CuFeO2/tetrabutylammonium bromide catalyzes selective synthesis of 1,4-disubstituted 1,2,3-triazoles in neat water at room temperature

Article abstract of DOI:10.1002/aoc.3526

A completely green medium including water as a solvent and antiviral CuFeO₂ as a catalyst is described for the synthesis of 1,4-disubstituted 1,2,3-triazoles. Excellent yields of products are obtained at room temperature. Cost effectiveness, hi

Full text of DOI:10.1002/aoc.3526

Full paper
Received: 6 February 2016
Revised: 9 April 2016
Accepted: 1 May 2016
Published online in Wiley Online Library
(wileyonlinelibrary.com) DOI 10.1002/aoc.3526
CuFeO /tetrabutylammonium bromide catalyzes
2
selective synthesis of 1,4-disubstituted 1,2,
3
-triazoles in neat water at room temperature
a,b
a
a
Abdol R. Hajipour *, Morteza Karimzadeh , Farzaneh Fakhari
and Hirbod Karimi
a
A completely green medium including water as a solvent and antiviral CuFeO
,4-disubstituted 1,2,3-triazoles. Excellent yields of products are obtained at room temperature. Cost effectiveness, high stability
and high recyclability of CuFeO along with antiviral properties of the catalyst make it a unique catalyst for cycloadditions of
2
as a catalyst is described for the synthesis of
1
2
phenylacetylene with a wide variety of aryl halides. Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: 1,2,3-triazoles; azide; cycloaddition; delafossite; ligand-free; phenylacetylene
of recyclability, which represents an obstacle for the utility of this
chemistry in parallel synthesis.
Introduction
[
1]
1,2,3-Triazoles are commonly seen in bioactive natural products
Heterogeneous catalysis is of paramount importance in many
areas. Heterogeneously catalyzed processes have recently been
brought to the attention of many scientists as comparatively more
efficient methodologies because facile recovery and reusability of
the catalysts are features of these processes. Also stability of the cat-
alyst and even sometimes its activity will be improved when a het-
erogeneous catalytic system id used. Most of the catalytic systems
used in this reaction involve a support, such as Cu(Ι) on activated
and have received much attention as synthetic targets due to their
[
2]
promising applications in numerous pharmaceuticals,
[3]
[4]
[5]
polymers, dyes and agrochemicals. 1,2,3-Triazoles are also as-
sociated with a wide range of biological properties such as
[6]
[7]
[7]
[8]
[8]
antiviral, antibacterial, antifungal, anticancer, anti-HIV
[9]
and antiallergic properties and antimicrobial activities against
[
10]
Gram-positive bacteria.
So, finding an efficient synthetic route
[
24]
[25]
[26]
for these scaffolds is highly desirable.
carbon,
copper(Ι) supported on polymer,
Cu(Ι)–zeoilte
[11]
Huisgen et al. reported the synthesis of 1,2,3-triazoles using
and so on. Also it should be mentioned that our research group re-
cently reported the synthesis of 1,2,3-triazoles using in situ genera-
tion of aryl azides via the reaction of heterogeneous aryldiazonium
silica sulfates and sodium azide, followed by coupling with a termi-
1,3-dipolar cycloaddition reactions of various alkynes and organic
azides. But this process gave a mixture of 1,4- and 1,5-disubstituted
[
12]
[13]
1,2,3-triazole isomers. Meldal et al. and King et al. found that
[
26,27]
copper(Ι) catalyzes azide–alkyne cycloaddition (CuAAC) and only
one regioisomer (1,4-disubstituted 1,2,3-triazole) can be obtained
using this procedure. Also they concluded that copper(Ι) can in-
crease the reaction rate. There are some other methods for produc-
ing these compounds including copper-free cycloaddition (CFC)
nal alkyne in the presence of copper catalyst.
Applying these
systems as a support on which to anchor another metal usually
via a linker is time-consuming and catalyst preparation becomes
lengthy and complicated. In 2012, Li and co-workers demonstrated
that magnetic CuFe O nanoparticles were inactive for such cyclo-
2
4
[13]
strategies, but their regioselectivity and/or rate of the reaction
is low. In some cases, CFCs need organic solvents and longer reac-
addition because copper is in the form of Cu(ΙΙ). Their observations
continued by adding sodium ascorbate to CuFe O nanoparticles.
2 4
[14]
tion times. It must be noted that all of the CFCs that have been
developed until now are in the field of chemical biology and poly-
[15]
mer chemistry
except in cases where CFCs use highly active
arynes formed through fluoride-promoted ortho-elimination of
*
Correspondence to: Abdol R. Hajipour, Pharmaceutical Research Laboratory,
Department of Chemistry, Isfahan University of Technology, Isfahan 84156,
Islamic Republic of Iran. Email: haji@cc.iut.ac.ir; arhajipour@wisc.edu
[
16]
o-(trimethylsilyl)aryl triflates. So, they are not performed for cy-
cloaddition of azides and terminal acetylenes unless in more strin-
gent requirements. Therefore, CuAAC is still the preferred
[17–19]
a Pharmaceutical Research Laboratory, Department of Chemistry, Isfahan
University of Technology, Isfahan 84156, Islamic Republic of Iran
choice.
Various types of copper catalysts have been investi-
gated for this cycloaddition. Most of them involve the use of metal
[
20,21]
salts in the presence of ligands
dium ascorbate,
or in situ reduction of Cu by so-
b Department of Neuroscience, University of Wisconsin, Medical School, 1300
University Avenue, Madison, WI, 53706-1532, USA
[
22,23]
but some of these procedures suffer from lack
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.

