A sustainable approach for efficient one-pot synthesis of 1-aryl 1,2,3-triazoles using copper iodide supported on 3-thionicotinyl-urea-modified magnetic nanoparticles in DES

Article abstract of DOI:10.1002/aoc.6255

An efficient and retrievable copper(I) catalyst was synthesized by immobilizing of copper iodide on 3-thionicotinyl-urea-modified magnetic nanoparticles and characterized using a variety of analysis techniques. The catalytic activity of these nanoparticle

Full text of DOI:10.1002/aoc.6255

Received: 20 October 2020
DOI: 10.1002/aoc.6255
Revised: 21 March 2021
Accepted: 22 March 2021
F U L L P A P E R
A sustainable approach for efficient one-pot synthesis of
1-aryl 1,2,3-triazoles using copper iodide supported on
3-thionicotinyl-urea-modified magnetic nanoparticles
in DES
Sogand Mirshafiee
| Arefe Salamatmanesh
| Akbar Heydari
Chemistry Department, Tarbiat Modares
University, Tehran, Iran
An efficient and retrievable copper(I) catalyst was synthesized by immobilizing
of copper iodide on 3-thionicotinyl-urea-modified magnetic nanoparticles and
characterized using a variety of analysis techniques. The catalytic activity of
these nanoparticles was investigated in the one-pot three-component reaction
of aryl halides, sodium azide, and terminal alkynes using choline chloride/
PEG deep eutectic mixture as a green and recoverable solvent. The PEGylated
deep eutectic solvent (DES), due to its favorable polarity and solubility, can
make an effective association of polar and non-polar reactants during the
reaction, thereby accelerating the catalysis process. An array of 1-aryl
1,2,3-triazoles were obtained in good to excellent yields. The catalyst system
can be readily recovered and reused at least five times with no appreciable loss
of its activity.
Correspondence
Akbar Heydari, Chemistry Department,
Tarbiat Modares University, P.O. Box
14155-4838, Tehran, Iran.
Email: heydar_a@modares.ac.ir
Funding information
Tarbiat Modares University
K E Y W O R D S
1-aryl 1,2,3-triazoles, 3-thionicotinyl-urea-modified magnetic nanoparticles, copper(I) catalyst,
deep eutectic solvent
1 | INTRODUCTION
synthesis of 1,2,3-triazoles has gained prominent atten-
tion.[9] 1,3-Dipolar cycloaddition reaction of azides with
1,2,3-Triazoles, as a significant class of nitrogen hetero-
cyclic compounds, have found widespread applications
in chemical, medicinal, pharmaceutical, biological and
material sciences.[1] They exhibit activities such as anti-
cancer,[2] anti-allergic,[3] anti-HIV,[4] anti-bacterial,[5]
and anti-fungal.[6] Furthermore, they are present in
agrochemicals and have also used in the synthesis of
dyes, corrosion inhibitors, and photo stabilizers.[7] The
high stability and tolerance of these nitrogen heterocy-
clic compounds to different conditions and functional
groups deserve them to be utilized as ligand for transi-
tion metals.[8] Due to these versatile applications, the
alkynes is one of the most approved protocols for the
synthesis of triazoles, which was initially put forward
by Huisgen et al. They performed this reaction without
using any metal catalyst; however, this procedure was
associated with high temperature, long reaction times,
low product yields, and lack of selectivity.[10] In
later years, Sharpless and Meldal groups independently
discovered the improved procedure involving Cu(I)-
catalyzed
azide–alkyne
1,3-dipolar
cycloaddition
(CuAAC), popularly known as the click reaction, for
the regioselective synthesis of 1,4-disubstituted
1,2,3-triazoles.[11] Since then, the CuAAC reaction has
been generally considered as the most attractive proto-
Sogand Mirshafiee and Arefe Salamatmanesh contributed equally.
col for the synthesis of 1,2,3-triazole framework.[12]
A
Appl Organomet Chem. 2021;e6255.
wileyonlinelibrary.com/journal/aoc
© 2021 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.6255

