Immobilized copper(II) on nitrogen-rich polymer-entrapped Fe3O4 nanoparticles: A highly loaded and magnetically recoverable catalyst for aqueous click chemistry

Article abstract of DOI:10.1002/aoc.3398

A heterogeneous magnetic copper catalyst was prepared via anchoring of copper sulfate onto multi-layered poly(2-dimethylaminoethyl acrylamide)-coated magnetic nanoparticles and was characterized using various techniques. The catalyst was found to be active, effective and selective for one-pot three-component reaction of alkyl halide, sodium azide and alkyne, known as copper-catalyzed click synthesis of 1,2,3-triazoles. As little as 0.3 mol% of catalyst was found to be effective under the optimum conditions. The catalyst could also be recycled and reused up to seven times without significant loss of activity. Thermal stability, high loading level of copper on catalyst, broad diversity of alkyl/benzyl/allyl bromide/chloride and alkyl/aryl terminal alkynes without isolation of azide intermediate, and good to excellent yields of products make this procedure highly economical.

Full text of DOI:10.1002/aoc.3398

Full paper
Received: 5 August 2015
Revised: 14 September 2015
Accepted: 2 October 2015
Published online in Wiley Online Library: 25 November 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3398
Immobilized copper(II) on nitrogen-rich
polymer-entrapped Fe3O4 nanoparticles: a
highly loaded and magnetically recoverable
catalyst for aqueous click chemistry
Nasrin Zohreha*, Seyed Hassan Hosseinib, Ali Pourjavadib and Craig Bennettc
A heterogeneous magnetic copper catalyst was prepared via anchoring of copper sulfate onto multi-layered poly(2-
dimethylaminoethyl acrylamide)-coated magnetic nanoparticles and was characterized using various techniques. The catalyst
was found to be active, effective and selective for one-pot three-component reaction of alkyl halide, sodium azide and alkyne,
known as copper-catalyzed click synthesis of 1,2,3-triazoles. As little as 0.3 mol% of catalyst was found to be effective under the
optimum conditions. The catalyst could also be recycled and reused up to seven times without significant loss of activity. Thermal
stability, high loading level of copper on catalyst, broad diversity of alkyl/benzyl/allyl bromide/chloride and alkyl/aryl terminal
alkynes without isolation of azide intermediate, and good to excellent yields of products make this procedure highly economical.
Copyright © 2015 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web-site.
Keywords: polymeric catalyst; magnetic separation; Cu-catalyzed click reaction
on solid supports for CuAAC.[27,35–41] Although these catalysts
Introduction
are efficient, each of them suffers from some drawbacks such as
multi-step catalyst preparation,[35,36] low loading (low amount of
No doubt one of the most significant developments in the catalysis
realm is heterogenization of homogeneous catalysts.[1,2] Easy
handling and separation minimizing the cost of production, excellent
reusability, and chemical and thermal stability of catalysts are out-
standing qualities making heterogeneous catalysts environmentally
benign.[3–5] Heterogenization has been achieved by functionalization
or immobilization of homogeneous catalysts on the surface of insol-
uble solids such as silica,[6,7] polymers,[8] magnetic nanoparticles[9]
and carbon materials.[10,11] Compared to others, magnetic nanoparti-
cles are special. They are in a superparamagnetic state at room
temperature, resulting in unique opportunities for excellent separa-
tion simply using an external magnet.[12–15] They have also good
stability, high surface area as well as low toxicity and price.[16,17]
After introducing the heterogenization concept, the conditions of
numerous catalyzed chemical reactions or industrial processes have
been modified using many heterogeneous catalytic systems.[18–21]
Among these transformations, the copper-catalyzed azide/alkyne
cyclization (CuAAC) reaction is one of the most important in the
realm of click reactions. This is because the resulting triazoles func-
tion as rigid linking units that can mimic the atom placement and
electronic properties of a peptide bond without the same suscepti-
bility to hydrolytic cleavage.[22,23] Triazoles are also multipurpose
building blocks in materials science, medicinal chemistry, drug
discovery,[24,25] organic chemistry and polymer science.[26–29]
Various heterogeneous systems have been realized by the co-
valent and non-covalent immobilization of copper species onto
a variety of supports for CuAAC. Most of them include supported
copper nanoparticles on solid beds.[30–34] Moreover, various N-
or C-ligand/Cu(I) complexes have been covalently immobilized
active catalyst species on the solid support),[41] long reaction
time,[35] tedious workup of catalyst[30] and product[32] and harsh
reaction conditions.[34,39,40] In most cases, the low loading prob-
lem of heterogeneous copper-based catalysts leads to the use of
a larger amount of catalyst or higher temperature[36] and longer
reaction time.[31,34,35,39,41] Immobilization of copper species onto
the surface of polymers is a good way to overcome this limitation,
since a large number of functionalities can be linked to copper. In
contrast to the use of polymers as supports used only for
heterogenization,[38] polymerization of a desired structure on
the surface of the support followed by immobilization of copper
species on it is an effective way to increase loading. However, only
a few examples of polymer-supported copper catalysts have been
reported based on this strategy for CuAAC reaction.[39,42,43] In a re-
cent study,[44] a very high-loading polymer-based copper catalyst
was reported, resulting in the use of parts per million amount of
catalyst for CuAAC reaction.
