Magnetic nano-Fe3O4@TiO2/Cu2O core-shell composite: An efficient novel catalyst for the regioselective synthesis of 1,2,3-triazoles using a click reaction

Article abstract of DOI:10.1039/c5ra06810j

A magnetic nano-Fe₃O₄@TiO₂/Cu₂O core-shell composite, optimized for the loading amount of Cu₂O, was successfully prepared and fully characterized by analyzing FT-IR, XRD, XPS, FEG-SEM, EDS, and VSM data. The catalytic activity of the nano-Fe₃O₄@TiO₂/Cu₂O core-shell composite was examined in a classical one-pot and three-component reaction of terminal alkynes, benzyl halides, and sodium azide in water that was observed to proceed smoothly and completed in good yields with high regioselectivity. The catalyst was conventionally recovered using an external magnet and was reused in at least five successive runs without an appreciable loss of activity. This journal is

Full text of DOI:10.1039/c5ra06810j

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DOI: 10.1039/C5RA06810J
Cite this DOI: 10.1039/c0xx00000x
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ARTICLE TYPE
Magnetically nano-Fe3O4@TiO2/Cu2O core-shell composite : An efficient
novel catalyst for the regio-selective synthesis of 1,2,3-triazoles : A click
reaction
Firouzeh Nemati,*a Majid M. Heravi,b and Ali Elhampoura
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Magnetic nano-Fe3O4@TiO2/Cu2O core-shell composite, of Cu2O, in various loading, has been
successfully prepared and fully characterized, by analyzing of different obtained data, including
FT-IR, XRD, XPS, FEG-SEM, EDS and VSM. The catalytic activity of nano-Fe3O4@TiO2/Cu2O
core-shell composite was examined in a classical, one pot, and three component reaction of
terminal alkynes, benzyal halides and sodium azide in water and observed, proceeding smoothly
and completed in good yields and high regioselectivity. The catalyst was conventionally
recovered using an external magnet and was reused at least in five successive runs, without
appreciable loss of activity.
Introduction
aggregation affects, their unique properties, associated with
catalytic reactions. To solve this problem, MNPs are frequently,
modified using suitable stabilizing coating materials in order to
prevent irreversible aggregation, retain their nanoscale properties
and preserve their finely dispersed active sites. Many materials
have been explored, being outer shells of iron oxides, such as
polymers,9 silica,10 titanium dioxide,11 zeolites12 and carbon.13
Recently, titanium dioxide have attracted great attention being
employed as a support, due to its unique surface properties, its
high chemical and thermal stability, non-toxicity, high catalytic
activity, as well as its great accessibility and moderate cost. The
appropriate electronic band structure and excellent surface
activity endowed TiO2 with very promising potentials in hydrogen
production, photovoltaic, photocatalysts, lithium-ion batteries,
fuel cells, gas sensors, detoxification, and supercapacitors.14 Thus,
further study on the performance of TiO2-based nanostructures is
still in much demands. Furthermore, the inclusion of Fe3O4 core
into TiO2 nanospheres makes them being easily recoverable by a
magnetic field for further possible effective use.In recent years,
multi component reactions (MCRs) have gained eminence as an
efficient access to assemble molecular complexity with attractive
biological features through the simple and readily available
starting materials in a one-pot operation.15
One of the most important development in the catalyzed-
organic reactions, is the synthesis of novel catalysts or reagents,
being readily available, inexpensive, selective, recyclable and
environmentally benign.1 In this context, nanoparticles find vast
applications due to their high surface to volume ratio and their
unique electronic properties, resulting in high catalytic activity
and tenability.2 Nano catalysts can often be isolated and recovered
through filtration or centrifugation methods. However, it should
be mentioned in spite of several advantages and merits,
experienced in utilization of nano catalysts, the inconvenience and
tedious separation, due to the nano size particles impose, few
limitations to the sustainability of the nanocatalytic strategy in
organic synthesis.3
To circumvent these problems, we contemplated to use an
heterogeneous nanocatalyst which
can be operationally
separated, other than filtration. Magnetite nanoparicles (Fe3O4)
have increasingly attracted interest in the past few years, due to
their unique features, including, low preparation cost, high
thermal and mechanical stability and adaptability for large-scale
production. Furthermore, their paramagnetic nature allows their
simple and efficient separation from the reaction mixture, without
using standard filtration, required in separation of heterogeneous
catalysts. Magnetite nanoparicles (Fe3O4) can be easily separated
from reaction mixture by using just an external magnet.4-7
However, using naked, magnetic nano particles (MNPs) shows a
serious drawback. The naked, magnetic nano particles (MNPs) are
inherently, subjected to aggregation in the reaction mixture,
mainly due to their small inter particle distance, high surface
energy and the existence of van der Waals forces.8 This
Among them, Huisgen 1,3-dipolar cycloaddition, which is
the reaction of a terminal alkyne and alkyl halide and sodium
azide, providing 1,2,3-triazoles, has attracted much attention from
biological and chemical points of view. The 1,2,3-triazole
moieties are widespread in pharmaceutical, agrochemicals, dyes,
corrosion inhibitors, phothostabilizers and phothographic
matereials.16 Since its discovery, the regioselectivity of catalyzed-
Huisgen reaction has been continuously under serious and wide
a Department Of Chemistry, Semnan University, Semnan, Iran, 35131-19111. E-mail: fnemati_1350@yahoo.com; fnemati@semnan.ac.ir.