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MIRSHAFIEE ET AL.
variety of catalytic systems including Cu(I) salt,
Cu(II) salt/reducing agent (sodium ascorbate), and
copper(II)/copper(0) comproportionation have been
used for click chemistry,[13] although most of the previ-
ous studies on CuAAC reactions are homogeneous
and/or involve 1,3-dipolar cycloaddition of pre-isolated
organic azides with alkynes, thus subjecting to major
limitations such as problematic separation of the cata-
lyst from the reaction medium and/or handling of toxic
and potentially explosive organic azides.[14] In recent
years, to avoid the formation of unstable azides,
one-pot multicomponent click reactions using in situ
generated organic azides from organic halides and
NaN3 have been developed.[15] The homogeneous
catalytic systems have priority in terms of activity and
selectivity over heterogeneous catalysts. However, from
the standpoint of sustainable chemistry, the use of
heterogeneous catalysts is highly desirable because of
their recoverability and reusability.[16] In this regard, a
large number of supported copper catalysts have been
reported for the synthesis of 1,4-disubstituted
1,2,3-triazoles. They are typically produced by immobili-
zation of copper species on various solid supports such
as alumina,[15] silica,[17] zeolite,[18] graphene,[19] iron
oxide,[20] and polymers.[21] Among them, magnetic iron
oxide nanoparticles have received a remarkable atten-
tion for use in catalytic reactions, because of their high
catalytic activity and easy separation.[22] Recently,
various heterogeneous copper catalytic systems for the
synthesis of 1,4-disubstituted 1,2,3-triazoles from unsta-
ble aryl azides and terminal alkynes have been
reported,[19,23] whereas there have been few reports on
one-pot multicomponent synthesis of 1,2,3-triazoles
from sodium azide, alkynes, and aryl halides as the
azide precursors, which most of them have used homo-
geneous copper catalysts.[24] Therefore, it might be
desirable to develop new methods for the regioselective
synthesis of triazoles using effective and recyclable
catalytic systems. With this in mind and following our
interest in the use of sustainable solvents and catalyst
recycling, we decided to study the application of a
copper-incorporated magnetic nanocatalyst for the one-
pot azidation/click reaction of aryl halides in PEGylated
DES as a green and sustainable reaction medium. DESs
are mixtures formed from Lewis or Brønsted acids and
bases, which are able to self-associate via reciprocal
hydrogen-bond interactions. Therefore, eutectic mix-
tures have a melting point lower than those of the
individual components.[25] In recent years, the applica-
tion of DESs in the field of metal-catalyzed organic
reactions has attracted considerable attention.[26]
biodegradable material, which has been known as a salt
component in deep eutectic solvents. In continuation
of our research on the development of efficient and
environmentally benign approach and in the line of our
very recent work,[27] herein, we report the synthesis of
silica coated magnetite nanoparticles modified with
1-propyl-3-thionicotinyl-urea as an effective ligand
followed by decoration with copper iodide nanoparticles
(MNPs@ThNU-CuI). After the characterization of the
prepared nanocatalyst, we applied it to efficiently
synthesize 1,4-disubstituted 1,2,3-triazoles through the
one-pot three-component reaction of terminal alkynes
with in situ generated organic azides from aryl iodides
and aryl bromides in choline chloride/PEG
200 (1:4) DES.
2 | EXPERIMENTAL SECTION
2.1 | General remarks
All materials were purchased from Merck and Aldrich
companies and used without any further purification.
The reaction was precisely monitored by thin-layer
chromatography (TLC). Preparative TLC was performed
on glass plates coated with silica gel 60 F-254 (0.2 mm).
Infrared spectra (IR) were recorded using the KBr pellet
method on a NICOLET FT-IR 100 spectrometer. The
X-ray diffraction (XRD) patterns were obtained at room
temperature using a Philips PW1730 diffractometer with
Co Kα radiation (α = 1.54056 Å), 40 kV voltage, 30 mA
current, and scanning rate of 0.05ꢀ/s over the range of
10–80ꢀ for 2θ. Scanning electron microscopy (SEM)
analysis was utilized to study the morphology and size
of the catalyst using a TESCAN MIRA III FE-SEM
instrument. Energy-dispersive X-ray spectroscopy (EDX)
analysis was performed in conjunction with SEM to
study the elemental composition of the catalyst. Trans-
mission electron microscopy (TEM) analysis was carried
out at 200 kV (Philips model CM300). Thermal gravi-
metric analysis (TGA) was recorded using a thermal
analyzer (SDT Q600) with a heating rate of 20ꢀC min−1
over a temperature range of 25–800ꢀC under flowing
argon. Magnetic saturation of the nanoparticles was
obtained using a vibrating magnetometer/alternating
gradient force magnetometer (VSM/AGFM, MDK Co.,
Iran). Inductively coupled plasma (ICP) technique was
performed using a Varlan Vista-Pro ICP-OE spectrome-
1
ter. H NMR and 13C NMR spectra were recorded on a
Bruker Avance (DRX 300 and 500 MHz) in pure deuter-
ated CDCl3 solvent with tetramethylsilane (TMS) as an
internal standard.
Choline chloride is
a
green, inexpensive, and