*
Correspondence to: Nasrin Zohreh, Department of Chemistry, Faculty of Science,
University of Qom, PO Box 37185-359, Qom, Iran. E-mail: n.zohreh@qom.ac.ir
a Department of Chemistry, Faculty of Science, University of Qom, PO Box 37185-
359, Qom, Iran
b Polymer Research Laboratory, Department of Chemistry, Sharif University of
Technology, Tehran, Iran
c
Department of Physics, Acadia University, Wolfville, Nova Scotia, Canada
Appl. Organometal. Chem. 2016, 30, 73–80
Copyright © 2015 John Wiley & Sons, Ltd.

N. Zohreh et al.
Scheme 1. Synthesis of catalyst MNP@PDMA-Cu.
In this context, we investigated the development of a novel het-
erogeneous copper catalyst based on poly(2-dimethylaminoethyl
acrylamide)-encapsulated magnetic nanoparticles purposing a high
loading of copper and easy magnetic recoverability. Also investigated
was a small library of 1,2,3-triazoles prepared in the presence of the
catalyst via three-component reaction of alkyl halide, sodium azide
and terminal alkynes under simple and mild reaction conditions.
TLC was performed with silica gel 60 F254 plates and UV light
was used for visualization. Fourier transform infrared (FT-IR) spectra
of samples were obtained using an ABB Bomem MB-100 FT-IR spec-
trophotometer. NMR spectra were recorded with a Bruker 500 MHz
NMR instrument. Thermogravimetric analysis (TGA) was conducted
under a nitrogen atmosphere with a TGA Q 50 thermogravimetric
analyzer. Morphology of the catalyst was observed with a scanning
electron microscopy (SEM) instrument (Philips XL30). Transmission
electron microscopy (TEM) images were obtained with a TOPCON-
002B electron microscope. The magnetic properties of the catalyst
were measured using a vibrating sample magnetometer (model
7400). Copper ions were measured using atomic absorption spec-
trometry (AAS; Shimadzu 680 A) or inductively coupled plasma
optical emission spectrometry (ICP-OES; Perkin-Elmer DV 4300).
Materials and methods
Ferric chloride hexahydrate (FeCl3ꢀ6H2O), ammonia (25%), ferrous
chloride tetrahydrate (FeCl2ꢀ4H2O), 3-(trimethoxysilyl)propyl-
methacrylate (MPS), N,N-dimethylethylenediamine and methy-
lenebisacrylamide (MBA) were obtained from Merck without
further purification. 2,2′-Azobisisobutyronitrile (AIBN; Kanto, 97%)
was recrystallized from ethanol and methyl acrylate (Sigma-Aldrich)
was distilled before use.
Figure 1. FT-IR spectra of (a) MNP, (b) MNP@MPS, (c) MNP@PMA, (d)
MNP@PDMA and (e) MNP@PDMA-Cu.
Figure 2. (a) XRD pattern and (b) RDP of MNP@PDMA.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 73–80

Immobilized copper (II) on nitrogen rich polymer
Figure 3. TGA curves of (a) MNP@MPS, (b) MNP@PMA, (c) MNP@PDMA and
(d) MNP@PDMA-Cu.
Figure 4. (a) TEM and (b) SEM images of MNP@PDMA-Cu.
Synthesis of modified magnetic nanoparticles (MNP@MPS)
Magnetic Fe3O4 nanoparticles were prepared using a chemical co-
precipitation method. An iron salt solution was obtained by mixing
13.6 g of FeCl3ꢀ6H2O (50.3 mmol) and 5 g of FeCl2ꢀ4H2O (25.1mmol)
in 500ml of deionized water under nitrogen at room temperature.
By dropwise addition of NH3 solution, the pH was adjusted to 12. A
black precipitate was formed after continuously stirring for 1 h. The
precipitate was magnetically separated and washed four times with
deionized water and two times with ethanol and was dried under
vacuum at 50 °C overnight (5.5g of product).
The resulting Fe3O4 nanoparticles (3g) were ultrasonically
suspended in 400 ml of an ethanol–water mixture (4:1) and the
pH of the solution was adjusted to 9 by adding ammonia solution.
Tetraethyl orthosilicate (15 ml) was added dropwise to the solution
at 50 °C in the presence of a constant nitrogen flow. The mixture
was stirred for 6 h. The silica-coated nanoparticles were then mag-
netically separated and washed three times with deionized water
and two times with ethanol. The final dark brown product (MNP)
was dried at 50 °C under vacuum for 24 h (7.8g of product).
Subsequently, 1.0 g of MNP was dispersed in 40 ml of a 4:1 mix-
ture of ethanol–water, and then 2 ml of ammonium hydroxide solu-
tion (25%) was added. Then, an excess amount (10 mmol per gram
of MNP) of MPS was added dropwise over a period of 10 min, and
the reaction mixture was stirred at 50 °C for 48 h. The modified
MNP@MPS were magnetically separated and washed three times
with methanol to remove any excess reagent and salts (0.96g of
product).