b Department of Chemistry, School of Science, Alzahra University, Vanak, Tehran, Iran.

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The nano-Fe3O4 particles were prepared in accordance to our
investigations and has attracted enormous attention of organic
chemists, worldwide.17
View Article Online
earlier report.28
DOI: 10.1039/C5RA06810J
Preparation of nano-Fe3O4@TiO2
There has been an ongoing interest to develop homogeneous
and heterogeneous metal catalysis such as CuO–CeO2,18 nano-
Cu,19 Cu/C,20 copper nanoparticles supported on agarose,21 Cu-
MOF,22 Copper immobilized onto the triazole functionalized
magnetic nanoparticle,23 Cu/SiO2,24 ruthenium complex,25
Nano-Fe3O4@TiO2 was synthesized according to
a
previously reported method,31 subjected to modification. The
prepared nanomagnetic Fe3O4 particles were dispersed in a
mixture of solvent 250 mL of absolute ethanol / 90 mL of
acetonitrile. This mixture was sonicated for 15 min, and then 1.5
mL of NH3·H2O solution (25 wt.%) was added. After the
continuous mechanical stirring for 30 min, 3 mL of tetrabutyl
titanate (TBOT), dissolved in 20 mL of absolute ethanol was
added drop-wise to the above suspension, under the continuous
mechanical stirring at 30 °C. The reaction mixture was further
mechanically stirred for 1.5 h to obtain Fe3O4@TiO2 core/shell
nanoparticles. The obtained product was collected by magnetic
separation and washed, three times with absolute ethanol.
26
supported CuBr on graphene oxide/Fe3O4 and Mesoporous
graphitic carbon nitride27 for a regioselective, three-component
reaction of alkyl halides, sodium azide and terminal alkynes.
However, most of the above methods suffer from drawbacks such
as the use of organic solvents, tedious experimental procedure to
separate the catalyst as well as the requirement for reducing agents
and stabilizing ligands. Therefore, there is still much demand to
develop an efficient and well defined heterogeneous catalyst for a
one pot, three component reaction of terminal alkynes, alkyl
halides and sodium azide.
Recently, we have used nano-Fe3O4 as an efficient and easily
separable catalyst in different organic reactions.28 As a part of our
continued interest to multi-component reactions,29 and our efforts
to develop the regioselective synthesis of 1,4-disubstituated 1,2,3-
triazoles, via click reaction,30 herein, we wish to report the
preparation of novel and recyclable catalyst system, composing
of a magnetic Fe3O4 core and TiO2 shell with microctystals of
Cu2O. The Fe3O4@TiO2/Cu2O composite is conveniently
prepared and its structure was fully characterized by XRD, FTIR,
XPS, SEM, TEM, EDX and VSM analysis. The catalytic activity
of this catalyst system was examined in the reaction of phenyl
acetylene, benzyl bromide and sodium azide, in water as a model
reaction, which proceeded smoothly to afford the corresponding,
1,4- substituted 1,2,3-triazole as sole product, regioselectively.