MIRSHAFIEE ET AL.
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2.2 | Preparation of copper iodide
immobilized on 3-thionicotinyl-urea-
modified magnetic nanoparticles
magnetically separated and washed several times with
water and ethanol before being dried under vacuum at
60ꢀC for 8 h.
2.2.1 | Preparation of silica-coated
magnetite nanoparticles
2.3 | Preparation of DESs
Magnetite nanoparticles were prepared by alkaline
hydrolysis of iron(II) chloride and iron(III) chloride
(molar ratio of 1:2) in an aqueous medium according to
the previously reported procedure.[22a] In order to synthe-
size silica-coated magnetite nanoparticles, Fe3O4
nanoparticles (1.0 g) were dispersed in 80-ml 4:1 ethanol/
water solution, then 1.5 ml of concentrated aqueous
ammonia (28 wt%) was added to the suspension until
the pH was raised to 10. Subsequently, tetraethyl
orthosilicate (TEOS, 1 ml) was added to the reaction
vessel, and the mixture was vigorously stirred at 40ꢀC for
18 h. The silica-coated magnetite nanoparticles were col-
lected magnetically and washed several times with water
and ethanol before being oven-dried at 60ꢀC for 8 h.
DESs were prepared according to the methods reported
previously.[24b,28] In order to synthesize DES, a certain
molar ratio (4: 1 or 2: 1) of HBD (PEG 200 or glycerol)
and HBA (choline chloride) was mixed and then heated
at 80ꢀC under continuous stirring until a homogeneous
and transparent liquid was formed. The obtained DESs
were used in reactions without any purification.
2.4 | General procedure for the synthesis
of 1-aryl 1,2,3-triazoles
A mixture of aryl halides (1.0 mmol), alkynes (1.0 mmol),
sodium azide (1.2 mmol), and catalyst (30 mg) was stirred
at 90ꢀC in choline chloride/PEG 200 (2 ml, 1:4) for the
appropriate time until the reaction was completed as
judged by TLC. After completion of the reaction, the
reaction medium was diluted by adding hot water (3 ml).
The resulting mixture was magnetically decanted,
followed by separation of the catalyst. The aqueous phase
was extracted with EtOAc (2 × 15 ml), and then the com-
bined organic phases were concentrated. Finally, the
pure products were obtained using chromatography on
silica gel. After the catalyst was separated, it was washed
with ethanol (3 × 10 ml) and dried under vacuum for
reuse under the same conditions.
2.2.2 | Synthesis of 3-thionicotinyl-N-
3-(triethoxysilyl) propyl-urea (1)
A
mixture
of
triethoxy(3-isocyanatopropyl)silane
(TESPIC) (5 mmol) and thionicotinamide (5 mmol) was
mixed in 40 ml of dry THF and heated at 60ꢀC for 24 h
under argon atmosphere. After this period, the solvent
was removed using rotatory evaporation. The obtained
yellow solid was washed with dry diethyl ether, followed
by drying at 40ꢀC under vacuum for 2 h to provide
material B.
3 | RESULTS AND DISCUSSION
3.1 | Catalyst preparation
2.2.3 | Preparation of 1-propyl-
3-thionicotinyl-urea immobilized on MNPs
(MNPs@ThNU) (2) and MNPs@ThNU-CuI
(3)
The process for the synthesis of the MNPs@ThNU-CuI
catalyst is schematically depicted in Scheme 1. Silica-
coated magnetite nanoparticles (Fe3O4@SiO2) were
prepared according to the reported procedures. At first,
Fe3O4 nanoparticles were prepared by the conventional
co-precipitation method. Then, to improve the chemical
stability of Fe3O4 nanoparticles, the surface of magnetic
Fe3O4 was modified with a thin layer of silica. On
the other hand, the reaction between triethoxy
(3-isocyanatopropyl)silane and thionicotinamide resulted
in the formation of the material 1. The final structure of
the catalyst (3) was obtained via the reaction of MNPs
with material 1 and subsequent treatment with copper
iodide.
The functionalized magnetic nanoparticles (MNPs@ThNU)
were prepared by treating about 1.0 g of Fe3O4@SiO2 in dry
toluene (50 ml) with 3 mmol of precursor 1. The resulting
suspension was then refluxed for 36 h under argon atmo-
sphere. The resulting nanoparticles were separated magneti-
cally and washed several times with toluene, ethanol, and
diethyl ether, followed by drying at 60ꢀC under vacuum for
8 h to provide MNPs@ThNU. In order to the preparation
of MNPs@ThNU-CuI, the resultant nanoparticles
(MNPs@ThNU) (1.0 g) and CuI (0.09 g, 0.5 mmol) were
suspended in 25 ml of ethanol and refluxed for 6 h under
argon atmosphere. The resulting nanoparticles were then

