Supported CuBr on graphene oxide/Fe3O4: A highly efficient, magnetically separable catalyst for the multi-gram scale synthesis of 1,2,3-triazoles

Article abstract of DOI:10.1039/c3ra45994b

A superparamagnetic graphene oxide (GO)/Fe₃O₄-CuBr catalyst was prepared via a simple chemical method and characterized by Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA), transmission electron microscopy (TEM), powder X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The GO/Fe₃O₄-CuBr catalyst could be dispersed homogeneously in water and further used as an excellent semi-heterogeneous catalyst for the one-pot multi-component Cu(i)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. 1,4-Disubstituted mono/bis-1,2,3-triazoles are readily obtained on a multi-gram scale by the reaction of aryl/alkyl halides, alkynes and sodium azide under microwave irradiation conditions in good to excellent yields. Moreover, GO/Fe₃O₄-CuBr could be separated conveniently from the reaction mixtures by an external permanent magnet and reused in at least six consecutive runs without a noticeable drop in the product yield and its catalytic activity.

Full text of DOI:10.1039/c3ra45994b

RSC Advances
View Article Online
View Journal | View Issue
PAPER
Supported CuBr on graphene oxide/Fe3O4: a highly
efficient, magnetically separable catalyst for the
multi-gram scale synthesis of 1,2,3-triazoles†
Cite this: RSC Adv., 2014, 4, 9830
*
Xingquan Xiong, Huixin Chen, Zhongke Tang and Yunbing Jiang
A superparamagnetic graphene oxide (GO)/Fe3O4–CuBr catalyst was prepared via a simple chemical
method and characterized by Fourier transform infrared (FTIR), thermal gravimetric analysis (TGA),
transmission electron microscopy (TEM), powder X-ray diffraction (XRD) and X-ray photoelectron
spectroscopy (XPS). The GO/Fe3O4–CuBr catalyst could be dispersed homogeneously in water and
further used as an excellent semi-heterogeneous catalyst for the one-pot multi-component Cu(I)-
catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC) reaction. 1,4-Disubstituted mono/bis-1,2,3-
triazoles are readily obtained on a multi-gram scale by the reaction of aryl/alkyl halides, alkynes and
sodium azide under microwave irradiation conditions in good to excellent yields. Moreover, GO/Fe3O4–
CuBr could be separated conveniently from the reaction mixtures by an external permanent magnet and
reused in at least six consecutive runs without a noticeable drop in the product yield and its catalytic activity.
Received 21st October 2013
Accepted 23rd January 2014
DOI: 10.1039/c3ra45994b
www.rsc.org/advances
In this regard, heterogenization of the copper catalysts can
be an attractive solution to this problem since the copper salts
Introduction
immobilized on a support can be easily separated from the
obtained products free of metal residues and recycled. There
has been considerable interest in the development of hetero-
geneous CuAAC catalytic systems that can be efficiently reused
whilst keeping the inherent activity of the catalytic center. Up to
now, a lot of efforts have been made to design and synthesize
recoverable catalysts. Immobilizing the CuAAC catalysts directly
onto various inorganic and organic supports,34 such as
In recent years, the Cu(I)-catalyzed azide-alkyne 1,3-dipolar
cycloaddition (CuAAC) reaction,1–5 which was coined as “click
reaction”, has attracted great attention not only from academia
but also for applications.6–11 In this context, many efforts have
been made to further develop CuAAC, which mainly focused on
one-pot multicomponent CuAAC reaction.12–33 The one-pot
multicomponent CuAAC reaction has been recognized as one of
the most attractive synthetic tools due to the green, efficient and
convenient preparation of 1,2,3-triazole derivatives, whose
subunits are extensively used in medicinal chemistry as a
pharmacophore to modify known bioactive molecules and to
potentiate their biological activities.
magnetic nanoparticles (MNPs),35–38 zeolite,39,40 polymers41–50
51–55
and SiO2
have been explored. However, the preparation
procedures of the catalysts supported on these materials were
relatively cumbersome and require multiple steps.
In recent years, carbocatalysis has been paid much attention
as it is cheap and easily obtained, and carbon materials have
been widely used as heterogeneous catalysts. Catalysts based on
carbon materials, such as activated carbon and carbon nano-
tubes, have also been studied as CuAAC catalyst supports.56,57
These catalysts showed high catalytic activity and could be
reused for several cycles, but they were difficult to separate from
the reaction mixtures, and ltration (or high speed centrifuga-
tion) was required.
Different from activated carbon and carbon nanotubes,
graphene oxide (GO) has been demonstrated as a promising
support for heterogeneous nanocatalysts due to their intrinsic
properties such as high chemically stability, large surface area
and good accessibility.58 Most importantly, GO has rich surface
functional groups (mainly epoxide, hydroxyl and carboxyl),
which made GO as a suitable support material for metal and
metal oxide nanoparticles. Recently, it was reported that many
Generally, copper salts and ligands have been used as
homogeneous catalyst systems to catalyze one-pot synthesis of
1,2,3-triazoles from aryl/alkyl halides, alkynes and sodium
azide. Although homogeneous copper catalysts have many
advantages, the homogeneous catalysts are difficult to be
recovered and reused, and the residual copper metal along with
the products can cause serious problems in the synthesis of
bioactive molecules. Moreover, it is difficult to be be used in
large-scale syntheses particular on environmental and
economic concerns.
College of Materials Science & Engineering, University of Huaqiao, Xiamen 361021,
China. E-mail: xxqluli@hqu.edu.cn
† Electronic supplementary information (ESI) available: The characterization of
the products 4–9 by 1H and 13C NMR spectra are given. See DOI:
10.1039/c3ra45994b
9830 | RSC Adv., 2014, 4, 9830–9837
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
types of inorganic nanomaterials could be deposited onto GO
nanosheet surfaces to impart new functionality to this
increasingly popular 2D nanomaterial in consideration of its
large surface area. For example, Fe3O4 nanoparticles (Fe3O4
NPs) has been successfully introduced on the surface or inter-
plane of GO.59–61 The unique properties of GO/Fe3O4 hybrids,
combining effects from GO and Fe3O4 NPs have opened a new
window for fabricating highly stable multifunctional nano-
materials by using these hybrids as support materials.
