut Charles Gerhardt, UMR5253, CMOS, 34095 Montpellier, France
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Nanowire CuO particles with an average diameter range of 2.5–3.7 nm were examined as catalysts for the 1,3-
dipolar cycloadditions of organic azides to terminal alkynes. The material was successfully synthesized at
room temperature from metallic copper powder by a facile solution-phase method in the presence of nitric
acid, sodium hydroxide (NaOH) and ethylene glycol (EG) as growth-directing agent. The crystallinity, purity,
morphology, specific surface areas and structural features of the as-prepared nanowires were characterized by
powder X-ray diffraction, Brunauer–Emmett–Teller (BET) method and high-Transmission Electron Microscopy.
Under mild reaction conditions, the addition of organic azides to terminal alkynes gives 1,4-disubstituted 1,2,3-
triazole as a single regioisomer in good yields with reusability of the catalyst. The present click reaction protocol
of terminal alkynes, via 1,3-dipolar cycloaddition with various organic azides allows the regioselective synthesis
of 1,2,3-triazole acyclic nucleosides in good yields. We have then initiated the one-pot tandem [3+2] cycload-
dition where benzylchloride was reacted with propargyl derivatives and sodium azide in the presence of CuO
nanoparticles as catalyst.
Received 26 March 2012
Received in revised form 16 May 2012
Accepted 17 May 2012
Available online 24 May 2012
Keywords:
Nanocrystalline copper (II) oxide
Click reaction
1,2,3-triazole acyclic nucleosides
Reusability
One-pot [3+2] cycloaddition
© 2012 Elsevier B.V. All rights reserved.
1. Introduction
been used for the catalytic [3+2] cycloaddition of azides with termi-
nal alkynes without solvent under microwave irradiation [15].
Modern drug discovery requires the identification and the optimi-
zation of synthetic routes to biological active molecules. Simple
methods that can quickly and easily generate a variety of molecules
have become more and more used. The enormous attention recently
gained by the click reaction began with the pivotal discovery by the
groups of Meldal [1] and Sharpless [2–4], in which copper(I) catalysis
was found to dramatically accelerate the reaction under mild condi-
tions. At the same time, a high regioselectivity was achieved toward
the 1,4-regioisomer of the triazole product. Consequently, this proto-
col has found increasing application in a variety of disciplines such as
organic chemistry [5] drug discovery and medicinal chemistry [6] and
bioconjugation [7]. A large number of protocols have been developed
for the click reaction with the use of copper-zeolites [8], Cu on char-
coal [9], Cu nano-powder [10], copper sulfate/sodium ascorbate sys-
tem, [11] silica supported copper catalyst, [12] and recently copper
nanoparticles [13]. The results obtained by any of these methods
are, in general, excellent. But, since the discovery that nanostructured
copper oxide has shown a general beneficial effect in the cycloaddi-
tion of alkynes and azides many groups have used it [14]. More re-
cently, CuO hollow nanospheres on acetylene black (CuO/AB) have
As a consequence of our interest in the synthesis of 1,2,3-triazole
acyclic nucleosides [16–21], we have identified that CuO nanoparticle
catalyzes efficiently the preparation of 1,4-disubstituted 1,2,3-triazole
by cycloaddition of alkynes to azides. The catalytic system which is
composed of recyclable CuO nanoparticles, in dioxane/water allows
the synthesis of 1,2,3-triazole acyclic nucleosides.
2. Experimental
2.1. Preparation of the CuO nanowire catalyst
Metallic cupper powder, nitric acid, sodium hydroxide (NaOH)
and ethylene glycol (EG) were purchased from Aldrich and used as
received. For a typical CuO nanowire synthesis, 1.0 g (0.0157 mol)
of metallic Cu was dissolved in 80 mL HNO3 solution (0.86 M).
20 mL of EG was poured into the aqueous solution. After the EG was
uniformly dispersed in the solution, 6.0 g (0.15 mol) of NaOH pellets
was added. After stirring for a few minutes, a blue suspension was
formed and left under stirring, at room temperature, for several
more hours until the blue suspension totally transformed to a black
suspension. The final black suspension was filtered and washed sev-
eral times with water and finally with ethanol. Finally, the product
was dried in air at 100 °C for 24 h. This process can be simply scaled
up for mass production.
⁎
Corresponding authors. Tel.: +212 524 434649; fax: +212 524 437408.
E-mail addresses: aitali@ucam.ac.ma (M. Ait Ali), hblazrek50@gmail.com
(H.B. Lazrek).
1566-7367/$ – see front matter © 2012 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2012.05.016

156
H. Elayadi et al. / Catalysis Communications 26 (2012) 155–158
Scheme 1.
Scheme 2.
Scheme 3.
3 mL of dioxane/water (2/1, v/v). The solution was stirred at reflux
(90 °C) for 2 h. Then, the solution was evaporated, and the residue
was applied to flash column (silica gel).