4 of 14
MIRSHAFIEE ET AL.
3.2 | Catalyst characterization
and 3337 cm−1 (stretching vibrations of N–H) in FT-IR
spectrum of material B (Figure 1b). Also, the peaks posi-
tioned at 2967 and 3042 cm−1 are assigned to C–H
stretching vibrations. The characteristic peaks appearing
at 590 and 1097 cm−1 are attributed to Fe–O and Si–O
stretching vibrations of Fe3O4 and SiO2, respectively
(Figure 1d–f ). After the immobilization of material B on
the surface of the magnetic nanoparticles, the mentioned
absorption bands for material B, belonging to C=O and
C=C vibrations, were negatively shifted and appeared at
1632 and 1566 cm−1, respectively, in the spectrum of
MNPs@ThNU (Figure 1e). These results verify the suc-
cessful grafting of the organic group on the surface of
Fe3O4@SiO2. After supporting of CuI nanoparticles on
the surface of the modified magnetic nanoparticles
The catalyst was fully characterized using various micro-
scopic and spectroscopic techniques such as FT-IR, XRD,
FE-SEM, EDX, TEM, TGA, VSM, and ICP.
FT-IR spectra of triethoxy(3-isocyanatopropyl)silane,
material B, Fe3O4, Fe3O4@SiO2, MNPs@ThNU, and
MNPs@ThNU-CuI are shown in Figure 1a–f. As shown
in Figure 1a, the sharp band appearing at 2272 cm−1 is
attributed to the NCO group. After the addition of
thionicotinamide to isocyanate linker, the isocyanate
peak at 2272 cm−1 disappeared, as shown in Figure 1b.
Simultaneously, new bands appeared at 1649 cm−1 (C=O
stretching vibration), 1579 cm−1 (C=C stretching vibra-
tion), 1417 cm−1 (C=C stretching vibration), and 3237
SCHEME 1 Preparation of MNPs@ThNU-CuI
FIGURE 1 The FT-IR spectra of triethoxy
(3-isocyanatopropyl)silane (a), material B (b),
Fe3O4 (c), Fe3O4@SiO2 (d), MNPs@ThNU (e),
and MNPs@ThNU-CuI (f)