Unfortunately, as far as we know, in spite of the development
of GO/Fe3O4 supported catalysts, GO/Fe3O4-supported CuAAC
catalysts have still not been reported. In addition, the above
noted papers reported only the synthesis of 1,4-disubstituted
mono-1,2,3-triazoles by using heterogeneous catalysts. In order
to further improve the efficiency and practicality of the CuAAC
reaction, herein we develop a green, efficient and scale-up
synthesis of 1,4-disubstituted mono/bis-1,2,3-triazoles from
aryl/alkyl halides, alkynes and sodium azide in water, which
catalyzed by magnetically recyclable GO/Fe3O4–CuBr via a
combination of one-pot multi-component CuAAC reaction and
microwave irradiation (Scheme 1).
Scheme 2 Schematic representation of the preparation and magnetic
separation of GO/Fe3O4–CuBr catalyst from water by an external
magnet after 30 s.
Table 1 FTIR and microanalysis of GO/Fe3O4–CuBr catalyst
FTIR (KBr, cmꢀ1
)
Microanalysis (wt%)
Sample
GO
GO/Fe3O4
GO/Fe3O4–CuBr
nC]O
1722
—
nC]C
1634
1644
1642
nFe–O
—
589
580
Cua
—
—
10.115
Cub
—
—
8.504
Preparation and characterization of
—
a
b
GO/Fe3O4–CuBr
AAS analysis results of fresh catalysts. AAS analysis results of GO/
Fe3O4–CuBr aer six consecutive trials.
The concise route for the preparation of GO/Fe3O4–CuBr is
outlined in Scheme 2.
GO and GO/Fe3O4 were prepared according to the modied
Hummer's method62,63 and Song's method,64 respectively. The
obtained GO/Fe3O4 was then treated with CuBr in ethanol at
reux temperature for 24 hours under a N2 atmosphere to
generate GO/Fe3O4–CuBr catalyst (Scheme 2). The catalyst has
been characterized by FTIR, TGA, atomic absorption spectros-
copy (AAS), TEM, XRD and XPS.
the complexing reaction with CuBr. Obviously, when GO/Fe3O4
complexed with CuBr, the –Fe–O– stretching peak of GO/Fe3O4
appeared at 589 cmꢀ1 was shied to 580 cmꢀ1. The character-
istic –C]C– bands appeared at 1644 cmꢀ1 were shied to 1642
cmꢀ1. The lowering in frequency of the above peaks indicates
the formation of the metal–ligand bond.
The percentage of copper contents of the fresh GO/Fe3O4–
CuBr and the recycled GO/Fe3O4–CuBr aer six consecutive
trials were determined by AAS (Table 1). The catalysts were
stirred in dil. HNO3 for 10 h and then subjected to AAS analysis.
The percentage of copper contents of them were found to be
10.115 and 8.504 wt%, respectively.
As can be seen from Table 1, the peaks at near 1722 cmꢀ1
were characteristic bands of C]O stretching vibration, indi-
cating that the GO was successfully synthesized. However, the
peak at 1722 cmꢀ1 disappeared due to the formation of –COOꢀ
aer coating with Fe3O4. In addition, Table 1 also showed the
FTIR spectra of GO/Fe3O4 and GO/Fe3O4–CuBr before and aer
The morphology GO/Fe3O4–CuBr and the reused catalyst was
determined by TEM. As Fig. 1a showed, Fe3O4 nanoparticles are
chemically deposited on GO with the aid of the –COOH on GO.
Some Fe3O4 aggregation is observed. The results of TEM
Scheme 1 One-pot synthesis of 1,4-disubstituted mono/bis-1,2,3-
triazoles catalyzed by GO/Fe3O4–CuBr in water under microwave Fig. 1 TEM images of GO/Fe3O4–CuBr (a) and the recycled catalyst
irradiation condition.
after 6 consecutive trials (b).
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9830–9837 | 9831

View Article Online
RSC Advances
Paper
indicated the nano-sized organic–inorganic hybrid materials the loss of the residual or absorbed solvent. The GO/Fe3O4–
were prepared. The morphology of the used catalyst did not CuBr catalyst possesses good thermal stabilities (up to 500 ꢁC),
show any signicant change even aer six reaction cycles, which which meets the demands for potential applications in
proved its robustness (Fig. 1b).
catalysis.
The XRD patterns of graphite, GO, GO/Fe3O4 and GO/
Fe and Cu elements were detected on the whole GO surface
by energy-dispersive X-ray analysis (EDX) analysis. Fig. 2 shows Fe3O4–CuBr are presented in Fig. 4. The original graphite
typical EDX mapping images of Fe (red) and Cu (green) shows a sharp characteristic diffraction peak at 2q ¼ 26.5ꢁ,
elements, which are from Fe3O4 and CuBr of GO/Fe3O4–CuBr (a) corresponding to the (002) crystal plane with a d-spacing of
and the recycled catalyst aer 6 consecutive trials (b), respec- 0.34 nm. Aer the oxidation treatment, the (002) diffraction
tively. Fig. 2a shows Fe3O4 and CuBr are uniformly coated onto peak for graphite shied to lower angle at 2q ¼ 12.5ꢁ, indi-
GO. However, Fig. 2b shows the Cu of the recycled catalyst aer cating the formation of GO. In comparison with the natural
six cycles was lower than the fresh catalyst.