Hajipour A. R., Karimzadeh M., Fakhari F. and Karimi H.
In such conditions, the reaction gave good yields, but they showed
that no solid material could be obtained after performing the reac-
tion. So, they concluded that the cycloaddition proceeds through a
show fair yields of 1,4-disubstituted 1,2,3-triazole derivatives in
the presence of air and in the absence of additives such as bases
and ligands. All of the aryl azides (Table 1, entries 1, 2, 4, 9 and
10) and even naphthyl azide (Table 1, entry 8) except 1-azido-4-
nitrobenzene (Table 1, entry 3) react well with phenylacetylene,
affording the 1,4-disubstituted 1,2,3-triazoles in fair yields. Alkyl
azides are also highly reactive under these conditions (Table 1, en-
tries 5, 6 and 7). The three-component reaction of aryl halide, so-
dium azide and phenylacetylene fails to give the corresponding
1,4-disubstituted 1,2,3-triazoles. It should be regarded that the cou-
pling of aryl halides with sodium azide can be done at higher
[
28]
homogeneous mechanism. In an effort to simplify these proce-
[
29]
dures, we use a simple, inexpensive and heterogeneous CuFeO
catalyst rather than a homogeneous mixture of CuFe and so-
dium ascorbate for such cycloaddition. Antiviral and antibacterial
2
2 4
O
[30]
properties of the catalyst were studied by Hua and co-workers.
High stability of the catalyst even in acidic conditions compared
[
31]
to other copper(Ι) catalysts such as Cu O makes it a unique cat-
2
alyst for copper-catalyzed reactions.
Therefore, in continuation of our researches to introduce efficient
temperatures. Also, special solvents are required to promote such
[32,33]
[33]
and green catalysts,
we report an efficient, convenient and
cross-coupling based on our previous study.
In addition, we
mild procedure for cycloaddition of phenylacetylene and aryl
azides using water as a solvent at room temperature. This method-
ology allows the synthesis a wide variety of 1,2,3-triazoles.
tested the three-component reaction of benzyl chlorides, sodium
azide and phenylacetylene. Progress of the reaction was followed
by TLC and no product is obtained after 2 h. Finally, in order to ex-
amine the reusability of the catalyst, spent CuFeO was easily recov-
2
ered from the reaction media and re-used. For recycling, after the
first use, the catalyst was separated from the reaction mixture by
centrifugation, washed several times with different solvents and fi-
Results and discussion
nally dried at 110 °C for 2 h. The regenerated CuFeO was used for
For optimizing the reaction, various reaction conditions were tested
by considering the reaction between phenylacetylene (1) and phe-
nyl azide (2) as starting materials (Scheme 1).
At first, a mixture of 1 and 2 (1 mmol and 1.2 mmol) in water was
stirred at room temperature in the presence of tetrabutylammonium
bromide (TBAB; 0.1 g per mole of phenylacetylene) as phase transfer
catalyst and the progress of the reaction was monitored by TLC. To
2
cycloaddition of 1 and 2 under the optimum reaction conditions to
study the performance of the re-used catalyst (Table 2). No signifi-
cant changes in yield of obtained 1,2,3-triazole are observed after
regeneration until the third cycle.
Experimental
investigate the role of CuFeO , the reaction was performed without
2
catalyst, with no product being obtained after 2 h. Alonso and co-
workers found that no product was formed when this reaction was
Instruments and reagents
All reagents and materials were obtained commercially from Merck,
and were used as received without further purification or drying.
performed with stoichiometric amount of CuCl
2
, copper powder
O after 2 h. It is noteworthy that they also used Et N as
a base in the reaction. In our experiment, a stoichiometric amount