MIRSHAFIEE ET AL.
5 of 14
(MNPs@ThNU), it was observed a negative shift in
absorption frequency of C=O, and its band was appeared
at 1624 cm−1. Further, a slight decrease was observed in
the intensity of the absorption peak corresponding to the
stretching vibration of C=O bond in the spectrum of
MNPs@ThNU-CuI indicating coordination of ligand with
copper iodide via C=S and C=O sites (Figure 1f ).
Although the characteristic weak peak at 670 cm−1 for
copper iodide did not appear because of the overlapping
of the bands around 600–700 cm−1, the presence of cop-
per iodide in the structure of MNPs@ThNU-CuI can be
confirmed by the above-mentioned changes as well as
XRD and elemental analyses.[29]
To determine the crystalline structure of the magnetic
nanoparticles, X-ray diffraction (XRD) analysis was per-
formed (Figure 2a–c). As shown in XRD patterns of pure
Fe3O4 (Figure 2a), Fe3O4@SiO2 (Figure 2b), and
MNPs@ThNU-CuI (Figure 2c), characteristic peaks at 2θ
values of 35.27ꢀ, 41.73ꢀ, 50.97ꢀ, 63.47ꢀ, 67.87ꢀ, and 74.73ꢀ
corresponding to diffraction lines (220), (311), (400),
(422), (511), and (440), respectively, represent well the
crystallinity of the present cubic magnetite in good agree-
ment with the reported values (JCPDS card no. 19-0629).
As presented in Figure 2b,c, the broad peaks in the 2θ
range from 21ꢀ to 30ꢀ are assigned to the silica phase,
indicating the core-shell structure of the catalyst. In XRD
pattern of MNPs@ThNU-CuI, the diffraction peaks
located at 2θ values of 25.5ꢀ, 29.5ꢀ, 42.2ꢀ, 50.0ꢀ, 61.2ꢀ,
67.45ꢀ, and 77.20ꢀ can be ascribed to cubic copper iodide
(JCPDS card no. 01–076-0207), which demonstrate the
immobilization of copper iodide on MNPs@ThNU
(Figure 2c). In addition, the appearance of characteristic
peaks of Fe3O4@SiO2 shows that the crystalline structure
of magnetic nanoparticles is maintained after each
modification.[30]
The morphological and structural features of the pre-
pared nanoparticles were investigated using the SEM and
TEM techniques (Figure 3a,b). The SEM image (Figure 3a)
shows that the MNPs@ThNU-CuI catalyst has a nearly
spherical morphology with a mean diameter of 43 nm.
Also, as shown in the TEM image of the catalyst, the
dark-colored spots can relate to Fe3O4 nanoparticles, and
the colorless regions can represent the silica shell. The
appearance of pale spots in the silica region can indicate
the presence of copper iodide nanoparticles on the
surface of the functionalized silica-coated magnetite
nanoparticles (Figure 3b). SEM and TEM images show
that the prepared nanoparticles are uniform in shape
and size.
The elemental composition of the obtained
nanomaterials was evaluated using EDX analysis. As
shown in Figure 3c, EDX pattern obviously approved the
presence of the expected elements in the structure of
MNPs@ThNU-CuI, namely, carbon, nitrogen, oxygen,
silicon, sulfur, iron, copper, and iodine with wt% of
14.46, 7.11, 40.07, 18.44, 0.87, 14.63, 1.78, and 2.64,
respectively.
The thermal behaviors of pure Fe3O4 nanoparticles
and MNPs@ThNU- CuI were characterized by ther-
mogravimetric analysis (Figure 4a,b). TGA curves of both
Fe3O4 nanoparticles and MNPs@ThNU-CuI show a
slight weight loss at temperatures below 150ꢀC, which
can be attributed to the physically adsorbed water. The
TGA curve of MNPs@ThNU-CuI shows also the other
two weight loss steps (Figure 4b). Over the range of
200–800ꢀC, the second and third steps of weight loss
FIGURE 2 The X-ray diffraction patterns of
Fe3O4 (a), Fe3O4@SiO2 (b), and MNPs@ThNU-
CuI (c)

6 of 14
MIRSHAFIEE ET AL.
FIGURE 3 SEM (a), TEM (b), and EDX (c) analysis of the catalyst
should correspond to the decomposition of organic moie-
ties (weight loss: 11.78 wt%) and the sublimation of
iodine, respectively. These results prove the attachment
of 1-propyl-3-thionicotinyl-urea moiety onto the surface
of MNPs (0.52 mmol g-1) and also determine the copper
content in the catalyst structure (0.3 mmol g−1). Further-
more, the loading amount of copper iodide species was
evaluated to be 0.32 mmol g−1 using ICP-OES
analysis.[21]
To assess the magnetic behaviors of the pure Fe3O4,
Fe3O4@SiO2, and MNPs@ThNU-CuI, the magnetic hys-
teresis measurements were carried out in an applied
magnetic field sweeping from −10 K to 10 K Oe at room
temperature using a vibrating sample magnetometer
(Figure 5a,b). The curves showed zero coercivity and zero
FIGURE 4 TGA curves of Fe3O4 (a) and MNPs@ThNU-
CuI (b)