graphite, the enhancement of the interlayer spacing of GO is
The thermal behaviors of GO, GO/Fe3O4 and GO/Fe3O4–CuBr mainly due to the presence of oxygen-containing functional
are further investigated by TGA. As shown in Fig. 3, the GO groups formed during oxidation on the graphite sheets. In
powders exhibit two steps of mass loss at 150 ꢁC and 300 ꢁC with addition, the characteristic peak of pristine graphite at 2q ¼
9% and 35% weight loss, which are attributed the removal of 26.5ꢁ disappears aer strong oxidation. These data suggest
adsorbed water and oxygen-containing functional groups, that graphite is successfully converted to GO aer oxidation by
respectively (Fig. 3a). An obvious weight loss (15 wt%) between Hummer's method. The main peaks in Fig. 4c at 2q ¼ 30.1ꢁ
350 ꢁC and 550 ꢁC is observed, which can be assigned to the (220), 35.6ꢁ (311), 43.6ꢁ (400), 53.6ꢁ (422), 57.5ꢁ (511), and 62.8ꢁ
decomposition and vaporization of various oxygen-containing (440) show the characteristics of Fe3O4 (JCPDS no. 19-629).
functional groups at different positions on the surface of the Three additional peaks at 2q ¼ 27.1ꢁ, 45.2ꢁ, and 53.2ꢁ corre-
GO/Fe3O4 hybrid composite (Fig. 3b). However, GO/Fe3O4–CuBr sponding to the (111), (220), and (311) planes of CuBr are
exhibits a higher thermal stability rather than both GO and GO/ observed in the pattern of the GO/Fe3O4–CuBr composite
Fe3O4 (Fig. 3c). A slow weight loss (about 1.5 wt%) at low (Fig. 4d), indicating the existence of CuBr. Fig. 4d shows the
temperature (<100 ꢁC) was observed, which could be assigned to diffraction peaks of Fe3O4 and CuBr all clearly broadened,
which suggested that both of them were successfully graed
onto GO sheets. These results of XRD conrm the successful
preparation of GO/Fe3O4–CuBr.
Magnetic properties of GO/Fe3O4–CuBr and the used GO/
Fe3O4–CuBr aer six recycling were investigated using VSM.
Fig. 1 shows the magnetization curves of the original GO/Fe3O4–
CuBr (Fig. 5a) and the used sample aer 6 recycling (Fig. 5b) at
room temperature. The obtained results revealed that the
samples had a suitable property for magnetic actuation and
manipulation. The values of saturation magnetization
decreased from 17.632 to 9.8049 emu gꢀ1 aer six consecutive
trials, which possibly originated from the decrease of loading
amount of Fe3O4 nanoparticles on the GO surface during using
under microwave heating condition.
Fig. 2 EDX elemental mapping images of the surface of GO/Fe3O4–
CuBr (a) and the recycled catalyst after 6 consecutive trials (b).
Fig. 4 XRD Patterns of graphite (a), GO (b), GO/Fe3O4 (c), GO/Fe3O4–
Fig. 3 TGA curves of GO (a), GO/Fe3O4 (b), GO/Fe3O4–CuBr (c).
9832 | RSC Adv., 2014, 4, 9830–9837
CuBr (d).
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 2 Effect of the Cu catalysts on the one-pot synthesis of 1-
benzyl-4-phenyl-1H-1,2,3-triazole under microwave assisted and
conventional heating conditionsa
Entry
Cu catalyst
Yieldb (%)
Yieldc (%)
Cu contentd (%)
1
2
3
Cu(OAc)2
CuBr
GO/Fe3O4–CuBr
Trace
65
98
Trace
96
98
—
6.540
0.012
a
Reagents and conditions: BnCl (0.50 mmol), PhC^CH (0.50 mmol),
NaN3 b(0.50 mmol), Cu catalyst (0.025 mmol Cu, 5 mol%), water (2.0
mL). Isolated yield under microwave irradiation condition, 10 min.
Isolated yield by using conventional heating, 8 h. Cu content of the
obtained 1,2,3-triazole under microwave irradiation condition.
c
d
Fig. 5 The magnetization curve of (a) GO/Fe3O4–CuBr and (b) GO/
Fe3O4–CuBr after 6 recycling.
XPS was used to study surface elemental composition of GO/
Fe3O4–CuBr and GO/Fe3O4–CuBr aer 6 recycling. As shown in
Fig. S13,† the C1s spectra can be deconvoluted into two main
components corresponding to carbon atoms in different func-
tional groups, which exhibits the presence of C–C (284.5 eV), C–
O groups (286.5 eV). The binding energies of Cu2p3/2 in GO/
Fe3O4–CuBr and the recycled GO/Fe3O4–CuBr catalyst were both
found to be around 932.5 eV (Fig. S14†), suggesting no change
in chemical valence of Cu(I) in the supported catalyst aer
6 recycling. In addition, the concentrations of surface Cu and Fe
atoms of them decreased from 3.54% and 4.79 to 2.76% and
4.39% aer 6 recycling, respectively, conrming only a few
Fe3O4 and CuBr from the GO/Fe3O4–CuBr catalyst were leached
into the solution aer 6 recycling. This may account for the
slight decrease in catalytic activity.
When CuBr and GO/Fe3O4–CuBr was used as catalyst, the yields
of the obtained 1,2,3-triazole were found to be 96% and 98%,
respectively (Table 2). Comparing with the traditional heating
method, the use of microwave irradiation could dramatically
reduce the reaction time. As a result, GO/Fe3O4–CuBr was used
in the subsequent investigations under microwave irradiation
condition because of its high reactivity, high selectivity and easy
separation.
Copper is an essential trace metal in man but it is toxic at
higher concentrations. Accordingly, the percentage of copper
contents of the obtained 1,2,3-triazole in the model reaction
under heterogeneous and homogeneous catalytic conditions
were determined by AAS (Table 2). The copper contents of the
product prepared by CuBr and GO/Fe3O4–CuBr as catalyst were
found to be 6.540 and 0.012 wt%, respectively. It could obvi-
ously reduce the level of copper metal in the nal products by
using GO/Fe3O4–CuBr as heterogeneous catalyst.