Preparation of nano-Fe3O4@TiO2/ Cu2O core-
shell magnetic composite
Four types of composite with different molar ratio of
Fe3O4@TiO2:Cu2O were synthesized. Nano- Fe3O4@TiO2
(0.036-0.324 g) was dispersed in 80 mL of deionized water. 5 mL
of (0.1 mol/L) CuCl2 solution was added into the aqueous
Fe3O4@TiO2 and sonicated for 15 min. Then, 1.8 mL of (1.0
mol/L) NaOH solution was added drop wise under ultra sonic
radiation. The resulting solution turned into light blue instantly,
indicating the formation of Cu(OH)2. Eventually, 12 mL of (0.1
mol/L) NH2OH.HCl was immediately injected over 5 sec. into the
solution. The solution was kept in the water bath for 1 h and
centrifuged for 3 min .Then the solution was decanted as much as
possible. After the top solution was decanted, the precipitate was
washed with 6 mL of a 1:1 volume ratio of water and ethanol for
three times. The nano-Fe3O4@TiO2/ Cu2O was collected as a
brown solid which can be stored in a tight vessel for several
months without any changes in color and activity.
Experimental
Material and Instruments
Chemical reagents in high purity were purchased from Merck
and Aldrich and were used without further purification. Melting
points were determined in open capillaries using an
Electrothermal 9100 without further corrections.1H NMR and 13
C
Synthesis
procedure
of
1,2,3-triazoles
:General
NMR spectra were recorded using Bruker DRX-400
a
spectrometer at 400 and 100 MHz respectively. FT-IR spectra
were obtained with potassium bromide pellets in the range of 400–
4000 cm-1 using a Shimadzu 8400s spectrometer. The purity of
the compounds, synthesized was monitored by TLC on
commercial aluminum-backed plates of silica gel 60 F254,
visualized , using ultraviolet light. X-ray diffraction (XRD) was
detected by Philips using Cu-Ka radiation of wavelength 1.54Å.
Scanning electron Microscopy, FE-SEM-EDX, analysis was
performed using Tescanvega II XMU Digital Scanning
Microscope. Samples were coated with gold at 10 mA for 2 min
prior to analysis. The magnetic properties were characterized
using a vibrating sample magnetometer (VSM, Lakeshore7407) at
In a round-bottomed flask, an appropriate, alpha-haloketone
(1 mmol) or alkyl halide (1 mmol), terminal alkyne (1 mmol),
sodium azide (1.1 mmol), in water (10 ml) were placed. Then, to
this mixture, nano-Fe3O4@TiO2/Cu2O magnetic composite (0.01
g) was added. The suspension was magnetically stirred under
reflux for the indicated time (Table 3). The progress of the
reaction was monitored by TLC (n-hexane: ethyl acetate; 7:3).
After the completion of the reaction, the solution was decanted as
much as possible. The left over residue, diluted with hot ethanol.
Then the catalyst was separated from this mixture by an external
magnet and washed with acetone (2×10 ml), dried in oven and
stored for use in subsequent run under the same conditions. After
separation of catalyst, the solution was evaporated to dryness, and
crude product was obtained. The crude products in some cases
were washed with 10 ml of ether and was re-crystallized from
EtOH/ H2O (3:1 v/v) to afford pure crystalline products. Some
room temperature. XPS Spectra of the sample using
a
Gammadata-scienta ESCA200 hemispherical analyzer equipped
with an Al Kα (1486.6 eV) Xray source were obtained.
Preparation of composite
Preparation of Fe3O4
2

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products had to be purified by chromatography on silica gel ,
using a short column (Table 3)
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DOI: 10.1039/C5RA06810J
Results and discussion
Synthesis of Composite
Scheme 1 shows the schematic illustration for the synthesis
of the Fe3O4@TiO2/Cu2O core-shell magnetic composite. The
Fe3O4@TiO2 based on Cu2O composite was prepared from
commercially inexpensive available materials. In the first step, the
magnetic Fe3O4 nanoparticles were prepared by co-perecipitation
of iron (II) and iron (III) ions in alkali medium. The TiO2 shell
was prepared by the hydrolysis of tetrabutyl titanate (TBOT) in an
absolute ethanol/acetonitrile mixture in the presence of the well
dispersed Fe3O4 nanocrystals by a sol-gel process. The as-
prepared Fe3O4@TiO2 nanoparticles were removed by magnetic
separation. The Fe3O4@TiO2/Cu2O composite was obtained by
reducing copper (II) hydroxide using hydroxylamine
hydrochloride in the presence of Fe3O4@TiO2. The structure of
Figure 1. The FT-IR spectra of Fe3O4, Fe3O4@TiO2 and
Fe3O4@TiO2/Cu2O.