MIRSHAFIEE ET AL.
7 of 14
FIGURE 5 Magnetization curves of Fe3O4
(a) and MNPs@ThNU-CuI (b)
remnants magnetization, indicating the super-
paramagnetic behavior of the nanoparticles. The satura-
tion magnetization (Ms) values are found to be 26.82 and
MNPs@ThNU-CuI, which are much lower than that of
pure Fe3O4 (Ms value: 63.29 emu g−1). This can be
ascribed to the silica coating of magnetite nanoparticles
as well as the presence of organometallic species in the
structure of MNPs@ThNU-CuI. Nevertheless, the
nanoparticles can be easily separated from the reaction
mixture by applying an external magnetic field.
3.3 | Catalyst activity in the synthesis of
1-aryl 1,2,3-triazoles
The catalytic activity of MNPs@ThNU-CuI was investi-
gated for the synthesis of 1,4-disubstituted-1,2,3-triazoles
through the one-pot three-component reactions between
aryl halides, sodium azide, and terminal alkynes. For our
SCHEME 2 The model reaction between iodobenzene, sodium
azide, and phenylacetylene
TABLE 1 Optimization of reaction conditions for one-pot synthesis of 1,4-disubstituted 1,2,3-triazolesa
Entry
Catalyst (mg)
Cu (mol%)
0.9
Solvent
Temp. (ꢀC)
Time (h)
Yieldb (%)
1
30
30
30
30
30
30
30
30
30
20
40
30c
0.0
EtOH
Reflux
90
8
83
2
0.9
DMSO
8
88
3
0.9
DMF
90
8
67
4
0.9
Choline azide
ChCl/gly (1:2)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
ChCl/PEG (1:4)
90
8
86
5
0.9
90
4
90
6
0.9
90
4
94
7
0.9
105
75
4
92
8
0.9
8
89
9
0.9
40
14
6
65
10
11
12
13
0.6
90
86
1.3
90
4
93
0.0
90
24
24
N.R
N.R
0.0
100
aReaction conditions: phenylacetylene (1.0 mmol), iodobenzene (1.0 mmol), sodium azide (1.2 mmol), and different values of MNPs@ThNU-CuI in solvent
(2.0 ml).
bIsolated yields.
c30 mg of Fe3O4 nanoparticles.

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MIRSHAFIEE ET AL.
TABLE 2 Multicomponent synthesis of 1,4-disubstituted 1,2,3-triazoles from aryl halides, terminal alkynes, and sodium azide using
MNPs@ThNU-CuIa
Entry
Aryl halide
Alkyne
Product
Time (h)
Yieldb (%)
1
4
94
2
3
4
4
5
5
92
94
88
5
6
6
6
83c
78c
7
6
87c

MIRSHAFIEE ET AL.
9 of 14
TABLE 2 (Continued)
Entry
Aryl halide
Alkyne
Product
Time (h)
Yieldb (%)
8
4
92
9
6
5
86
88
10
11
12
5
7
91
90c
13
7
83c
(Continues)

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MIRSHAFIEE ET AL.
TABLE 2 (Continued)
Entry
Aryl halide
Alkyne
Product
Time (h)
Yieldb (%)
14
8
86c
15
10
69c
16
17
10
88c
8
75c
aReaction conditions: alkyne (1.0 mmol), aryl halide (1.0 mmol), sodium azide (1.2 mmol), and 30 mg of MNPs@ThNU-CuI in choline chloride/PEG (1:4)
(2.0 ml). 90ꢀC.
bIsolated yields.
cThe reactions were performed at 95ꢀC.
initial screening experiments, a model reaction between
iodobenzene, sodium azide, and phenylacetylene was
chosen (Scheme 2).
200 (1:4) was found to be the best solvent in terms of time
and product yield (Table 1, entry 6). To investigate the
effect of temperature on the reaction efficiency, the model
reaction was performed at temperatures of 40ꢀ, 75ꢀ, 90ꢀ,
and 105ꢀC (Table 1, entries 6–9). The optimum tempera-
ture was found to be 90ꢀC. Subsequently, we performed
the reaction with different amounts of the catalyst rang-
ing from 20 to 40 mg (0.64 to 1.28 mol% Cu) under ideal
conditions (Table 1, entries 6, 10, and 11). When the
reaction was performed in the presence of pure Fe3O4 in
choline chloride/PEG 200 (1:4) at 90ꢀC, we observed no
desired product after 24 h (Table 1, entry 12). Also, in the
absence of the catalyst, the reaction was not carried out
There has always been a marked dependence of the
reaction efficiency on the solvent type, reaction tempera-
ture, and amount of catalyst. The results are shown in
Table 1. In order to inspect the effect of different solvents,
the model reaction was performed in the presence of vari-
ous solvents, as seen in Table 1, entries 1–6. The results
showed that the reactions proceeded in EtOH, DMSO,
DMF, choline azide, choline chloride/glycerol (1:2), and
choline chloride/PEG 200 with good to excellent yields.
Among the examined solvents, choline chloride/PEG