Effect of catalysts on the one-pot
CuAAC reaction under microwave
assisted and conventional heating
conditions
Synthesis of 1,4-disubstituted mono/
bis-1,2,3-triazoles catalyzed by GO/
Fe3O4–CuBr
For the initial screening experiments, NaN3, benzyl chloride Having determined the optimal conditions, we proceeded to
and phenyl acetylene were selected as the test substrates to investigate the scope of this one-pot CuAAC reaction of different
examine the effects of various CuAAC catalysts in water at 80 ꢁC halides and alkynes under the optimized reaction conditions in
under microwave irradiation and conventional heating condi- aqueous medium. The results are summarized in Table 3. The
tions (Table 2).
GO/Fe3O4–CuBr catalyzed CuAAC reaction of NaN3/halides with
Optimization studies revealed that CuAAC reaction could alkynes was performed under the standard condition: GO/
perform with low yield by using Cu(OAc)2 as catalyst (Table 2, Fe3O4–CuBr (5.0 mol%) as the catalyst and water as the solvent
entry 1). When CuBr was used as catalyst, CuAAC reaction could at 80 ꢁC without exclusion of air (Table 3). As shown in Table 3,
only give a moderate yield (Table 2, entry 2). Based on these all the reactions were completed within a time period of 5–25
frustrating results, we continued our research to improve the min with high selectivity and conversion, depending on the
yield of the product by using other catalysts. To our delight, the substrates. And the corresponding triazoles were obtained in
reaction performed smoothly with the use of GO/Fe3O4–CuBr good to excellent yields. In general, no signicant difference in
and could give an excellent yield (Table 2, entry 3).
reactivity was observed for the examined reactants with varied
Under conventional heating condition, we investigated the electronic properties. Both electron-rich and electron-poor
activity of the catalysts with respect to time for the formation of azides as reactants generated good to excellent yields of the
ꢁ
triazole and found 8 h is the optimized reaction time at 80 C. products. Moreover, this cycloaddition also proceeded
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9830–9837 | 9833

View Article Online
RSC Advances
Paper
Table 3 GO/Fe3O4–CuBr used in the one-pot CuAAC reaction for the
regiospecific formation of 1,4-disubstituted mono/bis-1,2,3-triazoles
under microwave irradiation in watera
Fe3O4–CuBr catalyst on multicomponent reaction of phenyl
acetylene, NaN3 and benzyl chloride. A series of catalytic
cycles were run to investigate the constancy of the catalyst
activity for this model reaction. Aer each run, the catalyst
was quickly concentrated to the side wall of the reactor via an
external permanent magnet. Aer a simple wash using
ethanol and air drying the catalyst was used for the next cycle.
The recovered catalyst could be added to fresh substrates
under identical conditions for six runs without a noticeable
drop in the product yield and its catalytic activity (Fig. 6). As
shown in Table 1, the copper content of the recycled catalyst
aer six cycles was found to be 8.504 wt% detected by AAS,
which lower than the esh catalyst (10.115 wt%). The
possible reason was the complexing ability between surface
functional groups (mainly epoxide, hydroxyl and carboxyl) of
GO and CuBr were relatively weak. It caused a slight decrease
of catalytic activity of GO/Fe3O4–CuBr catalyst aer several
recycles (the yield was reduced by 8% aer six recycles,
Fig. 4).
Entry
Halide
Alkyne
Time (min)
Yieldb (%)
1
2
5
92 (ref. 65)
98 (ref. 65)
10
3
4
8
5
96 (ref. 42)
90
5
15
90
6
7
8
15
18
20
89
91
88
Scale-up synthesis of 1-benzyl-4-
phenyl-1H-1,2,3-triazole
9
25
89
Prompted by the aforementioned interesting results like the
high catalytic activity of GO/Fe3O4–CuBr, we set out to further
clarify the practicality of the catalyst. To extend this strategy to
the multi-gram scale synthesis of 1,2,3-triazole derivatives, we
investigated the scale-up preparation of 1-benzyl-4-phenyl-1H-
1,2,3-triazole as a model reaction. Encouraged by the above
results, we increased the scale of the reaction to 5.0, 10.0, 20.0
and 40.0 mmol, keeping the reaction stoichiometry unchanged.
The reactions were found to proceed in good to excellent yields
without undesired side reactions. When the scale of the reac-
tion was increased to 40.0 mmol, the reaction was still found to
proceed successfully and the corresponding product was
obtained in 75% yield. Most importantly, when the scale of the
reaction was 10.0 mmol, the catalyst could be recycled and
reused at least four times. The detailed results were summa-
rized in the Table 4.
a
Reagents and conditions: R1X (0.50 mmol), R2CH2C^CH
(0.50 mmol) or R2CH(C^CH)2 (0.25 mmol), NaN3 (0.50 mmol), GO/
Fe3O4–CuBr (0.025 mmol Cu, 5.0 mol% of catalyst), water (2.0 mL),
b
480 W, 80 ꢁC. Isolated yields.
successfully in the case of diynes like 1,4-bis(prop-2-ynyloxy)-
benzene and 1,3-bis(prop-2-ynyloxy)benzene, although the
reaction time was longer than other substrates (Table 3, entries
6–9). These results highlight the compatibility of this cascade
process with a wide range of functionalities. Furthermore, it is
important to note that the corresponding triazoles were
obtained in high yields and regioselectivity. The structures of
the obtained products were conformed by FTIR, H NMR, 13C
1
NMR spectroscopy and mass spectrometry, respectively.
Remarkably, compared with other similar magnetic nano-
catalyst (such as MNPs–CuBr38), the GO/Fe3O4–CuBr catalyst
showed higher catalytic activity during the one-pot multicom-
ponent CuAAC reaction. For example, the one-pot reactions
could proceed smoothly to completion within 10 min (Table 3,
entries 1–3), and the products were isolated in excellent yields
(92–98%). The intrinsic properties (large surface area and good
accessibility) of GO might cause the extremely high catalytic
activity of GO/Fe3O4–CuBr.