X-ray diffraction spectra
Figure 2 shows X-ray diffraction patterns of Fe3O4@TiO2
and as-made samples with different Cu2O molar ratios (from 9:1
to 6:4 mole ratio of Fe3O4@TiO2 to Cu2O).The typical diffraction
peaks located approximately at 30.1, 35.5, 43.2, 53.4, 57.1 and
62.7 can be well assigned to the diffraction of Fe3O4 nanoparticles
with cubic phase from the (220), (311), (400), (422), (511) and
(440) planes, respectively. In addition, a broad diffraction peak
appeared at 2θ= 20-30 nm can be indexed to amorphous TiO2.34
The main peaks for the Fe3O4@TiO2 are similar to the standard
Fe3O4 particles (JCPDS card No. 19-629), which reveals that the
crystal structure of Fe3O4@TiO2 is well coated. No obvious
diffraction peak for the TiO2 is observed, suggesting amorphous
TiO2 coating is formed by the hydrolysis of tetrabutyl titanate
(TBOT) in the presence of the well dispersed Fe3O4 nanocrystals
by a sol-gel process. Compared to Fe3O4@TiO2, new diffraction
peaks located at 29.5 (110), 36.7 (111), 42.5 (200), 52.7 (211),
61.6 (220), and 73.7 (311) can be indexed to the diffraction of
Cu2O rhombic dodecaheadral crystals in the cubic phase (JCPDS
card no. 05-0667), which suggest the presence of Cu2O in the
desired prepared composites. No additional diffraction peaks were
observed, indicating the complete reduction of copper(II) to
copper(I). It was also observed that by increasing content of Cu2O
in samples, the intensity of XRD patterns becomes gradually
stronger due to the increase of the Cu2O / Fe3O4@TiO2 weight
ratio.
Scheme 1. Preparation of nano-Fe3O4@TiO2/Cu2O core-shell
composite.
Fe3O4@TiO2/Cu2O composite was fully characterized using,
the corresponding data, provided by FT-IR, SEM, TEM, XRD,
XPS and VSM techniques
Structure characterization of the composite
FT-IR spectra
Fig. 1 gives the FT-IR spectra pattern of Fe3O4, Fe3O4@TiO2
and Fe3O4@TiO2/Cu2O in the range of 4000-500 cm-1. FT-IR
spectra shows a broad peak in 700-500 cm-1, which is attributed
to the vibration of Metal-O functional group. The peak appeared
around 545 cm-1 can be assigned to the vibration of Fe-O
functional group.32 The Ti-O and Cu-O absorption peaks appeared
in 500 and 625 cm-1 respectively. Notably, in the Fe3O4@TiO2
and Fe3O4@TiO2/Cu2O samples the observed peak is relatively
broader. This may be attributed to the overlapping of Fe-O, Ti-O
and Cu-O peaks. The peaks appeared at 1118 and 1465 cm-1 for
the Fe3O4@TiO2 and Fe3O4@TiO2/Cu2O samples could
associated with the presence of stretching vibrations of Ti-O and
Fe-O-Ti bonds.33 The bands at 1628 cm-1 belong to H-O-H
bending vibration, indicating that several OH groups are present
in the sample as a result of TiO2 coating.
Figure 2. XRD patterns of Fe3O4@TiO2 and Fe3O4@TiO2/Cu2O
with different weight ratio.
3

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FE-SEM-EDS and TEM analysis
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DOI: 10.1039/C5RA06810J
The morphology and chemical purity of Fe3O4, Fe3O4@TiO2
and Fe3O4@TiO2/Cu2O core/shell composite (optimized amount)
were visualized by SEM and EDX analysis (Figure 3).