Synthesis of catalyst
An amount of 500 mg of MNP@MPS was dispersed ultrasonically in
200 ml of methanol in a 500 ml single-necked flask for 10 min. Then,
a mixture of 2 g of methyl acrylate (20mmol), 500mg of MBA
(3.2mmol) and 70mg of AIBN (0.43 mmol) was added to the flask
to initiate the polymerization. The mixture was completely deoxy-
genated by bubbling purified argon for 30 min. The flask, sub-
merged in a heating oil bath, was equipped with a fractionating
column, Liebig condenser and receiver. The reaction mixture was
heated from ambient temperature to boiling within 1 h and the re-
action was ended after about 100 ml of methanol was distilled from
the reaction mixture within 5 h. The obtained cross-linked
polymethacrylate-coated MNP (MNP@PMA) were collected by
magnetic separation and washed two times with water and three
times with methanol to eliminate excess reactants and a few gener-
ated copolymer microspheres (1.40 g of product).
An amount of 500 mg of MNP@PMA was dispersed ultrasonically
in 20 ml of methanol in a 50 ml single-necked flask for 10 min. Then,
15ml of N,N-dimethylethylenediamine (16 mmol) was added and
the mixture was stirred at 60 °C until the stretching vibration band
of carbonyl groups of polymethacrylate disappeared (about 48h).
Poly(dimethylaminoethyl acrylamide)-coated MNP (MNP@PDMA)
was magnetically separated and washed three times with methanol
to remove any excess reagent and then dried at 60 °C for 12 h
(0.53 g of product).
Table 1. Results of CHNS analysis
Entry
Sample
C (%)
H (%)
N (%)
S (%)
Loading (mmol gꢁ1
)
1
2
3
4
MNP@MPS
3.19
13.27
18.15
17.12
0.62
1.97
3.09
4.50
0.09
0.87
5.05
4.83
—
—
0.38a
MNP@PMA
0.28b for MBA; 1.61c for CO2Me
1.49d for NMe2
MNP@PDMA
MNP@PDMA-Cu
—
1.63
0.51 for SO4; 0.51e for Cu
aBased on carbon atom.
bBased on nitrogen atom.
cBased on carbon atom after subtracting the %C of MBA. %C of MBA can be calculated from the loading amount of MBA (0.28 mmol gꢁ1) which is 2.35%.
dBased on nitrogen atom after subtracting the %N of MBA which is 0.78% (0.87 ꢁ 0.09 = 0.78%).
eBased of sulfur atom in complexed CuSO4.
Appl. Organometal. Chem. 2016, 30, 73–80
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

N. Zohreh et al.
The resulting powdered material was subjected to an anchoring
(complexation) reaction. An amount of 0.5g of MNP@PDMA was
added to 30 ml of water and an excess of CuSO4 (1.5 g, 6 mmol)
was added to the solution. The mixture was vigorously stirred for
3 days at 70 °C. The solid catalyst (MNP@PDMA-Cu) was then mag-
netically separated, washed with water (5× 50 ml) and methanol
(2× 20 ml) and dried under vacuum at 50°C (0.49 g of product).
ascorbic acid (10mol%) were added to the solution. The reaction
mixture was stirred at room temperature and the completion of
the reaction was monitored using TLC. After completion of the reac-
tion, the catalyst was magnetically separated and washed several
times with ethanol followed by water and dried under vacuum.
The corresponding triazole was easily isolated by simple filtration
of the reaction mixture and crystalized from EtOAc–hexane. All syn-
thesized triazoles are known compounds.[42,43,45] However, charac-
terization data for some derivatives are given in the supporting
information.
General procedure for synthesis of 1,4-disubstituted triazoles
Primary halides (1mmol), NaN3 (1.5mmol) and terminal alkynes
(1mmol) were placed in a 10 ml round-bottom flask in water
(2ml). Subsequently, MNP@PDMA-Cu (5.26 mg, 0.3mol%) and
Results and discussion
Preparation of the copper catalyst MNP@PDMA-Cu was carried out
in a few steps as illustrated in Scheme 1. Magnetic Fe3O4 nanopar-
ticles were synthesized by typical chemical co-precipitation of FeCl3
and FeCl2 in alkaline pH and coated with silica using a sol–gel pro-
cess to obtain core–shell magnetic nanoparticles (Fe3O4@SiO2).[46]
Generally, coating of Fe3O4 nanoparticles with SiO2 layer can pre-
vent the Fe3O4 core from aggregation and can also provide Si–OH
groups for fine chemical functionalization and modification using
available alkoxysilane materials. Subsequently, the MNP substrate
was treated with MPS to produce MNP@MPS support. Coating with
MPS generates vinyl groups on the surface of the nanoparticles
which allow covalent grafting of polymer chains onto the nanopar-
ticle surface.
Distillation–precipitation copolymerization is the key step con-
ducted with MNP@MPS as the seed, methyl acrylate as monomer,
MBA as cross-linker and AIBN as initiator in methanol without any
surfactant. The resulting cross-linked polymers are insoluble in
methanol and continuously precipitate from the solution while
Figure 5. Vibrating sample magnetometry curves for (a) Fe3O4 and (b)
MNP@PDMA-Cu.
Table 2. Optimization of conditions for the click synthesis of triazoles using MNP@PDMA-Cu catalysta
Entry
Solvent
Catalyst (mol%)
T (°C)
Time (h)
NaN3 (eq.)