Reuse test of GO/Fe3O4–CuBr catalyst
For a true heterogeneous catalyst, the reusability is one of the
important properties. In order to make our catalytic system
Fig. 6 Reusability of the catalyst using sodium azide, benzyl chloride
greener and economical, we focused on reusability of GO/ and phenyl acetylene as starting materials.
9834 | RSC Adv., 2014, 4, 9830–9837
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
Table 4 Scale-up synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole
toluene) and NaN3 (99%) were purchased from Shanghai Sino-
pharm Chemicals Co., Propargyl alcohol (97%) was purchased
from Wuhan Hechang Chemicals Co., methyl 2-(prop-2-ynyloxy)
benzoate (97%) and 1-isopropyl-4-methyl-2-(prop-2-ynyloxy)-
benzene (98%) were purchased from Xiamen Lvyin Chemicals
Co. Compounds 5b, 6b and 7b (all of purity $ 98%) were
synthesized according to the literature procedures, respec-
tively.66–68 All other chemicals were used without further puri-
cation. All the one-pot CuAAC reactions were carried out in a
professional microwave reactor equipped with a stirring bar.
Entry
Scale (mmol)
H2O (mL)
Yielda (%)
1
0.5
0.5
5
2
2
98
94
96
92
88
86
80
75
2b
3
20
20
40
40
80
120
4c
5
5
10
10
20
40
6d
7
8
a
b
c
isolated yield. catalyst recycled and used for 4nd run. catalyst
recycled and used for 4nd run. d catalyst recycled and used for 4nd run.
Preparation of GO/Fe3O4–CuBr
catalyst
GO was synthesized according to previous methods.62,63 The GO/
Fe3O4 nanocomposite was prepared by the chemical co-precipi-
tation method similar to that reported previously.64 GO (200 mg)
was dispersed into deionized water (250 mL) under ultra-
sonication for 30 min. FeCl3 (1.0 mmol) was added into the
aqueous dispersion solution. The mixture was stirred overnight
at 65 ꢁC. A NH3$H2O solution (30 mL, 25–28%) and FeSO4$7H2O
(0. 5 mmol) were added, respectively. Aer the resulted mixture
was stirred for another 2 h at 65 ꢁC, the precipitate was separated
by an external permanent magnet, and was washed with distilled
water in turn until neutralization and dried under vacuum. The
GO/Fe3O4–CuBr nanocomposite was prepared as follows: in a
small Schlenk tube, the obtained GO/Fe3O4 (1.00 g) was then
treated with CuBr (0.20 g) in ethanol (50 mL), the mixture was
stirred under a N2 atmosphere at reux temperature for 12 hours.
The GO/Fe3O4–CuBr catalyst was separated by an external
permanent magnet, wash with deionized water and ethanol fol-
lowed by drying under vacuum at 60 ꢁC overnight for further use.
Conclusions
In summary, a new kind of GO/Fe3O4-supported semi-hetero-
geneous catalyst, namely GO/Fe3O4–CuBr, were rstly prepared.
It shows high catalytic activity for three-component CuAAC
reaction, and it has been used successfully for efficient, green
and scale-up preparation of 1,4-disubstituted mono/bis-1,2,3-
triazoles. More importantly, the magnetic GO/Fe3O4–CuBr
catalyst can be quickly and completely recovered by simply
applying an external magnet and the efficiency remains unal-
tered even aer four recycles when the scale of the reaction is
10.0 mmol. Furthermore, when the reaction is performed in
H2O on 40.0 mmol scale, the desired product was also obtained
in 75% yield. The mild reaction condition, high yields of
products, ease of work-up, ecologically clean procedure, and
scale-up synthesis will make the present method a useful and
important addition to the methodologies for the synthesis of
mono/bis-1,2,3-triazoles.
General procedure for one-pot
synthesis of the 1,2,3-triazoles
Experimental section
The primary halide, NaN3 and terminal alkyne in a 1 : 1 : 1
molar ratio followed by adding GO/Fe3O4–CuBr catalyst in a
10.0 mL round-bottomed ask (H2O, 2.0 mL). The mixture was
The IR spectra were obtained using a FTIR (4000–400 cmꢀ1
)
spectrometer (Nicolet Nexus FTIR spectrometer, USA) at 4 cmꢀ1
resolution and 32 scans. Samples were prepared using the KBr
disc method. The amount of copper in GO/Fe3O4–CuBr was
determined by AAS using standard methods with a Varian
AA275 atomic absorption spectrophotometer (USA). Size and
morphology images of GO/Fe3O4–CuBr were obtained by TEM
(Hitachi H-7650, Japan) operating at 100 KV aer a drop of
aqueous solution of the nanoparticles was deposited and dried
on a copper grid. NMR spectra were acquired in CDCl3 on a
Bruker DMX-400 spectrometer at 400 MHz for 1H NMR, 100
MHz for 13C NMR the chemical shis are given in d values from
TMS as an internal standard. Powder XRD was used to charac-
terize the crystalline structure of the nanoparticles on Bruker D8
Advance (Germany) using Cu Ka radiation. X-ray photoelectron
ꢁ
heated and stirred at 80 C under microwave irradiation (MW,
480 W) until TLC analysis showed that the reaction was
complete. Aer completion of the reaction, the catalyst was
separated conveniently from the reaction mixtures by an
external permanent magnet. Aer a simple wash using ethanol
and air drying the catalyst was used for the next cycle. the
reaction mixture was extracted with ethyl acetate for three
times. Then the combined organic layers were dried (MgSO4)
and evaporated under reduced pressure. The residue was nally
puried by ash chromatography on silica-gel to give the
desired 1,2,3-triazoles in 88–98% yields (Table 3).
spectroscopy (XPS) measurements were performed with ESCA Analytical and spectroscopic data of
2000 (VG Microtech) system.