2.2. General procedure for synthesis of 1,4-disubstituted 1,2,3-triazole
A suspension of nanostructured CuO (0.05 mmol, 5 mol %) was
All the spectroscopic data of the reaction products were compared
with those reported in the literature [16–21].
added to a mixture of alkyne 2 (1 mmol), and azide 1 (1.1 mmol) in
2.3. General procedure for one‐pot reaction
Propargyl derivatives (1 mmol), benzylchloride (1.1 mmol), and
sodium azide (1.1 mmol) in the presence of CuO nanoparticles
(0.05 mmol, 5 mol %) as catalyst were mixed in dioxane (3 mL) as sol-
vent. The reaction mixture was refluxed for 3 h. The products were
isolated by simple purification using flash column chromatography.
All the spectroscopic data of the reaction products were compared
with those reported in the literature [16–21].
2.4. Characterizations
X-ray diffraction patterns (XRD) were obtained with a Philips
X'Pert MPD diffractometer using Cu Kα radiation (λ=1.54178 Å).
Transmission Electron Microscopy (TEM) observations were carried
out at 100 kV (JEOL 1200 EXII). Samples for TEM measurements
were prepared by embedding the hybrid material in AGAR 100
resin, followed by ultramicrotomy techniques and deposition on
Fig. 1. TEM images of synthesized CuO nanowires.
Fig. 2. (a) XRD pattern of prepared CuO, (b) after the fourth cycle of the CuO.

H. Elayadi et al. / Catalysis Communications 26 (2012) 155–158
157
diffraction peaks arising from possible impurities such as Cu(OH)2,
CuNO3, Cu2O or Cu are detected, indicating the preparation of pure
phase CuO under the experimental conditions.
Average size of the obtained CuO particle shown in Fig. 1 is in the
range of 2.5–3.7 nm. The crystallite size was also calculated by X-ray
line broadening analysis using the Debye–Scherrer formula [22].
From XRD spectral in Fig. 2a, we found that the average CuO crystal-
lite size was ~4.0 nm, in good agreement with the results of TEM
image (Fig. 1b). The mean value of surface area of CuO catalyst was
52 m2/g from BET analysis. After the fourth cycle of the CuO catalyst
(Fig. 2b), the average crystallite size increases and reaches the value
of ~14 nm.
Preliminary investigation of the reaction of benzyl azide with
ethyl propiolate in the presence of CuO nanoparticle revealed that
the expected adduct was obtained as a single regioisomer. Next, the
1,3-dipolar cycloaddition of 1 to 2 (Scheme 1) was carried out in var-
ious solvents. The 1,3‐dipolar cycloaddition reactions did not proceed
in the absence of catalyst (Table 1, entry 1). Among the solvents test-
ed, polar protic solvents such as water or mixed solvents such as
dioxane/MeOH, CH3CN/H2O and toluene/H2O (Table 1, entries 8, 9,
12, 13) the corresponding triazole 3 was not formed. In dioxane, diox-
ane/IL or THF/H2O as solvent, the yield does not exceed 37% (Table 1,
entries 7, 10, 11). In contrast, when the reaction was carried out in di-
oxane/H2O (2/1,v/v), 1,2,3-triazole 3 was obtained in a good yield
(Table 1, entry 3). However, the combination dioxane/H2O (1/1,v/v)
leads to a moderate yield (Table 1, entry 6). Furthermore, the ratio
Fig. 3. The comparison of efficiency of catalysts' repeated use. Conditions: azide 1 (1,
1 mmol), alkynes (1 mmol), CuO (0.05 mmol, 5 mol %), 60 °C, solvent: (3 mL)
dioxane/H20 (2/1), 2 h.
2
copper grids. The specific surface areas were obtained by BET on a
Micromeritics Tristar 3000 after one night vacuum (10−2 mbar) at
120 °C. The average pore diameter and pore volume were calculated
by the BJH method. The NMR spectra were recorded on a Bruker spec-
trometer (AC 300 MHz). Chemical shifts are reported as δ values
(ppm) relative to TMS as a standard and the coupling constants J
values are given in Hz. FAB mass spectra were recorded on a Varian
MAT 311A spectrometer. TLC was performed on 60 F254 precoated
plastic plate silica gel (Merck). Column chromatography was per-
formed on silica gel (30–60 μm). All solvents were distilled and
dried before using. All the spectroscopic data of the reaction products
were compared with those reported in the literature [16–21].
Table 2
Synthesis of 1,4-disubstituted 1,2,3-triazole with different alkynes and azides.
Entry
4
5
Yield %a
6
3. Results and discussion
R1
R2
14
3
15
Ph-CH2-N3
Ph-CH2-N3
Ph-CH2-N3
CO2Et
H
H
CO2Et
CO2Et
CH2-PO(OEt)2
66
68
75
Morphology of the sample was studied by TEM. Fig. 1 shows a
panoramic image of the product obtained. Interestingly, the product
consisted of ultrafine crystallites. Closer observation revealed that
these ultrafine nanostructure materials were composed of nanowires.