MIRSHAFIEE ET AL.
11 of 14
even after a long reaction time (24 h) at high temperature
(100ꢀC) (Table 1, entry 13). According to the obtained
results, the highest efficiency (yield: 94%) was obtained
by carrying out the reaction using 30 mg (0.96 mol%) of
MNPs@ThNU-CuI at 90ꢀC in choline chloride/PEG
200 (1:4) (Table 1, entry 6).
supported copper(I) catalyst leading to a π-complex. In
the next step, the azide reagent, which has been gener-
ated in situ from reaction of sodium azide and the copper
catalyst-activated aryl halide assisted by DES, through its
lone pair attacks to the central metal of corresponding
copper-alkylidine complex resulting in a six-membered
metallacycle intermediate. Finally, ring contraction to a
copper(I) triazolide complex and subsequent protonolysis
affords the desired product as well as regeneration of
copper(I) catalyst.
In order to investigate the stability and reusability of
the catalyst, the model reaction between iodobenzene,
sodium azide, and phenylacetylene was carried out under
optimum conditions. In each cycle, after completion of
the reaction, the nanocatalyst was easily removed from
the reaction mixture using an external magnet, washed
with water and ethanol for several times and then dried
under vacuum at 70ꢀC to reuse in the next cycle. As
shown in Figure 6, MNPs@ThNU-CuI catalyst preserves
To explore the generality of this method, we extended
our studies to a variety of aryl halides (aryl iodides and
aryl bromides) and alkynes. According to the results
shown in Table 2, the reactions of phenylacetylene,
4-methyl phenylacetylene, or 2-pyridylacetylene with
sodium azide and aryl iodides bearing electron-rich and
electron-deficient groups in a 1:1.2:1 molar ratio were
carried out using MNPs@ThNU-CuI (0.96 mol%) at
90–95ꢀC in choline chloride/PEG 200 (1:4), and the
corresponding 1,4-disubstituted 1,2,3-triazoles were
obtained in good to excellent yields (Table 2, entries
1–10). Not surprisingly, when aryl bromides were used as
one of the substrates, a noticeable decrease of the yields
was observed (Table 2, entries 11–15). The aliphatic
alkyne (propargyl alcohol) as well as aromatic alkynes
reacted with iodobenzene and sodium azide by this pro-
cedure. However, bromobenzene afforded the same prod-
uct in a lower yield compared to more reactive aryl
iodide (Table 2, entries 10 and 16).
Based on the literature review and our observations, a
tentative mechanism for the synthesis of 1,2,3-triazoles
has been proposed (Scheme 3). Choline chloride/PEG
DES, due to its favorable polarity and solubility, is able to
make an effective association of polar and non-polar
reactants during the reaction, thus accelerating the catal-
ysis process. First, it is expected that the reaction begins
with the coordination of terminal alkyne to MNPs-
a
reasonable performance in the synthesis of
1,4-disubstituted-1,2,3-triazole after at least five cycles
without any appreciable loss of its activity (Figure 6a).
We also measured the amount of leached copper from
the heterogeneous metal catalyst during the course of the
reaction by ICP-OES analysis. For this purpose, the cata-
lyst was magnetically removed at half of the reaction
time, and then the experiment was continued in absence
of the catalyst for another 8 h under the same reaction
conditions. It was observed no further conversion in
residual mixture. The ICP-OES elemental analysis of the
filtrate showed the negligible amounts of copper leaching
(0.02%) after the first reaction. Moreover, the copper
loading amount in the fresh and the recycled catalyst
SCHEME 3 Proposed
mechanism for synthesis of
1,4-disubstituted-1,2,3-triazole