the 1,2,3-triazoles
n-Butyl bromide (99%), benzyl chloride (99%), Phenyl-
acetylene (97%), FeSO4$7H2O (99%), FeCl3 (99%), NH3$H2O Methyl 2-((1-benzyl-1H-1,2,3-triazol-4-yl) methoxy) benzoate
(30%), hydrogen peroxide (30%), propargyl bromide (80% in (Table 3 entry 4). M.p. (ꢁC): 108–109. IR (KBr) (nmax, cmꢀ1): 3151
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9830–9837 | 9835

View Article Online
RSC Advances
Paper
(w), 3075 (w), 3034 (w), 2952 (s), 1722 (s), 1598 (m), 1432 (m), 1H), 5.55 (s, 4H), 5.19 (s, 4H), 3.90 (s, 3H). 13C NMR (CDCl3) d:
1245 (s), 1083 (m), 815 (m), 765 (m), 704 (m); 1H NMR (400 MHz, 52.31 (1C, OCH3), 54.29 (2C, CH2Ph), 62.31 (2C, OCH2), 106.95,
CDCl3) d: 7.82 (d, J ¼ 7.7 Hz, 1H), 7.67 (s, 1H), 7.48 (t, J ¼ 7.8 Hz, 108.69, 127.79, 127.53, 128.14, 128.85, 129.18, 132.18, 134.42,
1H), 7.38 (s, 3H), 7.29 (d, J ¼ 4.9 Hz, 2H), 7.13 (d, J ¼ 8.4 Hz, 1H), 159.23, 166.53 (C–Ar). MS (ESI): m/z calc. for C28H26N6O4:
7.02 (t, J ¼ 7.5 Hz, 1H), 5.55 (s, 2H), 5.32 (s, 2H), 3.82 (s, 3H); 13
C
510.20, found: 511.13 [M + H]+.
NMR (CDCl3) d: 51.89 (1C, CH3), 54.29 (1C, CH2Ph), 63.60 (1C,
OCH2), 114.18, 120.62, 121.00, 123.21, 128.08, 128.76, 129.12,
131.75, 133.64, 134.57, 157.78 (C–Ar), 166.43 (1C, CO); MS (ESI):
m/z calc. for C18H17N3O3: 323.13, found: 324.04 [M + H]+, 346.02
[M + Na]+.
Acknowledgements
National Natural Science Foundation of China (no. 21004024),
Natural Science Foundation of Fujian province (no. 2011J01046)
Program for New Century Excellent Talents in University of
Fujian province (no. 2012FJ-NCET-ZR03) and Promotion
Program for Young and Middle-aged Teacher in Science and
Technology Research of Huaqiao University (ZQN-YX103) are
appreciated.
4-((2-Isopropyl-5-methylphenoxy)methyl)-1-benzyl-1H-1,2,3-
triazole (Table 3 entry 5). M.p. (ꢁC): 75–76. IR (KBr) (nmax
,
cmꢀ1): 2969 (m), 2923 (m), 2867 (s), 1616 (s), 1503 (s), 1447 (m),
1
1253 (m), 1174 (m), 1105 (m), 1026 (m), 822 (m); H NMR (400
MHz, CDCl3) d: 7.52 (s, 1H), 7.46–7.35 (m, 3H), 7.33–7.27 (m,
2H), 7.14–7.07 (m, 1H), 6.79 (d, J ¼ 5.5 Hz, 2H), 5.57 (s, 2H),
5.23 (s, 2H), 3.25 (dt, J ¼ 13.8, 6.9 Hz, 1H), 2.33 (s, 3H), 1.18 (d,
J ¼ 6.9 Hz, 6H); 13C NMR (CDCl3) d: 155.31, 145.37, 136.45,
134.63, 134.33, 129.13, 128.76, 127.99, 126.02, 122.26, 112.96
(C–Ar), 62.62 (1C, OCH2), 54.20 (1C, CH2Ph), 26.54 (1C, C),
22.77 (1C, CH3), 21.32 (2C, CH3); MS (ESI): m/z calc. for
Notes and references
1 C. W. Tornøe, C. Christensen and M. Meldal, J. Org. Chem.,
2002, 67, 3057.
2 V. V. Rostovtsev, L. G. Green, V. V. Fokin and K. B. Sharpless,
Angew. Chem., Int. Ed., 2002, 41, 2596.
C
20H23N3O: 321.18, found: 322.08 [M + H]+.
4-((4-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenoxy)methyl)-
1-benzyl-1H-1,2,3-triazole (Table 3 entry 6). M.p. (ꢁC): 202–204. IR
(KBr) (nmax, cmꢀ1): 3122 (w), 3106 (w), 2958 (m), 2907 (m), 2864
(m), 1512 (s), 1443 (m), 1228 (m), 1124 (m), 1047 (m), 806 (m), 702
(m); 1H NMR (400 MHz, CDCl3) d: 7.58 (s, 2H), 7.53–7.33 (m, 6H),
3 M. Morten and W. T. Christian, Chem. Rev., 2008, 108, 2952.
4 Q. Wang and C. Hawker, Chem.–Asian J., 2011, 6, 2568.
5 X. Q. Xiong, L. Cai and Z. K. Tang, Chin. J. Org. Chem., 2012,
32, 1410.
6 J. E. Moses and A. D. Moorhouse, Chem. Soc. Rev., 2007, 36,
1249.
7 R. K. Iha, K. L. Wooley, A. M. Nystrom, D. J. Burke, M. J. Kade
and C. J. Hawker, Chem. Rev., 2009, 109, 5620.
8 H. C. Kolb and K. B. Sharpless, Drug Discovery Today, 2003, 8,
1128.
7.29 (d, J ¼ 4.7 Hz, 4H), 6.90 (s, 4H), 5.55 (s, 4H), 5.14 (s, 4H). 13
C
NMR (CDCl3) d: 54.32 (1C, CH2Ph), 62.74 (2C, OCH2), 115.86,
128.13, 128.83, 129.15, 134.46, 152.18 (C–Ar). MS (ESI): m/z calc.
for C26H24N6O2: 452.20, found: 453.16 [M + H]+.