Most of the nanowires are densely packed and align well so as to form
compact nanowire arrays (Fig. 1). TEM image (Fig. 1b) further depicts
the characterization of well-aligned nanowire arrays. Careful scaling
of CuO nanowires reveals that they are 2.5–3.7 nm in diameter and
about 20 nm in length.
16
17
CO2Et
H
CO2Et
CO2Et
70
70
18
19
20
H
CH2-PO(OEt)2
CO2Et
78
71
74
XRD was used to examine the phase composition of the product.
Fig. 2 presents a typical XRD pattern of CuO nanowire. All diffraction
peaks are indexed to monoclinic CuO [JCPDS 41‐0254]. No other
CO2Et
H
CO2Et
Table 1
21
22
23
24
Ph-CH2-N3
Ph-CH2-N3
Ph-CH2-N3
Ph-CH2-N3
H
H
H
H
CH2-Urb
CH2-Thb
CH2-Adb
CH2-AzUrb
70
68
70
62
Synthesis of 1,4-disubstituted 1,2,3-triazole in different solvents.
Entry
CuO (mol%)
Solvent
Time (h)
Yielda
%
1
2
3
4
5
6
7
8
0
2.5
5
7.5
10
5
5
5
5
5
Dioxane/H2O
Dioxane/H2O
Dioxane/H2O
Dioxane/H2O
Dioxane/H2O
Dioxane/H2Ob
Dioxane
2
2
2
2
2
2
2
12
2
2
0
18
66
45
17
42
37
0
25
26
27
28
H
H
H
H
CH2-Ur
72
68
70
64
CH2-Th
CH2-Ad
CH2-AzUr
H2O
9
Dioxane/MeOH
Dioxane/ILc
THF/H2O
CH3CN/H2O
Toluene/H2O
0
10
11
12
13
26
25
0
5
5
5
2
2
2
0
Conditions: azide 4 (1, 1 mmol), alkynes 5 (1 mmol), CuO (0,05 mmol), 60 °C, solvent:
(3 mL) dioxane/H20 (2/1), 2 h.
Conditions: azide (1, 1 eq), alkynes (1 eq), 60 °C.
All the spectroscopic data of the reaction products were compared with those reported
All the spectroscopic data of the obtained products were compared with those reported
in the literature [16–21].
in the literature [16–21].
a
Isolated yield.
Dioxane/H2O (1/1).
a
b
Isolated yield.
b
c
Ur: uracil, Th: thymine, AzUr: 6-Azauracil, Ad: adenine.
IL: ionic liquid (1-butyl-3methyl imidazolium chloride).

158
H. Elayadi et al. / Catalysis Communications 26 (2012) 155–158
Table 3
4. Conclusion
Results for one‐pot tandem reactions.
Yield %a
61
In conclusion, the CuO nano acts as an efficient and recyclable cat-
Entry
29
Alkyne
alyst for the 1,3-dipolar cycloaddition of organic and sugar azides
with terminal alkynes and propargyl nucleobases, and allows the syn-
thesis of 1,2,3-triazole acyclic nucleosides. The one-pot reaction has
been performed efficiently to provide the desired products in good
yields.
The simple experimental procedure, mild reaction conditions, in-
expensive and recyclable catalyst, short reaction times and good
yields are the advantages of the procedure.
30
31
55
58
Conditions: azide (1, 1 mmol), alkynes (1 mmol), CuO (0,05 mmol), solvent: Dioxane
(3 mL), 90 °C, 3 h.
Acknowledgment
a
Isolated yield.
We thank Dr. S. Ananthan (Southern Research Institute Birming-
ham Alabama, USA) for his interest to this work and for his helpful
discussion.
of the catalyst CuO nano was also examined. The result showed that
5% of CuO nano was the optimum amount of the catalyst (Table 1,
entry 3).
Under the present reaction conditions, CuO (Scheme 2) nanopar-
ticle catalyst was also found to be reusable, although gradual decline
of activity was observed. The catalyst was separated by filtration,
washed with water, ethanol and acetone and dried at 100 °C over-
night before reuse. Such a procedure when applied for the 1,3-dipolar
cycloaddition of 1 to 2 gave the product in 59% yield in the second
run. The comparison of efficiency of catalyst on repeated use is
reported in Fig. 3. The gradual decrease of catalytic activity is proba-
bly due to the agglomeration of nanoparticles in the reaction medi-
um, acting negatively on the substrate–catalyst contact surface. This
is visualized by the increase of crystallite size from 4 nm to 14 nm
after the fourth cycle of the catalyst.
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Next, we studied the one-pot tandem [3+2] cycloaddition where
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azide in the presence of CuO nanoparticles as catalyst in dioxane as
solvent (Scheme 3). The reaction mixture was refluxed for 3 h and
the products were isolated by simple purification using flash column
chromatography. As shown in Table 3, the one-pot reaction
proceeded efficiently to provide the desired products in good yields.
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a powerful tool in 1,3-dipolar cycloaddition reactions.
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