Na ascorbate (mol%)
Yield (%)b
1
—
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
0.3
0.3
0.3
0.3
0.3
0.3
0.2
0.1
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
50
50
50
70
90
50
50
50
50
50
7
1
10
10
10
10
10
10
10
10
10
10
10
10
10
10
20
10
10
10
20
Trace
Trace
33
2
CH3CN
CHCl3
DMF
7
1
3
7
1
4
7
1
5
MeOH
H2O
7
1
78
6
7
1
89
7
MeOH–H2O (1:1)
tBuOH–H2O (1:1)
H2O
7
1
88
8
7
1
92
9
1.5
1.5
2
1
95
10
11
12
13
14
15
16
17
18
H2O
1
91
H2O
1
93
H2O
2
1
93
92c
H2O
2
1
H2O
3
1
94
H2O
2
1
91
H2O
2
1.5
1.5
1.5
96
H2O
2
93
H2O
4.5
93
aBenzyl bromide: 1 mmol; phenylacetylene: 1 mmol; solvent: 2 ml.
bIsolated yield.
cMixture of isomers.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 73–80

Immobilized copper (II) on nitrogen rich polymer
covalently grafting to the surface of the MNP@MPS. Grafting
becomes very efficient in the presence of vinyl groups of MPS on
the surface of MNP. In other words, without MPS modification, only
a minor part of the magnetic nanoparticles can be coated with a
complete layer of polymer chains instead of all of them. Simulta-
neous distillation of methanol generates multilayer polymeric
shell-grafted MNP (MNP@PDMA). Subsequently, amidation of
esteric groups with N,N-dimethylethylenediamine provides the
desired functional groups. We believe that the N,N-
dimethylethylenediamine on the surface of the polymer layer can
act as a ligand because of strong coordination of its N,N-dimethyl
group with copper, as shown in Scheme 1. Finally, anchoring of
Cu(II) obtained via complexation of copper sulfate and polymer
chains on the surface of MNP@PDMA affords the catalyst
MNP@PDMA-Cu.
The synthesized MNP@PDMA-Cu was characterized in detail
using a combination of methods. As shown in Fig. 1, to verify the
successful incorporation of the organic components, the chemical
compositions of MNP, MNP@MPS, MNP@PMA, MNP@PDMA and
MNP@PDMA-Cu were characterized using FT-IR spectroscopy. The
stretching vibrations at 582 and 1083 cmꢁ1, in all spectra, confirm
the maintenance of the Fe–O and Si–O bonds during the synthesis
processes. The absorption peaks at 2929, 1707 and 1404 cmꢁ1 in
Fig. 1(b) show successfully coating of MPS onto MNP and are
Table 3. MNP@PDMA-Cu-catalyzed three-component synthesis of 1,2,3-triazolesa
Entry
1
R
R′
Time (h)
Yield of 3 (%)b
PhCH2
Ph
2 (X = Br)
2.5 (X = Cl)
2 (X = Br)
3a: 96
3a: 90
3b: 91
3c: 95
3d: 97
3d: 93
3e: 90
3a: 94
3f: 91
2
3
4
4-MePhCH2
4-ClPhCH2
Ph
Ph
Ph
2 (X = Br)
4-NO2PhCH2
1.5 (X = Br)
1.5 (X = Cl)
2.5 (X = Br)
1.5 (X = OTs)
3 (X = Cl)
5
4-BrPhCH2
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
6
PhCH2
7
1-Naphthylmethyl
PhCOCH2
8
2.5 (X = Br)
3 (X = Br)
3 g: 87
3 h: 85
3i: 88
9
EtOCOCH2
10
11
12
MeCH2CH2
–CH2(CH2)2CH2–
Me(CH2)5CH2
3 (X = Br)
3 (X = Br)
3j: 90
3.5 (X = Br)
4 (X = Cl)
3 k: 80
3 k: 76
3 l: 84
3 m: 91
3 m:90
3n: 86
3n: 85
3o: 86
3p: 87
3q: 80
3r: 92
3 s: 85
3 t: 80
3u: 92
3u: 89
3v: 85
3w: 77
3w: 75
3x: 82
3y: 86
3y: 81
3z: 81
13
14
H2NCOCH2
Ph
Ph
2.5 (X = Br)
2 (X = Br)
(Me)2C¼CCH2
2 (X = Cl)
15
PhCH2
MeO2C
4.5 (X = Cl)
4 (X = OTs)
3.5 (X = Br)
4 (X = Br)
16c
17c
18d
19
4-NO2PhCH2
Allyl
MeO2C
MeO2C
EtO2C
PhCOCH2
PhCH2
4.5 (X = Br)
4.5 (X = Br)
3 (X = Br)
HOCH2
HOCH2
HOCH2
Me(CH2)3CH2
20
4-NO2PhCH2
Me(CH2)2CH2
PhCH2
21
4 (X = Br)
22
3.5 (X = Br)
3.5 (X = Cl)
3 (X = Br)
23
24
4-BrPhCH2
Me(CH2)3CH2
Me(CH2)3CH2
Me(CH2)5CH2
4 (X = Br)
4 (X = Cl)
25
26
PhCOCH2
Allyl
Me(CH2)3CH2
Me(CH2)3CH2
3.5 (X = Br)
3.5 (X = Br)
3.5 (X = Cl)
4 (X = Br)
27
EtOCOCH2CH2
Me(CH2)3CH2
aReaction conditions: alkyl halide (1 mmol), NaN3 (1.5 mmol), acetylene (1 mmol), MNP@PDMA-Cu (0.3 mol%), H2O (2 ml).
bIsolated yield.
cMeOH as solvent.
dEtOH as solvent.