Appearance of Au element in EDX analysis shows, the material
being coated by layer of Au proved by EDX and SEM
characterization. The SEM image of Fe3O4 shows that nearly
spherical nano particles were obtained with an average diameter
of about 15-20 nm. Moreover, the energy-dispersive X-ray
(EDAX) spectrum depicted in Figure 4(b), indicated that the
product is mainly composed of nano-Fe3O4. It can be observed
from Figure 3c that the as-synthesized Fe3O4@TiO2 core/shell still
keeping the morphological properties of Fe3O4 except for a
slightly larger particle size and stifle surface, where TiO2 are
coated on the Fe3O4 particles, uniformly. EDAX spectrum of
Fe3O4@TiO2 (Fig. 3d) core/shell nanoparticles shows the
elemental compositions are Fe, Ti and O.
Figure 4. TEM image of Fe3O4@TiO2/Cu2O (8:2) composite.
Figure 3e shows the SEM image of Fe3O4@TiO2/Cu2O
composite with the optimized amount of Cu2O required for
catalytic activity in synthesis of 1,4-disubstitured 1,2,3-triazoles.
The Cu2O shows rhombic dodecahedral structure and can be
easily distinguished in the hybrid material by their different shape
as marked in Fig. 3e. The EDX analysis on the obtained
Fe3O4@TiO2/Cu2O composite reveals the existence of Fe, Ti, Cu
and O elements, re-confirming the formation of Cu2O species on
the Fe3O4@TiO2 nano-spheres.
TEM image illustrated as Figure 4, shows, vividly, a uniform
coating of TiO2 thin layer (4nm) around the whole surface of
Fe3O4(20 nm) . The Cu2O as a bigger and dark particle can be
seen and distingushed in TEM image.
Magnetization study
Magnetic properties of synthesized Fe3O4, Fe3O4@TiO2 and
Fe3O4@TiO2/Cu2O core/shell composite were assessed by a
vibrating sample magnetometer at ambient temperature. As
illustrated in Figure 5 the saturation magnetization of the Fe3O4
MNPs are 61.6 emu/g and those for Fe3O4@TiO2 and
Fe3O4@TiO2/Cu2O core/shell composite are 29.9 and 24.11
emu/g, respectively. The decrease of the saturation magnetization
of Fe3O4 MNPs after surface coating with TiO2 and Cu2O can be
ascribed to the contribution of the non-magnetic materials.
Nonetheless, this magnetic property is adequate and the
Fe3O4@TiO2/Cu2O core/shell composite could be completely,
efficiently and rapidly, separated from the reaction mixture.
Figure 3. The FEG-SEM-EDS analysis of (a,b) Fe3O4; (c,d)
Fe3O4@TiO2 and (e,f) Fe3O4@TiO2/Cu2O (8:2) composite.
Figure 5. The magnetization curves of Fe3O4, Fe3O4@TiO2 and
Fe3O4@TiO2/Cu2O.
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XPS analysis
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DOI: 10.1039/C5RA06810J
The XPS elemental survey scans of the surface of
Fe3O4@TiO2/Cu2O composite are shown in Figure 6. The peaks,
corresponding to oxygen, titanium and copper were clearly
observed (Fig 6).
The corresponding high resolution XPS spectra of Ti2p, O1s
and Cu2p regions are shown in Figure 7. The Ti2p XPS spectra
showed two major peaks with binding energies of ca. 466.5 and
472.1, corresponding to Ti2p3/2 and Ti2p1/2, respectively,
characteristic of presence of TiO2 phase (Fig. 7a).35 The Fe signals
were not observed, indicating that the Fe3O4 core has well been
coated by the TiO2 shell. The carbon peak observed belongs to the
carbon tape, used for XPS analysis. The peak at 931.8 ev is
assigned to Cu2p3/2 and the other peak at 952.54 ev is assigned
to Cu2p1/2. The additional peaks to Cu2p3/2 and Cu2p1/2 are the
two shake-up satellite peaks, appearing at binding energies of
942.3 and 962.5 ev. These are expected for an open 3d6 shell,
corresponding to Cu+1 state and assigned to Cu2O in accordance
with data given in literature36 The O1s peak at 538.3 ev was found
over the catalyst surface can be assigned to OH species in
composite.
Figure. 6. XPS pattern of as-synthesized Fe3O4@TiO2/Cu2O
composite.