12 of 14
MIRSHAFIEE ET AL.
FIGURE 6 Recyclability of the nanocatalyst (a) and SEM image of the recovered catalyst (b)
TABLE 3 Comparison of the catalytic efficacy of MNPs@ThNU-CuI with the previously reported catalytic systems for the synthesis of
1,4-diphenyl-1H-1,2,3-triazole
Time
(h)
Temp.
(ꢀC)
Yielda
(%)
Entry Catalyst (mol% Cu)
Reaction conditions
Ref.
1
CuI (10)
Iodobenzene, phenylacetylene, NaN3,
N,N0-dimethylethylenediamine
(20 mol%), sodium ascorbate
15
50
87
Potratz et al.[31]
(10 mol%), ethanol-water (7:3)
2
3
4
5
6
7
CuI (10)
Iodobenzene, phenylacetylene, NaN3,
tetrabutylammonium hydroxide/
L-proline, (20 mol%), [BMIM]BF4
10
60
88
73
93
96
93
71
Yan and Wang[24c]
Chen et al.[32]
Porous Cu(0) (5)
CuI (20)
1-4-Iodoanisole, NaN3, L-proline (20 mol
%), iPr2NH (20 mol%), DMSO
2-Phenylacetylene
24/34
2.5/0.5
5
80/50
95/r.t.
75
1-Iodobenzene, NaN3, DBU (30 mol%),
DMSO
2-Phenylacetylene
Jiang et al.[24a]
CuI (10)
Iodobenzene, phenylacetylene, NaN3,
N,N-dimethyl-ethylenediamine
(20 mol%), ChCl/glycerol (1:2)
Kafle and Handy[24b]
Hosseini et al.[33]
Rizzi et al.[34]
CuI@SBA-15/PrEn/
ImPF6 (4.1)
1-Iodobenzene, NaN3, L-proline (10 mol
%), DMSO/H2O (2:1)
2-Phenylacetylene
8/8
r.t./80
65
CuSO4.5H2O (5)
Iodobenzene, phenylacetylene, NaN3,
L-proline (20 mol%), sodium ascorbate
(10 mol%), Na2CO3 (20 mol%),
DMSO/H2O (9:1)
24
8
9
Fe3O4@SiO2@AMBI/
Cu (20)
Iodobenzene, phenylacetylene, NaN3,
sodium ascorbate (30 mol%), DMSO/
H2O
2
4
100
90
96
94
Mehdipour and
Khodabakhshi[35]
b
MNPs@ThNU-CuI
(0.9)
Iodobenzene, phenylacetylene, NaN3,
ChCl/PEG (1:4)
-
aIsolated yields.
bThis work.

MIRSHAFIEE ET AL.
13 of 14
(after five times recycling) was checked by ICP analysis,
and it was found that the copper content of the
nanocatalyst has not decreased appreciably after the
reaction.
project administration; resources; software; supervision;
validation; visualization.
CONFLICT OF INTEREST
FE-SEM analysis was also performed for the recov-
ered MNPs@ThNU-CuI catalyst after five cycles. As can
be clearly seen in the SEM image (Figure 6b), the mor-
phology of the catalyst almost has remained constant
even after the fifth cycle.
There are no conflicts of interest to declare.
DATA AVAILABILITY STATEMENT
The data that supports the findings of this study are
available in the supporting information of this article.
To show the merit of the present approach for the
synthesis of 1-aryl 1,2,3-triazoles, the result obtained
using MNPs@ThNU-CuI has been compared with some
of those reported in the literature. As can be seen in
Table 3, the use of MNPs-supported copper(I) catalyst in
PEGylated DES as a sustainable and environmentally
friendly medium has provided a favorable reaction condi-
tion under which the desired product can be obtained in
high yield over short reaction time in the presence of a
lower catalyst loading. Further, both the catalyst and
solvent are able to recover.
ORCID
Sogand Mirshafiee https://orcid.org/0000-0003-0861-
8414
Arefe Salamatmanesh https://orcid.org/0000-0002-
2621-1637
Akbar Heydari https://orcid.org/0000-0003-2399-1401
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sogand mirshafiee: Conceptualization; data curation;
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Salamatmanesh: Conceptualization; data curation;
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Heydari: Conceptualization; data curation; formal analy-
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How to cite this article: Mirshafiee S,
Salamatmanesh A, Heydari A. A sustainable
approach for efficient one-pot synthesis of 1-aryl
1,2,3-triazoles using copper iodide supported on
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