Appl. Organometal. Chem. 2016, 30, 73–80
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

N. Zohreh et al.
attributed to C–H, esteric C¼O and C¼C bonds of MPS. The FT-IR
spectrum of MNP@PMA (Fig. 1(c)) shows a strong vibration band
at 1735 cmꢁ1 associated with esteric C¼O of polymethacrylate.
Comparing Figs. 1(c) and (d), disappearance of the stretching band
at 1735 cmꢁ1 and appearance of amidic C¼O band at 1638 cmꢁ1
can be observed indicating total substitution of CO2Me group with
N,N-dimethylethylenediamine via amidation. On complexation
with copper, the FT-IR spectrum of MNP@PDMA-Cu (Fig. 1(e))
shows a new band at 1120 cmꢁ1 attributed to S¼O of CuSO4. These
results confirm that the catalyst had been successfully prepared.
The crystallinity and phase composition of the resulting catalyst
were investigated using X-ray diffraction (XRD) and ring diffraction
pattern (RDP). The high-angle XRD pattern of MNP@PDMA is shown
in Fig. 2(a). Comparing with the XRD pattern of pure Fe3O4 nanopar-
ticles, it can be seen that all peaks are in the same region and inten-
sity. There is a broad diffraction peak at 2θ = 20° assigned to
amorphous silica coated on the surface of Fe3O4 nanospheres.[47]
This indicates that not all modifications cause a phase change in
Fe3O4. The RDP of the catalyst also shows the crystalline planes of
Fe3O4 (Fig. 2(b)).
In order to investigate the thermal stability and organic content
of MNP@MPS, MNP@PMA, MNP@PDMA and MNP@PDMA-Cu, TGA
was carried out (Fig. 3). Obvious weight losses below 150 °C are
assigned to the loss of the physically adsorbed water on the surface
of nanostructure materials. A weight loss of 4.1% in the TGA curve
of MNP@MPS (Fig. 3(a)) shows that organic content loaded on the
surface of MNP (loading of MPS) is 0.32 mmol gꢁ1. Since both
MNP@PMA and MNP@PDMA contain monomer and cross-linker,
calculation of accurate loading amount of –CO2Me or –NMe2 based
on TGA curves is not possible. However, according to the weight
losses between 200 and 900 °C in their TGA curves (Figs. 3(b) and
(c)), it is calculated that the content of PMA and PDMA on the
surface of MNP is about 21.5 and 29 wt%, respectively. TGA also
shows that the catalyst has high thermal stability of over 200°C.
The amount of NMe2 groups on MNP@PDMA was calculated
using the back-titration method. MNP@PDMA (50 mg) was
dispersed in water and an excess of HCl (0.1M) was added. The
mixture was stirred for 3 h until neutralization of all amine groups
on the surface of the catalyst. The excess HCl in solution was titrated
using NaOH (0.1M) in the presence of phenolphthalein. The
amount of NMe2 ligand loaded on the surface of MNP@PDMA is
found to be 1.58 mmol gꢁ1. CHNS elemental analysis also served
to calculate N,N-dimethylaminoethyl acrylamide or NMe2 loading
amount (see supporting information). According to the elemental
analyses (Table 1), NMe2 loading is calculated as about
1.49 mmolgꢁ1 which is in good agreement with the calculated
loading amount from titration.
The magnetization curves of bare Fe3O4 nanoparticles
and MNP@PMDA-Cu are shown in Figs. 5(a) and (b), respectively.
It can be seen that Fe3O4 and MNP@PDMA particles are
superparamagnetic with magnetic saturation values of about 64.1
and 24.3 emu gꢁ1, respectively. The 39.8 emu gꢁ1 reduction of satu-
ration magnetization is attributable to the presence of SiO2/PDMA
shell on Fe3O4 particles. However, the level of catalyst magnetiza-
tions is still sufficient to strongly respond to an external magnet
during catalyst recovery.
To evaluate the effectiveness of MNP@PDMA-Cu as a heteroge-
neous copper catalyst, one-pot three-component cycloaddition of
benzyl bromide, sodium azide and phenylacetylene was selected
as a model reaction for synthesis of 1,2,3-triazoles. The reaction
was evaluated under various optimizations (Table 2). In the prelim-
inary experiments, a variety of solvents were screened for exploring
their suitability as reaction media in the presence of a fixed catalyst
amount (1.0mol%). As evident from Table 2 (entries 1–8), a signifi-
cant effect on time and product yield is observed by changing the
solvents from aprotic to protic ones. This effect is probably because
of the poor solubility of NaN3 or ionic intermediates in aprotic sol-
vents. Among the protic solvents, water exhibits the greatest effect
and 89% of desired product 3a is obtained. However, using a mix-
ture of tBuOH and water gives better product yield, but the low cost
and green nature of water convinced us to use pure water as
solvent. Optimization of catalyst amount was then examined in
the reaction of equimolar ratio of reactant and 10mol% sodium
ascorbate. Increasing the reaction temperature to 50°C increases
the reaction yield to 95% in shorter reaction time (entry 9). Decreas-
ing the catalyst amount from 1.0 to 0.3mol% does not significantly
change the yield of product (entries 9–11). Increasing the reaction
temperature to 90 °C results in a mixture of cis- and trans-triazole iso-
mers (27%:73%; entries 11–13). It is also observed that increasing the
amount of NaN3 enhances the yield of product up to 96%, while
increasing the amount of sodium ascorbate reduces the yield of
product (entry 16). Consequently, in the presence of 0.3 mol%
MNP@PDMA-Cu catalyst, the reaction of benzyl bromide, sodium
azide and phenylacetylene in a ratio of 1:1.5:1 and 10 mol% sodium
ascorbate gives the best yield of 1,2,3-triazole 3a at 50 °C after 2 h.