Catalytic application of Fe3O4@TiO2/Cu2O
core-shell magnetic composite
After the successful preparation and fully characterized,
Fe3O4@TiO2/Cu2O core-shell magnetic composite, its catalytic
activity in different weight ratios of Cu2O were examined by a
model reaction of benzyl bromide, phenyl acetylene and sodium
azide (Huisgen cycloaddtion reaction), to obtain 1-benzyl-4-
phenyl-1H-1,2,3-triazole 4a ( Scheme2), as sole product ,using
0.01 g magnetic composite under reflux in water. The products
were obtained in high yield and excellent regioselectivity . The
result showed, this click reaction is proceeding regioselectively,
among the other merits concluded from the use of this novel
catalyst system for the aforementioned model reaction. In order to
establish the strategy, various terminal alkynes, different
substituted benzyl bromides and sodium azide were reacted in the
presence of catalytic amounts of Fe3O4@TiO2/Cu2O core-shell to
afford the corresponding 1,4-disubstituted-1,2,3-triazoles,
regioselectively in good yields (Table 3).
Scheme 2. Click reaction catalysed by nano-Fe3O4@TiO2/Cu2O
core-shell composite.
As shown in Table 1, the catalytic performance of
Fe3O4@TiO2/Cu2O magnetic composite with a weight ratio of 8:2
gave the best result. It was found that no change in yield was
obtained with increase of Cu2O loading in magnetic composite.
Therefore, the weight ratio of Fe3O4@TiO2:Cu2O 8:2 were
selected as one of optimal reaction conditions. The reaction of
benzylbromide (1 mmol), phenylacetylene (1 mmol) and sodium
azide (1.3 mmol) was also conducted in various solvents, different
temperatures and various loading of magnetic composite.
Figure 7. High resolution XPS spectra of Fe3O4@TiO2/Cu2O
composite which shows (a) Ti2p (b) Cu2p (c) O1s.
5

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Table 1 Optimization of Cu2O for magnetic composite in model
broaden the generality of the Fe3O4@TiO2/Cu2O magnetic
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reaction.
composite, we further investigated the posDsiObiI:li1t0y.1o0f39re/Cac5tRiAo0n6o81f0J
Entry
Fe3O4@TiO2( %)
Cu2O (%)
Yieldb(%)
phenacyl bromide with various terminal alkynes and sodium azide
in the presence of our novel catalyst, and found it promising and
fruitful (Scheme 3). The results are listed in Table 4. Under
optimal conditions for this one-pot, multi-component reaction,
phenacyl bromide 1 mmol, phenylacetylene 1 mmol and sodium
azide 1.3 mmol were reacted in the presence of 0.01 g magnetic
composite under reflux in water.
1
2
3
4
60
70
80
90
40
30
20
10
93
93
93
82
a
Reaction conditions: benzylbromide (1 mmol), sodium azide (1.3
mmol),phenylacetylene (1 mmol), and catalyst (0.010 g) in Water under
reflux.
b Isolated yield.
N
O
O
N
N
Fe3O4@TiO2/Cu2O
H2O, Reflux
Ph
Br
+
Ph
+
H
NaN3
The results for the optimization of the reaction conditions are
summarized in Table 2. In our delight, the reaction performed in
refluxing water, gave the highest yield of product which an inert
atmosphere is non-required (Table 2, entry 7). We carried out the
model reaction in the presence of Fe3O4@TiO2 as a catalyst under
reflux in water and the poor yield of product was formed even
after 2 h (Table 2, entry 8). As expected, the reaction did not
proceed in the absence of the catalyst, even after prolonged
reaction time (Table 2, entry 9). This indicates that the magnetic
composite as catalyst plays a crucial role in the regioselective
synthesis of 1-benzyl-4-phenyl-1H-1,2,3-triazole 4a. A higher
reaction temperature or the catalyst amount does not make an
obvious difference in the yield of product (Table 2, entries 6, 10).
But, a lower amount of catalyst decreased the yield of the reaction.
Ph
Ph
Scheme 2. Click reaction of phenacyl bromide, phenyl acetylene
and sodium azide.
In general, different substituted phenyl acetylenes and benzyl
halides bearing electron-donating substituents as well as electron-
withdrawing groups provided an array of 1,4-disubstituted 1,2,3-
triazoles smoothly and cleanly, in good to excellent yields (75-
93%) within relative short times 15-80 min of reaction times. As
shown in Tables 3 and 4, the aliphatic terminal alkynes bearing
hydroxyl as functional group gave the desired triazoles in higher
yields.