4-((4-((1-Butyl-1H-1,2,3-triazol-4-yl)methoxy)phenoxy)methyl)-
1-butyl-1H-1,2,3-tria-zole (Table 3 entry 7). M.p. (ꢁC): 125–127. IR
(KBr) (nmax, cmꢀ1): 3148 (w), 3096 (w), 2949 (s), 2881 (m), 1512 (s),
9 J.-F. Lutz, Angew. Chem., Int. Ed., 2007, 46, 1018.
1
1452 (s), 1219 (s), 1107 (w), 1047 (s), 827 (s), 573 (m); H NMR 10 W. H. Binder and R. Sachsenhofer, Macromol. Rapid
(400 MHz, CDCl3) d: 7.59 (s, 2H), 6.94 (s, 4H), 5.18 (s, 4H), 4.37 (t,
J ¼ 7.2 Hz, 4H), 1.98–1.82 (m, 4H), 1.44–1.32 (m, 4H), 0.97 (t, J ¼ 11 G. C. Tron, T. Pirali, R. A. Billington, P. L. Canonico, G. Sorba
7.3 Hz, 6H). 13C NMR (CDCl3) d: 31.60 (2C, CH3), 32.23 (2C,
and A. A. Genazzani, Med. Res. Rev., 2008, 28, 278.
CH3CH2), 50.15 (2C, CH3CH2CH2), 61.84 (2C, CH3CH2CH2CH2), 12 A. K. Feldman, B. Colasson and V. V. Fokin, Org. Lett., 2004,
62.79 (1C, OCH2), 115.29, 115.86, 122.39, 144.31, 152.82 (C–Ar). 6, 3897.
MS (ESI): m/z calc. for C20H28N6O2: 384.23, found: 385.12 [M + H]+. 13 P. Appukkuttan, W. Dehaen, V. V. Fokin and E. Van der
4-((3-((1-Benzyl-1H-1,2,3-triazol-4-yl)methoxy)phenoxy)methyl)-
Eycken, Org. Lett., 2004, 6, 4223.
1-benzyl-1H-1,2,3-triazole (Table 3 entry 8). M.p. (ꢁC): 171–172. 14 S. Chittaboina, F. Xie and Q. Wang, Tetrahedron Lett., 2005,
IR (KBr) (nmax, cmꢀ1): 3139 (w), 3088 (w), 3066 (w), 2924 (m),
46, 2331.
Commun., 2007, 28, 15.
2864 (m),1615 (s), 1494 (s), 1443 (m), 1382 (m), 1185 (s), 1021 15 H. S. G. Beckmann and V. Wittmann, Org. Lett., 2007, 9, 1.
(s), 831(m), 780 (m), 728 (m); 1H NMR (400 MHz, CDCl3) d: 7.57 16 K. Odlo, E. A. Høydahl and T. V. Hansen, Tetrahedron Lett.,
(s, 2H), 7.40 (dd, J ¼ 9.7, 6.1 Hz, 6H), 7.32–7.28 (m, 4H), 7.17 (d,
J ¼ 8.2 Hz, 1H), 6.60 (d, J ¼ 7.7 Hz, 3H), 5.55 (s, 4H), 5.16 (s, 17 C. T. Lee, S. L. Huang and B. H. Lipshutz, Adv. Synth. Catal.,
4H). 13C NMR (CDCl3) d: 54.31 (1C, CH2Ph), 62.12 (2C, OCH2),
2009, 351, 3139.
2007, 48, 2097.
102.12, 107.64, 128.15, 128.84, 129.17, 130.06, 134.44, 159.42 18 F. Friscourt and G. J. Boons, Org. Lett., 2010, 12, 4936.
(C–Ar). MS (ESI): m/z calc. for C26H24N6O2: 452.20, found: 19 J. D. Crowley and P. H. Bandeen, Dalton Trans., 2010, 39, 612.
453.15 [M + H]+.
20 F. Alonso, Y. Moglie, G. Radivoy and M. Yus, Adv. Synth.
Catal., 2010, 352, 3208.
Methyl 3,5-bis((1-benzyl-1H-1,2,3-triazol-4-yl) methoxy) benzoate
(Table 3 entry 9). M.p. (ꢁC): 146–147. IR (KBr) (nmax, cmꢀ1): 21 B. Kaboudin, Y. Abedia and T. Yokomatsu, Org. Biomol.
3146 (w), 3093 (w), 1720 (s), 1666 (s), 1596 (m), 1452 (m), 1299
(m), 1160 (s), 1049 (s), 817 (m), 721 (m); H NMR (400 MHz, 22 A. Megia-Fernandez, M. Ortega-Munoz, F. Hernandez-Mateo
Chem., 2012, 10, 4543.
1
˜
CDCl3) d: 7.56 (s, 2H), 7.38 (s, 6H), 7.30–7.25 (m, 6H), 6.80 (s,
9836 | RSC Adv., 2014, 4, 9830–9837
and F. Santoyo-Gonzalez, Adv. Synth. Catal., 2012, 354, 1797.
This journal is © The Royal Society of Chemistry 2014

View Article Online
Paper
RSC Advances
23 R. B. N. Baig and R. S. Varma, Chem. Commun., 2012, 48, 46 S. Wallyn, M. Lammens, R. K. O'reilly and F. D. Prez,
5853. J. Polym. Sci., Part A: Polym. Chem., 2011, 49, 2878.
24 A. N. Prasad, B. Thirupathi, G. Raju, R. Srinivas and 47 J. Albadi, M. Keshavarz, F. Shirini and M. Vafaie-nezhad,
B. M. Reddy, Catal. Sci. Technol., 2012, 2, 1264.
25 S. Hwang, H. Bae, S. Kim and S. Kim, Tetrahedron, 2012, 68, 48 E. Ozkal, S. Ozçubukçu, C. Jimenoa and M. A. Pericas, Catal.
Catal. Commun., 2012, 27, 17.
¨
`
1460.