These conditions were selected as the optimum ones (entry 16).
Inspired by the excellent catalytic activity of MNP@PDMA-Cu in
the model reaction under optimum conditions, scope of substrates
and limitations of CuAAC reaction were investigated for the synthe-
sis of a small library of 1,4-disubstituted 1,2,3-triazoles (Table 3). A
wide range of diversely substituted benzyl, allyl and alkyl halides
and dihalides were successfully subjected to the one-pot CuAAC re-
action. It is found that all reactions produce corresponding triazoles;
however, the reaction rates for chlorides are lower than those for
The amount of Cu(II) ions loaded in MNP@PDMA-Cu was calcu-
lated with AAS using standard samples. It is found that the amount
of Cu(II) ions loaded in MNP@PDMA-Cu is 0.57mmolgꢁ1. This load-
ing level of copper on the surface of the magnetic support is quite
high for a nonionic supported ligand.
TEM imaging of MNP@PDMA-Cu (Fig. 4(a)) provides strong
evidence that MNP (black cores) are encapsulated within multilayer
polymer (grey shell). The TEM image (Fig. 4(a)) also shows the good
dispersion of spherical nanoparticles onto the copolymer matrix,
with a size distribution and an average particle size of 6nm. The
surface morphology of MNP@PDMA-Cu was also examined using
SEM. As indicated in Fig. 4(b), a bulk polymeric structure with rough
surface is seen. The rough surface of the catalyst is due to the
presence of magnetic nanoparticles increasing the catalytic surface
and activity.
Figure 6. Results of recycling experiment.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 73–80

Immobilized copper (II) on nitrogen rich polymer
Table 4. Comparison of MNP@PDMA-Cu with reported catalysts in the synthesis of triazolesa
Entry
Catalyst
Copper loading on
Catalyst loading
(mol%)
Time (h)
T (°C)
Yield (%)
Ref.
catalyst (mmol gꢁ1
)
[49]
[50]
[34]
[51]
[31]
[52]
[53]
[53]
[54]
1
Functionalized chitosan/Cu
Ionic polymer/Cu
Nanoferrite–glutathione–Cu
MNP–CuBr
0.6
0.1
5
12
2.5
0.17
0.3
1
70
99
99
99
96
92
98
92
98
98
96
2
0.25
0.25
0.44
0.29
1.5
r.t.
3
2.5
1.46
10
120; MW
80; MW
r.t.
4
5
Cu/Al2O3
6
Cu(II)/clay
2
0.25
0.17
1
r.t.; sonic
70, 50; MW
70
7
Cu/SiO2
2.59
1.07
0.25
0.57
10
8
CuNPs/MagSilica
Cu NP/activated carbon
MNP@PDMA-Cu
4.3
0.5
0.3
9
3
70
10
2
50
This work
aClick reaction of benzylbromide, sodium azide and phenylacetylene.
bromides, so that the reaction time must be enhanced for an equiv-
alent transformation. It is also found that benzyl halides containing
electron-donating groups give products in lower yields or longer
reaction times. Aromatic and aliphatic acetylenes are also quantita-
tively converted to their corresponding triazoles in the presence of
0.3mol% MNP@PDMA-Cu. However, less reactive aliphatic alkynes
require longer reaction times compared to their aryl counterparts.
It is pleasing that electron-deficient acetylenes, which are normally
difficult substrates for CuAAC reaction,[48] react smoothly to
produce the desired products with acceptable time and yield.
These results show that MNP@PDMA-Cu is an active and selective
heterogeneous copper catalyst which effectively catalyzes three-
component cycloaddition of alkyl halide, alkyne and azide for
triazole synthesis.
The stability, recoverability and reusability of heterogeneous
metal-anchored catalysts are important in terms of practical appli-
cation and green chemistry. To address this concern, recycling ex-
periments were performed in consecutive runs of the reaction
under optimized conditions. After each run, the catalyst is easily
removed using an external magnet and easily recovered by
washing with ethanol, and vacuum drying. As indicated in Fig. 6,
MNP@PDMA-Cu can be successfully recovered and reused for up
to seven runs without significant loss of activity. However, after
each run the reaction takes a longer time to complete than the first
run, but this is attributed to mass loss of catalyst during catalyst sep-
aration and recycling and not to loss of catalyst activity. For this
concern, turnover frequency (TOF) of fresh catalyst and final
recycled catalyst was compared. After the seventh run the remain-
ing catalyst was separated and weighed. Based on this experiment,
TOF of recycled catalyst is 142 hꢁ1 which is almost equal to TOF of
fresh catalyst (160 hꢁ1). ICP analysis of recovered catalyst shows
that loading of copper is 0.54 mmol gꢁ1 which is almost same as
fresh catalyst loading (0.57 mmolgꢁ1 analyzed using ICP).
insoluble catalyst promotes the reaction under heterogeneous
conditions and that no copper species are released into the
reaction mixture.