Recycling and leaching of the catalyst
Table 2 Optimization of the three-component click synthesis of
4-phenyl-1H-1,2,3-triazole, 4a, using Fe3O4@TiO2/Cu2O
magnetic compositea
One of the main advantages of heterogeneous catalysis is the
ease of separation and their possible reusability in further runs.37
In this line the recyclability of Fe3O4@TiO2/Cu2O magnetic
composite was practically examined in a one-pot synthesis of 1-
Entr
y
Time
(h:min)
Yieldb
(%)
Catalyst (g)
Condition
H2O/ r.t
benzyl-4-phenyl-1H-1,2,3-triazole 4a under
optimized
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.010)
Fe3O4@TiO2/Cu2O
(0.015)
Fe3O4@TiO2/Cu2O
(0.020)
1
2
3
4
5
6
7
2
Trace
43
conditions. No significant loss in catalytic activity was observed
after five runs, suggesting that Cu2O leaching is not meaningful
for Fe3O4@TiO2/Cu2O magnetic composite (Figure 8). Another
test was done to determine that catalytic activity of
Fe3O4@TiO2/Cu2O composite is not due only to dissolved CuI
species in the solution. In this light, we performed an unfinished
experiments. First, we took starting materials and catalyst,
Fe3O4@TiO2/Cu2O composite in 3 mL water and refluxed the
mixture for 5 min to simulate the actual conditions. Then at this
point the catalyst was removed by an external magnet, while we
allow the reaction normally proceed, then we permitted, the
mixture being refulxed in the absence of the removed catalyst,
magnitically. No apperaciable progress was observed even after
2 h (monitored bt TLC). Thus it can be concluded that the
dissolved CuI species is not actually, involved in catalysis at least
by itsef alone.
H2O/ 60 oC
H2O/ 80 oC
H2O/ 110 oC
H2O/ Reflux
H2O/ Reflux
H2O/ Reflux
0:15
0:15
0:15
0:15
0:15
0:15
79
91
69
82
93
8
9
Fe3O4@TiO2(0.020)
H2O/ Reflux
H2O/ Reflux
2
24
Trace
-
-
Fe3O4@TiO2/Cu2O
(0.025)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
Fe3O4@TiO2/Cu2O
(0.020)
10
11
12
13
14
15
16
H2O/ Reflux
0:15
1:40
1
93
58
75
86
46
50
65
H2O/DMSO
(2:1)/ Reflux
CH3CN/
Reflux
EtOH/ Reflux
DMF/ 100 oC
0:45
1:45
1:45
2
93
91
88
85
100
50
0
DMSO/ 100
oC
Solvent free/
100 oC
a Reaction condition: Benzyl bromide(1 mmol), Sodium azide (1.3 mmol),
Phenylacetylene (1 mmol).
b Isolated yield.
1
2
3
4
Thus, with the optimized reaction condition in hand, the substrate
scope of reaction was extended to various structurally diverse
terminal alkynes and benzylhalides (Table 3). In an attempt to
Run
Figure. 8. Recycling results of the Fe3O4@TiO2/Cu2O composite.
6

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Table 3. Three-component click reaction of benzylhalides, terminal alkynes and sodium azide using Fe3O4@TiO2/Cu2O magnetic compositea
Time
YiDelOdIb: 10.1039/C5RA06810J
Entry
Halide precursor
Alkyne
Product
Mp.°C Lit
(min)
(%)
127-128
1
15
20
30
93
(126-127)30d
104-106
2
3
89
(105-106)39
153-156
84
(156-157)39
147-149
4
20
87
(150)40
77-79
5
6
20
20
91
(78-78.5)39
76-77
85
(77)39
127-128
7
8
9
20
25
25
89
(126-127)30d
104-106
83
(105-106)38
143-146
84
(142-145)41
147-149
10
25
84
(150)40
77-79
11
12
20
25
89
(78-78.5)39
76-77
86
(77)39
a Reaction condition: alkyl halide (1 mmol), NaN3 (1.3 mmol), acetylene (1 mmol), Fe3O4@TiO2/Cu2O (0.020 g), H2O (2 ml), reflux.
b Isolated yield.
7

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Table 4. Three-component click reaction of phenacylhalides, terminal alkynes and sodium azide using Fe3O4@TiO2/Cu2O magnetic
compositea
View Article Online
Time
(min.)