26 J. A. Shin, Y. G. Lim and K. H. Lee, J. Org. Chem., 2012, 77, 49 R. B. Nasir Baig and R. S. Varma, Green Chem., 2013, 15,
4117. 1839.
27 M. C. Hashjin, R. Ciyabi, M. Baharloui, G. Hosseini and 50 S. Roy, T. Chatterjee and Sk. M. Islam, Green Chem., 2013, 15,
H. Tavakoli, Chin. J. Chem., 2012, 30, 223. 2532.
28 M. Driowya, A. Puissant, G. Robert, P. Auberger, R. Benhida 51 T. Shamim and S. Paul, Catal. Lett., 2010, 136, 260.
Sci. Technol., 2012, 2, 195.
and K. Bougrin, Ultrason. Sonochem., 2012, 19, 1132.
29 Y. J. Shang, L. B. Ren and D. M. Wang, Chin. J. Chem., 2007,
25, 1202.
52 H. Sharghi, R. Khalifeh and M. M. Doroodmand, Adv. Synth.
Catal., 2009, 351, 207.
53 T. Miao and L. Wang, Synthesis, 2008, 363.
30 S. Mohammed, A. K. Padala, B. A. Dar, B. Singh, B. Sreedhar, 54 A. Coelho, P. Diz, O. Caamano and E. Sotelo, Adv. Synth.
R. A. Vishwakarma and S. B. Bharate, Tetrahedron, 2012, 68,
Catal., 2010, 352, 1179.
8156.
55 L. Wan and C. Cai, Catal. Lett., 2012, 142, 1134.
31 Z. J. Quan, Q. Xu, Z. Zhang, Y. X. Da and X. C. Wang, 56 B. H. Lipshutz and B. R. Ta, Angew. Chem., Int. Ed., 2006, 45,
Tetrahedron, 2013, 69, 881. 8235.
32 J. Zhang, G. Jin, S. Xiao, J. Wu and S. Cao, Tetrahedron, 2013, 57 H. Sharghi, M. H. Beyzavi, A. Safavi, M. M. Doroodmand and
69, 2352. R. Khalifeha, Adv. Synth. Catal., 2009, 351, 2391.
33 B. T. Ramanjaneyulu, V. Reddy, P. Arde, S. Mahesh and 58 B. F. Machadoab and P. Serp, Catal. Sci. Technol., 2012, 2, 54.
R. Vijaya Anand, Chem.–Asian J., 2013, 8, 1489.
34 B. Dervaux and F. E. Du Prez, Chem. Sci., 2012, 3, 959.
59 W. H. Shi, J. X. Zhu, D. H. Sim, Y. Y. Tay, Z. Y. Lu,
X. J. Sharma, Y. Zhang, M. Srinivasan, H. Hang, H. H. Hng
and Q. Y. Yan, J. Mater. Chem., 2011, 21, 3422.
˜
35 A. Megia-Fernandez, M. Ortega-Munoz, J. Lopez-Jaramillo,
F. Hernandez-Mateo and F. Santoyo-Gonzalez, Adv. Synth. 60 X. Y. Yang, Y. S. Wang, X. Huang, Y. F. Ma, Y. Huang,
Catal., 2010, 352, 3306.
36 R. Hudson, C. J. Li and A. Moores, Green Chem., 2012, 14,
622.
37 R. B. Nasir Baig and R. S. Varma, Green Chem., 2012, 14,
625.
R. C. Yang, H. Q. Duan and Y. S. Chen, J. Mater. Chem.,
2011, 21, 3448.
61 G. G. Zhou, D. W. Wang, F. Li, L. L. Zhang, N. Li, Z. S. Wu,
L. Wen, G. Q. Lu and H. M. Cheng, Chem. Mater., 2010, 22,
5306.
38 X. Q. Xiong and L. Cai, Catal. Sci. Technol., 2013, 3, 1301.
39 S. Chassaing, A. S. S. Sido, A. Alix, M. Kumarraja, P. Pale and
J. Sommer, Chem.–Eur. J., 2008, 14, 6713.
40 P. Kuhn, A. Alix, M. Kumarraja, B. Louis, P. Pale and
J. Sommer, Eur. J. Org. Chem., 2009, 423.
41 D. E. Bergbreiter, P. N. Hamilton and N. M. Koshti, J. Am.
Chem. Soc., 2007, 129, 10666.
62 W. Hummers and R. Offeman, J. Am. Chem. Soc., 1958, 80,
1339.
63 Y. X. Xu, H. Bai, G. W. Gewu Lu, C. Li and G. Q. Hi, J. Am.
Chem. Soc., 2008, 130, 5856.
64 Y. H. Song, Z. F. He, H. Q. Hou, X. L. Wang and L. Wang,
Electrochim. Acta, 2012, 71, 58.
´
65 Z. Gonda and Z. Novak, Dalton Trans., 2010, 39, 726.
42 C. Girard, E. Onen, M. Aufort, S. Beauviere, E. Samson and 66 S. Ates, Y. Y. Durmaz, L. Torun and Y. Yagci, J. Macromol.
J. Herscovici, Org. Lett., 2006, 8, 1689. Sci., Part A: Pure Appl.Chem., 2010, 47, 809.
43 T. R. Chan and V. V. Fokin, QSAR Comb. Sci., 2007, 26, 1274. 67 E. Khosravi, Y. Yagci and Y. Savelyev. New smart materials via
44 L. Bonami, W. Van Camp, D. Van Rijckegem and F. E. Du
metal mediated macromolecular engineering, Springer, 2008,
Prez, Macromol. Rapid Commun., 2009, 30, 34.
p. 93.
45 M. Lammens, J. Skey, S. Wallyn, R. O'Reilly and F. D. Prez, 68 J. G. Ha, J. Song, J. K. Lee, B. K. Cho and W. C. Zin, Chem.
Chem. Commun., 2010, 46, 8719.
Commun., 2012, 48, 3418.
This journal is © The Royal Society of Chemistry 2014
RSC Adv., 2014, 4, 9830–9837 | 9837