of CuFeO particles gives superior yields of products when com-
pared with other sources of copper such as copper powder, CuCl
and especially Cu O. Increased catalytic activity of CuFeO is proba-
bly due to the interesting layered-oxide structure of this compound
[34]
and Cu
2
3
1
The HNMR spectra were recorded with a Bruker AV400 spectrom-
1
eter. H NMR chemical shifts are reported in ppm relative to the re-
2
sidual proton signal of the NMR solvents. Coupling constants (J) are
reported in Hz. Powder X-ray diffraction patterns were recorded
using a Cu Kα radiation source with an XD-3 A diffractometer. Mor-
phology of the particles was obtained using a Cambridge Oxford
2
2
2
[35]
which is called delafossite and has an isotypic crystal structure.
When the amount of CuFeO is reduced to 30 mol%, the yields of
7060 scanning electron microscope connected to a four-quadrant
2
backscattered electron detector. The samples were dusted on
double-sided carbon tape placed on a metal stub and coated with
a layer of gold to minimize charging effects. A high-resolution
products are not affected, but with a further decrease of the catalyst
amount, lower yields are obtained and the reaction needs a longer
time. According to these results, we considered that the reaction
2
condition with 30 mol% of CuFeO is the most appropriate. Ratio
of 1 to 2 was also optimized. An excess amount of 2 (1.2) is generally
required to achieve the best results of coupling. Thus, the optimiza-
tion was performed with this ratio. We did not try to test reactions in
other solvents due to the excellent results obtained with water as a
green solvent. Thus, considering the operational simplicity and cost,
water (as a solvent) with 30 mol% of cheap and highly recyclable
Table 1. Scope of reaction of phenylacetylene with aryl azides
a
Entry
R
Time (h)
M.p. (°C)
Yield (%)
CuFeO at room temperature was selected as optimum.
To study the scope and generality of the method, various sub-
strates were used. We studied the reactivity of various azides with
2
1
2
3
4
5
6
7
8
9
Ph
4
4
170–172
197–200
160–163
225–227
102–104
126–128
150–152
199–201
159–161
172–175
90
83
45
85
85
92
78
80
90
82
m-O
p-O
p-H COCPh
2
NPh
2
NPh
24
12
4
1. It should be mentioned that under the optimized reaction condi-
3
tions, only one regioisomer (1,4-disubstituted triazole) was ob-
tained and all of the reactions are completed in 24 h. All reactions
Acetic acid ethyl ester
Bz
4
p-O
1-Naphthyl
p-H CPh
p-NCPh
2
NBz
12
12
12
12
3
10
a
Melting points of products.
Scheme 1. Reaction of phenylacetylene (1) with phenyl azide (2)
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. (2016)

CuFeO catalyzes click reaction
2
a
Table 2. Reusability of catalyst under optimum reaction conditions
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We have applied simple, cost–effective, environmentally benign
and recyclable CuFeO as a catalyst with antiviral and antibacterial
2
properties to the azide–alkyne cycloaddition. This catalyst removes
the requirement for inert atmosphere, toxic reagents and high
temperatures.
Supporting information
Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web site.
Acknowledgements
Figure 1S. XRD pattern of CuFeO
Figure 2S. SEM images of CuFeO
2
particles.
2
particles.
We gratefully acknowledge the funding support received for this
project from the Isfahan University of Technology (IUT), IR Iran. Fur-
ther financial support from the Center of Excellence in Sensor and
Green Chemistry Research (IUT) is gratefully acknowledged.
Figure 3S. FT-IR spectrum of CuFeO
Figure 4S. EDX spectra of CuFeO particles.
Table 1S. EDX data of CuFeO particles.
2
particles.
2
2
Appl. Organometal. Chem. (2016)
Copyright © 2016 John Wiley & Sons, Ltd.
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