YieDldObI: 10.1039/C5RA06810J
Entry
phenacylhalide
Alkyne
Product
Mp.°C Lit.
(%)
1
169-171
89
20
25
(171-172)30d
2
3
4
5
6
115-118
83
(116-119)30d
102-104
86
25
30
50
(100-103)30d
157-159
87
(156-158)30d
111-113
76
(110-113)30d
180-183
75
60
50
75
70
80
(180-183)30d
7
8
156-158
82
(157-160)30a
153-155
80
(151-154)30a
9
154-155
78
(154-155)30d
10
168-171
76
(167-170)30d
a Reaction condition: α-haloketones (1 mmol), NaN3 (1.3 mmol), acetylene (1 mmol), Fe3O4@TiO2/Cu2O (0.020 g), H2O (2 ml), reflux.
b Isolated yield.
commercially and readily available starting materials and the
Conclusion
green and abundent, water as solvent are the merits of this method.
Conducting the reaction in conventional conditions, convenient
work up procedure, easy recovery and efficient reusability of
catalyst are conspicuous features of this methodology. Further
studies on the scope and application of nano- Fe3O4@TiO2/Cu2O
magnetic composite are underway in our laboratory.
In summary, we have developed an efficient method for the
regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles
through a one-pot multi-component reaction of alkyl halides or
phenacyl bromide , terminal alkynes and sodium azide ,catalyzed
by novel and well characterizid nano-Fe3O4@TiO2/Cu2O core-
shell magnetic composite under reflux in water. Using,
8

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28 (a) F. Nemati, M. M. Heravi and R. Saeedi rad, Chin. J. Catal., 2012,
Acknowledgements
View Article Online
33, 1825-1831; (b) F. Janati, M. M. Heravi and A. M. Shokraie. Synth.
DOI: 10.1039/C5RA06810J
React. Inorg. Met. Org. Chem., 2015, 45, 1-5; (c) T. Alishiri, H. A.
Oskooei and M. M. Heravi, Synth. Commun., 2013, 43, 3357-3362.
29 (a) M. M. Heravi and Z. Faghihi, J. Iran. Chem. Soc., 2014, 11, 209-
224; (b) M. M. Heravi and S. Moghimi, Tetrahedron Lett., 2012, 53,
392-394; (c) M. M. Heravi and S. Moghimi, J. Iran. Chem. Soc.,
2011, 8, 306-373; (d) M. M Heravi, F. K. Behbahani, M. Daraie and
H. A. Oskooie, Mol. Diversity. 2009, 13, 375-378; (e) M. M. Heravi,
E. Hashemi, Y. Sh. Beheshtiha, Kh. Kamjou, M. Toolabi and N.
Hosseintash, J. Mol. Cat. A: Chem., 2014, 392, 173-180; (f) M. M.
Heravi, F. Mousavizadeh, N. Ghobadi and M. Tajbakhsh,
Tetrahedron Lett., 2014, 55, 1226-1228; (g) M. M. Heravi, Sh. Asadi
and B. M. Lashkariani, Mol. Diversity, 2013, 17, 389-407.
30 (a) A. Fazeli, H. A. Oskooie, Y. S. Beheshtiha, M. M. Heravi1 and H.
Valizadeh, Lett. Org. Chem., 2013, 10, 738-743; (b) A. Fazeli, H. A.
Oskooie, Y. S. Beheshtiha, M. M. Heravi, H. Valizadeh and F. F.
Bamoharram, Monatsh Chem., 2013, 144, 1407-1410; (c) M. M.
Heravi, A. Fazeli, H. A. Oskooie, Y. S. Beheshtiha and H. Valizadeh,
Synlett., 2012, 23, 2927-2930; (d) E. Hashemi, Y. S. Beheshtiha, S.
Ahmadi, M. M. Heravi, Transition Met Chem., 2014, 39, 593-601; (e)
M. M. Heravi, H. Hamidi and V. Zadsirjan, Curr. Org. Synth., 2014,
11, 647-675; (d) R. Mirsafaei, M. M. Heravi, Sh. Ahmadi, M. S.
Moslemin and T. Hosseinnejad, J. Mol. Catal. A: Chem. 2015, 402,
100-108.
The authors gratefully acknowledge Semnan University
Research Council for financial support of this work.
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