The MNP@PDMA-Cu catalyst was compared with other previ-
ously reported supported copper catalysts. The loading amounts
and catalytic performances of MNP@PDMA-Cu and other catalysts
are compared in Table 4. As is evident, compared to traditional sup-
ported copper catalysts, the MNP@PDMA-Cu catalyst shows rela-
tively high loading amount of copper on the surface. However, in
some cases (entries 6–8), where copper ions are adsorbed onto
non-modified supports, loading amounts are higher than for our
catalyst. But in those catalysts the leaching of copper is markedly
high because of weak interaction of copper with the unmodified
support surface. Also, the activity of MNP@PDMA-Cu is higher than
those high-loaded catalysts and as little as 0.3 mol% catalyst is
enough for completion of the reaction. This feature of the catalyst
is especially useful in large-scale applications where the amount
of expensive catalyst should be low.
Conclusions
We have developed copper-loaded nitrogen-rich polymer-
entrapped magnetic nanoparticles as an efficient heterogeneous
copper catalyst. The resulting catalyst was applied in regioselective
synthesis of 1,4-disubstituted 1,2,3-triazoles through one-pot reac-
tion of sodium azide, alkyl halide and terminal acetylenes in water
at 50 °C. A low amount of the catalyst showed excellent perfor-
mance for a variety of alkyl/benzyl/allyl halide/tosylate and acety-
lenes resulting from high loading of copper on the polymeric
layer. High stability and efficiency, easy magnetic recyclability and
reusability, simple reaction performance without sensitivity to air
and moisture, excellent yields and ease of product separation are
the most important aspects of the developed catalyst.
In order to investigate the possible leaching of species into the
reaction solution from the catalyst, two sets of experiments were
performed. Magnetic recovery of catalyst from hot reaction mixture
followed by ICP analysis of reaction solution shows that no detect-
able metal ions exist in the reaction solution after all seven runs. In
the second experiment, the model reaction of sodium azide,
phenylacetylene and benzyl bromide was performed under opti-
mized conditions and the MNP@PDMA-Cu catalyst was completely
removed from the reaction mixture using an external magnet after
60 min. Then, the reaction was allowed to stir for 4 h and no further
production of 3a was observed. These observations confirm that
Acknowledgments
We are grateful for financial support by the Iran National Elites
Foundation.
References
[1] F. Zaera, Chem. Soc. Rev. 2013, 42, 2746–2762.
[2] A. E. C. Collis, I. T. Horvath, Catal. Sci. Technol. 2011, 1, 912–919.
Appl. Organometal. Chem. 2016, 30, 73–80
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

N. Zohreh et al.
[3] A. Corma, H. Garcia, Adv. Synth. Catal. 2006, 348, 1391–1412.
[4] R. Mrowczynski, A. Nan, J. Liebscher, RSC Adv. 2014, 4, 5927–5952.
[5] D. E. DeVos, M. Dams, B. F. Sels, P. A. Jacobs, Chem. Rev. 2002, 102,
3615–3640.
[32] Y. Monguchi, K. Nozaki, T. Maejima, Y. Shimoda, Y. Sawama, Y. Kitamura,
Y. Kitadeb, H. Sajiki, Green Chem. 2013, 15, 490–495.
[33] F. Nadora, M. A. Volpeb, F. Alonsoc, A. Feldhoffd, A. Kirschninge,
G. Radivoya, Appl. Catal. A 2013, 455, 39–45.
[6] S. Wu, C. Y. Moua, H. P. Lin, Chem. Soc. Rev. 2013, 42, 3862–3875.
[7] E. L. Margelefsky, R. K. Zeidan, M. E. Davis, Chem. Soc. Rev. 2008, 37,
1118–1126.
[34] R. B. Nasir Baig, R. S. Varma, Green Chem. 2012, 14, 625–632.
[35] J. M. Collinson, J. D. E. T. Wilton-Ely, S. Diez-Gonzalez, Chem. Commun.
2013, 49, 11358–11360.
[8] M. Benaglia, A. Puglisi, F. Cozzi, Chem. Rev. 2003, 103, 3401–3429.
[9] M. B. Gawande, P. S. Branco, R. S. Varma, Chem. Soc. Rev. 2013, 42,
3371–3393.
[36] L. Wan, C. Cai, Catal. Lett. 2012, 142, 1134–1140.
[37] R. Mirsafaei, M. M. Heravi, S. Ahmadi, M. H. Moslemin, T. Hosseinnejad,
J. Mol. Catal. A 2015, 402, 100–108.
[10] J. L. Figueiredo, J. Mater. Chem. A 2013, 1, 9351–9364.
[11] C. Huang, C. Li, G. Shi, Energy Environ. Sci. 2012, 5, 8848–8868.
[12] L. M. Rossi, N. J. S. Costa, F. P. Silva, R. Wojcieszak, Green Chem. 2014, 16,
2906–2933.
[13] R. B. Nasir Bai, R. S. Varma, Chem. Commun. 2013, 49, 752–770.
[14] D. Ho, X. Sun, S. Sun, Acc. Chem. Res. 2011, 44, 875–882.
[15] N. A. Frey, S. Peng, K. Cheng, S. Sun, Chem. Soc. Rev. 2009, 38, 2532–2542.
[16] R. Abu-Reziq, H. Alper, D. Wang, M. L. Post, J. Am. Chem. Soc. 2006, 128,
5279–5282.
[17] N. T. S. Phan, C. W. Jones, J. Mol. Catal. A 2006, 253, 123–131.
[18] M. J. Climent, A. Corma, S. Iborra, Chem. Rev. 2011, 111, 1072–1133.
[19] A. Pourjavadi, S. H. Hosseini, F. Matloubi Moghaddam,
B. Koushki Foroushani, C. Bennett, Green Chem. 2013, 15, 2913–2919.
[20] P. Barbaro, F. A. Liguori, Heterogenized Homogeneous Catalysts for Fine
Chemicals Production, Springer Science & Business Media, Dordrecht,
2010.
[21] N. Zohreh, S. H. Hosseini, A. Pourjavadi, C. Bennett, RSC Adv. 2014, 4,
50047–50055.
[22] W. S. Horne, C. D. Stout, M. R. Ghadiri, J. Am. Chem. Soc. 2003, 125,
9372–9376.
[23] W. S. Horne, M. K. Yadav, C. D. Stout, M. R. Ghadiri, J. Am. Chem. Soc.
2004, 126, 15366–15367.
[24] C. O. Kappe, E. Van der Eicken, Chem. Soc. Rev. 2010, 39, 1280–1290.
[25] J. Lahann, Click Chemistry for Biotechnology and Materials Science, John
Wiley, Chichester, 2009.
[38] T. Suzuka, Y. Kawahara, K. Ooshiro, T. Nagamine, K. Ogihara, M. Higa,
Heterocycles 2012, 85, 615–626.
[39] J. Albadi, M. Keshavarz, Synth. Commun. 2013, 43, 2019–2030.
[40] S. Keshipour, A. Shaabani, Appl. Organometal. Chem. 2014, 28, 116–119.
[41] S. Roy, T. Chatterjee, M. Pramanik, A. S. Roy, A. Bhaumik, S. M. Islam,
J. Mol. Catal. A 2014, 386, 78–85.
[42] A. Pourjavadi, S. H. Hosseini, N. Zohreh, C. Bennett, RSC Adv. 2014, 4,
46418–46426.
[43] A. Pourjavadi, S. H. Hosseini, F. Matloubi Moghaddam, S. E. Ayati, RSC
Adv. 2015, 5, 29609–29617.
[44] Y. M. A. Yamada, S. M. Sarkar, Y. Uozumi, J. Am. Chem. Soc. 2012, 134,
9285–9290.
[45] A. Pourjavadi, M. Tajbakhsh, M. Farhang, S. H. Hosseini, RSC Adv. 2015,
39, 4591–4600.
[46] A. Pourjavadi, S. H. Hosseini, S. S. Amin, Chem. Eng. J. 2014, 247, 85–92.
[47] C. W. Lai, Y. H. Wang, C. H. Lai, M. J. Yang, C. Y. Chen, P. T. Chou,
C. S. Chan, Y. Chi, Y. C. Chen, J. K. Hsiao, Small 2008, 4, 218–224.
[48] J. G. Alvarez, J. Diez, J. Gimeno, F. J. Suarez, C. Vincent, Eur. J. Inorg.
Chem. 2012, 35, 5854–5863.
[49] M. Chtchigrovsky, A. Primo, P. Gonzalez, K. Molvinger, M. Robitzer,
F. Quignard, F. Taran, Angew. Chem. 2009, 121, 6030–6034.
[50] U. Sirion, Y. J. Bae, B. S. Lee, D. Y. Chi, Synlett 2008, 15, 2326–2330.
[51] X. Xiong, L. Cai, Catal. Sci. Technol. 2013, 3, 1301–1307.
[52] B. A. Dar, A. A. Bhowmik, A. Sharma, P. R. Sharma, A. Lazar, A. P. Singh,
M. Sharma, B. Singh, Appl. Clay Sci 2013, 80–81, 351–357.
[53] C. S. Radatz, L. do Amaral Soares, E. R. Vieira, D. Alves, D. Russowsky,
P. H. Schneider, New J. Chem. 2014, 38, 1410–1417.
[26] J. Gao, X. Zhang, S. Xu, F. Tan, X. Li, Y. Zhang, Z. Qu, X. Quan, J. Liu, Chem.
Eur. J. 2014, 20, 1957–1963.
[27] D. Wang, L. Etienne, M. Echeverria, S. Moya, D. Astruc, Chem. Eur. J.
2014, 20, 4047–4054 and references therein.
[54] F. Alonso, Y. Moglie, G. Radivoy, M. Yus, Adv. Synth. Catal. 2010, 352,
3208–3214.
[28] J. E. Hein, V. V. Fokin, Chem. Soc. Rev. 2010, 39, 1302–1315.
[29] K. F. Donnelly, A. Petronilho, M. Albrecht, Chem. Commun. 2013, 49,
1145–1159.
[30] T. Jin, M. Yan, Y. Yamamoto, Chem. Cat. Chem. 2012, 4, 1217–1229.
[31] N. Mukherjee, S. Ahammed, S. Bhadra, B. C. Ranu, Green Chem. 2013, 15,
389–397.
Supporting information
Additional supporting information may be found in the online ver-
sion of this article at the publisher’s web-site.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 73–80